MTM Exam # 3

What is Ran?

Ran is a small monomeric G protein (binds GTP or GDP)

One important stage of phagocytosis is ?

Fusion of phagosome with a lysosome to form a phagolysosome

What is exocytosis ?

Fusion of vesicle with plasma membrane

Describe actin

G-actin polymerizes into actin filaments F-actin has polarity -microfilaments (cytoskeleton) -thin myofilaments (contractile apparatus in muscle cells )

What is a glycosaminoglycan ?

GAGs are very long unbranched chain of negatively charged repeating amino-sugar + sugar acid) units

What are proteoglycans ?

GAGs+ proteins : hydrate, resist compression & fill spaces

The passage of IP3, Ca 2+, and cAMP from one cell's cytoplasm into that of the neighboring cells would occur via cell junctions made up of :

GAP JUNCTIONS -> CONNEXINS GAP junction : structure 6 connexin subunits/connexon 2 connexon = 1 channel few or thousand connexons/gap junctions

Which of the 4 types of cell-to cell junction forms a cell to cell communication portal that can couple cells electrically & chemically ?

GAP junction

which of the following GLUT transporter has the highest Km or lowest affinity for glucose

GLUT 2

What is a receptor found on glycolipids ?

GM1 ganglioside (receptor) sialic acid residue cholera toxin-diarrhea provides protection

Describe GAP

GTPase activating protein "OFF SWITCH" GAP likes phosphates-always takes them

What is GAP ?

GTPase activating protein OFF SWITCH

Name glycolipids

Galotocerebrodise GM1 ganglioside (has carbo sialic acid residue (NANA))

What is Gated Ion Channels

Gated channels are open only a span of time. Most gated channels are closed at the resting membrane potential. The probability that a gated channel will open is primarily determined by membrane potential, specific ligands or chemicals, and mechanical distoration

What forms the gel structurew of vitreous humor (eye)?

Gel structure of vitreous humor (eye) results from arrangement of collagen fibrils suspended in hyaluronan

What do Gems contain ? How does this lead to spinal muscular atrophy?

Gems contain the SMN ( survival of motor neurons) protein Mutation in the SMN causes defective snRNP assembly -> defective snRNP causes defective pre-mRNA splicing -> loss of motor neurons in spinal cord and brainstem

What is Spinal Muscular Atrophy ?

Gems contain the SMN ( survival of motor neurons) proteins mutated SMN- defective snRNP assembly and defective pre-mRNA splicing -> loss of motor neurons (initially in spinal cord and brainstem) Type I (at birth): WORST

What is the name of nucleoplasmic substructures that put together the snoRNPs and snRNPs?

Gems/CBs

Mitochondrial DNA are Gene ____?

Gene Rich ( 1 gene per 445 bp)

Why is hydroxylation of propyl & lysyl important?

Hydroxylation of propyl and lysyl residues are very important for interchain H bonds in final triple helix glycosylation of hydroxylaysines -single gal or glc sugars adeded disulfide bond formation ( in the propeptide C terminal): align 3 chains & initates triple helix formation -zippering mechanism from C->N RER chaperone proteins assist in the oligomerization of the chains HYDROXYLATION OF SELECTED PROLINE AND LYSINE RESIDUES

Tubular cristae are found in what type of cells ?

Tubular cristae are found in steroid secreting cells

What is GEF?

Guanidine nucleotide exchange factor ON SWITCH

What stabilizes the procollagen triple helix ?

H bonds btw 3 chains stabilize the procollagen triple helix

describe physiological buffers : extracellular buffers

HCO3-/CO2 BUFFER major extracelluar buffer produce from co2 and h2o phosphate is minor extracellular buffer

What type of proteoglycans is features in basal lamina ?

Heparan sulfate (heparin) proteoglycan (HSPG)

A 10 yr old patient had 3 days of severe diarrhea after developing a viral gastroenteritis. now, whenever she drinks milk, she experienciences nausea, ab pain , and flatuelence. she never had this happen b4 after drinking milk. which one of the following would be best advice for this patient

Her ability to drink milk should return in a few days

What is the enzyme involved in Tay-Sachs Disease ?

Hexosamindase A

What factors inhibit the TCA cycle

High NADH/NAD ratios High ATP/ADP ratios

allosteric regulation of PFK-1

High energy levels -high ATP -high citrate -allosteric inhibition low energy levels in cells high ADP/AMP High fructose 2,6 biphosphate allosteric activation

What is hydroxylation of selected proline and lysine residues dependent of ?

Hydroxylation of selected proline and lysine residues is vitamin c dependent

Where is hydroxyproline found?

Hydroxyproline is found only in collagen ( & elastin )

what is hyperosmotic solution

Hyoerosmotic solution - if the solution has greater osmotic pressure than the cell water moves out of the cell and shrinks in cell volume (ICF vl decreases) 1. excessive loss of h2o from ECF 2. ECF osmotic pressure rises 3. cells lose H2O to ECF by osmosis cells shrink consequences of dehydration -if more water than solutes is lost, cells shrink

Hyperglycemia and HSPG

Hyperglycemia DOWN REGULATION of HSPG -Collagen glycoslyation & crosslinking GBM thickening : increase in collagen decrease in HSPG -expansion of mesangial matrix

phagocytosis by neutrophils and macrophages: oxygen independent killing

hydrolytic enzymes lysozymes lactoferrin

What is constitutive secretion ?

-continuous in all cells -vesicles fuse on arrival secretion of ECM components by fibroblasts

Describe gap junctions

-coupling & uncoupling important during embryogenesis -channel is regulated by Ca2+ levels -high calcuim (or low pH) closes junction -high extracellular Ca2+, influx into damaged cell, closes gap junction -isolates cell, prevents spread of damage -important in wailing off cardiac infarction

What is Mucopolysaccharidoses? What is the clinical presentation of Mucopolysaccharidoses?

-defective degradation of GAGs (mucopolysachharides) MPS I-MPS VII all autosomal recessive - except hunter (x-linked) - coarse facial features -corneal clouding in some -joint stiffness; skeletal deformity -hepatosplenomegaly -mental retardation -hirsutism in some -arterial deposits -urinary excretion of the accumulated GAG often increased

What is I-cell disease ? (Mucolipidosis II)

-deficiency of N-acetylglucosamaine phosphatotransferase in Golgi -> fails to produce M6P - acid hydrolases lacking M6P are secreted extracellularly - > waste products accumulate to form inclusion bodies

Describe the nuclear envelope

-double lipid bilayer: inner and outer nuclear membranes with an intramembrane (perinuclear) space -outer membrane directly connected to RER -cytoplasmic side supported by intermediate filaments & studded w ribosomes -inner membrane directly supported by nuclear lamina -nuclear pore complexes (NPC )-acts as gates

What is the role of the nucleus ?

-double membrane-bound organelle -contains the nuclear genome -protects the DNA -organizes replication, transcription & RNA processing (helps regulate gene expression) -size vary with cell function

What is Replicative Segregation (Mitotic Segregation)?

-during cell division the distribution of mtDNA to daughter cell is random - daughter cells may have different degrees of heteroplasmy

Describe the genetic bottleneck for mtDNA

-during oogenesis * a restriction in the # of mitochondria * subsequent expansion -offspring have varying degrees of heteroplasmy compared to their mother -the bottlencek and threshold hypothesis expalin the varibale expressivity and reduced penetrance we see in mtDNA

Describe power stroke

-ea outer microtubule doublet is associated w inner & outer dynein arms dynein arms slide the outer microtubules doublets relative to another -> waving motion of cila and flagella

What is the role of elastin fibers ?

-elasticity -resilience (associated with fibrillin)

cell migration is important for :

-embryogenesis -tissue repair -infection control

describe the3 types of vesicular transport

-endocytosis -exocytosis -organellar vesicular fusion

Describe secondary active transport

-energy derived secondarily from energy stored in the form of ionic conc. diff btw the 2 sides of a membrane -Na gradient considered the driver solute

Describe endergonic reaction

-energy is absorbed -reaction in non-sponteaneous -delta G is positive (delta G> 0)

Describe exergonic reactions

-energy is released -reaction is SPONTANEOUS delta G is negative ( delta G less than 0)

SGLT (secondary active transporter)

-energy requiring process -glucose transport against concentration gradient SGLT 1 Enterocytes of small intestine straight part of proximal tubules (S3) SGLT2 -renal proximal convoluted tubule (s1) -90% of glucose reabsorption -inhibited by gliflozins (anti diabetic drugs)

Canthine oxidase: reperfusion injury

-enzyme involved in purine catabolism -produces uric acid and superoxide as a byproduct during ischemia-decreased oxygen, tissue damage and breakdown of purines to hypoxanthine re-perfusion hypoxanthine converted to uric acid and increased production of superoxide

What is the function of the mitochondria matrix?

-enzymes of oxidative metabolism - pyruvate oxidation -FA oxidation -TCA cycle -pyruvate dehydrogenases complex -citric acid cycle - glutamate dehydrogenase FA oxidation urea cycle replication transcription translation

What are 2 disadvantages of cholesterol in RBCs?

-excess cholesterol is transferred to the outer leaflet of the membrane (formation of flat, scalloped cells with projections -> increase SA of outer bilayer -> less deformable -less deformability leads to sequestration and destruction of the spleen -this destruction of acanthocytes produces hemolytic anemia

What is cytochalasins ?

-excreted by fungi -blocks F-actin depolymerization

Basal Lamina functions

-famous for underlying epithela - surrounds individual skeletal muscle cells, adipocyte, schwann cell of peripheral axons - inter posed between 2 cell sheets ( e.g. kidney glomerulus- as permeability barrier) -epithelia sheet -muscle -kidney glomerulus

Alz disease

-fatal neurodegenerative dirsorder -MOST COMMON CAUSE OF DEMENTIA - estimated to affect -10% americans >65 y 50 % ameicana > 85 y s/s -progressive impairment of visual spatial skill (gets lost), memory & cognition -short term memory loss -confusion, behavoiral & pyschotic symptoms, progressive memory loss (last to go =deepest memories) -loss of bodily functions (incontinence, mute) & withdrawl -death

RER

-flat cisternae -ribosomes + ribosphorin -protein production pathways : ER -> Golgi -> Endosomes -> lysosomes -> PM -> secretion -protein folding -glycosylation

Describe the erythrocyte cytoskeleton

-flexibility Spectrin network inside RBC Ankyrin - connection Band 3-Integral proteins (hook) Spectrin-network -Band 4.1 & F0actin connection Glycophorin-integral protein hook

What are 2 anchoring junctions formed by integrins ?

-focal adhesions -hemidesmmosomes

Describe Mucolipidoses

includes I-cell & Pseudo-Hurler polydystrophy = accumulation of glycoproteins & glycolipids

from a molecular biology perspective, what is the cause of cystic fibrosis?

incorrect protein folding causes degradation

What is the main cause of cystic fibrosis ?

incorrectly folding protein, this would still fx normally if transported to plasma membrane BUT chaperones wont pass it on and it is ejected back into cytosol & degraded CF AR Mutation in CFTR

metabolic increase in bicarbonate

increase hco3 decreased ventilation by lungs and retention of co2

Describe the process of acanthocye?

increase in cholesterol -> ACANTHOCYTE -> SPIKEY SPUR CELLS spleen -> abnormal RBCS -> destroy -> hemolytic anemia (decrease in RBC) MEDICAL CORRELATION : OH CIRRHOSIS

ADH regulates water retention by acting to increase water reabsorption in the kidney. if the ADH receptors are antagonized, what effect will this have of ecf osmolarity and ecf na concentration

increase in ecf osmolarity decrease in na concentration

What are the effects of uncouplers on the following parameters

increase in oxygen consumption decrease in ATP synthesis increase in body temperature increase in respiratory rate

the first physiological change that occurs upon infusing a hypertonic solutin iv into an experimental rat will be which of the following ?

increase the extracellular osmolality

A 60 year old female p/w acute onset of SOB that has progressively worsened over the past week. She now reports difficulty breathing at rest. She has smoked more that 2 or more packs/day of cigarettes for 40 yrs but quit 2 yr ago due to breathing issues. P/E reveals hyperexpansion of the chest (barrel chest) and severe respiratory distress. Her condition first developed as a result of :

increased elastin fiber breakdown in the pulmonary ECM DX: EMPHYSEMA elastin fibers keep skin from wrinkle

Compared w the resting state, vigourously contracting skeletal muscle shows :

increased reduction of pyruvate to lactate

The mitochondrial bottleneck hypothesis explains why....

individuals with mtDNA mutations may have different proportions of mutant mtDNA compared to their mothers or siblings

An individual taking exenobiotic, such as oh, medications, and other foreign chemical, can increase their risk for free radical injury through which one of the following mechanis,

induction of enzymes containig cytochrome c

What is Phagocytosis "cell eating"

ingestion of large particles, bacteria & dead cells into phagosomes -performed by specialized cells (macrophages, polymorphonuclear cells, and dendritic cells) -done as an important defense against infection or to clear biological debris

What is atractyloside

inhibit oxidative phosphorylation by inhibiting the ATP-ADP antiporter system

What is uncompetive inhibition

inhibitor binds only to enzyme substrate complex and does not have any affinity for free enzyme bc the enzyme is inactive when the uncompetive inhibitor is bound, but the inhibitor is not competing w substrate for binding, the inhibitor effectively removes some fraction of the enzyme molecules from the reaction given that Vmax depends onE, the observed vmax decreases and given that inhbitor binds only to the ES complex, only ES ( not free enzyme) is deleted from the reaction, so the S needed to reach 1/2 vmax-that is Km-declines by the same amount

What is enzyme inhibition?

inhibitors are molecules that interfere w catalysis, slowing or halting enzymatic reaction

Where do the enzymes and proteins found within the peroxisome come from?

Correctly folded and assembles cystolic proteins with an exposed

What has to happen before the collagen fibrils assemble into a collagen fiber?

Covalent cross links are formed w the aid of extracellular lysyl oxidase

covalent modification

Covalent modification is a rapid and transient process of regulating enzyme activity one or more of the aa residues in the enzyme molecule is covalently modified common modifying groups include phosphoryl, acetyl, adenyl, methyl, carboxyl, mysristoyl, palmitoyl, prenyl, hydroxyl, sulfate protein phosphatase -> insulin protein kinase -> glucagon & epi

What are glycosaminoglycans (GAGs)

Covalently linked to core protein (EXPECT HYALURONAN) to form a proteoglycan very long UNBRANCHED chains NEGATIVELY charged repeating DISSACHARIDES -amino sugar ( N-acetylglucosamine or N-acetylgalactosamine ; usually sulfated) plus -a sugar acid ( glucuronic or iduronic acid) negative charge attracts Na ions attracts H2O

Where are the ETC protein complexes located ?

Cristae of the inner membrane

Which of these is a well-known drug that blocks the depolymerization of F-actin and so disrupts the actin cytoskeleton ?

Cytochalasin

What two drugs blocks F-actin depolymerization ?

Cytochalasins Phalloidin

Which of these drugs inhibits the depolymerization of F-actin into G-actin and therein blocks any dynamic actions of the actin microfilamaents ?

Cytochalasins & phalloidin

What component is releases through BAX induced pores in the mitochondrial outer membrane during INTRINSIC APOPTOSIS to serve a pro-apoptic role that helps to activate the cystosolic capase cascade ?

Cytochrome C Explaination : Mitochondrial Pore Formation & Apoptosis Pro-apoptotic bcl-2 proteins (BAD, BAX) translocate from cytosol to mitochondrial membrane in response to cell damage/stress & signaling --> formation of pores in outer membrane (BAX) --> release pro-apoptotic factors (cytochrome C) into cytosol --> activate caspse cascade --> Apoptosis

Cytochrome C-activates apoptosis

Cytochrome C may be released from the inner mitochondrial membrane and leak into the cytosol, including apoptosis (cell death) apoptosis : programmed cell death triggered by stress dna damage ros pro-apoptotic signals

Compatmentalization

Cytoplasm : glycolysis, F.A. synthesis Mitochondria : Krebs cycle, ETC, F.A. oxidation Peroxisomes : Long chain F.A. oxidation Both mitochondria & cytosol : urea cycle, Heme biosynthesis

What is substrate level phosphorylation?

Cytoplasm-production of ATP molecules via transfer of a phosphate group from an intermediate high energy substrates directly to ADP

Which of the 4 types of cell to cell junction form thick BUTTON LIKE junctions based on strong cadherin-cadherin extracellular binding that anchor intertwined keratin intermediate filaments into an intracellular 'plaque' so as to form very strong anchors betwee cells that indirectly link the different sets of intracellular intermediate filaments. these junctions resemble spot welds and typically are found about midway down the side of a cell. these are ;

DESMOSOMES

the mechanism of vitamin E as an antioxidant is best described by which one of the following ?

vitamin paritcipates in the

An uncharged solute (s) that enters a cell by facilitated diffusion :

will be at eq when the extracellular (s )will be equal to the intracellular (s) na-k is only for na and k

A uncharged solute (S) that enters a cell by facilitated diffusion :

will be at equlibrium when the extracellular [S] will be equal to the intracellular [S] explanation : uncharge solute , = conc.

What is distribution of mitochondria in sperm ?

wrapped around flagellum

Lineweaver burk double reciprocal plot

x axis =1/S y axis =1/v0 point of intersection on x axis = -1/km point of interstection on y axis = 1/vmax slope km/vmax

What is Michalis-Menten Kinetics?

x-axis -substrate concentration y-axis -velocity of the reaction V V max= moles/sec or micromole/min max velocity a reaction can reach. directly proportional to amount of the enzyme and substrate (kcat not of enzymes) km (mM) = substrate conc at the half max velocity kcat (1/sec)= number of molecules of substrate converted to product per unit time on a single enzyme also called turnover number enzyme concentration is kept constant as the substrate concentration increases the velocity increase but after some conc. the graph flattens due to enzyme sat. the highest point on the graph is call Vmax.

Patho of GP91 mutations

x-linked 70% cases

Describe Barth Syndrome

x-linked cardiolipin synthesis disorder cardiomyopathy generalized muscle weakness and chronic fatigue neutropenia high mortality in infancy : Sudden infant death infection cardiac failure

Adrenoleukodystrophy

x-linked recessive mutation in ABCD1 gene disorder of beta oxidation VLCFA build up in adrenal gland, white matter and testes.

What causes gout ? S/S of gout

xanthine break down into -> uric acid hyperuricaemia -> gout (arthritis) urate crystals in a tophus acute gout with erythema of the great toe joint

is the nucleus a cellular organelle?

yes

describe carbonic anhydrase:

zinc containing enzyme location: GI mucosa, RBCs and kindney converts dissolved CO2 into carbonic acid kidneys regulate HCO3- reabsortpiton and synthesis erythrocytes - adjust conc of hco3 - in response to change in pco2

Both ECF and ICF Osmolality is what ?

~290 mOsm/kg H2O ecf osmolality - 2 (plasma (na+)) =290 icf osmolality - k+ +proteins + inorganic phosphates = 290

What causes Botulism ?

- botulin toxins destroy SNARES Clostridium botulinum (anaerobic soil bacteria that grow in inadequately sterilised canned foods-toxins enter GI tract)

What is the 2 main endocytic mechanisms ?

- bring material into cell -recycle plasma membrane components

What are the longer precursors of collagen called and where are they first synthesized?

Collagen chains are first synthesized in the RER as longer precursors: preprocollagens

How do collagen fibril form ?

Collagen fibrils form by lateral interaction of triple helices

why does osteogenesis imperfecta have such a large range in severity of the phenotype produced by different mutations ?

Collagen is a long molecule, and since the triple helix forms form C-terminus to N terminus a mutation in the n terminal region will not be as severe as one in the c terminal region

Describe Complex III, Cyt C, and Complex 4

Complex III : cytochrome c reducatase -complex III accepts electrons from ubiquinone and pumps 4 hydrogen ions across the inner mitochondrial membrane oxidizes ubiquinone and reduces cytochrome c. electrons from ubiquinone are transferred though cyctorchrome b to an FeS center to c1 , and finally to cytochrome c cytochrome c is a peripheral membrane protein, shuttling electrons from complex III to complex IV Complex iv: cyctochrome oxidase-transfers electrons from cytochrome c to oxygen, producing water

etiology of lactose malabsorption

Congential : AR disease Diarrhea from brith absent lactase, normal histology primary : genetically regulated reduction of lactase enzyme activity low intestinal lactase activity by school age secondary : -intestinal disease which affect large areas of the mucosal surface and which result in a decrease of digestive activity

What are collagen mutations ?

Connective tissue defects

What is the name of the protein family that forms the different gap junctions ?

Connexins

What is a peroxisome?

Contain 50 enzymes ( at pH 7.5) : all made on free ribosomes -present in all tissues ( especially liver & kidney) -carry out oxidative reactions -generate H2O2 for oxidative purposes -contain catalase (peroxidase) to destroy excess H2O2 -Involved in biosynthetic, degradative and detoxification reactions Human cells contain several hundred peroxisome

What is the famous kinase associated directly w the intracellular complex that forms around the integrins that cluster in a focal adhesion ?

Focal adhesion kinase (FAK)

What is one important difference between a focal adhesion and hemidesmosome?

Focal adhesions link to F-actin stress fibers

B/c glucose has several metabolic routes it might take once it arrives in the cytoplasm, which one of the following reaction would commit the glucose to following the glycolytic pathway ?

Fructose 6-P to fructose 1, 6 bis P

What is a lipid raft?

" Butter Island in a sea of oil" -rich in cholesterol & glycosphingolipids (long saturated tails) -> less fluid, thicker -thicker - stick up out of membrane : longer and straighter lipid tails -contain intergral & peripheral proteins: clustering enables to function together for transport into endocytic vesicles

what is mixed inhibition

" mixture" of competitive inhibition, in which the inhibitor can only bind the enzyme if the substrate has not already bound, and uncompetitive inhibition, in which the inhibitor can only bind the enzyme if the substrate has already bound

Describe the directionality of mircotubules

(-) ends = anchored in MTOC (-) ends = are very nucleus, microtubules radiate outward toward cell periphery microtubules grow or shrink by tubulin dimers

the delta G 0' values are determined under standard biochemical conditions and reflect the energy either required, or releasedm as a particular reaction proceeds. Given the delta G 0' values below, determine the overall delta G 0' for the following reaction:

+3 kcal/mol

What property of mircotubules allows motor proteins to move things (organelles and vesicles) around on a mircotubule network , when they cannot do so on an intermediate filament network ?

Largely b/c they have polarity

Name Lamin A mutations and diseases

* note : lamina C is a splice variant of lamina A, so an LMNA mutation could affect both proteins EMD - AD EMERY Dreifuss muscular dystrophy Dilated cardiomyopathy (DCM) Familial partial lipodystrophy Hutchinson -Gilford progeria

What are early endosomes?

Largely dereived from endocytotic vesicles, ph 7

principles of reaction coupling

- 2 reactions are coupled if they share a common intermediate -a common intermediate exist if a product of one reaction is a reactant of another -delta G of an overall reaction is the sum of two half reaction. the direction of one half of the reaction may be reversed based on the situation for calculation

What is Hereditary Spherocytosis?

- AD - Spectrin Defiency (not holding shape -> spheres ) -no flexibility - lysis in spleen -> SPLENOMEGALY -Hemolytic anemia

SER

- Branching sacs -no ribosomes -membrane lipids -lipoprotein -steroid hormone synthesis -muscle contraction -glycogen degradation -gluconeogenesis

What is Thermogenesis?

- Brown adipose tissue contains many specialised mitochondria equipped with the uncoupling protein (UCP; aka thermogenin) in their inner membrane UCP forms channels through membrane to allow protons to "leak" from intermembrane space into the matrix -uncouples proton gradient from ATP synthase and permits rapid metabolism of FA -> to generate heat oxidative metabolism : (TCA, ETC) all produce heat - so this rapid shuffling of protons dramatically increases heat production

Which 2 lysosomal storage diseases have no corneal clouding ?

- Hunter syndrome -metacrhomatic leukosystrophy

Secretion from the the Golgi to the extracellular compartment can take place via Constitutive or Regulated secretion. Which of the following secretions do you expect to use the regulated mechanism ?

- Insulin release from pancreatic cells -release of digestive enzymes into the GI track Note : Regulated ( released upon demand)

What are 2 types of peroxisomal reactions ?

- Oxidases: use O2 to remove H atoms for organic substrates - oxidation of organix compounds (uric acid, AAs, FAs, purines) -catalase: use H2O2 to oxidase toxins (alcohol): peroxidation reaction (important within liver and kidney) & when excess H2O2 accumulates - elimination H2O2 oxidise toxins (alcohol)

What is pulmonary surfactant ?

- Pulmonary surfactant is mixture of phospholipids, cholesterol and protein -Keep air sacs open - act like a mild detergent and breaks water tension -80% is phospholipid (largely phosphatidycholine and phosphatidylglycerol) - 10 % is protein and 10 % is cholesterol

Describe the RER protein synthesis ?

- RER captures selected proteins when they first are being made on the ribosomes (also captures the ribosomes) RER protein import is co-translational (translocation begins shortly after polypetide synthesis has begun) -ER "signal sequence" on protein directs protein & ribosome onto receptors embedded in ER membrane -free cytosolic ribosomes synthesise all other proteins & discharge them into cytosol ( proteins targeted to nucleus, mitochondria, peroxisomes, those destined for post-translational translocation, see future topics)

Describe mitochondrial translation

- Resembles bac. translation (translation begins with N-formyl methionine) -Relaxed codon usage -only 22 tRNAs cf. 30 or more in the cytoplasm (pair w more codons) -variant genetic code :4/64 codons have different meaning

Describe an overview of the ER

- SER & RER -Co-translational translocation - polypeptide processing -secretory pathway: -targeting/sorting -vesicular traffic

What is Chediak-Higashi syndrome?

- a different type of lysosomal disorder -Rare, autosomal recessive and dangerous -Involves the CHS1/LYST gene, encoding a lysosomal trafficking regulatory protein that normally induces vesicle fusion, mutations cause : -delayed fusion of pahgosome with lysome in leukocytes -autophagocyotsis of melansomes in melanocyte -> albinism/hypopigmentation -granular defects in NK cells & platelets these recurrent infections (life threatening)

What is Heteroplasmy ?

- a mixed population of mtDNA molecules -some mutated, others not Heteroplasmy and mtDNA disease * in mtDNA diseases there is commonly a positive correlation btw the proportion of mutated molecules & the severity of the disease * severe mutations in mtDNA are only observed in heteroplasmy bc they would b lethal un the homplasmic state

Equlibrium constant

- a mixture of chemical reactants and products tends to continue changing until eq is reached -at the eq conc. of reactants and products, the rates of the forward and reverse rxn are exactly = and no further net change occurs in the system - the conc. of reactants and products at eq define the eq constant, Keq int eh general reaction where a,b,c and d are the number of molecules of A, B, C, and D participating

Describe the process of transport of hydrolases to lysosomes

- acid dissociated cargo from M6P receptor -phosphate removed from cargo glycoprotein so it cannot rebind to M6P receptor -M6P Receptor proteins recycled back to TGN

Describe the transport of hydrolases to lysosomes ?

- acid dissociates cargo from M6P receptor -phosphate removed from cargo glycoprotein so it cannot rebind to M6P M6P Receptor proteins recyclyed back to transgolginetwork (TGN)

How do adherens junction differ from desomosomes ?

- adherens junctions connect to F-actin , not to IFs -adheren junctions are nerarer the apical surface ( the actin rich region) -form a continuous belt around cell, do not form " spot welds" -linker proteins = catenins ( important signaling molecules; GI & hepatic ca )

Name the 2 types of anchoring junctions

- adhesion belt ( cadherins) desmosomes (cadherins)

Describe adhesive glycoprotein : laminin

- anchors epithelial cells to basal lamina -laminin & collagen iv bind to form scaffold -also binds HSPGs, entactin, integrins -organize assembly of basal lamina by binding cell membrane receptors (integrins, dystroglycan) lamin receptor binding adhesion promotes cell growth & differentiation -most prevalent constituent of all basal laminae

Why does Lamin A cause many mutations ?

- architectural partners -chromatin partners -gene regulatory partners -signaling partners

describe the positive feedback control of childbirth

- baby moves deeper into mothers birth canal -cervix of uterus is stretched - nerve impulses sent to hypothalamus -hypothalamus sends impulses to posterior pituary where oxytocin is stored - posterior pit releases oxytocin travels to uterine muscle -uterus responds to oxytocin by contracting vigurously -at birthm stretching of cervix lessens and positive feedback cycle is broken

Review of CMT

- caused by failure to make connexin -32 these proteins are necessary for the intracellular gap junctions between coils of Schwann cell that wrap around the neuron the intracellular junctions seem to be critical in supplying nutrients to the distant reaches of the Schwann cell; if impaired -> demyelination & failure of peripheral neuron function

What is the cytoskeleton directly involved with ?

- changes in cell shape and cytokinesis - wound healing - organelle and vesicular transport -phagocytosis

What is the s/s of metachromatic leukodystrophy?

- cognitive deterioration -demyelination -progressive paralysis - dementia in adult form -nerve stain yellowish-brown with cresyl violet (metachromosia) - onset at 2 y ( typical for 50-60% of cases) -speech loss and weakness -gait disturbance, progressive loss of muscle tone -typically do not survive past childhood - juvenile form, onset at 4-13 y (20-30 %) -adult form (20 %) onset teenage years or later - behavioral problems (alcholism, drug abuse) -pyschiatric symptoms (delusions, hallucinations) survival 20-30 years

What is Arf-GTP (or Sar-GTP)?

- collects the coat protein - promote the binding of receptor membrane proteins to both cargo and the coat protein

Hypoxia-lactic acidosis

- decreased oxygen -no final electron acceptor accumulation of NADH and FADH2 conversion of NADH to NAD + in cytosol by LDH -anaerobic glycolysis increased lactic acid production and decreased ATP production

What is a late endosomes ?

- develop from early endosome supplemented with lysosomal hydrolytic enzymes, acidified - pH 6 endosomes serve as "sorting vesicles" in the vesicle trafficking pattern

What is Acanthocytosis/Spur cell anemia ?

- elevated cholesterol synthesis associated with chronic liver disease ( alcoholic liver disease, liver cirrhosis) -abnormal lipoproteins with high cholesterol content & high plasma cholesterol levels -produces increase cholesterol in RBC plasma membrane -abnormal RBCs are the "spur cells" (acanthrocytes)

What is the function of cell membrane in animal ?

- enclose and protects cells -maintains structure and function integrity -selective permeable according to charge, molecular mass, degree of hydrophilicity -defines inside vs. outside for cell and subcellular organelles -compartmentalization of biochemical activities.

What is feedback regulation

- end product of the pathway controls its own rate of synthesis -usually involves allosteric regulation of rate limiting enzyme -it also induces or represses the gene for transcription of the rate limiting enzyme

What are the 3 pathways to degradation in the lysosomes ?

- endocytosis -phagocytosis -autophagy

Where is most of the proinsulin processed into insulin?

- extracellular matrix -secretory vesicles

In classic mitochondrial inheritance, all children of an affected mother will be affected by the same mitochondrial disease. In humans, however, the inheritance pattern of mitochondrial disease is sometimes difficult to identify b/c of

- incomplete penetrance - variable expressivity

Describe collagen

- made by fibroblast (oseteoblast - bone chondroblast - cartilage) & also epithelial cell ( for the basal lamina)

What are the main functions of actin filaments ( microfilaments)

- maintenance of cell shape (tension-bearing elements ) -changes in cell shape - muscle contraction - cytoplasmic streaming -cell motility ( as in pseudopodia) -cell division ( clevage furrow formation)

Describe the processing in the Golgi

- molecules undergo ordered series of modification from cis to trans -N-linked oligosaccharide modification & O-linked glycosylation -proteins destined for lysosomes: tagged with mannose-6- phosphate in cis-Golgi SULPHATION in trans Golgi

In what will increase fluidity in a plasma membrane ?

- more UNsat f.a tails ( increase cis-double bond kinks) -more short chained phosholipids -increase temp -less cholesterol

When describing the Phases of phagocytosis, what is the correct sequence of events?

- phagocyte binding to "opsonin" molecules - phagocytic cup formed around foreign object - formation of phagolysosome - acidic hydrolases degraded ingested material

Name 5 phospholipids

- phosphatidyleethanolamine -phosphatidylserine -phosphatidycholine -sphingomyelin -sphingosine

What is the function of fibrous ECM proteins ?

- physical properties that impart strength &/or flexibility -water insoluable, extracellular, long-lived, strudy proteins - used in construction of loose & dense connective tissue, tendons, bone martix and caritliage form a web-like protein backbone to which other molecules can attach

What is the function of the RER ?

- produces proteins destined for ER, Golgi apparatus, endosomes, lysosomes, plasma membrane & secretion -lumen contains enzymes & chaperones to modifiy & help fold proteins - monitors assembly, retention, degradation of proteins

What happens epidermolysis bullosa simplex ?

- rupture of cells in the basal layer of epidermis - defective keratin filament network -rupture of keratin interfilaments connecting down to basal lamina (blisters and openings form beneath most of the epidermis, but not above the basal lamina )

Provide the stops for collagen i formation

- signal sequence directs growing polypeptide chain n 2 ER signal sequence cleaved hydroxylation of selected proline and lysine residues ( vitamin c dependent ) glycosylation of selected lysine residues assembly of pro alpha chain into procollagen triple helix procollagen transferred to Golgi and secreted to ECM

What are the functions of the SER ?

- steroid hormone synthesis (adrenal cortex, testes, leyding cells) -detoxification . enzymes in hepatocyte SER such as Cytpchrome P450 oxidize drugs to inactivate others -> made water soluble so they are excreted in urine -synthesize membrane lipids - plasma lipoprotein production (heptatocyte) -control muscle contraction and relaxation (as the specialized sarcoplasmic reticulum) -release and sequestration of Ca 2+ during cycles of skeletal muscle contraction

What are the basal lamina functions ?

- structure support for cells ( transmembrane intergrin receptors bind to collagen iv and laminin) -organize cells and tissues - scaffold for tissue regeneration -filter in the kidney glomerulus -thick, finely sieved basal lamina prevents macromolecules passing from blood into urine -collagen IV & HSPGs especially important -determines cell polarity -influences cell survival, proliferation, differentiation -selective barrier for cell migration

endergonic reactions proceed by coupling to exergonic process

- the conversion of metabolite A to metabolite B occurs w release of free energy -free energy is required to convert metabolite C to metabolite D -an endergonic process cannot exist independently but must be component of a coupled exergonic endergonic system where the overall net change is exergonic

Redox potential of various complexes (E0)

- the reduction potentila E0 is a measure of the tendency for a substrate (reactant) to accept electrons under standard conditions. -Redox reactions always involve a pair of half reactions, one an oxidation and other a reduction -oxygen has the highest redox potential -highest affinity for electrons

Describe Adherens junctions and cadherins

- this type of junction is strong enough to anchor/ connect cells together -these cell-cell junctions use the cadherins

What is Phalloidin ?

- toadstool mushroom -blocks F -actin depolymerization

How does intermediate filaments relate to detection of CA origin ?

- tumor cells typically lose normal apperance; difficult to determine cell type based on morphology -however, they can retain some differentiated properties of the cells from which they are derived, including expression of intermediate filaments -fluorescent-tagged antibodies can be used to determine if a tumor first originated in epithelial, mesenchymal or neuronal tissue -detection of metastasis, limited use

Describe Mitochondrial genome

-16569 bp -one circular DNA molecule -several thousand DNA molecules per cell -largely free of protein -37 number of genes -gene density :1/450 bp repetitive DNA : very little transcription : continuous transcription of multiple genes introns: absent 93% coding DNA recombination not evident Inheritance : exclusively maternal

Describe cholesterol membrane stability

-2-30 % of membrane (in both leaflets) -increase stability, stiffens -fills in gap when lipids are too fluid (i.e. if their is high unsaturation or a high temp) -steroid rings immobolize PL hydrocarbon chains: reduces phospholipid movement -rigid planar steroid ring structure -polar head group -nonpolar hydrocarbon tail

Describe cardiolipin of the inner membrane

-20% of inner membrane lipid -double phospholipid : 4 tails instead of 2 - made w/n mitochondria most other phospholipids are imported -inner membrane is very impermeabile to ions also binds to enzyme complexes to stabilize them -may help membrane maintenance cycles

Describe an integral transmembrane protein

-30 % total proteins, amphipathic -single/multipass proteins -often alpha helical in secondary protein structure -receptors (signaling, adhesion), channels, transporters/pumps

What is epidermolysis bullosa simplex?

-AD -Mutation in keratin 5 or 14 - blister form ABOVE basement membrane -fragile skin: minor mechanical friction / trauma -> recurrent blister formation

What is Tay-Sachs Disease ?

-Accumulation of Gangliosides (GM2) -Rapid and progressive neurodegeneration

What is metachromatic leukodystrophy?

-Accumulation of sulfatides - Autosomal recessive - Defective degradation of sulfatides (galacterocerbroside 3- sulfate & derivatives) -accumulation of sulfatides in cells=toxic to CNS; destruction of myelin of oligodendrocytes of progressive leukodystrophy in CNS &PNS -> paralysis & cognitive decline

What is the NPC molecular traffic ?

-Bidirectional communication -passive diffusion of small molecules -macromolecules : selective and active transport -imports all needed proteins (histones, polymerases, TF, and proteins that bind to RNA parts of nuclear components -exports mRNA, tRNA, ribosmone subunits

What is Emery-Dreifuss Muscular Dystrophy?

-Contractures, in the elbows, ankles, neck -> flexion deformity of elbows, limited neck flexion -muscle weakness & atrophy -conduction defects & arrythmias sudden HF common microscope shows fragile nuclei : nuclear envelope disrupted chromatin is actually extruded into the cytoplasm

What is I-cell dieases (Mucolipidosis II)

-Deficiency of the golgi N- acetylglucosamine phosphotransferase prevents formation of M6P tag - acid hydolases lacking M6P are secreted extracellularly undigested substrates accumulate as inclusion bodies that progressively damage cells

What are the mitochondrial metabolic function ?

-ETC -ATP Synthesis -Detoxification of reactive oxygen species -citric acid cycle (TCA) -oxidative phosphorylation -conversion of pyruvate acetyl coA - Beta oxidation of FA

Describe the Golgi Apparatus ?

-Flattened series of stacks (cisternae)- hollow pancakes -organized by mircrotubules - a major carbohydrate synthesis site (including GAGs) -adds O-linked oligosaccharides to proteins and lipids -modified N-linked oligosaccharide to mature structure -sorts proteins & lipids arriving from ER -dispatches proteins to lysosome (M6P tag), plasma membrane or secretory vesicles

trans-phosphorylation btw nucleotides

-GTP, UTP, & CTP or d-GTP, d-TTP, d-CTP, and d-ATP are energentically equivalent to ATP -in prep for various bio roles, these other nucleotide w same standard free energy are produced -ATP is the primary high energy phosphate produced in the cell. High ATP ratios in cell drives the reaction to produce other NTPs

What cause severe mtDNA mutations ?

-Giant deletions in the mtDNA (4-6kb) -deletions may be up to 7000 bp (40% of the mtDNA) -encompassing essential genes, like tRNA genes -always found in the heteroplasmic state -almost always sporadic -easy to detect by Southern blot or PCR -mtDNA template has high copy number

Describe another function of SER (hint: free glucose)

-Glycogen degradation and gluceneogenesis -Glucose 6-phospahatase (enzyme housed in SER membrane) = a SER membrane protein: removal of phosphate from G6P-> free glucose prominent in cells synthesis steroids, triglycerides and cholesterol increases when stimulated (to secrete steroids or detoxify drugs)

Describe the pathway of COP I

-Golgi -> Golgi (retrograde) cis-Golgi -> ER " one step back- retrograde"

Describe glycolipids

-Hold carbs oligossacharides -form much of the glycocalyx -only on extracellular leaflet

Describe the cytoskeleton

-Made of 3 types of cytosolic protein polymers forming filaments dynamic properties : certain filaments ( microtubules & actin microfilaments) can grow and shrink rapidly - these filament coordinate with each other - coordinate w external signals

What is MILS?

-Maternally Inherited Leigh syndrome -a subtype of Leigh syndrome -more severe b/c of greater degree of heteroplasmy - associated with mutations in the mitochondrial protein coding genes

What is X-linked Adrenoleukodystrophy? (XALD)

-Most common peroxisomal disorder -defect in transport of VLCFA -defective breakdown of VLCFA -defective membrane protein that imports VLCFAs VLCFA then accumulate in brain (glial cells) -> myelin breakdown Adrenal cortex -> adrenal atrophy * onset 5-10 y; apathy behavioural changes *spaspticity, ataxia, visual loss * death occurs a few years later

What is Pseudo -Hurler Polydystrophy ?

-Mucolipidosis III -milder form of I-cell disease -later onset -survival into adulthood

What is plasmalogen synthesis ?

-Phospholipids with HC chain linked to glycerol by an ETHER bond (not ester bond) - membrane components of heart and brain (80-90 % of myelin membrane phospholipid) -deficiency of abnormalilities in nerve cell myelination

What is PCD?

-Pirmary ciliary dyskinesia (PCD) -AR, with variable penetrance -1/15,000 -40, 000 births - immotile cilia & sperm -> retention of secretions & recurrent infection s/s -bronchitis -otitis media -sinusitus -infertility

Describe co-translation translocation

-Protein has an ER signal sequence (usually 15-20 aa at the Nterminus) -signal recognition particle (SRP) binds to ER signal sequence -SRP binds to SRP receptor in ER membrane -SRP complex brings the ribosome to a translocon & docks the ribosome SRP complex leaves & the ribosome then extrudes the growing polypeptide chain through the transcolon pore into the RER lumen

Describe the Peroxisome import signal

-Proteins made in the cytosol -C-terminal SKL (Ser-Lys-Leu) import signal -Import signals bind to peroxisomal translocators Peroxins (PEX genes) Import requires ATP -folded proteins enter

What is the clinical presentation of PEO?

-Ptosis: bilateral -late age of onset (18-40 yrs of age) -biochemical and histological muscle pathology ragged red muscle fibers -progressive muscle weakness and wasting -b/l ptosis -exercise intolerance

What are the 5 families of G proteins ?

-Ras -Rho -Rab -Ran -Arf 20 members in each family. total 100.

What happens in all major lysosomal storage diseases ?

-Recessive defects in lysosomal hydrolases -accumulation of partially degraded insoluble metabolites in lysosomes -> enlarged lysosmes that interfere with cell function -often affect nervous system -most severe -I cell (inclusion cell disease) -almost all hydrolytic enzymes missing from fibroblast lysosomes -unddigested substrates accumulate -> large inclusions in cells In lysosomal storage diseases : -lysosomal enzyme defiency -stored nonmetabolized products

Describe Chediak-Higashi Syndrome

-Recurrent infections -no vesicle fusion

What 2 things occur when there is a disruption at the neuromuscular junction ?

-SNARE complex does not form -membranes do not fuse

What is the role of the ECM ?

-Scaffold to stabilize physical structure and resist forces -influence cell behavoir : survival, development, migration, proliferation, shape, and function

What is Mucolipidoses? What dieases are considered to be mucolipidoses ?

-Sialidosis -I-cell disease -Pseudo-Hurler polydystrophy

What is the function of the SER?

-Steroid hormone synthesis ( adrenal cortex, testes, leydig cells) -detoxification -synthesize membrane lipids -plasma lipoprotein production (hepatocyte) -control muscle contraction & relaxation (as the specialized 'Sacroplasmic reticulum' -release and sequestration of Ca 2+ during cycles of skeletal muscle contraction - glycogen degradation & gluconeogenesis - prominent in cells synthesizing steroids, triglycerides and cholesterol -increases when stimulated ( to secrete steroids or detoxify drugs )

Which of these is function of the Golgi apparatus and not the RER?

-Sulfation of carbs or tyrosines -Phosphorylation of terminal mannose on lysosomal glycoproteins

What 2 theories explain the variable expressivity and reduced penetrance we see in mtDNA disease?

-The bottleneck -threshold hypothesis

What is beta-oxidation of VLCFA?

-VLCFA (>C24) can ONLY be degraded in peroxisome -initiated in peroxisome down to C10, completed in mitochondria -FA oxidation = major source of metabolic energy FA -> acetylCoA -> cytosol (used for biosynthesis of cholesterol and bile acids )

Describe Mitochondrial Mode of Inheritance

-Vertical pattern -children of affected males are not affected -all children of affected females are affected -highly variable presentation -some children may be unaffected due to reduced penetrance

Which of the following increase membrane fluidity ?

-Unsat F.A. tails (increase cis-double bond kinks) -increased temps -shorter chain F.A.

Describe Co Q

-When the rate of electron entry into the respiratory chain and the rate of electron transfer through the chain are mismatched, superoxide radical production increases 1. when mitochondria is not making ATP 2. High NADH/NAD ratio in matrix coq has a probability of passing an electron to O2 to make it a superoxide ion leads to formation of several free radicals like OH

What is Rho-GTP

-activates actin-polymerization & branching at leading edge - pushing cell forward & stretching actin web like cortex - contraction ( myosin motor proteins ) at rear propels the body forward to relax tension new focal contacts (integrins bound to ECM) are made at the front , old ones are dissembled at the back as the cell moves forward -repeat again and again

relationship between delta G 0' and delta G of a reaction

-actual free energy change delta G is function of reactant and product conc. at physiological conditions -a,b,c, d are actual conc. (starting conc.) of substrates and products prevailing in the system. R = unviersal gas constant T= absolute temperature Delta G of any reaction proceeding spontaneously toward its equlibrium is always negative, becomes less negative as the reaction proceeds, and is zero at the pt of eq. indicationg that no more work can be done by the reaction

What are small nucleolar RNPs= snoRNPS

-assist in assembly of ribosomal subunit in nucleolus snoRNA made by RNA pol II snoRNAs bind proteins -> snoRNPs snoRNAs contain short sequences complementary to rRNA base pairing between snoRNA (of a snoRNP) and pre-rRNA targets enzymes that catalyze base modification (methylation) of pre-rRNA

What is Leigh syndrome?

-associated with mutations in the mitochondrial protein coding genes -caused by mutations in >75 different genes - most are nuclear but also mitochondrial (80% of cases have mutations in nuclear genes, 20% in mitochondrial) -Genes involved in mitochondrial energy production (complexes I-V, pyruvate dehydrogenase, coenzyme Q)

metabolic and respiratory components of the acid base are interlinked

-bicarbonate is the metabolic component - pco2 is the respiratory component -they are interdependent : one tends to compensate for the untoward changes in the other

Electron transfer in oxidation reduction reactions :

-biological fuels like glucose is converted to CO2 not in a single, high energy releasing reaction but controlled oxidations -electrons removed during oxidation of biological fuels are transferred to coenzyme specialized for carrying the electrons -conezymes include -NAD, NADP, FAD, & FMN which is reduced to NADH, NAPH, FADH2, FMNH2 respectively NAD & NADP act as co enzymes but FMN and FAD act as prosthetic groups

What kind of reactions do peroxisomes carry out ?

-biosynthetic -degradative -detoxification

Decribe Scruvy s/s

-bleeding gums -loosened/lost teeth, petechiae (pinpoint hemorrhages around hair follicles, gum & nails) ecchymoses poor wound healing joint & leg pain poor bone development anemia tired weak w an irritable melacholy general fatigue -weak connective tissue is apparent -linked to fruit or vitamins deficiencies longer than 20-30 days DEFICIENCY OF VITAMIN C (ASCORBIC ACID)

Describe mitochondria transcription

-both strands are entirely transcribed -one promoter for ea strand -Giant transcript are processed by RNA endonucleases to generate separate tRNAs, rRNAs, and mRNAs

Describe desmomsomes

-buttonlike intercellular connection - analogous to spot weld -anchor intermediate filaments (IFs) -strong, extensive junctions -resist shearing forces in epithelial cell layers -cell-cell interaction mediated by cadherins regulate - cell motility -proliferation & differentiation contact inhibition

What is the function of the mitochondria outer membrane ?

-cardiolipin synthesis -lipid modification -FA elogation - FA desaturation phospholipid synthesis monoamine oxidase

Describe Nuclear Import through NPC

-cargo protein with NLS 'zip code' binds importin protein out in cytoplasm -importin-cargo complex interacts with nucleosporins and translocates insides

Which of the following is true of the mitochondrial genome ?

-carries both coding and non coding genes -closed circular chromosome - carries only protein coding genes necessary for ETC and ATP synthesis -packaged by supercoiling -low proportion of non-coding DNA -Carriers none of the protein-coding genes necessary for mitochondrial gene expression

What are the important functions of cytoskeletal microtubules?

-cell division -organelle mov't -

metabolic regulation by hormones

-cells require constant supply of fuel to provide energy for ATP generation : -mobilized and maintained by hormones ensure that cells have a constant source of glucose, f.a., aa for ATP generation and for cellular maintenance glucose-universal fuel for all human cells. hormones maintain blood glucose levels near 80-100 mg/dl insulin and glucagon - 2 major hormones required to regulate carb, lipid, and aa metabolism in accordance w the needs and capacities of individual tissues

transition state analogues

-chemical compounds w a chemical structure that resembles the t.s of a substrate molecule in an enzyme catalysed chemical reaction -enzyme inhibitors which resembles the t.s structure would bind more tightly to the enzyme than the actual substrate e.g. PCN -beta lactasmase inhibitor

name 2 examples of positive feedback - destabilizes the system

-childbirth - voltage gated sodium current

Describe Mitochondrial DNA (mtDNA)

-circular double stranded DNA -multiple copies per mitochondrion -usually > 1000 copies per cell ~ 16,569 per genome - devoid of histones, not packaged into chromatin -inherited maternally

Describe botulinum toxin ?

-cleaves v-SNARE from the motor neuron at the neuromuscular junction botulium toxin blocks release of acetylcholine, stopping muscle contraction

Describe pinocytosis "cell drinking"

-constitutive in all cells -extracellular fluid ingestion in endocytic 'pinosomes' -signals stimulate actin to remodel cytoskeleton -small protrusions close, endocytic vesicle carried along microtubules to cell center -useful for bulk nutrient uptake (solutes & proteins) -important function of the cells lining the GI track

What is Botulism: Flaccid Paralysis

-foodborne -wound -infant =1 of the many causes of infant hypotonia ( hypotonia : decreased muscle tone) "floppy baby' -constipation -loss of head control -hypotonia & hyporeflexia -respiratory difficulties Treatment : antitoxin / supportive ( for months )

Why do adhesive contacts?

-for motility or stability

Describe the cadherins in the adherens junction

-form continuous adhesion belt ( zonula adheren) in epithelia just below tight junctions cadherins bind to ACTIN cytoskeleton via catenins

ion channels

-gating mechanism -membrane potential -specific ligans -mechanical distortion

Explain Kearns-Sayre syndrome (KSS)

-giant deletion in the mtDNA -w/o bone marrow involvement - late onset -mtDNA with deletions in muscle, not in blood -typical ragged red fibers, (contain > 80 % mutated mtDNA) -progressive external opthalmoplegia, retinopathy, cerebellar ataxia, heart block -reduced, variable life expectancy s/s b/l ptosis myopathic facies hearing aid

Explain Pearson Syndrome

-giant deletion in the mtDNA -with bone marrow involvement -pediatric diseases -move severe than KSS - pancytopenia, all tissues have mtDNA with deletions -sideroblastic anemia, exocrie pancreatic failure -death usually before 4 years -some Pearson syndrome patients that survive undergo phenotype switching to Kearns-Sayre syndrome

coordinated secretion of insulin and glucagon : high carb meal

-highest levels of insulin secretion occur approx. 30-45 minutes after a high carb meal -lowest levels of glucagon occur after a high carb meal

Describe the inner membrane of the mitochondria ?

-impermeable to most molecules -cristae (increase S.A.) -hold electron transport chain (ETC) including ATP synthase

What does Connexin 26 cause

-in cells of the cochlea -> deafness

Inhibitors of protein complex:

-inhibitors of electron transport selectively inhibits individual complexes interrupting the flow of electron through respiratory chain stops proton pumping, ATP synthesis and oxygen uptake

what is the role of insulin in metabolism

-insulin is the major anabolic hormone that promotes the storage of nutrients -insulin promotes the use of glucose as a fuel by facilitating its transport into muscle & adipose tissue liver: glycogen synthesis f.a. and tg synthesis protein synthesis adipocytes fa and TG synthesis skeletal muscle protein synthesis glycogen synthesis

co-ordinated secretion of insulin and glucogon : high protein meal

-insulin level do not increase nearly as much as they do after a high carb meal -aa stimulate glucagon release more than insulin release-stimulates glucogenesis if blood glucose drops

Describe anchoring junction : focal adhesion

-integrin binding to ligand in ECM -> cytoplasmic tail binds to anchor proteins actin binding clusters the integrins giving tigher binding to ECM proteins -> formation of focal adhesions focal adhesions are uses as " feet" in migrating cells -used for motility

the extracellular fluid is divided into two parts, what are they ?

-interstial fluid -plasma

Which way do most of the carbs on the plasma membrane glycoproteins face ?

-inward except in lipid rafts -outward

Patho classification of lactic acidosis : hypoxic

-ischemia -shock, severe anemia, cardiac arrest -global hypoxia -carbon monoxide poisoning -respiratory failure -severe asthma, COPD, asphyxia -regional hypoperfusion limb or mesentric ischemia

How are secondary lysosomes made?

-late endosomes fuse with lysosome to deliver material and enzymes to produce a secondary lysosome or can instead reenter the sorting system by fusing with another late endosome late endosomes can also mature into a secondary lusosome via golgi supplementation and progressive acidification

Describe lipid rafts

-less fluid -endo/exocytosis (transport) -protein/cholesterol rich

What is Chediak-Higashi syndrome clinical presentation ?

-light skinned young child with silvery hair - eyes are very sensitive to sunlight - already has experiences many recurring life threatening infections involving mucosa -neutropenia and bruising develop over time -coagulation defects develop over time -may develop neuropathy and ataxia (varying neuro problems) -granular defects in NK cells and platelets observed

What is Tetanus (spastic paralysis)?

-linked to clostridium tetani- neurotoxin generally intro. via wound contamination 1st s/s ; trismus (lockjaw) -neck stiffness -dysphagia -pectoral & calf muscle rigidity Spatula test results in a bite instead of a gag reflex -> have tetanus Tx: surgical debridement, metronidazole ( decrease bac numbers ) -anti-tatanospasmin (diazepam, immunization) severe: trach & mech vent Tx:

Describe the proteoglycan (PG) Structure

-linker sugar groups covalently attach GAG to core protein -can form very large complexes when central PG proteins associate w a hyaluronan molecule to form aggregates

Structure of Animal cell membrane

-lipid bilayer with associated proteins (phospholipid bilayer) - intergral membrane protein -peripheral membrane protein -Glycolipid ( phospholipid modified-carry sugar chain) -carbo (" twig looking) -dynamic fluid like structure -inner leaflet faces cytoplasm

Describe the structure of the microtubules

-straight, hollow tubules, 25 nm diameter tubulin dimers: alpha and beta tubulin linear arrangements gives a protofilament x13 profilamanets around a central point form tubule alpha and beta tubulin dimers polmerise end to end : alpha subunit (NEGATIVE end) contacts beta subunit (POSITIVE end) of next dimer -> POLAR TUBULES

Describe metabolic homeostasis

-living cells require a constant source of fuels to derive ATP for the maintanance of normal cell function and growth -therefore, a balance must be achieved among carb, fat, and protein intake. their rates of oxidationm and their rates of storage when they are present in excess of immediate need -alternatively, when the demand for these substrates increasesm the rate of mobilization from storage site and the rate of their de novo synthesis also required balanced regulation control of balance fuel availability and tissue need -blood level of nutrient -hormone level -nerve impulse

Ca 2+ ATPase ( primary active transport)

-located in cell membrane and cellular organelles (SR, mitochondria) -pumps Ca 2+ to outside of cell or into cellular organelles to maintain low intracellular Ca2+ 1. the transport protein binds bothe ATP &Ca2+ 2. Energy from ATP changes the shape of the transport protein moves the ion across the membrane 3. the protein releases the ion and the remmants of ATP (ADP AND P) and closes Na-Ca and exchanger and Ca2+ pumps in the plasma mebrane bith extrude Ca 2+ from the cell Ca2+ pump sequesters Ca 2+ w/n the SR CA 2+ bound in the SR by calreticulin and calsequestrin

Where are the 3 final places the trans Golgi network sorts into?

-lysosome -plasma membrane -secretory vesicle

s/s of familial hypercholesterolemia

-major rish for CHD; premature atheroslerosis -xanthomata (fatty deposits) -corneal arcus -xanthelesmata

How does a plasma membrane look like under a TEM ?

-membranes appear trilaminar -Polar head groups attract osmium stain-become dark; center lipid tail section remains clear

What is mitochondrial replacement therapy and 3 parent babies ?

-methodologies to allow mother w mtDNA disease to have unaffected children -the nuclear genome of an affected zygote (from the mother) is transferred to another zygote from an unaffected donor -it can be transferred either as pronucleus or metaphase II spindle

Describe double reciprocal plot

-michalis menten equation can be algerbarically transformed into versions that r useful in the pratical determination of Km and Vmax and analysis of inihibitor action this way of writing the michaleis mentin equation emphaszies the linear relationship of 1/S w 1/V0 line waver burk double reciprocal plot : 1/V0 and 1/s -> u get a straight line graph advantage -allowing a more accurate determination of Vmax, which can only be approxiated from a simple plot of V0 vs S

Describe ragged red muscle fibers

-mitochondria stained red -large numbers of mitochondria -aggregation of mitochondria at plasma membrane give ragged appearance

Which of the following is true about PEO ?

-mitochondrial inheritance caused by giant deletions in the mtDNA AD inheritance caused by mutation in POLG or TWNK Adult onset b/l ptosis ragged- red muscle fibers

Describe the structure of the nuclear envelope ? (Lamina)

-mitosis: breakdown and reformation -prophase Lamin phosphorylated by CdK1 -NE breakdown -> release of Lamina A/C and Lamina B

NaK ATPase

-most abundant pump in higher organisms -heterodimer of an alpha subunit of 100, 000 MW and beta subunit of 55, 000 MW pumps 3 Na out of the for every 2 K pump into the cell

What is Hurler syndrome?

-most severe mucopolysaccharidosis (MPS IH) - deficiency of alpha-L-idouronidase -accumulation of dermatan sulphate & heparan sulpahate -initially normal growth but problems begin at a few months old

Why are mitochondrial DNA highly variable ?

-mtDNA has more variation than nuclear DNA variation consist mainly of SNPS & small deletions or insertions - accumulation of mutations occurs 10 fold faster compared to nuclear DNA -oxygen radicals formed as by-product of the ETC and oxidative phosphorylation are the likely cause of the high mutation rate of mtDNA -mtDNA does not undergo recombination & it follows uniparental inheritance * polymorphism are stably passed from mother to offspring over many generations -mitochondrial haplotypes are used to track maternal lineage

the pyruvate dehydrogenase complex PDH is the gateway btw glycolysis and the citric acid cycle

-multi enzyme complex 3 -inner mitochondrial membrane -irr. reaction -co enzyme -5 -converts pyruvate -> acetyl coA major regulatory point for metabolism

What are iso-enzymes

-multiple forms of the same enzyme catalyzing the same reaction -they differ in their physical and chemical properties -synthesized from different genes -an enzyme may be activate as monomer or oligomer -molecular heterogenity of enzyme may be produced after post translational modification

What is Progressive External Ophtalmoplegia (PEO)?

-multiple genes involved locus heterogeneity -involving nuclear and mitochondrial genes -AD Mutations in : POLG, encoding DNA polymerase gama TWNK, encoding the helicase Twinkle Also can have mitochondrial inheritance -mtDNA depletion or large deletions in the mtDNA

What is dystrophic epidemolysis bullosa ?

-mutation in collagen VII: absence of anchoring fibrils AR or AD * recessive form more severe -can be most severe and debiliating of these blistering disorders -down deep; skin falls off -causes syndactyl & scarring -relatively mild presentation is possible mucosa becomes involved in severe forms " the boy who skin fell off"

What is epidermolytic plantopalmar keratoderma ?

-mutation in keratin 9 (only expressed in palms and soles) - many different types of inheritance & acquired forms have all been observed

Overview of Mitochondria

-near sites of high ATP requirement -number/cell varies in diff tissues (1-several thousand) -numbers and energy producing increase with need via TCA & ETC

anaerobic glycolysis

-net energy gain during anaerobuc glycolysis is only 2 ATPs -NADH produced during anaerobic glycolysis is utilized during lactate dehydrogenase step

What is the nuclear lamina?

-network of proteins including lamin intermediate filaments that coat the inside of the inner nuclear membrane -high-tensile proteins, maintain nuclear shape and protect membranes -completely lines inner surface of nuclear envelope maintain structure and stability : attaches to integral membrane proteins & NPCs, protects DNA -Anchorage sites for chromosomes attach chromatin to inner membrane act as transcription regulator (bind TFs) -interact with inner membrane proteins breakdown & reformation of nuclear envelope during mitosis

Describe the filamin patho

-neural migragation patient w periventricular heteroptia caused by mutation in the filamin A gene

Describe RBC membrane and proteins

-no nucleus/organelles -is the only the remnant of a cell

What is Hutchinson-Gilford progeria syndrome?

-normal at birth and early infancy 18-24 months failure to thrive prominent eye, alopecia, lose subcutaneous fat, aged looking skin, joint stiffnessm arteriosclerosis at age 5 life expetancy 13 years old . Death from MI or CHF accelerated aging in children 1/4 million AD-sporadic

Describe the nuclear pore complex ( NPC)

-nucleoporins: glycoproteins if the NPC -cytoplasmic ring made of protein subunits Luminal ring: transmembrane proteins-connect to nucleoporins forming channel nuclear ring: formed into a "basket"

glycolysis in erythrocytes : rapport leubering cycle

-occurs in RBCs when they are delivering oxygen to tissues net ATP production during production of 2,3, BPG in RBCs=0 ATP -increase in 2,3 BPG shifts the oxygen dissociation curve to the right

Where are glycolipids located ? What is there role ?

-on surface of plasma membrane -only on outer leaflet (preferentially within lipid rafts) Role: -cell-cell recognition -protection (exposed apical surface of epithelial cells) -nerve conduction

What is the clinical presentation of Leigh Syndrome ?

-onset in first year - 50 % die by age 3 - progressive neuro, respiratory and cardiac degeneration (elevated lactic acid, hypotonia, spasticity, movement disorder, cerebellar ataxia, and peripheral neurophathy)

decribe the co2/bicarbonate buffer system

-open system which remains in eq w atmospheric air -most important buffer in plasma - max buffering capacity -metabolic CO2 -enters plasma - and equilibrates in plasma w H2CO3 non enzymatically amount of dissolved CO2= solubility co-effcient of co2 (0.03 at 1mm Hg) -partial pressure of carbon dioxide 40 mmHG -hence total concentration of dissolved co2 = 40 * 0.03 = 1.2 mmol/L At conc of 1.2 mmol/L of CO2 -HCO3 concentration is arounf 24 mmol/L pKa of bicarbonate buffer =6.1

What is nuclear lamina: internal scaffold ?

-organizes RNA & DNA synthesis -Lamins A, B, C form an intricate meshwork Lamins bind proteins associated with heterochromatin Lamins bind to emerin and other inner membrane integral proteins

Describe the outer membrane of the mitochondria ?

-permeable to small molecules & ions (~5-10kDa) -biochemical reactions -primarily lipids

Describe gap junctions

-permits free passage of ions and small intracellular signaling molecules (Ca 2+, IP3) Conncect cytoplasms via 2 connexons that connect intracellular space

Regulation by covalent modification

-phosphorylated PDH is inactive -dephosphorylated PDH is active depends on energy status of the cells determined by levels of acetly coA, NADH, and ATP Calcium ion stimulates the phosphatase, activating PDH. this important in skeletal muscle where ca ion released during contraction stimulates energy production

You could be considered "The Angel of Death "

-poly-ubiquitination - the proteasome

Gibbs free energy

-predicts the direction of chemical reaction -tells about exact equilibrium position of a reaction -predicts the amount of work that can be performed at constant temperature and pressure -heterotrophic cells acquire free energy from nutrient molecules and transform this free energy into ATP and other energy rich compounds capable of providing energy for biological work at constant temperature -free energy of a biochemical process is the same regardless of path or mechanism used to attain the final stage

What is N-linked glycosylation?

-premade precursor oligosaccharide 14 sugars (N-acetylglucosamine, mannose, and glucose) assembled together and transferred to polypeptide by Dolichol pyrophosphate (membrane bound lipid) -Oligosaccharide transferred to NH2 group of asparagine = "N-linked" .co-translational addition .immature 'precursor oligosaccharide' will be lightly trimmed before the protein can leave the RER

Describe a Lysosomes

-principal sites of intracellular digestion -filled with potentially dangerous soluble hydrolytic enzymes; acid hydrolases (-40 different enzymes) -proteases, nucleases, lipases, phospholipsaes, phosphatases, sulfatases - requiere acidic enviroment: pH 4.5-5.0 "garbage collecters /recycle center" Has a lipid bilayer & membrane transport protein & hydrolytic enzymes

Describe an overview of the Golgi Apparatus

-processing/maturation -packaging -transport

What are the roles of hyaluronan?

-produced during wound healing -created a cell-free space into which cell can migrate -main lubricant of joint fluid ( binds losts of H2O) -resist compressive forces in tissues and joints -forms backbone for large proteoglycan complexes AGGRECAN

What is Charcot-Marie Tooth Neuropathy

-progressive degeneration of peripheral nerves -muscle weakness -atrophy, i-mpairment of deep tendon reflexes - x-linked peripjeral neuropathy (sensory & motor) - most common inherited peripheral neuropathy in humans w a prevalance of 1/2500, s/s weakness atrophy of distal muscles depressed or absent deep tendon reflexes mild sensory loss -> progressive degeneration of the muscle of the foot, lower leg, hand and forearm not life threatening there are no good treatments for CMT custom made shoes and braces can minimize discomfort

Describe the nucleolus

-prominent subnuclear structure -makes the components of the ribosomal subunits -synthesis of of rRNA and assembly of ribosome units processing of rRNAs ( by snoRNP) and their assembly with ribosomal protein -size of nucleolus reflects number of ribosomes produced: reflects the level of protein production

Describe the nucleus

-protection -replication -separate ribosomes -regulation of transcription

Describe diabetic neuropathy

-proteinuria -progressive renal failure DM : most common cause of kidney failure in world & #1 indication for dialysis - glomerular basement membrane dysfunction

In exocytosis, what are 3 things that will happen inside the vesicles?

-proteolysis proinsulin -> insulin -concentration -release constitutive vesicle -> secretion regulated vesicle -> extracellular signal -> secretion

What is the role of cholesterol in the plasma membrane

-provides the plasma membrane stability

Phagocytosis by neutrophils and macrophages : oxygen dependent killing

-respiratory burst -> NADPH Oxidase myeloperoxidase system -> myeloperoxidase

function of Na/K ATPase

-responsible for maintiaint low Na and high K conc. in the cell -control cell vl - plays a role in resting membrane potentioal (RMP) by maintaining the asymmetric distrubution of Na + and K + across the cell membrane -contributes to RMP by about -4mV ( electrogenic)

Describe tight junction / zonula occludens

-secretory/absortptive eputhelium ( gut lumen) -form barrier for most solutes -completely encircle apical end of each cell to block off opening between them -transmembrane adhesion proteins have extracellular domains that join directly to each other - have intracellular domains that bind to adaptor proteins associated w cytoskeletal actin

Overview of the RER

-single lipid bilayer -oriented stacks of long flattened cisternae, studded on cytoplasmic side of with ribosomes

What is the clinical presentation of I cell disease ?

-skeletal abnormalities (lack of growth) -course features -restricted joint movement -pyschomotor retardation -enlarged liver, spleen, heart valves -death from CHF/RTI -life expentancy <10 yrs

The mitochondrial threshold hypothesis explains why ...

-some individuals with mutant mtDNA are affected while others are not -some individuals with mutant mtDNA are severely affected while others are mildly affected

Describe electrical coupling

-some nerve cells-rapid spread of action potentials sync contractions 9 transfer of ca 2+ btw adjacent cells) -coordinated depolarization of cardiac muscle -coordinated contractile waves in smooth muscle cells -intestine (perstalsis) -uterus (during birth)

What is the fibronectin functions

-stabilizes cell adhesions to ECM (via integrins) -cause cells to assume their normal shape & grow in the right direction ( algins cytoskeleton w fibronectin fibrils ) cell migration in embryogenesis wound healing: major role in tissue remodeling soluble fibronectin form : important in blood coagulation

relation btw standard free energy change and equlibrium constant

-standard dree energy change is directly related to the eq constant - the standart free energy change tells us in which direction and how far a given reaction must go to reach eq. when the initial conc. of each component is 1 M, the pH is 7, the temp. is 25 C, and the pressure is 1 atm thus delta G 0 prime is a constant it has characteristic , unchanging value for a given reaction

What happens in cytoplasmic translation ?

-standard genetic code -the initiator AA is methionine -more tRNAS

secondary active transport

-stored energy used from maintaing ionic gradients to fuel uphill transport of another solute 1. na binds 2 solute binds 3. translocation 4. na released 5. solute released

What is hereditary spherocytosis?

-strange RBCs, opaque & spheroidal, rigid with decrease deformability -sequestration and destruction by spleen : Hemolytic anemia -hemolytic anemia is the only anemia with splenomegaly -jaudince -gall stone stones (hyperbilirubinemia) AD inheritance -RBC cytoskeletal membrane defect nonfunctional skeletal membrane protein: spectrin, ankyrin or protein 4.1 -often spectrin deficiency -unstable membrane, loses fragments -unstable in the osmatic fragility test

Describe hemiadesmosomes and linking cells to ECM

-strongest anchor btw cell and ECM -basal surface epithelial cell and basement membrane- NONMOTILE Intracellular intermdiate filaments (keratin) are embedded into plaques Specific intefrin (apha/beta) link the intracellular plaques to ECM laminin Anchored by collagen VII fibrils in ECM ( anchors dermal epidermal junction; binds basal lamina to underlying connective tissue)

Describe microtubules function

-structural component Resist compression "support beams" =most rigid of the filaments Organize ER and Golgi apparatus "railroad" connecting -trans golgi network to cell surface -early endosomes to lat endosomes and lysosome compartments -intracellular transport (organelles, vesicles) -form spindle apparatus in mitotic cells -Act as motile elements in cilia and flagella

Describe the microtubule

-structure : hollow tubes; wall consist of 13 columns of tubulin molecules diameter : 25 nm with 15nm lumen protein subunits : tubulin, consisting of alpha tubulin & beta tubulin main functions : maintenance of cell shape (compression-resisting "girders") cell motility ( as cilia or flagella) chromosome movement in cell division organelle movements

Effect of increase in substrate concentration

-studying the effects of substrate concentration is affected by product formation -better to analyze intial velocities of the reaction V0-determined from slope of the progress curve at the beginning of the reaction -the graph represent initial velocities of the enzyme w different substrate concentration -V0 is differnt for different substrate concentrations

Ubiquinone (Co-Q)

-synthesized from cholesterol pathway by diverting isoprenoid intermediates into Co-Q production Statins- group of drugs which drecrease cholesterol synthesis by inhibiting HMG co A reductase enzyme adverse effect: decreased co-q synthesis-decreased ATP production -> myopathay, lactic acidosis

What reactions is carried out by peroxisome ?

-synthesizes bile acids - break peroxide down to water -synthesizes cholesterol and dolichol - oxidizes very long chain fatty acids -synthesizes plasmalogens -catabolizes purines

other phosphorylated compounds and thio-esters classified based on free energy of hydrolysis

-the phosphate compounds can be divided into 2 groups -high energy compounds -molecules havinf above ATP's free energy -low energy componds-molecules having energy below ATP's free energy

what are the s/s of heat stroke

-throbbing headache -no sweating -red, hot, dry skin n/v rapid strong pulse may lose consciousness

Membrane Proteins Functions

-transport (nutrients, metabolites, ions across bilayer) -anchor membrane to macromolecules to either side -receptors : receive external signals and transmit -enzymes (lactase in the apical membrane of GI epithelial cells -cell identity markers : such as MHC

Describe the mitochondria structure

-typically 1-3 microns long & 0.3 mircrons wide -double membrane enclosed structure (outer membrane & inner membrane) - intermembrane space -matrix -cristae : infolding fingers from inner membrane

What is Hunter's Syndrome ?

-x-linked -accumulation : heparan & dermatran sulfate enzyme def. iduronadate sulphate s/s NO CORNEAL CLOUDING

What is Barth syndrome ?

-x-linked cardioskeletal myopathy with neutropenia -mitochondrial disruption and dysfunction results in : -cardiomyopathy -generalized muscle weakness and chronic fatigue -neutropenia -sperm cell defects high mortality in infancy -sudden infant death -infection -cardiac failure

Is the plasma membrane asymmetrical ? If so, describe ?

-yes, extracellular (outer) leaflet : glycolipids -cytoplasmic inner leaflet : phosphatidylserine, carries a negative charge

What is Ca in the ICF

0.0001 mEq/L

Key points for desmosomes

1. IFs link to cytoplasmic plaques 2. plaques connected via cadherins 3. plaques contain intracellular anchor proteins that link to cellular itermediate filaments

five different dialysis bags, which are permeable to water but impermeable to glucose, are filled with 5 different glucose solutions, the bags are placed in different beakers containing a 0.5 M glucose solution for 80 minutes, and the mass of each bag is measure at regular intervals. the results are recorded on the graph. which lines on the graph represent the bags that had an initial glucose conc. higher than 0.5 M?

1 & 2

Describe the adherens junctions

1 type of anchoring junctions mechanically attach cells and their cytoskeleton (actin filaments) form continuous adhesion belt/ zonula adherens

Properties of Glut 1

1-2 mM (Km) Human erythrocyte BBB Blood retinal barrier blood placenta barrier blood testis barrier expressed in cell types w barrier functions, a high affinity glucose transport system

enzyme catalyzed reaction

1-3 substrates are oriented in the active site relation to ea. other in such a way that they take on the optimal orientation for the formation of the transition state 3. binding of the substrate results in removal of their hydration shells 4. stabilization of the transition state as a result of interaction btw the aa residues of the enzymes and the substrate-lowers activation energy 5-6 formation of products C and D

In the ECM the macromolecules are arranges into 2 general organizations :

1-interstial matrix : in spaces btw epithelial, endothelial, and muscle cell & the main component of connective tissue 2- basal lamina underlies and supports epithelia

When describing the process of protein synthesis in the RER, place the following in the correct order?

1. Signal recognition particle binds to ER signal sequence 2. SRP complex brings the ribosome to translocon 3. BiP binds peptide 4. N-linked glycosylation

What are the 4 phases of phagocytosis ?

1. Attachement: Phagocyte receptors bind to opsonins 2 Engulfment : receptor binding to foreign particles intiates actin filament assembly -> phagocytic cup around foreigner membreanes fuses together -> formation of phagosome 3. fusion with lysosome -> phagolysosome -microtubule motors direct phagosome to lysosome -fusion (via Rab, SNAREs, SNAP/NSF) 4. Digestion of ingested microbe/particle -acidic lysosomal hydrolases degraded ingested material -formation of residual body (indigestible material): accumulation of lipofucin or excreted from cell

What are the two main functions of peroxisome ?

1. Biosynthethic - Plasmalogen synthesis : ether type phospholipids -bile acid synthesis ( derived from cholesterol; occurs mainly in liver ) -lipid biosynthesis : cholesterol & dolichol ( both are also made by SER) 2. Degradative -very long chain fatty acids (VLCFA) beta oxidation * purine catabolism (xanthine oxidase) *breaks down H2O2 to water

When describing the formation of COP coated vesicles, what is the general sequence of events?

1. Cargo receptos bind "cargo proteins" and concretrate in membrane 2. Bound cargo proteins- receptors bind to coat protein 3. Vesicle buds out and pinches off from membrane 4. Coat proteins fall off, exposing SNARE

Flow of electrons to ubiquinon (Co-Q)

1. Complex 1 ( from NADH) 2. Complex 2 (from Succinate to FADH2) 3. Glycerol 3-po4 dehydrogenase 4. fatty acyl co-A dehydrogenase

Mechanism of production of reactive oxygen species :

1. Con enzyme Q -electron transport chain 2. Cytochrome P450 system 3. xanthine oxidase 4. ionizing radiations- xrays, gamma rays 5. NADPH oxidase -respiratory burst 6. mano amino oxidsae 7. peroxisomal fatty acid oxidation 8. smoking

describe insulin synthesis

1. insulin synthesised as preproinsulin in b-cell of endrocrine pancreas 2. pre-removed in RER prior to folding an S-S bridge formation 3. transported to Golgi -protease removes C-peptide 4. transported as storage vesicles into cytosol (contains insulin +C +peptide + zinc)

What are 3 types of mutations that can occur in the mtDNA?

1. Deletions or duplications 2. Point mutations in tRNA impair mitochondrial protein synthesis 3. Missense mutations in the coding regions -impair activity of complexes of oxidative phosphorylation

What are the 3 pathways to degradation in lysosomes ?

1. Endocytosis ( endocytosed heparan sulfate from the ECM) 2. Phagocytosis ( engulfed bac) 3. Autophagy (aged organelles ) MISFOLDED PROTEINS --> PROTEOSOME !

What are the 3 things wrong in Zellweger syndrome ?

1. Failure to import peroxisomal enzymes * membrane does not recognize the localization AA signal used to import peroxisomal proteins * PEROXISOME DEFIENCY * VLCFA accumulates in blood & tissue 2. LACK OF PLASMALOGEN * accumulation of VLFA in glial cell membrane ( no beta oxidation) -abnormal brain development -neuronal migration defects hypomyelination (due to LACK OF PLASMALOGEN) * accumulation of VLCFA in liver -> hepatomegaly and liver failure 3. No Bile acids : decrease fat absorption -> decrease ATP -> muscle weakness

Which of these is a function of the RER and not of the Golgi ?

1. Fastening a GPI anchor to a protein 2. Forming the disulfide bonds required within a protein 3. N-glycosylation of proteins 4. Enforced folding of polypeptide chains

Describe the Collagen Families

1. Fibrillar Type I, II, III, V 2. Fibrillar - Associate Collagen w Interrupted Triple Helices ( FACIT) aka connecting collagens VI, IX, XII 3. Sheet ( network)-forming collagen IV, X 4. Anchoring fibrils : VII

fate of glucose in liver

1. GLUT 2 2. Glucokinase 3. PPP 4. Aerobic glycolysis 5. glucineogenesis 6. PDH reaction 7. TCA 8. Glycogen synthesis 9. glycogenolysis

What diseases are associated with mutations in the mitochondrial protein-coding genes?

1. LHON 2. NARP 3. Leigh Syndrome 4. MILS

When describing formation of the clathrin coated vesicles carrying lysosomal enzymes out to the endosomes and lysomes, what is the sequence of events?

1. M6P receptors bind M6P tagged glycoproteins within the lumen of the Golgi 2. Adaptins link occupied receptors to Clathrin coat proteins 3. Vesicles pinched off parent membrane (by dymanin GTPase) 4. Coat proteins disassemble, exposing Rab-GTP & v-SNARE

What 2 diseases are associated with mutation in the mitochondrial tRNA genes?

1. MELAS 2. MERRF

When describing how cargo bound membrane receptors become incorparated into endocytotic clathrin-coated vesicles, what is correct sequence of events ?

1. Occupied receptors recruit adaptins & clusters 2. Clathrin assembly produces a membrane invagination 3. Vesicle budding proceeds through action of Dynamin GTPase 4. Ucoating of clathrin and adaptins

How is total body water distributed ?

1. intracellular 2. extracellular fluid

iron deficiency anemia

1. lethargy, tiredness, sob, dizzy, ha, cold hands/feet, pale skin, cp. and palpitations 2. decreased heme production decreased hb in RBC-decreased o2 delivery decreased cytochromes-decreased ATP production

what are the 3 treatment for hyponatremia

1. Osmotherapy treatment meant to draw water out of the brain by improving blood flow in the brain as well as reduce swelling and raised intracranial pressure in the skull. infusion rate depends on cause of hyponatremia, severity of hyponatremia, and whether it is acute or chronic acute hyponatremia (developed in <6 H) -slow IV infusion of 3% saline ( 50 ml bolus -hypertonic saline) -d/c drugs that may be causing hyponatremia -monitor serum na levels hrly chronic hyponatremia ( developed > 6 hrs) -slow iv infusion of 3% saline ( 100 ml bolus-hypertonic saline- may need to repeat) -look for intracranial patho ( brain injury, hemorrhage, neoplasm) -monitor serum Na level hourly -if severe hyponatremia ( < 120 mEq/L)- infusion of 3 % saline at 15 to 30 ml/hr plus iv furosemide (diuretic) 2x daily

Key features of TCA cycle

1. Oxaloacetate - first intermediate in TCA cycle (4C) -Required for gluconeogenesis 2. Citrate - source for f.a. synthesis (-) glycolysis at PFK1 (+) f.a. synthesis at ACC 3. Isocitrate dehydrogenase -chief regulatory enzyme of TCA cycle -mitochondrial isoform - produces NADH -cytosolic -produces NADPH 4. Alpha ketoglutarate dehydrogenase -multienzyme complex similiar to PDH -requires all the 5 co-enzymes 5. succinate thiokinase -all tissues- produces ATP -Gluconeogenix tissues-produces GTP -only example for substrate level phosphorylation in mitochondria and TCA 6. Succinyl Co-A used for Heme synthesis helps in utliization of ketone bodies

What are the 3 diseases associated with giant deletions in the mtDNA ?

1. PEO -same phenotypes as the autosomal PEOS 2. Kearns-Sayre syndrome (KSS) 3. Peasrson syndrome

Describe the 3 types of endocytosis

1. Pinocytosis 2. Phagocytosis -phagolysomes -ph 3. Receptor mediated -clatherin : accumulation before entry -calveolin: transcytosis (maternal IgG)

What are the 3 main endocytic mechanism ?

1. Pinocytosis : cell- drinking ( fluid & solutes) 2. Phagocytosis : cell-eating ( food, development, defense) 3. Receptor-mediated endocytosis -Clathrin- coated pits -caveolin-coated caveolae

In both constitutive and regulated secretions, what are the 3 main things that occur:

1. Proteolysis of vesicle contents by resident protease enzymes proalbumin-> albumin proinsulin -> insulin the precursor (pro) AA segment is cut off allowing caro to assume final form (the 'pre' signal AA sequence was cut off back in the RER 2. Concentration of contents (with zinc ion & pH change) 3. Release of cargo - & recycling of transport proteins from endosomes back to Golgi

Describe the process of receptor-mediated endocytosis

1. Receptor proteins accumulate in lipid rafts 2. Receptor-ligand complexes concentrated into coated pits by interaction with adaptins 3. Adaptin binding to clathrin triggers assmebly of clathrin lattice 4. Lattice causes clathrin coated pits to form 5. Clathrin -coated vesicles bud off to travel to the endosome

Describe receptor mediated endocytosis ?

1. Receptor proteins accumulate in lipid rafts 2. receptor ligand complexes concentrated in coated pits by interaction with adaptins 3. Adaptin biding to clathrin triggers assembly to clarthrin lattice 4. Lattice causes clathrin coated pits to form 5. clathrin coated vesicles bud off to travel to the endosomes

Describe the cellular secretory pathway?

1. Secreted proteins enter ER as they are being synthesized by ribosome 2. protein exits ER into vesicle 3. protein travels through the cisternae of the golgi apparatus 4. protein enters a secretory vesicle that fuse with cell membrane 5. protein is secreted from cell

Cellular defense against free radicals

1. antioxidant scavenging enzymes 2. non enzymatic antooxidants 3. cellular compartmentalization 4. sequestration 5. repair of damages cellular components

Phagocytosis

1. cell receptors recognize surface molecule on bacterium 2. acctin removed from phagosome 3. phagosome maturation - binding activates receptors that trigger actin assembly 4. degradation phagolysosome primary lysosome secondary lysosome

How does phagocytosis involve lysosomes ?

1. chemotaxis and adherence of microbe to phagocyte 2. ingestion of microbe by phagocyte 3. formation of phagosome 4. fusion of the phagosome with a lysosome to form a phagolysosome 5. digestion of ingested microbe by enzymes other dying cells/large extracellular material/debris

How is the citric acid cycle regulated?

1. citrate synthase 2. iso citrate dehydrogenase 3. alpha ketoglutarate dehydrogenase

phsophorylation and dephosphorylation

1. controlled processes -all or none events that either switch on or switch off sets of opposing metabolic pathways 2. depending upon the time with the fed -fasting cycle 3. all target proteins will be phosphorylated by protein kinases or 4. all target proteins wull be dephosphorylated by phosphoprotein phosphatases 5. the counter regulatory hormones (glucagon and insulin) thus control most of intermediary metabolism

Regulation of electron transport chain

1. efficiency of electron transport chain - 70- 80 efficient 2. remaining energy -lost as heat (major contributor to body temp) 3. activity of ETC - amount of ADP and oxygen availability -ADP stimulates respiration and ATP synthesis 4. regulation by T3/T4 stimulates synthesis of uncoupling proteins

Defining components of oxidative phosphorylation

1. electrons flow from electron donors (oxidizable substrates) through a chain of membrane bound carriers to a final electron acceptor w a large reduction potential (molecular oxygen, o2) 2. The free energy made avaialble by this "downhill" (exergonic) electron flow is coupled to the "uphill" transport of protons across a proton-impermeable membrane, conserving the free energy of fuel oxidation as a transmembrane electrochemical potential 3. the transmembrane flow of protons back down their concentration gradient through specific protein channels provides the free energy for synthesis of ATP, catalyzed by a membrane protein complex (ATP synthase) that couples proton flow to phosphorylation of ADP

Which of the following is degraded inside the lysosome ?

1. engulfed bacteria 2. aged organelles 3. endocytosed heparan sulfate from the ECM

Bicarbonate/CO2 Buffer System

1. eq during low pH or high h+ (right to left) 2. eq during high pH or low h+ ( left to right) CO2 if too much-> blown off by lungs HCO3 if too much -> excreted by kidneys

insulin release from b-cells

1. glucose enters cell -> glycolysis, TCA cycle and oxidative phosphorylation -> increase ATP 2. the high ATP :ADP ration closes ATP dependent K channel 3. the plasma membrane depolarizes 4. voltage gated ca+ channels open 5. high ca + promotes fusion of exocytotic vesicles with mebrane and insulin is secreted

Describe the negative feedback control of blood glucose levels high blood sugar

1. homeostasis blood glucose level (90 mg/100 ml) 2. stimulus blood glucose level rises 3. beta cells of pancreas release insulin into the blood 4. body cells take up more glucose/ liver takes up glucose and stores it as glycogen 5. blood glucose level declines

What are the three destinations for vesicles that bud off the Golgi ?

1. if have a mannose 6 phosphate (M6P) tag 2. regulated secretory pathway (include synaptic vesicles) - proteins contain a signal that selectively groups the, into regulated vesicle 3. constitutive secretion =default pathway, non regulated polarized cells (most cells): proteins contain signals or features that direct them to either the apical or the basolateral membrane

Describe the endocytic pathway (from plasma membrane to lysosomes)

1. maturation of early endosomes containing endocytic vesicles to late endosomes occurs via " Multivesicular bodies (MVBs)" MVBs shed vesicles to recycle material back to plasma membrane -gradually convert into late endosomes by fusing with each other or with other late endosomes -Late endosomes become endolysosomes and lysosomes by : -fusing with preexisiting lysosomes -progressive acidification and golgi supplementation -proteins destined to join MVB get a mono-ubiqutin tag -invagination of the endosome/MVB - allows lysosomal lipases to completely chew up interior vesicle -transforms into a lysosome allows for downregulation of receptors

What are non-muscle actin functions ?

1. microvilli 2. stress fibers 3. cell surface protrusions ( lamelipodia & filipodia) and cell migration 4. cytokinesis

Steady state water balance

1. muscular activity promotes sweating 2. sweating causes loss of blood plasma, resulting in hemoconcentration and increased blood osmolarity 3. increased blood osmolarity stimulates osmoreceptors in the hypothalamus 4. the hypothalamus stimulates the posterior pituary gland 5. the posterior pitutary gland secretes ADH into the blood 6. ADH acts on the kidney, increasing the water permeability of the renal tubules and collecting ducts, leading to increased reabsorption of water 7. plasma volume increases so blood osmolarity decreases after exercise and water ingestion

What are the clinical significance of electron transport chain

1. non shivering thermogenesis 2. hypoxia or anoxia -lactic acidosis 3. apotosis -cytochrome C 4. ubiquione or co enzyme Q-stains 5. production of free radical -electron escape 6. iron def. anemia- decreased heme proteins 7. mitochondrial poisons/uncouplers

Digestion of Carbohydrates

1. oral cavity- alpha amylase breaks doen starch to alpha dextrins 2. inactivated by stomach HCl 3. Secretion of pancreatic amylase and bicarb into the lumen of small intestines 4. alpha dextrins-are converted into limit dextrins, maltotriose, and maltose, and isomaltose 5. brush border enzymes break dowb di-saccharides to mono-saccharides

What is the functions of electron transport chain

1. oxidize reducing equivalents NADH and FADH2 derived from glycolysis and TCA cycle 2. Generate electrical energy by passing electrons to oxygen 3. electrical energy creates a proton gradient across inner mitochondrial membrane 4. proton gradient drives phosphorylation of ADP to ATP

Carb consumed in diet

1. polysaccharides: starch, dextrins 2. disaccharides-lactose, sucrose, maltose, and trehalose 3. monosaccharides: glucose, fructose, galactose 4. fibers: non digestible carb (soluble/insoluble) provides satiety provides bulk of the stools decreases incidence of colon ca decrease flatuelence maintains stool transit time

what is the preparatory phase

1. preparatory phase phosphorylation of glucose and its conversion to glyceraldehyde 3-phospahte first priming reaction

Catalysis at the active site

1. proximity and orientation align the reactive chemical groups and make them close together in an optimal geometry 2. bond stain structural rearrangement that could strain bounds of substrate into a position closer to the conformation of the transition state 3. general acid base catalysis transferring a proton to or form another molecule in order to stabilize developing charges in the t.s 4. covalent catalysis (conezymes): transient covalent bond w a cofactor or w residues int he enzyme active site 5. metal ion catalysis -prosthetic groups

what are the fates of glucose 6 phosphate

1. pyruvate + ATP 2. Glycogen 3. glucose for export to blood 4. Ribose 5-phosphate + NADPH

What is the animal cell membrane functions?

1. receive information 2. import and export of molecules 3. capacity for movement and expansions -Governs intercellular interactions and response to external signals -cell signaling -cell adhesions ( pulls self along a matrix or substrate, change shape) -Scaffold for biochemical activity (ATP production)

Regulation of PDH enzyme

1. regulation by end product inhibition (allosteric)

tissue specific cellular responses to insulin

1. reverse glucagon stimulated phosphorylation (activates phosphatases and decreases c-AMP) 2. Induces (anabolic) and repress (catabolic) the synthesis of specific enzymes 3. insulin stimulates glucose (GLUT 4) and aa transport into cells 4. insulin acts as a growth factor and has a general stimulatory effect on protein synthesis

describe competive inhibitor

1. shape & structure of inhibitor is very similiar to substrate 2. inhibitor mimic substrate (or t.s ) and firs into the active site 3. physcially blocks substrates access into the active site 4. KM gets larger, more substrate is needed to reach a given rate can still, however, ultimately achieve Vmax

Review the three main routes from the Golgi

1. signal mediated diversion to lysosome 2. signal mediated diversion to secretory vesicles (for regulated secretion) 3. constitutive secretory pathway

Describe the homeostatic control systems

1. stimulus produces change in variable 2. changed detected by receptor 3, input: information set along afferent pathway to control center 4. output: information sent along efferent pathway to effector 5. response of effector feeds back to influence magnitude of stimulus and returns variable to homeostasis

What are the cytoskeletal functions ?

1. structure and support 2. intracellular transport 3. contractility and motility 4. spatial organization

Describe the properties of free radicals

1. super oxide : produced by Co-Q, Cyt P 450 and NADPH oxidase. helps in generating other ROS hydrogen peroxide not a free radical but can generate them by reaction with transition metals hydroxyl radical: most reactive species, produced by fenton reaction. it initiates chain reactions that form lipid peroxides and organic radicals hyocholorus acid : produced during respiratory burst to destroy invading organism through a process called halogenation nitric oxide: reactive nitrogen species, combines w oxygen or oxygen containing radicals to produce additional RNOS peroxynitrire : oxidizing agent which can generate NO2 free radical

What is the function of cell-cell junction

1. tight junctions 2. adjerens junctions 3. desmonsome 4. gap junction -provides stength, stabilility, integration to cells and tissues -regulate movement of solutes, ions, and water btw neighboring cystosolic comapartments, across epithelial layers -couple cells chemically and electriacally so as to convey info bet them or link function

Operation of Nak ATPase

1. transporter binds 3 Na+ from cytosol 2. phopshorylation by ATP favor conformational change 3. Na is released K binds 4. Dephosphorylation favors original conformation 5. K is released to cytosol.cycle can repeat 3 na out 2 k in

How do we app Hendersen Hasselbach equation

1. understanding the behavoir of physiological buffer and acid base disorders 2. determination of the ionic form of an amino acid at a given pH 3. understanding drug absorption in the body

GLUT 3

1.6 mM brain (neurons) major transporter in the central nervous system; a high affinity system

Describe the steps of phagocytosis ?

1.ATTACHMENT -phagocyte bindinf to opsonin molecules 2. ENGULFMENT : binding of receptors to foreign particles initiates actin filament assembly -> phagocytic cup around foreigner membrane fuse together -> formation of phagosome 3. FUSION with lysosome - phagolysosome -microtubule motors direct phagosome to lysosome -Fusion (Rab, SNAREs, SNAP/NSF 4. DIGESTION of ingested microbe/particle -lysosomes: acidic hydrolases degrade ingested

Name 6 lysosomal storage diseases ?

1.Hurler Syndrome 2. Hunter Syndrome 3. Tay Sachs Disease 4. I-cell Disease 5. Metacrhomatic Leukodystrophy 6. Chediak Higsahi syndrome

What is Spinal Muscular atrophy ?

1/40 are carriers of this disorder Types I-IV ( at birth(worst), infantile, adolescence, adult (less)) Sudden onset, rapid progression -muscle weakness & atrophy -hypotonia -dyspahgia & feeding difficulities respiratory problems

what is sodium levels intracellular

10 mEq/L

What happens to rbc when placed in solutins of varying tonicities ?

100 -200 mOs : hypotonic, cell swelling 300 mOs ( in blood serum): isotonic, no change in cell vl 400 -500 mOs: hypertonic, cell shrinkage 50% of healthy rbc will lyse placed in 150 mOsm hypotonic soln

how many nucleus does the skeletal muscle cells have?

100-1000s

How many proteins are necessary for the function of the mitochondria ?

1000 proteins

What is Cl- in the ECF (most abundant anion in ECF)

103 mEq/L

Of the approximately 1000 proteins that function in the mitochondria, how many are encoded by the mtDNA?

13 mtDNA 37 genes total - involved in the ETC and oxidative phosphorylation 13 protein coding genes only 22 tRNA genes -disperesed, flanking other genes 2 rRNA genes

How many proteins encode in the mitochondria DNA ? & what encodes the remainder proteins

13 are encoded by mitochondria DNA, the remainder are encoded by the nucleus. The vast majority of proteins that are important in the mitondria function come from nucleus

what is k+ in the ICF

140 mEq/L

what is sodium levels in the extracellular fluid (most abundant cation on the outside )

142 mEq/L

GLUT 2

15 mM Liver kidney pancreatic Beta cell serosal surface of intestinal mucosa cells A high capacity, low affinity transporter may be used as glucose sensor in the pancreas

In microtubules motor proteins, how long does it take for neuron/ glial processes to diffuse?

17 minutes

Describe type I collagen :

2 alpha 1chain & one alpha 2 chain

How many membranes does the mitochondria have ? What are they ?

2 membranes 1. Outer membrane porins (integral proteins) allow free diffusion of small molecules and ions import receptors for larger proteins with signal 2. inner membrane -very IMPERMEABLE to small charged molecules ETC protein complexes import receptors for matrix proteins

Every human cell has the capacity to use glycolysis for energy production. Which one of the following statements correctly describes an aspect of glycolysis ?

2 molecules of ATP are used in the begining of the pathway

What are the 2 domains in MAPS ?

2 tubulin binding domain ( stabilizes mircrotubles ) 1 tubulin binding domain and 1 binding domain to another cellular molecule (anchors microtubule in a particular location)

How many nucleus does the cardiomyocytes have ?

2-3

What is Ca in the ECF

2.4 mEq/L

A solution of lactic acid (ph 3.8) is found ito contain 0.2 M in the dissociated form and 0.02 M undissociated form what is the pka of the acid?

2.8

a newly designed drug is a weak acid w a pka of 3.8. the drug enters cells via free diffusion through the membrane in its unchanged form. this will occur most readilty at which of the following pH values

2.8

Collagen superfamily has how many members ?

25 members

In microtubules motor proteins, how long does it take endothelial cells to diffuse?

27 seconds

What is chemical coupling ?

2nd messengers can flow from cell to cell -movement of molecules < 1,2 nm diameter; this allows free passage of ions, aa, nucleotides, many 2nd messengers (cAMP, IP3) -Hormone (secretin) binds to receptoor in pancreatic acinar cells; initiate " second messenger " cAMP pathway -stimulates metabolic response ( triggers secretion of contents of all secretory cells in network (bicarbonates, CCK, etc) -cAMP passes through gap junctions, stimulating the same response in many cells -stimulation of one cell results in secretion by many

Describes desmosomes

2nd type of anchoring junctions mechanically attach cells and their cytoskeleton ( INTERMEDIATE FILAMENTS ) great tensile strength

list countertransporters

3 Na-Ca Na-H Cl-HCO3

Pathogenesis of NADPH oxidase complex: 6 proteins

3 cytosolic -p40, 47, 67 2 membrane bound hetero dimer-gp92 and p22 hox 1 assembly protein

What is epidermolysis bullosa ?

3 forms ( identified by depth of blister formation in relation to basal lamina)

Thermodynamics of TCA cycle

3 irreversible steps of TCA 1. Citrate synthase 2. Iso-citrate dehydrogenase 3. alpha ketoglurate dehydrogenase

ECF osmolality is roughly which of the following

300 mOsm/kg H2O

How many genes are in the mitochondrial DNA (mtDNA)? Describe.

37 genes involved in the ETC and oxidative phosphorylation 13 protein coding genes only 22 tRNA genes -dispersed, flanking other genes -2 rRNA genes

In roughly how many different families can the known protein be classified

4

What is Cl- in the ICF

4 mEq/L

What is K+ level extracellular

4 mEq/L K+ is more inside than outside

How many sugars are removed from the N-linked precursor oligosaccharide before protein can leave the RER? What are the sugars ?

4 sugars removed ( 3 glucose and mannose) from RER oligosaccharride processing continues once protein arrives at the the Golgi (more n-linked trimming/addition of new sugars to chain/mofication of sugars

What is 45S pre-rRNA spliced into?

40 S (small ribosomal subunit) -18 S 60 S (large ribosomal subunit) 5.8 s rRNA 28 S rRNA

in a female what percentage of a female total mass is solids ?

45% is solids

GLUT 4

5 mM Adipose tissue skeletal muscle heart muscle insulin sensitive transporter ; in the presence of insulin, the number of GLUT 4 transporter increases on the cell surface, high affinity system

What percentage of the cell membrane is composed of oligosaccharides? What are they attached to?

5% of cell membrane is composed of oligosaccharides attached to glycoproteins, glycolipids, or proteoglycans.

Describe the cells sugar coat: Glycocalyx

5% of cell membrane is composed of oligosaccharides, attached to glycoproteins, glycolipids or proteoglycans

50 % of PCD patients have what syndrome ?

50 % have Kartagener syndrome -bronchietasis -situs inversus -chronic paranasal sinnutis -infertility

in a female what percentage of a female total mass is made of fluids ?

55% is fluids

What causes the autosomal recessive SMN-related spinal muscular atrophy?

Faulty pre-mRNA splicing

Describe the gap junction structure

6 connexin subunit/connexon 2 connexons =1 channel -few or thousands connexons/gap junction

energy yield for one molecule of glucose

7 ATPs

How many transmembrane regions do protein receptors have ?

7 or more

What % of proteins are made on the RER ? Where are the remainder of the proteins made.

70% - 30-40% free cytoselic ribosomes

What is phosphates ICF

75 mEq/L

What % of fiber is composed of elastin ?

90% elastin fiber core is covered with a sheath of microfibrils composed of glycoproteins mainly fibrillin

There are about 1000 proteins that function in the mitochondria. the genes encoding these protein can be found in either the mitochondrial genome or the nuclear genome. Approx. what proportion of these genes are nuclear vs. mitochondrial ?

99 % nuclear 1% mitochondrial

Describe the vitreous humor

> 99 % water - gel is non compressible but highly visoelastic structure proteoglycans cross collagen fibrils (II, IX) via specific binding sites on collagen fibrils -proteoglycans - collagen structures held apart by hyaluronan meshwork

approximately, how many human proteins are destined for the cell surface?

>150 human proteins are destined for the cell surfaced. GPI linked proteins are clipped and covalently attached to GPI anchor while still within RER

What are the 2 types of phosphorylation

ATP synthesis occurs in the body in 2 ways : substrate level phosphorylation oxidative phosphorylation

Describe arsenic poisoning

Contaminated groundwater is the greatest exposure risk: neurologic and cardiovascular toxicities dermatologic ( rain drop melanosis, keratosis) carcinogeb ( bladder ca from drinking contaminated H20 ) skin, lung, GI, liver, hematopoeitic and lymphatic ca as well prevention : decontamination of grownd water

Translocase systems

Adenine nucleotide translocase antiporter-moves ADP into the matirc and ATP out Phosphate translocase promotes symport of one H2PO4 and one H+ into the matrix favoured by the transmembrane proton gradient-protin motive force VDAC ATP and ADP cross the outer mitcochondrial membrane via the voltage dependent anion channel (VDAC)

Which of the 4 types of cell-to cell junctions features cadherins that use alpha and beta catenin as linker proteins that connect the junction to the actin microfilaments ?

Adherens junctions

What connects the ECM to cells ?

Adhesive glycoproteins lamin & fibronectin binds to different cellular integrins (transmembrane cell receptors)

Barth Syndrome is an X-linked cardiolipin synthesis disorder. Which of the following do you expect to be least affected by this disorder?

Adipose tissue (does not use mitochondria)

Describe stress fibers

Contractile bundle

What do all cells have? ( animal and prokaryotes)

All cells have a plasma membrane (cell membrane)

What is cytsoplasmic Ran GAP ? (in importin)

Converts Ran-GTP to Ran-GDP which then releases the importin

What is the structure of the aggrecan proteoglycan aggregate characteristic of cartilage?

A huge aggregation of proteoglycan molecules held organized around hyaluronic acid backbone

A woman affected with mitochondrial disorder will likely transmit the disease to

All her children vertical pattern children of affected males are not affected all children of affected females are affected

hendersen-hasselbach equation

A = ha -> ph=pKa A < HA -> negative, pH < pKa A> HA -> positive, pH > pKa

What is co-translational N-glycosylation ?

At an exposed Asn (asparagine)-x-x-ser/thr sequence -this modification also helps protein fold correctly -hydrophyllic sugar tree act like "water wings" lifting region - N-oligosaccharide interacts directly with some chaperones -N-oligosaccharide is used like a 'tag' to monitor whether a glycoprotein is ready to proceed to the Golgi

Gap junctions are known to couple cells electrically ( transmission of Ca 2+ waves between adjacent cells) what is one good example of this electrical coupling ?

Coordinated depolarization of cardiomyocytes in the heart

Glycosylphosphatidylinositol is ...

A glycolipid that covalently anchors peripheral proteins to outer leaflet

Where do the enzymes and proteins found within the peroxisome come from ?

Correctly folded and assembled cytosolic proteins with an exposed SKL AA sequence are brought into the organelle by the peroxin (PEX) membrane translocators

What is a lysosome ?

A lysosome contains digestive enzymes that break down worn out cell parts or substances entering the cell at the plasma membrane

For the reaction A -> B, delta G 0' = -60kj/mol. the reaction is started w 10mmol of A and no B is intitally present. After 24 hrs, analysis reveals, the presence of 2 mmol of B and 8 mmol of A. Which of the following is the most likely explaination?

B formation is kinetically slow; equilibrium has bot been reached by 24 hours

What impacts complex III

BAL Antimycin A

Which of the 4 types of cell to cell junction employs tight and strong cadherin-caherin coupling to produce a wide anchoring belt that extends all the way around the cell and connect by adaptor proteins to actin microfilaments in order to tightly pull cells in a tissue together

ADHERENS junction

Describe Cystic Fibrosis

AR Hereditary disorder characterized by lung congestion and infection and malabsoportion of nutrients.

Myeloperoxidase deficiency

AR Lack of bleach positive NBT test/rhodamine postive increased candida infections

Describe Zellweger syndrome

AR Mutation of PEX Disorder of peroxisome biosynthesis s/s hypotonia sz early death

Ran-GTP

Binds to importin protein and separates it from its cargo

What are the main functions of the peroxisome ?

Biosynthetic -Plasmalogen synthesis (ether-type phospholipids) -Bile acid synthesis ( derived from cholesterol ; occurs mainly in liver ) Lipid biosynthesis : cholesterol & dolichol (both are also made by SER) Degradative Beta oxidation of very long chain FA -purine catabolism (xanthine oxidase) breaks down peroxide (H2O2) to water

Pyruvate dehydrogenase deficiency

A schematic flow chart of the metabolic pathway that links pyruvate dehydrogenase def. to energy production, neurotransmitter biosynthesis, and the mechanism of action of the ketogenic diet

Pyruvate kinase deficiency

AR inheritance second most common cause for enzyme deficiency related hemolytic anemia (first G6PD deficiency) accumulation of substates proximal of pyruvate kinase decrease in lactare and ATPs in RBCs Decrease ATP -> inhibits Na K ATPase pump-> distrubs the cation gradient across the erthrocytic cell memrane causing the loss of postassium and water loss of membrane plasticity,deformability and development od creanation leads to premature destruction of RBCs in the reticuloendothelial cells of spleen and liver ( extra vascular hemolysis)

Angelman Syndrome (AS) is a complex genetic disorder that arises due to ineffective removal of misfolded proteins by directed degradation. It is characterized by severte developmental delays, speech impairment, microcephaly, epilepsy, and unique behavoir disorder. The specific enzyme lacking in AS patients notmally helps regulate protein degradation at nerve synapses, and its absence impairs synptatic plasticity and therefore, learning and memory. The absence of this specific enzyme prevents the COVALENT attachment of several specific small proteins to a misfolded protein that would normally target it for destruction. Given all the previous information, which of these enzymes do you think is deficient in Angelman Syndrome ?

A ubiquitin protein ligase ( an enzyme that attaches ubiquitins is a ubiquitin ligase"

What is Zelleweger syndrome?

AR, congetial membrane does not recognize the localization AA signal used to import peroxisomal proteins failure to import peroxisomal enzymes -peroxisome deficiency -VLCFA accumulates in blood and tissue -lack of plasmalogen - accumulation of VLCFAs in glial cell membrane ( no beta oxidation) abnormal brain developement -neural migration defects -hypomyelination (due to lack of plasmalogen) -accumulation of VLCFAs in liver -> hepatomegaly & liver failure -lack of bile acid -> decrease fat absorption -> decrease ATP -> muscle weakness

What enzyme actually makes most of the ATP through utilizing proton flow through its structure?

ATP Synthase

Actin polymerisation is ______

ATP dependent

ATP hydrolysis : phosphryl transfer

ATP hydrolysis per se usually accomplishes nothing but liberations of heat- which can not drive a chemical process in the isothermal system its a 2 step process in which part of the ATP molecule like phosphoryl, pyrophosphoryl or adenylate moiety is first transferred to a substrate molecule or active site of an enzyme by covalent modification and raise the free energy content second step is displacement of the added group

ATP

ATP is a high energy phosphate compound ~ P represents a phosphate group w a large and negative free energy of hydrolysis the standard free energy of hydrolysis of ATP = (-7.3 kcal/mol) for each of the beta and gamma phosphates -high energy bond -one whose reactions release a useful amount of energy to perform work

Which of these is a disease associated with Lamin A mutations ?

AD Emery-Dreifuss muscular dystrophy

What is lactase persistence?

AD trait persistent lactase activity has also observed in multiple small population throughout the word historically observed in pop who domesticated cows and consumed milk products into adulthood genetic analysis-established lactase persistence in adulthood

NARP Syndrome

ATPase 6

What is the mutated genes in NARP?

ATPase 6 gene of complex V (ATP Synthase)

An infant shows a severe failure to thrive. Genetic diagnostic reveals a single spontaneous mutation in codon 608 of the LMNA gene, he is diagnosed with Hutchinson-Gilford Progeria Syndrome. Which one of the following findings from a cell biopsy would you expect to be a direct effect of the mutation ?

Aberrations in nuclear architecture

Peroxisomes contain about how many enzymes ?

About 50

Plamapheresis or liver transplation are currently among the few successful treatment for ....

Acanthocytosis ("spur cell anemia")

What is Hurler's syndrome ?

Accumulation : heparan & dermatan sulfate Enzyme def : alpha iduronidase s/s CORNEAL CLOUDING

What is Lipodystrophy ?

Accumulation of adipose tissues in face and neck peripheral lipoatrophy with muscle prominence

What is sphingolipidoses? What diseases are considered as sphingolipodoses.

Accumulation of sphingolipid -Gaucher's disease (accumulation of glucocerebroside) Niemann-Pick diseases ( accumulation of sphingomyelin & cholesterol) Tay Sachs Disease (GM2 gangliosidosis) Metachromatic leukodystrophy ( accumulation of sulfatides)

What are Sphingolipidoses ?

Accumulation of sphingolipids -Gaucher's disease (accumulation of glucocerebrosides) Niemann-Pick disease (accumulation of sphigomyelin & cholesterol ) Tay Sachs disease (accumulation of GM2 gangliosidosis) Metachromatic leukodystrophy (MLD, accumulation of sulfatides & degeneration of myelin)

What is mucopolysaccharidoses? What diseases are considered to be mucopolyssacharidoses?

Accumulation of sulfated polysaccharides/GAGs) -Hurlers syndrome -Hunters syndrome -Pseudo-Hurler Polydystrophy -Sanfilippo syndrome -Morquio syndrome -Maroteaux-Lamy Syndrome -Sly Syndrome

What metabolite enters the TCA cycle?

Acetyl-CoA

Gating Mechanism-specific ligands

Acetylcholine gated Nicotinic receptor

What is the role of integrins ?

Act as principal receptors for ECM proteins integrins link ECM to INTRACELLULAR signaling -different alpha and beta chains pair in multiple ways -specific heterodimers bind to specific ECM components -adhesion-dependent activation of cytosolic signaling proteins regulate anchorage dependent growth -growth factor dependent cascades reverse integrin clustering, reduce adhesion -> more cell motility "velcro" principle ( many weak interactions allow cell migration movement -also function as cell-cell adhesion in leukocytes and plts

What is filamin ?

Actin filament web: cross linking proteins - makes 3D crosslinks -forms the cotical web of filaments under the plasma membrane ( to provide structure and support )

Microtubules are thought to participate in cell motility, but what part of the cytoskeleton is particularly important for providing the leading edge and trailing edge mov't that lead to cell migration ?

Actin microfilaments

Which element of the cytoskeleton are dynamic in that they can grow and shrink rapidly ?

Actin microfilaments and microtubules

What are 3 difference btw actin microfilaments and the different types of intermediate filaments ?

Actin microfilaments are thinner, are dynamic & show polarity

What is another pathway often utilized by growth factor receptor tyrosine kinases that is not often, if ever, used by the GPCR family ?

Activation of the phosphatidyl inositol 3-kinases (PI3K) to generate phosphatidyl 3, 4, 5 phosphoinositol and activate the Akt kinase

Membrane receptors bind to cargo molecules and then mysteriously concentrate into coated pits so that a clathrin lattice forms and produces a clathrin coated endocytotic vesicle. What mediates the concentration, clustering and interaction of the receptor cargo complexes with the clarithin protein complexes ?

Adaptin proteins

What is the first step in O-linked glycosylation? and where in the Golgi does this occur?

Addition of GalNac is the first step -usually occurs in the medial stacks of the Golgi O-linked glycisylation to threonine and serine

What is the treatment of gout ?

Allopurinol allopurinol is a xanthine oxidase inhibitor

What disease is associated with Collagen IV?

Alport syndrome Goodpasture syndrome

which of these are disease that stem from mutation in collagen IV

Alport syndrome Goodpasture syndrome alport syndrome common inherited cause of kidney failure mutation in alpha chain of type 4 collagen (basal lamina) nephritis & deafnesss hematuria, proteinuria, htn Goodpasture syndrome RARE AUTOIMMUNE disease onset : teens-20's & increase in males) autoantibodies against type IV collagen inflammatory destruction of basal membrane in kidney glomerulus and lung alveoli hemoptysis and glomerulonephritis with progressive renal failure

What causes Hutchinson-Gilford Progeria Syndrome?

Altered lamin A , unstable nuclear envelope bleb formation , loss of peripheral heterochromatic, nuclear pore complex clustering -progressive nuclear damage cells die prematurely - premature aging

What happens in Hutchinson-Gilford Progeria Syndrome ?

Altered lamin A -> unstable nuclear envelope (bleb formation, loss peripheral heterochromatin, NPC clustering) progressive nuclear damage

What is endocytosis ?

Always involves internalization of some portion of the plasma membrane -forms some type of intracellular vesicle from invaginated plasma membrane - diff fates await the different types of vesicles

Ribophorins/SRP receptors are required for :

Attachment of the ribosome to the rER

a randomized controlled trial of 200 people is published and finds drinking 8 ounces of cod liver and ground sardines improved athletic perfomance compared to drinking water. you see only 32 people in the intervention arm finished this study, while all 100 did in the warm arm, what type of bias is likely present?

Attrition bias -ppl dropping out of the study attrition causes a bias b/c

What is the characteristic of fibrous protein of the basal lamina ?

Collagen IV

What is autophagy ? Describe the process .

Autophagy is " cell maintenance" ER envelopes old organelles (degenerate mitochondria) to form an autophagosome fusion with a lysosome -lysosomal lipases break down all inner membranes -phagosomes and autophagosomes fuse with primary lysosomes -> autophagolysosome: digestion

Which of theses diseases is caused by mutations in the LMNA gene ?

Autosomal dominant Emery-Dreifuss muscular dystrophy

...... are reenforced with long neurofilaments which crosss link to microtubbules

Axons

Describe the basal lamina organization

Collagen IV binds to laminin forming a scaffold HSPG's bind to both laminin and Collagen IV, connecting the 2 networks

What is AZT ( Zidovudine)?

Antiretroviral therapy (ART), i.e. HIV -nucleoside analogue -competes with dTTP for incorporation into DNA by the viral reverse transcriptase -DNA polymerase delta is not inhibited -no effect on nuclear DNA replication DNA polymerase gamma is inhibited -depletion of mtDNA

In epithelial cells constitutive secretion, what surface secretes digestive enzymes and mucus?

Apical surface Apical membrane targeting : GPI-linked proteins & membrane proteins with long transmembrane domain associate with glycosphingolipids & cholesterol in lipid rafts -> & are directed to the apical surface

Which of these would be an important G-protein that triggers the initial steps that result in the formation of a coated vesicle that will travel down a mircrotubule?

Arf-GTP

What is Arsenic poisoning

Arsenite trivalent arsenic binds to SH groups of lipoic acid affects PDH Alpha keto glutarate dehydrogenase alpha keto acid dehydrogenase arsenate pentavalent arsenic prevents net synthesiss of ATP c/o inhibiting glycolysis-by competing w inorganic phosphate as a substrate for glyceraldehyde 3 phospahte dehydrogenase 1-arseno 3 phosphoglycerate is formed and spontanously hydrolyses to form 3 phosphoglycerate, by passing one of the steps where ATP is formed

Which of the following is the best interpretation of this figure?

Aspiring is associated with lowered risk of MI and heterogeneity is HIGH.

Which prokaryotic cell wall that stains pink?

Bacteria have a second cell membrane. Have an outer membrane and plasma membrane.

Which prokaryotic cell wall that stains purple?

Bacteria sturdy cell wall (brick wall), gram positive . (cell wall & plasma membrane )

Disorder: Botulism

Bacterial toxin -proteases that cleaves v-SNARE (synaptobrevin) prevents release of STIMULATOR neurotransmiter at neuromuscular junction --> flacid paralysis "floppy baby"

Disorder : Tetanus

Bacterial toxin proteases that cleaves v-SNAREs (synapotobrevin) prevents release of INHIBITORY neurotransmitter at neuromuscular juntion ->trismus (lock jaw)

What is the best description of a general phospholipid?

Basic polar head group attached by phosphate to a diacylglycerol

In epithelial cells constitutive secretion, what surface secretes basal lamina?

Basolateral surface Basolateral membrane targeting: proteins contain sorting signals

In Epidermolysis Bullosa Simplex, rupture of the keratin IFs occur where ?

Below most of the epidermis, but above the basal lamina

Beta tubulin _____the _____ to _____ shortly after assembly

Beta tubulin HYDROLYSES the GTP to GDP shortly after assembly

Beta tubulin is _____ with _____

Beta tubulin is capped with GTP

In the NPC Molecular Traffic, the communication is. _____

Bidirectional

Nuclear Traffic is ____

Bidirectional -through the NPC In IMPORTIN NLS Exit EXPORTIN NES Passive diffusion of small molecules proteins, snRNPs, RNAs, RNPs coming out energy dependent mediated transport

After the EGF tyrosine kinase receptor has dimerized and then auto-phosphorylated, which one of these possibilities is part of a signaling pathway typical of this type of receptor ?

Binding of GRB2 which binds SOS which then activates a membreane bound Ras-GTP that then brings about activation of the Raf/MAPK pathway

What is Nuclear Ran-GTP ? ( in importin)

Binds to importin and separates it from the cargo Ran-GTP importin transported back out to the cytoplasm

What is Osteogenesis Imperfecta (OI)?

Bone : Type I collagen embedded in ca phosphate matrix - mutation in type i collagen the procollagen alpha I chain genes most clinically severe phenotypes from substitiion for an invariant glycine triple helix forms C->N terminus gly mutations near C terminal = more deleterious; N terminal substitutions still permit sunstantial triple helix formation Range of phenotypic severity is very large from perinatal lethal to only mild predisposition to fractures

What is the treatment for Chediak-Higashi syndrome?

Bone marrow transplant therapy (to correct hematologic & immune defects)

The permeability of the gap junction can be regulated by intercellular signals. In particular, extended high intracellular Ca 2+ and / or prolonged low intracellular pH will close the gap junction. Why would this be the case ?

Both signals are indicators of cell death or extreme cell distress and closing the channel limits the spread of the damage

Importance of glycolysis as a predominant source of ATP:

Brain: exclusively dependent on glucose followed by ketone bodies RBCs no mitochondria cornea lens-limited blood supplu and very few mitochondria white muscle, renal medulla leukocytes -limited mitochondria ca cells - limited blood supply

What is an incoming vesicle ?

Bring the substances into the cell that are digested when the vesicle fuses with a lysosome

S/S of CF

Bronchiectasis -chronic cough & dyspnea -irreversible bronchial dilation & thickened bronchial walls -dilated central bronchi -hyperexpansion -mucoid impaction -> obstructiob & 2 y infection -> fibrosis -> brochietasis respiratory failure: most common cause of death

What is a primary lysosomes?

Bud directly from transgolgi network (TGN)- are small, dense and compact with low pH & packed with newly produced acid hydrolases -have not yet encountered material to digest

How do peroxisomes form ?

Bud directly off the ER and accumulate lipids and proteins from cytosol

AUTOIMMUNE attack on the proteins of the HEMIDESMOSOMES will result in which condition ?

Bullous Pemphigoid Common AUTOIMMUNE blistering disease -autobodies to hemidesmosomal proteins -disrupt the dermal epidermal junction -subepidermal blisters or psoriasiform pattern -ADULT ONSET > 60 yrs-itchy

Autoimmune attach on the proteins of the hemidesmosome will result in which condition ?

Bullous pemphigoid

When does Ran turn "on"

By binding GTP (GEFs exchange GDP for GTP)

Describe the correlation between glycocalyx and cancer cells

CA cell have diff glycicalyx than non ca cells anti ca therapy targets enxymes making tumor glycocalyx immune defenses; recognize different tumor glycocalyx

The linkage between cells at both the Adherens junction and the desmosomes are notably strong due to the use of a unique calcium incorparting protein family names the :

CADHERINS BIND CALCIUM (yellow dots separating subunits). Cell-cell adhesion = dependednt on calcium binding Desmosomes have specific cadherins demoglein & desmocollin) intracellular anchor proteins (desmoplakin &plakoglobin) link to IFs LINKERS PROTEINS -> CATENINS (important signaling molecules; GI & hepatatic CA) Adherens Junctions Major characteristics that differ from desomosomes adherens junctions connect to F-actin , not to IF -adherens junctions are nearer the apical surface (the actin-rich region) forms continuous belt around cell, do not form "spot welds"

Which of the following terms least associates with peroxisomes?

CARDIOLIPIN : made in mitochondria, inner membrane in mitochondria, cytochrome C

What are barbiturates?

CNS suppressants used to treat epilepsy acts on GABA A receptor and potentiate GABA mediated inhibitory effects by increasing the duration of Cl- channel opening -> hyperpolarization and CNS depression Inhibits complex 1 of ETC -> accumulation of NADH -> inhibits Krebs Effects 1. Decrease ATP production 2. Decrease O2 consumption 3. Decrease metabolic rate 4. Decreased CO2 production -> decrease respiratory drive -> coma -> death

Acid-Base Disorders

CO2 : 33- 44 pH: 7.35-7.45 HCO3 22-28

What is myosin II ?

CONTRACTILE ACTIVITY (both muscle and non muscle cell)

Name & describe 3 vesicular trafficking proteins

COPI COPII CLATHRIN

What is synaptotagims ?

Ca 2+ sensors that interact with t-SNARE to trigger membrane fusion. Other proteins split ATP to assist in dissociation of synaptobrevin from syntaxin- and seem to complete the membrane fusion

What is a synapototagmins ?

Ca 2+ sensors: calcium triggered fusion interact w t-SNARE

Cadherins require ____

Caherins require calcium to bind their subunits together 5 ca2+ binding cadherin repeats interact w the catenins ( alpha, beta, gamma)

What is Desmin-related myofibrillar myopathy ?

Cardiac disease that sometimes leads to death

Nuclear export

Cargo protein contains nuclear export signal (NES) exportin (export receptors in nucleus) binds NES and nucleoporins, exports

What is nuclear import ?

Cargo proteins contains Nuclear localization Signal (NLS) -importin (import receptors in cytosol) binds NLS and nucleoporins : imports

How do things travel to and from the Golgi ?

Cargo travels to and from the golgi by directed vesicular transport

Describe carriers

Carrier are only capable of facilitating downhill transport. Active side only accessible from one side at a time

What do singlet microtubules do ?

Carry intracellular cargo (vesicles, organelles, mRNA)

What enzyme found in the peroxisome degrades hydrogen peroxide ?

Catalase Peroxisomal Reactions : Catalase use H2O2 to oxidise toxins (alcohol): perioxidation reaction - important within liver and kidney & when excess H2O2 accumulates -> elimination of H2O2 OXIDASES : use O2 to remove H atoms from organic substrates -oxidation of organic compounds ( uric acid, AA, FA, purines)

Which of the following LINKER PROTEINS mediate the attachment of the cadherins to the cell actin cytoskeleton in the Adherens junction ?

Catenins LINKER PROTEINS = CATENINS

What do the pro-apoptotic proteins BAD and BAX do ?

Cause the pore to form in the side of the mitochondria so that proteins, ions, and other components are released into the cytosol where cause a caspase cascade

RanGAP

Causes Ran protein to hydrolyze GTP to GDP

What is Caveloae ?

Caveolea are indentions of lipid rafts areas of the plasma membrane that protect cells and seems alfo to function in cellular "mechanosensing"

Students in an intro lab class are able to isolate apocal and basolateral membrane from undifferentiated and differentiated gut epithelial cells. following isolation, the student can categorize the protein, lipid and carb makeup of each batch of isolated membranes. Results from these experiments help them to draw which of the following conclusions about cell membranes ?

Cell membranes have variable protein and lipid contents depending on their location in the cell.

Describe channels

Channels are only capable of facilitating downhill transport. Active site simultaneously accessible from both sides of membrane

What sorts unfolded proteins from folded proteins ?

Chaperone proteins (uses a budding transport vesicle)

What is involved in protein folding in RER ?

Chaperone proteins: BiP (a HSP70 member), Calnexin, Calreticulin, and various heat-shock proteins -recognize & bind unfolded/ misfolded -prevent protein aggregation and sequesters unfinished proteins within the RER -helps proteins fold correctly -give proteins at least a second chance before they are rejected and disposed of CHO & CHO triming enzymes can also a play a role in this cycle -move correctly folded proteins along toward the Golgi Disulfide bond formation by protein disulfide isomerase also plays a role in helping protein fold

GAGs function as a _____& _____ filter

Charge & size filter HSPG's are rich in the basal lamina of the kidney glomerulus -prevent macromolecules passing into urine from blood -GAGs serve as size selective & charge selective barrier Plasma is filtered into Bowman's space. Most proteins are (-) charged, as are the GAGs. Proteins prevented from escaping into urine DIABETES INDUCED CHANGES IN RENAL BASEMENT MEMBRANE CHANGE FILTER SELECTIVITY IN KIDNEY HSPG *- heparan sulfate proteoglycan

A mutation in the gene encoding a protein that normally induces vesicle fusion leads to an AR diseases featuring a crippled the lysosomal pathway do that delayed fusions, misdirected autophagocytosis and granular defects in natural killer cells and platelets frequently occur. The diseases is :

Chediak-Higashi syndrome

What does the cholera toxin cause ?

Cholera toxin causes the debilitating diarrhea of cholerea

Influenza virus utilizes lipid rafts in the plasma membrane for viral assembly and budding off new particles. What normal component of lipid rafts would be the most useful in providing structural support for the viral envelope?

Cholesterol

Describe cholesterol

Cholesterol is a sterol -inserts into both leaflets -provides structural stability -bulky -rigid steroid ring structure -polar head group nonpolar hydrocarbon tail

Relationship of nuclear lamina and chromatin

Chromatin fibers of chromosome bound directly to inner membrane by association with nuclear lamina at both centromeric and telomeric regions Ea. chromosome occupied defined territory does not overlap with another inactive x chromosome usually at edge of nucleus actively transcribed chromatin usually centrally located

Where are ciliated epithelia found ?

Ciliated epithelia are widespread in the respiratory tract, vas deferens, oviduct, epididymis

Which of the following describes the flow of proteins through the Golgi apparatus ?

Cis Golgi to Golgi stack to Trans Golgi

Feedback inhibition ensures that during aerobic metabolism of glucose, the flux of metabolites through glycolysis does not exceed the flux through the TCA cycle. Which one of the following TCA cycle intermediates is a feedback inhibitor of glycolysis ?

Citrate

Which anion is in the extracellular? put in order of most abundant

Cl- HCO3- Protein

How do acid hydrolases reach the inside of the lysosome?

Clathrin-coated vesicles derived from the Golgi are guided to merge with the lysosomal or endosomal membranes Explaination: lysosomal proteins (acid hydrolases) transported from TGN (transGolgi network to early/late endosomes (b/c of theM6P lysosomal sorting tag) -vesicles w material to be degraded/releases (i.e. from endocytosis) -> early endosome -> late endosome

Diagnosis of lactose intolerance

Clinical Ab pain, bloating, flatulence, nausea, or diarrhea occuring w/n a few hours after ingestion of a lactose containing meal provocative tests lacotse tolerance test -50 gm/oral lactose breath hydrogen test > 20 ppm is dignostic stool acidity test : measuring the pH and amount of sugars in stools test for lactase deficiency small bowel bx genetic test for primary lactase def

Co-enzyme Q source of free radicals

Co Q has a probability of passing an electron to O2 to make it an superoxide ion leads to formation of several free radicals like superoxide and hydroxyl ions damage enzymes, membrane lipids and n.a up to 4% free radical generation

Name two things that help proteins fold correctly ?

Co-translation N-glucosylation and protein disulfide isomerase (PDI) help proteins fold correctly.

What is the difference between co-translation translocation and post-translational translocation ?

Co-translational : transport INTO the RER post-translational possible for RER but typical for transport into OTHER ORGANELLES

What is a coat protein ?

Coat protein is driven to assemble into a curved lattice that deforms membrane vesicles bud off and attach by coat protein to a specific motor protein -travel down microtubule to reach destination

Which of these drugs bind tubulin subunits and prevent them from polymerizing into microtubules ?

Colchicine Vincristine , Vinblastine

What 3 drug binds tubulin subunits and prevent polymerisation ?

Colchicine : gout Vincristine , Vinblastine : tx of ca w high mitotic index

Fibroblast secrete _____

Collagen

Vitamin C is absolutely essential for the proper biosynthesis of ?

Collagen

What are the 2 main fibrous protein found in ECM ?

Collagen Elastin

In Ehlers Danlos syndrome what does a mutation in collagen III cause

Collagen III found in blood vessels and granulation tissue vascular type : arterial, intestinal, uterine rupture, easy bruising, thin translucent skin. varicose veins

Diabetic nephropathy initially involves damage to the glomerular basement membrane that first make it leaky and then cause it to thicken. What are the hperglycemia induced changes that start all this trouble ?

DOWN REGULATION of heparan sulfate proteoglycans and the glycisylation and cross-linking of collagen IV in the basal lamina

A young patient is examined who is hypotonic, experiencing dysphagia, and has an unusual type of muscular atrophy. Genetic diagnostic test reveals a mutation in the SMN gene. What is the major cause of this disease and what will be the result of it?

DX: Spinal Muscular Atrophy Defective snRNP assembly leads to defective splicing of pre-mRNA and is causing the loss of motor neurons

What is one way in which a membrane can be made less fluid?

Decrease the amount of phospholipids with unsat fatty acid tails

Phospholipids and cholesterol are important components of the pulmonary surfactant. What does this mixture do?

Defeats water tension to keep the air sacs open

How are the lysosomal Mucopolysaccaharidoses defined?

Defective degradation of glycosylaminoglycans (GAGs)

How are the lysosomal Mucopolysaccharidoses defines ?

Defective degradation of glycosylaminoglycans (GAGs) Explanation: Summary of Mucopolysaccharodpses Defective degradation of the glycosylaminoglycans (GAGs, once known as the "mucopolysaccharides") MPS I - MPS VII All autosomal recessive -expect Hunter (X-linked) -coarse facial features -corneal clouding in some - joint stiffness; skeletal deformity -hepatoslenomegaly MR Hirsutism in some Arterial deposits -urinary excretion of the accumulated GAG often increased

What is the molecular cause of primary ciliary dyskinesis (PCD)?

Defective dynein associated with cilia

What cause laminpathies ?

Defects in lamin assembly/attachement to nuclear envelope; symptoms typically develop during childhood -> fragile nuclear envelope (affects physically stressed tissues: muscle fibers, bone, skin, connective tissue) -> disruption of nuclear function: aberrant distribution of chromosomes or interaction with specific TFs is altered

What is the enzyme involved in Metachromatic leukodystrophy ?

Deficiency of ARSA (Arysulfatase A)

Which of the following describes I cell disease?

Deficiency of N-acetylglucosamine phosphotransferase -absence of the M6P tag -a defect during the glycoprotein processing in the Golgi

What diseases are implicated with ROS ?

Degenerative diseases (Alz) CA Aging

HSPG and diabetic nephropathy

Diabetic nephropathy: glomerular basement membrane dysfunction HSPG determine sievinf properties & also inhibit uncontrolled replication of cells attached to basement membrane

Which laminopathy focuses on heart problems and frequently leads to CHF ?

Dilated cardiomyopathy

A comatose lab tech is rushed to ED. she dies while u r examaning her. her most dramatic symptom is that her body is literally hot to touch, indicating an extreme high fever. you learn that her lab has been working on metabolic inhbitors and that there is a high likilihood she accidnetally ingested one. which one of the following is the most likely culprit?

Dinitrophenol

Why are targeting signals important?

Direct protein to a particular cellular location NLS→ into nucleus• SKL→ into peroxisomes• Mitochondrial signal sequences exist ER signal sequence → RER •internal KDEL→ return to RER (sol.) •internal KKXX→ return to RER (mem.)• M6P on end of oligosaccharide → lysosome Aside from lysosomal the other ER proteins:→ plasma membrane→ secretion

What guides oligomerization ?

Disulfide bonding of C-terminal propeptides terminal propeptided cleaved by N & C procollagen peptidases on cell surface collagen molecules spontaneously assemble covalent cross links formed by lysyl oxidase

Describe animal cell membrane?

Do not have outer membrane-just a plasma membrane, Cell coat: sugar coating (CHO)= glycocalyx (carbs on lipids/peptide)-surface markers to tell cells apart

Describe FACIT

Fibril Associated Collagen (VI, IX, XII) with Interrupted Triple helices organize fibril in the ECM : mediate interactions of collagen fibrils with other fibrils and ECM proteins, proteoglycans & GAGs - bind to surface of fibrillar collagens - 3 stranded structure interrupted by nonhelical domain -> more flexible than fibrillar collagens -ends not cleaved after secretion, retain the propeptide areas

What does fibrillin bind to ?

Fibrillin binds to elastin in addition to the outer sheath, fibrillin forms a micro-scaffold onto which elastins are intially deposisted

What is the Nuclear Pore Complex?

Doorway nucleosporin-glyoproteins

if these drugs are equally lipophillic, which of the following conditions would produce the highest rate of transport of the drug molecule into a cell of simple diffusion

Drug C mw 200 intracellular con. 0.3, 0.9

Five drugs are listed in the following table. if these drugs are all equally lipophillic, which of the following conditions would produce the highest rate of transport of the drug molecule into a cell by simple diffusion

Drug MW 200 ECF 0.9 ICF 0.3 .6 concentration gradient is high

What causes Barth syndrome ?

Due to an x-linked disorder in cardiolipin synthesis -w/o cardiolipin the inner membrane does not function correctly -> causing distorted mitochondria that do not work-giving the signs and symptoms

When is nucleolus formed ? Hows?

During interphase. Fathers arounds clusters of rRNA gene repeats ( the grouping of the p-arms of acrocentric chromosomes 13,14,15, 21, and 22 )

When is hnRNPs formed ?

During pre-mRNA processing

What powers the stroke of all the cilia in your body ?

Dynein

What is dynein?

Dynein carries material towards the negative end (RETROGRADE)

What diseases is associated with Collagen VII

Dystrophic epidermolysis bullosa

An 18 yr old make experiences a bout of diarrhea, after eating a small amount of a warm potato salad while on a picnic w his family. He estimates that the lost about 1 L of fluid. Concerned, his parents have him drink 250 ml of tap water as he driven to the ED of the local hospital. On arrival at the emergency room one hour later, which of the following changes to his fluid compartment vl and osmolarities would be expected after equilibration of the water he drank ?

ECF VL decrease ECF OSM decrease ICF OSM decrease ICF VL increase explanation : loss 1 l water- losing ECF , vl down in ecf osm in ecf decrease, 250 water diluted diarrhea losing electrolyte and vl osmo down in ecf water goes into icf vl , dilute icf osm if he just had diarrhea & didnt drink water ecf vl decrease ecf osm stay the same icf vl & osm stay the same

Adding water to ECF

ECF osmolality would be diluted initially compared to ICF Water would enter the ICF (swell the cell) to equilibrate the osmolality btw compartments water flow ecf -> icf ECF vl increases ECF Osmolarity decreases ICF volume increases ICF osmolarity decrease

adding hypertonic saline (excessive nacl intake) to ECF

ECF osmolality would increase greatly initially and fluid would be drawn out of the cells & into the ECF to lower the tonicity of the ECF This would contract the ICF volume and increase the ECF volume, as well as increase overall osmolality ECF volume increase ECF osmolarity increase ICF volume decrease ICF osmolarity increase water flow icf-> ecf

Describe fibroblast role

ECM components secreted locally assembled into organized meshwork covering cells that produce them

Where is the production site of all transmembrane proteins & membrane lipids (plasma membrane and most organelle membranes)?

ER

Describe the pathway of COP II

ER -> cis Golgi (anterograde) "two steps forward-anterograde"

What recognizes ER signal sequence on proteins ?

ER signal sequence on proteins are recognized by SRP (SIGNAL RECOGNITION PARTICLE) -> recognized by SRP receptors on ER membrane -> brings to translocon -> go into ER

What does the ETC do?

ETC uses energized electrons from NADH to pump protons into intermembrane space protons fall doen electochemical gradient through ATP synthases & spin the turnine to make ATP inner membrane very impermeable to hold ion gradient ( because of cardiolipin)

What stabilizes collagen ?

Each alpha chain is twisted into helix of 3 residues/turn stabilized by interchain H bonds -glycine every 3rd AA- small & open - allows for easy H bonding btw glycine backbone & polar groups on adjacent helix proline & hydroxyproline - 25 % makes kinks, fixed angle; helps helix formation also contains lysine & hydroxylysine triple helix - makes extremely strong -like the cables of suspension bridge -resist unwinding

Describe the life cycle of an endosome

Early endosome - neutral pH Late endosome -acidic pH fuses w lysosome Lysosome -> hydrolytic enzymes + H+ pump to maintain acidic pH

What diseases is associated with Collagen III

Ehelers- Danlos syndrome ( Collagen I, III, V)

An interesting case is encountered where the patient exhibited varicose vein, hypermobile joints and very odd hyperextensible skin. your colleague mentions that this is a genetic disease. you realize that this must be :

Ehlers' Danlos syndrome

What diseases is associated with Collagen V?

Ehlers-Danlos syndrome

What happens to misfolded proteins?

Ejected to cytosol deglycosylation ubiquination -> polyubiquination (mark for destruction) -proteasome

Describe Mitochondrial Crystalline inclusions

Electron microscopy crystal-like inclusion -consist mainly of precipitates of creatine kinase -railway-track or parking lot inclusions

What is the dominant ECM protein in arteries ? where else can they be found

Elstatin also, skin, lungs, uterus -high hydrophobic protein, rich in PROLINE AND GLYCINE ( not glycosylated & hydroxylysine )

Where are the proteins of the ETC found in a mitochondrion ?

Embedded in the cristae of the inner membrane Explanation : ETC is embedded in the INNER MEMBRANE

Which laminopathy centers on skeletal muscle weakness & atrophy, produces notable contractures, also features sudden HF and displays fragile nuclei under microscopic exam?

Emery -Dreifuss muscular dystrophy

Describe the process of endocytosis

Endosomes are sorting centers for material from the outside of the cell or Golgi -sending it to lysosome for destruction -back to the membrane/Golgi for further use

Describe primary active transport

Energy derived directly from breakdown of ATP -Transport solutes against their electrochemical gradient

What does procollagen's propeptide domain do ?

Enhance helix formation and prevent premature fibril formation

Describe the structure of the nucleus ?

Envelope is a DOUBLE LIPID BILAYER perinuclear space, continous

In Marfan syndrome, what gene is mutated ?

Fibrillin gene (FBN1) mutations 1500 mutations are known

Fibrillin is essential for both ______&______ of elastic fibers .

Fibrillin is essential for both the assembly and integrity of elastic fibers

Describe Marfan Syndrome

Fibrillin mutation AD common connective tissue disorder 1. 5000 weak elastic tissue heart : aortic root dilation & dissection aortic/mitral regurgitation eye: lens subluxation & retinal detachment skeleton : tall & thin long limbs & fingers (arachondactyl) funnel chest (pectus excavatum)

What does defective kerantin interfilaments cause ?

Epidermolysis bullosa simplex

Describe a normal erythrocytes and its benefits

Erythrocytes : optimal shape =spherical with dimple biconcave discs "doughnut " -max S.A. to vl -( deform ability ) -enhances O2 transfer

What is cellular respiration?

Eukaryotic cells living under aerobic condition oxidize their organic fuels to carbon dioxide and water this phase of fuel catabolism is called cellular respiration -refers to multicellular organism's uptake of O2 and release of CO2 organic fuel molecules-glucose, fatty acids, and some aa-are oxidized to yield 2 carbon fragments in the form od the acetyl group of acetyl co A

if poison such as cyanide stops the cellular production of ATP, which of the following process will cease ?

Exit of Na + from the cell

ECM is easy to overlook but plays very important roles in all tissues. ECM is espcially abundant in the connective tissues. What is the chief adhesive glycoprotein to which integrins bind in the interstial type ECM found in connective tissues?

Fibronectin Explaination : 2 types of adhesive glycoprotein bind to integrin Laminin Fibronectin ->interstitial matrix interstitial matrix : in spaces btw epithelial, endothelial, muscle cells, the main components of connective tissue

Which actin filament cross-linking protein is linked to the neuronal disorder, periventricular heterotopia, in which CNS neurons fail to migrate normally during the development of the brain ?

Filamin

What is a secretory vesicle ?

Fuses with plasma membrane as secretion occurs

What are the sources of acetyl Co-A

F.A. Palmitate The ketone body, acetoacetate the sugar glucose pyruvate ethanol

ATP synthase complex

F0 complex: made of 12 subunits C. H+ passes through ea. subunit from inter membrane space to matrix rotating the F0 complex (turbines) varies from (10 to 16) in different species F1 complex 3 beta subunits-stabilized by b2 and delta subunits central asymmetic shaft-composed of the e & gamma subunits which rotates along w F0 complex every 120 of the shaft encounters differnt beta subunits

What is Achondroplasia

FGFR3 mutation most common form of dwarfism AD 1/ 10, 000 mature ht < 4 ft

The rate of absorption of a drug taken orally is found to increase as the dose ingested is increased up to a point where further increases in dose result in no further increases in the rate of absorption. Absorption does not appear to result in the splitting of ATP. Which of the following processes best describes the drug absorption ?

Facilitated diffusion

Where are glycolipids found?

Facing outward from the outer leaflet of the plasma membrane

What is the basic cause of I cell disease (mucolipidosis II)?

Failure to produce the M6P carb tag to direct enzymes into the lysosomes

What type of intermediate fibers strengthen astrocytes in the CNS ?

Glial fibrillary acidic protein

B2 (riboflavin) deficiency

Glossitis -inflammation of tongue, magenta red colour, fissures atrophy of lingual papillae cheilosis: fissure in lips angular stomatis: inflammation at corners of mouth conjunctivitis oral-ocular genitial syndrome angular stomatitis, photophobia, scrotal dermatitis anemia and erythroid hypoplasia-due to decreased activation of B6

Name a SER membrane protein and describe role?

Glucose 6-phophatase. Removal of phosphate from G6P -> free glucose

What are GLUT transporters?

Glucose transporters are a wide group of membrane transporter that facilitate the transport of glucose across the plasma membrane, a process known as facilitated diffusion SGLT2 Familial renal glycouria apical surface of epithelia cells of kidney tubules GLUT2 Fanconi-Bickel syndr. GLUT 2 Fanoni-Bickel syndr. basolateral surface of epithelial cells of kidney tubules and SI heptacytes, pancreatic beta cells

After digestion of a piece of cake that contains, flour, milk, and sucrose as its primary ingredients, the major carbohydrate products that enter the blood are which of the following?

Glucose, galactose, and fructose

What are the mitochondrial matrix antioxidant enzymes ?

Glutathioe peroxidase superoxide dismutase

What two enzymes break down ROS ?

Gluthathione peroxidase (GPX), superoxide dimutase (SOD2)

Phosphatidyethanolamine, phosphatidylserine and phosphatidylcholine are similiar phospholipids. What links the the phospho-head group of each of these to the two fatty acid tails ?

Glycerol

What is glycosylphosphatidylinositol (GPI )anchor?

Glycolipid that attaches protein to plasma membrane

All the following take place inside the mitochondria, except ....

Glycolysis ( in the cytosol)

During the process of protein synthesis, what process happens in both the lumen of the rER and the lumen of the Golgi ?

Glycosylation

What is GPI?

Glycosylphosphatidylinositol- lipid anchor protein a glycolipid that COVANTENTLY anchors peripheral proteins to outer leaflet

Processing continues in _____ before procollagen molecules secreted

Golgi

Where does COP I go ?

Golgi -> RER

A male infant is born with b/l dislocated hips, restricted shoulder and elbow joints, cloudy corneas, and coarse facial features. Which of the following is the location of the dysfunctional enzyme responsible for the most likely diagnosis in this patient ?

Golgi apparatus

Describe the structure and function of the Golgi

Golgi is the distrubtion center for proteins and lipids from ER to vesicles and plasma membrane

Famously, allopurinol is used as an inhibitor of xanthine oxidase to suppress or eliminate the occurance of what peroxisome associated disease?

Gout

In UCP found in brown adipose tissues, what is due to clusters of mitochondria associated with large lipid droplets ?

Granular cytoplasm

What is the ECM ground substance?

Ground substance is primarily composed of water and large organic molecules such as glycosaminoglycans (GAGs), proteoglycans (PGs) with embedded glycoproteins

Describe GEF

Guanidine nucleotide exchange factor "ON SWITCH" "GEF LIKES TEA AND IS ACTIVE (LIKES TO RUN)

Describe the mRNA transport from nucleus to cytoplasm

Highly selective; prevents translation of incorrectly processed mRNA or nascent premRNAs RNA transported across NPC as RNA protein complexes (hnRNPs) Export proteins recognize mature mRNA (5'cap, poly A tail, spliced), and only allow these through the NPC

What type of macromolecules are imported into the nucleus?

Histones & polymerases -via selective, active, transport transcription factors snRNPS & snoRNPs

What is Homoplasmy?

Homogeneity in mtDNA the normal condition for wt mtDNA

_____ occurs when a person's cell carry a uniform population of mitochondrial DNA molecules

Homoplasmy Heteroplasmy - a mixed population of mtDNA molecules some mutated, others not Homoplasmy Homogeneity in mtDNA the normal condition for wt mtDNA Heteroplasmy and mtDNA disease - in mtDNA diesease there is a commonly positive correlation btw the proportion of mutated molecules and the severity of the diseases Severe mutations in the mtDNA are only observed in heteroplasmy bc they would be lethal in the homoplasmic state

All of the lysosomal mucopolysaccharidoses are autosomal recessive, except for:

Hunter syndrome

The most severe of the mucopolysaccharidoses involves an inability to degrade dermatan sulfate and heparan sulfate and is known as

Hurler syndrome

Which laminopathy features progressive nuclear damage that leads to premature aging in young children before 15 years of age ?

Hutchison-Gilford Progeria Syndrome

Which of the following glycosaminoglycans forms the largest/longest of the repeating disaccharide chains and doe not covalently attach to a core protein when forming part of a proteoglycan ?

Hyaluronan Hyaluronan : a unique GAG -structure : repeating sequence of ~ 25000 identical nonsulfated disaccharides (GlcNac-Glucuronic acid ) -chain length is huge -NOT COVANTLENTLY LINKED TO ANY CORE PROTEIN -synthesized by an enzyme on basl epithelial surface (all other GAGs, are made intracelluarly and exocytosed) -produced during wound healing -creates a cell-free space into which cells can migrate -main lubricant of joint fluid (binds lots of H2O) -resist compressive forces in tissues and joints -forms backbone for large proteoglycan complexes -Aggrecan

Name 5 GAGS that are covalently linked to form proteoglycan

Hyaluronana (not sulfated) Dermatan sulfate Chobdriutub sulfate Keratan sulfate Heparin (heparan sulfate)

What is a hydrolytic enzymes ? Names the acid hydrolases . What is there ideal pH?

Hydrolytic enzymes : acid hydrolases; active in acidic conditions acid hydrolases : nucleases proteases glycosidases lipases phosphatases sulfatases phospholipases pH: 4-4.5 (very acidic)

What is a hypoosmotic solution?

Hypoosmotic solution if the solution has less osmotic pressure than the cell water moves into the cell and swells in cell vl (icf vl increases) 1. excessive H2O enters the ECF 2. ECF osmotic pressure falls 3. H2O moves into cells by osmosis; cells swell consequences of hypotonic hydration (water gain) if more water than solutes is gained, cells swell

As a capable research scientist you were able to develop a successful gene replacement therapy to restore Golgi N-acetylglucosamine phosphotransferase. Which of these is/are diseases that will benefit from your treatment?

I-cell Disease & Pseudo- Hurler Polydystrophy I-cell (Mucolipodosis II): Deficiency of N-actylglucosamine phosphotranferase -absence of the M6P tag -acid hydrolases lacking M6P are secreted extracellularly -undigested substrates accumulate -undigested substrate accumulate inclusion bodies, progressively damaged -skeletal abnormalities -coarse features -restricted joint movement -psychomotor retardation -enlarged liver, spleen, heart valves death from CHF/RTI Pseudo-Hurler Polydystrophy (Mucolipidosis III) -milder form of I cell disease - residual enzyme activity - later onset -survival into adulthood

Inability of the golgi to produce the M6P tag produces the disease:

I-cell diseases

Describe normal ICF and ECF Compartments

ICF is 2/3 of TBW ECF is 1/3 of TBW Osmolarity of both ICF & ECF is ~ 300 mOsm/L

the provided image shows ionic distribution of K+, Cl-, and Na+, across cell membrane. the concentration of each ion is represented by the size of its label, where a larger label indicates a higher concentration. Which image correctly represents the distribution of K+, Cl-, and Na+ across a typical living cell membrane ?

IN ECF NA + CL- IN ICF K+ INORGANIC PHOSPHATES & negatively charged proteins

What type of collagen is fibril associated ?

IX : Cartiliage XII: Tendon, ligaments, some other tissues

What are the inhibitors of glycolysis

Idoacetate and methyl meuric chloride inhibit glyceraldehyde 3po4 dehydrogenase by binding to free sulfhydryl groups of the active site fluoride -inhibits enolase. therefore, no glucose will be expended, and the glucose level will stay the same. commonly used to measure blood glucose levels to prevent getting a false reading (too low) know the irreversible steps & the steps that yield energy

What is a residual body ?

If lysosome can not degrade material within it becomes a residual body that either expels material from cell or condenses down to become lipofuscin granule

Why is glycosylation important?

Important for correct folding, transport, and function.

Where do all the proteins needed within the nucleus (transcription facts, polymerase enzymes, binding proteins) come from?

Imported through the nuclear pore complexes

What is Scheie & Hurler-Scheie syndrome?

Mucopolysaccharidoses IS &HIS) MPS IS &MPS IHS -Residual alpha L-iduronidase activity - milder disease (Scheie=mildest type of MPS I)

Where are the peptidases located that convert procallagen into tropocollagen ?

In cell surface after secretion : collagen fibrils form cell surface peptidases remove N -& C propeptide extensions procollagen has now been converted into tropocagen" convalent processing necessary for additional crosslink formation

What is threshold hypothesis for mtDNA disorders ?

In heteroplasmy, the proportion of mutated mtDNA molecules must exceed a threshold before clinical or biochemical consequences occur this can result in reduced penetrance beyond the threshold, the severity of the consequence correlates with the proportion of mutated molecules

What is the biggest difference between regulated and constitutive secretion ?

In regulated secretions, vesicles do not fuse with plasma membrane until triggered by an intracellular signal

FACIT collagen bind to fibrillar collagens resulting in different fiber organizations. Describe the organization in tendons .

In tendons, organized parallel bundles aligned along the major axis of tension

Where is cytochrome p450 found and what does it do ?

In the hepatocyte SER. It oxidized drugs to inactivate others -> made water soluble so they are excreted in urine

Regulation of Iso citrate dehydrogenase

In well fed state, increase in ATP and NADH will inhit isocitrate dehydrogenase leading to accumulation of citrate. citrate will enter cytosol and inhibit glycolysis and activates f.a. synthesis

From a molecular biology perspective, what is the cause of CF?

Incorrect protein folding

What is another way in which a membrane can be made less fluid?

Increase the amount of cholesterol in the membrane

A retired 69 year old man comes in for a routine check up. he has s/s hyperglycemia 7 years ago & was later diagnosed w type 2 diabetes. he p/w recent weight gain, suboptimal diabetes control, and foot pain. he does not test his blood glucose levels at home. If his blood sugar levels are bot controlled which of the following is most likely to occur ?

Increased crosslinking and glycosylation of collagen IV and decreased HSPG levels as the glomerular basal lamina thickens GAGS function as a charge and size filter HSPG are rich in the basal lamina of the kidney glomerulus -prevent macromolecules passing into urine from blood -GAGs serves as a size slective & charge selective barrier -plasma is filtered into Bowman's space -most proteins are negative charged, as are the GAGs. Proteins prevented from escaping into urine Diabetes induced changes in renal basement membrane change filter selectivity in kidney diabetic nephoropathy: glomerular basement mebrane syfuntion HSPG determine seiving properties also inhibit uncontrolled replication of cells attached to basement membrane hperglycemia DOWN REGULATION of HSPG -collagen glycosylation and cross linking GBM thickening increase collagen, decrease HSPG -expansion of mesangial matrix a diabetic kidney glomerulus : mesangial cell hypertrophy, increase in ECM secretion. compresses surrounding capillary loops -> proteinuria, fluid retention, HTN, further damage -> renal failure

Which cation is in the intracellular space

K+ (most abundant ) Mg +

Disorder : I - cell disease

Inherited lysosomal storage disorder (AR) -defect in N-acetylglucosaminyl 1-transferease -> failure of the Golgi to phosphorylate mannose residues (decrease in mannose 6 P) on glycoproteiens -> proteins are secreted extracellularly rather than delivered to lysosomes s/s -course facial features -clouded corneas -increase plasma levels of lysosomal enzymes (fatal in childhood)

What are the three classes of membrane proteins ?

Integral Peripheral Lipid anchored

If a textbook describes calcium ion channel that will open to allow calcium ion to rush into the cell, of which protein ( or proteins) will this channel be composed?

Integral membrane proteins

What is FAK

Integrins also signal through focal adhesion kinase (FAK), regulating Rho GTPases ( & also MAPK & PI3K pathways) survival proliferation migration

What is hemidesmosomes ?

Integrins bind to intermediate filaments ( keratins) via adapter proteins, and to extracellular lamimin

Adhesion proteins of the ECM may seem like an unimportant detail; however, they serve as anchoring points that influence cell functions relating to survival, development, migration, proliferation, shape, orientation, and differentiated function. This is due to the fact that fibronection or laminin adhesion glycoproteins act as ligand for transmembrane :

Intergrin receptor proteins

GLUT 5

Intestinal epithelium spermatozoa this is actually a fructose transporter

What is apoptosis ?

Intrinsic (mitochondiral) & extrinsic pathways promote Caspase cascade -> cell death apotosis has been termed "programmed cell death"

What is a isoosmotic solution?

Isoosmotic solution if total osmotic pressure of the solution is equal to that of the cell. no water movement into or out of cell

During sx, exposed tissues are moistened with sterile solution to prevent shrinkage or lysis of the cells. Which of the following does the solution have to possess relative to cells in the tissue ?

Isotonic

How can Vitamin C deficiency cause scurvy?

It is a cofactor needed for the hydroxylation of proline and lysine in collagen

The hyperphosphorylation of the tau protein appears important in the early onset of Alz disease. What kind of protein is tau ?

It is a microtubule associated protein (MAP)

What happens to a protein that will not fold correctly within the RER lumen after repeated tries ?

It is ejected out into the cytosol where it is stripped of modifications and tagged with poly-ubiquitin so that it is destroyed by the proteasome

What is the ER membrane translocon ?

It is the gated transmembrane portal that responds to the signal sequence and causes the nascent protein to be translocated into the ER lumen

What effect does Cholera toxin have on signal transduction when it gets into its target cell?

It locks the the Gs alpha subunit into a permanent active state by ADP ribosylation it causes a strong increases in cystolic cAMP Cholera toxin : ADP ribosylation of G subunit toxins attach ADP ribose residue to G alpha stimulating protein and locks it into the active state ( by blocking its slow, but important, GTPase activity) ->activates membrane chloride and sodium ion channels on the membrane and activate the secretion pathways -> casuses the distinctive signs and symptoms of cholera

The Gs family of heterotrimeric G-protein are the best known. When GTP causes this complex to release the alpha subunit, what does the Gs alpha subunit do?

It travels down the inside of the plasma membrane and binds to and activates adenyl cyclase

What happens when Arf/Sar hydrolysis of GTP ?

It triggers uncoating of the vesicle-exposing SNAREs that will guide docking and fusion

What is Fick's first law of diffusion?

J= DA (Ca-Cb) / delta X J= flow of solute from region 1 to region 2 in the solution D= diffusion coefficient of the solute in a given solvent A= cross sectional area thru which the flow of solute is measured Ca-Cb or delta C = the difference in solute btw regions A & B delta X= distance between regions A and B

Classification of allosteric enzymes

K-class effectors alter the affinity K 50 affects the affinity of enzyme to the substrates V class effectors alter the Vmax affects the rate of enzyme catalysed reactions K50 is inversely proportional to affinity of the enzyme to the given substrate

The kinetics of an allosteric enzyme is shown int he graph. an experimental drug X is added, and the results are shown. Which of the following sets of findings best describes the effect of drug X on enzyme activity ?

K50 increases and Vmax- no change

When describing 'tag' vs 'destination' which of the following is correctly matched ?

KDEL - ER KKXX - ER M6P - Lysosome NLS - nucleus SKL-peroxisomes

B/l ptosis, retinopathy, ataxia, heart block, ADULT ONSET

KSS

what is pKa

Ka = dissociation constant of an acid indicate the strength of an acid pKa is negative log 10 Ka the lower the pKa value the stronger is the acid max buffering capacity occurs when pH=pKa the concentration of the conjugate base and of the conjugate acid are equal (50 % each) a conjugate acid/base can serve as an effective buffer when the pH of a solution is within approximately +/- 1 pH unit of the pKa of the weak acid

What is kinesin?

Kinesin carries material towards the positive end (ANTEROGRADE)

What is the characteristic adhesion glycoprotein of the basal lamina ?

LAMININ

What happens in Class IV LDL-R mutation ?

LDL-R does not cluster on cell surface causing ineffective endocytosis

What seems to be the chief problem with an LDL receptor that has suffered a class iv mutations ?

LDL-receptor complexes do not cluster into coated pits, possibly due to an inability to interact with adaptin proteins

Loss of central, high acuity vision

LHON

Where are Lamin A and C from ?

LMNA splice variants Lamin A & C form heterodimers

Where is Lamin B from ?

LMNB gene

Isoforms of LDH

Lactate dehydrogenase (LDH) consist of 4 subunits that can either of the muscle (M) or thr heart (H) type -5 types abnormal values LDH1 > LDH2 MI ( can alos be seen w hemolytic anemias, pernicous anemia, folate def. renal infract) LDH5> LDH 4 liver disease (cirrhosis, hepatistis, hepatic congestion)

B1 deficiency : Wet Beri Beri

Lactic acidosis congestive cardiac failure -high output cardiac failure arrythmias peripheral edema

What causes lipodystrophy?

Lamin A/C defect preLamin A interacts with an adipocytic TF -> impaired adipocyte differentiation

What causes dilated cardiomyopathy? How?

Lamin A/C defect (rare cause) Fragile nuclear lamina -> nuclear structures/ contents damaged -> cell death -> CHF

Which component of the nuclear lamina is produced as a splice variant product of the lamin A gene?

Lamin C

What causes Cdk1 to be inactivated ? How ?

Lamin dephsophorylation membrane vesicles now bind to chromosome surface-> nuclear envelope reassmebles around the chromosomes

When does Lamin Phosphorylation occur ? How does this happen ?

Lamin phsophorylation occurs during prophase by Cdk1 nuclear lamina dissembly -> nuclear envelope breaks down into vesiciles containing lamin B Lamin A & C released as free dimers Lamin B = anchored to inner membrane

Provide a brief description of Progeria

Lamina A fragile nuclear envelope s/s accelerated aging

What are the main proteins found in the nuclear lamina ?

Lamina A, B, C

Provide a brief description of Lipodystrophy

Lamina A/C defect s/s muscular-adipocyte differentation

Describe the nucleoplasm

Lamina lining- network of support

All epithelial tissues sit upon a basement membrane (basal lamina) that they, themselves have made. What adhesive glyocoproteins of the basal lamina typically binds to the transmembrane integrins ?

Laminin Basal lamina : functions -structural support for cells ( transmembrane integrin receptors bind to collagen 4 laminin) -organizes cell & tissues -scaffold for tissue reguration filter in the kidney glomerulus ; thick, finely sieved BL prevents macromolecules passing from blood into urine -collagen IV and HSPG espically important there -determines cell polarity -influences cell survical. proliferation, differentiation -selective barrier for cell migration basal lamina organization collage 4 binds to laminin forming a scaffold HSPG bind to both laminin and collagen 4 connecting the 2 networks laminin binds to the integrin transmembrane receptor proteins to anchor cell to basal lamina certain integrins also directly bind to collagen 4 at the basal lamina

what is the significance of km ?

Large Km of enzyme 2 reflects a low affinity of enzyme for the substrate. Small Km for enzyme 1 reflects high affinity of enzyme for the substrate -affinity/binding is inversely proportional to km value 1. useful parameter for characterizing the number and /or types of substrates that a particular enzyme will utilize 2. for comparing similar enzymes from diff tissues or diff organisms 3. useful foe evaluating the effects of mutations on protein functions for some genetic disease

If you had to come up with another name describing cellular autophagy, which of these would work ?

Large scale cell maintenance that clears old and defective organelles by engulfing them with an authophagosome and then merging with lysosomes until all components are broken down and digested into essential building blocks (for recycling)

Which of the following mtDNA diseases can display homoplasmy ?

Leber Hereditary Optic Neuropathy (LHON) -subacute, painless, b/l visual failure -median age of onset 24 yrs old optic nerve is the only affected tissue mutated genes subunits of complex I (NADH Dehydrogenase) - may be HOMOPLASMIC OR HETEROPLASMIC

What is LHON?

Leber's Herediatary Optic Neuropathy - associated with mutations in the mitochondrial protein coding genes -subacute, painless, b/l central visual failure -median age of onset 24 years -optic nerve is the only affected tissue -may be homoplasmic or heteroplasmic

What are any disease that interrupts myelin formation or enhances myelin degradation called ?

Leukodystrophy - Metachromatic leukpdystrophy (MLD, accumulation of sulfatides and degeneration of myelin) & Krabbe Disease are clearly lysosome related leukodystrophies by anyones' definition. Many other lysosome-related disease cause some damage.

What happens when cavin & caveolin proteins are present?

Lipid rafts form caveola that then can bud off to form transport vesicles that fuse with endosomes

What is lipid solubility ? ( factors affecting simple diffusion )

Lipid solubulity has the strongest influence on permeability as most substances in the body are hydrophillic and dont easily cross the lipid bilayer partition coefficient =olive oil/water solubility

What are the 2 plasma membrane components ?

Lipids & proteins

Which laminopahty center on abnormal distribution of fat, with the torso and legs staying lean while the face and neck accumualte mounds of fat?

Lipodystrophy

Which of the following terms is least associated with the RER ?

Lipoprotein production

The " ground substance" of the ECM is hydrated, compression- resistant gel. One of the major components are GAGs. What is a GAG?

Long Linear polysaccharides composed of repeated sugar acid and amino sugar disaccharide

An 18 Y old male began to experience b/l ptsosis. HIS FATHER IS AFFECTED, with more severe weakness of his eye muscle and general myopathy. The physician suspects a mitochondrial disease. Which of the following mutations is most likely causing the mitochindrial dysfunction?

Loss of function of TWNK NOTE : FATHER, IS NUCLEAR DNA MUTATION. it may be a mitochondrial disease, but might be from nuclear DNA ** Disease PEO (Progressive External Opthalmoplegia) -multiple genes involved -locus heterogeneity -involving nuclear and mitochondrial genes -most commonly AD Mutations in POLG encoding DNA polymerase gamma TWNK encoding the helicase Twinkle -also can have mitochondrial inheritance -mtDNA depletion or large deletions in the mtDNA Clinical presentation : Late age onset (18-40 y of age) biochemical and histological muscle pathology -ragged red muscle fibers -progressive muscle weakness and wasting b/l ptosis -excercise intolerance

In what temperature does plasma membrane become gel-like ?

Lower temperature phospolipid becomes gel like consistency.

What is BiP (Binding Protein)?

Lumenal ER chaperone that binds peptide in ER lumen and pulls it in & helps it fold

How is lysine and hydroxylysine deaminated ?

Lysines and hydroxylysines deaminated by lysyl oxidase ( extracellular) -> reactive aldehydes ( rew O2 & copper)

What is the likely fate of a free floating protein without a molecular tag located in the Golgi apparatus ?

Lysosomal protein

Trafficking Pathways thru endosomes and lysosomes ?

Lysosomal protein from transgolginetwork are delivered to early and late endosomes (M6P lysosomal sorting tag) vesicles with material to be degraded travel the pathway -> early endosome -> late endosome -> lysosome

What cellular body is the final destination for endocytosed material destined to be degraded ?

Lysosomes

What is the lysosome marker called ?

M6P on end of oligosaccharide

Lactic acidosis, stroke-like episodes

MELAS

What is MELAS ?

MELAS : Mitochondrial Encephalomyopathy, Lactic Acidosis and Stroke like episodes - mutation in the mitochondrial tRNA genes - stroke like episodes : vomiting, HA, visual disturbances -short stature - Diabetes -sensorineural hearing loss -maternally transmitted

MYOCLONIC sz, ragged red muscle fibers

MERRF

What is a s/e of AZT therapy?

MYOPATHY ( muscle weakness )

Provide an overview of ECM

Macromolecular network in spaces surrounding cells, composed of -fibrous structural proteins ( colalgens, elastin, fibrillin) -adhesive glycoproteins ( fibronectin, laminin, entactin) -gel of proteoglycan & hyalronan

Name 2 examples of competitive inhibitors

Malonate -TCA cycle Malonate competive inhibitor substrate : succinate succinate dehydrogenase : active site Statin -cholesterol synthesis HMG CoA reducatase : active site HMG CoA : substrate Pravastatin (competitive inhibitor)

Describe the muscular desmin IF

Muscle cells : desmin structures support myofibrils within cell, withstand mechanical stress, form protective network around ea. myofibril at the Z disk

What is the mutated gene in MERRF?

Mutated gene is tRNA Lysine

What mutation causes MILS?

Mutated genes : ATPase 6 gene of Complex V (ATP Synthase)

What mutation causes Emery-Dreifuss muscular dystrophy ?

Mutation can be in either Emerin or Lamin A/C

Disorder CF

Mutation in CFTR incorrect folding protein degradation s/s lung congestion & infection bronchiectasis chronic cough, dyspnea, bronchial dilation respiratory failure

How does the lysosomal/endosomal pathway gather proteins tagged int the cis-Golgi ?

Mannose -6- phospahate

When loss of function mutations in the mitochondrial gene encoding ATPase 6 occur in a living person, they are always heteroplasmic. If the proportion of mutated mitochondria is relatively high, which disease is most likely to present?

Maternally Inherited Leigh Syndrome Explaination: mutations in the mitochondrial gene encoding ATPase6 can cause either NARP Syndrome or Maternally Inherited Leigh Syndrome NARP (Neurogenic muscle weakness, ataxia, and Retinitis Pigmentosa) -late-childhood or adult onset peripheral neuropathy -ataxia, pigmentary retinopathy mutated genes: ATPase 6 gene of Complex V (ATP Synthase) Always heteroplasmic Maternally Inherited Leigh syndrome more severe form with with a larger proportion of mutated mtDNA - A subtype of Leigh Syndrome - Caused by the same mutations as NARP -More severe due to a greater degree of heteroplasmy NOTE : Complex V ATP Synthase - 17 sububuts 2 mtDNA/15 nDNA

Where does the mitochondria run the tricarboxylic acid cycle (krebs cycle)?

Matrix space TCA cycle =citric acid cycle=Kreb's cycle

In what temperature does plasma membrane become fluid ?

Melts from gel to a fluid, in higher temperature

Damage caused by ROS to cell components

Membrane attack hydroxyl radical-initation of chain reactiob by attacking double bonds of polysaturation f.a. propagation by O2to form peroxyradical and lipid peroxides degradation-malondialehyde in blood and urine b. proteins and peptides suspectible aa-proline, histidine, argining, cysteine, and methione cross links and aggregation DNA damage base alternations in the DNA and strand breaks

What is Peroxins ?

Membrane receptors actively import cytosolic proteins that bear an exposed SKL (serine-lysine-leucine) AA sequence

A deficiency in the enzyme arylsulfatase A causes an inability to degrade galactocerebroside 3-sulfate and its derivatives. This diseases is

Metachromatic leukodytrophy

What are simple ways to distinguish between an intermediate filaments and microfilaments ?

Microfilaments -thin -DYNAMIC -made from F-actin

What are MAPS ?

Microtubule associated proteins (MAPS) -protect MT from dissambly -inhibit tubulin dissociation (tau) -links MTs together to other cell structures

Describe the different configurations of the microtubules

Microtubule singlets (13 protofilaments , 25 nm diameter) =single vertical column of tubulin dimers -singlets : carry & move vesicles, organelles, and chromosomes -doublets : make up the axoneme (cilia & flagella :for motility) triplets : make up centrioles & basal bodies (MTOCs)= 9 triplets

Describe the mutation that occurs in cystic fibrosis?

Mutation in CFTR; crucial Cl- ion, channel (plasma transmembrane protein in epithelial cells ) "sweat test " - CF -predominant mutation is just : incorrectly folding protein this would still function normally if transported to plasma membrane-BUT-chaperones wont pass it on and it is ejected back into cyotosol and degraded --> CF

Disorder : Familial Hypercholesterolemia

Mutation in LDL receptors

What causes a AD Epidermolytic hyperkeratosis ?

Mutation in a keratin protein typical of the keratinocytes of the middle layers of the epidermis ( stratum spinosum)

X-linked Charcot Marie Tooth disease is caused by what ?

Mutation in connexin 32

What is the most common basic cause of Hereditary spherocytosis?

Mutation in spectrin or associated proteins

What are the 2 genetics systems to determine mitochondrial function ?

Mitochodrial Genome Nuclear genome

A 28 year old female visists her physician b/c of progressively weakening muscles in her thighs. Her father and his brother have a disorder of progressively weakening proximal muscles of the legs. No other abnormalities were discovered by physical exam. A muscle biopsy show ragged red fibers. What type of inclusions are most likely observed by electron-microscopic examination of the muscle specimen?

Mitochondrial crystalline Mitochondrial Crystalline Inclusions -electron microscopy -crystal like inclusions -consist of mainly precipitates of creatine kinase - 'railway-track' or 'parking lot' inclusion Ragged Red Muscle Fibers -mitochondria stained red -large numbers of mitochondria -aggregation of mitochondria at plasma membrane give 'ragged' appearance.

Pyruvate dehydrogenase complex deficiency (PDHc)

Mitochondrial matrix-multienzyme complex that provides the link btw glycolysis and the TCA cycle by catalysinf the conversion of pyruvate into acetyl coA deficiency -inability to convert pyruvate to acetyl co-A decrease. shunted to lactate dehydrogenase pathway to form lactic acid increase most common mutation E1 subunit-x linked dominant inheritance deficient NADH leading to deficient ATP-predominatly affects the brain severe energy deficit impacts on rain development in utero -> structural brain anomalies and epilepsy

MERRF Syndrome

Mitochondrial tRNA lysine

MELAS Syndrome

Mitochondrial tRNA-leucine

What does the Golgi apparatus do?

Modifies lipids and proteins from the ER; sort them and packages them in vesicles

Describe phospholipids

Most abundant types have : 1 hydrophillic (polar) head 2 hydrophobic (nonpolar) hydrocarbon, fatty acyl tails 1 polar head group + 2 hydrocarbon tails (14-24 C atoms) -1 Saturated -1 unsaturated ( > 1 cis-double bound -> kinks in chain) Tail length & degree of saturation determine membrane properties

What are glycoproteins ?

Most proteins on the outer membrane leaflet that are glycosylated. carbs sticking outward

What is Hunter syndrome ?

Mucopolysacchardidosis II) (MPS II) - defieiciency of iduronodate sulphatase (x-linked) -accumulation of dermatan sulphate and heparan sulphate -similiar to Hurler syndrome BUT later presentation (2-4 yrs) & milder course (survival into 30's) NO CORNEAL CLOUDING XLINKED-not autosomal recessive

What are the 4 major categories of lysosomal lipid storage diseases ?

Mucopolysaccharidoses Leukodystrophies Mucolipidoses Sphingolipidoses

What is the name for the double- membrane that encompasses and protects the chromatin ?

Nuclear envelope

What causes autosomal dominant epidermolysis bullosa simplex ?

Mutations in a keratin protein typical of the BASAL LAYER of the epidermis

What causes AD achondroplasia ?

Mutations in the FGFR3 RTK receptor that makes it constitutively active

What is MERRF ?

Myoclonus Epilepsy and Ragged Red Fibers - mutation in the mitochondrial tRNA genes -progressive myoclonic epilepsy and sz

What type of problem is caused by mutation in the desmin protein that forms intermediate filaments ?

Myofibrillar myopathies

What is a disease associated with the desmin intermediate fibers of myocardiocytes ?

Myofibrillar myopathy

Which motor proteins are associated with the actin microfilaments ?

Myosins

What forms the Mannose -6- phosphate residue ?

N-acetylglucosamine phosphotransferase within the cis-Golgi

Name the 3 posttranslational events that occur in the Golgi

N-oligosaccharides on ASPARIGINE O-oligosaccharides on SERINE and THREONINE Mannose 6 P to proteins for lysosomal trafficking

How do you make an integral membrane protein ?

N-terminal signal sequence (start-transfer signal) initiates translocation -an additional internal hydrophobic region of translocating protein begins folding to an alpha helical structure within pore=this constitutes a stop-transfer signal that anchors protein within membrane after ER signal sequence is cleaved off translocon separated from protein aplha helix now u have an integral membrane protein

What is niacin deficiency?

NAD + and NADP are cofactors involved in oxidation reduction reactions leads to pellagra 3 Ds: Diarrhea, dementia, dermatitis classic erythematous pigmented rash around the collar- CASAL NECKLACE 4th d-death

NAD+/NADH

NAD+: NADH ratio are high favouring hydride transfer from substrate to NAD to form NADH Generally involved in oxidations/catabolism predominatly mitochondria NAD+: NADH cycle are central in conversion of the chemical energy of carbon compounfs into phospho-anhydride bonds of ATP

Overview of pathways of transfer of electrons in the ETC

NADH : delta G= -53 kcal FADH (through oxidation of succinate) (delta G= -41 kcal

Leber's Hereditary Optic Neuropathy

NADH Dehydrogenase subunits

NADP-NADPH

NADPH: NADP ratios are higher favouring hydride transfer from NADPH to substrates Generally involved in reducations/anabolic pathway CYTOSOL gives reducing equivalents directly to f.a. synthesis, cholesterol synthesis and neutralize free radicals

your patient is suffering from chronic granulomatous disease which results in recurrent bouts of infection. CGD is characteized by an inability of phogocytic cells to kill invading microbes that they have engulfed bc these cells lack the ability to generate reactive oxygen species such as H2O2. A defect in which of the following enzymes is most likely the cause of the phagocytic cell dysfunction

NAPH oxidase

Muscle weakness, ataxia, retinitis pigmentosa

NARP

How is CGD diagnosed?

NBT test -microscopic slide test -nitroblur tetrazolium-yellow in color -superoxide reduces NBT to formazzan which is blue in color indicating normal levels of NADPH oxidase Di-hydro rhodamine test flow cytometry test phagocytic cells normally oxidize dihydrorhodamine to rhodamine which emit fluoresnce in the cell soter indication the levels of NADPH oxidase mist accurate for CGD

FGFR ______ regulates bone growth

NEGATIVELY -inhibits chondrocyte proliferation : inhibits cartilage growth; inhibits production of type II collagen by cartilage cells -long bones grow by replacement of cartilage at the epiphyseal growth plate -CONSTITUIVE ACTIVATION of RTK, FGFR3 -> type of dwarfism

What assist in dissociation of synaptobrevin from syntaxin, allowing membrane fusion.

NSF

Which cation is in the extracellular space?

Na (most abundant) Ca

list cotransporters

Na-glucose Na-AA Na-K-2 Cl NaCl KCl

What is the problem with an LDL receptor that has a class II mutation ?

Nascent LDL receptor protein will not fold correctly and is not transported to the Golgi

Overview of SER

Network of branching membranous sacs, chutes & tubules, continuous with RER cisternae, but lacks ribosomes & ribophorins. lacks ribosomes

What is NARP?

Neurogenic muscle weakness, Ataxia, and Retinitis Pigmentosa) -associated with mutations in the mitochondrial protein coding genes -late childhood or adult onset peripheral neuropathy -ataxia, pigmentary retinopathy

What is MPTP

Neurotoxin produced during illicit opoid synthesis of MPPP (analog of meperidine) drug induced parkinsonism

What kind of toxins are Botulinum toxins ?

Neurotoxins -cleave synaptobrevin ( v-SNARE) -vesicles carrying acetylcholine cannot fuse and release neurotransmitter at the neuromuscularjunction this will cause paralysis of respiratory & skeletal muscles : botulism is potentially fatal => flaccid paralysis

Are all proteins secreted?

No

Is proinsulin converted to insulin within the RER?

No

Can the 2 subunits able to assemble inside the nucleus ?

No- do not have the signaling

What is the name of the amino acid sequence that specifies proteins should be imported into the nucleus ?

Nuclear Localization Signal

what is the channel structure termed that permits entry to and exit from the nucleus ?

Nuclear Pore Complex (NPC)

Nuclear Export through NPC

Nuclear Ran GTP binds exportin Ran-GTP/exportin binds to cargo & nucleosporins & translocates through NPC Cytosolic Ran GAP converts Ran GTP into Ran GDP Ran GDP then releases exportin, which releases its cargo into cytoplasm Ran GDP and exportin then move back into nucleus Nuclear Ran GEF converts Ran GDP back to into active Ran GTP

What are the structures of the nucleus ?

Nuclear envelope 2 complete bilayer lipid membranes enclosed a perinuclear space studded with nuclear pores Nucleoplasm lamina (lining the inner membrane) Matrix- forms a fibrous scaffold that holds /supports: -nuclear particles (generally clustered snRNPS) -Heterochromatin &euchromatin- the ratio varies with cell-type & specific activity Nucleolus -large distinct nucleoplasmic region, not membrane bound -rna synthesis, ribosome subunit assembly location of functional snoRNPs

Where does O-linked glycosylation occur? Describe

O-linked glycosylation occurs ONLY in the Golgi -sugars attached to OH of selected serine or threonine residues

Describe Autophagy

OLD ORGANELLES fuse with lysosome for destruction if can not be degraded -> lipofucin (residual bodies)

What is oligosaccharrides ? What is there role?

Oligosaccharides, primary marker for cell recognition -attachement for bacteria, viruses, toxins, other cells -activated endothelial cells express selections which bind to oligosacharides on WBC and platelets -L-sectins recognize addressins on lymphoid organ cells

What seems to go wrong in a class V LDL receptor mutation ?

Once LDL has been released, the LDL receptors are not recylced back to the plasma membrane from the endosome

If a patient is heteroplasmic for a mtDNA mutation, under what circumstance will a clinical condition occur?

Only if the proportion of mutant mtDNA exceeds a threshold In heteroplasmy, the proportion of mutated mtDNA molecules must exceed a thrshold before clinical or biochemical consequences occur. This can result in reduced penetrance. Beyond the treshold, the severity of the consequence correlates with the proportion of mutated molecules

How are peroxisomes formed ?

Originate straight from the ER & pre-exisiting peroxisomes -growth by uptake of specific peroxisomal proteins and lipids from cytosol

Osmotic Coeffcient

Osmotic Coefficient for NaCl is 0.93, 150 mM NaCl= 300 mOsm/L 300 mOsm/L x0.93= 279 mOsm/l NaCl 275-300 mOsm/L as Normal ECF Osmolarity

What diseases is associated with Collagen I

Osteogenesis imperfecta Ehlers Danlos syndrome ( Collagen I, III, V)

Where is 5S rRNA (60S) transcribed ?

Outside the nucleolus by RNA Pol III

What is Reactive Oxygen Species (ROS)

Ox-Phos in mitochondria accidently produce most endogenous ROS ROS can inactiviate ETC e- acceptors: causing a further build up of ROS ROS damages protein, RNA, DNA (mtDNA: no histones & decrease in DNA repair) ROS implicated in degenerative diesease (Alz), CA, and aging

Describe the Reactive Oxygen Species (ROS)

Ox-Phos in mitochondria produces energy & most endogenous ROS ROS can inactivate ETC electron acceptors and therein cause a further build up of ROS ( lost electrons make more superoxides)

What process are mtDNA encoded proteins involved in ?

Oxidative phosphorylation (ETC or ATP synthases) 3/4 complexes in ETC, encoded in mtDNA complex I : NADH Dehydogenase complex III : Cytochrome b-c1 complex iv : Cytochrome oxidase ATP synthase ( Complex V): synthize ATP, carry out oxidative phosphorylation

What two things do mtDNA mutations affect?

Oxidative phosphorylation capacity and ATP production -tissues with high energy demands are most affected -lactic acidosis is common -ragged red muscle fibers and crystalline inclusions are common histological findings

B/L ptosis and RAGGED RED MUSCLE FIBERS

PEO

What is Zellweger spectrum ?

PEX mutations Defective peroxisomal biogenesis failure to import peroxisomal proteins -> empty peroxisome -Zellweger syndrome -neonatal adrenoleukodystrophy (NALD) -Infantile Refsum disease -Hyperpipecolactemia

which of the following best describes the activity level & phosphorylation state of the listed hepatic enzyme in an individual who consumed a carb rich mea about an hour ago.

PFK-1 ACTIVITY HIGH PFK2 ACTIVITY HIGH NO PHOSPHORYLATED FOR BOTH PYRUVATE KINASE ACTIVITY HIGH NO PHOSPHORYLATED

Describe the animal plasma membrane

PM glycocalyx-carb-oligosaccharide -integrity -structire -selective permeability : ion charge

Which anion is in the intracellular space

PO4 and organic anions proteins

Progressive External Ophtalmoplegia (AD)

POLG & TWNK

RER: _______ SYNTHESIS

PROTEIN SYNTHESIS Transmembrane go to PM, ER membrane Soluable -> secreted ER Signal sequence -> directs protein and ribosome onto receptor Free ribosome -> synthesis proteins into cytosol RER Pore complex -> Transcolon Signal Sequence KDEL -> Sol KKXX

As part of collagen biosynthesis, what is secreted by a fibroblast ?

PROcollagen

Which of these chemo drugs works through inhibiting the depolymerization of microtubules and thus blocks mitosis ?

Paclitaxel (PAXOL)

Which of these drugs binds assembled microtubules and freezes them in place so that they cannot depolymerize ?

Paclitaxel (Taxol)

What drug bind and stabilize microtubles (INHIBIT depolymerisation) ?

Paclitaxel (Taxol) -blocks mitosis (can not break down mitotic spindle) -treatment of cancers

Which cells are protein secreting ?

Pancreas plasma cells developing hematopoietic precursors cancer cells

What is the organization of actin within the cell ?

Parallel bundles and web-like organizations -initiated by specific nucleation proteins -stabilized by specific cross -linking proteins

What is opsonins ?

Proteins such as complements, antibodies (Fc), bac. oligosaccharides, apoptotic cell membrane - opsonins bind to receptor proteins on plasma membrane of phagocyte

B/L ptosis, ataxia, heart block, pancytopenia, CHILDHOOD ONSET

Pearson Syndrome

What is permeability coeffcient (P)? ( factors affecting simple diffusion)

Permeability Coeffecient (P) includes the membrane thickness, the diffusion coefficient of the solute w/n the membrane, and the solubility of the solute in the membrane

A newborn is evaluated in the ER due to sz & hypotonia. The doctors suspect the child may have Zaellwger, syndrome, an AR disorder. Which of these would be true if they are correct in this dx?

Peroxins do not recognize the SKL AA signal Failure to import enzymes into the peroxisome

Large scale engulfment of particles, large aggregates or cells involve major jaw like movement of the plasma membrane and the formation of large vacuole-like bodies is best referred as ?

Phagocytosis

What is phagocytosis?

Phagocytosis is triggered by various cell surface receptors, but it is clathrin independent

What is a phagolysosome ?

Phagosomes result that acidify & fuse with lysosome

A randomized controlled trial of 340 patients examined the effect of a combination carfizomib-lebalidomide-dexamethasone (Study arm A)or lenalidomide-dexamethasone (Study arm B). Drug safety, efficacy, and dosage were already establish in previous trials. What phase of a clinical trial is this study?

Phase III

ATP continued

Phosphate oxygen bound (phoso-anhydride bound) has a high free energy of hydrolysis the phosphate can be transferrred from ATP to other acceptor groups Act as a co-substrate, co factor or allosteric effector high energy is not synonymous w stability of the chemical bond in question, nor does it refer to energy required to break such bonds concept of high energy compounds implies that products of their hydrolytic cleavage are in more stable forms than original compound

Which two membrane lipids are amphipathic ( have a hydrophilic head and hydrophobic tail)?

Phospholipids and Glycolipids

Exportin

Picks up cargo when it binds Ran-GTP

A 4yr old female p/w prolonged HA. Her family reported that she gave gave inappropriate answers to questions and had STROKE like weakness on the right side of her body. Her mother reported a family hx of STROKE like behaviors. Her serum lab values were normal expect for lactate which was 3 fold higher than normal. MRI of the brain identified stroke like lesions. Which gene mutation is most likely responsible for her condition?

Point mutation in the mitochondrial lEucine tRNA Disease: MELAS Mitochondrial Encephalomyopathy Lactic Acidosis and Stroke like episodes) -stroke like episodes: vomitting. HA, visual disturbances -short stature -diabetes, -sensorineural hearing loss -maternally transmitted mutates gene: tRNA Leucine ALWAYS HETEROPLASMIC

A physician notes b/l ptosis in a 23 yr old female patient. Her father also suffers from b/l ptosis and has poor control of his facial muscles. The physician suspects an inherited disease affecting the mitochondria. Which gene mutation is most likely possible?

Point mutations i the nuclear PLOG gene encoding DNA Polymerase Gamma Explanation : The clinical presentation appear to be Progressive External Opthalmoplegia. Importantly the father is affected, which means the mode of inheritance can not be mitochondrial. Instead this is likely the AD form of PEO Mutations in POLG, encoding DNA Polymerase gamma & TWNK encoding the helicase Twinkle

Describe carbohydrate metabolism

Polyhydroxy aldehydes or ketones or substances which on hydrolysis yields these compounds av. calorie requirement for standard adult male: 2000 kcal/day contributed by carbohydrates: 50 to 65 % of total energy requirement energy yield for different food sources carb 4 kcal/gm triglycerides 9 kcal/gm proteins 4kcal/gm ethanol (not considered as a food source) : 7 kcal/gm

What two enzymes are involved in mtDNA replication and repair ?

Polymerase : DNA polymerase gamma (POLG) Helicase : Twinkle (TWNK)

Zidovudine (AZT) is a reverse transcriptase inhibitor used to treat HIV infections. It causes secondary mitochondrial myopathy b/c it is also an inhibitor of :

Polymerase gamma

What protein modification is a marker specifying that an incorrectly folded RER proteins must be destroyed in the proteosome?

Polyubiquination

What is the main function of the mitochondria ?

Power plant of the cell -most of the ATP production through aerobic respiration also cell signaling & apoptosis (i.e. muscle cells bright pink)

Which DNA polymerase & helicase are necessary for mitochondrial DNA replication?

Poymerase gamma & twinkle

What are the roles of protein in the plasma membrane ?

Proteins: transmembrane & peripheral -membrane channels/pumps : create ion concentration gradient (ATP-dependent calcium ion pump) -transporters : transport molecules across (glucose transporter) receptors : information relay (via signaling molecules) - subunit for the insulin receptor adhesion molecules: cell to cell, cell to ECM ( fibronectin receptor for adhension to the ECM) Gap junctions : communicate between cells: coupling (subunit prion for a gap junction complex)

Regulation of metabolic pathways

Principle of pathway regulation : - series of sequential reactions in which the product of one reaction is the substrate of the next reaction -each step is usually catalysed by a separate enzyme all the enzymes have the common function -> convert substrate to end product of that pathway they may have a branch point at which intermediate becomes the precursor for another pathway

Describe mitochondrial pore formation and its correlation with apoptosis ?

Pro-apoptotic bcl-2 proteins (BAD, bax) translocate from cytosol to mitochondrial membrane in response to cell damage/stress & signaling -> formation of pores in outer membrane (BAX) -> release pro-apoptotic factors ( cytochrome C) into cytosol -> activate caspase cascade -> apoptosis

Where does procollagen processing begin ?

Procoallagen processing begins in RER hydroxylation of proline (propyl) & lysine (lysyl) residues ; important for interchain H bonds glycosylation of hydroxylysines -single sugars added disulfide bond formation (propeptide C terminal) ; aligns chain, initiates triple helix formation-zippering mechanism C' -> N' H-bonds between 3 procollagen chains -> assembles the procollagen triple helix processing continues in Golgi before procollagen molecules secreted

What is the function of the mitochondria inner membrane ?

Production of ATP via the ETC and ATP synthases -ETC -Oxidative phosphorylation -transhydrogenase -transport systems -FA transport

What is the difference between a prokaryotic and animal cell?

Prokaryotes have a cell wall ( the prokaryote cell tiny, simple and sturdy because of the cell wall.), Prokaryotes also have a plasma membrane ( chemical barrier from outside world). Animal cells have no cell wall-depend on plasma membrane to keep self intact and safe from outside. Humans--> animals cell, so all human cell have a plasma membrane.

What are prolines and lysines converted to in the RER ?

Prolines and Lysines are converted to hydroxyproline and hydroxylysine by enzymes in the RER Why does deficiency of vitamin C cause scruvy ? all these ( proline & lysine post translational modification in RER) require vitamin C ( asorbic acid) & iron - this is where a deficiency in Vitamin C can cause scurvy 3& 4 hydroxyproline 5 hydroxylysine

Describe the modifications in ER

Protein Folding BiP, Calnexin and Calreticulin -> Chaperon help folding Signal Peptidase -> removes signal Add N-LINKED OLIGOSACCHARIDES -> Serine / Threonine sequence -> continue in Golgi Disulfide bonds - help with protein folding

What is the ECM ?

Protein fibers in " ground substance"

Protein-protein interaction

Protein kinase A is part of G-protein coupled receptor pathway which phosphoryates target enzyme and proteins inactive when regulatory and catalytuc subunits are together when the regulatory subunits R of protein kinase A bind the allosteric activator cAMP, they dissociate from the enzyme, thereby releasing active catalytic subunuts (c). inactive protein kinase A -> cAMP binding -> active protein kinase A

How are proteins sorted ?

Proteins are 'sorted" according to which receptor binds them with what vesicle the receptor will dock

What happens in the RER

Proteins are folded properly new protein chains are oligomerized into protein complexes GPI anchors are attached to new proteins that require them addition and partial processing of N-linked oligosaccharides protein disulfide isomerase forms disulfide bonds in proteins that require them

The mitochondrion has its own internal genome, yet most of its protein are transcribed in the cells nucleus. How do these proteins get into the mitochondria?

Proteins made in the cytosol have mitochondrial import signals in their AA sequence

How does the transport of electrons helps cells to generate energy ?

Protons are transmitted across the mitochondrial membrane by the ETC, building up a gradient which is used to drive ATP synthesis

Describe pumps

Pumps oppose the equilbrating systems to preserve intracellular concentration of solutes, particularly ion, which are comptabile w life

What is purine catabolism ?

Purines ( A,G) = degraded to uric acid Xanthine oxidase purine are converted into xanthine then into urate forexcretion

Process of transamination requires which of the following vitamins as cofactors

Pyridoxine (B6)

What metabolite formed from glycolysis is taken up into the mitochondria ?

Pyruvate

What 2 G proteins involved in cell movement

RAC RHO RAC -> rearranges actin to stretch front edge out into a lamellopodium old focal contact released Rho mediated new focal contacts made

Anaerobic glycolysis is the predominant source of ATPs in which of the following cells

RBCs

Where does COP II go ?

RER -> Golgi

What can the Reactive Oxygen Species damage ?

ROS can damage almost everything ; proteins, RNAs, DNA (mtDNA: NO HISTONES & decrease in DNA repair), lipids

What important G protein governs the docking of a microtuble associated coated vesicle with a tether protein on the target membrane ?

Rab-GTP

What does Rab-GTP do ?

Rab-GTP regulates initial docking and promotes binding of the SNARES; GTP then hydrolyzed to GDP

What causes a vesicle to dock ?

Rab-GTP, engages the tether protein

Describe the process of Export in the nucleus

Ran GTP binds to exportin together bind to cargo with NES tag go through NPC Ran GAP dephosphorylation Release exportin -> caro, and Ran GDP -exportin and Ran GDP back to nucleus GEF turns GDP -> GTP

Fill in the blank Any specific lysosomal storage disease is ______. However, overall, there is about ______ incidence of lysosomal storage disease among ____.

Rare 1 in 2500 newborn

What is Fanconi-Bickel Syndrome?

Rare AR condition chaaracterized by hepatorenal glycogen accumulation and proximal renal tubular dysfunction also called glycogen storage disease type XI Mutation in the GLUT2 transporter-hepatocytes, pancreatic beta cells, enterocytes, and renal tubular cells impaired transport of glucose, galactose, and fructose in these cells. s/s failure to thrive hepatomegaly ( secondary to glycogen accumulation) vit D resistnat rickets fasting ketotic hypoglycemia and postprandial hyperglycemia due to low heptatic uptake of glucose

What is Goodpasture Syndrome ?

Rare autoimmune diseases onset: teen-20, increase in males -autoantibodies against TYPE IV collagen ( alpha 3 chain) inflammatory destruction of basement membrane in kidney glomerulus & lung alveoli -hemoptysis & glomerulonephritis w progressive renal failure

What is De vivo diseases

Rare inherited disorder of nervous system AD GLUT 1 def low glucose in CSF/Brain refractory infantile sz microcephaly and motor dysfunction TX: Ketogenic diets

Describe the Chediak-Higashi syndrome

Rare, AR and dangerous -invoves CHS1/LYST gene, encoding lysosomal trafficking regulatory protein that normally induces vesicle fusion, mutations cause: -delayed fusion of phagsome with lysosome in leukocytes -autophagocytosis of melanosomes in melanocyes -> albinism/hypopigmentation -granular defects in NK cells and platelets -recurrent infection -> life threathening - also albinism and light sensitivity, coagulation trouble, possible neuropathy and ataxia

Certain tumor cells are known to have a plasma membrane Na+ channel that is activated by acidic extracellular pH. In these cells, of acid is added to the extracellular medium, which of the following would occur?

Rate of ATP utilization will increase

In an intact, cell, the actual free energy change associated with an enzyme catalyzed reaction is freq. different from the standard free energy change (delta G 0') of the same reaction bc in the intact cell

Reactants and products are not a 1 M conc.

What is GM1 Gangliodside?

Receptor for the cholera toxin, found in the intestinal epithelial cells . Target for cholera toxin

Medium scale invaginations of specific large or small molecules into fuzzy boundary pits that internalize into the cell to form a coated vesicle is best referred to as :

Receptor mediated endocytosis

What is Clathrin-coated pits ?

Receptor mediated endocytosis endocytosis of LDL bound to LDL receptor a coated pit has formed and will soon bud off as an endocytotic vesicle

What is the spectrin network ? Why is this important ?

Reinforces the bilayer ; makes a deformable network -4-5 tetramers of spectrin (alpha and beta chains) linked into a junctional complex held together by binding short F-actin & protein 4.1 -ankyrin binds bands 3; attaching spectrin cytoskeleton to membrane -protein 4.1 links actin to glycophorin (single pass transmembrane glycoprotein), also binds spectrin and band 3 band 3: multipass transmembrane protein It is important because it can withstand stresses and bends without breaking

What does the medial cisterna sort ?

Removal of Mannose addition of GLcNac

RanGEF

Removes GDP from Ran, replaces with a fresh GTP

Which small G-protein acts as a switch to promote actin polymerization and branching at the leading edge of a moving cell ?

Rho-GTP

What molecular switches are particularly important inactivating the dynamic extension of the actin cytoskeleton so as to form lamelipodia and similar structures as the leading edge of a cell that is moving or about to move ?

Rho-GTP family

Which of the following the least likely component of a human cell membrane ?

Ribonuclueoproteins

What Rotenone

Rotenone is an odorless, colorless, crystalline compound used as a broad spectrum insecticide, piscide, pesticide

Rotenone inhibits complex I

Rotenone, a common insecticide and sone barbiturates (amytal) inhibits complex I substrates yielding NADH cannot be oxidized as Complex I where NADH enters ETC is inhibited by rotenone However, substrates yielding FADH2, can still be oxidized because Complex I bypassed and electrons are donated to ubiquinone Addition of ADP to a suspension of mitochondria supplemented w malate and phosphate markedly stimulates oxygen uptake as ATP synthesis occurs. Oxygen uptake is markedly inhibited by rotenone, but when succinate is added, ATP synthesis and oxygen consumption resume until the supply of ADP is exhausted

What impacts complex I

Rotone Barbitirates piercicidin A MPTP Metformin

Which of the following is correctly matched ?

SER : Lipid synthesis Nucleolus :rRNA synthesis (NOTE: RER does not synthesis ribosome- ribosomes are beads on RER )

While we sleep, our brain still needs glucose. The liver plays a role in making glucose readily available. Which statement is CORRECT regarding this process ?

SER glucose-6-phosphatase dephosphorylates G6P -> free glucose

What does SNARE proteins provide ?

SNARE proteins provide specificity -v (vesicle) SNARE- proteins interact with t(target) SNARE proteins to form a functional complex (other proteins bind to this complex and induce the membrane fusion)

What are the cytoskeleton functions ?

SUPPORT & STRENGTH -maintains cell structure and dispereses tensil forces -cell-cell & cell-ECM adhesion CELL MOVEMENT -embrryogenesis -wound healing -leucocyte migration -cilia & flagella INTRACELLULAR MOVEMENT -phagocytosis -organelle transport -CYTOKINESIS -CHANGES IN CELL SHAPE

What is sodium dependent transporter (SGLT1)

Secondary active trsnsport harness the energy supplied by the movement of Na down its concentration gradient to power transport of glu/gal

What does a transport vesicle do?

Shuffles proteins to various locations such as the Golgi apparatus

What is the negatively charged acidic sugar residue on GM1 ganglioside ?

Sialic acid

The surface antigens of a newly discovered pathogen are negatively charged. The cell membranes of the patient's cell are also negatively charged, so that the pathogen is repelled from most cell. What structure/chemical are most responsible for the overall negative charge on the outer cell membrane of healthy cells?

Sialic acid sugars A cell's sugar coat: glycocalyx repulsion : negative charges from sialic acid sugars

Where is soluble tropoelastin secreted and assembled ?

Soluble troppelastin is secreted and assembled into elastic fibers close to plasma membrane little secondary structures -> stretchy -covalent crosslinking -fiber & sheet formation ( converting tropoelastin to elastin)

Aldehydes react ____

aldehydes react sponteneously -> covalently bond w ea other or w other lysines or hydroxylysines -usally at ends, intra & intermolecular links -stabilize side by side packing

In the NPC molecular traffic, what type of transport do the macromolecules utilize? what about small

Selective and active transport passive diffusion of small molecules

Why does the nucleus compartmentalize?

Separate nuclear and cytosolic enzymes concentrate substrates and enzymes where needed Protect DNA from harsh cytosolic enviroment Separate new pre-mRNA from ribosomes to prevent premature translation Regulate gene transcription , cell cycle and cytosolic metabolism through shuttling factors in and out of nucleus

Ran-GDP

Separates from importin or exportin to go its own way

What is neurological syndrome in neonates ?

Severe neuro dysfunction -hypotonia -hyporeflexia -sz -MR -dysphagia dysmorphic features -prominent forehead -hypertelorism -large fonatanelles hepatomegaly and liver dysfunction death is likely by 6-12 months

A 5 yr old girl falls through the ice while skating on an outdoor pond. She is removed from the water w/n 1 min but dry clothing is not available, and she is still cold and wet 20 min later. Which of the following mechanisms helps maintain the patient's core temperature during the period following her rescue?

Shivering

Which of these cells would normally be expected to have more than 1 nucleus?

Skeletal muscle cells

Due to the phospholipid bilayer that forms the bulk of a cell membrane, the membranes of cells and organelles allow certain types of molecules to pass through but not others. From what we have studied, which type of molecule do you think will pass MOST easily through the membrane of a cell or organelle ?

Small & hydrophobic

What does Signal Peptidase do?

Signal peptidase cleaves off an N-terminal signal peptide as protein enters ER lumen -some transmembrane proteins lack the cleavage site and retain the hydrophobic signal peptide sequence as an internal region these then become embedded within the membrane

When describing the process of protein synthesis in the rER, place the following in the correct order.

Signal recognition particle binds to ER signal sequence SRP complex brings the ribosome to a translocon BiP binds peptide N-linked glycosylation

Describe the nuclear genome

Size : 3, 300,000, 000 bp 23 in XX 24 in XY all linear 23 in haploid cells 46 in diploid cells several classes of histone and non histone protein ~ 30,000 genes 1/40,000 bp repetitive DNA large fraction transcription: most genes are transcribed individually introns in most genes % of coding DNA : 3% Recombination : at least once for each pair of homologs at meiosis inheritance: Medellian for sequences on X and autosomes, paternal for sequences on Y

What are the s/s of I-cell (I-inclusion bodies) disease ?

Skeletal abnormalities (lack of growth) coarse facial features restricted joint movement pyschomotor retardation enlarged liver, spleen, heart valves, death CHF/RTI life expectancy is less than 10 years

What does the cis Golgi network do ?

Sorting -phosphorylation of oligosaccharides on lysosomal proteins

Describe the basal lamina

Specialized ECM, flexible, thin -almost like a carpet all component produced by the cells resting upon it (epithelial cells) network of : type iv collagen laminin entactin/nidogen HSPGs(perlecan)

What is the name of the nucleoplasmic substructures that process and modify pre-mRNAs?

Speckles

What are the two nucleoplasmic particles? What is there role ?

Speckles : premRNA processing and modification by snRNPs CBs/Gems formation & maturation of snoRNPs and snRNPs

Which of the following correctly matches Speckles?

Speckles, mRNA modification

Which cells in the human body have flagellum?

Sperm cells have the only human flagellum as their " tail "

A patient w OH cirrhosis shows ascites, an umbilical hernia, and wasting omuscle. His blood work shows an increased reticulocyte count and increased LDL & cholesterol. Excess cholesterol is present in the RBC membrane. You expect to find all of the following in your alcoholic patient, EXPECT :

Spherocytosis You would see: -spur cells -acanthrocytosis -hemolytic anemia -sequestration and destruction of RBCs by spleen

A patient w oh developed pancreatitis that affected his exocrine pancreatic function. He exhibited discomfort after eating a high carb meal. the patient most likely had a reduced ability to digest which of the following ?

Starch

During exercise, stimulation of the TCA cycle results principally from which one of the following ?

Stimulation of the flux through several enzymes by a decreased NADH/D + ratio

Describe the intermediate filaments

Structure : fibrous proteins supercoiled into thicker cables diameter : 8-12 nm proteins subununits : one of several different proteins of the keratin family, depending on cell type Main function -maintain cell shape (tension-bearing elements) anchorage of nucleus and certain other organelles formation of nuclear lamina

Describe actin filaments (microfilaments)

Structure: two intertwined strands of actin , each a polymer of actin subunits Diameter : 7 nm Protein subunits : actin

What is the mutated gene in LHON?

Subsunits of complex i: NADH Dehydrogenase

A 30 year old male is seeking consultation for rapid deterioration of her central vision due to degeneration of her OPTIC NERVE. Her peripheral vision is unaffected. The patient most likely has a mutation in the gene encoding which of the following ?

Subunit 4 of Complex I (NADH Dehyrogenase) Disease : LHON (Leber's Hereditary Optic Neuropathy) S/S : Subacute, painless, b/l central visual failure Onset: median age of onset 24 yr OPTIC NERVE is the only affected tissue Mutated genes : Subunits of Complex I ( NADH Dehydrogenase ) MAY BE HOMOPLASMIC OR HETEROPLASMIC

A 76 y Caucasian female is eval. for painful lesions on her lips and a the corner of her mouth. She is mildy demented and lives alone. She is diagnosed w riboflavin def. (vitamin b2). activity of which of following enzymes is most likely decreased in this patient?

Succinate dehydrogenase

a 36 yr old greek man w viral pneumona has a self-limiting episode of hemolysis. over the next week, he has increased rate of reticulocytosis. which of the following compounds of the tca cycle serves as a precusor to heme synthesis?

Succinyl coA

What does the trans Golgi network sort?

Sulfation of tyrosine and carbohydrates

What does the trans Golgi network do ?

Sulfation of tyrosine and carbohydrates sorting into the lysosome, plasma membrane, secretory vesicle

What does the ran GTPase do?

Supplies the energy required for translocation of protein complexes through NPC

What is the full name of the SMN protein ?

Survival of motor neurons protein

Glucagon synthesis and secretion

Synthesized as a 160 aa prepropetide and cleaves to 29 aa in pancreatic alpha cells secretion suppressed by glucose and insulin pancreatic blood flows from beta cell and past alpha cells. so if insulin has been secreted bc of high glucose, glucagon is supressed catecholamines stimulate glucagon release plasma t1/2 ~ 6-7 min

What does the SER do

Synthesizes lipids and also performs various other functions

What is the role of the RER

Synthesizes the proteins and packages them in vesicles; vesicles commonly go to the Golgi apparatus

list the cell surface receptors ?

TESTORONE RECEPTOR IS NOT A CELL SURFACE RECEPTOR -INTRACELLULAR PROTEIN RECEPTORS

Which of the 4 types of cell-to cell junction forms a barrier that is impermeable to most solutes ?

TIGHT JUNCTION

Continuing with nucleolus formation, what produces the 45S pre-rRNA ?

TRANSCRIPTION -processed and modified to produce the modified 5.8S, 18S, and 28S rRNAS -mature rRNAs find & bind their specific proteins -pre-ribosomal subunits are exported to exported to cyotplasm

Describe epithelial intermediate filaments

TYPE I keratins (ACIDIC) TYPE II keratins (BASIC) epithelial cells and their derivatives ( i.e. hair and nails)

A famous disease that centers on the inability to degrade the GM2 type gangliosides is :

Tay-Sachs Disease

What does the the overlapping segment design provide ?

Tensile strength note : intermediate filaments lack of filament polarity

What happens in tetanus ?

Tetanospasmin also cleaves SNARES tetanus toxin ( tetanospasmin) -retrograded axonal transport up into spinal cord and into cell body of an inhibitory interneuron-where it cleaves synaptobrevin ( the v-SNARE) This prevents vesicle fusion & the release of GABS & glycine (inhibitory neurotransmitter) onto the motor neuron at the neuromuscular junction prolonged contraction of skeletal muscles=tetanus= violent spastic paralyis (potentially fatal)

(Fill in the blank ) You walk into the ER and encounter a distraught patient c/o neck stiffness, dysphagia & lock jaw. The patient states he had stepped on a rusty nail, but thought nothing of it. Chances are this patient was exposed to the _____ toxin, which degraded ____

Tetanus / synaptobrevin Tetanus toxins cleaves the synaptobrevin (the v-SNARE) synaptic vesicle = v-SNARE, synaptobrevin t-SNARE = syntaxin synaptonrevin tightly binds t-SNARE = syntaxin, in plasma membrane of axon terminals

You walk into the ER and encounter a peculiar patient. The patient complains of neck, stiffness, dyshagia, and LOCKJAW. The patient states they stepped on a rusty nail, but thought nothing of it. Chances are this patient was exposed to the ____, which degraded _____.

Tetanus/ synaptobrevin

An individual displays lactic acidemia as well as reduced activity of alpha ketoglurate dehydrogenase activity. the most likely single enzymatic mutation that leads to these changes would be in which one of the following proteins

The E1 subunit of pyruvate dehydrogenase

When a geneticist is discussing preproalbumin, what sequence is termed the 'pre' portion of this protein?

The ER-specific signal sequence

When a hormone binds to a receptor linked to a Gq heterotrimeric G protein, what happens ?

The Gq alpha subunit moves down the inside of the plasma membrane until it binds and activates phospholipase C GPCR signaling pathway using DAG and IP3 Gprotein is Gq activated when ligand binds to GPCR effector protein phospholipase C (PLC) PLC breaks down membreane inositol phosholipid to 2nd messsengers 1. Inositol 1,4,5 triphosphate

What happens when a hormone binds to a receptor linked to a Gi heterotrimeric G-protein ?

The alpha Gi protein dissociates from the heterotrimeric G protein, travels down inside the membrane and inactivates adenyl cyclase activation of this receptor will oppose the activation of a receptor linked w a Gs type G protein if phosphodiesterase is present, the levels of cAMP within the cell will fall PKA is much less likely to be acitvated by cAMP less phospho-CREB will be present in the nucleus and cAMP induced transcription will come to a halt Gi is to inhibit adenyl cyclase inhibit cAMP

Describe the endomembrane system ?

The endomembrane system : RER, SER, Golgi apparatus . vesicle transport Lipid metabolism, synthesis of cholesterol & most phospholipid -SER RER-membrane associated proteins, processing them to -> packed into vescicle to golgi for final step Golgi- receiving & sorting to proper places "post office" "shipping system" lipid and protein production and modification the main pathway for intreacellular traffic

Where do the enzyme reside that remove the N and C propeptide extensions from procollagen to produce tropocollagen ?

The exterior surface of the cell

What recognizes the signal sequence and brings the polypeptide and its ribosomes to the membrane of the RER?

The signal recognition particle

Hexokinase (1-3)

all hexoses Km low (high affinity) location : universal vmax low glucose 6-po4 inhibits the enzyme insulin no regulation

What property of microtubules allows them to associate with specific motor proteins, such as dynein and kinesin?

They have polarity a positive and negative end

Describe non-competive inhibition

The inhibitor usually binds to a different domain on the enzyme, other than the substrate binding site -> it does not matter whether the substrate is bound to the enzyme or not (equal affinity)-> Km remains the same according to the equation -> strong affinity for inhibitors prevent catalysis possibly due to distortion in enzyme conformation Vmax reduced

Describe gout disease

decrease in uric acid excretion (builds up in blood) uric acid forms after purine degradation key enzyme: xanthine oxidase tx: allopurinol ( xanthine oxidase inhibitor)

What crucial protein functions in the transporting the lysosomal enzymes from the trans Golgi netwoek to the late endosome or lysosome ?

The mannose 6 phosphate receptor

The pedigree shows a family with multiple generations affected with a myopathy that is characterized by degeneration of muscle fibers. There is considerable variability in the severity of the symptoms even amongst siblings. The most likely cause of this variable expression is :

The mitochondrial bottleneck offsprings have VARYING degrees of heteroplasmy compared to their mother during oognesis : a restriction in the number of mitochondria -subsequent expansion NOTE :threshold does not explain why there is a variation. threshold explains why some children present or severely affected and others not

A 56 y old mother with Leber's Hereditary Optic Neuropathy has 4 children, 3 of which also have LHON. Her eldest son, aged 34, however is not affected and has perfect vision. Which genetic mechanism explains the reduced penetrance observed in many mtDNA diseases?

The mitochondrial threshold theory Explanation: The theshold theory predicts that if an individual has a proportion of mutant mtDNA below a certain threshold, they will be completely unaffected. The disease will therefore show reduced penetrance. In heteroplasmy, the proportion of mutated mtDNA molecules must exceed a threshold before clinical or biochemical consequences occur. This can result in reduced penetrance Beyond the threshold, the severity of the consequence correlates with the proportion of mutated molecules.

describe hyperventilation

decrease pco2 decrease reabsoprtion of hco3 by kidneys

How do proteins made a cytosolic ribosome get into the mitochondria ?

The proteins have a 9-70 AA sequence exposed on their surface that serves as a signal tag that gets them specifically imported into the mitochondria

How do proteins made on cytosolic ribosomes get into the nucleus ?

The proteins have an exposed 2-22 AA sequence that serves as a signal tag that gets them specifically imported through the nuclear pores

delta G 0' is defined as the standard energy change when

The reactants are present in conc. of 1 Mol/L at pH 7

What is best way to interpret this figure ?

There is less likelihood for publication bias

How do proteins that are made and processed by the RER and then matured in the Golgi end up back in the ER?

These proteins have an exposed 4 AA sequence that serves as a signal tag that gets them sorted into vesicles that take them back to the ER lumen

Describe rate limiting step

This is the slowest step. changes in the rate limiting step influences the flux through the rest of the pathway it is usually the first committed step in a pathway allosteric in nature usually irreversible in nature

In tetanus, when the tetanus toxin cleaves the synaptobrevin ( the v-SNARE), what does it prevent ?

This prevents vesicle fusion and the release of GABA and glycine (inhibitory neurotransmitter) onto to the motor neuron of the neuromotor junction

What does the RER GPI transamindase do ?

This ultimately directs proteins into lipid raft of outer leaflet.

Describe a prokaryotic cell wall?

Tightly inner meshed & inner woven molecules. peptidoglycan ( carb linked to peptide/protein)

In the plasma membrane what determines the melting point ? (Tm)

Tm depends most on the ration of unsat : sat F.A. and amount of cholestrol

Elastin, unlike collagen, is not a particularly long protein. It has no hydroxylysine and it does not aggregate with other elastin molecules to form a triple helix. How, then do the elastic fibers, and sheaths form ?

Tropoeleastins are crosslinked into an interwoven structure that can be long and wide

During nuclear import through the NPC, what is the main role of Ran-GTP?

To interact with importin, causing it to let go of the cargo

Why are collagen fibrils interwoven with elastic fibers ?

To limit stretching and prevent tissue tearing

What process produces the 45S pre-rRNA? How?

Transcription processed and modified to produce the modified 5.8S, 18S, AND 28S rRNAs mature rRNA find and bind their specific receptors preribosomal subunits are exported to cytoplasm

Which of these functions is an unlikely role for an integral plasma membrane protein?

Transcription factor EB that stimulates expression of lysosomal enzymes

Decribe the polypeptide processing in the RER

Translocated polypeptides fold & are modified within the lumen of the RER : - proper folding -addition and processing of N-linled oligosaccharides ( carb clusters) -formation of disulfide bonds -addition of GPI anchors Oligomerization (of chains if necessary )

What are the two proteins that the RER captures. Describe each.

Transmembrane proteins (partly translocated across ER membrane)-> end up in plasma membrane, organelle membrane, or ER membrane -Soluble proteins ( translocated & released into the ER lumen) ->for secretion or itno the lumen of an organelle

What are membrane proteins functions?

Transport : nutrients, metabolites, ions across bilayer Anchor membrane to macromolecules on either side Receptors: receive external signals and transmit Enzymes : lactase in the apical mebrane of GI epithelial cells Cell identity markers : MHC TRANSPORT, ANCHORS, RECEPTORS, ENZYMES, MARKERS

Describe Caveolin-coated transport vesicles

Transport vesicles coated with caveolin & cavin function in transcytosis, endocytosis, membrane recycling and cell signaling

Describe Type IX collagen

Type IX colalgen bind and link type II fibrils and bind chondroitin sulfate (GAG)

Describe Type VI collagen

Type VI bind and link type I fibrils

Which of the following is TRUE of human mitochondrial DNA ?

Unlike nuclear DNA, there can be thousand of copies per cell - Gene Rich (1 gene per 445 bp) side note: devoid of histones, not packages into chromatin

Your friend is a scientist who has developed a new drug that unfortunately blocks the extracellular portion of most cell surface transmembrane transporter proteins. Which of the following processes do you expect to be most affected ?

Uptake of glucose into the cell

What is the role of phospholipid in pulmonary surfactant ?

Used in the treatment of infant respiratory distress syndrome (common i premature babies) mimic the pulmonary surfactant -commonly made of similar artificial substitutes

Which of the following pathways occurs in the peroxisome ?

VLVFA beta oxidation

What happens in mitochondrial translation ?

Variant genetic code fewer tRNAS the initiator AA is N-formyl-methionine

When describing the secretory pathway between RER and Golgi, which of the following statement is correct?

Vesicle docking is facilitated by Rab-GTP and its binding to the 'tethering protein' (note: vsnare/tsnares help in fusion)

When describing the secretory pathway between RER and Golgi, which of the following statement is correct ?

Vesicle docking is facilitated is facilitated by Rab-GTP and its binding to the "tethering protein"

In what direction can the vesicles move along the microtubules ?

Vesicles may move along the microtubules in both directions

Familial hypercholesterelomina is an inherited disorder that causes plasma LDL (bad) cholesterol cholesterol levels to become very high. The condition begins at birth and can cause heart attacks at an early age. At the molecular level there are 5 different types of this disorder. When considering a Class II mutation, what is the molecular basis of the defect?

Vesicular transport out of the RER does not occur, protein never reaches the Golgi Mutations LDL-R

Gating-mechanism membrane potential

Voltage-gated sodium channels -at the resting potential, voltage-gated Na+ channels are closed. -when the membrane is depolarized, conformational changes open the voltage gated channel

The plasma membrane is made up of a lipid bilayer, which determines the ability of substances to move in and out of the cell. which of the following substances are lipid soluble and water soluble, respectively?

Water soluble : Na+ & Glucose Lipid soluble : Co2 & O2

B1 DEFICIENCY: DRY BERI BERI

Wernickes' encephalopathy : 1. ataxia 2. confusion 3. opthalmoplegia korsakaoff syndrome 1. confabulation 2. memory loss 3. psychosis

When does Ran switch "off"

When bound to GDP ( GAPS hydrolyzes GTP)

Mutations which cause defects in the transport of very long chain fatty acids into the peroxisome cause what famous disease?

X-linked adrenoleukodystrophy

NADPH oxidase deficiency

XLINKED recessive -MC Lack of superoxide negative NBT test/abnormal dihydroradamine test increased catalase +ve infections

Describe the major nucleoplasmic structures ?

all visible microscopically, but lacking membranes nucleolus ( rRNA transcription &rRNA modification by snoRNPs) nucleoplasmic particles

What is a link protein ?

a protein like those that links proteoglycans to hyaluronic acid

assume that an increase in blood glucose conc. from 5 to 10 mM would result in insulin release by the pancreas. A mutation in pancreatic glucokinase can lead to decreased insulin secretion due to which one of the following event w/n the pancreatic beta cell?

a reduced ability to raise cAMP levels

what is the basal membrane

cell substratum contact generation of ion gradients

What is a proteoglycan ?

a simple core protein covalently linked to a very long unbranched negatively charged polysaccharide (=protein + GAG)

the biosynthesis of the collagen is of critical importance for all cells that contribute to the construction of the ECM. Where do all the important disulfide bonds form in procollagen during its processing within the cellular RER ?

Within the C-terminal propeptide piece disulfide bonds c-terminal propeptides

Where is a protein glycosylated with N-linked oligiosaccharide ?

Within the RER

Where does the blisters form in epidermolysis bullosa simplex ?

Within the basal layer of the epidermis (the stratum basale, but above the basal lamina

Describe hyaluronan

a unique GAG Structute : repeating sequence of ~ 25, 000- identical nonsulfated disachharides (GlcNac-Glucoronic acid) - chain length is Huge -not covalently linked to any core protein -synthesized by an enzyme on basal epithelial surface (all other GAGs, are made intracellularly, exocytosed)

In purine catabolism how many steps does xanthine oxidase catalyzes ?

Xanthine oxidases catalyzes two steps in this process

Could a faulty leaking mitochondrion be removed by the use of autophagy ?

Yes

Another disease features a defect in the membrane protein importation complexes so that they do not recognize the localization AA signal of cytosolic protein destined for the peroxisome. Several prominent peroxisomal functions become disrupted including a failure to synthesize plasmalogen. Lack of plasmalogen causes hypomyelination of glial cell membrane, and VLCFA also accumulate there. This result in abnormal brain development, neuronal migration defects and progressive hypomyelination. In addition, there is a lack of bile acids leading to a drop in fat absorption, a drop in ATP and general muscular weakness. Death is likely between 6-12 months.

Zellwinger syndrome

What protein is misfolded and subsequently degraded in the most common type of cystic fibrosis?

a cell surface chloride channel

What is GPI (glycosylphosphatidylinositol) anchor ? Where are they made.

a glycolipid . Glycolipids are made in the Golgi but then sent wherever in the cell they are needed.

RER

a membrane studded with attached ribosomes

What is GPI-Anchored protein?

a protein anchored to the outer membrane by attachment to a type of glycolipid GPI anchors link proteins to the outer leaflet fatty acylation or prenylation link proteins to inner leaflet

What is Ehlers Danlos syndrome

abnormal fibrillar collagen structure -connective tissue weakness : lacks adequate tensile strength -hyperextensible skin ( fragile, supsectible to trauma ) -hypermobile joints (dislocations) may have internal complications -rupture of colon -rupture of large arteries varicose veins ecchymoses

Disorder : Familial Hypercholesterolemia

abnormal receptor-mediated endocytosis mutation in LDL receptor no endocytosis - increase in plasma cholesterol -premature atheroscelrosis -xanthomas -corneal arcus

About how many acidic hydrolytic enzymes will be found within a mature lysosome?

about 40

Describe Tay Sach's Disease

accumulation of GM2 GANGLIOSIDES

describe acid base disorders

acid base disorfers are pathologic changes in carbon dioxide partial pressure (PCO2-) or serum bicarbonate (HCO3-) that typically produce abnormal arterial pH values acidemia is serum pH < 7.37 alkalemia is serum pH > 7.44 acidosis -physiologic processes that cause acid accumulation or alkali loss alkalosis -physicologic process that cause alkali accumulation or acid loss

Small G proteins are also regulated by?

actin cytoskeleton stationary fibroblast: cortical actin filaments & few focal contacts Rho : stress fibers and focal contacts Rac : lamellipodium that extends from the entire cirumference of the cell CDC42: filopodia- protrusion form adhesive contacts w substratum

What is spectrin ?

actin filament web: cross- linking proteins Spectrin forms 2D web ( held together by short actin filaments ) connecting to the underside of the plasma membrane -spectrin network linked to the membrane by ankyrin or similiar the weblike structural support allows biconcave cells to deform in capillaries and spring back unharmed DISEASE ASSOCIATED WITH SPECTRIN ; HEREDITARY SPHEROCYTOSIS

Describe thiamine

active form: thiamine pytophosphate (tpp) involved in : 1. oxidative decarboxylation : PDH, alpha KGDH, BCKDH 2. Transketolase causes for B1 deficiency 1. chronic oh 2. consuming polished rice patho 1. (-) of PDH : decrease acetyl co A and increase lactate 2. (-) of alpha ketoglurate dehydrogenase- decrease ATP production due to inhibition of TCA cycle and altered neurotransmitter levels

What is one important function of glycolipids on the plasma membrane ?

acts as a cell recognition signal flag for cell-cell recognition

What does the trans cisterna of the Golgi sort ?

addition of Galactose addition of NANA

Integrins focal ____& signaling

adhesions

what are the 2 types of glycolysis

aerbobic glycolysis anaerobic glycolysis

When is collagen fibrils form ?

after secretion : collagen fibrils form cell surface peptidase remove N& C propeptide extensions procollagen has now been converted into tropocollagen -covalent processing necessary for additional crosslink formation ectracellular self-assembly of collagen protein into collagen fibrils -fibrils crosslinking occurs due to lysine modification inter & intra molecular crosslinking strengthens the collagen fiber

Gap junctions

allows the passage of small eater soluble ions and molecules in the cytosol

The smallest subunit making up a microtubule

alpha & beta tubulin

Glucagon

alpha cells of pancreas counter regulatory increases c-AMP activate protein kinases

A 24 y woman p/q diarrhea, dysphagia, jaundice, and white transverse lines of the fingernails (Mee's lines). the patient is diagnosed w arsenic poisoning, which inhibits which one of the following enzymes ?

alpha ketoglutarate dehydrogenase

Describe GTP bound beta tubulin

alpha/beta dimer has HIGH affinity for other subunits

Describe GDP bound beta tubulin

alpha/beta dimer has a LOWER affinity

Which of these are diseases that stem from mutations in collagen IV ?

alport syndrome goodpasture syndrome

Describe complex 1

also called NADH-Q reductase or NADH dehydrogenase, is a flavoprotein containing FMN it oxidizes mitochondrial NADH and transfers electrons through FMN and iron-sulfur (FeS) complexes to ubiquinone provides enough energy to pump 4 proton from the matrix to the intermmembrane space

What is coarse regulation

alter enzyme quantity regulated by 2 principles 1. regulation of gene expression control the quatity and rate of enzyme syntheis-slow control process that may take hrs to day indcution or reprssion 2. the rate of enzyme degradation- can be slowed down or increased-ubiquitin/proteasome pathway and lysosomal pathway

The majority of calories in the US diet are derived from carbs, which can contain a variety of glycosidic bonds. which one of the following carbs contains glucosyl units linked through the 1,6 glycosidic bonds

amylopectin

Mysosin & actin filaments have ____ for each other.

an affinity

What is put on a nascent protein in the lumen of the RER ?

an immature premade oligosaccharide cluster of 14 sugars

What is a acanthocyte ?

an increase in cholesterol in erythrocyte distorts the cell shape. 5-10 irregular, blunt finger-like projections

hemidesmosome

anchors intermediate filaments in acell to the basal lamina

metabolism of glucose in RBCs

anerobic glycolysis ppp

what are the parts of the membrane protein?

apical (top) basolateral (middle/bottom)

Describe water channels

aquaporins pore diameter larger than water molecules but not as great as solute molecules found predominatly in rbc & epithelium of lungs, kidney and intestines

The type pf EC,M that contains collagen type IV is found in all theses locations

around each muscle cell supporting epithelial cells in the kidney glomerulus basal lamina famous for underlying epithelia also surronds individual of skeletal muscle cells, adipocytes, schwann cells of peripheral axons also can be interposed btween 2 cell sheets (kidney glomerulus ( as a permeability barrier epithelial sheet muscle kidney glomerulus

What is the clinical manifestation of Hurler's syndrome ?

at a few months old: -physical and mental retardation -growth stops at 2-4 years old - hepatosplenomegaly -deafness -skeletal deformity -coarse facial features - hirustism -thickened skin -corneal clouding -death <10 years old

the relationship btw substrate concentration and reaction rate can be represented quantitatively :

at high conc. of substrate the velocity of the reaction is 0 order. that is, it is constant and independent of substrate concentration at low con. of substrate the velocity of the reaction is first order. that is, it is proportional to substrate concentration. 1. when substrate conc.< km value (point A), Vi will be directly proportional to substrate conc. (first order kinectic) 2. when substrate con = km value (point B), vi will be half the max velocity 3. when substrate conc > km value (point C), vi will be equal to vmax and independent of substrate conc. further increases (zero order kinetics)

A potentially fatal autoimmune disorder known as pemphigus vulgaris cause blistering and raw sores on both skin and mucous membrane. what causes this disease ?

autoantibodies against desmosomal cadherins

Bullous pemphigoid is an autoimmune blistering disease that disrupts the dermal epidermal junction. what causes it ?

autoantibodies are produced against one of the hemidesmosomal proteins

Describe Pemphigus vulgaris

autoimmune disorder ( or genetic defect of desmosomal cadherins) -blistering & raw sores on skin & mucous membranes -skin pulls apart -> abnormal movement of fluid w/n skin -> blisters untreated = fatal ( systemic infection ) tx; steroid therapy

Insulin

beta cells of pancreas anabolic storage of nutrients decreases c-AMP activate protein phosphatases

Describe the pathology of Alz disease

beta-amyloid/sensile plaque (extracellular ) - accumulation of beta amyloid peptide, apoE also present -> progressive neuronal damage -neurofibrillary tangles (intraneuronal) from tau malfunction tau (MAP) becomes HYPERPHOSPHORYLATED -forms neurofibrillar tangles (NFTS) & accumulates in beta A plaques -mircotubules depolymerisation and disruption of axon transport

At low concentration, sodium chloride (NaCl) is a salt that completely dissociates in water. However, at very high concentrations some Na+ and Cl- ions will reassociate into NaCl. If 1.0 M solution of NaCl represents a very high NaCl concentration, what will the osmolarity (in osmoles/L) of this solution be?

between 1 and 2, b/c it will not completely dissociate explain : 1 M not dissociating . nacl only dissociates at 93% ( 2 x.93)

how is blood pH determined

blood pH is determined by the ratio btw : base component -plasma bicarbonate acid component - dissolved CO2

What are adhesive glycoproteins ?

bound to & enmeshed within the thick gel commonly-thick fibronectin, laminin, entactin

Which is the most common tissue affected in children suffering from pyruvate dehydrogenase def?

brain

an 82 y old woman was transported to the ED from nursing home bc she is c/o ha, fatigue, and of a change in her state over the past few hrs. She has a medical hx of dm & htn. on exam, she has decreased skin tugor, depressed reflexes, and disorientation to time, place, and person. initial lab results show : hypo na osmolality : 260 mOsm/kg H20 - decreased sodium and decreased osmalality

brain swelling due to increase fluid in ICF water moves only when differences in osmolality sodium low causing low osmolality changes in osmolality allows water to move change in osmatic pressure- water moves to the highest concentration what is the major cation in cell ? k+ what is the major anion in the cell ? inorganic phospahate what is concentration of Na IN THE CELL ? 10 what is concentration of cl-? 4

an 82 yr old women was transported to the ED from her nursing home bc c/o HA, fatigue, change in mental state over the past few hours. She has a medical history of diabetes and hypertension. on exam, she has decreased skin tugor, depressed reflexes, and disoriented to time, place, and person. initial lab results show :

brain swelling due to increase fluid in ICF - water moves when there is any imbalance

At low concentrations, NaCl is a salt that completely dissociates in water. however, at very high concentration some na & cl ions reassociate into nacl. if a 1.0 M solution of nacl represents a very high nacl concentration,what will the osmaolarity (in osmoles/l) of this solution be ?

btw 1 and 2

How does tight junctions/zonula occludens determine epithelial cell polarity ?

by seperating the apical domain from the basolateral domain; prevent free diffusion of membrane proteins -maintains directional transport -modulates free diffusion of substance accross the epithelia layer btw cells (paracellular pathway) ; particularly AA & monosaccharides from the gut lumen - most apical of the cell junctions -tightness of the junctions oftern midulated by paracrine signals

Describe desmosomes and their cadherins

cadherins bind calcium cell-cell adhesion =dependent on ca binding desmosomes have specific cadherins ( desmoglein & desmocollin) intracellular anchor proteins ( desmoplakin & plakoglobin) link to IFs

What is the role of ECM in bone and teeth ?

calcified

what is anerobic glycolysis

can occur in the absence of oxygen end product- lactate + ATP further proceeds in cytosol inefficient -partial oxidation

what divides the interstial fluid from plasma

capillary wall

What impacts complex II

carboxin TTFA

Describe carriers

carrier-mediated transport -substance can not be transported w/o the aid of a specific protein -transport along concentration gradient -active site only accessible from one side of membrane at a time Glucose transporter GLUT1-5 AA transporters Neutral AAs Basic AAs Acidic AAs

describe oxidorectases group 1

catalyse oxidation reduction reactions. electrons are removed from one substrate (donor-oxidized) and added to ssecond substrate (reduced) oxidases -transfer electron/hydrogen directly to oxygen to form water dehydrogenases -transfer hydrogen/electrons indirectly to oxygen to form water hydro peroxidases -use hydrogen peroxide as substrate to form water mono & dioxygenases -transfer either single atom or oxygen molecule

what are allosteric enzymes

catalyze essentially irreversible, rate limiting steps and are present early in the pathway do not follow michaelis-menten kinestics follow sigmoidal kinestics composed of multiple subunits-catalytic and regulatory positive and negative effectors -alter the affinity of the enzyme for its substrate K 0.5 or K 50) -modify the max catalytic activity of the enzyme (Vmax) or both

describe group 5 : isomerases

catalyze intramolecular rearrangement, catalyze conversion btw optical, positional, and geometric isomers isomerases aldose ketose isomerase epimerase racemase D and L forms mutase (inter molecular positional change of a chemical group)

Describe gap junction

cell communication can couple cells electrically and chemically -can allow free passage of ions, sugars, aa, nucleotides, vitamins, 2nd messengers (cAMP, IP3) -block passage of macromolecules ( protein, nucleic acid, polysaccharides, permeability varies, can be regulated

what is the lateral plasma membrane

cell contact and adhesions cell communication

what seperates the intracelluar fluid from extracellular fluid

cell membrane

What are the 4 main types of cell surface transmembrane receptors ?

cell surface receptors G-protein coupled receptos -adrenergic & olfactory receptors Receptor tytosine kinases (RTK) -GFRs, Insulin receptor Serine/theonine kinase receptors TGFBeta receptor Receptors w/o intrinsic kinase activity -ctyokine receptors, integrins ion channel linked receptors neurotransmitter receptors granule colony stimulating factor ?

Describe the prokaryotic plasma membrane?

cell wall and PM peptidoglycan

inhibitory interneuron

cell whose secretion is primarily affected by tetanus toxin

phosphoryl group transfer and ATP

cells obtain free energy in a chemical form by catabolism of nutrient molecules use that energy to make ATP ATP donates its energy for endergonic processes to synthesize macromolecules, mechanical motion and movement of substances against conc. gradient by converting ATP to ADP + pi or AMP + 2pi -most cases of energy transfer involves group transfer and not simple hydrolysis

Motor neuron

cells whosse secretion is primarily affected by botuliunum toxin

how does charge affect simple diffusion

charge - an electrical potential difference across a cell membrane will cause the movement of ions even if there is not a concentration gradient

What is lipid biosynthesis?

cholesterol and dolichol (although most is made in SER)

what is the most common basic cause of Acanthocytosis ?

chronic high cholesterol

What are the 3 sections of the Golgi stack ?

cis, medial, and trans cisterna

describe group 3: hydrolases

cleavage of a chemical bond w addition of water essentially an irreversible reaction -substrate is usually an ester or an amide digestive enzymes belong to hydrolases hydrolases - carbohydrates-amylases, lactase, sucrase lipids-pancreatic lipases proteins -pepsin, trypsin

insulin is synthesized in the beta cells of the pancreas as a proinsulin molecule. in order for proinsulin to be biologically active, which of the following posttranslational modifications of the hormone is req. ?

cleavage of peptide bonds

Describe tetanus toxin ?

cleave v-SNARE from the inhibitory spinal cord interneuron tetanus toxins prevents release of glycine and GABA which prevents relaxation of muscles inhibitory interneuron

Describe how tetanus toxin works

cleaves v-SNARE from the inhibitory spinal cord interneuron tetanus toxin prevents release of glycine and GABA, which prevents relaxation of muscles

Describe how botulinum toxin works

cleaves v-SNARE from the motor neuron at the NMJ botulinum toxin blocks release of acetylcholine, stopping muscle contraction

Why does Ehers Danlos syndrome occur

clinically & genetically heterogenous group of disorders -defective fibrillar collagen synthesis or structure

Folic Acid

coenzyme FH4 group transferred one carbon group one carbon metabolism

Pyroxidine (B6)

coenzyme PLP Group transferred amino or keto function : transamination reaction

What thiamen ? B1

coenzyme TPP group transfered : hydroxyl ethyl function : transketolase oxidative decarboxylation

biotin

coenzyme biotin group transferred co2 function carboxylation reaction

The ECM is often described as protein fibers in a "ground substance". What are the 2 major types of protein fibers ?

collagen elastin

Name two protein fibers

collagen fibers elastin fibers

In Ehlers Danlos syndrome what does a mutation in lysyl hydroxylase cause

collagen lacks structural stability occular fragility : retinal hemorrhage and detachment, corneal rupture hyphoscoliosis

Describe bullous pemphigoid

common autoimmune blistering disease -autoanitbodies to hemidesmosal protein -disrupt dermal epidermal junction -subepidermal blisters or psorias pattern -present > 60 y itchy

What is Alport syndrome ?

common inherited caused of kidney failure mutation in alpha chain 5 of type IV collagen ( in basal lamina) nephritis & deafness -hematuria, proteinuria, HTN

name reversible enzyme inhibition

competitive inhbition noncompetitive inhibition uncompetitive inhibitiob mixed inhibition

metabolism of glucose in brain

complete aerobic oxidation of glucose

What is important ?

complete pathway occurs in the mitochondrial matrix. some enzyme isoforms are present in the cytosol enzyme deficiences in TCA cycle are not compatible w life no direct hormone control -no covalent modification by hormones thyroid hormone increases mitochondrial ca required for activating TCA enzymes and increases UPC1 protein required for uncoupling oxidative phosphorylation in the electon transport chain

What is oligomycin?

completely blocks oxidation and phosphorylation by blocking the flow of protons through ATP synthase (-) F0 component

Describe the intermediate filament in the nuclear

component of polypeptides : lamins A, B, C location : nuclear lamina (inner lining of nuclear envelope )

Describe the vimentin-like intermediate filaments ?

component of polypeptides : vimentin many cells of mesenchymal origin (fibroblast, endothelial cells) desmin : in muscle glial fibrillary acidic protein : glial cells (astrocytes and some Schwann cells) peripherin : some neurons

Buffers

compound that stabilize the pH of a solution by removing or replacing lost H + act as shields or cushions-provide an immediate response to acid base disturbances. prevents sudden rise or fall of pH maintain the equilibrium of the reaction according to le chatelier principle mixture of weak acid and its conjugate base -release h+ when ph rises weak base and it conjugate acid -binds H+ when the pH drops weak acid does not fully dissociate in h20 moves forward or backward depending in concentration -> le chateliers principle weak acids do not ionize much and contribute to fewer H + (or OH-) have less effect on the pH

describe group 6

condensation of 2 molecules to form one molecules using energy in the form of ATP DNA ligases synthetases

Carrier mediated vs secondary active transport (similarities)

conformational change occurs once solute binds both mechanism uses specific carrier proteins both are saturable affinity plays a role in both mechanisms

Proton motive force

constitutes : 1. chemical potential energy-difference in H+ conc. 2. electrical pot. energy-proton moves out of membrane w/o counter ion

Describe the FGFR3 Mutation

constitutive expression of FGFR3 in chondrocytes so this mutation : -inhibits production of COLLAGEN II -restricts chondrocyte proliferation -cause excessive inhibition of bone growth (particularly of long bones)

Describe the matrix of the mitochondria

contains : pyruvate dehydrogenase complex citric acid cycle enzymes f.a beta oxidation enymes aa oxidation enzymes dna, ribosomes many other enzymes atp, adp, mg, ca, k, many soluble metabolic intermediate

What is fine regulation

control of activity of the enzymes -fast process 1. proteolysis 2. covalent modification 3. allosteric regulation 4. regulation of metabolic pathways 5. protein associate 6. compartmentalization

what is coarse regulation

control of number of enzymes-slow process induction repression

ionizing radiation

cosmic rays that continously bombard the earth which include radioactive chemicals and xrays high enough energy level-split water into hydroxyl and hydrogen radicals effects : -radiation damage to the skin -mutations -ca -cell death -generate organic radicals through direct collison w organic cellular components

Functionally what do gap junctions do ?

couple cells

What does the TCA cycle do ?

creates CO2 + NADH

cyanide/co inhibits complex iv

cyanide and carbon monoxide inhibit complex iv (cytochrome c oxidase). b/c complex iv is the terminal electron transfer complex, its inhibition cannot be bypassed. all components preceding complex iv become reduced, oxygen cannot be reduced, none of the complexes can pump protons and ATP is not syntheszed uncouplers such as DNP have no effect, bc there is no proton gradient. cyanide and carbon monoxide also bind to hemoglobin and it cannot carry oxygen. in these poioning, both the ability to transport oxygen and to synthesize ATP are impaired

What impacts complex IV

cynanide carbon monoxide

A 53 year old, previously successful man recently lost his job and is under investigation for racketerring. His wife returns home to find him slumped over the steering wheel of his idling car in the closed garage. he is unresponsive and has a cherry color to his lips and cheeks. which of the following is inhibited by the co in the car exhaust fumes ?

cytochrome oxidase

Describe cytochrome p450 system

cytochrome p450 enzymes are a major source of free radicals "leaked" from reactions they catalyse single electrons are transferred to O2 and an organic substrate, the possibility of accidentally generating and releasing free radical intermediate is high induction of P450 enzymes by alcohol, drugs, or chemical toxicants leads to increased cellular injury

What can cause situs inversus ( arrangement of internal organs is reversed )

decrease in ciliary activity affects cell motility during embryogenesis

describe metabolic acid accumulation

decrease in hco3- increased ventilation by lungs and decreased co2

a patient is diagnosed w an insulinoma, a rare neuroendricrine tumor, the cell of which are derived primarily from pancreatic beta cells. which of the following would logically be characteristic of an insulinoma ?

decreased glucose in the blood

In familial hypercholesterolemia, describe class II mutation ?

defective transport from RER in class I - synthesis ( do not make protein, truncated protein, null mutation ) Class II- transport class III - binding. receptors do not recognize particle class IV- clustering. receptors do not recognize adaptor proteins that clusters them together to form coated pit class V- does not recylce back to membrane- cant keep up w demand

Patho classification of lactic acidosis

delayed clearance renal or hepatic dysfunction pyruvate dehydrogenase dysfunction sepsis, thiamine deficiency catcholamine excess, alcholic and DKA Uncoupling of oxidative phosphorylation cyanide, salicaylate, methanol & ethylene glycol metabolites antiretrovial drugs, valpronic acid, biguanides, INH accelerated aerobic glycolysis increased effor, sepsis, seizures, large fructose loads, and maligancies

Which of the following parameters indicate whether the reaction A-> B, is thermodynamically favorable under standard state conditions at neutral pH?

delta G0'

standard free energy changes are additive

delta G0' of 2 consecutuve reactions/series of reactions are additive as long as the sum of the delta G 0' of the individual reaction is negative, the pathway can potetially proceed to completion even if some of the indicial componet reactions of the pathway have a positive delta G 0'

charge on amino acids

depends on 1. pKa of ionzible groups 2. pH of the surrounding medium-measures of acidity or basicity of the solution 3. amino acids w/o ionizable R groups -have 2 pKa values 4. amino acids with ionzable R groups have 3 pka values zwitterionic form

Which type of intermediate filament is characteristic of muscle cells ?

desmin

understanding drug absorption

determined by the drug's physiochemical properties, formulation, and route of administration drugs may cross cell membrane by 1. passive diffusion 2. facilitate diffusion 3. active transport 4. pinocytosis diffusion rate is directly proportional to gradient, molecules lipid solubility. size, degree of ionization, and the area of absorptive surface most drugs are weak organic acids or bases, existing in un-ionized and ionized forms in an aqueosous enviroment. the un-ionized form is lipid soluble and diffuses readily across cell membrane

SER

detoxification of drugs and toxins

During oogenesis, the expansion of mitochondria in the primordial germ cell, followed by a restriction of mitochondria in primary oocytes can result in ....

different proportion of mutant mtDNA in the offspring compared to the mother Explanation : Genetic Bottleneck for mtDNA During oogenis : * a restriction in the number of mitochondria * a subsequent expansion -offsprings have varying degrees of heteroplasmy compared to their mother

describe osmotic pressue

dissociated solutes 60mM glucose x1 diss. particles =60 mOsm/L 60 mM Nacl x 2 diss particles = 120 mOsm/L 60 mM CaCl2 x3 diss particles =180 mOsm/L

Solution A contains 10 mM glucose and solution B contains 1 mM glucose. If the glucose concentration in both solutions is doubled, by how much will the flux (flow) of glucose between the 2 solutions change?

doubled 10-1= 9 20-2= 18 Membrane thickness than another cell- will take longer for the flux to take it across the membrane

What is familial hypercholesterolemia?

due to mutations that disable the LDL receptor mutations in LDL-R: increase plasma cholesterol, increase in synthesis LDL AD inheritance 1/250 are heterozygotes 2-3x plasma cholesterol (homozygotes have 6x plasma cholesterol) Class II: defective transport from RER

How is the nucleolus formed ?

during interphase, gathers AROUNF CLUSTERS OF rRNA gene repeats (the grouping of the p-arms of acrocentric chromosomes 13,14,15,21, and 22)

Which type of epudermolysis bullosa features mutations in the deep type VII anchoring collagen of the papillary dermis

dystrophic

binding change mechanism-role of F1

each 120 rotation of the y subunit induces conformational changes in the beta dimeric subunits such that the nulceotide binding site alternate btw three stages : beta subunit starts in the ADP conformation, which binds ADP and Pi from the surrounding medium the subunit now changes conformation, assuming the ATP form that tightly binds and stabilizes ATP Finally the subunit changes to the empty conformation, which has very low affinity for ATP and it leaves the enzyme surface

Deamination and spontaneous covalent binding between lysine and hydroxylysines bind different tropocollagens together and strongly promoites the formation of collagen fibrils These events occur in the

extracellular space extracellular self assembly of collagen protein into collagen fibrils -fibril crosslinking occurs due to lysine modification -inter & intra molecular crosslinking strenthen the collagen fiber

What is Latrunculin ?

extracted from sea sponge binds G-actin monemers, so inhibits polymerization

What is the first destination of most small and medium sized molecules entering the cell through endocytosis ?

early endosomes

Describe cerebral edema

effects of hyponatremia on the brain water gain (low osmolality) within minutes after the development of hypotonicity, water gain causes swelling of the brain and a decrease in osmolality the normalization of brain vl occurs w/m a few hrs as a result of cellular loss of electrolytes (rapid adaptation) loss of sodium, potassium, and cl- (low osmolality)

during regulatory vl increase, many cell will decrease which of the following ?

efflux of K + influx of water

What do elastic fibers in the ECM provide?

elasticity & resilience (> 5x stretchy than rubber bands)

Elastic fibers consist of .....

elastin microfibrils

Name two types of coupling

electrical coupling chemical coupling

ATP hydrolysis: direct

energy released by direct hydrolysis of ATP is used for : to cycle some proteins bte 2 conformations to produce mechanical motion 1. muscle contractions 2. movement of ribosomes along m-RNA 3. Movement of enzymes along DNA 4. Signaling pathways

Describe trypsinogen and trypsin.

entrokinase * autoactivation* cathepsin B trypsingen -> trypsin chymotrypsiongen -> chymotrypsin proeleastase -> elastase kalikreinogen -> kalikrein pro-caboxypeptidase -> carboxy peptidase prophospholipases -> phospholipase procolipase -> colipase normal pathway : enterokinases is located in the brush border of the small intestine normal pathway: tyrpsingen autoactivation is a unique feature of human trysinogen abnormal pathway: cathepsin B is located w/n acinar cells

Describe metachromatic leukodystrophy

enzyme def. arylsulphatase A s/s NO CORNEAL CLOUDING

What is clinicial enzymology

enzymes in circulation are divided into two groups plasma specific enzymes - functional enzymes plasma nonspecific enzymes - non functional enzymes

Which cell have 1 nucleus ?

epithelial cells

Describe a normal RBC

erythrocyte, " dimple" max SA allows for O2

Describe steady-state water balance with intake and output

excess fluid -> increase u/o fluid deficit -> increased thirst intake ~2.5 L/day output ~ 2.5 L/day intake 1.3 l bevarages 0.9 l food oxidation 0.3 L output 1.5 l urine 0.9 l sweat/respiration 0.1 l excreted in feces

mechanism of ECF dilution

excessive water intake or water intoxication which lead to hyponatremia ( serum Na + <135 mEq/L) -infants, elderly, millitary personnel, marathon runners -Syndrome of Inappropriate Antidiuretic Hormone Secretion ( SIADH) Severe head injury or trauma

Blinding helps to reduce ____ biasis

expetancy bias

What are the s/s of heat exhaustation

faint or dizzy excessive sweating cool clammy skin n/v rapid weak pulse muscle cramps

FACIT collagen bind to fibrillar collagens resulting in different fiber organizations. Describe the organization in corneal stronal lamellae

fibers cross at 90 degree angles

Adhesion proteins of the ECM may seem like an unimportant detail; however, they serve as anchoring points that influence cell functions relating to survival, development, migration, proliferation, shape, orientation, and differentiated function. Two of these proteins are :

fibronectin laminin entactin

Review of the ECM

fibrous proteins : collagen & elastin embedded in viscous gel Ground substance -proteoglycans : GAGS Adhesive glycoproteins: laminin, fibronectin, entactin

TCA (tricarboxylic acid cycle)

final pathway-oxidative metabolism of carb, aa, and f.a. converge converting their carbon skeleton into CO2 amphibolic -providing carbon skeletons for gluconeogenesis (oxaloactate and malate), fatty acid synthesis (citrate), formation of aa from intermediates and vice versa atp production-oxidation of acetyl-coA along w the reduction of coenzymes, which are subsequently reoxidized to produce ATP

Describe the different types of enzyme regulation

fine regulation coarse regulation

insulin metabolism

first pass metabolism in liver half life 4-6 min threshold for insulin secretion -80 mg/dl of glucose regulators of insulin release major regulators glucose minor regulators aa neural input gut hormones epi

Describe regulation of glycolysis

first step regulation: glucokinase/hexokinase regulation at rate limiting step ( slowest) PFK1 -allosteric regulation PFK2-covalent modification Regulation associated w ATP homeostasis ATP/ADP/AMP ratios citrate and fructose 2,6 biphospahte ratios supply of glucose 6 po3-tissue dependent

What are protein complexes

flavoproteins with iron sulfur clusters as electron acceptors 1. NADH-Q Dehydrogenase (COMPLEX1) 2. SUCCINATE Q Dehydrogenase (COMPLEX II) Cytochrome w Heme as electron acceptors : 1. Q cytochrome c Reducatase (Complex III) ( B+ C1) 2. cytochrome C 3. Cytochrome c oxidase (heme + copper) (Complex IV) ( cyt a+a3) lipid derivative : from cholesterol synthesis 1. co-enzyme Q or ubiquione -mobile complex

What are the inhibitors of citric acid cylce

fluoroacetate fatal for grazing animals converted to fluro citrate- competitive inhibitor of aconsitase arsenite (-) alpha ketoglurate dehydrogenase by binding to SH groups of lipoate malonate competive inhibiot of succinate dehydrogenase

Carrier mediated versus secondary active transport (differences)

for carrier mediated transport-downhill transport of solute occurs, while secondary active transport uphill transport of solute occurs secondary active transport needs the driver solute to expend energy for the uphill transport of solute to occur, while carrier-mediated transport doe not require energy to be expended for downhill transport of solute

Free energy change of the reaction

for chemical reaction A->B free energy of a reaction delta G= GB-GA

What are CBs/Gems ?

formation & maturation of snoRNPs & snRNPs that go into the nucleolus (snoRNPs), and speckles (snRNPs)

What are secondary lysosomes ?

formed from fusion of primary lysosome with vesicular bodies containing digestible substrates -structure is larger and filled with substrates in various stages of degradation -can also develop from late endosomes through supplementation with lysosomal enzymes

What are the functions of the proteoglycans in the ECM ?

forms a porous, hydrated gel -fill spaces: occupy large volumes -resist compression-its padding structural : associate w each other, collagen & basal lamina cell signaling -bind growth factors -increase cell surface receptors binding affinity for the growth factos -cell migration -create cell free space -bind & regulate activity of proteases and their inhibitors -immobilize chemokines (during inflammation)

The mitochondrial genetic bottleneck is a hypothesis which attempt to explain why the children of a mother with a mitochondrial DNA disease might ....

have varying degrees of heteroplasmy Explanation; the mitochondrial genetic bottle neck hypothesis predicts that if a mother is heteroplasmic for a mitochondrial DNA mutation, her children might inherit different proportions of mutated DNA Genetic bottleneck for mtDNA During oogenis -a restriction in the number of mitochondria -a sunsequent expansion offspring have varying degrees of heteroplasmy compared to their mother The bottleneck and threshold hypothesis explain the variable expressivity and reduced penetrance we see in mtDNA diseases

a 78 yr old male is gardening outside on a hot day. after a while, the man is thirty, fatigued, profusely sweating and dizzy. he manages to go inside his home and call his daughter who reaches her fathers house right before he faints. what has likely happened to this individual ?

heat exhaustation

Describe the outer membrane of the mitochondria

freely permable to small molecule and ions

describe insulin

function: promotes fuel storage after a meal promotes growth stimulates glucose storage as glycogen (muscle and liver) stimulates f.a. synthesis and storage after a high carb meal stimulates aa uptake and protein synthesis

Describe nonselective pores (channels)

gap junctions found in epithelia, endothelia, smooth mucscle and cardiac muscle allow passage of water soluble molecules up to MW of 1200-1500 pathway for electrical current flow btw cells sync electrical activity of heart and gut

Describe cell cortex

gel -like network

Ratio of protein in plasma membrane

general cell plasma membranes are 1:1 protein to phospholipids (by weight ) .

What is chronic granulomatous disease

genetically heterogenous condition characterized by recurrent, life threatening bacterial and fungal infections and granuloma formation defect in NADPH oxidase comple (phagocyte oxidase) inability of phagocytes to destroy certain microbes (catalase positive) diagnosis is made by neutrophil function testing for superoxide prouction

What is gylcerol po4 shuttle

gives 1.5 atps for every nadh from cytosol. faster due to few molecules in the shuttle occurs predominantly in brain and skeletal muscle -enables it to sustain a very high rate of oxidative phosphorylation the use of FAD enables electrons from cytosolic NADH to be transported into mitochondria against an NADH concentration gradient IRREVERSIBLE

What is the malate-aspartate shuttle?

gives full 2.5 ATPs, slower occurs predominantly in liver, heart malate-asparate shuttle works only if the NADH/NAD ratio is highter in the cytosol than in the mitochondrial matrix. Also facilirates the exhchange of key intermediates btw mitochondria and the cytosol REVERSIBLE - the direction of the shuttle depends on the metabolic state of the cells

in counter regulatory hormones which one is catabolic

glucagon epi cortisol

role of glucogon in metabolism

glucagon acts to maintain fuel availability in the absence of dietary glucose liver glycigenolysis gluconeogenesis adipocytes lipolysis -tg breakdown skeletal muscle no effect

List the irreversible steps of glycolysis

glucokinase/hexokinase PFK-1/PFK2 Pyruvate kinase hormal regulation (mainly liver): insulin favor glycolysis and glucagon inhibits glycolysis

Overview of Mitochondria: energy -generating metabolism

glycolysis: occurs in cytoplasm pyruvate (from glycolysis) & FA enter mitochondrion and broken down to Acetyl CoA in MATRIX Acetyl CoA w/n matrix metabolized by TCA cycle reducing NAD + to NADH High energy electrons from NADH passed along ETC to O2 ETC pumps protons into the intermembrane space-generating a proton gradient across inner membrane Protons will normally flow from the intermembrane space back into the matrix by passing through ATP synthase -> this spins the turbine to drive ATP synthesis

What is GAG

glycosylaminoglycan -very long, unbranched, repeating amino-oligosaccharides

If there is no signal sequence what happens?

goes into the cytosol

What is niacin? B3

group 1 co enzyme coenzyme NAD + NADP function : redox reactions

What is riboflavin? B2

group I coenzyme coenzyme: FMN, FAD function: redox reactions

Describe the hendersen hasselbalch equation

helps in understanding the mammalian acid base physiology and is rountinely use in the treatment of acid base abnosmalities in individuals simple expression which related the pH, pKa and buffer action of a weak aci and its conjugate base or vice versa provides a quantatuve relationship btw the concnetration of a weak acid (HA) and its conjugate base (A-) used for calculating the pH or pKa of a solution containing known quamtaties of a weak acid and its conjugate base

MELAS is always____

heteroplasmic

MERRF is always ______

heteroplasmic

NARP is always ____

heteroplasmic

Giant deletions in the mtDNA are always ......

heteroplasmic (if homoplasmic -lethal)

Individuals with a mixed population of mtDNA molecules are said to exhibit :

heteroplasmy

a patient has tried many different " fad" diets to lose weight. which one of the following meals would lead to the lowest level of circulating glucagon shortly after the meal ?

high carb meal

Reactive nitrogen species

high concentration during inflammation -direct toxic effects: combining w iron containing compounds like Fe S centers, Hb and cytochromes Reactive nitrogen-oxygen species toxicity NO interacts w superoxide to form peroxynitrite (oxidizing agent)-lipid soluble peroxynitrite releases nitrogen dioxide free radical NO reacts w oxygen to form nitrogen trioxide nitrosylation (nitrosative stress)

Familial Hypercholesterolemia ( review )

high levels of LDL; premature atherosclerosis -major risk of coronary artery disease, CVA, MI -Xanthomas, xanthelemata -corneal arcus - mututation in receptor for LDL (LDL-R) casues increase plasma cholesterol, increase in synthesis of LDL 1/250 heterozygotes and have 2-3x plasma cholesterol 1/300,000 are homozygotes and have 6x plasma cholesterol

Negative feedback control of low blood glucose levels for : diabetic person not eating, drinking too much alcohol, hepatitis/kidney disorders

homeostasis : blood glucose level (90mg/100 ml) stimulus glucose level falls alpha cells of pancreas release glucagon liver breaks down glycogen and releases glucose blood glucose levels rises

Describe negative feedback for low bp

homeostasis : blood pressure in normal range stimulus: decrease blood pressure (arterial blood pressure falls below normal range) 2. baroreceptors in carotid sinuses and aortic arch are inhibited 3. decrease impulses from baroreceptors activiate cardioacceleratory center ( and inhibit cardioinhibitory center and stimulate vasomotor center) 4. increase in sympathetic impulses to heart cause increase hr increase contractility and increase co - vasomotor fibers stimulate vasoconstriction and increase total peripheral resistance 5. increase co and increase total peripheral resistance return blood pressure to homeostatic range.

Describe negative feedback control of bp (high blood pressure)

homeostasis : bp in normal range normal bp 120/70 mmHg Stimulus : increase blood pressure (arterial blood pressure rises above normal range) 2. baroreceptors in carotid sinuses and aortic arch are stimulated 3. increase impulses from baroreceptors stimulate cardioinhibitory center (and inhibit cardioacceleratory center) and inhibit vasomotor center 4. decrease sympathetic impulses to heart cause decrease hr, decrease contractility and decrease co -decrease rate of vasomotor impulses allows vaso dilation causing a decrease in total peripheral resistance 5. decrease co and decrease total peripheral resistance return blood pressure to homeostatic range

describe thermoregulation high body temperature

homeostasis : normal body temperature ( 35.6-37.8) increased body temperature ( when excercising ot the climate is hot) blood warmer than hypothalmic set point activates heat loss center in hypothalamus sweat glands activated secrete perspiration which is vaporized by body heat, helping to cool the body skin blood vessels dilate: capilalries become flushed w warm blood; heat radiates from skin surface

describe thermoregulation with cold temperature

homeostasis =normal body temperature 35.6-37.8 stimulus decreased body temperature ( due to cold enviromemental temp) blood cooler than hypothalmaic set point activates heat promoting center in hypthalamus skin blood vessels contrict: blood is divereted from skin capillaries and withdrwan to deeper tissues; min overall heat loss from skin surface skeletak muscles activated when more heat must be generated shivering begins increase body temp increase blood temp and hypothalamus heat promoting center shuts off

Describe "ground substance "

hydrated, compression-resistant gel permitting rapid diffusion of nutrients, metabolites and hormones between blood and tissue, composed of : proteoglygans adhesiveglycoproteins

pathogenesis of hypoxia induced cell injury

hypoxia is most common cause of cell injury initial decrease in ATP compensated by substrate level phosphorylation initial damage-reversible cell injury irreversible cell injury -if oxygen is not restored damage to : plasma membrane mitochondria lysosime nuclear membrane

What happens to improperly folded proteins ?

if a protein can not b fixed w chaperones after a few tries: 1. ejected back through the translocon out into cytosol 2. deglycisylated & ubiquainated in cytosol -poly-ubiquinaton to misfolded protein marks them for destruction - complex taken up by proteasome and degraded all the way to AA

freshly isolated, normal human rbc were placed in a solution composed of 150 mM NacCl and 75 mM urea. which of the following statements is TRUE regarding vl changes ?

if present, Na, K, 2 Cl cotransporter would be activated to bring vl back to normal

Describe the inner membrane of mitochondria

impermeable to most small molecules and ions, including H+ contains: respiratory electron carriers (complex 1-iv) ADP-ATP translocase ATP synthase other membrane transporter

describe group 4 : lyases

implies breaking apart. catalyzes the breaking of various chemical bonds by means other than hydrolysis and oxidation, oftern forming a new double bond or a new ring structure lysase differ from other enzymes in that they require only one substrate for the reaction in one direction, but 2 substrates for the reverse reaction lysasae carbon-carbon, decarboxylases carbon-oxygen carbonic anhydrase, synthases carbon-notrogen argino succinate lyase phosphorous -oxygen adenyl cyclase

The Na/H transporter in the plasma membrane of many cell types in which of the following ?

important for control of intracellular pH

Describe intermediate filaments in nuclear lamins

in all cells these IF's line inner surface of nuclear envelope to firm the fibrous web-like nuclear lamina - structural stability of nucleus, protects DNA -anchorage sites for chromosomes, TFs( transcription factors ) nuclear pores

Describe steady -state water balance

in blood vl + arterial baroreceptors -> ADH (thrist) increased plasma osmolality -> + osmoreceptors -> ADH (thrist) dry mouth + ADH (thirst) water uptake by GI tract - decreased blood vl -> baroreceptors -> renal -> renin -> angiotensin II -> ADH (thrist)

Where do aggrecan proteoglycan aggregate ?

in cartilage Hyaluronic acid forms central thread for the aggrgate, but is not covanelty bound to any of the proteins holding the GAGs -core proteoglycan proteins associate noncovalently with hyaluronic acid through " link proteins"

Describe the process of Import in the nucleus

in cytoplasm : NLS bind to importin goes thru NPC -Ran GTP binds to importin REMOVES the cargo together leave the nucleus Ran GAP dephosphorylates GTP -release importin and Ran GDP

Where are keratin filaments found ?

in epithelial cells

which of the following statements about ATP is correct ?

in most cases, the energy transfer involves group transfer and not simple hydrolysis of phospho-anhydride bonds

What does connexin 32 cause

in peripheral neurons x-linked charcot -marie tooth neuropathy

Oxygen dependent killing

in response to infectious agents and other stimuli, phagocytic cells like neutrophils and macrophages exhibit rapid consumption of oxygen and production of superoxide & its metabolites referred to as the respiratory burst major source of superoxide, hydrogen peroxide, the hydroxul radical, HOCL, RNOS Hypocholrus acid, hydroxyl radical and peroxynitrite can attack lipid membranes of bacteria and kill it NADPH oxidase superoxide dismutase myeloperoxidase fenton reaction inducible nitric oxide synthase

Where does procollagen processing begin ?

in the RER

Where is the phosphate added to a terminal mannose on an N-linked oligosaccharide to produced the M6P tag?

in the cis golgi network

Aside from sulfation or phosphorylation, where does the Golgi remove or add sugar residues to a produce final forms of O & N-linked oligosaccharides

in the cisternae of the golgi stacks

Where is Ran GAP located, in nuclear trafficking ?

in the cytoplasm

What does Connexin 50 cause

in the lens congenital cataracts -> blindness

Where are all proteins required for mtDNA replication and gene expression encoded?

in the nuclear genome Replication -independent of the cell cylce and nuclear DNA replication 2-10 copies of the mtDNA per mitochondria

Where are snoRNPs and snRNPs formed and matured ?

in the nucleoplasmic particle: CBs/Gems

Where is Ran GEF located, in nuclear trafficking ?

in the nucleus

Where is most of the Ran-GTP, in nuclear trafficking ?

in the nucleus

Where does sulfation of AA's or CHO's occur ?

in the trans Golgi

where does the sulfation of AA or protein linked oligosaccharides take place?

in the trans Golgi network

where do secretory vesicles originate ?

in the trans golgi network

XDH/oxidase

in undamaged tissue, xanthine oxidase exist as dehydrogenase that uses NAD+ rather than O2 as an electron acceptor in the pathway for degradation of purine (hypoxanthine -> xanthine -> uric acid) when o2 levels decrease, phosphorylation of ADP to ATP decreases, and degradation of ADP and adenine through xanthine oxidase increases. in the process, xanthine dehydrogenases is converted to an oxidase. if o2 levels are below the high km of the enzyme for o2 little damage is done. however, during reprufusion, when o2 levels return to normal, xanthine oxidase gnerate H202 AND O2 at the site of injury

What causes Barth syndrome ( an X-linked cardioskeletal myopathy with neutropenia and SIDS)?

inability to synthesize cardiolipin

describe irreversible inhibition

inhibitors binds convalently with or destroy a functional group on an enzyme that is essential for the enzyme activity, or form a highly stable noncovalent association 1. aspirin ( acetylsalicyclic acid) inhibits cycloxygenase activity by acetyllating Ser 530, which blocks access of arachindonate to the active site of the enzyme 2. acetaldehyde dehydrogenase has an active site cysteine residue that is irreversible modified by disulfiram, resulting in accumulation of alcohol and acetaldehyde in the blood 3. malathion, parathion- inhibits acetylcholinesterase (organophosphorous poisoning)

AZT (aka Zidovudine) is an antiretroviral drug used in HIV therapy. It acts as an inhibitor of the viral reverse transcriptase. It has many negative s/e including HA, fever, nausea, liver and muscle damage and lactic acidosis. Which of the following actions of AZT explains the s/e ? AZT.....

inhibits DNA Polymerase gamma - AZT aka Zidovudine Antiretroviral therapy (ART) e.g. HIV -Nucleoside analogue -competes with dTTP for incorporation into DNA by the viral reverse transcriptase DNA Polymerase DELTA is NOT INHIBITED NO EFFECT ON NUCLEAR DNA REPLICATION DNA POLYMERASE GAMMA IS INHIBITED -depletion of mtDNA -myopathy is s/e of AZT therapy

Where is the ETC located in the mitochondria ?

inner membrane

Describe the net energy conversion catalyzed by the mitochondrion

inner membrane changes chemical bond energy (NADH oxidation) into phosphate bond energy bond energy (as ATP)

What is oxidative phosphorylation?

inner mitochondrial membrane -production of ATP molecules from the redox reactions of an electron transport chain

in counter regulatory hormones which one is anabolic

insulin

What does laminin bind to the transmembrane receptor proteins to anchor cell to basal lamina ?

integrin

Both focal adhesions and hemidesmosomes focus on and form around a family of transmembrane receptor proteins. These are the :

integrins

What is a focal adhesison ?

integrins bind to actin stress fibers via adapter proteins, and to extracellular fibronectin

role of counter regulatory hormones in metabolism

inter tissue balance between the use and storage of glucose, fat, and protein is also accomplished by neuronal signals other hormones of metabolic homeostasis-epi, norepi, cortisol oppose insulin action the release is mediated by neuronal signal and not a direct influence from change in fuel resources

What is a quick way to distinguish cellular intermediate filaments from microtubules ?

intermediate filaments are -thin - lack dynamic changes -lack polarity - are not hollow

Describe anapleurotic reactions

intermediates of TCA cycle can be diverted to various biosynthetic pathways removal of any of the intermediates from the TCA cycle removes the 4 carbons that are used to regenerate oxaloacetate during ea. turn of the cycle. with depletion of oxaloacetate, it is impossible to continue oxidizing acetyl coA to enable the TCA cycle to keep running, cell have to supply enough 4 carbons intermediates from degradation of carb or certain aa to compensate for the rate main reaction 1. pyruvate carboxylase-major anapleurotic reaction 2. degradation of glucogenic aa

lactose intolerance

intolerance to lactose containing foods s/s of lactose intolerance -ab pain -flatulence -nausea -bloating -diarrhea after ingestion of milk or milk containing products higher prevalence in african americans, hispanics, asians, native americans lowest prevalence in europeans

primary active transport

intrinsic proteins active site accessible from one side at a time against electrochemical gradient oppose equilibrating system ATPase transporter Ion ATPase (ion pump) Na/K ATPase H-ATPase Ca- ATPASE

Why is transcytosis important ?

involves both exocytosis and endocytosis -maternal IgG antibodies in breast milk are transported across intestinal epithelial cells -pH determines direction Fc receptor binds IgG tightly at low pH - 6.0 in intenstinal lumen transcytosis across epithelium fuses with basal membrane at pH 7, the binding becomes weak, IgG is then released.

proteins in ICF

is 40 mEq/L

pH : potential of hydrogen

is a way of quantifying the balance of acids and bases in the body depends on H+ concentration in the body cells/enzymes work best at H + concentration =40 x10 -9 Eq/L pH is calculated using log function pH= -log 10 [h+] = 7.4 ph is INVERSELY proptional to H+ conc. non linear due to log function (curved)

Provide a brief description of Spinal Muscular Atrophy

mutation in SMN defective snRNP defective splicing loss of motor neuron s/s muscle weakness dysphasia respiratory problems

during surgery, exposed tissues are moistened w sterile solution to prevent shrinkage or lysis of the cells. which of the following does the solution have to posses relative to cells in the tissue?

isotonic

during surgery, exposed tissues are moistened w sterile soln to prevent shrinkage or lysis of the cell. which of the following does the solution have to possess relative to cells in the tissue ?

isotonic explain: isotonic typical of ecf - no change at all and movement of water , normal 0.9% is what is normal in the ecf isoosmotic takes into account everything w in that solution

Laminin is the characteristic adhesion glycoprotein of the basal lamin. How does this hold a cell in place?

it binds to transmembrane integrins and to the collagen IV scaffold

How does cardiplipin differ from a normal membrane phospholipid ?

it is a double phospholipid, with 2 phosphates and 4 FA tails

What is creatine kinase

it is an isoenzyme in the brain subunit BB in the heart subunit MB in the skeletal muscle subunit MM

What effect does pertussis toxin have on signal transduction when it gets into its target cell?

it locks the Gi alpha subunit into a permanent inactive state by ADP ribosylation it casuses a strong increaase in cystolic cAMP Pertusis toxin, whooping cough ADP ribosylation of G alpha inhibitory -locks Gi into a GDP bound inactive state =inactivates Gi -> prolonged and inapporopriate cAMP response ALL 3 OF THESE BACTERIAL TOXINS CAUSE PROLONG INCREASE IN CYSTOLIC cAMP & cAMP signaling, but by different mechanism and in different cells

Desmosomes

join the intermediate filaments in one cell to those in a neighbor

Adherens junctions

joins ACTIN bundle in one cell to similiar bundle in a neighboring cell

In Ehlers Danlos syndrome what does a defect in converting procollagen I into collagen I cause

joint hypermobility note: mutation in collagen V cause joint hypermobility & hyperextensible of skin

what is in the icf

k+, proteins, and inorganic phosphates

treatment for PDHC Deficiency

ketogenic diet (high fat low carb diet) -> bypass the metabolic block, providing a direct source of acetyl-coA, leading to ameliaroation of some symptoms high dose of vitmain B1 -cofactor for E1 subunit

Which of the following intermediates is formed as an alternate fate of pyruvate when tissues expericience hypoxia ?

lactate

Under conditions of anerobic glycolysis, the NAD required by glyceraldehyde 3 phosphate dehydrogenase is supplied by a reaction catalyzed by which of the following enzymes ?

lactate dehydrogenase

patho of PDHc def

lactic acidosis and neurodegenrative patho which include sz, intellectual disability, microephaly alteration in neurotransmitter synthesis -glutamate/GABA

Patho of lactose intolerance

lactose in the colon is converted to short chain f.a. and hydrogen gas by the intestinal bac fermented to lactic acid, methane, and hydrogen gas osmotic diarrhea-due to partially digested lactose/lactic acid flatulence-due to to production of various gases

In regards to the mitochondria, what is found in most cell?

lamellar cristae

What are 2 adhesive glycoproteins ?

laminin : MAIN ADHESIVE protein for basal laminina fibronectin : is the main adhesive protein everywhere else

Describe the nucleoli

large prominent dense nucleolus active cellular protein synthesis ( a lot of ribosomes needed ) possible to have 2 or more nucleoli in a very active cell

Describe non gated (leak) ion channels

leak channels are always open, allowing the passage of sodium ions (Na+) and potassium (K+) across the membrane to maintain the resting membrane potential of -70 mV

describe steroid receptors

ligand activated nuclear receptors

Lipid anchored (peripheral) proteins

lipid group inserts into either side of bilayer many signaling and adhesions proteins are of this form

Living cell require a source of free energy

living cells constantly perform work. they require energy for maintianing their highly organzied structures, synthesizing cellular component, generating electric currents cells are isothermal systems-function at constant temperatute and pressures heat flow is not a source of energy for cells: bc heat can do work only as it passes to a zone or object at a lower temperature the only source of energy is the Gibbs free energy

Peripheral proteins

located entirely outside but associated with inner/outer leaflet by noncovalent (often electrostatic) interactions part of cytoskeleton, cytochrome C

H/K ATPase

located in parietal cells in gastric glands of GI tract and epithelial cells of renal system -acidify urine and control acid base balance basis for secreting hydrocholoric acid in the stomach digestive secretions

role of counter regulatory hormones in metabolism

low blood glucose -> alpha cell of pancreas -> glucagon low blood glucose -> hypothalamic -> ANS -> NOREPI Low blood glucose -> pituitary ACTH -> ADRENAL low blood glucose -> hypthalamus -> ans -> adrenal -> cortisol & epi

Which of the following most accurately summarizes the effects of hyperventiliation on arterial pCO2, serum pH and serum bicarb concentration

low co2 low bicarb increase in PH

enzyme-catalyzed reaction

lower activation energy by convalent and non covalent interactions between substrate and enzyme formation of each weak interaction in the ES complex -> release of free energy that stabilizes the interaction overall free energy released binding energy

what is bindind energy

lowers substrate entropy , causing substrate desolvation conformational change in the enzyme (induced fit ) accounts for specificity of enzymes for their substrates

Protein X is a membrane protein that transports Protein Y from the RER to the Golgi. Protein X is translated into the _____ and contains an AA sequence that acts as an RER tag. It moves into a ____ vesicle and brings Protein Y to the Golgi. After release of its cargo, it returns to the RER via a ____ vesicle

lumen of RER , COP II, COP I

There are 3 main destinations for secretory vesicles that bud off the trans Golgi network. In addition to the regulated or constitutive secretory pathways, what is the third destination?

lysosomes

What type of macromolecules are exported out of the nucleus ?

mRNA, tRNA, ribosomes

glucokinase (4)

mainly glucose km high low affinity location - mainly liver and beta cells of pancreas vmax - high glucose 6-po4 no inhbition insulin positive regulation (genetic induction)

what is feed-forward regulation?

mainly pathways involved in disposal of toxic substances enzymes have high Km value allorsteric activation through a compound related to substrate supply

impact of chemical reactions and pH

maintenance of Ph in the normal range -essential for the body as it affects ionization of proteins activity of enzymes ion channels hb o2 saturation curve decrease in pH -increase in sympathetic tone sudden changes in the pH of cells and plasma could lead to devastating consequences regulated by various mechanism chemical buffering : immediate regulation pulmonary activity: couple of hours renal activity: 1-2 days

how do enzymes work

many common reactions in cells entail chemical events that are unfavorable or unlikely in the cellular environment, such as the transient formation of unstable charged intermediate or the collision of 2 or more molecules in the precise orientation required for reaction enzymes provides a specific enviroment w/n which a given reaction can occur more rapidly take place w/n the confines of a pocket on the enzyme called the active site

Describe cell invasion

matrix metalloproteinases (MMPs) play a major role in invasion -collagenases -tissues contain proteinase inhibitors (TIMPs) stored in ECM; their release and activation under tight control -allows tissue remodeling & selective cell migration ( for implantation, tissue repair, immune response) -uncontrolled digestion of ECM occurs in tumor invasion

Gated mechanism -mechanical

mechanosensitive sodium channels pacinian corpuscle

Peroxisomes are .....

membrane bound organelles involved in : - beta oxidation VLCFA -alpha oxidation of branched FA -catabolism of AA & ethanol -synthesis of cholesterol, bile acid & plasmalogens (key membrane PHOSPHOLIPID) contain CATALASE for oxidative reactions (H2O2)

Describe proteins

membrane channels/pump - ion concentration gradient transporters- transport molecules structural change

Describe the fluid mosaic model

membrane is mosaic fluidity: is essential for exocytosis, endocytosis, membrane trafficking and biogeneis inner & outer leaflets are asymmetric =different phospholipids in outer vs inner leaflet lipid and protein show lateral diffusion in plane of leaflet glycoproteins and glycolipds on outer leaflet

Which one of the factors would need to be lower to contribute to the greater net flux of Solute A compared to Solute B shown in the graph assuming the solutes are of identical size and charge ?

membrane thickness

Describe a diabetic kidney glomerulus

mesangial cell hypertrophy & increase in ECM secretion compresses surrounding capillary loops proteinuria, fluid retention, htn , further damage -> renal failure

A person was admitted in a coma. analysis of the abg pco2 30 hco3 5 ph 7.2

metabolic acidosis

What causes of acid base imbalance

metabolic acidosis DM ( ketoacidosis) Lactic acidosis (lactic acid) respiratory acidosis chronic obstructive airways disease severe asthma airway obstruction metabolic alkalosis vomiting (loss of hydrogen ion) respiratory alkalosis hyperventilation (anxiety, fever) salicylate poisoning (aspirin)

Describe glucagon

mobilizes fuels maintain blood glucose levels during fasting activates gluconeogenesis and glycigeolysis (liver) during fasting activates f.a. release from adipose tissue

describe epi

mobilizes fuels during acute stress stimulates glucose production from glycogen (muscle and liver) stimulates f.a. release from adipose tissue

Describe the processing in the Golgi

molecules undergo ordered series of modification as they pass from cis to trans including : 1. maturation/modification of N-linked oligosaccharides 2. on proteins destined for lysosomes: a mannose-6-phosphate residue is formed at the end of the N-linked oligosaccharide 3. O-linked glycosylation linked to threonine or serine 4. Sulfation of AA's or CHO's occurs in the trans golgi

How many senescent RBCs are engulffed by macrophages each day?

more than >1000

Chemiosmotic theory of ATP production

most ATP synthesis is respiring cells come from the electrochemical gradient across the inner membrane of mitochondria creadted by using the energy of NADH and FADH2 formed by breaking down of energy rich molecules such as glucose

lactic acidosis

most common cause of metabolic acidosis elevated lactic acid greater than 5mM (normal 1.2 mM) decreased plasma pH and bicarb due to over production or under utilization of lactic acid

what are the s/s of chronic granulomatous disease

most common organs involved-lung,skin, lymph, nodes, and liver infections ( descending order of frequency) pneumonia abscessess (skin, tissue, organs) supprarative adenitis osteomyelitis bacteremia/fungemia superficial skin infections (cellulitis/impetigo)

Composition of ICF vs ECF

most ions are present in milliequivalent quantities mEQ/L=mmol/Lx valence ECF -Na+ ( and its attendant anions, primarily Cl- and HCO3-) is the major determinant of the osmolality of ECF High NA + and low K+ ICF K+ ( and its attendant anions, primarily proteins and inorganic phosphates) is the major determinant of osmolality of ICF High K+ and low Na +

Summary of Digestion

mouth (salivary glands) carbs : salivary amylase -> polysaccharides, dissaccharides -> stomach -> duodenum (pancreatic, liver) -> pancreatic amylase -> dissacharrides -> epithelium of small intestine -> dissacharides -> monsasscahrides lipids -> bile salts (liver) lipase (pancreas) f.a. monoglycerides proteins pepsin -> polypeptides trypsin, chymotrypsin, carboxypeptidase (pancreas) -> peptidases AA The enzymes involved in digesting carbs, lipid and proteins are depicted in relation to the region of the digestive tract where each functions

Describe the matrix of the mitochondria ?

mtDNA mt ribosomes, tRNA, rRNA holds enzymes for oxidative metabolism: TCA, FA oxidation, pyruvate metabolism

Kearns-Sayre Syndrome

mtDNA Giant Deletion

Pearson Syndrome

mtDNA Giant Deletion

Progressive External Ophthalmoplegia (Mitochondrial)

mtDNA Giant deletion

glucagon release does not alter muscle metabolism bc of which one of the following ?

muscle cells lack the glucagon receptor

Provide a brief description of Emery-Dreifuss muscular dystrophy?

mutation in Emrin or Lamin A/C S/S Contractures muscle weakness fragile nuclei

what is the mutation in dystrophic eb

mutation in collagen vii papillary dermis anchoring fibrils institinal collagen -" butterfly children ": extremely fragile skin, minor mechanical friction/trauma -> recurrent deep blister formation

What is the mutation in EB simplex?

mutation in keratin 5 or 14

What is epidermolytic hyperkeratosis ?

mutation in kertin 1 or 10 -AD - Keratins 1& 10: suprabasilar differentiation of keratinocytes -red skin & blisters at birth -defect weakness structural stabililty of keratinocytes -> easy blistering -chronic wound healing - hyperproliferation & thickened scaly skin

What is the mutation in junctional EB

mutation in laminin, integrins, or hemidesmosomal proteins

A 17 y old female p/w progressively worsening MYOCLONIC SZ. A bx of her skeletal muscle reveals RAGGED RED FIBERS and crystalline mitochondrial inclusions. Her physician suspects her condition is caused by a mitochondrial DNA mutation. Which mutation is most likely?

mutation in the mitochondrial tRNA for lysine MERRF (Myoclonus Epilepsy and RAGGED RED FIBERS) -progressive myoclonic epilepsy and sz mutated gene: mutation in tRNA Lysine (K) always heteroplasmic

What is the cause of the AD Marfan's syndrome ?

mutations in fibrillin that disrupts the formation of elastic fibers and elastic sheaths

what is in the ecf

na, cl, and hco3

Which of the following statements is/are correct? The nucleus is formed ...

nb. nucleolus no relation to heterochromation A: around clusters of rRNA gene repeats for the synthesis of rRNA and assembly of ribosome subunits

A 62 yr old woman eats a high carb meal. her plasma glucose concentration rises and this result in increased secretion from the pancreatic islet cells. the insulin response is an example of which of the following

negative feedback

Name 3 examples of negative feedback -stabilizes the system

negative feedback control of blood gluocse levels negative feedback control of b/p negative feeback control of thermoregulation

What is an astrocyte ?

nervous system IF Astrocytes mechanical strength from Glial Fibrillary acid protein (GFAP) IFs

Describe axonal intermediate filament

neurofilament proteins (NF-L, NF-M, NF-H) Location: neurons

Pellagra is a classic triad of s/s which include diarrhea, dementia, and dermatisis. These symptoms develop in individuals w which of the following vit def.

niacin

Describe PCD/Kartagener syndrome

nodal cilia help drive the flow of packets of sonic hedgehog (a protein) and retinoic acid ( an organic chemicl related to vitamin A) both of which are morphogens which are important for left -right development. Both of these compounds are critical for patterning embryonic development.

Where is the mRNA for pre-TSH (beta) translated ?

on the RER The beta subunit of TSH recognizes the receptor TSH is a secreted glycoprotein, as is the alpha subunit

Where would you find the insulin receptor ?

on the plasma membrane

Describe the stoichiometry of ATP

one full rotation of F0 F1 complex caused by 12 hydrogen ions one rotation produces 3 atps one NADH pushes 10 hydrogen ions into the intermedmbrane space one FADH2 pushes 6 hydrogen ions into the intermembrane space so 1 NADH produces 2.5 ATPS and FADH produces 1.5 ATPS

a buffer pair HA/A- has a pk of 6.4. at a blood ph of 7.4 the concentration of HA is

one tenth of A-

describe variation in ph

normal pH is 7.37 -7.43 acidic: arterial ph < 7.37 alkalemia : arterial ph > 7.43 due to log relationship change in pH below 7.4 will show a larger change in H+ ion concentration when compared to change in pH above 7.4

Signals that regulate homeostasis

nutrient status : the concentration of nutrient or metabolites in the blood-affects the rate at which they are used or stored in different tissues hormones: carry messages to their individual tissues about the physiologic state of the body and the nutrient and supply and demand the CNS - uses neural signal to control tissue metabolism, either directly or through the release of hormones

Describe the cell-cell junctions

occluding junction : tight junction anchoring junctions communicating junctions : gap junctions ( connexins)

in how many stages does cellular respiration occur :

occurs in 3 stages 1. acetyl coA production 2. Acetyl coA oxidation 3. electron transfer and oxidative phosphorylation

Describe oxidative phosphorylation

occurs in mitochondria accounts for most of the ATP synthesized in the cells all oxidative steps in the d egradation of carbs, fats, aa converge at this final stage of cellular respiration, in which the energy of oxidation drives the synthesis of ATP

What is glycolysis : salient features

occurs in the cytoplam of all the cells in the body prepartory (entry) pathway for glucose metabolism immediate/basal source of energy (ATP) is provided by this pathway it provides intermediates like pyruvate, glucose 6-po4, and dihyroxyacetone phosphate for other pathways hub for carbohydrate metabolism- all carbs are finally converted to glucose or intermediates of glycolysis before being metabolized

what is aerobic glycolysis

occurs in the presence of oxygen end products-pyruvate + NADH + ATP further proceed in the mitochondria -TCA efficient -leads to ccomplete oxidation

oxidative stress

occurs when the rate of ROS and RNOS production overbalances the rate of their removal by cellular defense mechanism ROS RNOS Cell defenses : antioxidants enzymes

Describe cell migration

often in response to external signals (cehmotaxis) -> initial cell polaization reorganization of cell architerure main motor - leading front edge ( active polymerization)

Oligomycin -inhibts complex V

oligomycin inhibits respiration, but in contrast to electron transport inhibitors, it is not a direct inhibitor of the electron transport system. instead it inhibits the proton channel of ATP synthase. it causes an accumulation of protons in the intermembrane space, bc the proton pump system is still intact, but the proton channel is blocked the addition of the uncoupler DNP after oxygen uptake has been inhibited by oligomycin illustrates this point: DNP dissipates the proton gradient and stimulates oxygen uptake as the electron transport system attempts to reestablish the proton gradient

What kind of carb is attached to the typical membrane glycoprotein ?

oligossaccharide

Where is preproinsulin mRNA translated? Describe the process

on the RER translocated signal peptide is cleaved off after n-terminal signal is cleaved, proinsulin is made as one long protein containing the intace B,C, &A chain sequences- it is not N-glycosylated a. proinsulin is folded into roughly the right shape (Bchain) a. three disulfide bounds are made by w/e the enzyme is called -once folding is accomplished and disulfide bridges are put into place, proinsulin moves on into the Golgi

Describe fibronectin

organize the ECM and helps cells connect to it - interacts w integrins

Golgi

organized membrane complex for modification, sorting, packaging of lipids and proteins

what is the van't hoff's equation

osmolality vs osmolarity <1% difference osmotic pressue = number of ions formed by dissociation of a solute molecule x c= the molar concentration of solute r= ideal gas constant t=absolute temperature

ADH regulates water retention by acting to increase water reabsorption in the kidneys. If the ADH receptors are antagonized (keep it from acting), what effect will this have on the extracellular fluid osmolarity and extracellular fluid Na + concentration ?

osmolarity increase Na+ conc. increase not diluting the solute in the ECF (blood side) reabsportion blood side - not being diluted

Where does the biosynthesis of cardiolipin take place ?

outer membrane

Describe the structure of mitochondria

outer mitochondrial membrane -permable to most molecules up to 10kDa the inner mitochondrial membrane is freely permeable to uncharged small molecules such as o2, water, co2, nh3, and moncarboxylic acids, such as 3 hydroxybutryic acid and acetoacetic acid in their undissociated, more lipid soluble form all other molecules require special transporter to cross inner membrane tissues w high demand for aerobic metabolism contain thousand of mitcohondria per cell

What is the shape of the mitochondria in hepatocyte?

oval with numerous cristae

What is protein disulfide isomerase (PDI)?

oxidation of free SH groups on cyteines to form disulfide (S-S) bonds (="cystine crossbridges") -helps many proteins fold correctly -many proteins do not assume mature form until a large number of disulfide bonds have been made -once disulfides are in place chaperone proteins can have a bigger effect

oxygen as a radical

oxygen is a bi-radical, a molecule that has 2 unpaired electrons in separate orbitals with parallel spins oxygen can accept single electron at a time to form the following reactive oxygen specie 1. super oxide O2 2. hydrogen peroxide -H2O2 3. Hydroxyl radical OH most powerful

In trancytosis of maternals IgG's in intestine, what is the pH of the intestinal lumen ?

pH-6

any aa can have a net positive, negative charge or neutral depending on the pH of the solution

pKa of carboxyl group = 2.3 pKa of amino group =9.5 if the pH of the solution is 1 or more units below the pKA of the group= the protons is on the group -if the pH of the solution is 1 or more units above the pka of the group the proton is off the group

from the picos what is the p of the study ?

participant without cardiovascular disease looking at population & not the sample - criteria for est. a meta analysis -picos est is b4- not in conclusion i- intervention : aspirin c-comparison group : no aspirin, placebo or no treatment studies w no placebo / no treatment - not blinded as a participant -> can not have a double blind study o-outcome of interest. how is cardiovascular disease defined bleeding, stroke, mi s-study type : randomized clinical trials, at least a thousand participants follow up w/n 1 yr

What is osmosis?

passive transport concentration gradient net movement of water high concentration and nacl solution displacing water molecule water moves toward high solute

what is transient changes in cell volume

permeant solutes can give rise to temporary, but not permanent, changes in osmotic pressure. therefore, transient changes in cell volume occur in response to changes in the extracellular concentration of permeant solutes adding a permeant solute such as urea to the ECF will increase ECF osmolality and intially shrink cells. Urea will gradually equilibrate across the membrane and abolishes the intitially imposed osmotic gradient, the cell re-swells to it initial vl

What are 2 examples of electrical coupling ?

perstalsis (intestines) uterus contraction ( during birth)

In trancytosis of maternals IgG's in intestine, what is the pH of the blood and interstitial fluid ?

ph-7

What are laminopathies?

rare defects in components of the nuclear lamina of the nuclear envelope -skeletak/cardiac muscular dystrophies -lipodystrophy -progeria (premature aging)

Describe chronoc granulomatous disease

phagocytes can kill numerous microorganism despite its defects b/c most m/o endogenously produce hydrogen peroxide, which the chronic granulomatous disease-affected phagocyte can modify and use against the organism in the phagosome catalase positive organism - have catalase which neutralize hydrogen peroxide by the bacteria-cannot be destroyed -granulomas-chronic recurrent infections and ansecess formation incidence in USA (descending order of frequency): Apergillus, s.a. pseudomonas, serratia and nordia

a group of 100 healthy human subjects are randomized to receive a new oral drug for which safety has already been established, to determine the optimum dose at which the drug shows biological activity. which of the following best describes the phase of this trial?

phase 2

describe urinary buffers

phosphate major and alomost ideal urinary buffer ammonia

Why is the plasma membrane asymmetry important ?

phosphatidylserine is flipped into outer leaflet during apoptosis (programmed cell death )

Describe the lipid bilayer

phospholipid -phosphate -inside hydrophobic tails -outside hydrophyllic heads-polar - glycolipid-suage outer leaflet-face ECM Cholesterol - steroid-OH structural stability both leaflet

What are the three types of lipids in the plasma membrane?

phospholipids glycolipds cholesterol

What binds to a cAMP Response element (CRE) element in the nucleus ?

phosphorylated CREB PKA catalytic subunit also enter nucleus & phosphorylate (activate) TF including CREB, which bind to the CRE ( cAMP Responsive Element) in the promoter of cAMP-resposive genes

Why is intracellular kinase activity so often important in intracellular signaling ?

phosphorylation is a widely utilized wat to active or inactive a protein 2 important types of intracellular signaling proteins a. kinases (tyrosine kinases, serine/threonine kinases) b.GTP-binding proteins ("G proteins") both are "molecular switches" regulated by phosphorylation or binding GTP switch can be reversed to turn off signal cascade SIGNALING BY PHOSPHORYLATION Kinases activates phosphatase inactivates signaling by gtp binding protein gtp binding activates gtp hydrolysis inactivates

There are different way of decribing intercellular communication. Using both a bichemical and tissue perspective, all of the following are a type of intercellular communication except for :

phosphorylation of lamin A is INTRACELLUAR cell-cell communication endocrine : hormone secretion into blood by endocrine gland paracrine neuronal contact dependent autocrine

What is lipofuscin ?

pigmented lipids ( " age pigments " ) that accumulate in multiple organs

Small sip-like internalizations of extracellular content into a small endocytotic vesicle is best referred to as :

pinocytosis

Examples of non competitive inhibition

poisons and heavy metals -cyanide- cytochrome oxidase fluoride- enolase iodactate-glyceraldehyde 3-p-dehydrogenase acetazolamide-carbonic anhydrase lead-ferrochelatase

Insulin

polypeptide hormone 2 polypeptide chains A-chain - 21 aa B-chain- 30 aa linked by 2 interchain disulfide bonds the A chian has an additional intrachan disulfide bond

What protein modification is a marker specifying than an incorrectly folded RER protein must be destroyed in the proteosome?

polyubiquination (ubiquitin pushes misfolded proteins out -> cytosol -> proteosome ) N-glycanase : removes carbo when out in cytosol

Who is at risk for developing scruvy?

poorly supplied seamen, pirates, hermits, wildnerness expolores, infants, the elderly, alcoholics, and heavy smokers vitamin C is sensitive to heat and easily lost through cooking

What are speckles?

pre-mRNA processing and modification by the snRNPs (are made by the CBs/Gems)

Glycolysis

preparatory phase - energy investment phase splitting phase- glucose 6c split into 3 carbon compounds payoff phase energy yield phase

What is the first law of thermodynamics?

principle of the conservation of energy : defination for any physical or chemical change the total amount of energy in the universe remains constant; energy may change form, or it may be transported from one region to another, but it can not be created or destroyed talk about heat content of the system : delta H entralpy it reflects the number and kinds of chemical bonds in the reactants and products when a chemical reaction releases heat, it is said to be exothermic, the heat content of the products is less than that of the reactants, and the change in enthalpy, delta H has by convention a negative value

What is secreted by a fibroblast making collagen ?

pro-alpha collagen chains assembled into a triple helix (procollagen)

Describe properties of protein mediated transport

reaction rate saturation conformation change specificity competitive inhibition lower km=higher affinity d-galactose d-arabinose d-xylose d-mannose

Fine Regulation : Proteolysis : activation of proenzyme

proenzymes also known as zymogens is a rapid method of increasing activity, but as a regulatory mechanism, it has the disadvantage of not being a reversible process proenzyme are generally synthesized in abundance stored in secretory granules and covalently activated upon release from their storage site -pancreatic proteases similiar process is seen in activation of clotting factors

ionazible drugs

proportion if ionzible drug absorbed -enviromental pH -drug's pka -when the pH is lower than the pka, the un-ionzed form of a weak acid predominates, but the ionzible form of a weak base ( quinidine) predominates when a weak acid is given orally-> most of the drug in the stomach is un-ionized, favouring diffusion through the gastric mucosa (aspirin) aspirin pka 2.97

How are proline and lysine converted to hydroxyproline & hydroxylysine ?

propyl 3- hydroxylase propyl 4- hydroxylase lysyl hydroxylase all require ascorbic acid (vitamin C ) & iron

What is the role of glycocalyx

protection (protection from acids, enzymes, clumping, dehydration) recognition and cell adhesion repulsion : negative charge from sialic aid sugars embryonic development : guides embryonic cells to destination

Give two examples of co-translational ?

protein folding N-glycosylation

describe intracellular buffers

proteins most abundant intracellular buffers -hmg is major intracellular buffer organic phosphates ex: AMP, ADP, ATP, 2,3 DPG

What is myosin I ?

protrusions w actin rich structures (microvilli)

Describe cortisol

provides for changing requirement during stress stimulates aa mobilization from muscle protein stimulate gluconeogenesis in order to produce glucose for liver glycogen synthesis stimulate f.a. release from adipose tissue

you do a literature search on the benefits of omega 3-f.a supplementation on preventing coronary artery disease but can not find any article on it, despote many " nutriotionists" and websites supporting its use. what type of bias may be present ?

publication bias only positive finds published-null findings do not get published

Describe pumps

pumps oppose the equilibrating systems to preserve intracellular concentrations of solutes, particularly ions, which are compatible w life --> chemical driving force -> electrochemical driving force <--- electrical driving force

Conversion to oxaloacetate

pyruvate can be converted to OAA by pyruvate carboxylase replenish intermediates of the TCA cycle as well acts as first step in gluconeogenesis ABC enzyme : ATP, Biotin and CO2 Obligate allosteric activator -acetyl CoA

formation of lactate

pyruvate can be reduced in the ctyosol by NADH, forming lactate and regenerating NAD during anaerobic situation in the cell. NADH which is produced by glycolysis must be reconverted to NAD so that carbons of glucose can continue to flow throufh glyclysis in anaerobic metoblism/RBCs lactate is released by tissues (e.g. RBCs or exercising muscle) and is used by liver for gluconeogensis or by tissues such as the heart and kidney

Conversion to Alanine

pyruvate can be transaminated to form the aa alanine the enzyme involved is alanine transaminase which requires pyroxidal phosphate (b6) as a cofactor synthesis of non essential amino acid

Fate of pyruvate : conversion to Acetyl coA IRREVERSIBLE

pyruvate can enter mitochondria -symport w H + ions occurs during aerobic conditions converted by pyruvate dehydrogenase complex to acetyl Co-A by a process called oxidative decarboxylation which can enter the TCA cycle

What is bioenergetics?

quantitative study of energy transduction -changes of one form of energy into another that occurs in the living cells, and the nature & function of all chemical process underlying these transductions knowledge of these principles facilitates a perception of how energy producing and energy utlizing reactions occur w/n the same cell and how an organism is able to accomplish various work functions bioenergetics obey laws of thermodynamics

Nucleolus

rRNA synthesis large prominent -> protein synthesis, increase in number of ribosomes

In Ehlers Danlos syndrome what does a mutation in collagen V cause

rare joint hypermobility hyperextensible skin

Insulin receptor signaling

receptor tyrosine kinase -alpha subunits bind insulin -autophosphorylation of tyrosine residues on Beta subunits -phosphorylates insulin receptor substrate IRS IRS activates multiple second messengers 1. Ras protein -MAP kinase pathway ( cell growth) 2. PI3 kinases pathaway ( metabolism)

Describe protein functions

receptors : signal molecules-information- response Adhesion molecules-connect cell-cell or cell to ECM Gap junctions : fast information-coupling (heart beat)

What is apical plasma membrane?

regulation of nutrients and water intake regulated secretion protection

Importin

releases cargo when it binds Ran-GTP

What does the cis cisterna Golgi sort ?

removal of Mannose

Describe hypoventilation due to lung disease

retention of Co2 production and retention of HCO3- by kidneys

How is the ECM in tendons ?

ropelike

What is the shape of the mitochondria in skeletal muscle cells ?

rows, nestled between myofibrils

What is the s/s of Tay Sach's Disease ?

s/s -Blindness -cherry-red macula -muscular weakness - seizures

How is PK deficiency diagnosed

s/s anemia -destruction of RBCs splenomegaly jaundice -increase in uncomjugated bilirubin pigment gall stones-precipation of bilirubin dx test - -periphral smear-reticulocytosis, echinocytes (hedge hog shaped) -increased uncomjugated bilirubin -normal LDH and Haptoglobin -increased 2,3 BPG Hexokinase deficiency phosphofructokinase 1- def left shifterd increased affinity right shifted (reduced affinity) pyruvate kinases def increase in 2, 3 DPG-shift of graph to the right

Tight junctions

seals neighboring cells together in an epithelial sheet to prevent leakage of molecules btw them

RER is prominent in what type of cells ?

secretory cells (pancreatic acinar cells, plasma cells)

Describe tight junctions

selective permeability barrier near APICAL end of cell

The plasma membrane is _____

selectively permeable membrane

what is the best way to interpret this figure?

serum vitamin D is associated with lowered risk for bladder cancer, heterogenity is low

a 5 yr old girl falls through the ice while skating on an outdoor pond. she is removed from the water w/n 1 min, but dry clothing is not available and she is still cold and wet for 20 minlater. which of the following mechanism helps maintain the patients core temp during the period following the rescue

shivering explaination : negative feedback-thermoregulation -increase skeletal muscle contraction, vasoconstriction, maintain homeostatis sweating is vasodilation

What is the role of ECM in cartiliage ?

shock-absorbing

Describe the preprocollagen signal sequence ?

signal sequence directs growing polypeptide chain into RER signal sequence is cleaved

explain the GPCRs signaling pathway using cAMP

signaling molecule or ligand (hormone or growth factor binds to the receptor) inactive G protein become activated by gtp & binds to adenyl cylcase ->cAMP

describe passive transport

simple diffusion brownian motion equalize contration downhill transport from high to low !

Classify enzymes

simple enzyme- made only of protein complex enzyme-also called holo-enzyme apo-protein -protein part co-factor non protein part cofactor : one or more inorganic ions fe, cu, zn, mn complex organic or metallo-organic molecules -co enzyme (vitmains) prosthetic groups -cofactors covently bound to enzymes

RER

site of co-and-post translational protein modifications contain protein chaperones responsible for production and assembly of most membrane associated proteins

regeneration of NAD+ in cytosol

site of glycolysis stall in hypoxia

What are the 3 main s/s of osteogenisis imperfecta ?

skeletal deformaties fractures (bone fragility) blue sclera type 1 OI is mild type 2 perinatal lethal type 2 deforming type 4 mild deforming

Cell migration is promoted by Rac-GTP and Rho-GTP and associated proteins that remodel the actin microfilaments and re-arrange the focal adhesions so that a cell can extend its front edge and then drag its hindmost portion forward. What kind of proteins are Rac and Rho ?

small G-proteins that act as molecular switches to induce a chain of events

What is ubiquinone?

small lipid soluble compound found in the inner membrane of animal mitochondria made of isoprenoid units derived from cholesterol synthesis it diffuses w/n the inner membrane accepts, electrons from mitochondrial flavoproteins, and transfers them to complex III (QH2-cytochrome c reductase) ubiquinone can carry either one or 2 electron and is thought to be a major source of superoxide radicals in the cell

What important nuclear riboprotein put together in Gems is important in the processing and assembly of the 45S pre-ribosomal RNA ?

snoRNA

What does the cis Golgi network sort ?

sorting : phosphorylation of oligosaccharides on lysosomal proteins

Describe the active site

specific pocket or cleft -substrate binding site enzymes bind to substrate to form the enzyme-substrate complex (ES) ES converted to EP and product released theories for substrate binding 1. fisher -loc and key model - rigid 2. koshland -induced fit model -flexible

What term is used to name abnormal spheroidal erythrocytes that have lost their ability to deform, prove unstable in osmotic fragility test, lose fragments of membrane and are uniformly small and opaque ?

spherocytes

SER

steroid hormone synthesis and synthesis of membrane lipids biosynthesis of plasma lipoprotein complexes glycogen degradation and gluconeogenesis

What are the intracellular receptors ?

steroid hormones vitmain d deriviatives thyroid hormones retonic acid

the body utilizes negative feedback systems to maintain homeostasis. The flow diagram provided shows the standard components of all negative feedback systems. which component of the negative feedback system is missing at the point labeled x on the diagram ?

stimulus -> sensor -> control center (afferent) CNS -> effectors (may be multiple-slow down or speed up) responds to both increase or decrease in the parameter

What is the role of collagen fibers ?

strengthen resist stretching and organizes the ECM

What factor activate the TCA cycle

substrate acetyl Co A low ATP/NADH levels matrix Ca + levels

factors affecting the rate of enzyme catalyzed reaction

substrate concentration enzyme concentration temperature pH product concentration presence of activator and inhibitors

properties of active site

substrate specific sterospecific made up of reactive amino acids polar ( Glu, Asp, Lys, Arg, Cys, His, Ser, Tyr ) more than just the amino acid residues involved in the bond formation or breakage; it is a complex region on the enzyme that can adjust its structure to accomodate the proper substrate and stabilize the transition state

PDH

subunits e1-pyruvate decarboxylase/dehydrogenase e2- dihydro-lipoyl transcetylase e3 dihydrolipoyl dehydrogenase coenzymes e1 thiamine pyro phospahate (TPP) (B1) e2 lipoic acid coenzyme A (B5) E3-NAD-Niacin (B3) FAD -Riboflavin (B2)

name irreversible enzyme inhibition

suicide inhibitors transitions state analogue

describe suicide inhibitors

suicide inhibitors (mechanism-based inactivation)- the inhibitor binds to the active site where it is modified by the enzyme to produce a reactive group that reacts irreversible to form a stable inhibitor-enzyme complex allopurinol-xanthine oxidase inhibitor 5-flurouracil-thymidylate synthetase inhibitor

A patient with chronic granulomtous disease, who is c/o fever, dermatitis, and diarrhea, is seen in your clinic. the genetic form of this disease results in the inability to generate, primarily, which of the following molecules ?

superoxide

What is the synaptic vesicle v-SNARE ?

synaptobrevin

Where is the synaptobrevin tightly bind to the axonal membrane t-SNARE ?

syntaxin

Which of these is an important reaction that is NOT carried out by a peroxisome ?

synthesizes glycogen from excess glucose molecules

What protein on the membrane of an early endosome guides an incoming vesicle into a correct fusion ?

t-SNARE

What is the mutated gene in MELAS called?

tRNA Leucine

Describe coenzymes group 1

take part in reactions transfering hydrogen or electrons

What are the group II conenzymes

take part in reactions transferring groups other than hydrogen

what is the best way to interpret this finding?

vitamin D is associated with fewer injuries

Describe Alz & relationship w/ tau

tau (MAP) -> hyperphosphorylated tau - behaves abnormally -forms neurofibrrillar tangles (NFTs) -decrease functional microtubules (depolymerization and disruption of axon transport)

Name a famous MAP ?

tau protein neuronal MAP hyperphosphorylated in Alz disease

Hexokinase vs Glucokinase

the Km for hexokinase is significant lower (0.2 mM) than that of glucokinase (10 mM) the Vmax for hexokinase (0.1 ... is alos significantly lower than glucokinase 1.5 ...)

What determine the physical properties of connective tissue ?

the abundance of ECM in connective tissue determines its physical properties

What is axoneme ?

the central strand of a flagellum or cilium -dynein (axonemal -type dynein) MTOC= basal body

Describe the electron transport chain

the electron transport chain is a series of protein complexes embedded in the inner mitochondrial membrane electrons captured from donor molecules are transferred through these complexes through a sequence of linked oxidation and reduction reactions

What is the significance of lactase

the enzyme lactase is a membrane bound enzyme located in the brush border or microvilli of jejunum and terminal ileum lactase hydrolyzes lactose into its constituent monsaccharides, glucose and glactose, which are then transported across the lining of the small intestine non inducible enzyme decrease w age defiency leads to lactose intolerance

Adding Isotonic Saline (0.9 % NaCl) to ECF

the fluid will stay in the ECF bc its isotonic, expanding ECF water flow is none ECF vl: increases ECF osmolarity : no change ICF vl: no change ICF Osmolarity: no change

Antimycin inhibits -complex III

the inhibition of complex III by antimycin A prevents transfer of electrons from either complex I or FADH2 containing flavoprotein to cytochrome C in this case, components preceding complex III become fully reduced and those after it become oxidized the oxygen uptake curve shows that the stimulation of respiration by ADP is inhibited by antimycin A but that the addition of succinate does not relieve the inhibition asorbic acid can reduce cytochrome c and addition of ascorbic acid restores respiration illustrating the complex iv is unaffected by antimycin A

What is net flux? factors affecting simple diffusion

the net flux of a molecule is directly proportional to the size of the chemical driving force ( concentration gradient). if an ion is involved, the net flux is proportional to both the chemical and electrical driving forces ( electrochemical gradient)

effect of pH

the pH decides the charge on the aa residues at rh active site the net charge on the enzyme would be influence the substrate binding and catalytic activity some enzymes have different optimum pH pepsin 1-2 acid phosphatase 4-5 trypsin 6-7 alkaline phosphate 9-10

what factor affect simple diffusion ?

the principle force driving the passive diffusion of an uncharged solute across the plasma membrane is the difference in concentration btw the inside and outside of the cell

Describe homeostasis

the process by which an organisms internal enviroment is kept stable in spite of changes in the external enviroment this steady state balance must exist for all LIVING systems in a living system, energy is continually used to keep the organism away from equilibrium homeostasis is a dynamic process that allows for a variable to fluctuate w/n a predictable and often narrow range the human body is not at equilibrium but is in homeostasis or steady state balance

reaction co-ordinate diagram

the rate depends on energy barrier (hill) btw S and P required for : -alignment of reacting groups -transient unstable charged molecules bond rearrangements the difference in energy levels of grounf state and transition state is called activation energy delta G the summit of the hill is called the transition state ( fleeting molecular moment in which events such as bond breakage, bond formation, and charge development have proceed to the precise point at which decay to substrate or decay to product are equally likely higher the activation energy - slower is the rate of the reaction

describe the thermodynamic systems

the reacting system-is the collection of matter that is undergoing a particular chemical or physical process; it may be an organism, a cell or two reacting comppungs type of thermodynamic system include: living cells and organisms are open systems-exchanging both material and energy of the surroundings isolated system closed system open system the reacting system + surrounding =universe

Which one of the following statement about the pyruvate dehydrogenase multienzyme complex is correct ?

the reaction of pyruvate dehydrogenase involves decarboxylation and oxidation of pyruvate then formation of acetyl coA

what is molecular size?

the smaller the molecule, the faster it penetrates. the larger and more irregular in shape the molecule, the lower the membrane permeability

Prolonged FLACCID paralysis

the type of paralysis produced by botulinum toxin

effect of temperature

the velocity of enzyme reaction increases when the temperature is increased reaches a mx then falls increase in temp -result in high activation energy of the molecules and more molecular collision and interaction for the reaction to proceed faster when the temp is increase more than the optinum temp, denaturation of the enzyme occurs and the reaction velocity drops the temperature at which max amount of substrate is converted to the product per unit time is called the optimum temperature heat inactivation of enzyme

Define and the properties of enzymes

thermo labile biocatalyst which accelerate the rate of a chemical reaction several fold w/o itself undergoing any chemical change properties specific for a reaction highly specialized proteins (except catalytic RNAs) function in aq solutions under very mild fluctuation in temp and pH lower activation energy of reactants to attain transition state faster does not dictate the equ and direction of the reaction (but reaction reaches eq much faster)

What do Goodpasture syndrome and Alport Syndrome have in common ?

they both involve disrupted collagen IV in the basal lamina of the glomerulus

Which of the following statement is true regarding enzymes ?

they decrease the activation energy so that the reaction attain t.s faster

what is one unusual thing about the cadherin proteins that form a strong cell-cell junctions ?

they must bind calcium ion in order to bind all their subsunits together

Prolonged SPASTIC paralysis

this type of paralysis is produced by TETANUS toxin

overview of homeostasis

thousand of processes are going on in the body that are all regulated by control systems failure of a control system will lead to pathlogy or death

Describe filopodium

tight parallel bundle

Tonicity of solutions

tonicity of a solution is only determined by the impermeant solutes tonicity determine steady state cell volume 280 mOsm/L -> 140 mM NaCl : isotonic - no change 280 mOsm/L -> 100 mM NaCl: hyptonic -cell swells 280 mOsm/L -> 180 mM NaCl : hypertonic -cell shrinks

Describe the pathway of Clathrin

trans Golgi -> lysosomes

What process utilized routinely by the epithelium of your GI track lining, links endocytosis to exocytosis ?

transcytosis

describe transferases group 2

transfer a chemical group from one molecule to another; thus they have 2 substrates and 2 products amino transferase methyl transferase phosphototransferase ( kinases)

What is the role of the ECM in the corneal stroma?

transparent

What is facilitative glucose transporter (GLUTs)

transported down their conc. grandient conformational change of proteins after binding to glu/gal/fru

chemical reactions in the

trillions of chemical reactions occur simultaneously in the body produces several acids that increase the hydrogen uon concentration of the blood or other body fluids and tend to lower the pH

Describe Type I collagen :

two alpha 1 and one alpha 2 chain PREprocollagen : signal sequence, directs to RER for synthesis ER processing begins with cleavage of signal sequence : Preprocollagen -> procollagen procollagens propeptide domains enhance helix formation & prevent premature fibril formation

which one of the following vitamins or enzymes is unable to protect against free radical damage

vitamin b6

What type of collagen are fibril forming ?

type I collagen : skin, bone, tendon, blood vessels, cornea type II collagen : catiliage, intervertebral disk, vitreous body type III: blood vessels, fetal skin

What type of collagen of network forming ?

type IV - basement membrane type VII - benaeath stratified squamous epithelia

What is basal lamina is largely made up of _____

type IV collagen ( a sheet forming collagen) basal lamina: think sheetlike network of ECM components

Describe syntaxin

typical t-SNARE for the axonal membrane

What are uncouplers

uncouplers dissipate the proton gradient by transporting protons back into mitochondria, bypassing the ATP synthase, decreasing ATP synthesis and generating heat uncouplers are typically hydrophobic compounds and either weak acids or bases, w pKa near pH 7 1. physiological : thermogenin channel-non shivering thermogenesis 2. pathological 2,4 dinitrophenol, high dose aspiring and pentacholorophenol

non-shivering thermogenesis

uncoupling protein -1 (UPC1) known as thermogenin, is found exclusively in brown adipose tissue UCP1 provides body heat during cold stress in the young and in some adult animals ( and can be induced upon mild cold exposure) accomplishes by uncoupling the proton gradient, allowing transport of protons but bypassing the ATPase, thereby generating heat ( thermogensis) instead of ATP

derivation of Gibbs free energy equation

under the conditions existing in biological systems (including constant temperature and pressure), changes in free energy, enthalpy and entropy are related to each other quantitatively by the equation : by convention, delta S has a positive sign when entropy increases delta H as noted above has a negative sign, when heat is released by the system to it surroundings. T= absolute temperature in kelvin (c+273) either of these conditions, both of which are typical of energentically favourable process, tends to make delta G negative delta G: change in free energy -energy available to do work -approaches zero as reaction proceeds to equlibrium -predicts whether a reaction is favorable delta H: change in enthalpy -heat released or absordbed during a reaction -does not predict whether a reaction is favorable delta S: change in entropy -measure of randomness -does not predict whether a reaction is favorable

what is the second law of thermodynamics

universe always tends toward increasing: disorder: in all natural processes, the entropy ( disorderliness) of the universe increase delta S entrophy =quatitative expression of the degree of disorder or randomness in a system energy is a system that is unavailable for useful work the total entropy of the universe must increase if a process must occur spontaneously living systems are never at eq w their surroundings constant transaction btw system and surrounding explain how organisms can create order w/n themselves but increases the disorder of the surrounding

What increase fluidity in the plasma membrane

unsaturated f.a (increase in cis-double bonds) short f.a. chains increase temp less cholesterol

What causes a vesicle to fuse?

v & t-snares, NSF/SNAPS vesicular-SNARE (v-SNARE) binds to compatible target SNARE (t-snare) to guide and promote vesicular fusion with target membrane

Upon command of the local synaptotagmins, what type of protein guides the docking of a synaptic vesicle filled with neurotransmitters to the axonal membrane adjacent to the synapse and then helps promote membrane fusion so that release will occur?

v-SNARE

What type of protein guides the docking of a secretory vesicle with the correct spot on a plasma membrane and then helps promote membrane fusion so that secretion will occur?

v-SNARE

Which of these is an important protein that guides a microtubule associated coated vesicle to the correct target membrane then helps promote membrane fusion ?

v-SNARE

(fill in the blank) The _________ is/are instrumental in bringing the vesicle membrane and correct specific target membrane close together and guiding proper membrane fusion so that the vesicle empties out its contents.

v-SNARE & t-SNARE v-vesicle t- target membrane

What are the two key players in endocytosis ?

v-SNARES: proteins in the vesicle t-SNARES: proteins in the membrane

Describe synaptobrevin

v-snare for synpatic vesicle primary target for most botulism toxins primary target for tetanus toxin

effect of increase in enzyme concentration

velocity of the reaction is directly proportional to the enzyme concentration provided the substrate concentration is unlimited at a given substrate concentration, the initial velocity of an enzyme catalyzed reaction is proportional to the enzyme concentration property made use of in determining the levels of enzymes in plasma, serum or tissue

describe the regeneration of NAD +

very little NAD in cytosol NADH-> NAD + 2 electrons in aerobic tissues : by transferring the electrons to mitochondria produce ATP by shuttle mechanisms in anaerobic tissue or aerobic tissues devoid of oxygen : by producing lactic acid

What is myosin V?

vesicle and organelle transport

What is regulated secretion ?

vesicles wait for an external signal then -> rapid secretion secretion of hormones, neurotransmitters, digestive enzymes intracellular signal is usually increase cytosolic Ca 2+ ( from extracellular fluid or released by second messenger from the intracellular stores)

How are mRNPS (pre-mRNA -->mature mRNP) exported to the cytosol ? What happens next

via the NPC - translated either on free cytosolic ribosome or on ribosomes attached on to surface of the RER