RUSM- Mini 1

What is an acute/dynamic risk of suicide and who is in this category

"impulsiveness/volatility" - substance use -psychic angst (after high distress event) - depression - hopelessness - support system loss - change in therapeutic alliance - suicide plan/intention - easy access to lethal methods - "doom"/"gloom" delusions or marked existential questions

Anaplerotic reactions

"refilling of TCA cycle" those that can replete TCA cycle intermediates so that if in the instance that TCA cycle intermediates become depleted, pyruvate at the expense of ATP can be converted to oxaloacetate to restart the cycle **this is carried out by pyruvate carboxylase: synthesizes oxaloacetate from pyruvate, in this way pyruvate can supply both substrates for the first step of the TCA cycle, oxaloacetate and Acetyl-CoA *** anaplerotic reactions can also come from catabolism of AA to make alpha-ketogutarate or succinyl-CoA or other intermediates

Loss of telomeres creates

"sticky ends" of DNA which are hot spots for DNA repair or recombination

What is a chronic/static risk of suicide and who is in this category

"things you can not change" - attempts in past - family/ peer suicide - particular psychiatric illness (bipolar, depression, schizophrenia) - chronic/terminal illness/ pain (chronic pain) - high risk group

Incidence rate

# new cases/ # at risk to be a new case ** attack rate= incidence rate when denominator is limited to ppl with a particular risk at a specified time

osmolarity

# of osmotically active particles per liter of solution (mOsm/L)

osmolality

# of osomtically active particles per kg (mOsm/kg H20)

GTP does NOT

- actually signal anything alone- it has to be part of GSalpha in order to do so - it does not phos. anything either nor does it stabilize the alpha-subunit in its inactive form

Suicide prevention in primary care settings

- adequate policies and practices - training and recog. of risk and quality of care - screening - pt and fam education - accurate diagnosis and treatment - referral to specialist care - continuous care - documentation *** think of health promotion lecture what level of prevention would be needed here? secondary care

Fat droplets are prominent in:

- adipocytes (fat cells) - adrenal cortex cells - liver and other cells including steroid-secreting cells

Neural crest derivatives

- adrenal medulla - pigment cells PNS: - ganglia (sensory- pseudounipolar neurons & autonomic- postganglionic neurons) - schwann cells (PNS myelin Meninges - Pia and arachnoid mater Head - Pharyngeal arch cartilage and bone - odontoblasts - parafollicular (C) cells Heart - Aorticopulmonary septum - Endocardial cushions

Describe initiation of translation

- after pre-RNA is transcribed its process to form mature mRNA (RNA binding proteins including the small subunit of the ribosome) - the specialized start tRNA with Met binds the SMALLL subunit of ribosome at start codon in the P site - next the large subunit of ribosome and otehr associated factors bidn the complex " initiation complex'

Ligands activate receptors by causing an allosteric (structural) change in the receptor, what are these?

- agonists: cause this change and activate the receptor - antagonists: bind the receptor, block the binding site- binds competitively, and do NOT activate (no structural change) so these do not activate BUT they do block agonist action (these are mostly artificial in our body) - inverse agonists: bind the receptor and stabilize the inactive site (can reduce activity from baseline level) - so lowers activity, stabilizes the inactive form

the four major molecules (carbs, lipids, proteins, nucleotides):

- all assemble into higher order structures - all assembly by polymerization or aggregations -monomer structures determine the shape, zise, and functionality of the higher order structures

Which AA are found in the active site

- glycine (gly, g) - Serine (ser, s) - threonine (thr, t) - tyrosine (tyr, y) - tryptophan (trp, w) - Aspartate (asp, d) - Glutamate (glu, e)

Which enzyme are involved in the regulation of glycolysis

- glycogen phosphorylase - hexokinase - phosphofructiokinase - regulation by fructose 2,6 bisphosphate - pyruvate kinase * these steps are differentially regulated in different organs, depending on need! There are exergonic steps- they have a substantial negative delta G

A cytoplasmic inclusion whose function is in energy storage

- glycogen rosettes (they are aggregates of carbohydrate polymer in which glucose is stored , it is not surrounded by a membrane) - liver cells and skeletal muscle are 2 major glycogen storage sites

the major energy catabolism of carbohydrates is done during

- glycolysis - TCA cycle - Oxidative phosphorylation

Major energy producing metabolic pathways include

- glycolysis - TCA cycle - oxidative phosphorylation - glycogenesis - glycogenolysis - hexose monosphosphate shunt (PPP) - fatty acid synthesis - fatty acid degradation - amino acid catabolism - urea cycle

Pyruvate (a central intermediary) can be generated from

- glycolysis (if you need energy) - Lactate (from anaerobic metabolism occuring in erythrocytes and mucle - Alanine and other AA (protein breakdown

Mutations can cause loss of functions two types are

- haploinsufficiency: heterozygots dont have enough of activity of gene product and the dose is too low in heterozygotes - dominant negative: presence of mutant form causes normal copt to not function properly, commonly occurs in proteins that make homodimers or higher multimers

What is confidentiality and why should we do it

- unless otherwise required by law providers must keep private any communication that occurs in the context of treatment why ? - respect for patients - allow discussion of sensitive topis - encourages care-seeking - prevents harmful consequences for the patient

Insulin signals the liver, skeletal muscle, adipose tissue and other organs to

- use glucose as the principal energy source - increase uptake of glucose - turn on glycolysis - store fat in adipose tissue - store glucose as glycogen in muscle - general anabolic signaling

List completely non-polar biological molecules

- waxes - triglycerides (fat) - cholesterol esters) these all tend to form solids or fat (unless they are small,like the hydrocardons in gasoline)

Examples of hypoxic situations

- wound healing - tumor formation - blood clots - Anemia - Lung Disorders - Circulatory problems

The endoderm forms parenchyma of

-liver -pancreas - submandibular and sublingual glands - follicles or thyroid gland (not C cells)

Metabolic regulation works through

-metabolites - phosphorylation - protein expression

a triglyceride is made up of

1 glycerol, 3 fatty acids

The philadelphia (Ph) chromosome

a short chromosome containing centromere of 22 and the tip of the q arm of 9 - it is the product of a reciprocal translocation - the translocation brings together the two genes BCR- ABL with effects detailed in following slides ** needed to diagnose Chronic mylogenic leukemia (CML)

Nucleotides are made up of

a sugar, phosphate and base

Suicide inhibitor binds to the

active site like a competitive inhibitor but it is NOT reversible

Calmodulin dependent kinase II (Cam KII), calmodulin, IP3 receptor, and phospholipase C gamma

all serve some function related to calcium signaling, either upstream or downstream to an increase in calcium concentration

suicidality

all suicide related behaviors and thoughts including completing or attempting suicide, suicidal ideation or communications

A replisome contains

all the polymerases, helicases, and topoisomerases needed for both leading and lagging strand synthesis

Inhibition for hexokinase step in glycolysis is via

allosteric product inhibition using G6P, inhibiting Hexokinase and glucokinase enzymes

Noncompetitive inhibition binds to the

allosteric site (decreases vmax, km unchanged)

reflecting

allows for interpretation and reframing, which either leads to pt feeling better understood or allows for the patient to correct the physicians interpretation

Which TCA cycle enzyme has the same mechanism as PDH

alpha-ketoglutarate dehydrogenase - it has lipoic acid, thymine to carry out rx, and FADH

if a father is affected by an x-linked dominant disease his daughter will be

also affected (she must have her fathers x-chromosome) - X-linked inheritance excludes father to son. father only gives Y to son - for x-linked dominant more females than males are affected

Different isoforms (also known as splice variants) are made by

alternative splicing ** a change in the reading frame often results in truncated proteins ** alternative splicing results in altered protein sequence and function ex. BRCA1 gene is alternately splice in response to DNA damage

In the FED state dietary preotins, sugars (polysaccharides) and fats are digested in the mouth, stomach, and intestines to yield

amino acids, simple sugars, and fatty acids and glycerol - ALL of which can be broken down further into glucose

to form vesicles or bilayer sheets the lipids that constitute them must be

amphipathic

Which karyotype is more useful

banded karyotype

Nucleosides are a

base and a sugar

Vesicles, or liposomes are

bilayers enclosing a limited aqueous compartment. they are typically spherically shaped, the bilayer forming the outer layer of the sphere

repressors typically bind near the RNA entry site or the trancriptional strat site and block transcription by physical obstruction, while enhacers can

bind near but typically bind at a distance, then bend DNA as it associated with transcription factors that recruit RNA polymerase to its binding site

DNA polymerase alpha

binds the single stranded stranded DNA and creates a RNA primer then a short segment of DNA with a 3' end to be used by DNA polymerase delta

the golgi appartus is

biochemically compartmentalized

Hydrogen Peroxide is converted to water and oxygen by

catalase - Hydrogen peroxide can also be converted to the highly reactive Hydroxyl radical (OH. ), which can be catalyzed by free iron - Hydrogen peroxide can also be converted to water by glutathione peroxidase

What happens in Complex I: NADH dehydrogenase ( a proton pump)

catalyzes conversion of NADH to NAD+ (NADH + FMN --> NAD+ + FMNH) - transferse 2 electrons to flavine mononucleotide (contains riboflavin) - electrons are then transfered further to a series of iron-sulfer clusters - the final step is transfer to oxidized CoQ (Ubiquinone) which becomes reduced to CoQH2 (ubiquinol) - 2 electrone from NADH are transfered. CoQH2 also carries 2 electrons. It picks up 2 protons from the matrix as counter charges **** There are 4 protons (H+) pumped for each NADH (this is carried out by the membrane portion of the enzyme )

Tail folding takes place which is mainly due to the growth of

caudal portion of neural tube - also results in demarcation of the foregut, midgut, and hingut

Ligands activate nuclear hormone (intracellular) receptors by

causing large allosteric changes, first in the ligand binding domain, and then in other domains - the ligands are typically hydrophobic, and they bind in hydrophobic pockets in the ligand-binding domain of the receptor - this causes an alpha-helix to reorient and cap the ligand, essentially burying it in the middle of the protein - this releases HSP90 proteins (for class I receptors) - coactivator proteins can bind and the DNA binding domain is exposed for binding to the response elements on the DNA

___ is found on caveolae

caveolin

One member of the ORC is

cdc6

MCM (helicase) can only enter the pre-replication complex after

cdc6 has been phosphorylated and left the complex

cyclin E is a partial activator of

cdk. An increase in active Cdk will result in frequent cell cycles

Cyclin B is the cyclin which complexes with

cdk1 to form M-cyclin which is responsible for the regulation of the metaphase to anaphase transition and all the actions listed in the question

Cyclin E complexes with

cdk2 to form G1/S-cyclin. G1/S cyclin phosphorylates Rb protein and participates in the initiation of DNA replication

Paracrine signaling

cell releases chemical signal that affects other nearby cells (this is localized it occurs from one cell and the signal is sent to various other cells (ex. in inflammation cells make prostaglandins to help)

Describe the development of the inner cells mass (embryoblast)

cells of the inner cell mass differentiate into an 1. Epiblast: simple columnar cells 2. Hypoblast: simple cuboidal cells ** together these two layers form the BILAMINAR GERM DISC - at this point the blastocyst cavity has become the primitive yolk sac in the center - and the amniotic cavity (formed via programmed cell death) within the epiblast layer

Synaptic signaling

cells release a chemical signal that travels very short distances to affect electrical signaling in adjacent cells (very specific goes from 1 neuron to 1 synapse) ex. nerves " to move your finger you have a synapse on the motor neuron

Endocrine signaling

cells release a signal that travels long distances to reach target cells (these are systemic and have receptors all over) Ex. insulin from pancreas or adrenaline these are endocrine hormones

Regulation of metabolism can be at the

cellular level (local) or global as signaled by hormones or circulating nutrients

The most abundant biomacromolecule

cellulose - this is a dietary fiber. It is NOT digested in a significant extent in humans because we lack an enzyme to break the beta (1-4) glycosidic bond, as do other mammals - ruminants and beavers rely on gut micro-organisms to break down the cellulose into glucose as an energy source

this stucture is a cylindrical organelle that contains 9 triplet microtubules clusters

centriole

Which DNA seq is found in highly compacted state at all stages of cell cycle except when undergoing replication

centromeres - this is one of the few places that stary highly compacted (telmoeres it similar)

With growth of the brain vesicles, the embryonic disc bulges into the amniotic cavity and then folds

cephalocaudally, this folding= head fold Consequences of cranio-caudal folding: - reposition the heart tubes into the presumptive thoracic region (heart tube is positioned ventral to foregut and caudal to oral cavity and brain) also the septum transversum moves caudal to pericardial cavity (where it will form the central tendon of the diaphram), whereas prior to folding it was cranial to it

There is a large family of complex glycolipids using ____ as the fundamental lipid and with various branched sugars

ceramide

Agonist

compound that evokes normal receptor response ex. adrenaline (epinephrine) and isoproterenol (an artificial compound) are agonist of beta-adrenergic receptor * agonists cause an allosteric change in a receptor conformation to an active state

During prophase the

condensation of chromosomes occur

chat with friend over coffee

contact signaling

The intracellular side of RTKS all

contain tyrosine kinase activatiy that auto-phosphorylates and the can phosphorylate other subsrtates - dimerization is characteristic of the mechanism of activation of the RTKs that then leads to the tyrosine autophosphorylation

fully mature mRNA

contains ONLY exons. No introns or extragenic sequences **good for creating human genomic DNA library about CODING region

stress fibers are made up of

contractle actin-myosin bundles in non-muscle cells

Catabolism is the

conversion of complex food and storage molecules (complease carbs, protein, fat, TAG, or glycogen) into simpler components like monosaccharides (simple sugars, fatty acids, and AA) that can be utilized for energy

explain energy transduction in oxidative phosphorylation

conversion of glucose to reducing power (NADH) to proton gradient to ATP - this is energy transduction - it converts oxygen to H2O- O2 is the source of oxidative enrgy. It creates a proton chemical gradient

Energy transduction

conversion of glucose to reducing power to proton gradient to ATP

During aerobic glycolysis pyruvate is

converted to Acetyl CoA for energy

Glutathione peroxidase

converts reduced G-SH to oxidized GS-SG - this is a selenium-containing enzyme that is present in both cytoplasm and mitochondria. In addition to H2O2, it also attakes lipid peroxides (Lipid-O-OH)

Allelic heterogeneity

could explain why a certain disease like cystic fibrosis can be cause by hundreds of diff. mutations within the CF gene - allelic heterogeneity is basically many alleles all in the same gene

When two parents are related what chance of disease increases

could only be autosomal recessive - also, both parents would HAVE to be carriers and therefore the risk of next child to be affected is 1/4

development proceeds ___ to ___

cranially to caudally "clear finger b4 toes, clear elbow b4 knee, clear eye b4 hand etc"

Each ORC

creates 2 replication forks, each containing a replisome

Endodeoxyribonucleases

cut the DNA internally at sites designated by protein binding (ZFN or TALENs or meganucleases) or nucleic acid binding (CRISPER-Cas9) sites that are specific. The endonuclease than cuts the DNA allowing the integration or recombination with the linearized recombinant DNA

In the cell cycle ____ mediate the transition between phases

cyclins

Give an example of a first line of defense against toxins, one that plays a MAJOR role in drug detoxification

cytochromes p450 (CYPs)- in sER

Cleavage furrow formation occurs during

cytokinesis - this happens after the completion of mitosis

tubulin and importin would be found in the

cytoplasm

suicidal communications

direct or indirect expressions of suicidal ideation or of intent to harm or kill self, expressed verbally or through writing, artwork, or other means

Chemiosmotic Hypothesis

discovered by Peter Mitchell in 1961 - States that oxidative phosphorylation and ATP are synthesized by chemiosmosis (NOT substrate level phosphorylation- so no CHEMICAL mediator is required) **NO COVALENT CHEM NEEDED - basically proposes that ATP synthesis was driven by a proton gradient (via conformational mechanisms)

breach of confidentiality ex

discussion in public places - tempting to have conversation concerning pts care in medical center elevators, cafeterias, and hallways as well as at parties or conferences

ASO (allele specific oligonucleotide) probes that are 15-20 bp long can

distinguish between two different single nucleotide polymorphisms (SNPs). Longer probes cannot distinguish between the two SNPs ** shorter one good for identifying someone with sickle cell **these probes can be used to rapidly determine which individual has the "normal" allele and which has the "mutant" allele

As demonstrated by the slide on hearing loss, for autosomal recessive diseases a person who is a double heterozygote..

does not have the disease

you need affected parents for a disease to be considered

dominant

A mutation in gene encoding a structural protein results in a

dominant disease

What kinds of cells contribute to the placenta

early in development, cells in the blastocyst which are destines to become the placenta become trophoblasts that line a blastocystic cavity, with a inner cell mass composed of embryoblasts destines to become the fetus

Trimeric G-proteins stimulate or inhibit

effector targets, initiating a second messenger cascade

Ion-channel coupled receptors

effects of ligands that bind ion channels are often referred to as ionotropic effects) ex. nicotinic ach receptor

Oxidative phosphorylation aka

electron transport. Converts high energy electrons (reducing power) to ATP and makes water from oxygen

At week 2 of development the inner cell mass is referred to as the

embryoblast

Morula enters the uterine cavity at the

end of day 4/beginning of day 5

listening to a broadcasts is like

endocrine signaling

Notochord is derived from

endoderm - notochord is derived from the notochordal plate which is composed of cells in the endodermal layer, which detach and migrate into the mesodermal layer

functions of lipids

energy storage, compartmentation-membranes, signaling molecules (steroids) , vitamins - dietary lipids give you energy and heart disease

Substrate level phosphorylation refers to

enzymatic reactions where there is a direct transfer of phosphate to ADP from a substrate or enzyme. ** this is DIFF that oxidative phosphorylation where a conformational change drives ATP synthesis and the energy is supplied by a proton gradient

The mitochondria contains the

enzymes for the TCA cycle, including pyruvate dehydrogenase ---everything has to get in and out by transport---

Once the endodermal ferm layer is formed

epiblast cells then form a middle layer between the "old" epiblast and hypoblast layers -- forming the intraembryonic mesoderm **cells in this layer are highly organized @ midline you have the notochordal process and going laterally you have paraxial (closet to notochord), intermediate, and then lateral plate mesoderm

BMP-4 (bone morphogenetic protein) penetrates into the ectoderm and induces it to form the

epidermis, hair and nails

Name the 6C sugar epimers

epimers differ only by stereochemistry at one position (this is distinct from being stereoisomers) - Mannose - Glucose - Galactose (glucose and galactose are C4 epimers) (glucose and mannose are C2 epimers)

Vasoconstrictores

epinephrine, angiotensin, vasopressin

The Telomere (which is highly repetitive DNA) is

essential to agiing it is on only prior to birth in implementation or in cells that must be immortilized (ex; sperm) or in instances of cancer

repeating

essentially sending back the same or nearly the same statement, pt feels heard, if used to much pt could feel "parroted" orrr that the interviewer has no thoughts of their own

lipids store

ester bonds

what type of bond attaches fatty acids to glycerol

ester bonds - these are important and occur in the fat (triglycerides) and in the membrane glycerophospholipids.

True or false; NADH can cross the inner mitochondrial membrane

FALSE!!!!!!!!!! NOOO NADH CANNOT ever ever by itself cross the inner mitochondrial membrane so how? malate/aspartate shuttle is used

True or false: ozone is a free radical

FALSE, it is not a free radical but it is highly reactive

Colchine arrests the cell in this phase of the cell cycle.. this phase is the one where chromosomes become condensed and aligned prior to equal partition into daughter cells

M phase (mitosis )

DNA is replicated in the S phase under control of

MCM and CDC6

During states of LOW energy will there be more or less PDH activity

MORE PDH activity - Ca2+ activates the phosphatase and activates PDH- Ca2+ is increased during skeletal muscle activity and signals an energy demand - pyruvate inhibits the kinase (keeps PDH dephosphorylated) and activates PDH

Describe the GAPDH (glyceraldehyde phosphate dehydrogenase) step (step 6) in glycolysis

Main thing is tioether formation, oxidation (it harvets NADH), forms a higher energy thioester bond - a high-energy sulfo-ester bond is formed between the enzyme and GAP by oxidation with NAD+ , this generates reducing equivalents in the form of NADH, which can be further converted to ATP in the mitochondria * the high energy bond can be transfered to a phosphate ester (replacing the sulfo-ester) by simple substitituion

The interaction of what loops the mRNA

Poly A tail- PABP - eIF4G - eIF4F interaction * eIF4G links PABP and the cap binding proteins, eIF4F ** the poly A tail stays associated with 5' cap via eIF4F/eIF4G/ PABP to the ribosome so that the ribosome can reload in the cytosol

Leading strand synthesis has only a single

RNA primer and the Pol epsilon continues to add nucleotides unto the RNA primer of another newly replicated region is found - the RNA primers are removed and the 3' end of the upstream strand fills the primer region - DNA ligase seals the DNA fragments into the lagging strand

Telomeres cannot be fully copied by DNA polymerases due to the

RNA primers needed to start each 5' end

Fen 1 binds

RNashe H

increased synthesis of enzymes for detoxification would occur in the

ROUGH ER

In ETC each complex donates its electrons to the next species with incresingly

higher electron affinity (redox potential) - 2 electrons gives up ~ 50 kcal/mol energy --> several ATP ** steps with large decreases correspond to those that pump protons

Older parents have

higher mutation in eggs and sperm

Ferrous iron (Fe2+) can through the fenton reaction produce

highly aggressive hydroxyl radicals and Fe3+ from less dangerous hydrogen peroxide *** the fenton reaction is considered an important possible source of hydroxyl radicals. This is why iron is kept chelated in the body and typically kept in the Fe3+ form

For any given recessive disease, the risk of a woman being a carrier is less than the probability of her being

homozygote normal

Other GPCRs can bind or act as

hormones or neurotransmitters

It is the differences in the molecular response to

hormones, as dictated by distinct genetic and regulatory features, that give the particular characteristic metabolic response for an organ - the system sense changes in demand it provides central and peripheral responses through endocrine system and other mechanisms. this goes through intracellular sig. pathways to change the cellular level response (diff for each organ)

the helix structure is due to what type of bonding

hydrogen bonding between bases (base pairing)

lysosomes contain

hydrolases

the ___ drives lipid assembly into membranes, protein folding, and to some extent DNA duplex formation

hydrophobic effect

Proteins can insert into membranes because they have

hydrophobic residues (in the lipid bilayers and cores of soluble proteins)

lipids self-assemble due to their

hydrophobicity - a key aspect of lipids is their hydrophobicity: all lipids are hydrophobic to some extent. Some may also have a polar part (amphipathic)

Polarity realtes to ___

hydrophobicity and this is a MAJOR determinant of protein structure

if dominant, ask if males and females are equally often affected

if yes, autosomal - if no, x-linked (should have 2x as many affected females than males)

0.3 million adults made no plands and attempted suicide what could this say about this group

impulsivity - acting w/o thinking about it - could be after a traumatic event

Where can you find pantothenic acid (vitamin B5)

in CoA - this is a vitamin that is required in the diet, but is sufficiently common that deficiences are rare and occur only with general dietary deficits

Km vs Kd

in Km you are worried about how fast it can bind it reflects the Kcat which shows how fast substrate binds and how fast you can convert substrate to product. Kd is simply a binding constant and it is way simpler

mitosis

in all cells by germ cells - produces 2 identical cells - each has 46 chromosomes, @N - 1 S phase, 1 division

Sugars can also be structural components can you give an example

in chondroitin sulfate- they form an integral and substantal part of CT - chondroitin-sulfate repeat provides alot of negative charge to the sugar chains that keeps them hydrated, and apart. This provides the elasticity and compressibility required in CT

When is revealing info to pts relatives or friends acceptable

in emergencies BUT this needs careful consideration physicians MUST break confidentiality in som situations: - pt is suspected of child or elder abuse - pt is at sig risk of suicide - pt poses a serious threat to another person - pt poses a risk to public safety (ex: an impaired driver)

meiosis

in just germ cells- eggs and sperm - produces 4 different cells - each has 23 chromosomes, 1N - 1 S phase, 2 divisions

What are the diff uses for glycogen stored in liver vs glycogen stored in the muscle

in liver: it is stored to provide circulating glucose during fasting in muscle: it is stored to provide glucose for energy during contraction (exercise)

kinesin and dyenin

in microtubules

Role of AMP in muscle

in muscle under extreme conditions of anoxia and depletion of ATP, AMP activates glycogen phosphorylase B without it being phosphorylated

Where can CoQ be found

in the inner membrane of the mitochondria

How do you view chromosomes in the lab

in the microscope - the chromosomes are obtained from a cell in mitosis (metaphase): bc they are condensed (they are also usually cultured WBC) - phylohaemagglutinin (PHA): growth inducer for WBCs - colchicine (colcemid): inhibits formation of the spindle stops cell division in metaphase - hypotonic saline with a fixative to stop enzymes from breaking down chromosomes - giemsa: stain which has given name to g-banding - trypsin: protease used before staining if banded karyotype if the aim

During M phase the chromosomes are

inactive, condensed, and NOT transcribed to mRNA

External (foreign) ligands

include sensory inputs (heat, light, pressure, odorants, taste, auditory) - there are receptors, of various types to detect these (ex. xenobiotics)

There are alot of ways to pharmaceutically inhibit DNA replication (directly or via substrate depletion). This can be done using drugs that inhibit what?

inhibitors of polymerases and inhibitors of dTTP production

miRNA

inhibitors of translation or transcription - derived from by binding the template DNA strand in transciption D-loop and impede the processivity of the RNA polymerase

What does ATP do to activity of PFK1 in glycolysis

inhibits PFK (signals that cell has sufficient energy at moment) - citrate and phosphoenolypyruvae also inhibit it * citrate signals the state of the mitochondrion. If there is citrate shuttled from mitochondrion, this signals saturation in TCA cycle and glycolysis should be slowed

The HRE or hormone response element

is a DNA segment that can act as a transcriptional activator or as a repressor to make more or less RNA

K- homology splicing regulatory protein (K)

is a member of the dicer complex that produces miRNAs and helps to identify target RNas for both dicer function and general degradation - AU rich regions of mRNA (ARE) bind K ** for the mRNA genes required for muscle differentiation (like p21, myogenin or MyoD)- K targets the mRNAs for destruction so these genes are NOT turned on in non-muscle cells

2,3- Bisphosphoglycerate

is made in step 7 (PGK) - it is a side path ONLY used by RBC - 2,3- bisphosphoglycerate is a regulater of hemoglobin - the amount of this changes in response to altitude and in pregnancy - the effect is to lower the affinity of hemoglobin for oxygen and thereby increases delivery to tissues in conditions of low oxygen tension, or deliver more to a fetus - the amount of 2,3-BPG is regulated by phosphatase that breaks it back down to 3-phosphoglycerate

pulse ox

is measuring saturation in the TISSUES

Myosin light chain

is phosphorylated by myosin light chain kinase - MLC-kinase is only activated when bound by calcium/calmodulin - this is the signal for stimulating contraction in smooth muscle ----A calcium channel blocker prevents calcium influx into the cell across the plasma membrane keeping the myosin light chain kinase inactive. Myosin light chains that have beome dephodphorylated by a protein phosphatase remain in the inactive state and the muscle cell relaxes

COP-II

is the coat protein for vesicles transported in an anterograde direction from RER --> golgi

Clamodulin

is the common mediator of many intracellular effects of calium ion conc. inrease - it binds 4 calcium ions, undergoes sig. structural change on binding calcium and then procedds to interact with other target proteins to mediate many calcium effects

The F1 portion of the F0F1 ATPase (complex V)

is the hexameric head composed of alpha and beta subunits plus several others

rRNA

is transcribed and partially assembled in nucleuos - forms scaffoold of ribosomes (holds mRNAs and tRNAs during translation)

only 1.5% of the genome

is used to encode proteins

Phosphofructokinase is irreversible in the ATP --> ADP direction meaning

it CANNOT produce ATP. It only consumes it - phosphoglycerate kinase reaction on other hand is reversible and can both consum and produce ATP

The nuclear organizer is actively transcirbed all the time so

it cant be in a highly compated form except in Mphase where it is one of the very last things to coil up

What does cyclin A do

it complexes with cdk2 or cdk1 which forms S-cyclin. S-cyclin regulated the G2 checkpoint and ensure that the DNA is completely duplicated before mitosis

In week 3 what happens to the primitive streak

it enlarges and migrates cranially - the primitive streak elongates to occupy approximately half the length of the embryo - cranial end of streak proliferates to give primitive (Hensens) node - narrow groove (primitive groove) forms that is continuous with primitive pit - epiblast cells near the primitive streak, detach from one another and migrate through the primitive streak - firstly these cells invade the hypoblast layer and displace the original hypoblast cells *** once the original hypoblast cells are replaced definitive - the endoderm is formed (associates with yolk sac

Cancer cells have a high rate of glycolysis, so they have elevated activity of rate limiting enzyme of glycolysis (PFK-1). What does fructose 2,6-bisphosphate do to the activity of PFK1

it increases PFK-1 activity - fructose 2-6, bisphosphate metbaolite is formed by the kinase subunit (PFK2) of the bifunctional enzyme

Describe the Triose Phosphate isomerase step of glycolysis (step 5)

it interconverts DHAP and GAP - GAP (glyceraldehyde 3-phosphate) is what feeds into the following glycolytic steps

Describe step 7 (3-phosphoglycerate kinase- PKG) step of glycolysis

it is ATP generation step (SUBSTRATE LEVEL PHOSPHORYLATION) *remember 2 ATP/glucose -- the side path of this reaction that generated 2,3-BPG is only active in RBC.

If the transcript has an IRES

it is NOT capped and eIF4G is proteolyzed, then eIF4G binds IRES instead of eIF4F

What does the fumarase enzyme do in TCA cycle

it is a freely reversible hydratase that makes fumarate into L-Malata

Define a boundary

it is an edge of appropriate professional, clinical behavior - a situation that disconnects whats expected and accepted social, physical, and psychological boundaries that separate physicians from patients - derived from ethics code, cultural morality, and jurisprudence - sometimes difficult to identiy clearly

Why is phosphoenol-pyruvate (PEP) an important intermediate

it is part of glucose synthesis through gluconeogenesis, being made from oxaloacetate (not pyruvate)

Once NADH is in the mitochondrial matrix

it is ready to do electron transport

What is the fate of lactate

it is recycled in the blood stream to the liver to be reconverted to glucose using gluconeogenesis (cori cycle). OR it is reconverted to pyruvate when oxidative conditions are re-estabilished and used for energy production. It used to be thought that cori cycle was predominant, but more recent work indicates most of the lactate is used locally for energy

Methylation

remedy: - demethylation (chemical or enzymatic) - base excision repair (usually) - nucleotide excision repair (transcription coupld nucleotide excision repair and global nucleotide excision repair) IF not repaired: SNP (single nucleotide polymorphisms)

Oxidation is

loss of electrons (OIL RIG)

Incorporation of dideoxynucleotides (ddNTP) into DNA results in the

loss of the 3' OH and the immediate termination of polymerization ex. Antiviral drug Acyclovir is a ddGTP- used for herpes and Acyclovir in conjunction with ACT- treats HIV ** AZT inhibits the reverse transcriptase modification

90/60

low blood pressure

increased km means

lower affinity

Pyruvate is a major

nexus in metabolism. There are several other sig metabolites with multiple possible fates that also serve as metabolic nexus points- some other important ones are Acetyl-CoA and Glucose-6-phosphate

Metabolism of proteins and amino acids MUST include metabolic pathways for excreting

nitrogenous compounds

if a microdeletion is 3 nucleotides long there will be

no frameshift but there will be one full codon lost * the one codon loss will result in a sequence that is shorter by one AA

the endomembrane system is a series of compartments that work together to

package, label, and ship proteins and molecules

talking with people at cocktail party is like

paracrine signaling

kinetochore

parts of the chromosomes that serve as attachment sites for microtubules

the large subunit of ribosome catalyzes the

peptide bond formation by activation of peptidyl transferase

Proteins are coupled via ___ bonds

peptide bonds! and peptide bonds are amide bonds (bonds between a carboxylate group and an amine) * proteins are liner polymers of AA- the principla seq is from the 20 cardinal AA

the small ribosomal subunit contains the

peptidyl-tRNA binding (P) site that binds the tRNA molecule - it all holds the incoming tRNA and AA - the small subunit also initiates protein synthese

Macromolecules have emergent properties as a result of their folding and gross structure that allow them to

perform unique functions, such as enzymatic activity

Some detoxification occurs in the ____ of hepatocytes

peroxisomes

catalase is found only in

peroxisomes

the compound phenol is broken down in

peroxisomes

How much energy does glycolysis produce? Does it require oxygen?

produces 2 ATP/glucose + 2 NADH and by itself does NOT require oxygen (if operating anaerobically, the energy yield is 2 ATP; the NADH is NOT used to make ATP

Which AA is found in break/kinds in alph helices

proline (pro, p)

which AAs are found in collagen

proline (pro,p) glycine, (gly,g)

mutational inactivation of PTEN causes

prolonged phosphorylation of PIP2 to PIP3, and activation of the anti-apoptotic pathway

disassembly of the nuclear envelope occurs in

prometaphase of mitosis

the ___ is NEVER found in an exon

promoter sequence ** in contrast introns are in between the exon sequences. However alternate splicing leaves these in place in some isoforms and leaves only a portion in place in other isoforms

a mitogen

promotes cell division

DNA duplex formation requires

proper matching of hydrogen bonds- mismatching will leave H-bonds unsatisfied or with water, and cause a kink in the DNA structure it is also driven by stacking interactions between bases and the hydrophobic effect (exclusion of water) between the bases

The nuclear envelope breaks down and chromatin is condensed into distinct chromosomes in

prophase

the breakdown of the nucleolus occurs in

prophase of mitosis

Proteins are degraded by

proteases and by the proteasome (targeted degradatin)

What is one problem that can occur duing protein folding

protein aggregation - an unfolded protein chan will fold to bury its hydrophobic AA away from water BUTTTT - there are many newly synthesized unfolded proteins in cytosol or ER lumen with exposed hydrophobic domains and is LEFT ALONE these hydrophobic domains on diff proteins will just as easily bind other hydrophobic domains of other unfolded proteins (and permanently aggregate) as they will fold * chaperons prevent this process

Glucagon activates

protein kinase A

phosphorylation of PKA can be reversed by

protein phosphatases

____ within the cell is the balance between protein synthesis and protein degradation

protein turnover

Amino acids constitue

proteins and they can be - non-polar - polar - charged (acidic or basic) - small - cyclic - or have sulfurs

one type of proteins that are translated on the rough ER rather than on free ribosomes are

proteins that need to be secreted out of the cell (also integral membrane proteins of the plasma membrane ) - this is why rER --> golgi --> plasma membrane is called the secretory pathway

Adenine and guanine are

purines (two rings)

Fatty acid synthesis

purpose is to synthesize fat from excess nutrients for storage in adipose tissue. It uses NADPH from the hexose monophosphate shunt

urea cycle

purpose is to synthesize urea for disposal of excess nitrogen

Cytosine, thymine, and uracil are

pyrimidins (one ring)

___ ends glycolysis

pyruvate

Describe the process of gluconeogenesis:

pyruvate is considered the start point (it CANNOT be directly reversed to phosphoenolpyruvate and so it goes through 2 other reactions which are: - conversion to oxaloacetate - conversion of oxaloacetate to phosphoenolpyruvate *** the intermediate oxaloacetate is a TCA cycle intermediate and allows TCA cycle to feed into gluconeogenesis --- from phosphoenolpyruvate, glycolysis is reversed until Fructose 1,6 bisphosphate - where a separate enzyme is required to convert it to Fructose-6-phosphate - the reversal results in glucose-6-phosphate. Another gluconeogenic enzyme, glucose phosphatase, is required to convert G6-phosphate to glucose

From fructose 1,6-bisphosphate to PEP, glycolytic reactions are reversible up until

pyruvate kinase

Fructose 1,6-bisphosphate stimulates/activates

pyruvate kinase

What enzyme converts phosphoenolpyruvate (PEP) to pyruvate

pyruvate kinase (PK) - this is the last step (Step 10) of glycolysis, it is biologically irreversible (exergonic) and it is a regulated step - pyruvate kinase is regulated through feed-forward and hormonal mechanisms - it is an energy producing step (makes 2 ATP) and a regulated step, both by hormone and local metabolites *** PEP is a major intermediate of gluconeogenesis

Disulphide bond formation, protein folding, GPI (glycophosphatidylinositol) anchoring addition to membrane protiens, and cleavage of the ER signal equence are all done in the

rER

the sER grows out of the

rER

Insulin could be found in the

rER - bc it is secreted out of the cell- therefore it would possess an ER signal and be translated by ribosomes bound to the ER

the 1st part of the endomembrane system includes the

rER (includes nuclear envelope) and sER (smooth because doesnt have bound ribosomes)

secretory pathway goes from

rER --> transport vesicle --> golgi apparatus --> secretory vesicle --> fuse with plasma membrane

What does the DNA in the nucleolus encode

rRNA

Galactokinase Deficiency

rare AR deficiency in galactokinase Abnormalities: - elevated galactose in blood and urine - elevated galactitol (a metabolite of galactose) * this is treated with dietary restriction

In someone who is affected by an autosomal recessive disease their parents are

rarely affected - parents are expected to be hetereozygotes ** likelihood of autosomal recessive increases if parents are related

Delta G = 0

reaction is at equilibrium and NO change in reactant or product concentrations will occur

Delta G > zero

reaction will go backwards as written - the reactions had lower initial energy than the products (endergonic reaction) *** requires energy put in from the environment

Belmont report

ethical foundation for research regulations regarding: autonomy, beneficence, and justice

Nuclear receptors alter

gene transcription (typically by recruitment of other transcription factors) - for each receptor there are Hormone Response Elements (HRE) that are specific for that hormone - thus a hormone can activate or repress a large set of genes that contain the appropriate response element. The response elements themselves can also vary somewhat between genes and still bind the same receptors, and thus provide diff levels of response for diff genes

Insulin

generally dephosphorylates (activated pyruvate kinase)

mutations in the telomerase, shelterin proteins or the telomerase RNA

generally results in altered aging

During the fasting state, what two processes take place

glycogenolysis (break down of glycogen) and gluconeogenesis (forming new glucose)

Ex of G protein coupled receptor signaling

glycogenolysis initiated by epinephrine action in the muscle or by glucagon in the liver

a ganglioside is aka

glycolipid

blood type antigens are an example of a

glycolipid ( does immune recognition) -- sugar trees help in identifying blood antigens carbohydrate trees attached to lipids or to proteins (ex. blood antigens) can be: - n-linked (protein Asn) - o-linked (protein Ser) - ceramide linked

transformation of glucose to pyruvate; generates small amount of energy quickly

glycolysis

In the FED state, in the presence of insulin, what is the major energy pathway in most cells:

glycolysis - insulin signals the body to use incoming glucose as the main energy source

What type of proteins are induce by hypoxia?

glycolytic proteins - can make ATP for you and generate ATP when you need it

Glycoprotein ex:

glycose-aminoglycans

carbohydrates use

glycosidic (ether) bonds

A mutation in a gene encoding a transcription factor or other regulatory protein can

go either recessive or dominant

O-linked glycosylation occurs in the

golgi

Structural proteins have a

half-life months- years (these are very long lived) Ex. many times secreted proteins of tissues (like collagen)

Long-lived proteins have

half-life of days to weeks * this is the majority of proteins in the cell

Short-lived proteins have a

half-life of minutes to hours ex. many regulatory proteins (like transcription factors) and misfolded proteins

A mutation that leads to loss of function, 1/2 amount of product-not enough

haploinsufficiency (a structural mutation, loss of function) - leads to dominant inheritance ex. one copy of a diseased gene is not producing the protein and the other copy is NOT able to prevent the disease even though it is normal

boundary violation

harmful, or potentially harmful to the patient

boundary crossing

harmless, non-exploitative possibly even supportive

protein synthesis or translation on free ribosomes the

ribosomes translate mRNAs into polypeptide chains (in cytosol) - tRNA brings AA to the ribosome , the amino terminus is leading with MET codon - this process takes about a minute for protein to be translated

both cholesterol and phospholipids are synthesized in the

sER

Receptor binding follows a

saturation curve (amount of binding increases with increase hormone concentration then it saturates because it uses up the active sites)

Ligases

seal the 3' end of a DNA fragment to the 5' end of the next fragment

implementing standardized suicide screening instruments and way sto recognize early detection for pts at risk of suicide is what level of prevention

secondary

the endomembrane system forms the

secretory and endocytic pathways

lysosomes are part of the

secretory pathway and received proteins translated in the rER - all proteins translated in rER receive N-linked glycosylation in ER -- all these proteins then go to the golgi and it is here from the transgolgi that some vesicles travel to the lysosomes

Thymine and uracil differ only by a

single methyl group (thymine is the one with the methyl)

DNA binding proteins can induce

sliding or nucleosome rearrangments. this is often seen in regulatory regions of DNA

RTKs activate

small G protein Ras (works as oncogene - prolonged mitogenic effects)

Ras, Ran, and Arf are all

small G-proteins involved in other responses

Ras is a

small g-protein, as distinct from the trimeric g proteins it is activated by growth factor receptors - small g-proteins require GEF proteins for activation and GTP/GDP exchange and req GAPs for GTP hydroolisis and termination of action (Ras is active with GTP, inactive with GDP - when Ras can no longer hydrolyze its bound GTP, it is locked in active state forever - cancer) --- Ras starts a protein kinase cascade that leads to activation of the mitogen-activated protein kinases (MAP kinases). Raf is the first protein kinase in this cascase, the on that is directly activated by Ras-GTP

Electrolytes are

small ions, typically present in high concentration (mM-M)

Uncouplers are

small weak acids that a hydrophobic in both their protonated and unprotonates states (can cross membranes and ferry protons across) - uncoupling proteins can carry out a similar, regulated fx (leak protons, make heat in brown fat- activated by faaty acids released in response to hormone) - BOTh carry protons down their electrochemical gradient, acting as proton transporers - this results in loss of the electrochemical gradient, less ATP produced, and the energy is turned into heat

Thousands of compounds are metabolized/broken down in the smooth ER (in many tissues by it is concentrated in the liver. MOST drugs ingested into the human body are broken down in the

smooth ER (using cytochrome p450- CYPs)

suicide more prevelant in western states bc

substance abuse seasonal depression native american population: higher rates of suicide/alcoholism greater access to weapons

The compostion of the genome can

tell you if you are closely related to somone else

At the ends of DNA many kilobases of repeated sequence is called a

telomere

Chromosomes decondense and the nuclear enevelope forms in

telophase

the hydrolysis of GTP to GDP in G protein mediated signaling cascade

terminated the signal and Galpha-GDP rebinds beta/gamma

What accounts for the "redundancy" in codons

the 3' or third nucleotide is called the "wobble" base because in many blocks it encodes the same AA regardless of the nucleotide used * several codons encode the same AA

In a metaphase chromosome

the DNA is inactive due to being tightly condensed first into a chromosome then into chromatin

Glycolysis makes pyruvate which can feed into

the TCA cycle for energy production

empathy is

the ability to understand the feelings of others

incomplete penetrance is

the absence of disease in some people carrying the disease geneotype

Describe reducing sugars

the aldehyde or keto group in the linear form= a reducing group - this occurs on the 1 position of mannose, glucose, and galactose and on the 2 position of fructose - when any of these positions are used in a glycosidic bon, they are no longer reducing ( a reducing test can be used to quickly test for sugar in the urine, but is subject to interference by other reducing substances)

Chargaffs rules

the amount of A and T are equal in DNA and the amount of G and C is equal in DNA (helped to denote double helical structure) - this is not true in RNA which will form base pairs and many parts will be single stranded or in loops (so bp ratios are good way of distinguising RNA from DNA and singl stranded from double stranded

Day 6 post-fertilization

the blastocyst is still not implanted in the endometrium

Justice

the idea that burdens and benefits of new or experimental treatments must be distributed equally among all groups in society - requires that procedures uphold the spirit of existing laws and are fair to all individuals involved

Inner membrane of mitochondria vs outer membrane

the inner membrane is tightly sealed to most ions and molecules in contrast, the outer membrane is relatively permeable to small ions and molecules BUT NOT TO PROTEINS. there are specific proteins trapped in the intermembrane space that are critical for mitochondrial function (ex. cytochrome C) ** transport across the inner membrane requires specific mechanisms (substrates like O2 will diffuse in but bigger things like pyruvate and fatty acids need transporters)

Electron transport chain (oxidative phosphorylation- include ATP synthase and transporters) takes place on

the inner membrane of the mitochondria

Metabolism=

the interconversion of food, storage molecules and energy through highly regulated chemical reactions that adapt to changes in food supply and energy demands

Explain splicing

the intron is excised and the 5' end of intron is attached to an adenine near the 3' end of the intron. This forms a loop of the intron comprising more than 2/3 of the intron - the 3' end of the intron is excised at the same time as the two exons are ligated together

During phospholipid biosynthesis in the smooth ER all phospholipids are initially inserted into

the leaflet of the bilayer of the sER membrane that faces the CYTOPLASM

transcription is completed in the nucleus, and once it ceases

the mRNA is exported to the cytoplasm where it is translated by the ribosome into an AA sequence producing a protein

ATP is

the main energy currency in the cell

Cards (mainly glucose), fats, and proteins are

the main energy that we get from food

What feature of tRNA prevents its further degradation

the majority of the tRNA is base paired

Nucleosomes "breathe" in their binding of DNA allowing a few milliseconds each second for

the nucleosomes to slide or rearrange on the DNA

Fitness

the number of offspring that reach reproductive age divided by the average number for the population - in dominant disease: redcuded fitness --> expect lowered incidence in the next generation - we observe constant incidence: so we conclude that the bad alleles we are losing from unfitness are being replaced with new mutations

If asked which structure is the chain terminator what should you look for

the one without a 3'OH

who is the one always responsible for maintaining the relationship boundaries

the physician

suicide treatment/prevention is multifactorial it includes

the physicians role and associated health care teams

Macromolecules (in the case of nucleotides, carbs, and proteins) are derived by

the polymerization of small components

Negative predicitve value

the probability that a person with a negative test result is a true negative (does not have the condition being tested for) TN/ ALL N

CoQH2

the reduced form of the electron carrier coenzyme Q (it is ubiquinol) ** gets the hydrogens from FADH2 - CoQH2 carries 2 electrons. these electrons can be fed into the ETC

During cytokinesis

the separation of two daughter cells occurs

Enzyme coupled receptors

the signal molecule is in the form of a dimer the ligands bind and it dimerizes into monomeric form of enzyme this is what results in enzymatic activity of the cell

Delta G is

the standard state free energy of a reaction (it is the overall free energy of the reaction and includes the effects of concentration) * this value reflects the actual concentrations - it reflects the energy obtained by having the reaction proceed at 1M concentrations of all reactants and products

Embryology is defined as

the study of development "in utero" between the point of fertilization of the female egg (oocyte) by the male spermatozoon (single sperm) and the time of birth

the half-life of a protein is defined as

the time it takes for the concentration of the radiolabeled target protein to be reduced by 50% relative to the level at the beginning of the chase

What is the name of the channel that pushes the ER protein through

the translocon

During folding of embryo which disc is it that forms

the trilaminar disc

In dominant disorders the parents are

usually affected - if nonaffected parents, affected offspring- a mutation would generally ONLY hit one offspring, not two

compartment volumes from dye concentration formula

v= M - (M excreted)/ c

What AA are found in the interior of the protein

valine (val, v) leucine (leu, L) isoleucine (ile, I)

intercalation

remedy: - global or transcription coupled nucleotide excision repair remove surround region of one of the strands of DNA If not repaired: distorts DNA structure: may cause nucleosomes rearrangements, mutagenesis if it persists through replication

for x-linked dominant

all female offspring of an affected father should be affected

both ___ and ___ majore storage site are the muscle and the liver

glycogen and protein

For basic residues

pH < pka = +1 pH > pk= 0

For acidic residues

pH < pka = 0 pH > pk= -1

what sugar does RNA use

ribose, deoxyribose for DNA

For protein synthesis translation occurs on

ribosomes

all proteins are translated on

ribosomes

1/3 of all diseases can be correlated to

splicing errors

Availabilty of ATP, CTP, GTP, and UTP can regulate

transcription

Splicing occurs simultaneously with

transcription

snRNA

- participate in RNA splicing - used in ribonulceoproteins like splicesomes and telomerase

All transcripts made will have:

5' UTR (untranslated region) 3' UTR coding region (may have introns)

Describe the Hexokinase step (step 1) in glycolysis

(Exergonic, -Delta G, Regulated, strongly favorable step) it is a phosphorylation step that uses ATP- this phosphorylation TRAPS glucose, commiting it into the cell - it traps it because there are NO transported for glucose-6-phosphate (G6P) **** this can only be reversed in gluconeogenic tissues such as the liver and kidney that have the enzyme glucose-6-phosphatase, which catalyzes the conversion of G6P--> glucose + Pi [buttt most tissues dont have glucose-6-phosphatase and must utilize the G6P (ex glycogen storage ot glycolysis)

List NON-radical Oxidants

(O3), Ozone (1O2), Singlet oxygen (HOCl-), hypochlorous acid (ONOO-), peroxynitrite

List free radical oxidants

(RO2.) , Peroxyl (RO.) , Alkoxyl (HO2.), Hydroperoxyl (NO.) , Nitric oxide

RBCs role in metabolism

(aka erythrocytes) are specialized for oxygen delivery. They have NOO mitochondria.. so they dont do oxidative metabolism and rely exclusivley on ANAEROBIC METABOLISM (glycolysis) for energy - RBC requires glucose all the time

Diabetes

(excess glucose in the urine) this is a metabolic disease, a disorder of glucose regulation, a dysfunction of insulin signaling (insulin controls carb metabolism day to day) - this req long term treatment - type II is prevelant bs of rising levels of obesity sx: freq urination, fasting glucose above normal which is 100mg/dL

G-protein coupled receptors

(signal binds to GPCRS- activates enzyme and activates G protein)

Describe Pyruvate kinase deficiency in erythrocytes

* remember RBCs rely on anaerobic glycolysis for ATP synthesis (glucose --> lactate) this deficiency causes - hemolytic anemia (cell rupture leads to this) - abnormal RBC shape - enlarged spleen - elevated bilirubin - low O2 affinity of hemoglobin ** partial deficieny of any glycolytic enzyme reduces ATP synthesis. Low ATP makes it difficult to maintain ion gradients, causing osmotic fragility. These pts have residual enzyme activty of 5-25% ** note enzymatic deficiences in glycolysis are usually rare bc this pathway is sooo critical, deficiencies are usually lethal. this however is just one example of a congenital deficiency in specific isozyme of metabolism

Describe the phosphofructokinase I step (step 3) in glycolysis

** KEY REGULATORY POINT, COMMITTED STEP - "slowest step, rate limiting, most regulated- exergonic (irreversible under typical intracellular conditions) PFK or PFK1 - uses ATP (kinase) and phosphorylates the 1-position of fructose-6-phosphate. This is the second preparative step for conversion to 3-carbon sugars (it prepares for cleavage) - once this step is done, the chemistry of progressing through PEP and to pyruvate will proceed *** PFK (aka PFK I) is highly regulated by BOTH local metabolites and by hormone control

The effect of CoQ recycling is that

- 2 CoQH2 are used - 4 protons are pumped from matrix to intermembrane space - 2 cytochrome cs are reduce (carry electrons) - 1 CoQH2 is generate --- in general only 1 CoQH2 condumsed, 4 protons pumped, 2 electrons transferred from CoQH2 to 2 cytochrome c

Ex of Uncouplers

- 2,4 Dinitrophenol - FCCP, CCCP, and many other - Acetylsalicylate (aspirin) in high concentrations (causes aspirin toxicity) - all the uncouplers work by rapidly carrying protons across the inner mitochondrial membran e

Compositon of genome:

- 27% is transcribed into mRNAs that will mature and be translated into proteins - 26% of genomes is intrones - 1.5% is used to encode proteins -20% of genomes= long interspersed elements (LINE: named L#, L1 is the most abundant it makes up 13% of the genome - this is a vestige of a virus that is kept quiet by Alu -13% of the genome is short interspersed elements (SINE)- these have varied name, Alu is the most abundant making up 7% of the genome (this prevents other genes from jumping around- it stops viral rep/infections and encodes RNA responsible for protein maturation) - 11% are transposons (movable "jumping" genes) - 8% are heterochromatin (centromeres, telomeres, etc)

What are some ways the tRNA control activity

- 3' end is modified by adding CCA or CCG to make it a recognizable substrate for tRNA synthases - 3' end are protected by the addition of an amino acid to the 3' OH (tRNA synthase action) - 5' end protected by base pairing ** tRNA binds into pocket via hydrogen bonding of the synthase with the tRNAs anticodon loop used for base pairing with the transcript - this ensures the AA adds to only the correct RNA (tRNA synthases use ATP to charge the tRNAs)

Mature mRNAs have

- 5' cap (guanosine triphosphate, added such that triphophate links the 5' position of the ribose of both the capping guanosine and the first nucleoside of the transcript) - NO introns (any intron left will become an exon by inclusion in mature mRNA) **** introns are noncoding- they are cutt out by splicesomes -could be done before completion of transcript (you always have one less intron than exon) - Leader sequence (5' UTR)- this is recognized by binding proteins that participate in assembly of RNA into the ribonucleoprotein - Tail sequence (3' UTR): long because there is no exact point of termination of transcription in eukaryotes - polyadenylation of tail sequence: occurs after release of transcript and endonuclease trimming **** for messenger RNA, the RNA is immediately modified as the RNA region is released from the D-loop

Pyruvate can go to

- Acetyl CoA via PDH (for energy or fat synthesis) - lactate in muscle during anaerobic exercise or in erythrocytes - Oxaloacetate for gluconeogeneis (in liver or kidney) to maintain circulating glucose, or anaplerotic reaction- refilling the TCA cycle - acetaldehyde and subsequently ethanol or acetate, typically in microorganisms during anaerobic metabolism

What are the germ layers that provide derivatives

- surface ectoderm - neuroectoderm - neural crest - endoderm - mesoderm

What are the 3 principal ways in which regulation of metabolism can occur:

- Allosteric: local metabolite regulation (non-competitive): "Feedback and feedforward mechanisms" - Phosphorylation and dephosphorylation (covalent modification- other types of this can also occur) - Changes in enzyme levels (can be increased, decreased, or sequestered in endomsomes)

What are the diff DNA polymerases and what do the do

- Alpha: is the primase in eukaryotes - Delta: synthesizes lagging strand - Epsilon: synthesizes leading strand - Beta: involved with DNA repair - Gamma: is the mitochondrial DNA polymerase

What are two things of clinical imporatance that can affect ribosomes

- Antibiotics and - Ricin: which removes and Adenine base from the elongation factor binding site preventing elongation

The ATP/ADP antiporter in oxidative phosphorylation is inhibited by

- Atractyloside - Bongrekate * both prevent the exchange of ADP for ATP. Thus there will be NO substrate for the ATPase and no way for ATP to leave the mitochondrion, backing up the proton gradient and Electron transport

Inhibitors of Cytochrome C Oxidase (Complex IV)

- Azide: a small heme-binding molecule. Used experimentally as a bacteriostat (stops ATP) - CO: binds heme tightly. Typically CO reacts first with heme in blood, displacing O2 and requires larger dose. While it does inhibit cytochrome oxidase, it is the loss of oxygen carrying capacity that causes initial symptoms - Cyanide: a poison used for suicide and found naturally in some nuts and fruit. Hydrogent cyanide (HCN) is highly diffusible and distributes reapidly thoughout the body. this is why it is popular in suicide pills *** treatment : CN- binds tightly to Fe3+ on the hemes in cytochrome oxidase but not Fe2+ containing hemes - so one tx is to provide an oxidizer such as amyl nitrite or sodium nitrite to create met-hb by oxidizing the hb heme from Fe2+ to Fe3+ . CN- binds tightly to the methemoglobin, and is prevented from binding to cytochrome oxidase sx of cyanide poisioning: - lactic acidosis, hyperventilation, rapid LOC * Konzo is a disorder from eating Cassava roots- contain something that makes cyanide when crushed. if not processed presents as spastic paresis that can lead to musculoskeletal deformities

DNA structures

- B form (canonical right-handed helix form- most common, used by watson and crick) - A form - Z- form (left handed, rare)

Pro-apoptotic regulators (still part of Bcl-2 family or proteins)

- Bax - Bak - BOK - BIM - BID - BAD - NOXA - PUMA ** form channel in outer mitochondrial membrane, releases cyt C + AIP (apoptosis inducing factor) from mitochondrial intermembrane space --activated caspases from the "apoptosome"--this is cytC +proteins in cytoplasm--**** DOESNT do this when bound to anti-apoptotic--- no channel will form

Anti-apoptotic regulators

- Bcl-2 - Bcl-XL - Bcl-W - MCL-1 - Bcl-B *** presence of growth factors increase amt of anti-apoptotic BCL proteins within the cell preventing apoptosis, some tumor cells can also upregulate expression of anti-apoptotic BCL2 proteins- allows the tumor to grow without enough growth factor required by normal cells

Receptors for epinephrine and norepinephrine vary:

- Beta adrenergic: beta 1, 2, 3: generally act of Gs which activates adenylyl cyclase and activates ca2+ channels - Alpha adrenergic: alpha 1 and alpha 2 can go either way to Gi: inhibits adenylyl cyclase OR to Gq with activates phospholipase c-beta with increase intracellular calcium

Majore metabolic pathways for fatty acid degradation

- Beta-oxidation: breakdown of fatty acids to Acetyl CoA; this takes place in mitochondria. It makes energy (ATP) from fat stores - TCA cycle: breakdown of Acetyl (acetyl coA) to CO2 with production of reducing equivalents (NADH and CoQH2) In mitochondria - Oxidative phosphorylation: electron transport. Converts high energy electrons (reducing power) to ATP and makes water from oxygen

In a typical 70kg man what amount of fat, protein , and glycogen will he have

- Fat: 15 kg= 135,000kcal - Protein: 6kg= 24,000kcal - Glycogen: 0.2kg= 800kcal

To work, what products and waste need to be exported and cofactors be recycled

- CO2 - ATP (gets out via ATP/ADP antiporter) - NADH to NAD+

when a stop codon is reached what do you writed at the end of your protein sequence

- COOH

Terminolocy in embryology

- Cranial (Head) - Caudal (feet/tail) - Ventral (front) - Dorsal (back) ex. - Anterior chest wall is ventral to spine - A upper limb is cranial to a lower - The spine is dorsal to the anterior chest wall

The 2' position of the sugar is a __ for DNA and __ in RNA

- DNA= hydrogen - Hydroxyl= in RNA

Nonmaleficence

- First do no harm/ needless harm - refrain from providing ineffective treatments or acting with malice toward patients

What are poitns of regulation of replication

- G1 checkpoint - loss of CDC6 to form initiaton complex - availability of ATP, dATP, dCTP, dGTP, and dTTP

The endoderm forms the epithelial lining of

- GI tract: foregut, midgut, hindgut - Low RS: larynx, trachea, bronchi, lungs - Genitourinary system: urinary bladder, urethra, and lower vagina - Pharyngeal pouches: auditory tube and middle ear, palatine tonsils, parathyroid glands, thymus

Describe hormonal regulation of pyruvate kinase in the liver

- Glucagon BLOCKS the actions of pyruvate kinase, turning glycolysis off (pyruvate will be phosphorylated and inactive) - Insulin can reverse this by dephosphorylation

For carbohydrate metabolism in the FED state which processes occur

- Glycolysis: the transformation of glucose to pyruvate; generates small amount of energy quickly - Glycogenesis: synthesis of glycogen from excess glucose and galactose (stores glucose for use during fasting)

What makes RNA double helices different from DNA double helices

- Helix is most often a A-form helic - helical regions typically form as short helixes of 5-100 bp length - in most RNAs the helixes are intramolecular (the RNA forms a helix with itslef) -loops and bulges often occur between helical regions - folding is required for proper maturation

What are long term responses to hypoxia:

- Hypoxia activated Hypoxia-inducible factor (HIF). This transcription factor drives the expression of genes for glycolysis, angiogenesis, iron absorption in intestine, erythropoietin synthesis in kidney (this is actually active in tumors- it aids in generating vasculature)

How can AA be classified

- Ketogenic: those that feed only into Acetyl CoA - Glucogenic: those that feed into pyruvate or can replenish TCA cycle intermediates. Glucogenic AA can be gluconeogenesis precursors - ketogenic and glucogenic: those whose breakdown results in both Acetyl CoA and TCA cycle intermediates

Different organs have diff metabolic fx that are designed to complement and supplemnet each other- which organs are involved in metabolism

- Liver - Muscle - Adipose - Kidney - Intestine - RBCs - Brain

pkas of side chains of - Lys - Arg - HIs - Cys - Tyr - Asp - Glu

- Lys : 10.5 - Arg: 12.5 - His: 6.0 - Cys: 8.3 - Tyr: 10 - Asp: 3.9 - Glu: 4.3

The role of the brain in metabolism

- MAJOR fuel is glucose, and it metabolizes little fat - During starvation or a long fast, the brain can adapt to using ketone bodies for fuel

What is the role of muscle in metabolism?

- MAJOR storage site for protein and glycogen - provides movement - muscle lacks glucose-6-phosphatase and cannot make glucose for other organs - bc of its glycogen stores muscle can function anaerobically for a short time

Mesoderm derivatives

- Muscle Musculoskeletal - smooth, cardiac, skeletal muscle - connective tissue - Bon and cartilage ALL serous membranes Cardiovascular - blood, lymph, cardiovascular organs - spleen Adrenal cortex Genitourinary -Kidneys and ureters -Gonads and genital tracts Dura mater

Glycolipids and glycoproteins involve various sugars like

- N-acetylglucosamine - fucose - mannose

The reducing equivalents from the TCA cycle...

- NADH - FADH - CoQH2 -----are alll made from the oxidation of Acetyl-CoA- these reducing equivalents feed into oxidative phosphorylation in the mitochondria and this makes the bulk of the ATP

the main reducing equivalent in biosynthetic reactions

- NADPH

How can oxygen become a free radical?

- O2 can pick up an electron and become a free-radical. This is a one-electronn transfer, it can happen when a single electron strays away from the ETC and attaches itself to an O2 molecules * single electrons are typically in free radical forms- can be of CoQ or other redox intermediates - most likely sources are complexes I (NADH-Q reductase), II (succinate dehydrogenase) and III (QH2-c reductase) - other sources of stray electrons incluse many flavoprotein enzymes and exposure to ionizing radiation * Free radical formation can happen as a result of specific enzymes and reactions: NADPH oxidase or xanthine oxidase

Which transporters are involved in the movement of substrates and products of oxidative phosphorylation into and out of the mitochondria?

- Pyruvate antiporter (pyruvate in, OH- out) - Phosphate Antiporter (phosphate in, OH- out) - ATP/ADP antiporter (exchanges ATP for ADP, ADP in, ATP out) - Glutamate/Aspartate antiporter (glutamate in, aspartate out ) - Malate/ alpha-ketogluterate antiporter (malate in, alpha-ketoglutarate out) ****** One that work together to make shuttle systems: - The malate/aspartate shuttle - The Glycerol-3-phosphate shuttle

what type of DNA causes problems in gene expression and creates diversity

- Repititve DNA (hot spots for chromosomal breakage) - Transposable DNA: can cause insertions or deletions in coding seq when they move - Recombination between repeats can result in extra gene or loss of regions of DNA - Pseudogens: genes due to duplication or reinserted mRNA that is then mutated to nonfunctional form (could be cause interruption of regulation, insertion of a repressor, loss of processing signal sequences)

Inhibitors of Complex I (NADH Dehydrogenase)

- Rotenone ( a once commonly used rate poison) - Amytal

What is the role of the Liver in metabolism

- Stores glycogen (puts glucose out into circulation), protein and fat - maintains blood levels of glucose during the fasted and stressed state - synthesizes fat from carbohydrate and AA during the fed state - MAJOR site of biosynthesis and processing between the intestines and other organs (the liver makes cholesterol) - also detoxifies

What are some enzymes that destroy free radicals and how do they do this

- Superoxide dismutae: turns more reactive superoxide into less reactive hydrogen peroxide. This enzyme is ubiquitous.. it is a manganese-containing enzyme in the mitochondria and a copper-zinc containing enzyme in the cytoplasem (2 O2.- + 2H+ --> O2 + H2O2) - Catalase: destroys hydrogen peroxide. This heme-containing enzyme is widespread in cells and body fluids, but most concentrated in peroxisomes (2 H2O2 --> O2 + 2 H2O) - Glutathione peroxidase: destroys hydrogen peroxide, it is present in the cytoplasm and mitochondria

What are the 3 fates of Acetyl-CoA (AcCoA)?

- TCA cycle entry - FA synthesis - ketone body production

Fates of Acetyl CoA (AcCoA):

- TCA cycle entry for energy production - FA synthesis, for energy storage (anabolic) - Ketone body productiong, during starvation

What are the cofactors present in the pyruvate dehydrogenase reaction

- TPP - thiamine pyrophosphate - lipoic acid - CoA - FAD/ FADH2 - NAD+/ NADH

Some hormone induce cell response mediated by cAMP:

- TSH (thyroid hormone synthesis and secretion) - Luteinizing hormone (LH) - profesterone secretion - Adrenaline- glycogen breakdown - Parathormone - bone resorption

Type I and Type II nuclear receptor hormone action:

- Type I : hormone goes through plasma membrane binds to NR/HSP complex these two dissociate then the NR form a homodimer which passes through the nulcear pore and then travels to bind on the nuclear DNA which in bound to the HRE or hormone response elements - Type II: the hormone is already in cytoplasm just has to pass through the nuclear pore and then it binds to an already bound heterodimer made of thyroid and retinoic acid

Role of Vitamin E in terms of free radicals

- Vitamin E is a fat-soluble vitamin whose principal role is as an antioxidant. it can act to break free-radical chain propagation. It is a free-radical scavenger

give ex. of a perioxisome biogenesis disorder (PBD)

- Zellweger spectrum disorders ( results from a fauiluer in peroxisome formation giving rise to metabolic abnomalities - impaired neuronal migration, neuronal posiitoning, brain development - pts show postedevelopmental sensorineuronal degeneration that leads to progressive loss of hearing and vision - LACK OF MYELIN - has abnormal plasmalogens and increase VLCFA

What could explain a child getting 6 copies of a gene while the mother only had 2

- a gene duplication event due to repetitive DNA

Two examples of things that can slow respiration

- a low NAD/NADH ratio will slow respiration (availability of reducing agent) - a steep proton gradient will slow electron transfer and respiration

Autonomy

- ability of person to make their own decisions Autonomous individuals act intentionall, with understanding, and without controlling influences (not simply allowing patients to make their own decisions)

Protein metabolites come from

- absorption (fed state) - muscle breakdown (fasted) and they are used for - protein synthesis (fed) - energy generation (fed and fasted) - gluconeogenesis (fasted/starving) *** in energy metabolism proteins can feed into -pyruvate - acetyl-coA - or directly into the TCA cycle

Beneficence

- action done for the benefit of others (to prevent or remove harm or simply improve the situation of others - can include protectings rights or others, rescuing a person in danger, and helping individuals with disabilities * especially for physicians it is important to weight the benefits against the possible risks of an action (includes not only the individual patient, but policies and practices for the community good)

GPCRs can induce responses other than elevating cAMP. Some ex:

- activatin cGMP phosphodiesterase (in vision) - inhibition of adenylate cyclase - activation of phospholipase C - activate potassium channels - inhibit calcium channels - regulate actin cytoskeleton

Glucose-6-Phosphate can be generated from

- glucose uptake - glycogen breakdown - galactose uptake - gluconeogenesis

What are some fat soluble dietary oxidants

- alpha-tocopherol (vitamin E) - retinoids - carotenoids (vitamin A) - ubiquinone (CoQ, reduced) **** diets high in antioxidants have been associated with health benefits but intervention studies have shown no consistent benefits when a single antioxidant is given in medium to high doses

groups with increased suicide risk

- american indians/alaska natives - active dute military and military veteranns - individuals in justice and child welfare settings - individuals who engage in non-suicidal self-injury - individuals who have attempted suicide - ppl with mental/or substance use disorders - medical conditions -older men - LGBT populations - men in midlife - individuals bereved by suicide

What are some water soluble dietary oxidants

- ascorbic acid (vitamin C): in addition to its role as a free-radical scavenger it is an important cofactor in a number of enzymes, including prolyl hydroxylase. That enzyme is key to post-translational modification of collagen. The sx of vitamin C deficiency are strongly related to collagen defects - uric acid - sulfhydryl compound - phytochemicals

Which AA are found on the exterior of a protein

- aspartate (asp, d) - glutamate (glu, e) - lysine (lys, k) - arginine (arg, r) - histidine (his, h)

Between what weeks would a babys bith be denoted as TERM

- between 37 and just less than 40 weeks from onset of LMP - Between 35 and just less than 38 week post fertilization (weeks of pregnancy) ----baby can be born up to 3 weeks early and still be TERM---

Whether a lipid forms vesicles, membranes, or micelles depends on the individual lipid structure and the bulk conditons. if this is so then can you describe shape thats needed to form bilayer? how about micelles?

- bilayer sheet (membranes form when the size of the headgroups and aliphateic hydrocardon chains are similar) - micelles form when the polar headgroup is relatively larger than the aliphatic hydrocarbon chains

functions of lipid rafts

- by clustering signaling molecules together in close proximity, they are thought of as "signaling platforms" - they also do cellular trafficking of membrane proteins - lipid rafts form caveolae

What things can regulate transcription maturation

- c-terminus of the RNA pol II phosphorylation state - splice site conanoical sequence motif and folding - tissue, cell cycle, metabolic state specific RNA binding proteins - mRNA editing

Exl of gene regulation through activation of adenylate cyclase

- cAMP/PKA mechanism has many potential phosphorylation targets- the pathway that regulates gene expression via phosphorylation of a specific transcripitonal regulator, CREB

What are two ways NADH can be used

- can be used for ATP synthesis in the mitochondrion - can be recycled to NAD+ by conversion of pyruvate to lactate during anaerobic metabolism

an activated PKA

- can phosphorylate a nuclear transcription factor (typically as a result of increased cAMP) - an activated PKA does phos of many substrates involved in metabolic control ex. - glycogen phos. kinase (which breaks down glycogen) - pyruvate kinase - phosphofructokinase2

Glucose-6-Phosphate can go to

- glucose, during gluconeogenesis - pyruvate via glycolysis, for energy - hexose monophosphate shunt to make NADPH or ribose or both - glycogen for glucose storage in liver and muscle - galactose synthesis, if needed, for lactose or glycoprotein and glycolipid synthesis

Inhibitition of bacterial replication and transciprtion are different than the drugs used to inhibit these process in EUkaroytes. Drugs can target waht parts of bacterial

- cell wall - DNA synthesis/ RNA synthesis - plasma membrane - ribosomes - metabolic pathway ** translation inhibition of bacteris is also drug targeted - these drugs have low cross reactivity to human cytoplasmic ribosomes BUT do have some cross reactivity to mitochondrial ribosomes

ex of cofactors

- coenzyme A - NAD and FAD

what kinds of chromosomal regions are NOT transcriptionally active

- constituitive heterochromatin is mostly around centromeres and near telomere (<6% of total DNA) - other repeat areas may also be in heterochromatin * heterochromatin is condensed even in interphase

Types of signaling: (based on how far the signal is going)

- contact dependent - paracrine (autocrine is the same as this but also acts on itself) - synaptic - endocrine

function of bile acids

- critical for digestion and absorption of fats and fat-soluble vitamins in the small intestine - many waste products, including bilirubin, are eliminated from the body by secretion into bile and elimination in feces

protective factors against suicide

- cultural/ religious beliefs/ fear of outcome - future orientation/goals - sense of responsibility to family - impulse control/emotional regulation

types of structural abnormalities in chromosomes

- deletion (del) - inversion (inv) - duplication (dup): a segment is present where it usually should be and in an additional position- presence of 2 copis of a region (sometimes) on same chromosome and it is still present on the other copy of the chromosome so three copies total - insertion (ins): a segment is moved- presence of an extra chromosome piece coming from somewhere else in the genome where it is no loner present, so 2 copies of the area in total - ring (r): any chromosome that looses the telomeres at both ends will become a ring, problem is instability in cell division (also mitosis) - translocation, reciprocal (t) - translocation, robertsonian (der) or (rob) - isochromosome (iso) - a chromosome with two identical arms (imagine the spindle apparatus attaching on top and bottom of centromere (instead of at sides and pulling centromere apart in wrong direction)- also seen in turner syndrom and monosomy x

Elements of informed consent in reasearch

- disclosure (inform of risk/benefit) - understanding (allow for asking questions) - voluntariness - competence (a designated surrogate may provide consent it it is in the participants best interest) - consent/assent (must authorize their participation)

Negative test result

- disease absent - within reference range - represent normal finding

Positive test result

- disease is present - outside reference range - represents abnormal value

Inherited mutations can either be

- dominant: if mutation is evident in heterozygotes - recessive: is some individuals with gene dont express the effect ** if mutation affects somatic cell- may result in cancer

ATP (1 GTP equivalent) is used to charge each tRNA

- eEF1 utilizes 1 GTP each time it loads a charged tRNA into the A site of ribosome - eEF2 utilizes 1 GTP each time it pushes the ribosome forward one codon (translation translocation

List the Nonpolar AA

- glycine - alanine - valine - leucine - isoleucine -phenylalanine - tryptophan - methionine - proline

Physicians have an obligation to create condition necessary for autonomous choices- how can they aid in this?

- educate pts so they understand situation - calm emotions and address fears that interfere with a patient ability to make decisions - counsel patient when their choices seem to be disruptive to health and well-being

Oxidative phosphorylation includes

- electron transport - proton gradient - ATP synthesis

Amino acids have specific catabolic pathways, what can they be used for

- energy (muslce and other tissues). this can occur in the fed state when excess protein is eaten. Excess means more than is required to build proteins - also used for glucose synthesis in the liver or kidney (gluconeogenesis) during fasting *** these catabolic pathways feed into one or more of the following: - pyruvate (glucogenic) - acetyl coA (ketogenic) - TCA cycle intermediates

Surface ectoderm (which is associated with amniotic cavity) what are its derivatives

- epidermis - hair, nails - inner ear, external ear - enamel of teeth - lens of eye - adenohypophysis (anterior pituitary: rathke pouch) - parotid gland - anal cnal below pectinate line - mammary gland

Type os intermediate filaments

- epithelia express keratins - CT, muscle cells and clial cells show vimentin and vimentin-related - Nerve cells have nuerofilaments - nuclear lamins

The kidneys role in metabolism is to

- excrete nitrogen (nitrogen metabolism--- MOST of the nitrogen we get is from eating protein; fat and carbs generally have nitrogen in them) - exretes urea - some protein storage

clathrin

- exists in both the assemble and unassembled form inside the cell - all the diff types of receptors that cluster in clathrin-coated pits can be found in the same pit - clathrin binds adaptins that bind the cytoplasmic tails of receptors, but does NOT bind the tails directly

Main metabolic pathways during the fasted state (main metabolic pathways for fatty acid degradation)

- fat catabolism - beta-oxidation - TCA cycle - oxidative phosphorylation

Which pathways are invovled in fed state anabolism

- fatty acid synthesis - hexose monosphosphate shunt (HMP or PPP) - glycogen storage

The particular response of an organ in metabolism depends on the metabolic demand (its role in metabolism and its energetic needs)

- fed - fasted - starved - exercised - stress (depends on a linked series of systemic and intracellular events) theese states will affect hormones which go through intracellular signal pathways to change cellular level response/regulation then targets organs

Which enzymes moves specific phospholipids from the extracellular leaflet of the bilayer to the CYTOPLASMIC leaflet (extracellular --> cytoplasmic)

- flippase (and this uses ATP)

Which enzyme moves specific phospholipids from the cytoplasmic leaflet to the EXTRACELLULAR leaflet (cytoplasmic --> extracellular)

- floppase (uses ATP)

Describe the introduction of fructose to glycolytic intermediates

- fructose can be converted to the glycolytic intermediate Fructose-6-phosphate by hexokinase- BUT hexokinase is usually saturated with glucose. So another mechanism is needed ..... Fructokinase converts fructose into fructose-1-phosphate (not a glycolytic intermediate).. Aldolase B will convert this to glyceraldehyde and DHAP- DHAP goes to glyceraldehyde-3-phosphate - glyceraldehyde gets converted to glyceraldehyde-3-phosphate by triose kinase - glycolysis proceeds as normal ** since fructose enters glycolysis lower down and is present typically only in the fed state - it is used for energy OR converted to fat (in the liver) - the conversion of fructose to fat is of concern in diets because of the recent prevalent use of high fructose syrups in processed foods

Ex of Glycolipids constituted of various sugars and modifies sugars:

- galactose - glucose - fucose - N- acetyl-glucosamine (GlcNac) - N-acetyl-galactosamine (GalNac) - N-acetyl-neuraminic acid (NANA)

Name the 6C sugars (hexoses)

- glucose - galactose - mannose - fructose (5 membered ring but has 6C)

glucagon promotes

- glucose delivery from the liver to the circulation - gluconeogenesis - glycogenolysis

What are the three irreversible steps of glycolysis

- hexokinase (adds phosphate to glucose to trap it into cell) - phosphofructokinase (COMMITTED STEP- stuck completing glycolysis) - pryuvate kinase (under normal conditions they are irreversible- need separate enzyme and ATP to reverse) - they are EXERGONIC: have a highly negative delta G

The basic AA are

- histidine - lysine - arginine

Professional ethics is not

- how you feel about a topic - the sincerity of your personal beliefs - religious or moral convictions or right and wrong - not the law

Example of Inhactivatiy K so that differentiation CAN occur

- human antigen R (HuR) is activated and translocated into the nucleus in response to hormonal signals that the cell should differentiat into a muscle cell - the same signal that activates HuR also activated p38 (a kinase that phosphorylates K- thereby inactivating it) - just like K, huR binds to AU-rich regions (ARE) - when mRNas lose K they are somewhat more stable, but the binding of HuR makes them EXTREMELY stable- allowing differentiation

cell signals can be

- hydrophilic - hydrophobic - external (foreign)

Describe what occurs in Asphyxiation

- hypoxia (can be caused by other events such as acute anemia, ischemia, along with asphyxiation) - low oxygen (CO poisoing- blocks Hb, ETF, and O2 usage) - lactic acidosis (glycolysis is activated by low ATP, the TCA cycle is inoperable (high NADH), AcCoA accumulates, PDH shut down; pyruvate is diverted to lactate. Lactate is sent into the circulation

if recessive, ask if males and females are equally affected

- if yes, autosomal - if no, x-linked (should have more affected males than females) --- if in doubt, look at how many independent bad alleles are necessary to explain the people that are affected by the disease: for x-recessive, 1 bad allele inheriter from grandmother through carrier females can lead to affected people occuring several places in a pedigree --- for autosomal recessive this would usually necessitate several independent bad alleles in the unrelated spouses (but not if pedigree shows conanguinity). Fewer bad alleles are usually more probable, so disease in two different generations is more likely for x-linked recessive than autosomal recessive

is one parent of the affected children affected?

- if yes, disease is dominent - if nom disease is recessive --- Caveat: new mutation or reduced penetrance can make this question less informative for a single nucleus family, answer for the overall pattern (extended family)

Glycolipids (part of carbs) serve in

- immune recognition - physical barrier

Nucleotide excision repair (NER)

- in all stages but M phase - removes things larger than a single base (fixes bulky lesions- adducts larger than a few atoms) * mutations in repair proteins for G-NER can cause Xeroderma Pigmentosa

ATP is the main energy storage in cellular energy- where does it keep its energy

- in its high-energy phosphate bonds (you break these to make energy) - AMP (one phosphate) - ADP (2 phosphates) - ATP (3 phosphates)

F26BP is regulated by hormonal regulaation such that

- insulin activated PFK1 in liver by increasing F26BP - glucagon inhibits PFK1 in liver by decreasing F26BP

How does fructose 2,6- bisphosphate (F26BP) hormonally regulate PFK1 in glycolysis

- insulin activates PFK1 in liver by increasing F26BP - glucagon inhibits PFK1 in liver by decreasing F26BP

what hormone status must there be for gluconeogenesis to occur

- insulin must be low - glucagon must be high - cortisol, epinephrine and norepinephrine may also be high ** During fasting, insulin drops and glucagon increases. Glucagon simulates glycogen breakdown to supply circulating glucose, and with extended fasting, will then also induce gluconeogenesis (the synthesis of glucose from precursors)

Types of transmembrane mechanisms

- ion-channel coupled receptors - G-protein coupled receptors - enzyme coupled receptors (tyrosine kinases) - intracellular receptors

GTP

- is burriend in the protein it DOES NOT actually signal anything by itself, it DOES NOT do phoshorylation either or stabilize alpha subunit in inactive form

If a pt came to you and shortly after comitted suicide there is a standard of care and allegations which are

- is there adequate identification and evaluation of risk and protective factors? - was a reasonable treatment plan developed based on the assessment of the patients clinical need? - was the treatment plan appropriately implemented and modified based on an ongoing assessment of the pt need? - is the clinician professionally currennt regarding the assessment and treatment of pt with suicidal behaviors - was documentaion in the pt recor adequate to support the appropriate care was provided in terms of the assessment, treatment, and ongoing monitoring of the pt?

What are the first steps in gastrulation

- it begins with a linear midline condensation of cells known which form the primitive streak * once this happens the cranio-caudal and R and L axis of the embryo are firmly established. If this goes wrong it is likely to be due to mutations in the genese involved in left/right symmetry (ex. lefty gene) --ex. dextrocardia

In Tay-sachs disease

- it is a lysosomal storage disease - in this disease hexosaminidase A is deficient, resulting in the buildup of GM2 ganglioside in lysosomes leading to mental retardation, blindness, and mortality - a treatment would involve reducing GM2 ganglioside levels by increasing hexosaminidase A activity

What diseases/ aspects of life are affected by oxidative stress

- it is associate with aging (bc damage to DNA, proteins, and other molecules may be irreversible) . Also in neurodegeneratic disorders such as alzheimers, ALS, parkinsons, and huntingtons - it is linked to artherosclerosis through the oxidation of LDL - reactive oxygen species are required for normal muscle function, but HIGH amounts are associated with muscle fatigue - reactive oxygen species also implicated in age-related cancers

You decide to panopto your lectures and skip breakfast in favor of going to the gym where you have an intense 3 hour workout. You then go to McDonalds and spend a relaxing hr enjoying a Big Mac. What is the main fate of glucose being taken up into your muscles at this point?

- it is used directly for energy by the muscles AND Is being stored by glycogen - While glucose is being used for the energy needed by the muscles, the muscles are also busy replenishing their glycogen stores

What is the Net energy gain in glycolysis

- it uses 2 ATP to prime glucose - generates 4 ATP plus 2 NADH per glucose NET: 2 ATP plus 2 NADH per glucose

Regulation of electron transport usually through limitation of substrates (mass action)

- lack of ADP, NADH, CoQH2, or oxygen can all slow the rate of ATP production * all rx linked so inhibition or back up at any point will slow the whole chain (goes for linkng proton gradient to ATP production) if ATP builds and there is little ADP: - F0F1 ATPase will slow for lack of substrate this will cause the usage of proton electrochemical gradient to also slow - the proton electrochemical gradient will increase a bit bc it is not being utilized. the increased proton gradient will slow the ETC (the increased gradient opposes the further pumping of protons) - the slower rate of electron transport means less oxygen consumption and less NADH being used, NADH concentrations will increase

What are the 5 possible fates of pyruvate

- lactate (anaerobic metabolism) - AcetylCoA- aerobic energy production, fatty acid synthesis (to TCA cycle) - Oxaloacetate- anapleurotic reactions (refilling of TCA intermediates) or Start point of gluconeogenesis (liver glucose production) - Ethanol- in microorganisms during fermentation - Alanine- nitrogen transport

What are the gluconeogenic precursors

- lactate (from anaerobic glycolytic metabolism) - Alanine and glutamine from protein breakdown - Glycerol from fat breakdown - other products that feed into the TCA cycle

Dark G Bands

- later replicaition - fewer transcriptionall active genes - more condensed chromatin structure - porbably have shorter loop structures - higher in A-T basepairs - stain with quinacrine (q-bands) and are light with R-banding (R= reverse)

GPCR inactivation mechanisms:

- ligand dissociates, terminating signl - phos. by GRK , followed by binding of arrestin. Blocking further interaction of the Gprotein with receptor - endocytosis, leading to either internal storage and recycling, or leading to lysosomal degradation

Glycolysis is regulated according to circulating glucose levels via insulin/glucagon and by the following:

- local metabolite control ( energy, cofactors, feed forward and feedback regulation) - Accroding to need (muscle and brain)

Phenocopy

- looks like a known genetic disorder by is caused by environmental influence ex. Holt-Oram syndrome among other sxs have reduced development of especially upper limbd that may be mimicked if a mother is receiving the drug thalidomide during pregnancy

The GPCR signal can be terminated in 3 ways:

- loss of ligand binding (unbinding) - phosphorylation by specific kinases and subsequent binding of arrestin to the GPCR - internalization by endocytosis

Mutations can cause gain of functions by

- over-expression of a protein - or by protein structure changes

How is the alpha-ketoglutarate dehydrogenase step of TCA cycle do

- makes alpha-ketoglutarate into succinyl-coA -this is catalyzed by an enzyme complex that works exactly like pyruvate dehydrogenase. Similar subunits, same coenzymes. it is irreversible too like pyruvate dehydrogenase (delta g= -8.0kcal/mol) - this step produces CO2 and reducing power (NADH) regulated ALLOSTERICALLY - inhibited by: NADH and succinyl-CoA - Activated by Ca2+

Give an example of an instance where a 3'--> 5' exonuclease would be used

- mismatches (incorporation of the wrong base) distort the 3-dimensional shape of the DNA. The shape change results in a clogged active site - this mismatch prevents movement of the polymerase to the next base and the pause favors the reversal of polymerization (3'-5' exonuclease action). - once the mic-incorporated base is removed, polymerization resumes with another nucleotide triphosphate fitted into the active site

list some rare types of inheritance

- mitochondrial is from mother to every offspring (contra AD which goes to 1/2 of offspring) from father to none - y-linked is from male to male to male - sex limited will be all affected of same sex, but for ex. show the male to male inheritance, and can be passed through a female which excludes Y-linked

ATP is critical for

- movement - biosynthesis - ion gradients - heat - coupled to other reactions

Which two parts of body are NOT responsive to glucagon

- muscle (does not have glucagon receptors) - adipose tissue (genrally unresponsive to glucagon)

SImilarities found in DNA and RNA

- nucleoside phosphates are used to make polymers, DNA and RNA - hydrogen bonding is used to pair antiparallel strands - base pairing occurs between purine and a pyrimidine, A to C and C to G (G-C bond way strong 3 H bonds)

The major macromolecules include

- nucleotides (DNA) - proteins - carbohydrates - lipids ----those are major but can also include - Metabolites, small molcules like glucose, ATP etc and hormones, or neurotranmitters - Electrolytes: like cations and anions etc. - xenobiotics: these are molecule that are perhaps not synthesized in the body or are not a normal part of metabolizm they are foreign compounds the body must degrade or excrete before they accumulate and cause damage

Small molecules assemble of polymerize, can you give examples

- nucleotides to DNA - AA to peptides to proteins - lipids to membranes - sugars to complex carbs

Repressors can prevent transcription via

- obstruction of promotor by repressor - forcing nucleosomal rearrangement such that RNA polymerase cannot bind promotor - acting through an interactin protein that obstructs promotor directly or indirectly

Klinefelter syndrome (47, XXY)

- occurs in 1/1000 males - boys with developmental delay and/or learning disabilities and social maladjutments or men seeking help for infertility - more than avg length, long limbs, small testis producing reduced levels of testosterone, reduced sexual function - 55% experience gynecomastia (when breast development occurs, risk of breast cancer) causes: 56% extra maternal X 44% extra paternal X 15% are mosaics (mosaicism for content); caused by non-disjunction in MITOSIS complications (something present in less than 50% of pt with the syndrome) : - obestiy , diabetes, problems in thyroid fx and pulmonary disease

Allelic Heterogeneity

- onle one gene - for variation has two or more alleles - phenotype can be same or diff *** caused by diff alleles at the same locus (=same gene)- sxs may be same of diff ex. we know more than 200 alleles of the CFTR gene and they ALL result in some level of cystic fibrosis

role of GTP in G protein mediated signaling

- permits catalytic activation - binds GTP --> hydrolyzes it: provides energy (why 1 GPCR can activate many proteins) - GTP activates Gsalpha when it gets hydrolyzed it turns of GTP automatically - internal mechanism that acts as an internal clock for alpha subunit activity

Regulation through cAMP cascade

- phosphorylation (many protein substrates) - gene transcription Pathways are similar through the PKA step

Mutations can lead to abnormal splicing, give and example

- point mutations in canonical sequences lead to use of secondary splice sites or the splice site in another inton *** if a splice acceptor or donor is - added: it changes the size of the exons - lost: choice of exonc and inclusion of introns may occur ex. mutation causing hemoglobin varient HbE: causes use of aberrant splicing that leads to a frameshift and therefore to reduced production of protein

Consequences of repetitive DNA

- promotes gene repair by using a copy from another chromosome after the double strand breaks - allows gene duplication by misalignment at a repeat during recombination or repair - allows gene deletion by misalignment of repeats during recombination or repair

How can proteins be modified after translation

- proteolysis - disulfide bonds - glycosylation - phosphorylation - lipidation

Acetyl-CoA is a substrate for the TCA cycle and it is also an intermediary. What are the 3 sources of Acetyl-CoA (AcCoA)

- pyruvate - Beta-oxidation of fatty acids - ketone bodies

Acetyl CoA is the substrate for the TCA cycle- it is also a central intermediary... what are some sources of AcCoA

- pyruvate - beta-oxidation of fatty acids - ketone bodies

What are 3 sources of Acetyl CoA

- pyruvate - beta-oxidation of fatty acids - ketone bodies

Acetyl-CoA (the substrate for the TCA cycle and a central intermediary) can come from

- pyruvate - beta-oxidation of fatty acids - ketone bodies - amino acid catabolism

name two central intermediaries in metabolism

- pyruvate it ends glycosis and is a central intermediary with several possible fates - Acetyl-CoA is the substrate for the TCA cycle- also a central intermediary

Name parts of glycolysis that are regulated by glycolysis

- pyruvate kinase - glucose transporters (not glycolytic enzymes) - Phosphofructokinase (rate limiting so this is MAJOR regulator of glycolysis)

Describe the structure of Coenzyme Q or ubiqunone

- quinone headgroup - hydrocarbon tail to provide hydrophobicity and lipid solubility ( stays in membrane) - CoQ is ALWAYS membrane bound

The endomembrane system consists of

- rER (includes the nuclear envelope) - sER - golgi body - lysosomes - endosome + transport and secretory vesicles - plasma membrane - peroxisomes which form from budding off of ER

Warning signs of suicide

- recent threats or actions to hurt/ kill self - focusing, talking, writing about suicide, death - hoplessness/trapped - reckless behavior - increased substance use - anxiety/sleep problems - sig change in behavior/mood

Inactivation of GPCR singal via internalization

- receptors can be regulated via endocytosis 1. they can be sequestered internally by an endosome, and eventually returned to the surface for reuse OR 2. they can degrade in the lysosome to decrease the total number of receptors in the cell ( ligand falls off receptor and can go back up to the surface or get degraded - ex. B2 type adrenergic receptors in lungs- B agonists in inhalers are ineffective after a while because it gets desensitized)

Penetrance

- reduced penetrance means that an individual had the disease by they DID NOT pass it on - person has genotype but does not exhibit sx ex. camptodactyly ex in pwrpt - a non-penetrant person is one who has the predisposing genotype by DOES NOT show sx's - this used to only occur in dominant disease, now it is also a similar observation in recessive diseases ex. common in cancers also ----reduced penetrance is symbolized by an exclamation mark in pedigrees

Glycoproteins (part of carbs) serve in

- regulation of folding - structural proteins

What is remedy for mismatch and what happens if not repaired

- remedy: polymerase uses a 3' to 5' exonuclease to repair mismatches immediately (proof-reading) - exonucleases remove the mismatch after a singl strand or double strand break is made (mismatch repair or base excision repair) IF NOT REPAIRED: - a single nucleotide polymorphism (SNP) is created: may result in changes in restriction sites to form a restriction fragment length polymorphism (RFLP), change in binding of proteins or change in protein sequence

How do telomeres protect DNA ends

- repeats protect important sequences from exonuclease action - folding protects 5' end (telomerase (TERC and TERT) hold the 3' end in a D loop and the shelterins (most of the other proteins) help the DNA to also form a T-loop) - prevents exonuclease binding and action on both 3' and 5' ends

If the nucleosome is NOT sitting on DNA what two things can there be to hold it in place

- replication specific proteins - transcription specific proteins * so DNA never stays naked except for a microsecond or two

What are the multiple functions of RNA

- structural (ribosomes) - catalytics (ribozymes) - carriers ( tRNA) - transcriptional regulation (splicing) - translational regulation (siRNA, miRNA)- there is currently being discovered a huge degree of regulation based on microRNA

The end result of scramblases, flippases, and floppases

- results in the phospholipids being distributed asymmetrically in the two leaflets of the plasma membrane ex. ALL negatively charged phosphatidylserine (PS) is located in leaflet facing the cytoplasm of smoothER - during apoptosis, some of the phosphatidyl serine gets moved to other leaflet (now faces extracellular fluid)- it acts as "eat me" signal to pagocytic cells

Ex of beneficence

- resuscitating a drowning victim - providing vaccinations for the general population -encouraging a pt to quit smoking and start and exercise program - talking to the community about STD prevention

Name the 5C sugars (pentoses)

- ribose (in RNA) - 2- deoxyribose (in DNA)

the Polar AA are

- serine - threonine - tyrosine - asparagine - glutamine - cysteine

What are 3 functions of TCA cycle intermediates

- serve as start points in anabolic reactions - serve as end points for catabolism of many AA - are involved in other pathways and transport mechanisms

Rate of protein turnover contains

- short-lived proteins - long-live proteins - structural proteins

additional suicide risk correlations

- significant sleep problems - medication changes within past two week (antidepressants like SSRIS takes apprx. 2 weeks to fully affect so must watch pts mood at this time) - particular medications - institutional settings (ex. jail, prison, mental health facilities)

In Social Ecological model for suicide what are risks factors for: societal, community, relationships, and individual

- societal: availability of lethal means and unsafe media portrayals - community: few available supportive relationships and barriers to health care - relationships: high conflict or violent relationships and family history of suicide - individual: mental illness, substance use, previous suicide attempt, impulsivity/ aggression

In Social Ecological model for suicide what are protective factors for following: societal, community, relationships, individual

- societal: availability of phys and mental health care and restrictions on lethal means - community: safe/supportive school/community environment, sources of continued care -relationships: connected to individuals, family, community, institutions and having supportive healthcare - individual: coping and problem solving skills, reasons for living, and moral objections

Most therapeutics have specific targets and work at a molecular level to treat sxs and affect cures - pharmacological treatments are developed from a molecular basis into therapeutics can you give examples

- some diseases may arise from specific molecular events such as genetic mutation giving rise to a congential disease or in other cases the causes are more complex such as bacterial infection or high blood glucose (but this is why its important to know how body works at molecular level - to be able to make therapeutics that target these events - genetic disease affect nucleic acids and proteins - sickle cell anemia affects proteins - artherosclerosis affects lipids - diabetes mellitus affect carbs Diseases that involve biochem include - congenital diseases - metabolic syndrom, diabetes - vitamin deficiencies - cancer - cardiovascular disease

tRNA processing includes

- splicing (not the same as in mRNA) - 3' end modification

List the sugar polymers

- starch (a mixture of amylose and amylopectin) - glycogen - cellulose

TCA cycle intermediates serve as

- start points in anabolic reaction - end points for catabolism of many amino acids - are involved in other pathways and transport mechanisms

TCA cycle intermediates serve as

- start points in anabolic reactions - end points for catabolism of many AAs - involved in other pathways and transport mechanisms

how does the mitochondrion generate a proton gradient

- start with reducing equivalents from glycolysis and TCA cycle - these give up electrons that are then ferried among various species with increasingly higher affinity (higher redox potential) - as they are transferred they give up energy that is used to pump protons across the inner mitochondrial membrane - the proton gradient drives F1FO- ATPase **** at end O2 combines with these protons to form H2O

Examples of disaccharides

- sucrose - lactose - maltose (2 glucose molecules in alpha 1-4 linkage) - maltodextrin (3 glucose molecules in alpha 1-4 linkage)

What are the functions of the enzymes in the sER

- synthesis of phospholipids - synthesis of cholesterol - synthesis of steroids and sex hormones (from cholesterol) - Regulate cytoplasmic Ca++ level (stroes ca2+ and tiggers a signal in the cytoplasm) - detoxify durgs and poisons (ex. cytp450)

GPCRS can act in sensory transduction such as

- taste receptors - odorant receptors - phermone receptors - vision receptors

In the Polyol Pathway why would sorbitol build up

- the enzyme aldose reductase that makes sorbitol is activated by high glucose (sorbitol can accumulate in some cells during hyperglycemia and cause osmotic effects: retina/lens/kidney/nerve cells) - cells without sorbitol dehydrogenase which would convert sorbitol to fructose have a build up of sorbitol sorbitol is membrane impermeable and increases the intracellular osmolarity, some pathologies associated with this are: - lenses: catarct formation - nerves: peripheral neuropathy - retina: retinophathy (microvascular effects) - Kidney: nephropathy (microvascular effects)

Nonpolar amino acids cluster in

- the interior of soluble proteins - & on the surface of membrane proteins

What occurs in sirenomelia aka "mermaid syndrome"

- thought to be due to loss of mesoderm in the lumbar-sacral region rare (1 in 60-100,000) congenital developmental disorder characterized by anomalies of the lower spine and the lower limb * affected infants born with partial or complete fusion of legs externally * internally aditional malformations may also occur including genitourinary, GI, anomalies of lumbarsacral spine and pelvic and absence (agenesis) or underdevelopment of kidneys

The effects of insulin can be categorized into 3 types:

- through phosphatase pathway and de-phosphorylation of relevant enzymes - through changes in metabolites (indirectly from de-phosphorylation) - effects on protein synthesis- both general and specific

For the Complex V (F0F1 ATPase)

- to get a full 360 rotation requires 10H+ - 1 full rotation makes 3 ATP - you need at least 3 H+ to make 1 ATP

Ex of boundary issues

- treatment of family members (problem of confidentiality, objectivity, and conflict of interest) - social/business interactions (parties lead to slippery slope with pts) - gifts (small gifts acceptable, big gifts should be politely declined/ also avoid giving out excessively large amounts of drug samples - ideology (physicians ideology shouldnt get in way of what is doing best for pt) - sexual relationships (even with former pt- also avoid seductive/revealing clothing) - touch (let pt know what they should expect/ prepare them for touch)

Other inactivation possibilites of GPCR

- trimeric g-protein signaling is terminated by its intrinsic GTPase - formation of cAMP is reversed by the presence of phosphodiesterases that break cAMP to AMP -phosphorylation by PKA is reversed by protein phosphatases, in some cases specific, and in other cases, general protein phosphatases (meaning they have many phosphor-protein substrates)

sugars are hydroxylated chains with a repeat formula of

-CH2O- (ratio of 1:2:1)

Secondary structure motifs

-alpha-helices -beta-sheets -turns (alpha-helices and beta sheets, tend to maximize the hydrogen bonding in the core of the protein- the regular repeat structures form the hydrogen bonds for all the available backbone amide carbonyl and nitrogen groups)

The acidic amino acids are

-aspartic acid - glutamic acid

If someone who is suicidal is sitting in your offic ex of some things you can ask

-direct: have you though about killing yourself - plan/method: have you thought of how you might accomplish it - access to meand: do you have that weapon at home - chronic risk factors: have you ever tried? how close did you come? - acute risk factors: how much are you drinking/using - protective factors: what kind of hope do you have? what is keeping you going - collateral info: who do you talk to? do you mind if i talk with you family?

Anaerobic glycolysis occurs in

-erythrocytes: they have no mitochondria and obtain ALL their energy from glycolysis and anaerobic metabolism. They obtain 2 ATP/glucose and release lactate to circulation -exercising muscle: during high intensity exercise, muscle can generate ATP from glycolysis beyond what oxidative phosphorylation can supply. Rapid degradation of glycogen and fast enzyme is glycolysis help sustain contractions

role of GTP in a G-protein mediated signaling path

-permits catalytic activation - if bind GTP and hydrolyze it: provides energy (this is why 1 GPCR can activate many proteins) - GTP activated Gsalpha - when it gets hydrolyzed it trns of GTP - automatic/internal mech (so it acts as a internal clock for alpha-subunit activity)

Suicide involves multiple factors what are they

-psychological - cultural (values) -social (social support) - biological (family history/ if you haver ever had a friend do so) 90-95% who complete suicide have mental illness

To work, what substrates does the mitochondria need

-pyruvate -fatty acids - ADP - NADH - O2 - Pi

Macromolecular assemblies include

-ribosomes -membranes - chromosomes - starch,glycogen

Where do we get energy ?

-solar energy derives the energetics of life on earth - plants use light (photons) to split H20 and to fix CO2 thi produces oxygen in the atmosphere and stored reducing equivalents in the form of the following (fats, oils, carbs, proteins)

Upon cyclization of a sugar the ___ position becomes a stereocenter. This is reversible process but the cyclized forms are generally favored and more stable. the 2 forms of glucose are designated as alpha (shown with hydroxyl down) or beta (shown with the hydroxyl up)

1 position carbon

the base attaches to the

1'-carbon of the ribose sugars

The compartments of the endomembrane system can be

1) connected directly, or 2) exchange material through vesicular transport

the size of a prokaryote

1-10 microns

Describe to mechanisms of Lipid peroxidation

1. 2 normal polyunsalipids with a carbon between the are susceptible to oxidation - if this C reacts with superoxide ion - it can make a free radical that is then oxidized at its ends (two aldehydes at its ends)- this is Malondialdehyde: a product of lipid oxidation that can crosslink proteins and DNA (you can measure this to check for oxidative damage) 2. Radical causes chemistry to occur. Ex: Peroxide reacting with a mono-unsaturated or more usually a poly-unsaturate lipid to form a free radical -the lipid radical reacts with molecular oxygen (O2( to generate a lipid peroxyl radical this can move to another molecule and repeat the process, leaving behing a peroxide lipid) *** free radical generation therefore can cause more than stoichiometric damge - it is rather catalytic in nature

Primary ethical principles relevant to clinical practive

1. Beneficence : acting for the benefit of others 2. Nonmaleficence: do no harm 3. Autonomy: individuals rights to choose or refuse 4. Justice: fairness and equity- distribution of scarce resources

What are the chain of events that allow the cell to know when to undergo replication

1. CDC6 concentration increases through the cell cycle stage called G1 2. Transcription of cell cycle specific proteins is directed by E2F 3. cdk2 and cycline are made under the direction of E2F 4. cdk2 phosphorylates CDC6 to start replication (CDC6 needed to be removed to start replication)

Just prior to implantation of blastocyst in the uterus the Trophoblast (outer cell mass) differentiates into

1. Cytotrophoblasts and 2. Syncytiotrophoblasts (these are invading) && at this point the blastocystic cavity is no referred to as the blastocoel

Describe an instance where there is a problem at the end of replication

1. DNA replication is initiate at the origin, the replication bubble grows as the 2 replication forks move in opposite direction 2. finally only one primer remains on each daughter DNA molecule 3. the last primers are removed by a 5'--> 3' exonuclease, but no DNA polymerase can fill the resulting gaps because there is no 3'OH available to which a nucleotide can be added 4. each round of replication generated shorter and shorter DNA molecules FIX THIS WITH TELOMERASE

PDH is a large, highly regulated enzyme. It comprises 3 distinct enzymatic activities, what are theses?

1. De-carboxylase (via E1- pyruvate dehydrogenase) 2. Lipoamide reductase/transacetylase (via E2 dihydrolipoyl transacetylase) 3. Dihydro-lipoyl dehydrogenase (FAD-dependent) (E3)

Embryologists divide development into 3 periods what are they

1. Germinal (pre-embryonic): (0-2weeks post fertilization)- implantation and formation of the bilamnar disc 2. Embryonic Period (3-8 weeks post fertilization)- PERIOD OF GREATEST SENSITIVITY- all major organ systems beigin to develop. At the end of the embryonic period, the embryo is only about an inch long 3. Fetal Period (9-38 weeks or till birth): growth and maturation **clinicians call these trimesters- during which they are looking for landmarks the baby should be reaching

What are 3 types of damge free radicals can cause?

1. Loss of Function of proteins - oxidation of Cys and Met side chains - disruption of iron-sulfur centers in redox enzymes - breakage of peptide bonds 2. DNA: oxidation of bases - Most common: 8-oxoguanine (this can be removed by base excision repair) - also double-strand breaks 3. Lipids - Oxidation of polyunsaturated, process of "peroxidation" (but NOT saturated and monounsaturated) fatty acids, causing rancidity - mechanism is by free-radical propagation

Steps in DNA replication:

1. ORC binds origins (origin binding complex) 2. CDC6 joins the ORC 3. Helicase (MCM) binds CDC 6 and begins uncoiling DNA 4. single stranded binding proteins cover exposed and uncoiled DNA (RPA) 5. PCNA/clamp binds CDC6 6. Polymerase alpha begins primers (polymerase binds to the PCNA - 3 polymerases to a side "like a charm bracelet" ) 7. Polymerase delta is switched in for extension from primers for first 20-50 bp - lagging strands restart with primase every 250 bp or so - polymerase delta switched into lagging strand complex - the leading strand polymerase is switched to polymerase epsilon then continues without interruption - the lagging strand primers are removed by RNase H and FEN1 - DNA ligase seals nicks in DNA until it is double stranded

Upon entering the uterus, fluid is then secreted within the morula and occupies the space found between the cells. This divides the morula into 2 parts which are

1. Outer cell mass (trophoblast): will give rise to the fetal portion of the placenta 2. inncer cell mass (embryoblast): which will become the baby - the whole structure becomes the blastocyst (at this point the zona pellucida is degenerating and you have a fluid cavity called blastocystic cavity Blastomere --> Morula --> Blastocyst

In malate/asparte shuttle

1. Oxaloacetate to malate (convertes NADH to NAD+) can cross membrane as malate 2. Malate once in mitochondiral matrix is then converted to oxaloacetate regenerating NADH that can go to complex I of the ETC 3. Oxaloacetate is combined with glutamate and then this seperates into aspartate and alph-ketogluterate 4. as aspartate gous out to cytosol, glutamate can come in 5. oxaloacetate is then again regenerated in the cytosol --cycle continues

Macromolecules provide much of the functionality of cells, which underly the functionality of tissues, organs, organ systems, and organisms so of these functions include

1. Structure 2. Flexibility 3. Movement 4. Chemistry (enzymatic) 5. Infomation storage and info transfer 6. Comparmentalization of function 7. sensory detection 8. communication

How do cells maintain a high NADPH/NADP+ ratio?

1. Via cytoplasmis NADPH/NADP+ - some irreversible reactions in the metabolic pathways reduce NADP+ to NADPH (ex: Glucose-6-phosphate dehydrogense- from HMP or pentose phosphate pathy, & the Malic enzyme (malate --> pyruvate) 2. Via Mitochondrial antioxidant defenses - A transhydrogenase is fueled by proton gradient uses NADH to maintain a high NADPH/NADP+ ratio in the mitochondrial matrix for the glutathione reductase reaction

Four functional components of ion channels

1. a pore region 2. a selectivity filter 3. a gating mechanism 4. inactivation particle- gate is open but this gets in this way

Functions of peroxisomes

1. breakdown of very long chain fatty acids 2. detoxification 3. formation of bile acids 4. formation of myeline

the first mitotic division occurs about ____ after the beginning of fertilization

30 hrs

List major regulated steps in glycolysis to TCA cycle (9 steps)

1. entry of glucose 2. conversion of Glu to G6P (hexokinase/glucokinase) 3. Conversion of G6P to glycogen or glycogen to G6P (glycogenesis and glycogenolysis) 4. PFK1 and reciprocal regulation of F1,6BP (glycolysis vs gluconeogenesis) 5. Pyruvate Kinase 6. Pyruvate Dehydrogenase 7. Citrate Synthase 8. Isocitrate dehydrogenase 9. Alphaketoglutarate dehydrogenase

public health approach to improving patient care

1. epidemiologic investigation 2. community input 3. intervention 4. evaluation and dissemination

The health care provider must consider four main area when evaluating justice:

1. fair distribution of scarce resources 2. competing needs 3. rights and obligations 4. potential conflicts with established legislation Ex. at first there was not enough flu shot to go around soo only at risk individuals got priority like immunosuppressed and healthcare providers- this doe not go by justice

For risk management of suicide you should

1. gather and analyze info (adequate suicide risk assessment and treatment planning, include past treatment info, stay professionally current- clinical condition and treatments) 2. communicate : patient, physicians/treatment team, family, support system 3. document: suicide risk assessments and patient care and the decisions making process

Steps of GPCR ex. glycogenolysis initiated by epinephrine action

1. gucagon binds receptor causing conformational change 2. the change in the receptor is communication to the G-protein, Gs 3. Gs releases GDP and binds GTP in response to the receptor 4. Gs splits into Gsalph-GTP plus betagamma 5. Gsalpha-GTP activated adenylate cyclase, synthesizing cAMP from ATP 6. cAMP binds to protein kinase A (PKA) activating it 7. PKA phosphorylates glycogen phosphorylase kinase 8. Glycogen phosphorylase kinase phosphorylates glycogen phosphorylase 9. Glycogen phosphorylase degrades glycogen to glucose-1-phosphate ** this is an amplification cascade

4 cardinal skills that physicians use in physical exam

1. inspection 2. palpation 3. percussion 4. auscultation

What structures lead up to a mitotic chromosome

1. naked DNA (all histones removed) [DNA double helix]- DNA rarely exist like this --90% of the time DNA is in 2,3,4 form MOSTLY 3-- 2. nucleosomes "beads" (histone plus DNA) [DNA wrapped around histone]= Euchromatin (between 2-3 you are in euchromatin) 3. Nucleofilament (30-nm fiber) [nucleosomes coiled into a chromatin fiber]- Most of the time DNA is like this- it is tightly packed by not completely packed (3-4 you are in heterochromatin) 4. Nucleofilament coiled and anchored to a scaffold protein [further condensation of chromatin]= heterochromatin (all repetitive sequences are packed up in nucleofilaments) -- 5. Mitotic chormosome (highly condensed chromatin) [duplicated chromosome]- DNA rarely exist like this its only like this in active division like in mitosis and meiosis

FUnctions of caveolae

1. organized cell signaling 2. transcytosis 3. can buffer mechanical tension on plasma membrane - prevents breaking under stress - caveolae form if a lipid raft becomes coated with protein caveloin - forms caveola

lateral foding coverts the "trilaminar disc" into a roughly cylindrical embryo of 3 concentric tubes:

1. outer ectoderm 2. middle mesoderm 3. inner endoderm EXCEPTIONS - No ectoderm in region of umbilicus (otherwise no way to get nutrition to the primitive gut tube NO mesoderm in - oropharyngeal membrane (only ectoderm and endoderm) ruptures in week 4 to form an opening of the foregut that communicates with the amniotic fluid - cloacal membrane (ectoderm and endoderm) ruptures in week 7 to form an opening of the anus

3 main purposes of the TCA cycle

1. oxidizes Acetate to CO2 for energy 2. Generates reducing equivalents in form of NADH and CoQH2 (seen in pwrpt as FADH2) these can be converted to ATP in oxidative phosphorylation 3. Entry point for Amino acid catabolites, it is a way point for: - amino acid synthesis - porphyrin synthesis - & serve to feed AA and pyruvate towards gluconeogenesis by increasing the oxaloacetate concentration

types of enzymes

1. oxido-reductases 2. transferases 3. hydrolases 4. lyases 5. isomerases 6. ligases

List the 3 mesoderms found on the R and L hand sides of the notochord

1. paraxial mesoderm: a thickened mass running longitudinally on either side of the notochord 2. Lateral plate mesoderm: a thin layer lateral to the paraxial mesoderm 3. Intermediate mesoderm: connects paraxial and lateral plate mesoderm

How does Complex V (F1F0 ATPase) function

1. protons enter the alpha subunit and travel through a channel and bind to the c- subunits 2. the C-subunits rotate in membrane (number of c-subunits varies for diff types of F0F1 ATPases and for diff species 3. rotation of ring of c-subuints forces the gamma subunit to rotate and it extends from the mmebrane into the center of the F1 part 4. as gamma subunit rotates inside the hexamer of alpha/beta subunits, the conformation of the alpha and beta subunits change 5. ATP synthesis occurs on the beta subunits (there are 3 ) ***** one full rotation of all c-subunits (and therefore gamma subunit) drives synthesis of 3 ATP molecules - one full rotation req each c-subunit to be protonated- or translocation of one proton - the number of c-subunits determines the ratio of protons to ATP made. The number of C-subunits is though to be 8 or 10 in humans. In either case, its not far from a ratio of 3 protons per ATP

Genetic

1. relating to genes or heredity. "all the cells in the body contain the same genetic information" relating to genetics. "an attempt to control mosquitoes by genetic techniques" 2. relating to origin, or arising from a common origin. "the genetic relations between languages"

List some concerns in the physician patient relationship

1. respect for patients values, preferences and expressed needs 2. Coordination of care and integration of services 3. Communication: dissemination of accurate, timely, and appropriate information, education about implication of disease 4. Enhancing physical comfort 5. Emotional support and alleviation of fears and anxiety 6. Involvment of family and friends 7. transition and continuity from one locus of care to another

4 general mechanisms of catalysis

1. sepcific substrate interaction 2. binding transition state optimaly 3. providing covalent chem. 4. providing acid base chem - chymotrypsin does 2,3,4 -

What are the 8 ACGME medical competencies

1. systems based practice 2. professionalism 3. interpersonal and communication skilla 4. patient care 5. practice-based learning and improvement 6. medical knowledge 7. inter-professional skills 8. personal and professional development

Steps of how telomere is made

1. telomerase extends the 3' end of the DNA, translocates, and repeats (new telomere repeat made by reverse transcriptase of telomerase) 2. Primase subunit of DNA polymerase alpha makes RNA primer 3. DNA polymerase alpha extends 3' end of RNA primer with DNA 4. RNA primer is removed by nucleases - This proces uses a reverse transcriptase uses RNA--> DNA and continues adding to the 3' end and makes it longer and longer (this process is repeated thousands of times in early development then stopped after 11 kilobases reached) - only active in early embyronic period Clinical correlation : Dyskertosis Congenita, bone marrow failure (aplastic anemia) and some forms of cancer

The initiation stage is complete when the RNA is greater than

10 bases long * capping enzyme binding and capping of the RNA if the RNA will be a mRNA is hallmark of end of initiation

size of eukaryote

10- 100 microns some bigger

Humans are born with how much telomeric repeats

11 kilobases by age 60 it is only about 4 kilobases remaining - immortalized cells keep a small amount of active telomerase throughout life (ex. t-cells, b-cells, and sperm)

breathing

12-20bpm: normal breathing >20bpm: tachypnea <12bpm: bradypnea

What forms a nucleosome

146bp of DNA wrap around a histone octamer complex and the linking regions between octamers is bound by histone H1 to form a nucleosome - the packing of nucleosomes into tighter structures is accomplished by deacytilation of nucleosome H4 subunits. These structures are called toroids, or 30nm fibers - toroids (30 nm fibers) can be further assembled onto a protein scaffold to ultimately form chromatin

in males we see increase in suicide attempts in

15-19 y/o and then after age 65

Total ATP yield from anaerobic

2 ATP - only going through glycolysis (FASt but not efficient)

Usually the net ATP production per glucose of aerobic glycolysis

2 ATP / glucose

Anaerobic glycolysis generates

2 ATP net per glucose

AT base pair is made of

2 H bonds

NADH carries __ electrons

2 electrons - each NADH-delivered electron pumps about 5 protons - it requires 3+ protons to make an ATP

NADH carriers are carring

2 electrons and 2 H+

In lateral folding the

2 lateral sides of amniotic cavity must come together as must two sides of the ectoderm * IF NOT you will get a defect (opening anteriorly) - this can be on the anterior aspect of any of the body cavities or ALL. As ectoderm contributes to the epidermis and mesoderm to dermis, muscle then opening will be in the relevant cavity

Ribose or deoxyribose is attache to what end

2' (OH for ribose, H for deoxyribose)

The cranial (anterior) neuropore closes at day

25-26 (before caudal)

The caudal (posterior) neuropore closes at day

27-28 (after caudal ) * At this stage NEURULATION IS COMPLETE and the closed tubular structure gives rise to several dilations, the brain vesicles (wider cephalic end) and a narrow portion, the spinal cord

Normal ICF and ECF

275 - 290 mosmol/kgxH20

Menstraual cycle is considered to be ___ days in duration

28 days - ovulation of the 14th day (with fertilization occuring <24hrs later)

Polyploidy

3 (rarely 4) copies of all chromosomes; not viable; 3 copies= triploid - one of the most common reasons for early pregnancy loss

GC base pair is made of

3 H bonds (making them stronger than AT)

Each codon requires

3 nucleotides bu encodes 1 AA - protein encoding 150 AA will have 450 nucleotides

the last 200 bp end of the DNA forms a

3 stranded region of DNA known as a D-loop

downstream means toward to

3' end

The 5' end of the primary transcript is encoded as the

3' end of the promotor region

There is no specific sequence for first nucleotides in a transcript but it is always complementary to DNA just

3' of promoter and TATA box

To incorporate nucleotides you must have a

3'OH on base you are adding to

Total ATP yield from Aerobic metabolism

32 ATP (or 36-38) - 7 from glycolysis - 5 from PDH - 20 from TA (slow but efficient) ** 10 H+ pumped by NADH (2.5 ATP/NADH) 6 H+ by CoQH2 (1.5 per CoQH2- same things as FADH2)

Birth takes place how many weeks after fertilization

38 weeks after fertilization (or 266 days) - this is known as the length of pregnancy aka gestation

Birth takes place how many weeks after the last mentrual peroid

40 weeks (or 280 days) from the onset of the last menstrual period * a clinician will ask when was the first day of your last menstrual period (NOT when your egg was fertilized)..so what you do is count 40 weeks from the last menstrual period, you substract by 2 to get the 38 weeks-this gives you approximation of fertilization

At the end of prophase, how many chromosome does a mitotic human cell have

46 ; DNA is doubled at end of prohphase but it is still together in a single chromosome - at end of anaphase it is 92 bc the daughter chromatids have now seperated into separate chromosomes but the membranes have yet to form separate daughter cells

How do you read this karyotype 46XX,inv(10)(p11.2;q21.)

46 total number of chromosomes XX- sex chromosomes, female inv= type of structural abnormality (inversion) 10 = the chromosome involved p11.2;q21.2 = breakpoints in abnormality (in this case the area between these two has been flipped around) ** abnormalitiles can be balanace or unbalanced - balanced: nothing gained or lost - unbalanced: either too much or too little material

What is the karyotype for downsyndrome

47XX+21 (trisomy)

What is the direction of reading of a DNA strand

5' --> 3' - only 3' to 5' exonucleases can process in from the 3' end. Other DNA binding proteins bind DNA by attaching to the 5' end and scanning until the recognition sequence is found - orrr it can more commonly attach directly to a specific recognition sequence

the initiation factor eIF4F bindings the pre-mRNA shortly after its

5' cap is added * eIF4F is attached to both the cap and eIF4G ** eIFrG and PABP are attached to the 3' end and the transcript throughout each round of translation - they recruit additional initiation factors and Met-tRNA - then as a complex it scans 5' to 3' searching for the first AUG, placing the first tRNA and ribosome on start codon ** nuclear exit is facilitated by complete complex. After exit from the nucleus, AUG binds Met-tRNA GTP hydrolyzed and 60S subunit (large subunit) is recruited - ALL other initiations occur in the cytoplasm - PABP and eIF4 (has F and G subunits) complex- load ribosomes at cap to use transcript many times

upstream means toward the

5' end

remember unless otherwase specified ALL nucleic acids are

5' on the left and 3' on the right

The uppermost L have corner in a DNA molecule is always labeled as

5' this is always opposite to the 3'OH (it runs from 5'--> 3' toward the bottom or right)

DNA is synthesized

5' to 3'

Polymerization must occur

5' to 3' because nucleotide triphosphatases provide both the new nucleotide and the energy (phosphodiester bond ) needed to catalyze the new nucleotide into place

Reading 50,000 nucleotides would take you

50 seconds

Heart rate within normal range

60-100BPM

general distribution of body water

60-40-20 Total body water= 60% body weight ICF= 40% body weight ECF= 20% body weight

GPCRs are

7 TM integral membrane proteins that activate G-proteins

GPCRS have similar characteristics of

7 transmembrane alpha-helices (7 TM receptors) - they are integral membrane proteins and bind a ligand in a pocket, typically in the TM region. Ligand binding activates them

Bradycardia

<60 bpm

Tachycardia

> 100 bpm

Fertilization occurs in the

Ampullary region of the R or L uterine tube (there are 3 parts of uterine tube: isthmus, ampulla, infundibulum)

Which macromolecule is non-polar or amphiphathic molecules that constitute membrenaes, fats, oils, waxes, and detergents

Lipids

The proton motive force that drives ATP synthesis consists of

A proton concentration gradient (high outside) and an electrical potential (positive outside)

At what points of the TCA cycle do Amino acids eneter

AA go to pyruvate then enter via oxaloacetate also AA enter via - alpha-ketoglutarate - succinyl coA - fumarate - or directly into oxalaoacetate (instead of going through pyruvate)

Hexokinase is activated by

ADP

What are some diseases/ mutations that can occur to elongation factors in translation

ADP-ribosylated by diphtheria toxin- prevents elongation stafe of protein synthesis (affects EF2 which is used in the translocation of "P" site tRNA to the "E" site after peptide bone formation)

At the 3' end of splice site (acceptor) there is an

AG (splic acceptor)

Uncoupling protein 1, UCP1, Termogenin of brown fat

AKA thermogenin - brown fat exists in hibernating animals and infants and serve to maintain temperature - adrenergic stimulation of fatty release causes activation of UCP1

in maternal inheritance the mother passes the disease on to

ALL offsprince while the father passes it on to none

Hydrophobic molecules (benzene), very small neutral molecules (O2, CO2), water

ALL pass through plasma membrane easily

PFK1 in glycolysis is allosterically regulated by

AMP, ATP, citrate, Fructose 2,6 Bisphosphate (F2,6BP), also by ADP, and phosphoenolpyruvate --- ADP, AMP, F2,6BP (activate) ATP, citrate, phosphoenolpyruvate (inhibited) *** this step is the 2nd regulated step of glycolysis - it is the comitted step.. it is highly regulated by metabolites and hormone control

Which is less digestible amylose or amylopectin

AMYLOSE IS LESS DIGESTIBLE (it is linear, while amylopectin is branched) - branches make it more digestible

vasodilators

ANF, ACH, bradykinin

Division of inner cell mass and trophoblasts is occuring

AT THE SAME TIME

Apoptosome formation in response to internal apoptotic signals requires energy in the form of

ATP

Glycolysis itself makes some ____, and some cells rely on this for their entire energy supply (erythrocytes)

ATP

During ANaerobic glycolysis

ATP is needed due to - low oxygen - insufficient oxidative phosphorylation * glycolysis is limited by NAD+ availability for GAPDH step - pyruvate is shunted to lactate to regenerate NAD+ from NADH to keep glyceraldehyde-3-p running. (no net NADH production, but there is fast ATP production via glycolysis and lactate dehydrogenase) - Lactic acidosis may occur (if lactate accumulates in blood)

Fatty acid synthesis also requires

ATP- from oxidative phosphorylation & NADPH from the hexose monophosphate shunt (HMP; also called the pentose phosphate pathway or PPP) - note the HMP or PPP produces NADPH AND can ALSO produce ribose, as ribose-5-phosphate

start codon

AUG (methionine)

Pyruvate dehydrogenase is inhibited by

Acetyl-CoA and NADH

The body can take the same molecule in cell signaling (ex. ACH) and use it in many different places to do many diff things where can ach act and what diff functions does it do

Ach can act on - heart pacemaker cell (the receptor here is a muscarinic receptor) this acts to decrease rate of firing and leads to bradycardia - salivary gland (also a muscarinc receptor) leads to increase secretion of ca2+ and salivary release --> muscarine ACH receptors mediate firing rates or secretion in two diff cell types through G-protein coupled mechanisms -skeletal muscle (nicotinic ach receptor- mediate electrical signaling by opening ion channels in response to ACH binding) this causes changes in electical signal and result in contraction

UNphosphorylated PDH is

Active

Ex. of a disorder that results from the deficiency of a single perioxisomal enzyme or tansporter

Adrenoleukodystrophy (ALK) - mutation in ABDC1 gene - affects the myelin in the CNS , the adrenal cortex, and the leydig cells in the testes has normal plasmologen level but also increassed VLCFA

Describe the Aldolase step of glycolysis (step 4)

Aldolase cleaves F1, 6BP (fructose 1,6-bisphosphate) - it takes a 6C --> two 3C sugars - it generates Glyceraldehyde 3-phosphate (GAP) and dihydroxyacetone phosphate (DHAP)--- DHAP must be converted to GAP using triose phosphate isomerase. * this is NOT exergonic- it lies near equilibrium **** there are 3 forms of aldolase A, B, and C - B is most common in liver and also cleaves fructose-1-phosphate as part of fructose metabolism (deficiency of this enzyme causes hereditary fructose intolerance) - A occurs in adult muscle and erythrocytes - C is expressd in the brain

The urea cycle converts

Amino groups and CO2 to urea

Seperation of sister chromatids begins in

Anaphase

Which phase do homologous chromosomes separate

Anaphase I

Which phase do sister chromatids separate

Anaphase II

Inhibitors of Cytochrome b-c1 (cytochrome reductase, complex III)

Antimycin A- an antibiotic, doesnt allow H+ to move through

Anchored to the centrosomes, these structure radiate out into the cytoplasm surrounding the mitotic spindle

Astral microtubules

What is diff between concentration vs electrical gradient

BOTH are mechanism for storing energy (but only the electrical gradient depends on charge)

Describe a congenital abnormality that can be detected at birth or during ultrasouns scans in pregnancy

Baby with intestines growing outside of body- you would see a bump on the ultrasound - one that may not be visible externally at birth is Dextrocardia (heart on R when should be towards L) ** one example of deformation that was missed from clinician was- a scan had showed a girl had normal rectum but skin had grown over the opening and a chanel had developed between bowel and the vagina.. feces was travelling through the channel (known as a fistula) and being excreted out of a diff hole to the rectum - stool and urine were coming out of same hole and this was noticed by the mother

What is Bax

Bax is a proapoptotic member of the bcl-2 protein family and inhibits the antiapoptotic actions of bcl-2 * if apoptosis was OFF then Bax would be down-regulated and bcl-2 would be up-regulated

What does Bax do

Bax works to activated cyt c which will then act on caspases that will cause cell destruction

Is Bcl-2 an anti-apoptotic or pro-apoptotic protein

Bcl-2 is an anti-apoptotic protein

The last AA added is the

C- terminus of the protein

What coordinate transcription with pre-mRNA processing

C-terminal domain of RNA pol II

if the disease is x-linked recessive, a healthy male

CANNOT be a carrier unless he has the disease - so if a male is not a carrier of an x-linked recessive disease (he would be affected it so).. his chances to pass on the disease-causing gene are very rare

During anaerobic glycolysis NADH

CANNOT be used (there is no oxidative phosphorylation) - if NADH not used, the NAD+ concentration will drop - NAD+ is a cofactor/substrate for G3P- dehydrogenase - if NAD+ is low, the reaction will hault, and glycolysis will hault - to recycle NAD+, pyruvate is converted to lactate (lactic acid) and NADH to NAD+

if in closed garage with gas-powered car running- what type of poisoning could you have/what complex would be blocked

CO- carbon monoxide poisoning - blocks Complex IV, cytochrome oxidase (inhibits utilization of oxygen, CO also binds Hb and reduces oxygen delivery) *** during this time a lack of ATP due to loss of oxidative phosphorylation and the increase in AMP will signal a substantial increase in the rate of glycolysis to try to supply ATP anaerobically -- a pt with this could develp lactic acidosis due to anaerobic metabolism trying to sustain energy needs

primary structure of a protein is made of

COVALENT linear chains of AA

What will high amounts of Ca2+ and Acetyl CoA do to the activity of PDH

Ca2+ (along with increased pyruvate) will cause MORE PDH activity: because it activates phosphatase- which takes the phosphate off of PDH activating it AcCoA (along with ATP, NADH, citrate, Malonyl-coA) will cause LESS PDH activity: because it activates the kinase which phosphorylates PDH make it INACTIVE

Classic Galactosemia

Caused by a deficiency of galactose 1-phosphate-uridyl transferase abnormalities it causes: - galactose in the blood and urine after milk consumption - Galactose 1-phosphate accumulates in cells, phosphate depleted - presents shortly after birth with feeding difficulties, vomiting - risk of liver damage, also cataracts and neurological delay

List some antibiotics that inhibit protein translation in bacterial genome without effect on the eukaryotic genome

Chloramphenicol, macrolides, and lincosamides - bind 50s ribosomal subunit - prevent peptide bond formation - STOP protein synthesis Aminoglycosides - bind 30S ribosomal subunit - impair proofreding, resulting in production of fault proteins Tetracyclines - bind to 30S ribosomal subunit - block the binding of tRNAs, thereby inhibiting protein synthesis

Describe the structure and function of Coenzyme A (CoA)

CoA is a combination of ADP, pantothenic acid (vitamin B5) and cysteamine (which has a sulfhydryl group which also to make thioester= high enerygy bond- it connects to carbonyl groups in a high energy bond- has energy comparable to an ATP phosphate bond) - it acts as a carrier for high-energy acyl bonds ** remember CoA is added onto pyruvate

Cytochrome B-C1 complex (complex III) aka cytochrome reductase works by

CoQH2 (ubiquinone) delivering 2 electrons, 4H+ into intermembrane space per 2 electrons moved, 2 electrons are moved to 2 cytochrome C (1 electron each) - one electron travels through an iron-sulfur and heme c to cytochrome c - second electron travels a diff path through hemes BL and BH and ultimately to the oxidized CoQ

What are the 3 main complexes of the ETC that are transmembrane proteins

Complex I - NADH Dehydrogenase complex Complex III- Cytochrome b-c1 complex (cytochrome reductase) Complex IV- cytochrome oxidase

name all the complexs on the ETC

Complex I: NADH dehydrogenase Complex II: Succinate Dehydrogenase (part of TCA) Complex III: Cytochromase b-c1 complex (cytochrome reductase) Complex IV: Cytochrome Oxidase (makes H20 from O2) Complex V: F0F1 ATPase

Formation of the notochord

Complex process. Essentially the notochord is formed from the notochordal plate (np) - once formed the notochord will detach from the underlying endoderm ** the notochord induces the ectoderm to thicken to form the neural plate (neural induction)

What does lactate dehydrogenase do?

Converts pyruvate to lactate It recycles NADH to provide GAP (dehydrogenase substrate) * lactate dehydrogenase is reversible and tends to follow the NADH concentrations (if it is high in the cytosol)

What is the cyclin and cdk partner for S-cdk (aka S-cyclin)

Cyclin A, cdk2 and cdk1

What is the cyclin and cdk partner for M-cdk (aka M-cyclin)

Cyclin B, cdk1

What is the cyclin and cdk partner found in the G1-cdk (aka G1 cyclin)

Cyclin D and cdk4, cdk6

What is the cyclin and cdk partner found in the G1/S-Cdk (aka G1/S cyclin)

Cyclin E, cdk2

Glycolysis takes place in the

Cytosol (pyruvate is made in the cytosol and has to pass through the mitochondrial membrane into the matrix- where it becomes acetyl-coA and goes through the TCA cycle)

In grouping of non-banded chromosomes which are acrocentric

D (13-15): large acrocentric G (21-22, Y): small acrocentric

Micelles are also formed from amphipathic molecules called

DETERGENTS - these differ from membrane lipids in that they tend to not form bilayers, but rather form micelles (in most cases bc polar headgroup ia bigger than the hydrophobic acyl chain - however the bile acid detergents have somewhat diff. micellar structures - in all cases, detergents have the ability to carry out hydrophobic molecules in their cores, thus effectively dissolving oils and fats

Response elements are

DNA

the building block of nucleic acids are used to make both

DNA and RNA

Nucleosomes can breathe if they are rearranged by

DNA binging proteins like the end targed ot second messanger systems ( ex. E2F or cyclic AMP response element binding protein, and CREB ) - additional enhancers like Fos and Jun and repressors can bind after the area is opened and recruit transcription factors and RNA polymerases (force nucleosomal rearrangment to make promotor accessible)

____ is the hallmark of programmed cell death (apoptosis)

DNA degradation - apoptosis works through several diff. pathways and ultimately through action of caspases, which induce DNA degradation by endonucleases.

DNA can only be used for transcription or replication when the

DNA is freed of nucleosomes enough to allow the transcriptional machinery to function

The only enzymes we are responsible for knowing in MINI I (:

DNA polymerases, ligase, and topoisomerase in addition to CDC6 (not in the replisome)

thymise is found only in

DNA, uracil only in RNA

central dogma of molecular biology

DNA-(transcription)-> RNA -(translation)-> Protein

Effective treatment boundaries

DO NOT create walls, instead they define a fluctuating, reasonably neutral, safe sapce that enables the dynamis interaction between phys and pt

Extraembryonic mesoderm

DOES NOT contribute to the embyro - intraembryonic mesoderm does

Apoptotic death ____ apoptosis

DOES NOT induce apoptosis does however do the following: - activation of caspase 3 to cleave cellular proteins - cytochrome c release from mitochondria - Fas death receptor binding to an extracellular ligand - increase in the intraceelular ratio of Bax to Bcl-2

On what day does gastrulation commence

Day 14

What is the Delta G for the hydrolysis of ATP ( ATP +H2O --> ADP + Pi )

Delta G = -7.3 kcal/mol Delta G less than -7.3 kcal/mol

E1 of Pyruvate Dehydrogenase

Dexcarboxylase activity (Pyruvate Decarboxylase), E1 - Pruvate is reacted with thiamine to form a hydroxyl-ethy adduct. There is loss of CO2 *Thymine Pyrophosphate (TPP) is vitamin B1- if this is deficient the brain cant use glucose and you end up with neurological damge, and you can also have GY symptoms- this is called Beriberi Disease

E3 of PDH

Dihydrolipoyl dehydrogenase activity, E3 - Oxidizes lipoyl from reduced (FAD) to oxidized (FADH2) - harvests the reducing equivalents to FADHs- a bound cofactor - FADH2 subsequently donates the reducing equivalents to the soluble cofactor, NAD+, making NADH

Give ex of how ppl how abused uncouplers

Dinitrophenol - this drug uncouples oxidative phos. by carrying H+ across inner mitochondrial membrane * was once sold for weight reduction - too toxic so pulled from market - it prevents ATP synthesis and causes lactic acidosis similar to cyanide but electron flow is NOT blocked, but accelerated. Electron carriers and coenzymes are mainly in the oxidized state. Hyperthermia is characteristic and can be the immediate cause of death

What are some mutations/moditifcations that can lead to disease in certain initiation factors

Diseases associated with loss of eIF2B (required to deliver the Met-tRNA to the "P" site in the preinitiation complex - vanishing white matter disease (a leukodystrophy) - reticulocyte apoptosis in response to iron defiicieny Cancers often have reduced levels or mutated eIF3 (is required for assembly of the 40s subunit onto a 5' cap or IRES) Wasting diseases (when too much eIF4G phosphorylated) and Polio (or any picornavirus)- proteolysis of eIF4G (usually helps to stop translation or modified to allow IRES use) prevents use of host transcript whereas viral RNA is used for translation preferentially

In transcription what does something writing as E#F and TF#A signify

E#F= factor used in transcription (enhancer) ** E2F= a transcription co-repressor when bound to Rb protein, and a transcription enhancer is NOT bound to Rb TF#A= factor used in transcription (RNA pol II binding elongation or termination; # is roman numeral) *** TFII assists TFI in forcing RNA pol II to stop transcrbing in the DNA region

the stability, arrangement and function of actin filaments depends on the

actin-binding proteins

Rb protein when over expressed binds

E2F and acts as a corepressor of cell cycle specific genes

Integrins bind the

ECM and cytoskeleton when active

elongation in translation occurs using charge tRNAs bound to

EF2

Which of the following can ONLY use glucose as a fuel source: Brain OR erythrocytes

ERYTHROCYTES!! - they donnot have a mitochondria so they cannot use ketone bodies- they are entirely reliant on anaerobic glycolysis for energy - The brain on the other hand can adjust to using ketone bodies, lower the req. for glucose

What does the aconitase step of TCA cycle do

Establishes an equilibrium between citrate (90%), aconitate (3%-notshowninslides), and isocitrate (7%) - the delta G is slightly positive (+1.6kcal/mol)

Which germ layer will form the epithelium of the small and large intestine which are components of GI

Endoderm

Step 9 of glycolysis involves

Enolase- carries out a dehydration reaction

E2 of Pyruvate Dehydrogenase

Enzymatix activity (Dihydrolipoyl Acetyl Transferase), E2 - Lipois acid is attached through an amide bond to the enzyme at a lysine residue - Thiamine pyrophosphate (TPP) donates the bound hydroxyethyl to lipoyl moiety (this breaks the disulfide bond, one sulfur is reduced (-SH) and the other sulfur now has an acetate group attached as a thioester bond - CoA comes in and replaces its sulfur for the lipoyl sulfur and creates: Acetyl-CoA and reduce lipoyl

What is needed for opening and initiaton for eukaryotic replication

Enzymes the open up the DNA helix): - topoisomerase - helicase (MCM) - single stranded region of DNA - single stranded binging proteins (RPA) Enzymes that initiate the DNA Synthesis on both leading and lagging strands : - free 3' end of nucleic acid (NEED THIS!- if not terminated) - DNA polymerase alpha

Gene expression is highly regulate. What are two types of regulation

Episomal Regulation - methylation (nucleosomes tighter) - acetylation (looser) - nucleosomal structure Temporal, spatial and environmental regulation - second messenger system regulation via transcription factors - transcription and/or expression of regulators - metabolite concentrations - energy availabilty

Name one beneficial role that ROS can play

Ex. NOX2 (NADPH oxidase) - is a plasma membrane bound enzyme that specifically makes ROS, it actively generate the superoxide radical which becomes H2O2 as a mechanism for killing phagocytosed bacteria

What part of the F0F1 ATPase is inhibited by oligomycin

F0 - this is the transmembrane portion

true or false : mitochondria do vesicular transport

FALSE mitochondria DO NOT do vesicular transport

true or false sucrose is reducing sugar

FALSE!!! it is not reducing bc of its linkage (sucrose is NON-reducing sugar)

True or false: fructose can be converted to glycogen

FALSE!!!! fructose enters glycolysis and cannot be converted to glycogen, but rather will be used for energy or fat synthesis

True or false: During anaerobic metabolism, glycolysis cannot be used as the main source of ATP

FALSE!!!!! during anaerobic metabolism- glycolysis CAN also be used as the main source of ATP

true or false: the polymerase epsiolon replaces the polymerase delta on both leading and lagging strand

FALSE!!!!!! only on leading strand is it replaced

True or false the transcript contains the promoter sequence and the TATA box

FALSE!!!!!!!!! NO! the transcripts NEVER contain the promoter sequence nor TATA box

delta G < zero

FAVORABLE: reaction is spontaneous and will go forward in the direction written *** this implies that reactants had higher initial energy than the products (Exergonic reaction) - the negative energy is given from the reactants to the environment (change in temp or entropy)

Type I error in epi

False + (test positive, but does not have disease)

Type II error in epi

False - (test comes out negative but you actually do have disease)

Base excision repair (BER) disease

Familial Adenomatous Polyposis (MYH form)

__ is NOT convertible to glucose

Fat (fatty acid metabolism is CANNOT be used to generate glucose)

Which iron causes production of the Hydroxyl radical

Fe2+ (ferrous Fe)

Name for the reaction that convertes hydrogen peroxide to the highly reactive hydroxyl radical

Fenton Reaction (H202 + Fe2+ --> HO. + OH- + Fe3+)

ex of noncompetitive inhibitor

G6P is one to hexokinase - non-nucleoside reverse transcriptase inhibitors (NNRTs) is another examplpes - vmax decreased - km unchanged

What is the output of the TCA cycle

For energy the TCA cycle makes - GTP= 1 ATP equivalent - Reducing equivilents in the form of : 3 NADH, 1 FADH2 (--> CoQH2) Waste: 2 CO2 from Acetyl CoA

small G proteins require ___ to become inactivated

GAP (GTPase activativing protein) to hydrolyze GTP to GDP

Which part of the trimeric G-protein pathway serves a role analogous to GAPs

G-alpha (it works as an internal clock built into G-proteins)

Many different cells are permanently arrested in this phase of the cell cycle

G0

What phase is AKA quiescence

G0

Oncogenic factors from tumor viruses target the growth suppressor function of this phase of the cell cyle

G1

Most of the CKIs function at what checkpoint

G1 (p21, the major cyclin dependent kinase inhibitor (CKI) inhibits G1/S cyclin and S-cyclin

Which phase is typically shorter in a transformed cell ?

G1 ex. embryonic cells divide much faster but dont have many things to do so they dont stay there for long but a cell like hepatocytes would have a little longer of a G1 because they have so much to do in G1!

During which stage of the cell cycle is there the least amount of DNA

G1 - has exactly 1 copy of each maternal chromosome and 1 copy of each paternal chromosome S- [DNA] slowly increases as it is replicated G2- cell has the most amount of DNA due to a dull duplication (now 2 copies) of the maternal and paternal chromosome M- the concentration of DNA decreases as sister chromatid are pulled apart

Replication begins at the end of

G1 due to the phosphorylation of cdc6. The phosphorylated cdc6 allows the assembly of the replisome by falling out of the pre-replication complex at each origin (this is the G1 checkpoint)

RNA and protein synthese occur in

G1 of interphase

Which two cyclin-cdk complexes use cdk2

G1/S- cdk and S-cdk

Mutagenic events leading to DNA damage are repaired during this phase of the cell cycle , this is the stage of the cell cycle that immediately precedes mitosis

G2

The safety gap prior to nuclear division of mitosis is

G2 phase

Hexokinase is inhibited (regulated) by

G6P **** GLUCOKINASE IS NOT INHIBITED BY G6P

small G proteins require ___ to become activated

GEFs (guanosine exchange factors)

Which type of receptors use second messenger systems

GPCRs - nuclear receptors do not because they bind directly to their effectors (transcription regulators) - ion channels do not do it often either because second messenger systems serve to change the electrical signal

There are fewer g proteins than

GPCRs BUT still a substantial variety. some have relatively specifc effectors

reducded levels of G6P dehydrogenase generates less NADPH which is then insufficient to maintain

GSH in a reduced form, which is essential for maintaining RBC integrit

Timeric, large G-proteins bind

GTP (active state) - causes separation of their alpha subunit, with the GTP from beta-gamma subunit complex--> which can also activate down stream effectors GDP (inactive state)

signaling is terminated by

GTP hydrolysis, ligand unbinding, phosphorylation, and endocytosis

The 5' end of splic site (splice donor) has a

GU (splice donor) ** if this mutates to GA or anything else, there will be NO splicing- this leads to many diseases - splice acceptor has AG

Descibe the introduction of galactose to glycolytic intermediates

Galactose is phosphorylated to galactose-1-phosphate by a specific kinase, galactokinase - UDP-glucose (from glycogen synthesis) is used to make UDP-galactose and glucose-1-phosphate - an epimerase converts this UDP-Galactose to UDP-glucose (recovers the UDP-glucose used in step 2 of this reaction) - galactose uptake and utilization feeds directly into glycogen synthesis, but can also simply be used for energy by converting G1P to G6P for entry into glycolysis - G1P can also be converted to UDP-glucose for glycogen storage

At the end of week 2: ____ commences

Gastrulation - this results in the bilaminar germ disc (aka epiblast and hypoblast) being transformed into a trilaminar disc consisting of ectoderm, endoderm, and mesoderm ** the epiblast layer grows into the hypoblast layer kicking cells out which then makes endoderm - then another layer between endoderm and epiblast forms and this is the mesoderm and then the epiblast becomes known as the ectoderm (associated with amniotic cavity)

Substrates and products of mitochondrial oxidation are transported across the inner mitochondrial membrane by antiporters. What comes in vs what comes out?

IN: - reducing equivalents - pyruvate, fatty acids - ADP - phosphate OUT: - ATP

alpha- adrenergic receptors can inhibit adenylate cyclase by using

Gi

inhibition of cAMP is done by

Gi

Some G-proteins can interact at the level of the effector to modulate function.

Gi is a G-protein that mediates responses to receptors such as alpha-adrenergic receptors - can interact with Gi to inhibit adenylate cyclase

A person eats an early dinner, goes to sleep with NO snack, wakes the next morning, and skips breakfast. Just before going to eat lunch, the main action of glucagon in the liver is to carry out what function that helps to sustain blood glucose?

Glucagon will stimulate glycogenolysis and gluconeogenesis; lipolysis will also be active. Glucagon INHIBITS glycolysis and glycogenesis. The main action of glucagon is to help maintain blood sugar through glycogenolysis and gluconeogenesis. At lunch time, this person will have gone 16-18 hrs without food and will be in a fasting/early starvation phase. In this case, much of the liver glycogen stores have been activated. so best answer= gluconeogenesis

What is the isoenzyme of hexokinase

Glucokinase- it is found in the liver and the pancrease Hexokinase is found in muscles and all other tissues

Deficiency in what enzyme impairs the ability of an erythrocyte to form NADPH, resulting in hemolysis

Glucose-6-Phosphate dehydrogenase deficiency - it causes hemolysis due to the oxidant stress via making H2O2 (can be caused by certain drugs, infections, and fava beans) ** causes hemolytic anemia (aka as Favism): inability to detoxify oxidizing agents (IN MALES)

Glutathione reduction of peroxide

Glutathione (synthesized in all cells) is made from 3 AAs (glutamate, cysteine, and glycine); while it is comoposed of amide bond linkages, the glutamate is joined to the cys through the gamma-carboxyl rather than the alpha-carboxyl (it is present at high concentrations (~0.1%) in all cells & helps to maintain the redox state of the cell - reduced glutathione (G-SH) is essential for antioxidant defense [ becomes oxidized form GS-SG via glutathione peroxidase] - oxidized glutathione (GS-SG [has disulfide bond between cysteines- this is chemically the same as disulfides in proteins]) is formed as part of the defense against oxidants. From this GSH can be regenerated via a reduction reaction using NADPH catalyzed by glutathione reductase

In terms of HIF (hypoxia-inducible factor) what occurs during a state of hypoxia

HIF alpha is NOT degraded ( because PH which would normally hydroxylate it- tagging it for ubiquination is not active w/o O2) so instead HIF alpha binds with HIF beta and stimulate transcription

What is the rate limiting enzyme for de novo synthesis of ENDOGENOUS cholesterol? and what is it inhibited by

HMG CoA reductase - this is an integral membran protein in SMOOTH ER membrane, biosynthesis of it is tightly regulated - this enzyme is targeted/inhibited by STATIN drugs that reduce blood cholesterol

phosphorylated PDH is

INACTIVE- phosphorylated by glucagon

Ex of Mitochondrial Myopathies

Here is 2 examples of mitochondrial myopathies that result for maternally inherited defects in genes encoding mitochondrial tRNAs: - MELAS: mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes - MERRF: myoclonic epilepsy and ragged red fibers

What are two causes of fructose intolerance

Hereditary Fructose Intolerance due to aldolase B deficiency (Autosomal recessive) abnormalities: - fructose in blood and urine after fructose containing meal. Urine positive for "reducing substance" but no glucose present - Fructose 1-phosphate accumulates in liver and affects ATP production due to limitied Pi availability - Hypoglycemia and nausea after fructose-containing meal due to lack of ATP in hepatocytes and therefore lack of gluconeogenesis -aversion to sweet foods - presents at time of weaning - risk of liver damage, due to phosphate depletion OR Fructose Malabsorption- fructose carriers (Glut5) gut transporter is deficient

the alpha1 adrenergic receptor activates the

IP3 system. This requires activation of a Gq protein, whose alpha-subunite-GTp- complex activated phospholipase C

The following fix dsDNA breaks (HR, MMEJ, and NHEJ) what makes them different?

Homologous recombination (HR): uses sister chromatids while still attached to each other (G2 to metaphase) Microhomology mediated end joining (MMEJ): uses repeitive DNA like microsatelites or gene copies on the same DNA Non homologous End joining (NHEJ): puts two ends of DNA together

What does glucagon do to glycolysis

INHIBITS glycolysis - active in the fasted state (low circulating glucose, or a rise in AA) - inhibits PFK1 - inhibits liver pyruvate kinase - also affects other pathways ** glucagon mainly targets the liver

In the FED state the prinicipal signaling molecule is

INSULIN (it is released from the Beta cells of the islets of langerhans in pancreas **insulin make u betaaa*) It fx to - promote glucose use by adipose, muscle and liver and some other tissues - upregulates Glut4 in skeletal muscle and adipose - promotes general anabolism - activates LPL (works to take up lipoproteins) in adipose

How do some virus' get viral transcripts used instead of host transcripts

IRES *** initaition can be started WITHOUT the 5'cap in only this very special case - this req the eIF4G to bind a specialized stem loop structure called an IRES - eIF4G must be either proteolyzed or modified (modified eIF4G CANNOT bind eIF4F- this stops 5' cap recognition) ex.. in picornaviruses (ex. polio) subvert translation for its own RNA use (proteolyzes eIF4G and Viral RNA has IRES ** this is also used in apoptosis

Define Ischemic cell injury (Localized ischemia) and what occurs during the process

Impairment of blood supply to the TISSUE, leading to partial or complete oxygen deficiency (hypoxia, anoxia) - loss of ATP generation through oxidative phosphorylation - failure or ion pumps resulting is osmotic stress - stimulation of glycolysis - lactic acid formation to continue anaerobic metabolism as an ATP supply - tissue acidification - leaky membranes - Activation of lysosomal enzymes

Give an example of uncoupling

In step 6- in the presence of arsenate, we still form 3-phosphoglycerate from glyceraldehyde 3-phosphate, but we do not get ATP in the process (this is because the intermediate, 1-arsenate, 3-phosphoglycerate, spontaneously breaks down to 3 phosphoglycerate) * this also affects pyruvate dehydrogenase

What will happen to rate of glycolysis during a state with a lack of oxygen

In the absence of oxidative phosphorylation, the intracellular ATP levels will drop. The increase in AMP will activate glycolysis. So the rate of glycolysis will INCREASE

What are the functions of proteins? (they are the most versatile molecule)

In the diet they are: a source of energy and AA to rebuild new proteins they also have a myraid of other functions: chemistry, movement, communication, transport etc - proteins are the product of information carried oh the genome Other ex of functions: -structure -receptor signaling -catalysts -carriers of small molecules (ex. hb, albumin)

Where are most of the reactive oxygen species generated?

In the mitochondria

Giva an example of feed-forward regulation?

In the pyruvate kinase step of glycolysis - if Fructose 1,6- bisphosphate, which was generate in the committed step of glycolysis (PFK1 step), accumulates it signals pyruvate kinase to process phosphoenolpyruvate (PEP) to pyruvate and complete glycolysis

Lyonization is known as

Inactivation of every extraneous x-chromosome (irreversible for that cell and its descendants) ex. X-linked Anhidrotic Dysplasia - gives variation in patterns of inactivation (it is random)- so diff woman will have diff areas without sweat glands (mosaic female carriers)

What activates/inhibits isocitrate dehydrogenase?

Inhibited by: NADH (its own product) and ATP Activated by: ADP and Ca2+

___ must be closely regulated to avoid exacerbating ROS damage

Iron

Which enzyme forma alpha-ketogluterate in TCA cycle

Isocitrate dehydrogenase - alph-ketogluterate is an important metabolic intermediate- it participates in transamination reactions, shuttles, and is converted to and from glutamat and glutamine - this step produces CO2 and reducing power (NADH) This step is regulated ALLOSTERICALLY - inhibited by: ATP and NADH - activated by: ADP and Ca2+

Which two steps in TCA cycle make CO2 and are allosterically inhibited

Isocitrate dehydrogenase and alpha-ketoglutarate dehydrogenase complex

Explain the Cori Cylce

It explains the recycling of lactate from anaerobic exercise - accumulating lactate stores reducing equivalents until there is enough O2 to recover it and convert it to glucose - this is part of the "oxygen debt" accumulated at start of exercise ** most of the lactate is NOT reprocessed to glucose, but instead is taken up in various tissues and utilized for energy (after being converted back to pyruvate) - in exercise, the initial anaerobic part of the exercise builds up some lactate and creates and oxygen debt. this is repaid at the end of the exercise regimen when there is sufficient oxygen not needed for exercise that can oxidize the lactate back to pyruvate, which is then fed to the TCA cycle and oxidative phosphorylation

What does it mean when it is said that the GPCR signaling cascade for glycogenolysis initiate by epinephrine is a amplification cascade/ process- which steps make this so

It means it leads to 10's of 1000s of molecules even if only a small amount of ligand is used (this permits a very small amount of hormone to mobilize large amounts of glucose - this cascade is mediated by receptors, G-proteins, cAMP, and PKA There is amplification every single time a catalytic event occurs within the signaling pathway: 1. Activation of Gs by glucagon receptor, several Gs can be activated for each bound receptor 2. Synthesis of cAMP by adenylate cyclase, many cAMP generated by each active enzyme 3. Phosphorylation of glycogen phosphorylase kinase by PKA; PKA is an enzyme and can phosphorylate many glycogen phosphorylase kinase 4. phosphorylation of glycogen phosphorylase by glycogen phosphorylase kinase

What does uncoupling mean

It means the reaction goes as usual but NO ATP is made in the process. Uncoupling is more a general term and happens in other reaction and describes that when two processes are normally obligatorily coupled, when uncoupled, one occurs without the other Ex: arsenate

What does global regulation of metabolism respond to and use?

It responds to - hormones - circulation nutrients, especially glucose - neural input it uses: second messenger signaling

What does local regulation of metabolism respond to and use?

It responds to - the state of the cell - to the state of the pathway it uses: intracellular metabolite levels AND allosteric regulation

Main intracellular cation

K+

Kd=

K+/K- where K+ is the kinetic association constant and K- is the kinetic dissociation constant ( this value represents the affinity in concentration units, which is more convenient to think about)

the concentration of a hormone that gives half max binding is signified by what term (it describes the binding strength in concentration units)

Kd ( so a Kd value of 50nM indicates that at that concentration of the ligand, the receptors are 50% bound

What is the main product of pyruvate during ANaerobic metabolism in muscle?

Lactate! - Pyruvate is diverted to lactate during anaerobic metabolism to replenish NAD+

PDH deficiency can cause

Leigh Syndrome (which also includes other deficiencies in oxidative phosphorylation) causes - lactic acidosis: accumulating pyruvate is converted to lactic acid, also alanine - malfunction of the brain, which depends on glucose oxidation - severe deficiency (<20% residual activity): neonatal acidosis and death - moderate deficiency (20-40% residual activity): brain damage with microcephaly, mental and motor retardation, optical atrophy, death in childhood - milder deficiency (40-50% residual activity): slowly progressice spinocerebellar ataxia, carbohydrate intolerance

During states of HIGH energy would PDH be more or less active

Less PDH activity - ATP - AcCoA - NADH - Citrate - Malonyl-CoA all activate kinase which phosphorylates PDH inactivting it * NADH and AcCoA are direct allosteric inhibitors of PDH (this represents local signaling. If NADH or AcCoA get too high, PDH activity will be blocked and pyruvate will accumulate)

Can you give an example of where you would find fat droplets

Leydig cells! - these are testosterone producing cell of the testis that tend to have conspicuous lipid droplets that are associeated with sER. - leydig cells are making alot of cholesterol (precursor for the steroid hormone testosterone), which collects in lipid droplets

Low ATP and GTP ___ replication and _______ transcription and translation

Low ATP and GTP PREVENT replication and REDUCE transcription and translation * G1 checkpoint req significant phosphorylation events- remember CDC6 phophorylation is "GO!" for replication initiation - with low GTP: initiation is delayed bc eIF2 cant load 60S and EF1 and EF2 cannot load new tRNAs or translocate ribosome - with low ATP: tRNA cannot be charged and RNA polymerases hesitate when they should incorporate Adenine

Mismatch repair (MMR) disease

Lynch syndrome (CS) also known as Hereditary Non-polypsis colon cancer (HNPCC) - high rate of cancer, colorectal cancer, ovarian and endometrial cancer - early onset and higher freq of colon polyps

Lipids MUST be moved from site of synthesis in sER to ALL the other cell membranes. What are the 4 possible mechanisms for lipid movement within, across, and between membrane bilayers?

Membrane lipids can: 1. laterally diffuse within the bilayer 2. Translocate between two leaflets of the bilayer (scramblases etc.) 3. Move through the cytosol from one bilayer to another by attaching to a cytosolic lipid-transfer protein (this is not specific, not targeted; it carries the lipid through the cytoplasm - it drops the lipids to an area with less of them, this works in the mitochondria but it doesnt recieve a vesicle) 4. Get carried by vesicular transport (pinched off vesicles carrying phospholipids and cholesterol)

What is Metabolite Regulation, along with 3 exampls of how it could work?

Metabolite regulation can reflect local intermediate concentrations from the same pathway - it can also sense the energy state of the cell - can do cofactor/substrate restriction - uses ALLOSTERIC protein regulation (the enzymes that are affected have built in sites for regulation that are distinct and distant from the active site- regulators can change activity by binding to these sites non-competitively- either decrease (non-competitive inhibition) or increase. 3 types: 1. Feedback inhibition of a linear pathway. The product D blocks further entry into the pathway by inhibiting the first step 2. Feedforward activation: High concentrations of A promotes its own entry into the pathway 3. Energy Charge/State Regulation: ATP inhibits further production of ATP, whereas ADP activates the pathway to generate more ATP (this is common in glycolysis)

Homologous chromosomes are paired and the kinetochores of sister chromatids are "pointed" toward the same spindle pole during

Metaphase I

Delayed age of onset

Missed or delayed diagnosis often occurs if a disease that is typically diagnosed in juveniles (such as asthma) is present in adults, and vice versa (such as arthritis). Depending on the disease, ages of onset may impact features such as phenotype, as is the case in Parkinson's and Huntington's diseases.

Proteins are typically described from the

N-terminus (free amino terminues) to the C- terminus (this is also the direction of synthesis on the ribosome)

Describe fructose metabolism

Most, but not all of the fructose is processed by the liver - fructose is a substrate for glucokinase in the liver, but the Km is very high..so glucokinase does not effectively phosphorylate fructose (glucokinase typically has too low an affinity for fructose to be relevant) , but has to go via the fructokinase pathway - in other tissues with hexokinase, fructose is a substrate, but hexokinase is typically saturated by glucose. So again, the fructokinase pathway is needed

the first AA is the

N-terminus of protiein (always Met in humans)

Which component of ETF is the highest energy electron donor

NADH (this means it has the lowest redoc potential and yields the highest energy when electrons are combined with an electron acceptor- such as oxygen )

Malate/Aspartate shuttle

Moves an NADH from the cytosol to the matrix of mitochondrion without gaining mass ** this is believed to be predominant mechanism in humans,except in perhaps brown fat * brown fat (in infants and to small extent in adults mostly around neck and kidneys-its main fx is to generate heat, the energy lost due to heat in this cycle is consistent with the role of brown fat) uses the glycerophosphate shuttle (less efficient bc the product is reduced CoQH2 (this loses redox potential diff between NADH and CoQ)

What is Myc

Myc is a transcripiton factor that acts to up regulate 15% of all genes. It is found only in the cytoplasm in the nucleus and NEVER acts as a growth factor/hormone. Overexpression of Myc results in increased levels of Arf which removes Mdm2 from p53. p53 can then be phosphorylated and act as a transcription factor for p21 (the CKI that inhibits S-cyclin and G1/S-cyclin) Over-production of p21 results in the inability of the cell to progess through the G1 checkpoint

As part of the antioxidant defense system, the mitochondrial proton gradient drives the conversion of 2 redox reagents in the mitochondrial matrix. What are the reactants and products of this reaction

NADH and NADP+ converted to NADPH and NAD+ ** this rx utilizes energy from the proton gradient to convert NADH to NADPH as NADPH is required to maintain glutathione in a reduced state in the mitochondrial matrix. The mitochondrial NAD(P) transhydrogenase (NNT) carries out this function

Name a part of the ETC that can generate superoxide

NADH dehydrogenase (Complex I) - at the point of FMNH+ , O2 can come in and snag an electron generating the superoxide ion This process is favorable under the following conditions: - electron carriers in the reduced state - NADH is abundant - Oxygen is deficient - Steep electrochemical proton gradient * Flavoproteins in other locations than the mitochondria often have direct formation of superoxide and subsequently, hydrogen peroxide

For antioxidant defense, cells have to maintain a high

NADPH/NADP+ ratio (glutathione reductase uses NADPH to make the oxidixed GS-SG to the reduced form G-SH) - NADPH can be obtained vis Hexose Monophosphate shunt or other pathways (NADP dependent malate dehydrogenase--- remember this DOES NOT exist in RBCs)

Does the entry of fructose and galactose into glycolysis cause a rise in insulin?

NO - they are mostly digestedin the liver.. and their entry into the cell is via the glucose transporter

Can you make glucose from acetyl-coA?

NO - Fat is degraded into Acetyl-coA - YOU CANNOT make glucose from acetyl-coA

Can protein self replicate?

NO! protein cannot replicate and cannot transmit information back to DNA - however DNA and RNA can self-replicate

Is biotin needed to form acetyl-coA from pyruvate (using pyruvate dehydrogenase)

NO!!!! biotin is needed for ATP-dependent carboxylation reactions, such as pyruvate carboxylase

ALL lipids are

NONpolar to some extent - many lipids are also amphipathic where the polar and non-polar parts are segregated within the molecule. Amphipathic lipids are required constituents of: - micelles, vesicles, and bilayer sheets, and other exotic structures

Does the succinate dehydrogenase also use NAD+

NOOO!!! it uses FAD and coenzyme Q

Personal ethics is

NOT biomedical ethics

What happens if there is a large deletion in the DNA loop

NOTHING it just gets shorter

main extracellular cation

Na+

Hydrophobic ligands most often

activate transcription factors of the nuclear hormone receptor family. these are NOT membrane bound receptors

What is the source of oxidative energy

O2 - it creates a proton chemical gradient

Superoxide (O2.-)

O2 is converted to superoxide as a byproduct or for destruction of other molecules - it is reactive, though not the most reactive ROS (this is the Hydroxyl Radical OH.) - Superoxide: will NOT cross membranes because it is an anion but hydrogen peroxide will (superoxide is converted to the less reactive hydrogen peroxide via superoxide dismutase) * Superoxide causes damage to a wide variety of biomolecules (lipids, proteins, DNA)

DNA polymerase epsilon takes over

ONLY on leading strand

ATP synthase is blocked by

Oligomycin (blocks ATPase builds up proton gradient)

Ex of Arsenite poisioning (NOT ARSENTATE)

PDH (pyruvate dehydrogenase) - arsenite (H2AsO3-) binds to reduced lipoic acid and chelates the two sulfurs. This prevents further transferase activity and kills the activity of PDH

Origin sequences on the DNA are bound to the

Origin recognition complex (ORC)

When the baby has NOT been born by the forty weeks from onset of LMP (this is referring to the expected due date for the baby, and is not suggesting anything about the baby or mothers health) - also define as baby being born AFTER 38 weeks post-fertilization (after 38 weeks of pregnancy)

Overdue (aka post-term or post-date)

Fe3+ is more ____ than Fe2+

Oxidized - an oxidized atom is more positive than a reduced one

Oxidative metabolism by ___ enzymes in hepatocytes is a primary mechanizm of drug metabolism

P450 (oxidative demethylation)

all polymerases sit on a

PCNA (proliferating cells nuclear antigen)= trimeric sliding clamp

In an actual replisome

PCNA binds both polymerase delta and epsilon and all copies of PCNA at the replisomes are close to eachother in 3-dimensional space

GIve an example of a membrane lipid

Phosphatidylchoine - polar head group: choline and phosphate - glycerol backbone - fatty acids, the principal hydrophobic component [on these molecules the first flycerol position (1) typically contains a saturated fatty acid (no doube bond) , the middle 2-position will contain a unsaturated fatty acid with a double bond - this is typical for many lipids)

Example of boundary issues

Physicians needs being met before patients needs: - spending more time with attractive patients - scheduling patients outside of reg. hours or giving special late appointments - offering more freq follow up than is medically necessary

Ex of autonomy

Presenting all treatment options to a pt, explaining risks in terms that a pt can understand, ensuring the pt understands risks and agrees to all procedures before going into surgery

during which phase does recombination occur between homologous chromosomes, synaptonemal complexes begin forming

Prophase I

Which enzyme converts pyruvate to Acetyl CoA, describe its function

Pyruvate Dehydrogenase - critical enzyme at focal point between glycolysis and TCA cycle - it functions as an oxidation reaction due to the loss of CO2 from pyruvate, all while adding a CoA PDH utilizes 3 vitamins as cofactors (B1, 2 , 3) a 4th vitamin is part of a substrate (B5) and non-vitamin cofactor, lipoic acid. Deficiencies in these enzymes lead to deficiences in oxidative metabolism and shortage of energy PDH is HIGHLY EXERGONIC. IRREVERSIBLE

What enzyme of the TCA cycle is a biotin requiring enzyme

Pyruvate carboxylase (biotin- Vitamin B7 or H) - biotin is a cofactor commonly found in carboxylation or decarboxylation reactions. It is a vitamin but is common and rarely deficient- if is deficient causes GI symptoms and dermatitis

Give an example of Metabolic regulation via phosphorylation ( a covalent mechanism):

Pyruvate kinase in glycolysis - it is inactivated by phosphorylation (phosphorylation state is regulated by glucagon) - Activated or DEphosphorylated by insulin

trimeric large G proteins are distinguishes from small G-proteins like RAS because

RAS is monomeric and does not have complete intrinsice GTPase, they are therefore regulated by other proteins that permit GTP hydrolysis (like GTPase accelerating protein or GAPs0

What kind of enzyme is telomerase

RNA dependent DNA polymerase (aka reverse transcriptases)

RNA polymerase works only on

RNA nucleotides

Can you describe the activation of an RTK

Receptor tyrosin kinases, RTKs, bind the growth factor, the dimerizes, then autophosphorylates tyrosines. The dimerized and phosphorylates receptor can asseble a "molecular scaffold" of interacting proteins that carry out a variety of cellular functions. In some cases the RTKs molecular scaffold works through signaling pathways like acting through Ras or Tor

Which organ or tissue undergoes OBLIGATORY ANaerobic metabolism?

Red blood cells!!! remember they have NO mitochondria and cannot carry out oxidative phosphorylation - THe brain is less tolerant to anaerobic metabolism it can only survive a few minutes upon oxygen deprivation

Double strnad DNA breakage

Remedy: double strand break repair: recombination repair - non homologous end joining (NHEJ) : DNA ends have come apart, no complimentary sequence is available Homologous recombination uses the second copy of the chormosome as template - micro homology (single displacement annealing)(MMEJ) is used if a small homologous region is found close enough than a single strand invasion occurs and is ued to repair its compliment - large homology is the SAME AS crossing over. uses strand invasion by both DNA strands repairing both strands at same time IF NOT REPAIRED: cells undergo DNA loss and apoptosis

What happens to the ETC if you block Complex I with Rotenone

Remember that Complex II is still free to initiate ETC (provided there is succinate available as the substrate) * so steps in the TCA cycle that generate CoQH2 eill be able to produce ATP (usually most effective only in labs)

FAD

Riboflavin (Vitamin B2) - does transfer of reducing equivalents from lipoic acid to FAD Deficiency sxs: - fissures in the corners of the mouth, inflammation of the tongue showing a reddish purple coloration, skin disease, and often severe irritation of the eyes

Reciprocal vs Robertsonian translocation

Robertsonian: translocation is for acrocentric chromosomes only and essentially is centromere fusion. The centromere fusion is often described as rob (first chromosome; second chromosome) (q10:q10)- in other words the centromere is described as q10 * out of live births: risk is 1/10 for downsyndrome Karyotype: 46XY, rob(14;21)), +21 Reciprocal: for any type of chromosome and involved break points in chromosome arms * almost every case is differnt; developmental defects common - the unbalands version affects multiple genes and leads to multiple affected tissues - common: mental retardation and heart defects - anything is possible! ex: karyotype balanced for: 46,XX,t(8;18)(p21.1;q21.1)

SNOW DROP

Southern Blot- Dna Northern blot- RNA Ooooooooo Western blot- Proteins

In ETC a combination of high mitochondrial NADH and oxidized ubiquinone indicates that electrons cannot be transferred from NADH to ubiquinone. What type of inhibitor could we be dealing/what complex is being blocked?

Rotenone ( a natural insecticide) blocks action of complex I *Amytal would also block complex I *** if complex I is blocked oxygen consumption will decrease some

Synthesis of nuclear DNA occurs in

S phase

This stage of cell cycle is one blocked by cancer chemotherapy drugs designed to block DNA replication

S phase

Unwinding of chromation occurs in

S phase

Which phase of cell cycle typically lasts 6-8 hrs in avg adult

S phase

during which phase of the cell cycle is DNA replicated

S phase, G1 prepares the cell for S phase

Which two cyclin-cdk complexes use cdk1

S-cdk and M-cdk

Which step of glycolysis can arsenic poisoning occur?

STEP 7 Phosphoglycerate Kinase is skipped- no Substrate level phosphorylation - arsenic can form arsenate: AsO43- which is a phosphate analog - arsenate can substitute for phosphate in the transfer reaction transferring an arsenate to the 1-position - however the arsenate bond is labile, and falls apart- giving back 3-phosphoglycerate (3PG) with no ATP production - therefore, arsenate is considered an "uncoupler" because it uncouples the formation of 3PG from ATP production

Psychotherapeutic and Medical Interventions for suicide

Screening and assessment - detection instruments - risk assessment instruments - assessment of clinical characteristics of suicidal behaviors -psychosocial assessment (ex. settings, past history, etc) Psychotherapies: - cognitive behavioral therapy - problem solving/solution focused therapy - dialectical behavior therapy - interpersonal therapy - cultural considerations - faith-based interventions Medication: - mood stabilizers - anti- psychotics - antidepressant Medical treatment - outpt care - acute/inpt acre - electroconvulsive therapy - after-discharge irsk - treatment adherence

Loss of telomeres results in

Senescence - cells no longer replicate DNA nor undergo full cell cycle - Senescent T cells result in compromised immunity since the gene rearrangments required in T cell differentiation would be impossible since replication cannot occur - senescent cells are more susceptible to mutation without repair and thus increased apoptosis

Double strnad break repair diseases

Short stature, microcephaly and endocrin dysfunction (SSMED) - congenital short stature - progressive growth failure - microcephaly at birth - hypergonadotropic hypogonadism - multinodular goiter - diabetes mellitus Axatia-Telangiectasis (A-T) - cerebellar ataxia (early childhood) - thymus hypoplasia - immunodeficiency - lyphoreticular malignancies - sensitivity to ionizing radiation (x-rays) - dilation of small vessels (telangiectasia)

Major nucleotide forms

Small building blocks - ATP, GTP, CTP, UTP and their deoxy forms dTTP etc Cofactors - NAD, FAD, FMN, CoA DNA RNA Amorphous RNAs: -mRNA(long strands- also has a transient structure), siRNA (small)- does post transcriptional regulation , miRNA (microRNA) RNAS with discrete structures: tRNA and rRNA -- all RNAS carry info

Which step of glycolysis is inhibited by fluoride

Step 9- Enolase - this is though to be one action of fluoride that helps to prevent dental karies

Ricin (lectin from castor beans)

Stops elongation and tRNA Binding by breaking the glycosidic bond of A4324 in the 28S rRNA (large subunit) *** bad bc A4324 and its surround sequence is required for binding of elongation factors

Which is the only NON SOLUBLE enzyme of the TCA cycle

Succinate dehydrogenase - it is NOT soluble, but rathet it is a contituent of the inner mitochondrial membrane. The enzyme donates the hydrogen of its FADH2 directly to the respiratory chain intermediate CoQ to for CoQH2

Substrate level phosphorylation step of TCA cycle

Succinate thiokinase (aka succinyl CoA synthetase) - the high energy thioseter bond in the CoA-S-C=O part of the molecule is simply substituted by a phosphate - the high energy phosphate bond is preserved by transer to a histidine on the protein, and then further transferred to the GDP. The product, GTP is equivalent to making an ATP and the phosphate is readily transferred to ADP to make ATP

During what step of TCA cycle is there substrate level phosphorylation

Succinyl-CoA Synthetase (aka Succinate Thiokinase) step - it generate GTP whil converting Succinyl-CoA to Succinate

the last 2-30kb of each chromosome forms a

T-loop (telomeric loop)

Pathway that makes NADH

TCA cycle

The ____ is an important part of AA metabolism

TCA cycle

breakdown of acetyl (acetyl coA) to CO2 with production of reducing equivalents (NADH and CoQH2)

TCA cycle

Coding sequence is manually encoded as

THE SAME EXACT strand going from left to right but wherever there is a T just put a U

if GTP becomes bound and is NOT hydrolyzed even in the presence of GAP

THIS CAN BE a mutation that can lead to cancer

Excess free iron in the body is

TOXIC bc it catalyzes hydroxyl radical formation from superoxide - Fe2+ can be generated by superoxide from free Fe3+ - Fe2+ generates OH. from hydrogen peroxide - hydrogen peroxide is generated normally from superoxide by catalyic action of enzymes

Is the PDH part of glycolysis or TCA cycle

TRICK!! neither

True or false: mitochondrial DNA mutates at a much faster rate than nuclear DNA, increasing the chance of mitochondrial myopathies from mitochondrially enxoded genes

TRUE

true or false: the pryuvate dehydrogenase reaction is irreversible

TRUE

True or false: Delta Gs are additive for sequential and couple reactions

TRUE ! if reaction A --> reaction B has Delta G 1 and reaction B --> reaction C has Delta G2 A --> C Delta G= Delta G1 + Delta G2 *** this is good bc you can compute the standard state free energy for glucose going to pyruvate through glycolysis by simply adding the standard state energies for all the intermediate reactions

True or false: the pyruvate dehydrogenase step makes CO2

TRUE!

ATP is a cosubstrate of PFK-1. ATP is also an inhibitor of PFK-1 at higher concentrations. What explains this phenomenon

There are two sites on PFK-1 that bind ATP: the active site and an allosteric site - as an allosteric inhibitor: ATP doesnt compete with a substrate of the enzymatic reaction but does compete with ADP and AMP, which can displace ATP from the allosteric site and activate the enzyme allosterically

What are PH (HIF prolyl hydroxylases) activated by and used for

These are used in normoxic conditions, PH hydroxylated HIF alpha (hypoxia-inducible factor)- ubiquinating it and sending it to the proteasom to be degraded ** PH is activated by oxygen and uses oxygen. It also requires ascorbate (vitamin C) and iron as cofactors

What is needed for okazaki fragement resolution in eukaryotic dna replication

These enzymes remove the RNA primers at origins and on Okazaki fragments: - Rnase H and FEN1 - ligase

What is needed for elongation in eukaryotic replication

These extend the DNA strand until another strand is encountered - nucleotide triphosphates - Clamp (PCNA) - Dna polymerase delta - DAN polymerase epsilon

Stop codon

UAA, UAG, UGA "u are annoying, u are gross, u go away"

Which are free carriers in the lipid and intermembrane space

Ubiquinone and cytochrome c

In between the oxidized CoQ (ubiquinone) and the reduced CoQH2 (ubiquinol) what can be found

Ubisemiquinone ( a free radical)- it picks up and electron and can combine with H+ ** this free radical form is usually found only when bound to a protein to keep them from reactin covalently to other molecules

Michaelis menten equaton

V= Vmax x [S]/ Km + [S]

competitive inhibition

Vmax unchanged, Km increase

The cell has to know

WHEN TO UNDERGO REPLICATION

Formation of the neural crest cells

WIth fusion of the neural folds, the neural tube separates from the surface ectoderm - cells at the crest of the neuroectoderm dissociate (break away) to form the neural crest (NC) population of cells - these give rise to a host of cell types and structures that will migrate to different parts of the developing embryo - the surface ectoderm will then form the epidermis of the skin and other structures

what can acidosis with hyperventilation suggest

a problem with ATP synthesis that puts glycolysis in overdrive and leads to lactic acidosis (anything below normal blood pH 7.4)

Describe termination of translation

When the "A' site tRNA is a stop codon- termination factors bind the ribosom and the catalytic stage destabilized the complex while the peptide/protein is cleaved from the "P" site tRNA. - the peptide/protein is released

if a father passes on the disease to his son it can not be

X-linked dominant - it would be autosomal dominant - father to son inheritance excludes the X

Nucleotide excision repair (NER) diseases

Xeroderma Pigmentosa - photosensitivity (sunburn in minutes) - skin lesions last weeks - childhood skin cancer Trichothiodystrophy - photosensitivity - rough scaling skin - brittle hair - impaired mental function Cockayne syndrome (CS) - failure to grow/thrive - microcephaly at birth - photosensitivity - premature aging - liver failure if given metronidazole

Describe enzyme up or down-regulation

You can change the amount of enzyme present by altering the expression of the enzyme: can do this by changing DNA transcription or translation of mRNA to protein ex. Cortisol- stimulates or represses protein expression through DNA transcription **** another ex: - rather than changing transcription or translation, the glucose transporter GLUT4 is delivered from internal vesicle stores to the plasma membrane to increase glucose uptake in repsonse to insulin stimulation

The binding equation form hormones/ signals is (the equation is used to compute the extent of receptor binding at a particular ligand concentration, assuming Kd is known)

[RL]= R0 [L]/ [L] + Kd (this can be used to determine the Kd value from the titration data) B= [RL] Bmax= R0

If you are asked which of these structures is RNA what should you look for

a -OH in the 2' position - for DNA it would be a simple -H in the 2' position

Receptor + ligand=

a NONCOVALENT reaction (rather than chemical reactions soooo R+L <- -> RL (this reversed unbinding reaction can be characterized by an equilibrium constant called the binding dissociation constant or Kd (

What is the definition of permaturity

a baby born before 37 weeks from the onset of the last mentrual period (LMP) ** nml would be 40 weeks - can also be defined as baby born before 35 weeks (post-fertilization) aka before 35 weeks of pregnancy ** nml would be 38 weeks after fertilization (38 weeks of pregnancy) -In simple terms: born 3 weeks before their expected due date-

more breakdown than synthesis indicates

a catabolic state that BURNS lean tissues

What is the difference between a chemical gradient and an electrical gradient

a chemical gradient has to do with concentration and a electrical gradient has to do with voltage

Chromosomes in prometaphase is less condensed and shows more bands than

a chromosomes in metaphase

The health and wellness of patients depends on

a collaborative effort between physician and patient - this is the importance of establishing rapport in the physician-patient relationship - this relationship determines the quality and completeness of information that is elicited and understood - mutual respect and trust is critical

What is a shelterin

a complex formed once telomerase has added several kilobases of telomere repeats, a series of proteins bind and shelter the chromosomal ends from destruction by exonucleases and repair by the DNA repair systems- this complex is known as shelterin

For implantation to be completed following the formation of the bilaminar germ disc, the "embryo" is completely embedded in the endometrium, and the defect is closed by

a fibrin plug AKA fibrin coagulum on approximately day 9/10 - this plug must be formed or else a spontaneous abortion could occur * at this point also the bilaminar germ dis is suspended in the blastocyst cavity, separated from the cytotrophoblast above by the amniotic cavity and the cytotrophoblast below by the primitive yolk sac which is formed by the blastocyst cavity

Many origins are used on each chromosome and each replication fork has

a full replisome making leading and lagging strands

Genetic marker

a gene or short sequence of DNA used to identify a chromosome or to locate other genes on a genetic map.

Assembly of smaller molecules like in the case of lipids is dervied by

a large NON-COVALENT assembly of smaller lipids (ex. membranes)

Amylose is

a linear, non-branched chain of glucose molecules connected by alpha (1-4) glycosidic bonds ( it is a much less digestible- (it is more resistant starch)- than amylopectin - amylose forms more compact, less hydrated structures and is digested much slower (fewer end points, and the more compact, less hydrated structure makes it less accessible to digestive enzymes - starchy foods should be cooked in order to hydrate the amylose and amylopection, prior to eating. otherwise it is much less digestible and will be absorbed much more slowly

Redox potential is

a measure of the affinity for electrons

FEN1 is

a nuclease that removes RNA primers

what is assent

a parent/guadrian must consent to the research but a child must assent

Glycogen is

a polymer of glucose. It is the storage form for glucose. Major site of storage is muscle (this glucose ONLY used by muscle) and liver (glucose from the liver is sent to circulation) - its is only a 24 hr supply that is available so other mechanisms for generating glucose must be found on a prolonged fast

Cytochrome P450 (CYPs) is

a superfamily of heme-containing enzymes (many isoforms)- different ones can catalyze different reaction types, but mainly hydroxylation - it has 57 sequenced genes and can be induced and inhibited - it occurs in most tissues (EXCEPT muscles and erythrocytes), the highest amount in the liver (sER) - most are membrane bound

lipid rafts form a

a thicke bilayer that causes some transmembrane proteins to cluster there (need 24-25 hydrophobic AA to cross wider plasma membrane inside lipid raft (as a result transmembrnae proteins with longer domains selectively cluster in lipid rafts (includes many signaling proteins

Fat

a triglyceride, a triester of glycerol and 3 fatty acids. - its MAJOR storge is in adipocytes, but can also be found in liver and muscle (this fat can be used when undergoing movement)

Maltose is made up of

a two glucose linked by alpha (1-4) linkage [this linkage is also found in glycogen] - results from starch/glycogen breakdown in the gut

MHEJ

a type of homologous recombination - double strand break outside of metaphse

Resting metabolic rate (RMR)

a typical person burns ~70 kcal/hr (~300kJ; 1 kcal= 4.184J) per hour during waking. At night this drops somewhat to (~60 kcal/hr)

RNA polymerase requires

a) nucleosomes to be moved out of the way b) transcription regulators to bind DNA c) transcription factors must bind regulators and DNA at start site

Sensitivity

abilitiy to identify the ppl who have the condition "sick" True Positive/ All D+ *** more valuable in situations where it is useful to reduce false negative results (catch all cases)

Specificity

ability to identify people who do NOT have the condition "people who are well" True Negative/ All D- **more valuble in situations where its useful to reduce false positive results (avoid overdiagnosis)

During fasting, your body will rely on glycogen for

about a day and after that will start to breakdown proteins - during fasting, gluconeogenesis starts immediately and then increases production

The intestines role in metabolism is to

absorb nutrients from digested food and pass them on to the liver and blood (so works in food digestions and absorption)

Fat droplets ( a cytoplasmic inclusion) are

accumulations of lipid molecules - they are numerous and large in cells synthesizing alot of lipid

paraphrasing

acknowledges the pts statement via a similar, not exact comment

Microvillis are made of

actin

myosin is a

actin binding protein

Microfilaments are composed of

actin, the most abundant protein in cells of eukaryotes

Glucokinase of hexokinase (in the liver)

adds a phosphate that traps it in the cell

The bases used in DNA are

adenine, cytosine, guanine and thymine

The bases used in RNA are

adenine, cytosine, guanine and uracil

Gi and Gs both regulate

adenylate cyclase

Gsalpha-GTP activates

adenylate cyclase (which makes cAMP)

the principal energy source during the fasted state is

adipose tissue

An activated PKA

affects metabolism (glycogen phosphorylase kinase, pyruvate kinase, phosphofructokinase 2) and transcription

lipids are not soluble in water except as

aggregates in the form of micelles or vesicles or membrane sheets. Even so they are more properly referred to as dispersions rather than having been dissolved

Ligands that activate

agonists

ligand that activates are

agonists

3' exonuclease activity

aids in prood reading ability it removes wrong nucleotides from the 3' end of the new DNA strand right after their incorporation, a mutation in this will cause the mutation rate to go up

the common sugars contain an ____ or ____ within its structure that permits cyclization

aldehyde or ketone (because central carbons in sugars are typically asymmetric- they each constitute a stereocenter- in linear diagrams this is indicated by which direction the hydroxyl group is drawn (to left or right), these are called fischer projections

more synthesis that breakdown indicates

an anabolic state that BUILDS lead tissues

DP1

an enhacer that binds E2F to cause looping to make CDC6, MCM and DNA pol epsilon gene product in late G1 * genes like CDC6 DONT require looping at some stages of cell cylce

Karyotype

an ordered display of all chromosomes from one cell - chromosomes are ordered according to size and postiion of centromere - metacentric (in middle) - submetacentric (between middle and end) - acrocentric (towards top)- has satellites at top (these contain genes for rRNA

Migration of sister chromatids toward opp. poles and separation of paired kinetochores occurs in

anaphase

When CREB is phosphorylated it can bind to CRE

and activate the transcription machinery ** CREB is most common, enhancer (E2F second most common)

The TCA cycle takes a 2C Acetyl CoA

and combines it with a 4C oxaloacetate to make a 6C citrate, rearranges to isocitrate then goes on through cycle losing 2 CO2 at two different steps all while harvesting reducing equivalents

Ligands that prevent activation are

antagonists

ligand that prevents activation are

antagonists

the middle loop of the mature tRNA is called the

anti-codon loop * encodes the complimentary sequence to the mRNA codon

the template sequence is manually encoded as the

antiparallel (5' for new strand will be on the right) sequence remember starts 5' --> 3' (always looking for AUG (on template this is TAC- remember to translate strand backwards) unless told you are in the middle of the strand) rememeber in RNA T's turn into Us (A-U)

in order to form a stable duplex with a DNA fragment the sequences must be

antiparallel and complimentary

Mosaic

anyone that has two cell lines that differ from each other but originated in the same zygote

blebbing happens only is

apoptosis - cell shrinkage - plasma membrane blebbing (caused by detachment of plasma membrand from underlying actin filmanets of the cell cytoskeleton) - aggregation of chromatin - fragmentation of the nucleus - oligonucleosomal DNA fragmentaion - caspase cascade activation *** in apoptosis the dead or dying cell is phagocytosed by macrophages [ phosphatidylsering (PS) on extracellular leaflet acts as eat me signal] - there is NOOO leakage of cellular contents or inflammation like in necrosis, apoptotic cell death is imperceptible to the organism "hiding the corpse" (W/O triggering inflammation) * these changes are seen when the effectors (caspases) are activated [caspase cascade- one can activate many]

Interphase chromosomes

are all NOT condensed (therefore both copies of nomral genes are active) - EXCEPT the Barr body (it stays condensed even after other chromosomes in interphase)

Hydrophilic cell signals

are carried in the circulation, they require cell surface/membrane receptors to transmit the signal or they can be transported inside the cell by endocytosis

the rER and sER

are connected directly and can exchange material by diffusion

Type I nuclear hormone (intracellular) receptors

are in the cytosol bound to heat shock proteins before they are bound and then they move into nucleus once bound

Hydrophobic cell signals

are transported by carrier proteins these can diffuse through the membrane to carry out signaling (ligands like this can act as transcriptional activators/repressors) Ex: testosterone, estrogen - these sometimes need an intracellular signal but NO call surface receptor like what is needed for hydrophilic ligands

Replication typically progresses at a rate of 2000 nt per sec thus many origins

are used to copy the 3.2 billion base pairs of the human genome

facultative heterochromatin

area that is heterochromatin in some cells and euchromatin in other cells

Which AA is found in the interace between polar/nonpolar regions

aromatic ones - phenylalanine (phe, F) - Tyrosine (tyr, Y) - tryptophan (trp, W)

Overexpression of Myc, p21, and Wee1 results in cells

arrested in G1 or forced into G0 due to the inhibition of the cyclins

Arsenate is different from arsenite bc

arsenate has 4 oxygens while arsenite has 3. Arsenate has NOTHING to do with PDH - arsenate substitutes for phosphate, uncouples both oxidate and substrate level phosphorylation (arsenate prevents phosphoglycerate kinase in glycolysis from carrying out ATP production)

Sacrococcygeal Tetratoma (SCT)

as grastrulation is nearing completion the primitive streak diminishes in size (small insignificant structure in sarcococcygeal region)- it normally disappears by end of week 4 - remnant or primitive streak may persist and give rise to this tumour (SCT) - it is most common tumour of new born (1/35-40,000 live births; 80% in females) THESE ARE NONMALIGNANT AND NOT TO BE CONFUSED WITH - Chordomas (bone tumors that develop from remnant of the notochord)- located in the lumbosacral region, or less commonly at the base of the skull (30% MALIGNANT and poor prognosis)

During week 2 as implementation is STILL occuring (not completed yet)

as the cell mass is differentiating into epiblast and hypoblast, a small cavity appears within the epiblast. This cavity enlarges to become the amniotic cavity and the cells along the margin of the cavity are called amnioblasts which forms the amniotic membrane (amnion) * the AMNION= a PROTECTIVE MEMBRAN which eventually surrounds the entire embryo. It begins to develop on the 8th day ** remember at this point you have NOT finished implantation

HIF-alpha is marked for destruction through an oxygen-dependent reaction that hydroxylated prolines (prolyl hydroxylase). Like the prolyl hydroxylase that modifies collage, this enzyme also requires

ascorbate (vitamin C)

At what types of steps does regulation most occur

at exergonic steps (strong negative delta G- meaning they are biologically irreversible, and strongly favorable) - most regulation occurs by changing enzyme activity Ex: in glycolysis the main regulatory steps are exergonic - Hexokinase - Phosphofructokinase (PFK or PFK1) - Pyruvate kinase

The centromic DNA (which is highly repetitive)

attaches to the kinetochore and separates chromosomes in M phase

active listening includes

attending to verbal and non-verbal cues

talking to yourself is like

autocrine signaling

BER

base excision repair - if persists into G2 - fixes single base problems - uses AP endonucleas to cleave DNA and repair - MutS is used- removes base while leaving the sugar phosphate intact ** repairs mis-incorporate base of modified base- occurs at any time in cell cycel

what are two ways of protecting RNA from degradation

base pair the strands to protect them (ex. in tRNA the 5' end is protected by base pairing) - or you can block the ends to protect them (5' cap on mRNA)

B form DNA (form most commonly used- it is used by Watson & crick) is made by

base pairing (hydrogen bonding of a purine to a pyrimidine on the opposite strand) NOTE: other forms of helix are possible and helices of different types are used to regulate the use of nucleic acid differentially

Male pts with hemizygous X-linked G6P-dehydrogenase deficiency, have pathologic consequences that are more apparent in erythrocytes than in other cells, such as liver cells. What explains this

bc erythrocytes lack a mitochondria, they rely on the HMP pathway for ATP production

Describe why hemolytic anemia occurs in erythrocytes during oxidative stress

bc they are highly dependent on using the HMP shunt to maintain high NADPH/NADP+ ratios. (they have no mitochondria or other enzymes that can generate NADPH) sooo a deficiency in HMP enzyme glucose-6- phosphate dehydrogenase results in weakened anti-oxidant capacity - a high oxidant load can deplete the NADPH and cause oxidativ stress- ultimately weakening membrane integrity and causing protein oxidative damage

FRUCTOSE WILL NOT

be converted into glycogen

Why are disulfide bonds unable to form in the cytosol

because it is a reducing environment

Increased use of the Polyol Pathways reduces NADPH levels

because it is used with aldose reductase in converting glucose into sorbitol reduction of NADPH: - affects the intracellular redox state: less GSH (Glutathione (GSH) is a thiol that plays several major roles in the cell, including maintenance of the redox balance, fighting reactive oxygen and nitrogen species, and the detoxification of many other toxins and stress-inducing factor) - more ROS - Less NO made - More subject to oxidative stress

Why is DNA rarly ever in the naked DNA double helix form

because its so fragile without protein- it only exsists this way the instant before and after a protein binds it

Epinephrine can activate both

beta- and alpha- adrenergic receptors and both acan make an impact of adenylate cyalse. Whether it goes up or down depens on the particular response of the cell - how many of each receptor type - their location - the concentration of epinephrine - timing of the response

Fatty acid degradation is called

beta-oxidation and is carried out to use fat for energy

The zygote (fertilized egg) starts as a single cell and undergoes a series of rapid mitotic divisions leading to 2-cell, 4-cell, ...16 cell stage etc. With each mitotic division the cytoplasm is partitioned (cleaved) to form increasingly smaller and more compacted ___

blastomeres - these are compacted and cannot expand because of the zona pellucida

What to complexes contribute to CoQH2

both NADH dehydrogenase and succinate dehydrogenase make CoQH2 - succinate dehydrogenase is part of the TCA cycle - ALL the CoQH2 goe to cytochrome b-c1 complex *** If NADH dehydrogenase not working you can still get CoQH2 from succinate dehydrogenase and vice veras

primary transcripts contain

both exons and introns and end at a poly adenylation/termination sequence

Template strand

bound by RNA polymerase and used for base pairing of nucleotides during transcription *** rememeber A pairs with U in RNA (NO T's) * growing RNA is assembled 5' --> 3', antiparallel to template strand

phosphodiesterases

break cAMP to AMP- reversing its formation * these also usually break cGMP to GMP (Viagra works here by inhibiting the phosphodiesterase, keeping the cGMP level high and causing increased relaxation

The TCA cycle is

break down of acetyl (Acetyl coA) to CO2 with production of reducing equivalents (NADH and CoQH2). In mitochondria

Beta oxidation is the

breakdown of fatty acids to Acetyl CoA; this takes place in the mitochondria. It ultimately makes energy (ATP) from fat stores

Glycogenolysis

breakdown of glycogen for supplying glucose to circulation (liver) or for immediate energy needs (muslce)

During prometaphse the

breakdown of the nuclear envelope occurs

catabolism

breaking down (complex --> simple)

During the 1st and 2nd week of development the syncytiotrophoblast

breaks down the endometrial lining to allow incorporation of the blastocyst into the uterine wall (i.e. implant)

anabolism

building up ( simple --> complex)

DNA is written 5' to 3' so when asked for the complementary strand you will be looking for a match

but in the 3' to 5' (first nucleotide in the synthesized DNA should be complementary to the last nucleotide in the template strands)

What enzyme combines oxaloacetate + AcCoA to give citrate

citrate synthat - regulated via product inhibition by citrate

Prior to NO being made

cGMP is upregulated in the target cells - calcium rise, Gq is activated and IP3 and DAG increase

BOTH Galpha-GTP and Betagamma

can act as to stimulate downstream effectors

DNA bending

can cause an enhancer element that is far from the promoter in the linear DNA molecule to interact with transcription-initiation complex, stimulating transcription

Macromolecules

can form large complex structures. They typically are chemical polymers of a limited set of monomers, OR noncovalent assemblies of smaller units (ex. membranes)

Different receptors receiving a hormone or neurotransmitters

can give a variety of effects depending on the location of the body depending on the receptors and intracellular mechanisms in place

What are the 5 fates of pyruvate

can go to - lactate (anaerobic metabolism) - in muscles and liver - acetyl-coA for aerobic enegy production, fatty acid synthesis (TCA cycle- energy) - oxaloacetate- anaplerotic reactions (refilling of TCA intermediates) or the first reaction point of gluconeogenesis (liver glucose production- gluconeogenesis) - Ethanol- in microorganisms during fermentation, which occurs anarobically- in microbes - Alanine- via the enzyme alanine transaminase (ALT) for nitrogen transport ----- the direction pyruvate goes is determined by hormonal and local regulation---

Telomerase is reactivated in

cancers

Insufficient apoptosis is seen in

cancers such as breast cancer and lymphoma, and also in autoimmune diseases, such as rheumatoid arthritis and systemic lupus erythematosus - HIV/AIDS involves apoptotic depletion of CD4+ helper T cells

recognition of ______ as antigens can be an important aspect of immune recognition as foreign or self

carbohydrates

Difference between chemical and electrical gradient

chemical has to do with concentration, electrical has to do with voltage

The TCA cycle completes the

chemical oxidation of glucose (and other things) - all the acetyl thats fed in is turned into CO2 - as we oxidize food, we harvested the reducing equivalents in the forms of NADH, FADH2, or CoQH2 - the reducing equivalents are then combined with oxygen in oxidative phosphorylation to make ATP

Cytochrome P450 (CYPs) work on unusual

chemicals (drugs, poisonous compounds, carcinogens obtained from eating and breathing) it converts them to a form (by adding oxygen) more readily flushed from the body ( makes them more H20 soluble- and more easily washed out)

Phospholipase C mediates

cleavage of the headgroup between the glycerol and the and the phosphate - ex. it cleaves PIP2 to generate IP3 and DAG

Polar amino acids

cluster on the surface of soluble proteins

only 1.5% or less of the human genome is used for

coding proteins= mRNA

for females suicide rate

comes up at 50 then goes back down

the probe and the sequence to which it hybridizes must be

complementary to eachother and can be DNA or RNA. Usually the probe is DNA since DNA is more stable than RNA, but a DNA probe can hybridize to RNA as well as DNA. Introns are composed of nucleotides and on can design a probe that will hybridize to intronic sequences

What does Complex IV, Cytochrome oxidase do

completes the oxidation process- synthesizes water from oxygen and electrons and protons -- Complex IV received electrons from 4 cytochrome C (one at a time through same binding site) - takes up 8 protons- 4 pumped, 4 go to water - an iron copper center takes up the electrons to feed them to oxygen * oxygen is thought to get in via successive oxidation and reduction of the heme iron and the bound oxygen, the energy lost from elecctrons causes conformational changes that result in proton pumping

For tRNA and rRNA it folds into a mature 3-dimensional form as soon as the

complimentary sequence of RNA is released from the D-loop, well before the transcript is completed - polycistronic (= more than one RNA per transcript) RNA is cut into smaller RNA

Institutional review board (IRB) what is it what does it do

composed of at least 5 member with varying backgrounds including a scientist, a non scientist, and a community member responsibilites: - is proposed experiment ethical - does it present an undue risk to participants - are study questions valid - are researchers qualified - are risks proportionate to anticipated benefits - periodic review: monitor data collection to endure participant safety and well-being

Antagonist

compound that blocks the action of an agonist ex. propranolol is an antagonist for beta- adrenergic receptors * antagonists bind competitively to same site as agonist but DO NOT cause normal downstream response. DO NOT cause allosteric change to an active conformation. They CAN block the action of agonists because they bind the site and block agonists from binding (similar to and enzyme competitive inhibitor)

Inverse agonist

compound that decreases the activity of a receptor, it stabilizes the inactive form of the receptor ex. for some GPCRs (like histamine H3) this can decrease the baseline activity (activity in the absence of any lignad) - thus inverse agonists are only relevant for receptors that have some activity even in the absence of agonists

what is the tightest packing on DNA

deacetylated histones and methylated DNA

suicide inhibitors

decrease vmax, km unchanged (like non-competitive inhibition)

uncompetitive inhibition

decreased km and vmax

noncompetitive inhibition

decreased vmax, km unchanged

Acetylation H4

decreases compaction (DNA must be unpacked- decondensed- to allow proteins to act on the DNA)

Acetate from acetyl coA is

degraded to CO2 in the TCA cycle

NAD is the most common cofactor of

dehydrogenases (these are enzymes that transfer hydrogen from a substrate to NAD+ )

the total energy available from a proton

delta G= -4.6kcal/mol -- anout 3H+/ATP

Ethanol and methanol are both

designed for substrate ADH (act competitively with eachother) ethanol is more efficiently digested

Southern blots CANNOT

detect whether a gene is expressed or not ** they only detect genetic material (unexpressed DNA) - they CANNOT detect either part of gene expression, transcription or translation **sooo they would not be used to compare cancer cells to normal cells

Depending on their exact shape amphipathic molecules can be classified as:

detergents: tend to form micelles or membranous lipids: can form bilayers as vesicles or membranes

different cut points yield

different sensitivities and specificities

restriction enzymes create

double stranded DNA breaks from cleaving both strands of duplex DNA - some restriction enzymes create "sticky ends" when the cut creates a 3' or 5' overhanging single-stranded end, while other restriction enzymes create "blunt ends" if the restriction site is methylated, the restriction enzyme will not cut the restriction sequence

Alpha means the -OH is pointing

down

dynein

drags molecules in

Chromatin forms

duplicated chromosomes after association with centromeres as the DNA is prepared for cell division

role of calcium in muscle

during muscle contraction, Ca2+ is release from the sacroplasmic reticulum. it then binds to the calmodulin subunit of phosphorylase kinase activating it without phosphorylation. Phosphorylase kinase can then activate glycogen phosphorylase, causing glycogen degradation

In translation what does something written as eIF# , EF#, TF# signifiy

eIF#= facute used in translation initiation ** eIF2= initiation factor that catalyzes GTP and puts the 60S subunit onto the 40s/tRNA/mRNA complex EF#= factor used in translation elongation ** EF2 or eEF2= translation factor that catalyzes GTP to move the ribosome/tRNA/mRNA complex one codon toward the 3' end of the transcript TF#= factor used for translation termination (NOT roman numeral, roman numeral is for transcription) ** TF2 and eTF2 assists TF1 and TF3 in recognizing a stop codon then causing the realease of the peptide, tRNAs and the ribosome subunits from the mRNA

if you dont use it, you lose it! this is a general feature of

every organelle, in every cell - when a cell needs more of one type of organelle, it will make more of that type - when it needs less it will degrade that type by a process called autophagy (this keeps cell from wasting energy by having organelles it doesnt need)

Describe how an antioxidant can work

ex. Vitamin C, ascorbate ( a soluble antioxidant vitamin) - antioxidants scavenge free radicals. They do do by forming a free radical that is insufficiently reactive to cause damage, but reactive enough to destroy other, more dangerous free radicals - so Vitamin C (or ascorbic acid) goes through stable free radical intermediates and ends up as Dehydroascorbic acid (which is an oxidized form that you can get rid of)

Locus Heterogeneity

ex. deaf mutism (aka congenital deafness) - theere is likely to be ~100 diff genetic conditions that lead to cong. deafness in these cases - there are two or more genes that can lead to the same outcome - for variation there is atleast one bad allele per gene - the phenotype produced is the same *** caused by invovlement of diff loci= diff genes (sx's should be idneitcal)

locus heterogeneity (same concept of linkage heterogeneity)

ex. one gene name in one family and a different gene name in a different family - if there is only ONE gene name this indicated it is not locus heterogeneity

Trisomy

excess of one chromosomes - only trisomy of 13,18,21, or C,Y are compatible with life ** in trisomy 21, 80% of conceptions die in utero - trisomy 16 is the most common of all (it is common at the time of zygote formation and in investigation of spontaneous abortions) ** not all non-disjunctions show a maternal age effect, with trisomy 16 as one important exception

Class I nuclear receptors

exist in the cytosol pre-bound with HSP90. Hormone binding releases HSP90 and the receptor then dimerizes and is translocated to the nucleus

__ are the mRNA degradation system

exosomes

Hepatocytes in the liver do much/most of the detoxification in the body because they

filter all of the ingested material coming from the gut (absorbed food substances - like sugars and AA) are transported via the hepatic portal vein to the liver- fats are transported through the lacteal into the lymphatic system)

CIrculating glucose in the blood is stored as

glycogen in muscle and converted to fatty acids and stored as triglyceride in adipose and liver

The transfer of electrons down the ETC results in

export of protons from the mitochondrial matrix into the intra-membrane space (the matrix is relatively more basic)

Both mRNA and tRNA are spliced and have

extra bases added to the 3' ends mRNA: 3' poly A tRNA: 3' CCA or UCA added

After going through the entire secretory pathway proteins are secreted into the

extracellular space

The Extraembryonic mesodermal layer is also formed by it is uncertain which cells undergo mitosis to form it (could be maybe epiblast/hypoblasts) but cavities are formed within this layer to form the

extraembryonic cavity - further rearrangement via programmed cell death of bridged in the extraembryonic mesodermal layer then results in the primitive yolk sac becoming the secondary yolk sac & the extraembryonic cavity is now called the chorionic cavity - the extraembryonic mesoderm that lines the inside of the cytotrophoblast is now known as the Chorionic Plate

The preferred energy source in the fasted state

fat

Since fructose is NOT converted to glycogen what is the excess converted to

fat - it is usually present in the fed state, and glycolysis is active- this is why it is not converted to glycogen

During LONG fasting and starvation

fat (adipose breaks TAG into fatty acids) is the main energy source for most organs EXCEPT - brain CANNOT use fatty acids as energy source - RBCs are exclusively dependent on glycolysis and glucose for their energy (they have no mitochondria and cant undergo beta oxidation to break down fat

name for cytoplasmic inclusion seen in cells making alot of lipid

fat droplets - considered a cytoplasmic inclusion because it is NOT surrounded by a membrane (*remember glycogen rosettes were another type of cytoplasmic inclusion)

suicide

fatal self-inflicted destructive act with explicit or inferred intent to die 1:11 suicide attempts will be carried out to completion

The main fuel for the body during fasting and for muscles during exercise

fatty acids

> 100.4 degrees F

febrile below this is afebrile

AA catabolism occurs in the

fed or fasted state

Fat synthesis occurs in the

fed state and requires reducing equivalents made by the hexose monophosphate shunt

sympathy is

feeling sorry for someone

Pregnancy begins when the

female egg (oocyte) is fertilized by the male spermatozoon (single sperm). It is then called a zygote

What two ways can cholesterol be made in the body

first off it is made in the sER - slightly less than half of the cholesterol in the body derived from biosynthesis de novo (ENDOGENOUS cholesterol) - we do this still even if we dont eat cholesterol - the rest of the cholesterol is taken up from food per day (EXOGENOUS cholesterol)

which small nuclear ribonucleoprotiens are in charge of splicing

first splicesomes (snRNA) bind the intron canonical sequence then snRNPs recognize 5' and 3' splice sites - the type used along with the proteins that bind the RNA determine which exons are fused to eachother, this leads to alternate splicing of mRNA for physciological needs

NHEJ

fixes double strand break outside of metaphase

HR

fixes double strnad break

Global nucleotide excision repair (GNER)

fixes large molecules attached to DNA, mismatches or intercalators- XPC looks for abnormal helix

G2

follows S phase and is where the DNA is where replication is checked and the cell is prepared for mitosis and cytokinesis

eIF4G and eIF4F make a complex and circularize RNA what is this essential for

for getting the RNA out of the nucleus - exportins wont take it out of nucleus till it is circularized

Neuroectoderm derivatives

forms neural tube - CNS - retina and optic nerve - neurohypophysis (posterior pituitary) - astrocytes - oligodendrocytes (CNS myelin)

phosphate deoxyribose

forms the backbone linkages at the 5' and 3' postions of the ribose or deoxyribose

Where in body could the polyol pathway be seen

fructose is found in high concentrations in seminal fluid. Seminal vesicles use two enzymes to produce fructose from glucose. Sperm use the fructose as an energy source

Accuracy

function of the tests sensitivity and specificity (as well as the conditions prevalance) (TP + TN)/ ALL

Reduction is

gain of electrion (OIL RIG)

What two sugars can also feed into glycolysis

galactose and fructose

What two sugars feed into glycolysis

galactose and fructose

What are the most imporatnt "selectable markers' used in recombinant DNA technology when using bacteria

genes for antibiotic resistance enables the reasearcher to easily identify bacteria that contain cloned DNA fragments. Only bacteria that have been transformed with a vector containing the antibiotic resistance gene will grow on the antibiotic containing medium

Transposobal regions of DNA (which make up 11%- they are moving "jumping" genes) these may cause

genomic changes when they are inserted or excised causing: - increase or decrease the spacing between regulatory units from genes (changing expression) - insert or delete protein coding regions changing exons (may alter protein function, localization or regulation - alter gene expression by creating pseudogens (non-functional gene copis or non-expressed copies)

Where does a mutation have to occur to be inheritable

germ line cells

Our bodies need to use two types of metabolism what are they, and which trumps the other?

global and local regulation LOCAL will trump global bc for example if a local hepatocyte has NO ATP it will not make fat even if globally it is being signaled to do so

the principal signaling molecule during the fasted state is

glucagon

In the FASTING state the main signaling molecule is

glucagon from the alpha cells

The activity of glucokinase as a function of glucose conc. vs the activity of hexokinase..how do the differ on graph

glucokinase shows cooperative binding and hexokinase is a saturation curve

The brain and blood cells require a constant source of

glucose

The prefereed energy source in the fed state

glucose

Sucrose is made up of

glucose and fructose connected by a alpha (1-2) linkage - found in table sugar, made from sugar cane or beets - sucrose is NON-REDUCING because the anomeric carbons in glucose and fructose are tied up in glycosidic bonds (as a result neither glucose nor fructose can linearize to form an aldehyde or ketone

Lactose is made up of

glucose and galactose connected by a beta (1-4) linkage - note that lactose intolerance is common in adults due to lack of lactase - Lactose is found in milk sugar, digested by lactase in the gut in infants - this is a reducing sugar

Glucagon signals

glucose production by the liver from glycogen store or gluconeogenesis

Glycogen is

glucose storage in animals. it is linear alpha (1-4) glucose chains, plus branches formed by alpha (1-6) glycosidic bonds [these branches occur more often than in amylopectin, occuring ever 8-12 residues - this means more free ends, and more hydrated dendrimer-

Amylopectin is

glucose storage in plants that animals CAN digest - alpha (1-4) glycosidic bonds with branch points of alpha (1-6) glycosidic bonds [ these branches occur every 24-30 glucose residues)

Insulin works to increase the number of

glucose transporters available

Galactose feed into glycolysis at the level of

glucose-6-phosphate * it can be used for energy or glycogen storage

Fructose feeds into glycolysis at

glyceraldehyde-3-phosphate ** when fructose comes in you dont have the option to store it as glycogen- so any excess fructose gets stored as fat..and this is why fructose gets a bad rep

___ is used as the first pass energy resource when we go into a fasting state

glycogen

polar organic molecules, sugar ions (H+, Na+ , K+ , Ca2+, Cl-), proteins, and other large molecules

have difficulty passing via simple diffusion through the hydrophbic plasma membrane

Ruisse and guinea

have increases suicide rates - china and india make up about 50%

for the suicide inquiry no matter what you always ask #6 what is this

have you done anything or started to do anything, or prepared to do anything to end your life? (ex. collect pills, buy gun, etc)

Folding of the trilaminar derm dic can be done via

head folding or tail folding

methylated DNA=

heterochromatin

pathway that makes NADPH

hexose monophosphate shunt (HMP)

pathway whose purpose is to 1) make reducing equivalents in the form of NADPH and 2) make ribose

hexose monophosphate shunt (HMP) also called the pentose phosphate pathway (PPP)

Hexokinase transfers the phosphate to

hexoses - NOT possible with free phsophate and hexose (for energetic reasons)

140/90

high: stage 1 hypertension

180+/120+

high: stage 2 hypertension

decreased km means

higher affinity

A high C and G content would

increase DNA methylation and reduce episomal arrangements of nucleosomes

G1 phase is characterized by

increase in cell size and duplication of organelles (occurs prior to rep. in S phase)

unsaturated fatty acids

increase membrane fluidity

Describe the process of glucose entering from digestion (carbohydrate flow among organs in the FED state)

increased glucose from digestion is delivered from intestines through the portal circulation to the liver, the liver buffers the amount of glucose going into the circulation - Excess glucose in the liver is stored as glycogen and converted to fat and exported as VLDL to adipose tissue - High circulating glucose enters pancreatic beta-cells and signals insulin secretion (insulin is secreted in response to high glucose)

What could be involved ina possible loss of cell cycle control that occurs in prostate carcinoma?

increased transcripiton of gene regulatory proteins such as E2F

Methylation of Cytosine

increases DNA compaction

Complexes I, II, III, IV are

independent

Each side of the origin of replication forms an

independent replication fork

Nucleotides function in

information storage in DNA, information transfer (transcription to mRNA), and translation from rRNA and tRNA to protein - catalytic (enzymatic) function - energy transduction (ATP) - cofactors (NADH)

alpha- adrenergic receptors

inhibit adenylate cyclase with help from Gi

What does decreased NAD+ and increased NADH do to the TCA cycle

inhibit it

What activates/inhibits alpha-keto glutarate dehydrogenase complex

inhibited by: NADH and succinyl CoA (products) Activated by: Ca2+

If eIF4G (subunit of eIF4) is lost or phosphorylated then

initiation and re-initiation are aborted (stopping translation) - eIF4G cleaved by caspase 3 occurs in apoptosis - cleavage by some viral proteases (ex. polio) eIF4G is utilized in a different way for IRES mediated intitiation - viral may cut eIF4g, removes regulatory sites and stops host 5' cap dependent transcription - breast cancer has a concomitant rise in IRES (internal ribosome entry site) containing mRNA and an elevation of eIF4G

In the polio virus

initiation factor 4 (eIF4G) is proteolyzed to prevent reinitiating of host mRNAs - and instead initiates transcription on IRES (stress response trancripts whose proteins lead to apoptosis) * there is no re-initiation of 5'cap containing mRNA in cytoplasm

The bilaminar germ disc is made up of

inner cell mass splitting into epiblast and hypoblast layer

The electron transport chain occurs in the

inner mitochondrial membrane

ETC generated a proton chemical gradient across the

inner mitochondrial membrane - high proton concentration on the outside (intermembrane space/cytosol); low concentration in the matrix (typical diff is 10 fold or about 1pH unit- this is the chemical gradient - positive voltage on the outside relative to the inside because protons are exported. the voltage is conventionally given as inside relative to the outside, so it is a negative voltage (~200mv) this is the electrical gradient - electrical gradient across membrane affects transport of other charge substrates ** we get less energy out of pH gradient than charge gradient

Frameshift mutations

insertions or deletions of nucleotides may result in a shift in the reading frame or insertion of a stop codon * many result in shortened protein bc new frame has stop codon * all frame shifts change the AA sequence

Anbolism occurs in the fed state and is promoted by

insulin

Expression of glucokinase is upregulated by

insulin

In skeletal and cardiac MUSCLE and ADIPOSE tissue

insulin induces the transport of GLUT4 from the endosome to the plasma membrane - this increases the uptake of glucose - GLUT1 provides the basal uptake

Tertiary structure is driven by

interactions of side chains - this is domain structure

Keratins are

intermediate filaments that allow for mechanical stabilitiy to the cell and resist stretching, allowing the cell to respond to tension

Nuclear hormone receptor ligands aka

intracellular receptors ( respond to hydrophobic ligands - such as steroids like cortisol, estradiol , testosterone..and also vitamin D3, thyroxine "a thyroid hormone" and retinoic acid which is derived from vitamin A

G protein coupled receptor signaling has

intrinsic GTPase activity- GTP hydrolysis (an activated alpha subunit attached to GTP has effector activation it can go activate more g-proteins or other things

mature mRNA does NOT have

intronic sequences

Receptor-mediated endocytosis of ligand-receptor complexes is a selective process that requires

invagination of the cell membrane to form clathrin-coated pits and vesicles ex. LDL

What is the Haber-Weiss rection

iron catalysis of hydroxyl radical formation from superoxide

Describe the Polyol Pathway (fructose biosynthesis)

it is the synthesis of sorbitol and fructose - sorbitol is an intermediate metabolite, BUT can accumulate in some cells during hyperglycemia: hyperglycemia is associated with diabetes and some of the pathology associated with diabetic hyperglycemia can be attributed, in part at least, to the effects of sorbitol accumulation and activation of the polyol pathway ----In cells with insulin insensitive glucose transport (liver, lens, kidney, and neurons): high circulating glucose leads to high intracellular glucose which then activates and puches the aldose reductase reaction towards sorbitol. Only some cells will have aldose reductase, and not all cells that have aldose reductase will have sorbitol dehydrogenase (ones without sorbitol dehydrogenase have a build up of sorbitol)

Since the Malate Dehydrogenase step of the TCA cycle has an unfavorable equilibrium what happens to the concentration of oxaloacetate in the mitochondria

it is very low - however [NAD+] is about 5x higher than [NADH] and this helps to drive the reaction OXALOACETATE IS NOOTTTTTTT increased during the TCA cycle

When pyruvate is converted to lactate what happens to blood pH

it lowers pH due to lactic acidosis

How does acyclovir act to stop the production of the herpes virus

it misses the 3'OH so what guanosine tries to incorporate it stops production, you NEED a 3'OH to continue adding bases (nucleotides will be incorporated but this will ALWAYS BE THE LAST BASE (chain terminators)

What must a cyclin do in order for it to be degraded

it must first activate a cdk. The activated Cdk phosphorylates proteins which in turn ubiquinate the cyclin. The ubiquinated cyclin is targeted to the proteasome to be degraded

if a new protein is destined for the ER

it must have a N-terminal signal sequence on the peptide - the ER targeting requires a signal peptide in amino terminus of protein which binds the signal recognition particle (SRP) - SRP releasese the signal peptide sequence and feeds it into the translocon of the ER - generally the singal sequence is removed after entry into the ER * pH inside the ER is optimal for formation of disulfide bonds

What does CKI do

it put a break on the cell, it inhibits bound cyclin dependent kinases which would usually work to phosphorylate Rb Phosphorylation of Rb allows it to dissociate from E2F which will go on and stimulate movement in the cell cycle BUT in the presence of CKI.. None of this happens :/ sooo the Rb is stuck with E2F till further notice

The TCA cycle requires transport of substrates into the mitochondrion, what are these

it req - pyruvate from glycolysis - fatty acids from circulation- carnitine shuttle these go through specific carriers and require assistance from the proton gradient establishe by the electron transport chain - the electron generated (reducing equivalents= high energy electron) drive proton transport

Describe further differentiation of the lateral plate mesoderm

it splits into 2 layers as a result of Coelomic spaces fusing 1. Parietal (somatic) layer 2. Visceral (splanchic) layer * these layers line the intraembryonic cavity and surround organs - the parietal layer plus overlying ectoderm form the lateral and ventral body walls - the visceral layer and the underlying endoderm for the wall of the gut tube * if no spaces- no division

What does insulin do to glycolysis

it works in adipose tissue, muscle and liver to ACTIVATE glycolysis - it is active in the fed state (when there is high circulating glucose) - upregulates Glut4 transporters - activates PFK1 - activates pyruvate kinase - increases glucokinase synthesis - is pleiotropic (has multiple effects on other metabolic paths, generally is anabolic and increases synthesis)

Citrate synthase can be inhibited by

its own product citrate * citrate can also move out of the mitochondria and inhibit phosphofructokinase

desmosomes

join the intermediate filaments in one cell to those in a nieghbor cell

protein, carbs and lipids are

key structural components of the body and major energy sourves in our foods

kinesin

kicks moleculse out

Fructose intolerance

lack of fructokinase - benign condition (1: 130,000, Autosomal recessive) - fructose in urine

Monosomy

lack of one chromosome - only monosomy X is compatible with life (more than 99% of these die in utero)

One of the affects are arsenite poisoning is

lactic acidosis, which accounts for the reduced blood pH

When two replication forks meet the

lagging strand DNA of one fork is ligated to the leading strand of the neighboring fork

Hutchinson gilford progeria syndrom (HGPS) is due to a mutation in

lamin A protein ( a nuclear lamin that makes the nuclear lamina) - inadequaate structural support for nuclear envelope causes it to take abnormal shape - could cause problems with mitosis- ppl with this have an appearance of aging beging in childhood

hnRNA

largest class of RNA - this is partially matured or nascent RNA- from here theyre processed into mRNA, rRNA, or tRNA

Rank DNA in its Least complex form to its most complex form

least complex is: DNA sequence (ACGC pattern) - DNA base pairing - DNA helical type - histone mediated packing - chromatin Most complex: chromosome

GPCR inactivation mecahnism

ligand dissociates, terminating the signal --> stimulates GRK to phosphorylate GPCR on multiple sites, tags it for arrestin binding, arrestin binds to the phosphorylated GPCR and inactivates the protein. So GPCR is desensitized to the ligand even if its concentration increases --> endocytosis leading to either internal storage and recycling or leading to lysosomal degradation - most GPCRS can be inactivated by one or more of these mechanisms

The number of unsaturated fatty acids and their degree of unsaturation contributes to the overall

lipid fluidity

The sER synthesizes almost all of the major classes of cellular _____

lipids. including: - all cholesterol - all steroid hormones (from cholesterol) - all major classes of phospholipids

OIls are a hydrophobic

liqud - while fats are a hydrophbic solid or semisolid

ex of UNcompetitive inhibitor

lithuin inhibition of inositol monophosphate - decrease vmax, decrease km

Type II nuclear hormone (intracellular) receptor)

live in the nucleus, ligands move into the nucleus then bind to them "already sitting on response elements before being activated)

Glycogen storage occurs in the

liver and muscle principally - in the fed state, muscle and liver will replenish glycogen stores to normal levels

Regulation of the TCA cycle is mostly done through

local metabolite regulation ** in 3 principal locales: - citrate synthase - isocitrate dehydrogenase - alpha-ketoglutarate dehydrogenase *** all mainly local mechanisms - all product inhibition - energy state/need (ATP/ADP, Ca2+ ) - cofactor recycling (NADH/NAD+ limited supply)

q arm

long arm of chromatid

At anaphase ___ stay assembled inside the cell

lysosomes

protein degradation occurs in

lysosomes and proteasomes

5' cap is unique for

mRNA ** it makes RNA NOT susceptiple to 5' exonucleases

all blue regions are potential

mRNA (80% of the blue regions are introns - will be cutt out and not expressed)

RNA polymerase II makes

mRNA in the nucleus

if the transcript does not have 5' cap then the

mRNA will NOT stay circularized and it will be degraded

Cardiolipin is found

mainly in mitochondrial inner membrane, where it constitutes about 20% of total lipid

The main purpose of the mitochondria is to

make ATP

If the cell needs alot of sER products (lipids, membranes, cholesterol, steroid hormones etc.), it will

make/contain more sER to contain more of the membrane-bound enzymes

Peroxidation and fragmentation of fatty acids can form

malondialdehyde, which can cross-link proteins and DNA

Sorting of lysosoms is regulated by

mannose-6-phosphate receptors

TCA cycle takes place in the

matrix of the mitochondria

Week 3 is the start of the embryonic period (weeks 3-8) and it is the period of

maximal sensitivity to congenital malformations @ week 5 you are most at risk for picking up a viral infection

Describe situations in which anaerobic metabolism may be used

may be used during brief or intermittent high intensity exercise and hypoxic conditions to produce ATP. Glycolytic enzymes are fast and can produce ATP rapidly, but at the cost of producing lactate and having an inefficient process (only 2 ATP/glucose). This causes an "oxygen deficit" that has to be made up later

second messenget sysems employ

membrane bound receptos to transfer signals through the membrane

Food intake is sporadic and not timed with energy needs what is the solution to this timing problem

metabolism! it allows you to eat whenever and have energy for later

RNA interfernece (RNAi) is mediated by

miRNA 1. miRNAs are generally made from large hnRNA that are produced due to cellular signals to regulate translation of mRNA (cell proliferation, differentiation, apoptosis) 2. Some viral RNAs are processed to be siRNAs to shut down host gene expression 3. therapeutically siRNAs can be used to treat age-related macular degeneration (AMD) (ex. vascular endothelial growth factor over production leads to AMD, siRNA targeted to the VEGF mRNA stops the vascular expansion behind the retina)

___ are things required or taken in smaller quantities -- nucleotides, vitmains, etc

micronutrients

cilia and flagella are made from

microtubules

ciliary movement, vesicular transport and the structure of centrioles depend on

microtubules

MMR

mismatch repair - editing during polymeraization (DNA pol proof reading only in delta and epsilon) or immediately afterwards - S phase, early G2 - uses Mut S and Mut L to recognize the mismatech, no removal of base from sugar phosphate bone *** repairs mis incorporated base during replication - occurs immediately after the replication of that region of DNA

the power house of the cell

mitochondria

cytochrome found only in the

mitochondria (which does NOT do vesicular transport to and from rER)

Breakdown of fatty acids occurs in the

mitochondria via beta oxidation

TCA cycle occurs in the

mitochondrial matrix

Telophase is characterized by

mitotic spindle dissociation and kinetochore MT dissassembly

The electrical gradient contributes ____ energy to proton transduction than the concentration gradient

more ** this is bc the cytosol buffers the intermembrane space and prevents a steep concentration gradient

if the restriction system of a bacterium is knocked out the bactrium would be

more susceptible to infections by viruses * restriction enzyme system of bacterium is to protect it from viruses that could destroy the bacterium

quaternary structure is

more than one polypeptide (ex. heme is 4 distinct polypeptides)

At 16 cell stage the zygote is called a

morula - as cleavage continues, the morula is still passing down uterine tube towards uterus

The methylation of the cytosines and deacytlation of the histones allow the nucleosomes to fole the DNA into its

most inactive and compact form

mitochondrial diseases are passed from

mother to ALL offspring - for a mitochondrial disease to end transmission there must be a male in between the affected female ending the transmission

When assmbling into protines you have

multiple domains and multiple subunits A protein is roughly a functional unit

What method would you use for the diagnosis of CNS infection at an early stage

multiplex microarray

Mitochondrial myopathies are typically present as

muscle myopathies (weakness) and/or neurological symptoms due to impaired mitochondrial function * these are genetic diseases leading to impaired mitochondrial oxidation - they can be caused by mutations in mitochondrial DNA, or in nuclear genes coding for mitochondrial proteins - mutations in mitochondrial DNA can either be homoplasmic (present in all mitochondrial DNA) or heteroplasmic (present in some but not all of the mitochondrial DNA) Prevention: screening for mutations in parents, along with nuclear-cytoplasmic transplantation in the zygote

Dominant negative mutations

must result in LOF of another gene product (normally seen in mutimeric proteins) ** dominant mutations must cause their effect in single allele dosage (heterozygous state)- the hemizygosity of the X chromosome- the mutations in X are generally dominant in males due to only having one copy

Pleiotropy

mutation in one gene has more than one effect, effects in more than one physiological system ex. cystic fibrosis has a large # of signs and sxs that are all present in the most severely affected ppl by may also show variable expressivity ... this includes change in ionic content of sweat (salty sweat), lack of secretion of pancreatic digestive enzymes, a plug in the GI tract at time of birth, heavy mucus in lungs leading to infections and reduced lung capacity, absence or degeneration of was defence in male leading to infertility

Osmolarity formula

n x c (n= number of particles in solution) (c= conc- mol/L)

Chromatid

name of either L or R half of the metaphase chromosome

Plasmids are

naturally occuring "mini chromsomes" that contain features that help a bacterium withstand the antibiotics produced by other organisms such as fungi ** they sometimes enhance bacterial resistance to antibiotics

What will go on to form the oropharyngeal membrane?

near the end of week 2 the embryo is still a bilaminar germ disc, but in the future head (cephalic) region, the hypoblast is thickened (from simple cuboidal to simple Columnar) - these columnar cells are firmly attached to the overlying epiblast and this region is called the prechordal/oropharyngeal plate and with the layer above will form the oropharyngeal membrane

inflammation happens ONLY in

necrosis - necrosis is caused by ACUTE injury ex. burns, freezing, blunt trauma to tissues, intense UV radiation, acute chemical poisioning & anything that quickly depletes cell of ATP : - hypoxia (kills cardiac muscles during heart attack and neurons in brain during ischemic stroke)

List processes that are involved in necrosis

necrosis is the response to cell injury or toxins includs - random DNA degradation - inflammation - and cell and nuclear swelling

Plasma membrane rupture is signal of

necrotic cells that induce and inflammatory response as a result of their death - necrotic cells also have loss of mitochondria and release of enzymes

Fusion of the 5th somite results in formation of the

neural tube - HOWEVER at this time fusion is incomplete and the tube communicates with the amniotic fluid via the cranial (anterior) and caudal (posterior) neuropores

Implantation is complete once

no more cells are in the uterine cavity

suicide attempt

non-fatal, self-inflicated destructive act with explicit or inferred intent to die (puts you in a high risk group) - 3 % of ppl will attempt in their lifetime (650,000 emergency medical treatment)

sucrose is a

non-reducing sugar

Receptor+ ligand is what kind of bond

noncovalent bond

120/80

normal blood pressure

Volume

normal= full increased= bounding decreased= weak

Aldose reductase deficiency

normally this enzyme is not required, but it is important in case of high galactose levels * enzyme is normally present in the liver, kidney, retina, lens, nerve tissue, seminal vesicles, and ovaries

hydrophobic ligands work typically via

nuclear hormone receptors which are transcription factors by binding to specific response elements on DNA ex. ARE)

Exportin and histones would be found in the

nuclear interior

Intracellular receptors

nuclear receptors; steroid hormone family receptors - hydrophobic molecules - go through lipid bilayer binds the receptor and acts as a transcription activator or inhibitor

In addition to forming a variety of helices

nucleic acids utilize proteins to for complex forms that provide biochemistry for life - DNA structures with proteins can be used to protect DNA during a variety of stages of the cell cycle

The nuclear organizer (has pre-rRNA gene repeats) this makes up the

nucleolus (all chromosomes have atleast 1 aggregated in the nucleolus- it increases transcription and this is why the nucleolus is so dark

What structures breakdown during mitosis

nucleolus, ER, nuclear lamina, and golgi body

Nucleotides are

nucleosides with phosphates

Metaphase chromosomes are tightly coiled around histones to form

nucleosomes

DNA or RNA polymers are made of

nucleotides

tRNA are matured in the

nucleus

RNA binding proteins bind the mature mRNA and facilitate the exit of the mRNA out of the

nucleus * the RNA bidning protein PABP (Poly A binding protein) binds the 3' poly A tail and protects it. It also binds translation factors that bind the 5' cap causing the mRNA to effectively circularize. This is required for the transcript to be exported out of the nucleus to the cytoplasm ** PABP is required for transport out of the nucleus

Maturation of RNA requires RNases and many of these reside in the

nucleus ** secondary structure reduces access by RNases

Majority of the Notochorde degenerates as bodies of the vertebrae form; but remnants still persist as the

nucleus polposus of a IV disc

preparation for translation begins in the

nucleus usually but can also occur in older transcript in the cytoplasm

Carbohydrates are a

nutritional source of energy and energy storage form - includes glycolipids and glycoproteins

healthy parents of a child with an autosomal recessive disease are

obligatory carriers

Neural Tube Defects (NTD's)

occur bc of a defect in the neurulation process - Anencephaly= failure to close in the cranial (anteroneuropore) region, most of the brain fails to form - Spina bifida= failure to close more caudally (like spinal cord area) - lots of types, vary severity * incidence apprx. 1/1,500 births - 50-70% NTDs can be prevented if females take 400 micrograms of folic acid daily

protein catabolism

occurs during the fed state, in the TCA cycle

Fatty acid synthesis

occurs principally in the liver - occurs when there is sufficient carb influx to raise [Acetyl-CoA] beyond what is needed for energy needs - Acetyl-CoA is turned into fatty acids and combined with glycerol phosphate to make TAGs - these are then packaged into lipo-protein particles called VLDL (very low density lipoprotein) - VLDL is then exported to the circulation where it will traffic the TAGs to adipose tissue (when fed)

Contact dependent signaling

occurs through the membrane bound proteins, such as gap junctions or integrins (ex: common in growth tissues it can stop them from growing- growth inhibition)

There are about 865 GPCR genes in the human genomes most are for

odorant receptors

siRNA

often viral origin - used by viruses to down regulate host gene expression (cleaves mRNA)

Can you give another examples of the cell regulating its organelle numeber via the induction of cytochrome p450 (CYPs)?

one important drug metabolized by smoothER is the barbituate- phenobarbital (the most widely used anticonvulsant worldwide) - when large amounts of certain compounds (like this drug phenobarbital) enter the system the SMOOTH ER in liver hepatocytes doubles in surface area in a couple of days - the reason it does this is because the cell recognizes that it needs more CYPs and needs more membrane to put them in - AFTER stopping phnobarbital, the hepatocytes will degrade the excess sER within a couple of days by autophagy

A scramblase moves phospholipids from

one leaflet of the bilayer to the other in both directions ( do not require ATP)

the ER (rough and smooth) is

one, interconnected branching tubule - A membrane protein or lipid can diffuse from one end of the (connected) membrane to the other; so can a soluble protein in the (connected) lumen

After the first 10 or so nucleotides are laid down some of the transcription factors are exchanged for

ones that promote elongation

Which polymerases are the ones that have proofreading functions

only DNA polymerase delta and epsilon ( a 3' to 5' exonuclease can remove a mis-incorporated base- defense against mutation) so for DNA alpha an error will remain their unless it is removed by delta/epsilons repair enzyme removes it (THIS DOES NOT increase mutation rates because the primers are removed by RNase H and FEN1)

Helices are formed from strands running in

opposite directions: the 5' end of one is opposite to the 3' end of the other (ANTIPARALLEL)

Microtubules function in

organelle transport- ex. axonal transport

The leading strand begins at

origins and travels toward a replication fork

During apoptosis phosphatidylserine appears on the

outerleaflet of the plasma membrnae (normally it is on the inner leaflet- this change signals it for induced cell death)

electron transport. Converts high energy electons (reducing power) to ATP and makes water from oxygen

oxidative phosphorylation

The carbon is CO2 (O=C=O) is very

oxidized (2 electronegative oxygens attached to it)

CoQ

oxidized coenzyme Q (it is ubiquinone)

Glycolysis ____ the glucose partially in its conversion to pyruvate and harvests the reducing equivalents at ___

oxidizes glucose partially - reducing equivalents at NADH (glycolysis converts glucose, a 6 carbon sugar to pyruvate, 2 three carbon molecules)

Metabolism harvests reducting equivalents (food) and recombines them with

oxygen. this generates the energy that supports - temp - biosynthesis - mechanical movement the results are water and CO2

Nucleic acids use

phosphodiester and hydrogen bonds

Arsenate prevenets which enzyme from carrying out ATP production in glycolysis

phosphoglycerate kinase - 2 ATPs are NOT made at this step so the ney yield of ATP per glucose would be zero

3 components of membranes include

phospholids, cholesterol, and proteins

PKA can

phosphorylate a nuclear transcription factor and once it is phosphorylated it can turn transcripiton on or off- this affects gene transcription (this is typically a result of persistent elevated cAMP, some cAMP increases are very transient and are more important for metabolic changes or actue regulation

PI3-kinase is recruite by some RTKs and activated. This leads to

phosphorylation of PI, PIP, or PIP2 on the inositol-3-position. Leads to formation of PIP3 (PI(3,4,5)P3)

Signaling mechanisms reflect the

physical characteristics of the messenger: hydrophobis vs. hydrophilic

over 50-70% of those who completed suicide have had contact with health services in the days to months before their death... elaborate on how this can be stopped

physicians are reticent to talk to their pateints about suicide - primary care is CRITICAL setting for detecting the two most common risk factors for suicide: depression and alcoholism - prevention is diff. than treatment

the efficiency of cloning is improved if the

plasmid DNA is de-phosphorylated after cleavage to prevent the plasmid from closing and ligating to itself

Men (assuming puberty at age 15) accumulate _____ with age

point mutations ** gametes from men have many more point mutations than gametes from women

Proteins can assemble into even larger complexes like

ribosomes and the nuclear pore complex

In order for mRNA to be transported out of the nucleus...

polyadenylation must occur - exiting of the nucleus requires that mRNAs are polyadenylated, poly A binding protein (PABP) has bound the poly A tail, the eIF4F and eIF4G complex has bound the 5' cap and the PABP and that the eIF3 has bound the eIF4/PABP complex and the small subunit of the ribosome with met-tRNA

the 3' UTR contains the

polyadenylation sequence

Protein is a

polymer of AA's - it provides both fx and a site of storage for AA. - AAs can be metabolized to make glucose and enrgy . Major storage site is skeletal muscle followed by liver (can also be found in kidneys and intestine)

Explain polymerase switching

polymerase alpha binds the open region of DNA and participates in primer formation - PCNA (sliding clamp) binds the primed region and replaces polymerase alpha with polymerase delta - polymerase delta falls off after it runs into a primer or is replaced after 200-500 bp with polymerase epsilon -polymerase epsilon replaces the polymerase delta ONLY on the leading strand

polymerase delta binds PCNA but also binds what

polymerase alpha, FEN1, and DNA ligase

Cleavage of the pyrophosphate from the incoming base provides the enery source for

polymerization and movement of the polymerase to the next base - further cleavage of pyrophosphate into inorganic phosphate prevents feedback inhibition and accelerates polymerization since the concentration of the products is very low

Amino acids derived from protein digestion in the intestines go into the

portal circulation, and some go to the general circulation and can help supply energy or can supply building blocks for protein synthesis - during fasting or starvation, protein breakdown supplies some energy and more critically precursors for gluconeogenesis

Enhancers are

position and orientation independent. So deleting 500 bp from a 3,700 bp region should simply bring the enhancer slightly closer to the promoter that it is activating and not change the transcription stimulation of the RNA polymerase much, if at all

ex of positive redox potential

positively charged items have a stronger affinity for electrons and hence a more positive redox potential - oxygen has a very positive redox potential ** the Carrier NADH has a negative redox potential *** electrons move from atoms, ions, or molecules with negative redox potential to ones with higher more positive potential

The blastocyst normally implants on the

posterior superior wall of the uterus by end of day 6 beginning of day 7 post fertilization - implantation is into the functional layer of the endometrium

In eukaryotes dene expression is controlled at

posttranscriptional and posttranslational processes

Class II Nuclear receptors

pre-exist bound to the DNA. Ligand binding causes release of co-repressors and recruitment of coactivator proteins

130/80

prehypertension

for a disease to be dominant it must be

present in DIRECT line through several generations - just bc it is present in several generations does NOT make it dominant - remember for dominant- offspring, parent, grandparent must all be affected in direct line

Long repetitive DNA (like a telomere)

prevents harm from exonucleases and allows proteins to bind and protext the ends of the DNA - length changes with age - telomerase is active only until early embryonis period except for sperm and lymphocyte

colchicine

prevents the assembly of microtubules and therefore prevents formation of the mitotic spindle

The sequence of AA conjoined through peptide bonds represent the

primary structure

5' exonuclease activity of a DNA polymerase aids in

primer removal

Positive predictive value

probability that a person with a positive test result is a true positive (has the condition being tested for) TP/ ALL P

Coupled reactions are

reactions where two reactions occur simultaneously on one enzyme. ** the delta G of one reaction will be unfavorable and the Delta G of another is strongle favorable (negative) - by coupling these the overall reaction could have a favorable free energy EX: reactions where the hydrolysis of ATP is coupled to a reaction to drive it forward ATP + Pyruvate + CO2 --> Oxaloacetate + ADP + Pi - here the hydrolysis of ATP provides the energy for carboxylation reaction

A mutation in a gene encoding an enzyme often results in a

recessive disease

Mitochondria neither

recieve nor give off vesicular transport

women accumulate ____ errors with age

recombination ** gametes from women have many more chromosomal rearrangements than gametes from men

Energy stores in the body are stored in a chemically ___ state

reduced

The carbon in a methyl group such as -CH2- or -CH4 is highly

reduced * thus fat if verrry reduced because it is a chain of hydrocarbons: glucose less so, because it contains a hydroxyl group for each carbon

When on of the respiratory chain complexes is blocked, everything upstream of the block is in the

reduced state and everything downstream of the block is oxidized

Most simple sugars are

reducing

Calcium-induced calcium release

refers to the self-reinforcinf effect of calcium release on the action of the IPS receptors to sustain calcium release - this occurs through the binding of calcium to the IP3 receptor. - this can give rise to calicum waves but this is the result of the effect

During telophase the

reformation of the nuclear envelope occurs

when counting from centromere how would you say 11, 12, 13

region 1 band 1 (closest to centromere) * counting starts at centromere and numbers increase when going away Region 1 band 2 Region 1 band 3

Heart rhythm can be

regular, regularly irregular, irregularly irregular

Glucokinase regulation

regulated by Fructose-6-phosphate and glucose itself - they regulate through nuclear localization via glucokinase regulatory protein (GKRP), which is in the nucleus (high F6p promotes nuclear localization and binding of glucokinase to GKRP, glucose promotes release from GKRP and return to the cytoplasm)

Beta cells of the pancreas

release insulin to signal the presence of glucose in the blood

The unsaturated fatty acid that is usually found in the 2 position can be

released in response to hormone such as histamine and act as a signlaing molecule or precursor (ex. arachidonic acid forming prostaglandins)

ionizing radition

remedy depends on lesion made: - base excision repair - nucleotide excision repair - single strand repair - double strand repair if not repaired: transcription and replication stop; apoptosis

free radical effects

remedy: - base excision repair- region around missing base removed then resynthesized and ligated if not repaired: transcription and replication stop; apoptosis

During the 3rd and 4th week of development the endodermal layer will form

simple columnar cells that line the inside of the stomach

single strand DNA breakage

remedy: - mostly ligation (no nucleotide or base missing) - coupled polymerization and ligation (uses DNA pol alpha) if bases are missing * DNA pol beta, delta, or epsilon will be used to fill in the gap before ligation If not repaired: transcription and replication will stop

Thymine dimerization:

remedy: - removal of affected bases and surrounding sequence - transcription coupled nucleotide excision repair - global nucleotide excision repiar If not repaired: - transcription and replication arrest

Multiple base changes

remedy: - transcription coupled nucleotide excision repair - global nucleotide excision repair - recombination based repair If not repaird - frame shifts - altered regulation, splicing, gene function - inversion, deletions, insetion, indel and duplication

Tautomerization

remedy: 3' to 5' exonuclease removal at time of replication - or spontaneous reversion if it occurs at time outside of replication IF not repaired: SNP

alkylation

remedy: affected base and the surrounding bases are removed by transcription coupldd nucleotide excision repair (TcNER) or global nucleotide excision repair (GNER) IF NOT repaired: - transcription and replication will arrest at the sites and induce apoptosis - SNP will form

Deamination

remedy: base excision repair or nucleotide excision repair IF NOT Repaired: SNP forms

What could be a useful treatment for someone with Leigh Syndrome

remember this is associated with defects in PDH, TCA cycle enzymes or in oxidative phosphorylation, where defects in PDH are the more common ***** in some cases increased thiamine in the diet can overcome a low thiamine affinity in the E1 subunit of PDH, and alleviate the defect

transcripiton coupled nucleotide excision repair (TcNER)

repairs large molecules attached to DNA, mismatches or intercalators - required ACTive transcription gene

Each chromosome has 8 different

repeat nucleotides- and these can be repeated about 10,000 times more

polymerase delta

replicates the lagging strand

polymerase epsilon

replicates the leading strand

The lagging strands begin at the

replication forks and travel toward the origin

DNA polymerase delta

required for elongation of the primers created by DNA polymerase alpha

the shortest distance btween 2 points on a specimen that can still be distinguished by observer/camera

resolution

What processes take place in the inner mitochondrial membrane

respiratory chain (ETC) and ATP synthase

Protein kinase A

responds to cAMP and typically works independently of calcium concentration

Gq mediates the

response of GPCRs to increase calcium concentration - activation of Gq to make Gqalpha-GTP

telomerase is a

reverse transcriptase of RNA directed DNA polymerase

All stages of DNA packing are

reversible

What two vitamins or cofactors are directly involved in the ETC

riboflavin and niacin (both required in making FADH and NADH)

The RNA polymerase subunit of DNA polymerase alpha uses

ribonucleoties NOT 2' deoxyribonucleotide

Once seperated from securin what does separase do

securin is inhibited by the APC (anaphase promoting complex) this allows separase to separate itself from securin seperase works to break down cohesion and breaks sister chromatids apart- hence the reason why its called APC ! it promotes the pulling apart of a chromosome during anaphase

lipids____ into membranes, micelles, and vesicles

self-assemble - structures can form spontaneously in vitro, or under regulated conditions in vivo

in order to be translated mRNA must be

sent out of the nucleus

Both smooth ER and rough ER function in

sequestering intracellular Ca2+ - release of Ca2+ from ER in response to cellular signals plays an important role in a variety of cellular signaling pathways * mitochondria also function in sequestering calcium - in the muscle: smooth ER forms special structure sarcoplasmic reticulum that plays a major role in muscle contraction

In x-linked recessive for a daughter to be affected

she will most likely have atleast one bad allele coming the father.. who would therefore also have to be affected

p arm

short arm of chromatid

DNA profiles used in DNA fingerprinting

short tandemly repeated variable DNA sequences

Second messenger signaling

signaling systems where initial signal (1st messenger) binds external receptor (such as a hormone binding a hormone receptor, and then induces the production of another signal internal to the cell (the 2nd messenger) ex. cAMP mediate signaling and calcium mediated signaling - epinephrine would be a hormone that binds to a cell and by binding beta-adrenergic receptors, causes and increase in cAMP. cAMP is, therefore, the second messenger - ACH, a first messenger, can cause changes in calcium levels in some cells; in this case calcium is the second messenger - other second messengers: IP3, diacylglycerol, arachidonate, and cGMP, some receptor tyrosine kinases are also used as second messengers

second messenger pathways alter the availability of

specific enhancers and repressors - some hormone regulation of transcription is via direct DNA binding of the homrone. Steroid hormone receptors are a good example (ex.: vitamin D3 binding to receptor activates Calbindin gene- increases uptake of calcium by intestines )

Translation can be regulated by the

stability of mRNA (ex. HUR, AUR1, PABP) - RNA interference by miRNA - HuR bind 3' ends and increases stabilitty - PABP binds poly A tail and increases stability as well as nuclear export - AUR1 binds AU rich sequences and decreases stability

Examples of competitive inhibitors

statins (lower cholesterol) and alcohol dehydrogenase - vmax unchanged - km increased

Describe elongation of translation

step 1: tRNA loaded into A site under guidance of eEF1. strat tRNA goes to E site , second tRNA with dipeptide attached to P site and new acyl tRNA to A site step 2: tRNA in E site is ejected from complex, then peptide bond forms shifting the peptide from P site tRNA to the A site amino acid Step 3: mRNA/tRNA complex shift again with tRNA in P going to the E site and A (new tRNA) going to the P site **** eEF2 (NOTTTT same as E2F) catalyzes GTP to provide energy for this translocation 3 steps repeated till stop codon is reached

which step of glycolysis produces a high energy thioester bond

step 6 (using glyceraldehyde phosphate dehydrogenase- GAPDH)

Many sugars are related by changes in

stereochemistry

sER is abundant in cells engaged in steroid synthesis because

steroid hormones are synthesized from cholesterol

What does AMP do to activity of PFK1 in glycolysis

stimulate PFK (signals that cell is low in energy, singal that there is low ATP) - ADP also activates it

nucleotides

store and carry information

Coding strand

strand that is the DNA equivalent to the RNA that is produced - this is where DNA is read from - NOT USED IN TRANSCRIPTION

Percussion involves

striking the bodys surface lightly, but sharply to determine the position, size, and density of the underlying structures as well as to detect fluid or air in a cavity - sound reverberations assume different characteristics depending on the features of the underling structures ** resultant sound described as: - flat (extremely dull): over solid areas (ex. bone) - Dull (thudlike): over dense areas (ex. fluid, liver, spleen) -Resonant (hollow,low-pitched)- over air (ex. lung tissues - Hyper-resonant: over increased aire (i.e hyperinflation (ex. COPD) - Tympanic: (hollow, high-pitched, "drum-like") over air (ex. intestines)

What is used for regulation in the TCA cycle

substrate and cofactor Enzymatic regulation at the following enzymes: - citrate synthase - isocitrate dehydrogenase - alpha-ketoglutarate dehydrogrenase By limiting cofactors (NADH in particular) By ATP and ADP concentrations in mitochondrion By mass action coupling to oxidative phosphorylation

the information in the genetic code specifies

substrate specificity in the proteins, that lets them make and modify lipids, carbs, hemes, steroids, and other molecules that are also essential

CoQ is also made in the TCA cycle by

succinate dehydrogenase

Only one enzyme of the TCA cycle is an integral protein of the inner mitochondrial membrane which one is it

succinate dehydrogenase

Which TCA cycle step feeds into CoQ of oxidative phosphorylation

succinate dehydrogenase gives its reduing equivalents to make CoQH2

10th leading cause of death (2017)

suicide trends: -apprx. 1 mill worldwide every yr -2017: 27,172 suicides in the USA -third leading cause of death for american youth -suicides out-number homicides by 2 to 1 - suicide is 4 times as common in men and especially high in men > 65 y/o

The ferric iron (Fe3+) can be converted to the ferrous iron (Fe2+) by

superoxide

During fasting, the liver

supplies glucose to glucose-requiring organs (brain and RBC) there are 2 sources of glucose: 1. glycogenolysis: glycogen breakdown to form glucose 2. gluconeogenesis: synthesis of glucose in the liver * EARLY in the fast the liver begins to break down its glycogen stores to keep blood glucose sufficientyl high to support brain and erythrocyte function * muscle lacks the enzyme glucose-6-phosphatase soo muscle glycogen stores cant be used to supply glucose to any other organ

In ETC energetically the movmeent of 3 H+ is required to

supply energy to make an ATP under the concentration conditions of the inside of the mitochondrion. Note that the 11 kcal/mol listed is much higher than the standard state energy required for ATP syntehis (+7.3kcal/mol) this is because of the typically low ADP and high ATP concentrations in the mitochondrion - this # , 3 protons, closely matches what is expected from the structure of the F0F1 ATPase

One of the majore roles of the TCA cycle is to

supply reducing equivalents for energy production. These are generated in the form of NADH and CoQH2

nails are dervied from the

surface ectoderm

in a congenital trait

symptoms are present at birth ex. a newborn evaluated for intersex because of ambiguous external genitalia

Congenital

symptoms present at birth (doesnt mean its inherited, could be from viral disease in utero) congenital DOES NOT = genetic genetic DOES NOT = congenital ex. congenital deafness

phone conversation is like

synaptic signaling (one on one)

The cells of the cytotrophblast undergo mitosis, and some of them are added to the

syncytiotrophoblast layer

Glycogenesis

synthesis of glycogen for storage of glucose

signaling can be

systemic or localized: contact, autocrine, paracrine, endocrine, or synaptic

Most chromosomes have 2 or more

tRNA genes (but one chromosomes has 1) these prevent mutations

DNA polymerase epsilon

takes over elongation of the leading stranf from DNA polymerase delta

PDEF is the

target of viagra and similar drugs - it is a cGMP-specific phosphodiesterase that inactivates cGMP by turning it into GMP. Therefore its inhibition potentiates the effects of those vasodilatory through NO

The 5' cap and the 3' poly-A tail have which respective functions

the cap provides transcript stability and directs the ribosome to the 5' end of the message to initiate translation - the 3' poly A tail provides transcript stability (it is not involved with transcriptional termination)

the 3' end of the tRNA is attached to

the carboxyl of the AA by the appropriate aminoacyl transferase * each aminoacyl transferase can only add one AA but can use any of the tRNAs that encode that AA

Neurulation

the embryonic formation of the neural tube by closure of the neural plate - the appearance of the notochord in the 3rd week of development induces the overlying ectoderm to thicken and form the neural plate which is composed of neuroectodermal cells - the neural plate extends towards the primitive streak - by end of 3rd week, the lateral edges of the plate become elevated to form the neural folds and neural groove - in the mid-line, the fold gradually fuse at the 5th somite in the cervical region and moves cranially and caudally *** most development occurs cranially to caudally but here its occuring in both directions

pleiotropy and variable expressivity are both about

the extent of symptoms in those who are affected ex of pleiotropy: a mutation in one gene has more than one effect, effects in more than on physiological system - cystic fibrosis has many signs and sxs that are all present in most severly affected people but may also show variable expressivity

x-linked recessive - for there to be an affected daughter

the father must also be affected (atleast one bad allele)

How do you use the codon table

the first of 5' nucleotide of a codon is readfrom the left side block of rows of the chart, the center nucleotide is read via the columns and the thirs or 3' nucleotide is read from the individual rows of reach block

Describe how the uteroplacental circulation is developed

the trophoblastic lacunae that are formed in the syncytiotrophoblast become continuous with the maternal via the syncytiotrophoblasts eroding the endothelial lining of the maternal capillaries (sinusoids) - the lacunae become continuous with the sinusoids - maternal blood enters into the lacunar system, establising the uteroplacental circulation -- at this point cytotrophoblasts also develop primary villi which are surrounded by the syncytium (this is visible at the end of week 2)

what two hormones regulate glycolysis

the two hormone of metabolism: glucagon and insulin ** glycolysis id central to regulating the daily metabolic needs of the body in various fed, fasting, starving, stressed, or excercised states

What does cyclin D do

there are 3 complexes of it with either cdk4 or cdk6 to form G1-cyclin. G1-cyclin regulated the growth of the cell in G1 and ensures enough nutrient are stored before expression of cyclin E

What does it mean in nonmaleficence to not cause any needless harm

there are many beneficial therapies that may also have serious risks ex. chemo - toxic to body but life saving (the patient must decide whether the potential benefits outweigh the potential harms)

Should only make referrals when

there is a clear benefit to the pt, not to avoid challenging or complex problems - they should not be made to avoid possible deaths in hospitals for statistic purposes and referral charges or fee-splitting is unethical (and potentially illegal) ** referalls fine in clinical practic but usually bad exam answers. Solve the problem with the info you have, dont choose answers that refer to another physician or ethics committee

The presence of uracil in DNA would only be possible if

there was a need for a primer which could only be laid down by DNA primase

If alternative splicing were prevented by a "super-spliceosome"- which would unfailingly remove all possible introns

there would be fewer unique proteins

Point mutations

these are single nucleotide changes usually caused by deamination or methylation of bases that result in misreading of the parental strand during DNA replication or repair - Silent: has no efect on protein sequence (same AA encoded) - Missense: AA substitution (diff AA encoded) - Nonsense: substitutes an AA with STOP codon (shorter protien)

Ribosomes are found in TWO locations in the cytoplasm (also in a 3rd place- mitochondrial ribosomes inside mitochondria )

these two places are 1. free 3. bound to the rough ER - the ribosomes are in different places because they are translating DIFFERENT sets of proteins - ribosomes in each place are identical and switch back and forth depending on which message they are translating at the time

What are some characteristics of peptide bonds in proteins

they have - partial double-bond character (this is why they do not rotate along the C-N bond because they have partial double bond characteristics - therefore 6 atoms lie within a plane: the carbonyl oxygen, the alpha-cardon (central carbon of the AA), the carbonyl carbon Etc.) - rigid and planar - trans configuration - uncharged but polar

only soluble carriers in ETC are NADH and cytochrome C

they would be able to freely diffuse in the mitochondrial inter membrane space

The major storage site for triglycerisdes (FAT)

this is adipose tissues role in metabolism (it delivers fatty acids when there is a demand for them)

Describe the phosphoglucose isomerase step (Step 2) in glycolysis

this is an isomerization step of glucose to fructose that lies near equilibrium because there is similar concentrations of both substrate and products (reversible- there is little energy change) - you are moving aldose into a keto group and then you can recyclize into a fructose moiety

Regulation of conversion of glucose to glucose-6-phosphate occurs at many levels, what are they

this is the hexokinase (in muscle and other tissues) and glucokinase (liver, pancreas, kidney) step it is regulated by - tissue specific isozymes - km values tuned differently in the isozymes - allosteric regulation - sequestration (glucokinase) - expression

At week 2 of Development the cytotrophoblasts, syncytioblasts and the embryoblast (ICM) continue their development at different rates

this is the point where development of the bilaminar germ disc, and amnion are formed and implantation is complete (by end of week 2)

ATG

this is the stop codon found in DNA CODING sequence remember in RNA this becomes AUG - this means start you would write down H2N-Met beneath an AUG (for coding sequence you read it as it is, just change T--> U) *** for template strand you have to make the antiparallel strand so start in this case would be TAC-- the RNA template would be AUG ***for mRNA you literally just translate strand how it is written and do not have to change anything

What can are some causes of lactate acidosis?

this occurs when lacatate levels rise in the blood - can be caused by heacy exercise and other pathological conditions (loss of oxygen, poisoning by some metabolic inhibitors, ischemia)

high risk groups

those that are known to have a higher than avg suicide rate

suicidal ideation

thoughts of harming yourself - 16% of ppl will have suicidal thoughts at some point

Different proteins display different rates of folding in the ER, and those rates determine the

time required for transport to the cell surface

Protein kinase a, PKA has a number of substartes that depend on

tissue specificity - diff tissues raise cAMP in response to distinc hormonse and some hormones decrease cAMP levels vis GPCRs (acting through Gi) or by tyrosine kinase receptor mechanisms. This the particular cellular response depends on the receptors present on the cell surface, whether there are other hormones acting at the same time, and on the targets present in the particular cell type

If phospholipids when being made in the smooth ER are placed in leaflet facing the cytoplasm then how do they reach the other leaflet to each out the bilayer?

to even out both leaflets, a scramblase (in smooth ER) scrambles the phospholipids equally into both leaflets (this DOES NOT need energy because you are at a less activated state - & scramblases are not specific it just constantly scrambles the phospholipids and its 50-50 on each side - LATER, flippases and floppases (in golgi and plasma membrane) rearrange phospholipids to give the asymmetric plasma membrane arrangement ( NEEDS ATP

what is the purpose of gluconeogenesis

to maintain circulating glucose concentrations and prevent hypoglycemia during long term fasting (>4hr) - this occurs in the LIVER and the KIDNEY and it synthesizes glucose to export for circulation (remember the the brain and RBCs CANNOT use fat)

prevalence rates

total # cases/ # in a define population - point prevalence: # of cases at certain time - period prevalence: # of cases over a period of time (often over 12 months) - lifetime prevalence (# of cases in reference to total life time)

tRNA

transcribed in nucleus - become acylated in cytoplasm and participate in translation

Describe how the Transcription of antioxidant genes is stimulated

transcription factor NRF2 (this is the master regulator of cellular redox state- a nuclear transcrpition factor) stimulated transcription of antioxidant genes by binding to the antioxidant response element (ARE) in promoters and enhancers - The sensors on KEAP1 are cysteines that become oxidized in the presense of "inducers" such as oxidative stress (this oxidation is similar to what happens with GSH: a disulfide bond between the cysteines is formed)- KEP1 and NRF2 are release from eachother. NRF2 goes on to stimulate transcription in nucleus * genes regulated by this: genes for enzymes of glutathiones metabolism and NADPH production, genes for proteostasis proteins (proteasome, autophagy), genes for enzymes of phase 2 drug metabolism) - in the ABSENCE of oxidative stress KEAP1 is inactive and causes degradation of NRF2 in the proteasome

Nuclear Hormone (intracellular) receptors are

transcription factors

The intracellular receptors, or nuclear hormone receptors are

transcription factors ( the steroid receptor family modifies gene transcription in response to a variety of hydrophobic hormones: androgens, estrogen, progesterone, Vitamin D (calcitrol), Vitamin A (retinoic acid), and the thyroid hormone

cytoskelteal protein, mitochondrial protein, perioxisomal protein and nuclear protein are all

translated on ribosomes free in the cytosol

Glucose transporters

transports glucose across the cell membrane - it can work in either direction - they are an example of facilitated diffusion (uniporters) - can transport other sugars as well ex: to increase the uptake of glucose and its storage as glycogen and fat, muscle and adipose tissue express an insulin-responsice glucose transporter (GLUT 4) in addition to GLUT1, which will dramatically increase glucose uptake in the presence of insulin

what are the spaces that are formed in the syncytiotrophoblast layer that allow for the nutrition of the developing embryo vis diffusion

trophoblastic lacunae (these are formed via programmed cell death)

true or false: both DNA and RNA can form a helix

true

true or false: primary care & other are held to a diff standard than those with specific expertise in mental health care

true

True or false: oxidative phosphorylation makes wayy more ATP than glycolysis

true!

true or false: phosphoglycerate mutase and enolase work near equilibrium

true!

true or false: pt have the freedom to decide and the right to decline treatment

true! a competent pat can refuse live saving treatment (ex blood transfusions, surgery, mechanical ventilation, renal dialysis, antibiotis, cariopulmonary resuscitaton, and tube feedings * pts do not have to posses terminal illnes to refuse treatment

microtubules are composed of

tubulin and are involved in motility - as the principal protein in the composition of the axoneme (core of cilium or flagellum) - microtubule motor= kinesin, an ATPase

less than 2% of DNA will

turn into mature rRNA by tanscription

CoQH2 carries ___ electrons, while cytochrome C carries just one electron

two

Where does galactose come from

typically milk and milk-based products contain lactose - lactase deficiency in the gut results in lactose intolerance - lactase breaks lactose into glucose and galactose Galactose can be used for - energy - milk production - glycolipids, glycoproteins, glycosaminoglycans

Metabolites are

typically small molecules that are intermediates in biochemical pathways or act as regulators of function (ex. glucose, ATP, hormones, neurotransmitter)

To replicate, DNA MUST

uncoil from chromatin and the nucleosomes. It is instead held and manipulated by replication specific proteins - DNA that is available for transcription and use in a growth phase of the cell cycle is held and manipulated by transcription specific proteins

Topoisomerases

uncoil the supercoiled DNA into simple helical DNA

Euchromatin, an active form of DNA (DNA undergoing transcription, recombination, and repair or replicating DNA) must be

unpacked

Rb only binds to E2F when it is

unphosphorylated. Rb binds to E2F, a transcripiton factor necessary to up-regulate many of the genes necessary for progression through S phase. When the cdk-cyclin active complexes phosphorylate Rb, it can no longer bind to E2F, releasing E2F to bind to the promoters of S phase genes

Beta mean the -OH is pointing

up "you beta look up"

the majority of enhancers bind

upstream of the promotor

if the sequence is RNA how do you manually encode

use AS IS

Telomerases contains a RNA which it can

use as a template to form the end sequence

Anabolism is the

use of simple metabolites (simple sugars, fatty acids, and AA) to generate more complex molecules for storage ( glycogen, TAG, and protein) and for maintenance and growth (new proteins and membranes) including specialized molecules such as heme, cholesterol and nucleotides (purines and pyrimidines).

Hexose Monophosphate Shunt

uses glucose-6-phosphate as a start point - it converts 6-carbon sugars to 5- carbon sugars - produces NADPH as reducing equivalents (key for fatty acid synthesis) and also CO2 - can convert the intermediate ribulose 5-phosphate into either: ribose 5-phosphate for nucleotide synthesis or in glycolytic intermediates for energy production

Chaperonines regulated protein foding by

using their ATPas activity to bind and release themselves from hydrophobic regions of the protein

Expressivity

variable expressivity= diff in severity or in age of onset for seemingly identical genotype (mostly seen in dominant diseases) - person will always have some sxs in these cases..... variable expressivity is kind of saying "he only shows some sxs" ..."this person shows more sxs"

Most nuclear receptors bind to

very specific DNA sequences that most often are inverted repeats- these are called hormone response elements (HRE) - for steroid hormone (SRE), estrogen its (ERE) and for androgen its (ARE) - there are a variety of these elements. some can bind several diff. steroid hormone receptors and others are more specific (this allows each receptor to influence a set of genes that may be overlapping with a set of genes targets by another receptor)

Bilayers occur in

vesicles, but may also form largey, flatter sheets that constitue plasma membrane, the ER, etc. - bilayers have two monolayers juxtaposed with their non-polar (hydrophobic) parts together, and the polar parts interaction with water.

lateral folding and head and tail folding of the embryo leads directly to formation of the

vitelline duct

What occurs in an error of meiosis?

when a numerical error occurs, there are two possibilities: - the conception develops into a fetus that dies - the baby that develops will be disabled - many genes will be present in the "wrong number"= aneuploid

RNA based viruses are an exception

where RNA can be replicated and reverse transcribed

Autocrine signaling

where the cell releases a chemical signal that affects itself

The forms of DNA or RNA structure determine

which proteins can interact with the DNA and therefore determines the activities in which the nucleic acid can participate

Because of their final locations (tubulin, exportin, importin, and histone)

would be translated on ribosome free in the cytosol and NEVER interact with the rER (remember rER sends things out)

if disease is passed from male to male this excludes

x-linked inheritance

presence of both males and females decreases the probabiliy of a disease being

x-linked recessive

In oxidative phosphorylation

you combine reducing equivalents from TCA cycle with O2 to make ATP- reoxidxed cofactors (NADH and CoQH2- get recycled)

What is the main gist of oxidative phosphorylation

youre pumping H+ from the matrix into the intermembrane space creating a chemical and electrical gradient. You generate reducing equivalents going through the ETC until you reach O2 and this is then used to reduce O2 to H2O and you have ATP synthase where H+ is never used up completely but is constantly going back and forth

The blastocyst lies free in the uterine cavity for about a day while the

zona pellucida disappears