Biochem and Immuno

18022 Pharm company in final stages of designing new NSAID agent develops 2 different oral formulations of drug. 2 groups of volunteers are administered a different formulation and avg plasma drug levels are monitoed over the next 12 hours. Results are shown below: Compared to red curve, formulation represented by blue curve is likely to have which charcteristic? a. delayed intestinal reabs b. enhanced CYP enzyme induction c. increased biliary excretion d. increased enterohepatic cycling e. reduced first pass metabolism

**a. delayed intestinal absorption Graph shows plasma drug conc. time curves Blue curve - reduced and delayed peak Red curve - sustained release prep Absorption of orally administrred drug depends on rate at which it dissolves in GI fluids. Capsules and tablets are designed with active ingredient embedded in insoluble matrix or encapsulated with coatings that dissolve at diff rates to delay absorption Advantage of slow drg abs: sustained release 1. reduced incideince of adverse effects due to dampening of peaks 2. longer duration of therapeutic effect due to prolonged absorption of drug 3. improved patient compliance due to less frequent administration b. enchanced cyp enzyme induction would lead to decreased serum drug levels faster c. increased biliary excretion would be expected to decreased peak serum levels but not explain the delay in peak d. increased enterohepatic cycling - prolong drug's effects longer than expected given drug half life e. reduced first pass metabolism would result in higher peak serum levels due to increased quantities of drug entering circulation

Collagen synthesis

1. collagen genes transcrbed in nucleus IN RER: 2. collagen alpha chains synthesized by RER bind ribosomes and are directed into cisternae of RER - specific proline and lysine residues are post translationally hydroxylate to hydroxyproline and hydroxylysine by prolyl hydroxylase and lysyl hydroxylase - vitamin C is neccessary for hydroxylation and post trans stuff 3. glycosylation of hydroxylysine residues 4. assembly of pro alpha chains into procollagen triple helix - via H and S bonds - problems forming triple helix = osteogenesis imperfecta 5. procollagen transferred to Golgi and secreted into ECM 6. terminal pro-peptides (tropocollagen) cleaved by N and C procollagen peptidiases -problems with cleavage = EHler's DAnlos (type 3?) 7. collagen molecules spontaneously assemble (fibrils) 8. covalent cross links formed by lysyl oxidase (copper is a cofactor) - form of Ehlers Danlos due to defective crosslinking by lysyl oxidase ((AR inheritance) + Menkes disease

64 What 2 processes are vit B12 importantin?

1. methylmalonyl coA -> succinyl coA - MMA builds up and impairs myelin synthesis 2. homocysteine -> methionine - lack of methionine impairs DNA synthesis

2031 Intracellular receptors and molecules that can bind DNA

1. trans fctors - mYc, CREB 2. steroid receptors 3. thyroid hormone receptors - intranuclear R 4. fat soluble vitamin R - vitamin A and D have intranuclear R Receptor/ligand complex bind DNA at hormone reesponse elements in promotor region of target genes to alter gene trx

What is the function of RNA polymerase 1? polymerase 3?

1: Transcribe rRNA compoents 3: transcribes tRNA, 5s ribosomal RNA an other small RNA molecules (weakly affected by amatoxins)

Inheritance of PKU

AR

Inheritance of leukocyte adhesion deficiency?

AR

IL-12

Activates Th1 cells and NK cells

In what immune deficiency do you have small or absent lymph nodes?

Agammaglobulinemia (X linked) -> hypoplasia of lymphoid tissues - lymph nodes, tonsils

C3a, C4a, C5a

Anaphylotoxins- trigger histamine rlease from mast cells -> vasodilation and enhanced vascular permability. C5a also recruits and activates PMNs, monocytes, eosinphils and basophils. C4a is least active and plays minor role in leukocyte recruitment.

489 Research evaluates effect of serum proteins in health and disease states. Purified insoluble elastin is exposed to stimulated neutrophils which results in degradation of elastin molecules into smaller peptides. Process can be inhibited by adding serum from healthy volunteers but not from specific patient population. What is the strongest recommendation for patients from this specific population? a. avoidance of competitive sports participation b. avoidance of immunosuppressive agents c. avoidance of second hand smoke d. periodic aortic diameter monitoring e. regular bone density measurement f. regular opthalmologic exam

Avoid second hand smoke Neutrophil elastase is released by PMN and MOs as primary protease resoinble for eC elastin degradation 0> major serum inhibitor of eleastase is alpha 1 AT -> panacinar emphysema - unopposed action of neutrophile elastae on alveolar walls -> tobacco increases inflammation: PMN and MO activation and inactivates already low quantitis of AAT through ox of crucial methionine residue, patients with AAT deiciency should be counseled to avoid smoking and exposure to second hand smoke

34 A boy with poor prenatal care has orbital hypertelorism, submucous cleft palate, and bifid uvula. Echo shows RV hypertrophy, pulm stenosis with VSD and overridicing aorta (ToF).Dx is confirmed by FISH. Findings are consistent with? a. abnormal ciliary motility b. chromsome microdeletion c. defect in fibrillin synthsis d. genomic imprinting e. mutation of tumor supressor gene f. nucleotide repeat expansion

Chromosome microdeletion Chromosome 22q11.2 microdeletion - DiGeorge syndrome - cause: defective neural crest migration into derivates of 3rd and 4th pharyngeal paouches -> maldevelopment of thymus and PTH -> T cell deficiency and hypocalcemia + interrupted aortic arch, tetraolgy of fallow + dysmorphic facial features: orbital hypertelorism, short palpebral fissures, short philtrum, cleft palate and bifid uvuala - dx by lack of FISh signal -> microdeletion

Characteristics of DiGeorge syndrome/velocardiofacial syndrome/chromosome 22q11.2 microdeletion

Craniofacial: orbital hypertelorism, cleft palate, short palpebral fissures, short philtrum, bifid uvula Cause: defective neural crest migration of 3rd and 4th pharyngeal pouches - no thymus and parathyroid

What is ornithine decarboxylase function?

DNA stabilization and repair Inhibition leads to decreased cell growth and increased apoptosis Enfornithine - topical used to decrease rate of facial hair growth

15881 What effectdoes metformin have on B12?

Decreases B12 absorption-> defiiency in long term use

541 Pathophys of hyper IgM syndrome?

Defective signaling between CD4 T and B cells Normal class switching in B cells occurs by splicing out DNA coding for different types of the heavy chain constant region until desired isotype is reached - variable region which codes for antigenic specificity of the Ab stays the same Class switching occurs when CD40L on activated CD4+ T binds to CD40 on B cell Path: CD40 (rare, AR) or CD40L (common, XLR)deficiency -> prevents normal class switching -> native IgM producing state Clinical features: recurrent sinopulm, GI, and opportunistic infection (Pneumocystis, Cryptosporidium)

12278 What is reverse transcription PCR used for?

Detection and quantifacition of mRNA in a sample Produces a complementary DNA strand -> ampliied by PCR ->contains exons of a gene along 5 and 3' untranslated region - canont detect changes in parts of gene that are not transcribed -> promoter and enhancer regins

How does FISH work?

Directly localizes genes to respective chromosomes using a labeled DNA probe complementary to sequence of interst - chromosomal position

298 Mechanism of FAS mediated cell apoptosis

Fas R stimualte extrinsic pathway of apoptosis through cytoplasmic component known as death domain: 1. FassL binds -> Rs trimerize -> allow death domain to form binding site for Ras associaed death domain (FADD) 2. R boound FADD stimulates activation of initiator caspases 8 and 10 which stimulate activation cascade -> activation of executioner caspases (3 & 6) 3. initiate terminal processes of apoptosis -> DNA cleavage, fragmentation of nucleus, organelle autodigestion, plasma membrane blebbing FasR is on T lymphocytes and plays an important role in ppathogenesis of numerous disease -> once activated: T lymphocytes express FasL -> bind to Fas on same or adjacent cell -> resistant during clonal expansion but become sensitive with stimulation - in constant presence of stimulating self Ags -> T lymphocytes eventually undergo apoptosis in activation induced cell death -> mutations of FAs or FASL imapir this process ->excess acumulation of autoreactive T cells and development of autoimmune disease such as SLE

1066 35 yo man has progressive fatigue with dark urine and back pain. 2 days ago he ate some large flat beans from Egypt. PE: jaundice and pallor. lab reveals hgb of 8. Further eval shows deficiency of enzyme in conversion of g6p to ribulose 5 phosphate. Substance gneerated during converstion is necessary for which biochemical process? a. ADP phosphorylation b. FA synthesis c. glyogen storeage d. ketone body syntheis e. protein degradation

FA synthesis Pt has G6PD deficiency - catalyzes first step in PPP : produces NADPH 1. oxidative portion generates 2 molecules of NADPH while converted g6p to r5p 2. non ox pathway reversible converts r5p substrate for nucleotide synthesis or glycolytic intermediate that can be used for energy production PPP is main source of NADPH so pathway is active in anabolic processes 1. cells experiencing high ox stress - RBCs in which NADPH is used to rengerate reduced glutathione - antiox that maintains cell integrity 2. organs such as liver and adrenal cortex involved in reductive biosyntheiss (anabolic processes) -> synthesis of FA, cholesterol, steroids 3. phagocytic cells generating resp. burst via NADPH oxidase 4. cyt p450 metabolism Pts with G6PD deficincy-> RBCs cant maintain sppled of reduced glutathione in periods of increased ox stress which can occur wit fava beans, meds (sulfa drugs, dapsone, primaquine), infections (pneumonia, viral hepatitis) -> acute hemolytic anemia and jaundice a ADP phosphorylation - NADH can be used as reducing agent to convert ADP to ATP during ox phos - NADPH cannot be used - NAD+ is used in catabolic processes to carry reducing equabalents away c. glycogen synthase does not require NADPH d. Ketone synthesis formed in liver during fasting when there is increased fat degradation - cytosolic HMG-coA synthease is starting point of chlesterol synthesis wheras mt version of enzyme is rate limiting step in ketone body synthesis: ketones formed in mt - does not rquire NADPH but cholesterol synthesis does e. protein degradation - broken down AAs undergo transamination that funnel amine Nitrogen into glutamate -> deaminated to produce ammonia - urea cycle converts ammonia into urea for urine elimination - this is a catabolic process

1412 Pt with CF has a mutation in exon of gene. Abnormal mRNA is isolated from cultured epithelial cells and its cDNA is synthesized. Amplified cDNA samples from both patient and healthy sibling are analyzed using gel electrophoresis and compared to DNA fragments of known size to determine bp length. Results are shown below and show a 101 bp DNA of affected pt. compared to 129 bp DNA of normal. Which is responsible? a. frameshift mutation b. nonsense mutation

Frameshift mutaiton Pt. DNA is 28 bps smaller which is not divisible by 3 so the mutation is oout of frame -> nonfuctional protein due to incorporaiton of incorrect AAs NOT a nonsense mutations because these are single base substitutions that reuslt in intro of premature stop codon - gel ephoresis is being performed on cDNA not on prtein and the results indicare length of mature RNA transcript - termination of RNA transcription occurs by specific sequences in 3' UTR that causes RNA hairpin loop formation and/or recruitment of termination factors -> point mutations (vs frameshift mutation) in exon of a gene are unlikely to affect total cDNA size

1720 GPCRs which bind through Gq or Gs

Gq: GnRH, TRH, Ag2, ADH (V1) -> activate phospholipase C -> IP3 and DAG -> activate protein kinase C Gs: PTH, ACTH, TSH, ADH V2 -> activate adenylate cyclase -> protein kinase A

Common facial abnormality in Marfan syndrome

High arched palate with crowded teeth and narrow face

556 5 yo stung by a bee has edematous and erythematous plaque with mild central pallor. Residual stinger located central to the lesion is readily extracted. Physical exam is otherwise not signiciant. Which substance is directly responsible for skin findings observed in patient? a. C3b b. IL-2 c. histamine d. lysozyme e. TNF-alpha

Histamine Child has type 1 HS to insect sting and has wheal and flare reaction - erythematous papule or plaque often with central pallor (wheal) and peripheral erythema (flare) Path: Initial allergen exposure -Ab class switching from IgM to IgE (IL-4) -> IgE produced by B lymphocytes and plasma cells binds to high affinity IgE Fc receptors on basophils and mast cells -> re-exposure to allergen results in cross linking of bound IgE Abs with subsequent degranulation and releae of inflammatiory mediators (histamine, tryptase, leukotrienes, prostaglandins) -> localized vasodilation and increased vasc permeability result in wheal and flare lesion - widespread release of these agents can also cause systemic vasodilation, bronchoconstriction, massive fluid shifts, anaphylactic shock and potential death a. C3b - opsonin - in type 3 HS; binds to CR1 Rs on RBCs -> facilitates their clearance in liver and spleen b. IL-2 - produced by Th1 lymphocytes -> increases proliferation and activity of helper, cytotoxic and regulatory T cells and NK cells - induce MO and CD8 (type 4) inflammatory reactins Vs, IL-4 which drives production of Th2 cells - humoral immunity and Type 1 hS + class switching to IgE C. lysozyme -antimicrobial enzyme in PMN granules and body secretoins - tears, mucus - hydrolyzes bonds within peptidoglycan cell walls of bacterial organisms - important component of innate immunity, not HS rxns E. tnf-alpha is pro-inflammatory cytokine produced by MOs and T cells that indues and maintains granuloma formation - importnat for host defense against TB - plays role in pathogenic of inalammtory conditions as RA, psoriasis IBD

IFN-gamam

Increased MHC expression, promotes Th1 cell differentiation. Produced primarily by activated T cells and NK cells

Immotile cilia, infertility, situs invertus, chronic sinusitis, bronchiectasis inheritance: AR path: microtubular defect in dynein arm

Kartagener syndrome

Killed vs. live vaccines

Killed - Inactivated pathogen - humoral immunity only - Influenza, Salk, rabies, hep A, typhoid Vi Live - small dose of live pathogen - cell mediated and humoral immunity -Attention Teachers, please vaccines small, beautiful young infants with MMR regularly - adenoverius, typhoid oral, polio (sabin), varicella, small pox, bcg, yellow fever, influenza, MMR, rotavirus FA 111

Leukocyte adhesion deficiency syndrome is caused by

LAD 1: Absence of CD18 - can't form beta 2 integrins Mac-1 and LAD-1 on leukocytes that bind endothelial cells during tight adhesion, crawling Clinical: recurrent skin infection without pus formation, delayed detachment of umbilical cord nad poor wound healing LAD 2: no delay in umbilical cord and fever/les severe infections LAD 3; severe reucrrent bacterial infections, delayed umbilical cord separation, bleeding complications due to affected beta -3 integrins on plateles

Who does medicare and medicaid cover?

Medicare -pts 65 and older, ALS patients, end stage renal disease pts, disabilities Medicaid - homeless, undocumented immigrants, pregnant women, low income families A. inpatent B. ooutpatient and medical devices C. optional capitated plan with cision and dental D. optional prescription drug plaan

Researchers studying eukaryotic genome structure extract DNA from exocrine pancreatic cells. Isolate small circular DNA that resemble bacterial chromosome. They code for proteins, tRNA and rRNA. From which cell structure did DNA molecules originate? a. ER b. nucleolus c. nucleus d. mitochondria e. exocrine granules

Mitochondria Have their own small circular DNA with different genetic code - endosymbiotic theory that mitochondria originated as prokaryotic cells that were later engulfed by ancient eukaryotes - codes for proteins involved in ox phos (some), rRna and tRNA for mt protein syntehsis

11914 Presentation of MERRF

Mitochondrial myopathy and encephalopathy with ragged red fibers Mt myopathy -> uable to use ox pho to produce adequate ATP -> organ systems such as brain and skeletal muscle are most affected due to high metabolic demand relative to other tissues Clinical: 1. muscle weakness and myalgia 2. lactic acidosis due to impaired aerobic glycolysis 3. nervous system dysfunction - neuropathy and seizures 4. ragged red fibers

What is the role of neutrophils and plasma cells in hypersensitivy reactions?

Neutrophils - occur in type 3 HS due to immune complexes which activate complement and cause neutrophil mediated tissue damagevia release of lysosomal enzymes - associated with vasculitis and sytemic manifestation Plasma cells - produce Igs which are responsible for type 2 and 3 HS - either direct Ab mediated damage or Ab-antigen complex activates complement

1334 12 yo boy is brought to offie due to gait instability and pruritic skin rash for several weeks. Mom reports he has been irritable and had loose stools. Several episodes of same rash that resolve spontaneously. Exam shows scaly, erythmatous skin lesions in sun eposed areas and cerebellar ataxia. Lab eval shows increased levels of neutral AAs in urine. Pt symptoms would respond to which supplement. a. ascorbate b niacin d. pyridozine e. riboflavin f. thiamine g. tocopherol

Niacin Pt has Hartnup disease - inactivating mutations affecting neutral AA transporrter -> impaired transport of neutral AAs (particualrly tryptophan) in small intestine and prox tubule of kidney - inheritance: AR - tryptophan is essential AA for precursor to niacin, serotonin and melatonin -> responsible for generation of half of NAD+ required for redox rxn - clinical: due to niacin defficiency: 1. pellagra like skin eruptions - red rash post sun exposure 2. cerebellar ataxia - early childhood that bcomes less severe with increasing age Diagnosis is confirmed by detecting excessive amounts of neutral amino acids - alalnine, serine, threynone, valine, leucine, phenylalanine, tyrosine, tryptophan in urine TrX: high protein diet with daily niacin or nicotinamide supplementation results in significant symptom improvement D. pyrodixine - coenzyme in decarbox and transamination of AA including metabolism of typtophan to niacin - deficiency of pyridoxine leads to anemia -> peripheral neuropathy and dermatitis - supplementation in hartnup disease is not effective due to udnerlying tryptophan melabs E. RIboflavin produces FMN and FAD coenzymes for enzymes in elecctron transport. Defieicny: sore throat, stomatitis, glossitis, normocytic anemia, seborrheic dermatitis F. Thiamine- conezyme for 1. transketolase 2. alpha ketoglutarate dehydrogenase 3. pyruvate dehydrogenase G. tocopheron is fat soluble and scavenges free readicals and results in neuro dysfuction and hemolytic anemia

Microdeletion syndrome due to genomic imprinting

Prader-Willi and Angelman syndrome PW: paternal gnees are deleted (15q) and maternal genes are silenced -> short stature, obesity, hypotonia, hypogonadism Angelman: maternal genes are deleted and paternal genes are silence - microcephaly, ataxia, hand flapping movements, frequent laughter (happy pupper)

IL-4

Produced by Th2 cells -> activates B cells > igE isotype swithcing and promotes Th2 cell differentiation

1247 Where in the cell does vitamin C act as a cofactor to hydroxylate collagen alpha chains? What are symptoms of vitamin C deficiency?

RER Vitamin C deficiency - gingival swelling and bleeding, petechiae, exxhymoses, poor wound healing, perifollicular hemorrhages and coiled corkscrew hairs Often in alcoholics, elderly, and poor

Environmental agent that inhibits protein synthesos?

Ricin = cleaves rRNA component of eukaryotic 60s subunit

17447 MHC class 2 expression defect wold result in what?

Sever combined immunodeficiency - MHC2 is necessary for activation of B and T cells

11950 Receptor proteins are isolated and purified from tissue sample. Detailed analysis shows a protein containing 30 AA motif coordinating a Zn molecule. R for which hormone was isolated? a. ACTH b. ADH c. Epi d. Glucagon e. GH f. Insulin g. thyroid hormone

Thyroid hormone Zinc finger structure respresents common DNA binding domain in humans - bind via cysteine and histidine residues -> stable, finger shaped structure containing 2 antiparallel B strands and an alpha helix - only intracellular R + transcription factors bind DNA -> thyroid hormone is only intracellular R ACTH, ADH, EPi and glucagon are Gprotein coupled R Insulin and growth hormone are intrinsic and assocated tyrosine kinase R

2030 Genetic study reveals single base mutation involveing DNA segment that encodes protein in -25 bp regoin. Mutation affects which process? a. DNA methylation b. polypeptide folding following translation c. post trx RNa splicing d. rna elongation e. trx initiaton f. translation init

Transcription initiation -25 bp region is part of promotor - TATA box - gene transcription begins when RNA pol 2 attaches to promotor regions that requires general transcription factors -> DNA enchancer region binds activator proteins that associated with transcription factors and RNA pol 2 at promoter -> increases gene expression -> promotoers are not directly translated into prptein, promtor mutoations can cause gene expression by altering RNA pol 2 and transcription factors to bind

Defective tumor supressor gene encoded proteins hamartin (TSC1) and tuberin (TSC2)

Tuberous sclerosis Clinical: 1. cutaeneous angiofibromas 2. brain hamartomas 3. cardiac rhabdomyomas

b8283 Linkage disequilibrium

Two genetic loci are in linkage disequilibrium when their respective alleles are inherited together in the same gemete more or less than expected by chance alone given corresponding allele frequencies - result of physical proximity of genes on same chromosome -

What happens in Arthus reaction?

Type 3 HS Local subacute immune complex mediated HS rxn -> intradermal injection of Ag into presensitized person (already has circulating IgG) -> immune complex formation in the skin -> edema, necrosis and activation of complement

Thromboxane A2

Vasocontriction and platelet aggreagation

Bradykinin function:

Vasodilation, increase vascular permeability, smooth muscle contraction and pain mediation

What does deficiency of autoimmune regulator (AIRE) cause in negative selection of T cells lead to?

autoimmune polyendocrine syndrome 1 (AIRE-1) AIRE is responsible for expressing tissue-restricted self antigens in the thymus

Which enzyme removes thymidine dimers formed by UV radiation?

nucleotide excision repair pathway - UV specific endonuclease Deficiency: xeroderma pigmentosum inheritance: AR

747 Man comes to ED post MVA - hypotensive and bleeding. Receives blood, develops difficulty breathing, chills and pain in chest and back. Urine drainage shows brown urine. What is most likely case of pt's findings? a. CD8 mediated cytotox b. complement mediated cell lysis c. vascular deposition of immune complexes

Complement mediated cell lysis Pt is undergoing acute hemolytic transufion reaction - fever, chills, hypotension, dyspnea, chest or back pain, hemoglobinuria, DIC, renal failure - ocurrs within mninutes to hours of a blood transfusion and is due to ABO incompatibility between donor and recipient - ex of type 2 HS: anti-ABO Abs bind corresponding Ags on transfused donor EBCs -> complement activation -> vasodilation and symptos of shock -> cell lysis via MAC

I cell disease

I-cell disease (inclusion cell disease/mucolipidosis type II)—inherited lysosomal storage disorder; defect in N-acetylglucosaminyl-1-phosphotransferase → failure of the Golgi to phosphorylate mannose residues (forming mannose-6-phosphate) on glycoproteins → proteins are secreted extracellularly rather than delivered to lysosomes. Results in coarse facial features, gingival hyperplasia, clouded corneas, restricted joint movements, claw hand deformities, kyphoscoliosis, and high plasma levels of lysosomal enzymes. Often fatal in childhood.

7791 Researcher evaluating a nuclear enzyme inhibitor for treatment of inherited disorder. Nuclear enzyme catalyzes the methylation of cytosine resideues in DNA using S-adenosyl-methionine (SAM) as methyl donor. Enzyme plays crucial role in which genetic process? a. aneuploidy b. epistassi c. imprinting d. meiotic nonjisjunction e. pleiotropy

Imprinting DNA methylation - addition of methyl groups to nucleotide resiues - often adenine and cytosine by DNA methyl transferase which uses SAM as methyl donor - epigenetic process that modifies gene expression without altering genetic code - methylation usually silences genes - ex) Fragile X - increased number of CGG trinucleotide repeats on fragile X mental retarfatin FMR1 gene -> hypermethylation of cytosine residdues and FMR1 inactivation Cytosine methylation also used in genomic imprinting - offsprings genes are expressed in parent specific manner - allele inherited from father may be inactivated or imprinted by methylation so only mom's allele is expressed B. epistasis - allele of one gene affects phenotype expression of alleles in another gene E. pleitrophy - single gene influences multiple phenotype traits

What is the result of conjugating a polysaccharide vaccine to toxoid?

Induces T cell dependent response -> long termimmnity - but still need booster T cells stimulate B lymphocytes -> production of memory B cells

2035 Whicih step in processing and handling of mRNA occurs within cytoplasm of cells? a. 5' terminal GTP addition b. 5' methylation of terminal guanine c. poly adenylation to 3' end d. snRNP interaction e. removal of intervening sequences f. interaction with P bodies

Interaction with P bodies Post transcription: unprocessed mRNA or hnRNA undergoes 5' capping, poly A tail addition and intron splicing (by snrnP) in nucleus -> leaves nucleus bound to packaging proteins Cytoplasm: mRNA complexes associated with ribosomes to undergo translation - certain mRNA sequences associated with proteins in P bodies - foci within eukaryotic cells involved in mRNA turnover and regulation. Role: translation repression and mRNA decay, RNA exonucleases, decapping enzymes and quality control and microRNA induced mRNA silencing, mRNA storage - some are released and utilized for translation later. B 5' methyl cap addition occurs in nucleu and protects mRNA from exonucleases

What does patchy necrosis of a transplanted organ demonstrate?

Ischemic damage 1. ischemia during attempted resusicatio of donor or during transport of organ 2. acutely during initial perfusion of organ after transplanation 3. atherosclerosis in donor

1614b What process is undergone by B cells in germinal matrix? a. isotype switching b. negative selection c. tolerance development d. VDJ recombination e. VJ recombination

Isotype switching B cells enter the lymph node when they are mature - migrate to lymphoid organs and tissues where they are exposed to Ags Germinal centers: site of B cell proliferation during immune response - undergo isotype switching once they are exposed to T cells and bind Cd40 L on T cells - heavy chain constant regions: distinguish 5 isotypes -> isotype switching occurs through geneetic rearrangement of heavy chain constant regions - modulated by T cell cytookines - variable regions are Ag specific - light chains B. negative selection - T cells in thymic medulla - due to AIRE D. recomb of VDJ and CJ occurs via DNA rearrangment -occurs in B cel maturation within bone marrow - affinity maturation occurs in germinal centers through somatic hypermutation

What would dopamine hydroxylase defiiency cause?

Lack of Norep synthesis from Dopa Dysautonomia - ptosis, orthostatic hypotension, hypoglycemia and hypothermia

559 T cell development

Pro-T cells arrive at thymus (from bone marrow) as double negative cells - no CD4 or CD8 -> rearrangement of B chain genes of TCR -> double positive cells - both CD4 and CD8 antigens - immature T lymphocytes -> process of a chain rearrangement of TCR occurs followed by positive selectin in thymic corex and negative selection in thymic medullar. once processes are complete, final maturation step is loss of either CD4 or CD8

1417 Large complexes containing protein and RNA. Found freely floating in cytoplasma nd bound to ER. Synthesized where?

Referring to ribosomes - which are made in the nucleolus - contains ribosomal DNA - rRNA is comined with ribosomal proteins that are translated in cytoplasm and imported into nucleus -> subunits are then exported to cytoplasm to fully mature

2029 Scientists developing drug that affects bacterial protein synthesis. Drug inhibits molecules that recognize a stop codon in an mRNA fragment. Which molecule is the target of this drug? a. releasing factor 1 f. uncharged tRNA

Releasing factor 1 When ribosomes encounter a stop codon, releasing factor proteins bind to robosome and stimualte release of polppe chain and dissolution of mRNA ribosome complex Uncharged DNA does not interact with mRNA and ribosomes during proein synthesis

What is base excision repair used for?

Repairs non bulky DNA base alterations, depurinations, alkylation, oxidation, deamination NOt the same thing as nucleotide excision repair or mismatch repair

Pathophys of metaplasia

Reprogramming of undifferentiated mesenchymal cells -> substitute dfferentiatied cell type for another differentiated cell type not commonly found in that tissue (bone formatino in muscle tissue after muscle injury)

Lysosomal storage diseases

Review your chart!!

1022 A man undergoing gng needs to form PEP from oxaloacetation which requires a nucleoside triphosphate as a cofactor. Which rxn directly synthesizes this cofactr? -

Succinyl coA -> succinate forms GTP Generated by substrate level phosphorylation like succinyl coA to succinate -> high energy thioester transofmration - GTP then transP ADP to ATP -> utilized by GTP hydrozyling enzymes such as PEP carboxykinase (oxaloacetete -> PEP)

806 Man has cystic fibrosis and pancreatic ducts are lined with squamous epithelium with areas of keratinization. Finding of squamous metaplasia in pancreatic ducts is due to deficiency of: a. riboflavin b. vit A d. vit E f. vit C

vit A Maintains orderly differentiation of specialized epithelia including mucus secreting columnar epithelium - deficiency : squamous metaplasia to keratinizing epithelium a. riboflavin (B2) and C are water soluble not affected by fat malabs c. vit E - deficiency causes infertility and decreased in serum phospholipids

A brother is donating his kidney to his siter. What is the prob that their HLA Ags will match?

1:4

1714 Healthy 22 o man weights 70 kg and volunteers for new drug experiement. VD = 10 L and first order kinetics. Drug clearance is 7 L/hr. Rpeating 2nd dose when 75% of drug is eliminated will minimize toxicity while maintaining trough lebels above minimum inhibitory concentration. Based on these research findings, which is most appropriate dosing interval for drug? a. 1 hour b. 1.5 hours c. 2 hours d. 2.5 hours e. 3 hours

2 hours t1/2 = (0.7*Vd)/Cl T1/2 = 1 hour Takes 2 half lifes to eliminate 75% of drug 1 t1/2 = 50 % of drug eliminated 2 t1/2 - 75% of drug elminiated

8480 Steps in inflammatory leukocyte accumulation in tissues:

1. margination: increased vascular leakage in microvasculature leads to hemoconcentration and decreased wall shear stress -> improves contact of neutrophils with endothelial lining 2. rolling: neutrophils roll on endothelium via loose binding of sialyated carb groups such as sialyl lewis X of PSGL-1 to L seelctin on PMNs or E selectin/P selectin on endothelial cells - cytokine stimulation greatly increasesexpression of endothelial selectins 3. activation: slow rolling allows leukocytes to sample the chemokines secreted by inflamed tissue - activates integrins by inducing signaling cascade that results in conformational change in integrins necessary for binding 4. tight adhesion and crawling: PMNs become firmly attached to endothelium via binding of CD18 beta 2 integrins (Mac-1 and LFA-1) to intercellular adhesion molecule -1 (ICAM) on endothelial cells 5. Transmigration through squeezing between cells via integrin attachments and adherence to platelet endothelial cell adhesion molecuel 1 (PECAM-1). Found primarily at peripheral intercellular junction of endothelial cells.

Leukotrienes (other than B4) cause what

1. vasocontrisction 2. bronchocontriction 3. increased in vasc perm

An HIV positive man with CD4 < 50 starts anti retroviral therapy. 2 weeks later there is further enlargement of the lymph nodes. Improved function of which of the following cells accounts for this enlargement?

CD4+ T cells -> required to activate B cells -> lymph node enlargement via follicle formation

1825 Infant born with protruding tongue, excessive skin at nape of neck, upslanting palpebral fissures. Weak, symmetric startle reflex. harsh systolic murmuer at LLSB. Normal genitalia. Mom has 2 spontaensous abortion in last 3 years. Echo confirms presence of VSD. Which karyotype is likely? d. 46 XX t (14,21) e. 47 XX + 18

46 XX t(14,21) Robertsonian translocation causing Down sundrome - inherited from unaffected parent with balanced translocation - between 2 nonhomologus chromosomes - fusion of 2 long arms and 2 short arms - affected parent is asymptomatic because they have normal gentic complement - ovum contains translocated chromosome and normal chromosome 21 is fertiilized with sperm containing normal set of chromosomes - reusltant fetus has unbalanced RObertsonian translocation with 46 chromosomes and 3 copies of chromosome 21 - another possible gamete has no copies of chromosome 21 -> increased risk of miscarriage

What is G6P converted to in the HMP shunt and what does it produce?

6-phosphogluconolactone by G6PD Produces NADPH

2039 Which enzyme is active in the nucleolus?

RNA pol 1 Produces 45s ribosomal RNA (most rRNA) This is why malignant cells have prominent nucleoli - large number of ribosomae production

Inheritance of classic galactosemia

AR

How does diabetes affect blood vessels?

Advanced glycosoylation end products Nonenzymatically attaches to proteins and lipids -> forms reverse glycosylation products that stabilize into irreversible products -> in hyperglycemia: AGEs accumulate and stimualte LDL deposition in BV walls and inflammatory cell invasion that causes athersclerosis and microangiopathic complication - high glucose levels in aqueous humor may induce nonenzymatic glycation of pens proteins -> cataracts

In what disease is their absence of germinal centers and primary lymphoid follicles?

Agammaglobulinemia

What determines the folding of a protein?

AA sequence of primary structure Heat shock proteins assist in spontaneous refolding

During hypoxic conditions, which enzyme is inhibited? a. enolase b. lactate dehdyrogenase c. pyruvate carboxylase d. pyruvate dehydrogenase e. pyruvate kinase

Anaerobic metabolism due to lack of O2 Pyruvate has 3 fates at the end of glycolysis: 1. lactate dehydrogease -> lactic acid (anaerobic) -> regenerates NAD+ from NADH 2. pyruvate carboxylase -> oxaloacetate -> regenerates glucose from pyruvate in gng 3. pyruvate dehydrogenase -> acetyl coA (aerobic) -> acetyl-coA is oxidized in the TCA cycle -> inhibited in lack of O2 due to IC accumulation of NADH

14805 Mechanism of resistance against adalimumab

Antidrug Abs common in Ig based anti-TNF agents - adalimumab and infliximab - know these are Abs bc they end in "ab" - degraded via endocytosis in RET system Rare in etanercept - recomb. TNF-R fusin protein - know this is R fusion protein bc ends in "cept"

What is asparagina AA useful for?

Rapidly dividing tumor ells need asparagine (from aspartate) bc it cannot produce it quickly enough for itself Chemotherapy drug: asparaginase - decerases asparagine conc. in tumor cells -> tumor lysis

2025 Transcriptional enhancers

Bind activator proteins that facilitate bending of DNA -> allows activator proteins to interact with general transcription factors adn RNA pol 2 at the promotor -> increasing rate of transcription - located pstream of downstream from gene being transcribed and may be near the gene or thousands of base pairs away - identified within introns of gene being trasncribed as well as on separate chromosomes - can be upstream, downsteam or within introons of genes - silerncers are similar to enhancers - decrease transcription rate by binding represoosr proteins

2086 16 yo girl with history of anemia since childhood is evaluated for genetic abnormality after several members of family are also anemic. She has point mutation in beta-globin gene which has resulted in sub of G to C in mRNA promotor region. Which cellular process is impaired due to gene mutation/ a. co translation protein targeting to ER b. intiiation of translation c. peptide bond formation d. ribosome translocation during polypep elongation e. termination of pp synthesis

B. initiation of translation Pt has beta thalasemia due to inherited B globin gene mutation in Kozak sequence - consensus sequence that helps translation in eykoaryotes - requires assembly of ribosomal subunits 60s and 40s, mRNA, initiation factors, initiation tRNA charged with methionine and GTP - 40s subunit binds to 5' cap of MRNA and scans for AUG start methionine codon - when positioned near beginning of RNA molecule and surrounded by Kozak consensus sequence it is initiatior of translation - analogous to Shine Dalgarno seuqnece in E coli - GCC - purine positioned 3 bases upstream from AUG appears to play a key ole in initiation process a. co translation protein targeting is mediated by N terminal AA sequence of elongating polypeptide - signal sequence is signal recognition particle which helps transport protein to RER c. peptide bond formation catalyzed by peptidyl transferase ribozyme that resides in large ribosome subunit - defect in rRNA coding for ribosomes would be required to interfere with this process d. ribosome translocation during polypep elongation - catalyzed by elongation factor 2 and requires GTP hydrolysis e. termination of polypep synthesis occurs at stop codons which recruits releasing factor 1 - mutations in stop codons can result in continued and inapporp translation of mRNA into 3' UTR - long nonfunctional polypep

558 Porcess of T cell development

Begins in first trimester of gestation at the thymus Produced in bone marrow -> migrate to thymus to mature Subcapsular zone: 1. Pro T cells arrive as double negative - no CD4 or CD8 2. TCR gene rearrangment occurs with simulatanous exp of cd4 and cd8 Cortex: 3. alpha genes rearrange to produce functional alpha-beta TCR 4. negative and positive selection occurs with cells that fail either of these tests being elimnated by apoptosis - positive: T cells expressing TCR bind self mHC is alowed to survive - cells expressing TCR not specific for self MHC are eliminated by apoptosis - occurs after TCR DNA rearrangement and prior to negative selection - interaction of T cells with thymic cortical epithelial cells expressing self MHC - responsible for deelopment of T cells that can recognize self Medulla: -negative: after positive selection - process by which T cells posessing TCRs that bind high affinity to self antigen or self MHC 1 or 2 are elminated by apoptosis - interaction of developing T cells with thymic medullary epithelial and dendritic cells - eliminates T cells that may be ovrly autoreactive against self antigens and play a role in autoimmunity if not destroyed - results in population of T cells that have low affinity for self MHC molecules

Where in the liver is ammonia metabolized?

Begins in mt -> urea produced in the cytoplasm -> t Ammonia brought to liver by portal circulation

15509 26 yo man has fever and lethargy. Abruptly began felling fever, chills, vomiting and diarrhea several hours ago and lightheadedness and lethargy. Had an episode of epistaxis after a bar fight 3 days ago. Does not use drugs. Temp is 102, bp is 90/60 and pulse is 120. Diffuse erythmatous rash, mild mucosal erythema and purulent discharge in nostril which was packed wound. Which process is most essential in pathogeneiss? a. activation of TLR by bacterial components b. binding of T cell receptors by bacterial secretory products d. phagocytosis of bacteria in blood by PMN e. presentatin of processes Ags by dendritic cells

Binding of T cell R by bacterial secretory product Pt has Staph toxic shock syndrome - cause: tampon use or nasal wound packing for a long time -> provides medium for localized S aureus proliferation and elaboration of pyrogenic toxin Super Ag (TSST-1 into bloodstream) -- symptoms: rapid onset high fever, hypotension, multiorgan failure and diffuse rash - path: reelased by strains that have mobiel genetic element via bacteriophage or plasmid -> exotoxins that bind to invariant chain of MHC2 on APC without first being internalized and processes - (normally processed by the phagolysosome) -> interacts iwth variable part of T cell R beta chain -> nonspecific stimulaton of total T cells and massive release of inflammatory cytokines- Il-1, 2, TNF alpha-beta, IFN gamma -> symptoms a. activation of toll like Rs is caused by septiss

What is a mutation that prevents maturation of pro B cells into pre B cells caused by?

Bruton tyorsine kinase Causes X linked agammaglobulinemia - - hypogammaglobulinemia and recurrent infections after maternal IgG is depleted - decreased in CD19+ cells on flow cytometry

1441 Boy with history of recurrent granulomatous skin infections and prior episode of Aspergillus pneumonia undergoes partial hepatectomy to treat poorly draining liver abscess. Inactinvating mutation in structural component of PMN oxidase enzyme. Pt most likely has increased vulnerability to infections caused by which pathogen. a. burkholderia b. enterococcus c. giardia

Burkholderia Chronic granulomatous disease - mutation: NADPH ox - path: impaired resp. burst - inhibits phagocytic intracellular killing - recurrent infection with: catalase positive bacteria and fungi - bc they degrade their own H2O2 via catalase -> no bleach formation for phagolytic activity - diffuse granuloma formation -Burkholderia, Serratia, Staph aureus, Nocardia, Aspergillus

2044 Biologists undertake series of experiences designed to classify proteins involved in various intracellular signaling pathways. During on experiment, protein mix obtained from cell culture is separated by gel ephoresis and transferred to membrane. Labeled dsDNA probes used to detect protein of interest. Which protein is detected? a. Ras b. c Jun c. B1 adrenoreceptor d. S 100 e. adenylate cyclase

C Jun*** Blotting techniques: Southwestern blot is used to identify and isolate proteins that bind DNA NOT DNA ITSELF: Target protein binds to labeled, dsDNA homologous to protein regulatory sequence. C-Jun and C-Fos are nuclear transcription factors that bind DNA via leucine zipper motif. Genes that code for c-Ju and C-Fos are protooncogenes -> become oncogenes following mutation or with constituve expression a. Ras - protooncogene that codes for membrane bound G protein -> activates Map kinase and trx but does not bind directly to DNA C and E. B1 AR -> Gs protein R in cell membrane -> AC cleaves AT to orm caMP -> activates protein kinase A d S100 is a ca binding protein similar to calmodulin important for intracell fucntin such a protein phos and cell growth and differentiation. S100 is marker for cells of neural crest derivation - melanocytes, Schwann cells and langer hans cells and dendritic cells

2079 Candida antigen injected into skin of patient reveals no signs of inflammation in 48 hours. Same test performed in mother produces 12 mm of skin induraion within 48 hours. Which cells are directly involved in response observed in the mother? a. CD4+ T lymphocytes and fibroblasts d. CD4+ T and MOs e. CD8+ T and eosinophils

CD4+ T cells and MOs Type 4 HS rxn - MOs present the injected candida to CD4+ Th cells -> secrete cytokines that recruit CD8+ T cells to area and produce induration and redness - CD4 and CD8 both produce IFN gamma which stimulates phagocytosis of candida by MOs - candidal skin test used as positive control for TB skin test bc everyone is sensitized to it No fibroblasts involved

Why do you not get lactic acid production in McArdle disease?

Cannot break down glycogen to produce glucose -> pyruvate -> lactate

TCR DNA rearrangement

Cause: joining of V, D, J and C regions of TCR gene and process of junctional flexibility, N and P region nucleotide addition, alternative joining of genes and multiple peptides combining to form intact R Mature TCR is formed from joining of a and b segment -> protiens are membrane bound in close association iwth cd4 or cd8 as costimulatory cd28 and cd45

In which disorder is B cell differentiation into plasma cells impaired?

Common variable immune deficiency - defect in B cell differentiation - cause is unknown - decrease in plasma cells and Ig overall - increase risk of autoimmune disease, bronchiectasis, lymphoma and sinopulm infection Increased risk of bacterial, enterovirus, Giardia infections - usually in late childhood

15255 Man received laceratino while waterskiing and has small laceratin on dorsum of R foot - edema, erythema, hemorrhagic bullae. Increase in lactic acid levels. Culture shows curved, gram neg rods. Which is greatest risk factor? a. condition causing iron overlaod b. bacterial nasal colonizatin c. exposure to infected rodent urine

Condition causing iron overload Vibrio vulnificans - iron overload or liver disease causes increased risk bc irno is an expoenential growth catalyst

Function of ribonucleotide reducatase

Converts ribose sugars attached to a base to their deoxyribose forms for use in DNA synthesis -> negatively regulated by accumulation of deoxyribose nucleotides Activity determined by cellular rpoliferation rate - increased cell division requires more deoxyribose nucleotides

What does the medulla of a lymph node contain?

Cords - B cells, plasma cells, MOs Sinuses - reticular cells, MOs

1332 12 yo boy that has an MI. Lab shows increased serum methionine. Which amino acid is essential in this pt?

Cysteine Patient has homocystinuria due to cystathionine synthase deficiency -> path: cannot form cysteine from homocysteine therefore cysteine is essential and homocysteine buildup funnels down methionine synthase pathway -> increased methionine - clinical: 1. hypercoag and thromboembolic occlusion because homocystiene is prothrombotic - possibility of stroke or MI like in this pt 2. homocystinuria 3. marfanoid habiitus 4. lens subluxation - downward and inward (vs up and out in Marfan's) 5. kyphosis 6. intellectual disability Methionine is used to form SAM - methyl donor in many transferase reactions -> forms homocysteine -> which can form cysteine in the body via vitamin B6 or reforms methionine via B12 for methyl donor Homocystinuria can be caused by different types: all AR inheritance 1. cystathionine synthase deficiency 2. methionine synthase deficiency - methinione becomes essential in this cause -> cystinuria - also need extra B6, B12 and folate in the diet 3. Decreased affinity of cystathionin synthase for pyrodixal phosphate -> need to supplement B6 and cystine in diet FA pg 84 review

What does the subcapsular sinus of a lymph node contain?

Direct communication with afferent lymphatic vessels and cortical sinsues that line the trabecula Cortical sinuses are continusou with medulalry sinuses and single efferent lymphatic channel exiting the hilu

587 8 yo male with long history of recurrent pulmonary infections has unsteady gait, slow language development, his eyes and head do not move smoothly when he is looking at moving objects. Exam reveals numerous superficial blanching nests of distended capillaries on sun exposed areas of his skin. Genetic defect in kids plays a role in. a. mitochondrial iron transport b. DNA break repair c. purine catabolism d. HLA class 2 Ag expression e. sphingolipid degradation

DNA break repair Ataxia Telangiectasia - clinical: 1. ataxia, 2. telangiectasia. 3. increased risk of sinopulmonary infection due to IgA deficiency - cause: AR inheritance mutation in ATM gene responsible for DNA break repair -> hypersensitive to xray radiation that causes multiple chromosomal breaks - defect in nonhomologous end joining A. mitochodrial iron transport is important for heme synthesis - inhibited by lead -> hypochromic anemia D. HLA class 2 Ag expression is defective in bare lymphocyte syyndrome - immunoddeficiency resulting from defect in expression of HLA class 2 antigens on surfaces of Ag presenting cells - needed to present foreign antigens to T cells and elicit both cell mediated and humoral repsonse - T cells must first activate B cells to mature and undergo class switching E. Sphingolipid degradation is defective in Niemann Pick disease - cause: AR defect in sphingomyelinase and results in accumulation of sphingomyelin within monocytic cells leading to death in early childhood - HSM, anemia, motor neuropathy, hypotonia, areflexia, cherry red spot on macula

What controls DNA methylation?

DNA methyltransferases

2101 Nursing home resident has a 2 day history of fever, vomiting and progressive lethargy. PMH sig for advanced dementia and stroke. BP is 88/62 and pulse is high and regular. Lethargic but arousable. Lab results should AG metabolic acidosis and increased lactic acid level and leukocytosis. Which is the cause of AG? a. decreaed ox phos b. impaired hepatic gng c. impaired renal bicarb reabs d. increased lipolsis and ketogenesis e. increased protein breakdown

Decreased ox phos This pt has fever, low bp ,leukocytosis indicates septic shock - decreased bicarb and increasedAG indicates AG metabolic acidosis secondary to lactic acidosis In this pt, septic shock is due to end organ hypoperfusion due to low bP -> impaires tissue oxygenation and decreases ox phos -> NADH buildup and shunting of pyruate to lactate following glycolysis - hepatic hypoperfusion during sepsis also causes lactic acidosis in the liver as primary site of lactate clerace via conversion back to glucose B. impaired hepatic gng does cause lactic acidosis but occurs due to inborn errors of metabolism and present in infancy with LA and hypoglycemia - pyruvate carboxylase deficiency, glucuose 6 phosphatase defieicny C. impaired renal bicarb reabs -> type 2 RTA or multiple myeloma and drug tox (acetazolamide) d. increased lipolysis and ketogeneiss occurs in DKA e. increased protein breakdown occurs in chronic metabolic acidosis but does not cause acidosis

1501 1 day old boy diagnosed with hyperphenulalaninemia by newborn screening. Placed on special Phe restricted diet with tyrosine supplementation. parents are counseled on boy's condition and informed of necessary dietary destrictions. Also instructed to return to physician for regular follow up visits. Several months later, lab tests indicate that infnat has normal serum Phe level. Careful exam reveals neuro abnormalities, including axial hypotonia and microcephaly. Further workup is notable for elevated prolactin and physician suspects cofactor decency. Which enzyme is likely deficient? a. dihydrobiopterin reductae b. dopamine beta hydrozylase c. Phe hydroxylase d. Phenylethanolamine N methyltransferase e. tyrosinase

Dihydropterin reductase Pt has PKU - deficiency of dihydropterin reductase which reduces BH2 to BH4 which is a cofactor for Phe hydroxylase conersion of Phe to Tyr - indicate: hyperphe and elevated prolactin 1. reduced BH4 results in ineffective Phe OHase conversion of Phe to Tyr -> hyperPhe 2. reduced tyrosine -> decreased conversion to dopamine by tyrosine hydroxylase which also uses dihydropterin reducatase as a cofactor-> decreased Dopa -> decreased inhibition of prolactin in CNS Phe levels can be controlled but downstream deficiencies of Nts - dopamine, NE, Epi, serotonin leads to progressive neuro deterioriation in these pts _ apllor in substantia nigra, locus ceruleus and vagal nucleus dorsalis C. classic PKU due to Phe hydrozylase deficieny. This pt has normal levels due t dietary therapy and supplementaiton but low dopamine. Classic PKU does not dififcult producing dopamine with adequate tyrosine. e. tyrosinase deficiency causes albinism - lack of pigment in skina nd hair due to absent melanin production - melanin is synthesized in melanocytes from tyrosine by tyrosinase

Mutation in an intron of gene. what is the effect? a. disruption of onrmal splicing by creation of a new splice site b. disruption of mRNA polyadenylation

Disruption of onrmal spicing by creation of new splice site RNA splicing enzyme(s) grab RNA and "loop it"; an intron is cut out and the exons on either side of the intron are adjoined, like this: exon1—intron—exon2 => exon1—exon2 Typically, this splicing occurs at the very edges of the intron (what I denoted with the "—" character). But in our case, a mutation within the intron is causing RNA splicing enzyme to recognize a new site: the splicer cuts within the intron (instead of at the very edge, as it should). So, we get something that looks like this: exon1—intr—exon2

1434 Drug targets enzyme mediated nucleotide removal in 5 to 3' direction -> inhibition of bacterial growth. Which enzyme is the target? a. DNA pol 1 b. DNA pol 3 c. gyrase d. helicase e. ligase f. primase

DnA pol 1 - only DNA pol that has 5 to 3' exonuclasee activity to remove RNA primer created by RNA primase, replace with DNA, and repair damaged DNA sequences All DNA pols have 3 to 5' exonuclease activity to preserve replication fidelity - remove mismatched base pairs during DNA replication

Mutations that cause an abnormal gene to affect the product of a wild type gene in the same cell

Dominant negative mutation ex) certain oncogene p53 mutations -> translation of protien product that prevents wildype p53 from binding to promoter

1467 Preventive disease specialists working in developing country are investigating vaccination options to limit the spread of poliomyelitis. As part of study, 2 pts are vaccinated against polio. One pt has intramuscualr inactivated vacine and other pt has live attenuated oral vaccine. One month after, levels of which poliovirus Abs will differ the most between these 2 pts? a. duodenal luminal IgA b. serum igA d. serum IgG

Duodenal luminal IgA - stimulation of local secretory IgA is promoted when corresponding mucosal surfaces are directly stimulated by Ag - live attentuated vacccines produce stronger mucosal IgA repsonse vs. inactivated Secretory IgA is produced via stimualtion of mesenteric lymph node and Peyer patch B cells -> become activated and migrate to LP underling the intestinal mucosa -> differentiate into plasma cells -> synthesize IgA dimers (linked by J chain) -> bind to polymeric Ig R on basolateral surface of intestinal epithelial cells and undergo transcytosis -> linked IgA dimer is released into intestinal lumen -> portion remains attached to Ab = secretory component Mucosal immunity ihbits attachment to intestinal epithelial cells

What condition does telomerase mutation cause?

Dyskeratosis congenita - mucocutaneous changes (oral leukoplakia, dystrophic nails), bone marrow failure, pulm fibrosis due to alveolar epithelial cell dysgunction - dysfunction of EPIthelial NOT ENDOthelial cells (vascular endothelial cells are differentiated) - hematopoietic stem cells Telomerase: 1. RNA template 2. Reverse trasncriptase -> adds TTAGG from template

Protein degradation - how do you know which pathway?

Endogenous proteins are degraded by proteasomes Exogenous proteins are degraded by lysosomal proteases

1067b 23 yo man had a problem metabolzing sugar as a child but does not have any dietary restrictions now. Urine shows positive copper reduction test but glucose ox dipstick is negative. Which enyme is deficient? a. acid alpha glucosidase b. aldolase B c. fructokinase

Fructokinase Pt has essential fructosuria - benign - inheritance: AR - causes some dietary fructose excreted in urine unchanged due to defective fructokinase - since it is a reducing sugar, detected by copper reduction tst - glucose oxidase used to asvertain presence of urinary glucose and does not test positive in fructose or galactose Vs. aldolase B - hereditary fructose inteolerance: inability to metabolize fructose 1 P -> toxic and ccumulates in cells and depletes intracellular P -> pts beomce acutely symptmatic and develop liver failure

934 Man has progressive vision impiarment. Hz of diabetes and HTN. Fundoscopy reveals diminished red reflex bilaterally with obscuration of retinall detail. Determined that the pt's condition is in part due to intracellular accumulation of sorbitol. Sorbitol is normally metabolized into which substance before being excreted from most cells? a. fructose b. galactitol c. galactose d. glucose e. xylulose

Fructose 1. Glucose is converted into sorbital via aldose reductase - sorbitol cannot cross cell membrane and is trapped inside the cell where it forms 2. Sorbitol dehydrogenase is abel to convert sorbitol into fructose to prevent accumulatino when glucose levels are normal In hyperglycemia (chronic), sorbitol accumulates in tissues with lower sorbital dehydrogenase activity - retina, lens, kidney and peripheral nerves - increased sorbitol accumulation increases cellular osmotic and oxidative stress and contributes to pathogensis of diabetic retinopathy, neuropathy, and nephropathy -> lens fibers degnerate-> cataract formation + oxidative stress due to NADPH depletion (by aldose reductase) FA 81 b. galactitol - congenital cataracts in galactosemia or GALK deficiency c. galactose - high levels converted to galacitol via aldose reductase e. xylulose - intermediate in pentose phosphate pathway - used to generate NADPH for cholesterol and FA synthesis and ribose 5 P for nucleotide synthesis

1068b Researchers hypothesize that different monosaccherides delivered to liver have diffrent rates of IC metabolism. Which substance is likely to have the fastest rate of metabolism in glycolytic pathway? a. fructose 1 P b. galactose 1 P

Fructose 1 P Fructose is metabolized directly to glyceraldehyde 3 P which bypasses PFK which is a key RLS -> fructose is metabolized faster than other monosaccs and rapidly absorbed Vs. galactose 1 P - enters cucle as glucose 6 P but still needs to be metabolized by PFK-1 into fructose 1,6bP

1421Boy has fragile X with CGG trinucleotide repeats in gene onX chromosome. Which causes clinical condition? a. exon deleetion b. gene methylation c. impaired intro splicing d imprinting e. mismatch repair defect

Gene methylation FMR mutaiton on long arm of chromosome x -> CGG repeats expanded during meiosis in oocytes -> causes FMR1 hypermethylation -> inactivates FMR1 - preventing transcription and production of fragile X mental retardation protein - degree measured by southern blot and measure CGG repeats

What is the difference between Von Gierke and Cori disease?

Gng is intact in Cori disease so it is milder - defeect in debranching enzymes - normal blood lactate - accumulation of limit dextrin like structures in the cytosol

1710 New aminoglycoside is particular effective against pseudomonas. Volume of distribution is measured in a group of volunteers and is determined to be 4.5 L. New drug has which of the following properties? a. Low MW b. lipophilic c. does not bind to albumin d. highly charged e. high oral bioavailabiltiy

Highly charged Volume of distribution: Vd = amont of drug given (mg)/plasma concentration of drug (mg/L) Total body water avg = 41 L EC fluid volume is 14 L (1/) Plasma volume = 3 L Interstitial fluid makes up the rest Drug enters plasma compartment IV -> if drug has Large MW, bound to albumin or highly charged then drug remains in plasma comparment and VD is low as in the case (3-5 L) If drug has small molecular wight but is hydrophilic it can distribute into interstitial fluid outside of BVs and intravascular compartment => VD 14-16 L (plasma volume plus interstitial volume) If drug has small molecualr weight and is uncharged it can cross cell membrances and reach intracellular comparment -> highest VD 41 L Drugs that are bound in tissues exhibit highest VD -> higher than totla body water because accumulate within cells radily and maintain low plasma concentration Binding to plasma proteins retains drug in plasma comparments and prevents diffusion into extravascular compartment Bioavailablty measures absorption and unrelated to drug distribution

1472 Electron microscopy of eukaryotic cell during interphase of cell cycle shows 10 nm thick chromatin fibers with beads on a string apperanace. Chromatin fibers are extracted and treated with endonuclease -> preferentially cleaves string portions of chromatin. Eval of beads reveals they are composed of DNA wrapped raound a core of proteins. Which protien is most likely found outside of this core and helps promote chromatic compaction? a. histone H1 b. histone H3 c. histone H4 d. snRNP

Histone H1 Nucloesomes: structureal subunits within nucleus of eukaryotic cells that are composed of Dna wrapped around ocore of histone proteins -> histone core made of 2 molecules each of H2a, h2b, h3 and h4 (8 histone proteins) - negatively charged DNa double helix wraps around positively charged histone core twice - h1 is located outside of histone core - facilitate packaging of nucleosomes into more compact structures by binding and linking segments of DNA that lie between nucleosomes - beads on string appearnce -> coiling and protein association to form chromosomes d. snRNPs splice out introns from pre mrna to form mature mrna

Microarray analysis?

Hybridization of large number of probes at one time - genomic DNA or cDNA analyzed is labeled with fluroescent tag and placed on a gene chip containing complementary sequences for a large number of genes - degree of fluorsence coresponse to mRNA expressed in sample

14772 Pathophys of cachexia

Hypermetabolic state driven by elevated pro inflammatory cytokines - TNF-alpha, IL-6 -> stimualte the ubiquitin proteasome pathway to degrade skeletal muscle proteins (actin, myosin)

Man has super high conc of triglycerides and milky serum. What is deficiency?

Lipoprotein lipase Familial hyperchylomicroemia FA pg 94 review the other familial dyslipidemias

1887 Which tissues cannot use ketones?

Liver and RBCs Ketone bodies yield energy by being metabolized to acetyl coA in the mitochondria RBCs don't have mt Liver does not have succinyl coA acetoacetate coA transferase to convert acetoacetate to acetyl coA Heart and skeletal muscle use ketones first, and reserve glucose for the brain - in severe starvation, the brain also begins to use ketones

Difference between liver and muscle during periods of hypoglycemia

Liver nad kidney: g6Pase converts G6P to glucose to help maintain blood glucose levels during periods of fasting Musscles: lack G6Pase -> utilize G6P for glycolysis during muscle contraction This is why there is no muscle weakness in Von Gierke disease (type 1): glucose 6 P can be used for glycolysis in muscles to produce energy - but the liver and kidney cannot convert G6P to Glucose -> severe hypoglycemia

998 8 month old boy has failure to thrive, develop delay, seizures, opthalmoplegie, hypotonia. Lab shows elevated serum LDH. Studies show reduced pyruvate dehydrogenase enzyme activity in freshly isolated peripheral blood lymphocytes and cultured fibroblasts. Increasing which substnace in his diet will help generate energy without elevating lactate levels? a. alanine b. asparagine c. galactose d. glycerol e. lysine f. serine

Lysine Pyruvate dehydrogenase deficiency -> buildup of pyruvate -> shunted to lactate via lactate dehydrogenase - lactic acidosis and alanine accumulation - manage disease via ketogenic diet: high fat, low carb diet with moderate levels of protein - forced production of ketone bodies from fat and AA catabolism to fuel the body in place of glucose - glucose absence -> decreased pyruvate -> decreased lactate Lysine and leucine are exclusively ketogenic -> cannot be metabolzied to pyruvate

Concentration of which AA would be different in abnormal elastin compared to normal elastin. The abnormal elastin shows a decreased number of cross links

Lysine Which is cross linked by lysyl hydroxylase Since the abnormal elastin has a decreased number of cross links, lysine is decreased Difference b/w collagen and elastin: both have proline, lysine, glycine - elastin residues are NON hydroxylated vs hydroxylated in collagen FA pg 52

Which AAs are strictly ketogenic?

Lysine and leucine -> metabolized into acetyl coA -> ketones

11930 2 yo boy has failure to thrive and developmental delay. PMH significant for reccurent ear infection. Exam shows coarse facial feature, corneal clouding, HSM, resutricted joint mobility. Mass spec shows deficiency phosphrylation of mannose residues on certain glycoproteins in Golgi apparatus. NOrmally these proteins are transported to which cellular location. a. EC space b. lysosome c. mt d. nucleus e. plasma membrane

Lysosome Patient has inclusion (I cell) disese -> inheritance: AR -> cause: defects in protein targeting - process by which prpteins are transported to appropriate intra or extracellular location - post-translational modifications (folding, glycosoluation, phosphorylated) function as markers that help guide protein to final destination Proteins targeted for lysosomes: modified differently than those destined for EC secretion: Golgi body phosphotransferase enzyme catalyses phorphrylation of manose residudes on lysosome bound proteins -> traverse golgi network and transported to lysosome where they degrade cell components -> path: defective phosphotransferase enzyme casues EC secretion of these proteins and accuumulation of cellular debris in lysosome -> forming inclusion bodies seen in I cell disease -> clinical: failure to thrive and cognitive deficits in first year of life along with characteristic physical features - coarse facial features, corneal clouding -> typically fatal a. Translation in ER -> secretoary proteins go to Golgi -> packaged into vesicles that fuse with plasma membrane and facilitate EC protein secretion c. mt proteins sythesized in cytosl -> contain specific mt targeting sequences -> translocases detect sequences and shuttle protein into and between different mt comparments d, nucleus - present nuclear localization signal to nuclear pore complexes on nuclear envelope -> different nuclear export signal required for proteins to leavenucleus e. peripheral membrane proteins modified via lipidation in which hydrophoc lipid anchor is covalently atached -> protein interaction with cell membrane

762 How are MOs activated?

MOs acts as APC to naive Th0 cell -- binds MHC 2 -> MO secretes IL-12 -> Th1 differentiation -> Th1 produces IGN-gamma -> MO and CD8 activation against intracellular organisms like TB IL-12 R deiciency - susceptible to severe, persistent mycobacterial infections

Which immune cells stimulate fibroblass?

MOs secrete TGF-beta -> stimulates fibroblasts to release collagen and form scar tissue

What does deficiency of branched chain ketoacid dehydrogenase cause?

Maple syrup urine disease No carboxylation of alpha-ketoacid derivatives of leucine, isoleucine and valine CNS defects, intellectual disability, death cofactor: thiamine I Love Vermont maple syrup

Strain of E Coli produces temp sensitive tryptophan synthase and needs exogenous tryptophan for growth, does not grow at 30 degrees, only 42. Which mutation is responsible? a. frameshift b. missense c. insertion

Missense -> results in single AA change Missense mutations involve a nucleotide substitution resulting in changed amino acids. Sometimes the effects of missense mutations may be only apparent under certain environmental conditions; such missense mutations are called conditional mutations. Many missense mutations result in proteins that are still functional, at least to some degree. Also, all the other answers would probably leave you with either a greatly altered or non-functional protein.

14 yo has 1 month history of migraines, vomiting and multiple seizures. Hearing loss since the age of 11. Mom and grandma have high tone hearing loss. Loss of vision in half of right eye. Upper and LE weakness. lactic acidosis. Pt has mutation in what? a. mt tRNA Leu b. endoplasmic reticulum glycosyltransferase c. lysosomal alpha glucosidase

Mt tRNA Leucine - indicated by hx of mom and grandma with hearing loss too Pt has MELAS: 1. mt encephalopathy 2. lactic acidosis 3. stroke like episodes (seizures) Presents with: Recurrent severe headaches Muscle weakness (myopathy) Hearing loss Stroke-like episodes with a loss of consciousness, seizures, and other problems affecting the nervous system.

1019 8 yo boy evaluated for exercise intolerance, fatigue, muscle pain and cramps during exercise and severe muscle stiffness following strenuous activity. Forearm ischemic exercise test is performed by applying BP cuff on patient's exercising forearm and sampling blood lactate several minutes after exercise. Blood sample shows no rise in lactate. Biochem analysis shows absent lactate dehydrogenase. Strenuous activity leads to inhibiton of glycolysis in skeletal muscle due to intracellular depletion of which substance? a. AMP b. carnitine c. citrate d. FADH2 e. NAD+ f. pyruvate

NAD+ Glycolysis: glucose -> pyruvate -> aerobic: acetal coA -> TCA cycle -> anaerobic: lactate (anaerobic glycolysis) via lactate dehydrogenase Aerobic: reduces NAD+ to NADH -> NAD+ must be regenerated for glycolysis to continue -> NAD+ is converted to NADH in TCA cycle -> NADH reconverted to NAD+ in ETC as energy in NADH is utilized to synthesize ATP Anaerobic: NAD+ is regenerated from NADH when pyruvate is converted to lactate via lactate dehydrogenase so glycolysis can continue -> in LDH deficiency, inhibits glycolysis in strenuously exercising muscles as muscle cells cannot regenerate NAD+ (via lactic acidosis) -> exercise leads to muscle breakdown, pain and fatigue as insufficient energy is being produced in exercising muscle

571 4 yo boy just recovered from severe staph pneumonia. Hx o recurrent LAD and skin infections. Flow cytomtry revels absence of green fluoresence produced by normal PMNs. Condition is due to impaired activity of which enzyme? a. adenosine demainase b cyt c oxidase c. myeloperixoidease d. NADPH oxidase

NADPH oxidase Pt. has chronic granulomatous disease - inheritance: x linked - NADPH oxidase deficiency - membrane bound complex that catalyzes reduction of O2 to O2- superoxide within phagolysosomes (ox. burst) -> intracellular killing of organisms ingested by phagocytes - recurrent bacterial and fungal infections - pneumnoa, sin and organ absecesses, suppurative adenites osteomyelitis - Dx: nitroblue tetrazolium test - lack of blue color within ccells or hihydrororohdamine (DHR testin) - - measures superoxide radical production and produces fluroeseence green (positive test = no green color) a. adenosine deaminase - SCID b. cytochrome c oxidase - terminal enzyme of mt resp. chain - deficiency is due to AR mutations and results in variable myopathic and encephalopathic findings c. myeloperoxidase in PMN azurophilic granules that aid in intracellular killing by catalyzing production of hypochllrite bleach from H2O2 and chloride - reucrrent candida

A pilot hasn't eaten anything for 2 weeks, has only had water. What condition does he have? a. increased N retention b. decreased N retention c. positive nitrogen balance d. negative N balance e. normal N balance

Negative N balance Negative nitrogen balance - N excreted from body > than amount of N ingested - basically protein is being used which is what is happening in starvation due to gng - burns, tissue injury, fever, hyperthyroidism, wasting diseases and periods of fasting Positive nitrogen balance - N intake is greater than the loss of N (or use of N) - increase in total body pool of N - occurs in periods of growth/storage - periods of growth, hypothyroidism, tissue repair, and pregnancy.

Presentation of vit E deficiency

Neurologic presentation may appear similar to vitamin B12 deficiency - loss of joint position, muscle weakness due to lateral corticospnal tract, ataxia, but without megaloblastic anemia, hypersegmented neutrophils, or serum methylmalonic acid levels. Can sometimes cause hemolysis due to lack of anioxidant activity that normal vit E does

12299 Comparing surface Ags X and Y that come from 2 diff. viruses.Obtain Abs against Ag X and attach to assay plate. Fixed quantity of radiolabeled X is added to plate. Unlabeled Y Ags are added in increasing concentrations to each plate, and plates are washed to remove unbound Ags. Radioactivity of X antigen shows no change over time. Which describes the results? a. Ags X and Y have no epitopes in common b. Ags X and Y have same epitopes

No epitopes in comon No change in radioactivity with increasing Y Ag indicates that antigen Y cannot bind the available Abs and is washed off -> shares no epitopes with antigen X Vs. same epitopes - you would see a decrease in radioactivity of Ag X bc increasing amount of unlabeled Y would compete for the binding spots and displace

The Hib vaccine does not protect against what

Non=typeable H flu - sinusitis, otitis media = local disease

8328 Kid with Down syndrome has restriction fragment length polymorphism analysis conducted to determine parental origin of extra chromosome. DNA samples from the child, mom, father are obtained and DNA is gragmented with restriction enzyme. Analysis for child, hows 3 different bands - 2 from mom and 1 from dad. In which event did nondisjunction ocur? a. meternal meiosis 1 b. maternal meiosis 2

Occurs in meiosis 1 because the child has 2 different bands from the mother - menaing he inherited both of her homologus chomosomes - which normally sparate during meiosis 1 -> this also results in an increased likelihood of trisomy If nondisjunctino had occured in meiosis 2, the child's analysis would show only 2 bands - single from father and darker thicker band from the mother which signified inheritance of both sister chromatids (produce equal size resitriction fragments)- which normally separate during meiosis 2

What is the product of multiple drug resistance gene MDR?

P glycoprotein - ATP depdent efflux pump in tumor cells and intestinal/renal epithalial cells to eliminate foreign compounds from the body

2067 6 yo with lesch nyhan syndrome would have increased activity of which enzyme as a result? a. aspartate carbamoyltransferase b. dihydroorotase c. phosphoribosyl pyrophosphate amidotransferase

PRPP amidotransferase Lesh-Nyhan - inheritance: AR - dystonia, choereoathtosis, self mutilation and hyperricemia - deficiency of HGPRT purine salvage pathway to convert hypoxanthine back to IMP and guanine back to GMP -> increased degradation of guanine and hypoxanthine bases into uric acid -> increasing demand for de novo pyrine synthesis from PRPP a. aspartate carbamoyltransferase and dihydroorotase are involved in pyrimidine synthesis

Which process is occurring in the liver due to a glucagonoma? a. decreased activity of carnitine acetyltransferase b. increased activity of acetyl coA carboxylase c. inhibition of ketogenesis d. partial oxidation of FA

Partial ox of FAs a. CAT1 and CAT2 are important enzymes of fatty acid beta oxidation - this would be increased in glucagonoma c) acetyl CoA carboxylase is used for fatty acid synthesis - this is decreased by glucagon and increased by insulin d) glucagon increases ketogenesis1G

Defieicny of acid alpha glucosidase causes what?

Pompe type 2 glyocogen storage disease -cardiomyopathy -muscle weakness -hypotonia

How are fungi killed by immune system?

Phagocytic cells detect pattern recognition receptors and destory funfi - innate immune system

How are antigens presented on MHC 2?

Phagocytosed proteins are degraded within lysosomes and attach to the invariant chain (produced in the ER) in the lysosome iteself -> transported to cell surface

14921 Patient has strep pneumo infection. PMNs are elevated, platelets are high end of normal and Hgb is normal. Serum levels of which is likely to be elevated? c. prealbumin d. procalcitonin e. transferrin

Procalcitonin - acute phase reactant produced by monocytes and C cells of thyroid - increased in response to bacterial toxins and decrease in response to viral infections -> used to seuggest community acquired pneumonia - has positive and negative properties Positive APRs - serum levels rise in inflammation: - fibrinogen, CRP, ferritin, hepcidin, ceruloplasmin, haptoglobin, vWF, complement, ESR Negative APRs: decrease in inflammation: - albumin, transferrin, transthyretin (prealbumin) C and D. Prealbumin and transferrin are negative APRs and are decreased in this patient - prealbum also decreases in malnutrition - transferrin is used to determine iron status transferrin is downregulated in inflammation by the body so there is less iron availble for potential pathogens ALso have increased hepcidin -> decreases intesitnal absorption of iron -> decreased in blood

What is affinity maturation?

Process of enhancing hypervariable region Ag binding affinity that occurs after initial binding of Ag to membrane bound Ig on naive B lymphocyte and subsequent migration of B lymphocyte to lymph node - B cells interact with Th cells within the germinal center of secondary lymphoid tissue in order to secrete immunoglobulins with higher affinity for specific antigens. - occurs after Th cell activation of B cell Accomplished by somatic hypermutation where DNA coding for Ig variable region is mutated randomly at a high rate -> result sin new Ig with similar better or worse affinity for Ag Clonal selection: only B cells expressing Ab with enhanced affinity for Ag will be selected for - increasing Ab affinity with repeated Ab exposure - process does not occur in T lymphocyte maturation

What is the function of IL-17?

Produced by Th17 cells and recruits PMNs in addition to stimulating production of antimicrobial peptides - IL-17 improves host defense against fungi and bacteria at epithelial and mucosal surfaces - dysregulation has been implicated in many autoimmune

Function of IL-3

Produced by activated T cells Growth and differentiation of stem cells in bone marrow

793 Infant has clitoromegaly and partial fusion of laboscrotal folds. Karyotype is 46 XX. Abdominal imaging shows bilateral adrenal hyperplasia. Deficiency enzymeis repsonsible for which reaction? a. cholesterol -> pregnenolone b. dehydroepiandroestone -> androstenedione c. progesterone -> 11 - deoxycorticosterone d. progesterone -> 17 hydroxyprogesterone

Progesterone -> 11 deoxycorticosterone Congenital adrenal hyperplasia - cause: 21 hydroxylase deficiency which is most common: catalyses progesterone -> 11deoxycorticosterone -> defective formation of aldo and (11DOC which has some aldo activity) and cortisol -> increased feedback to pituitary due to low cortisol -> icreased ACTH which all gets funnelled zona reticularis and forms increased testosterone -> virilizatoin in girls and precoscious puberty and salt wasting in boys

1372 4 day old infant is lethargic, poor feeding, vomiting, exageratted DTRs and clonus. Pt. has inherited condition that results in impaired transport of ornithine from cytosol to mt. Restiction of which substance can improve pt. condition? a. medium chain triglycerides b. proteins c. pyridoxine

Proteins Impaired transport of ornithine into mt is caused by ornithine translocase deficiency -> defect in urea cycle -. cannot convert ammonia into urea for excretion -> ammonia accumulates -> asterixis and lethargy, vomiting, seizures and edema in infancy -> trx: - protein restriction is main trx to prevent excess ammonia - or meds that provide a way to excrete excess N and remove ammonia

2069 Pt. anaphylaxis due to antigen specific IgE Abs attached to high affinity R on surface of mast cells and basophils. Which mechanism is likely to trigger vasoactive substance release? a. Ab R covalent binding b. Ab -R dissocaition c. R aggregation d. R detachment from cell surfac e. R internalization

R aggregation** High affinity IgE receptor on mast cells and basophils plays primary rle in mediating allergic response - R binds Fc portion of circulating IgE coating cell with various Ag specific IgE molecules - when multivalent aAg comes in contact -> multiple IgE molecules cross link -> aggregation of FceR R on mast cell surface -> R clumping leads to activation of non-R tyrosine kinases -> intracellular cascade that results in mast cell and basophil degranulation a. Ab-R do not bind covalenetly - strong binding is due to many weak noncovalent forces - no formation of covalent bonds -> b. high strength means dissociation is not likely - most IgE in body is bound to surface of mast cells and basophils and not circulating freely e. R internalization occurs in synaptic desensitization to excessive Nt stimulation + R mediated endocytosis of substances such as iron (transferrin R) and cholesterol (LDL )

Which cells have low sorbitol dehydrogenase activity?

Schwann cells, renal mesangium, lens, retinal, endothelial Osmotic cellular injuryf

1936 Toxic insult specific to kinesin. Which is absent from tissues on histo exam as a result? a. Nissl substance in pyramidal neurons b. secretory vesicles in nerve terminals c. T tubules d. desmosomes in epithelial lining e. microvilli in intestinal epithelial cells

Secretory vesicles in nerve terminals Kinesin - micrtubule associatied motor protein whose function is anterograde transport of intracellular vesicles and organeleles towards gorwing end of microtubule - uses energy derived from ATP hydrolysis to move along microtubule

1130 Woman has celiac disease, recurrent pneumonia, splenic laceration and anaphylaxis with blood tranfusion. What is diagnosis? a. ABO incompatibility b. selective IgA def

Selective IgA deficiency Presentsas: 1. autoimmuen disrdeors - celiac disease 2. recurrent sinopulm infections - sinusitis, pneumonia 3. anaphylazis in blood transufsion 4. GI (mucosal) infections - Giardia Anaphylaxis: form Ige against IgA Abs -> transfusion of blood products with IgA -> fatal anaphylaxis - should receive blood products washed of residual lasma or from igA deficiency donor

What happens in serum sickness?

Serum sickness is type 3 HS Abs to foreign proteins are produced and 1-2 weeks later -> Ag-Ab complexes form and deposit in tissues -> complement activation -> inflammation and tissue damage - causes decrease in serum C3 Histo: fibrinoid necrosis and intense PMN infilitration - neutrophil enzymes damage endothelial cells Symptoms: fever, pruritic skin rash, arthralgias that begin 7-14 days after Ag exposure, LAD and proteinuria are possible Serum sickness like rxns can occur with some drugs - that act as haptens - penicillin, infection (hep B), chimeric monoclonal abs )rituximab, infliximab), nonhuman Igs (venom antitoxins) Can also cause neutropenia due to C5a release -> PMN attraction to site of immune complex deposition - but also caused by things other than serum sickness

361 What ar anti smith abs in lupus specific for?

Smith is a protein that binds to snRNP in the cytoplasm to form ribonucleoproteins that splice introns - snRNPs splice introns from mRNA segments Anti-smith Abs prevent the formation of ribonucleoprotein complexes and prevent intron splicing

2036 6 month old boy has mutaiton in assembly of snRNPs in motor neurons. Impaired function of which cellular element? Characteristic of whatt disease?

Spliceosome Spinal muscular atrophy (SMN1) - delayed motor development and flaccid paralysis - mutaiton in survival motor neuron SMN1 gene - encodes a protein involved in assembly of SnRNPS in LMNS - degeneration of anterior horn cells in the spinal cord

A prediabetic pt. comes for consulation for bariatric surgery. Which food should he avoid in addition to a balanced diet? a. nuts b. starches c. protein d. gluten

Starches Lead to insuline resistance and hyperglycemia -> diabetes Nothig to do with bariatric surgery

1475 What are the steps in base excision repair?

Steps in base exicision repair: 1. glycosylase - cleaves altered base leaving an AP site 2. endonuclease cleaves 5' end and lyase cleaves 3' end 3. DNA pol fill the nucleotide gap 4. ligase seals the nick

11916 Woman has severe L ccalf pain post embolectomy. Left calf is swollen, tense, tender and pain worsens with dorsiflexion of L foot. Distal pulses are abset. Suspected injury of reperfused muscles due to overproduction of ROS. Which enzyme helps neutralize these toxic molecules? a. cytochrome oxidase b. CYP450 c. MPO d. NADPH ox e. superox dismutase

Superoxide dismutase** Pt as acute comparment syndrome secondary to reperfusion injury -> restoration of arterial blood flow to affected limb floods ischemic tissue with o2 -> O2 reacts with xanthine ox, NADPH ox and NO synthase to form ROS: superoxide, hydroxyl radicals, and singlet O -> disrupts cellular functions leading to: 1. DNA mutations 2. protein syntheiss disruption 3. membrane lipid perox Antioxidant enzymes such as Superoxide dismutase, glutathione perox and catalase convert ROS to O2 and water -> neutralizing cell damage potential -> ROS generated during cell respirationare neutralized by antiox before they become problematic but in postischemic state, ROs productino exceeds neutralizing capability of antiox enzymes -> increaesd cell inury and death A. cytochrome ox is final component in ETC: O2 to water while establoshing proton gradient nccessary for synthesis of ATP B. cytochrome p450 enzymes metabolise endogenous toxins as well as drugs -> cpaable of producing ROS -> hepatoox C. MPO - in PMNs -> converts H2O2 to hypochlorous acid (bleach) which causes ox damage to host cells D. NADPH ox catalyzes reduction of molecular O2 to superoxide free radicals -> bacterial desutction by phagocytic cells -> deficiency leads to chronic graunlomatous disease - unable to destroy catalase positie organisms

757 Biologists researching morphologic change associated with reversible cell injury. Clamp hepatic artery and see cells exposed to more ischemia have reduced numbers of ribosomes attached to ER. Structural change will impair which cell function? a. ATP production b. drug detox c. synthesis of cell membrane proteins d. synthesis of cytosolic proteins e. synthesis of steroid hormones

Synthesis of cell membraneproteins 1. free ribosomes -> translate proteins that go to - cytosol - nucleosol - peroxisome - mt proteins 2. attached ribosomes bind to RER after protein translation begins - 1. secretory proteins 2. cell memrbane proteins 2. proteins with ER, glogi 3. lysosomal proteins Well developed in protein secreting cells (pancreatic and plasma cells), ribosomes attach to RER via translocon, protein complex containing ribophorins that bind large 60s subunit A. Atp produced in cytosol during glycolsis and mt during ox phos - synthesised by free ribosomes b and E. steroid hormone syntehsis and drug detox performed by proteins in smooth ER - no binding to ribosomes as it lacks translocon complex

732 Man has strep bacteremia. PMH of MVA 2 yeaers ago in which he had abdominal truma and required emergency laparatomy due to internal bleeding. Impairment of which mechanism contributed to severity of patient's infection? a. complement production b. immediated hypersensitivity cd. systemic bacterial clearance e. type 1 IFN release

Systemic bacterial clearance This patient is probably asplenic secondary to splenic rupture due to trauma - spleen produces opsonizing Ab against encapsulated bacteria -> cannot clear encapsualted spaces -> decreaed systemic bacterial clerance

Spleen:

Systemic lymphoid system component - 6% of CO - most splenic capillaries are open ended and sinusoids - permit whole blood to flow into red pulp cords - form reticular meshwork that acts as fine seive with spaces as small as 1 micron in diameter - large numbers of MOs line red pulp cords and sinuosids and ingest particular matter that becomes trapped - splenic red pulp importnat for: 1. destroy abnormal rBCs and emergency storeage of RBCs and platelts that cn be delived into circulation when needed 2. clearance of circulating bacteria that become lodged. MOs present captured antigens ot B and T cells residing in slenic white pulp -> IR

In which types of immune deficiency is there an increased risk of infection following live vaccines?

T cell immunity deficiency - HIV, SCID

Cell connections

Tight junctions - zonula occludens: 1st component junctional complex - apeices of glandular cells and consist of 2 closely adherent cytoplasmic membranes without intervening space Hemidesmosomes - half desmosomes that extend from basal surface of keratinocytes in stratified squamous epithelium to attach to basal lamina (Abs against -> bullous pemphigoid) Intermediate junctions - zonula adherens: delicate netowrk of cytoplasmic filaments that radiate from cell membrane to hold adjacent cells together - second component of junctinal complex - actin = cytoplasmic anchor Desmosomes - small circular patches circumferentially around cells - 3rd component of junctional complex - common in stratified squamous epithelium - contribute to structural cohesiveness of tissues subject to mechanical stressors - anchor = intermediate filament (Abs against -> pemphigus vulgaris) Gap junctions - cell to cell communication -ex) osteocytes within concentric lamella of bony matrix -> canaliculi radiate from each lacunae to create reticular network with adjacent lacunae and cytoplasmic processes of osteocytes lie within these canaliculi

1035 Which enzyme converts fructose 6 P to ribose 5?

Transketolase Occurs in pentose phosphate pathway - generates NADPH for use in reductive reactions (ox) and R5P (nonox) - When R5P is produced in excess, transketolase and transaldolase can produce glycoltic intermediates glyceraldehyde 3 P and fructose 6 P for ATP generation When R5P demand excess production capability of ox pathway, nonox pathway functions in reverse and transketolase and transaldolase catalyze convertin of G6P and F6P back to R5P

What enzymes does thiamine deficiency impair?

Transketolast - hexose monophosphate pathway RBC ketolase decrease -> Wernicke Korsakoff and beriberi

IL-2 receptor mechanism

Transmembrane protein complex acts via multi pathways 1. JAK STAT signaling component 2. MAP kinase pathway 3. Phosphoinositide 3 kinase

2068 Patient with cellulitis is given cefazolin. After infusion started, she experiences SOB, diguse itching and dizziness. BP is 64/38 and HR is 130/mi. On exam , there is diffuse erythematous skin rash and bilateral wheezing. Which is elevated in pt serum as a result of med rxn? a. 5-HIAA b. alk phos c. calcitonin d. MPO e. tryptase

Tryptase Pt in anaphylaxis due to cefazolin - type 1 HS -> icnreased vasc perm and multisystem edema -> massive shifting of intravasc fluid to extravasc compartment - symptoms begin within seconds to minutes after intravasc exposure to inciting factor - insect strings, IV meds but can take up to 2 hours to develop with oral antigens - path: widespread mast cell and basophil degranulation and histamine and tryptase release - tryptase is a mast cell specific enzyme and elevated tryptase is used to support clinical dx of anaphylaxis after pt. is stabilized - it is preformed b. alk phos highest in bones, liver, placenta d. MPO is found in PMNs - increases in inflammation and infection but does not rise n response to acute allergic rxn

1133 Type 4 hypersensitiviy pathogenesis

Type 4: delayed type hypersensitivity 1. sensitization phase: creates hapten specific T cells and taes 10-14 days - cutaneous dendritic APCcells take up hapten and expresse them on MHC1 and 2 as hapten conjugated peptides. Dendritic cells travel to draining lymph nodes and interact with hapten sensitive CD4+ and CD8+ T ells -> activation and clonal expansion. 2. elicitation phase - 2-3 days post re exposure to same antigen. Can occur immediately following sensitization if highly antigenic Ag such as poison ivy (urushiol). In this phase, hapten is taken up by skin cells and causes activation of hapten sensitized T cells in dermis and epidermis. Results in inflamamtory response and clinical manifestatins of contact dermatitis. Rash is pruritic with papules, vesicles, and bullae and forms linear streaks Depending on the hapten, can be mediated by cytotoxic CD8+ t cells or CD4+ Th1 cells - indirect damage by MO activation. Ex) poison ivy - hapten = urushiol - highly antigenic - Cd8+ cells are primary effector- directly destroy keratinocytes expressing haptenated proteins

Albinism is caused by defiicnency of?

Tyrosinase Inhibits dopa -> melanin producition in melanocytes

11674: Which enzyme is importnat in initiating expression of antigens on MHC1 on APC for presentaiton on CD8+ T cells? 1. acid phosphatase d. myeloperoxidase e. ubiquitin ligase

Ubiquitin ligase initiates UPP by recognizing proein substrates and catalyzing ubiquitin atachment for tagging -> broken down into AA for catalbolsim to protein fragments that are recycled - peptide fragments can be coupled to MHC1 in ER and present on cell surace - Cd8+ T cells recognize viral protiens and trigger apoptosis of cell by activating caspase casccade via perforin and granzyme release (cyt C leaks from mt membrane a. acid phosphatase - found in lysosomes of most cells and hydrolyzes organic phosphates - not involved in antigen presentation d. MPO - resp burst of PMNs and release into phagocytic vaculoe and EC space as part of IR

1340 Neonate has progressive lethargy, vomiting and poor feeding. Mom reports uneventful pregnancy and perinatal course. breastfeeds and no medical problems. Infant is somnolent and dehydrated with decreased muscle tone. Lab reveals metabolic acidosis with increased AG, ketosis and hypoglycemia. Eval reveals increaed propionic acid due to defective conversion of propionyl-coA to methylmalonyl coA. Pt is unable to use which AA for energy production? a. alanine b. aspartate c. glutamate d. lysine e. Phe f. valine

Valine Several essential AAs - valine, isoleucine, methionine and threonin + odd chain FAs results in generation of propionyl-coA -> methylmalonylcoA catalized by biotin dependent propCoA carboxylase -> isomerization generates syccinlcoA -> TCA cycle Prx: propionic acidemia inheritance: AR organic acidemia caused by congenital deficiency of propionyl coA carboxylse - catalyzes conversion of propCoA -> methylmalonylcoA -> excepss propionic acid accumulates -> metabolic acidosis - hypoglycemia and ketosis are secondary to acidosis - affected pts presents 1-2 weeks post birth with lethargy, poor feeding, vomiting and hypotonia - treatment involves starting a low protein diet containing minimal amounts of valine,iisoleucine, methioine and threonine A. alanine transaminase catalyzes amino group from alanine to alpha ketoglutarate -> pyrivate production used for gng b. aspartate is non essential -> oxaloacetate -> TCA by aspartate transaminase c. glutamate - deaminated by glutamate dehydrogenase to form TCA cycle intermediate alpha ketoglutarate

745 NK cell mechanism

Virus and tumor cell apoptosis via perforin and granzyme 1. Express CD16 or CD56 2. Do not require thymus for maturation and are present in athymic pts 3. No Ag speciic activities and do not require exposure to antigen for activation 4. No antigen memory 5. Activated by IFN gamma and IL-12

1048 Woman with eccentric dietary habits presents iwth HA, vomiting, papilledema, dry skin and HSM. What is the cause of pt conditino? a. thiamine defieicn d. riboflavin defieciency c. vit C overuse f. vit E overuse g. vit A overuse

Vit A overuse Acute tox (one big dose): HA, vomiting, vertigo and blurred vision Chronic tox: long term ingestion of high dose vit A, alopecia, dry skin, hyperlipidemia and hepatotox and HSM (bc vit A normally found in the lier) and visual difficulties - papilledema suggestive of intracranial HTN (pseudotumor cerebri) Teratogenic effects: microcephaly, cardiac anomlaies, fetal death

Vit C tox

false negative stool guiac results -diarrhea, abdominal bloating

What enzyme and process will be deficiency in riboflavin deficiency?

Vitamin B2 Erythrocyte glutathione reductase - uses bound FAD (derived from B2) and NADPH as cofactors to reduce disulfide bonds Prsents with: normocytic anemia, infalmmation of the lips (cheilosis), mouth (stomatits), and tongue (glossitis)

540 IgG Autoabs against RBC antigen are able to cause cell lysis after binding the C1 complement component. Which is complement binding sire for Ig molecule? a

When C1 is activated, it can release the catalytic factors responsible for next steps in classical complement pathway. In order to be activated, C1 must bind Fc portion of 2 different Abs at specific C1 binding site = Fc portion closer to the hinge region IgM is more effective at this because it circulates as a pentamer -> more binding sites versus IgG which is a monomer A and B- hypervariable regions of Fab portion of light and heavy chain of IgG molecule respectively. These regions of Ig protein are referred to as complementarity determining regions of Ab = structure determines what Ag will be bound. C - disulfide bonds that hold heavy chain together E - Fc receptor binding site on constant region of heavy chai of IgG Ig molecule. May also be J chain binding site for IgA (dimeric) adnd IgM (pentameric) t hold together

Ability of one dieasse or trait to be caused by mutations in multiple different genes (only caused by one gene but there is more than one gene that can cause it)

locus heterogeneity ex) familial hypercholesterolemia

537 18 month white boy has eczematous rash, severe bouts of resp. infection that require hospitalization, increased bleeding time. CBC shows WBC count of 9,000 (normal) and low platelets. Platelets are abnormally small and deformed on peripheral blood smear. Which is most likely diagnosis? a. CML b. HUS c. aplastic anemia D. wiskott aldrich e. digeorge f. chediak higashi g. ataxia telangiextasia syndrome

Wiskott Aldrich Child has: 1. eczema 2. recurrent infections 3. tcp Cause: x-linked rcessive Path: combined B and T lymphocyte disorder -> increased risk of pyogenic infection due to inability to mount humoral response against organisms with PS capsule T cell defect leads to infection with opportunistic pathogens - pneumocystis, herpes Infections worsen as patient ages and becomes more apparently initially after transplacental maternal IgG and maternal mucosal IgA derived from colostrum are degraded at 6 months Trx: HLA matched bone marrow transplant

Immune deficiency with persistent diarrhea, recurrent otitis media, pneumococcal pneumonia, Giardia lamblia. Low serum levels of all Ig types.

X-linked agammaglobulinemia due to bruton tyrosine kinas mutation - infetion with encapsulated bacteria and enterovirsuses and Giardia due to lack of igA opsonization and neutralization (+ some other parsites and virus) Vs. hyper IgM syndrome - mutation in CD40/CD40L (T cell) -> cannot stimulate isotype switching by B cell

17446 5 yo has a persistent cough and recurrent ear ingections and lower resp. tract infections. Lab shows normal amounts of B, T cells and Ig. Genetic testing shows muttion in TAP1 gene, which encodoes a protein involved in the transport of cytosolic molecules into the ER. Which process is likely impaired by this mutation? a. cytotixic T cell activation by MHC 1 b. MHC class 2 molecules expression on B cells

a. cytotixic T cell activation by MHC 1 FA 100 MHC 1 expression pathway: 1. endogenous proteins of viral or cytosolic proteins degraded by proteasome -> fragments enter RER via TAP1 (transporter of antigen processing) 2. bound to MHC class 1 in ER -> translocated to cell membrane 3. activate CD8 cells through interactins wit TCR and CD8 Deficiency: bare lymphocyte syndrome - granulomatous skin lesions, freq. resp infections despite normal lymphocyte and Ig levels

1479 Microbioligsts investigating sugar metabolism by E coli. Both strains grow viable colonies on lactose media. Each strain culture on glucose. Colonies undergo Western blot precessing labeled for B galactosidase. WT colonies have trace B galactosideas. Mutant colonies express it. Variant strain contains a mutation that inhibits binding of certain protein to regularory sequence. WHich location did mutation ocur? a. activator protein CAP binding site b. operator locus c. RNA pol cistron

a. opeator locus Lac operon is regulated by: 1. negatively - binding of represor protein (encoded by lac I) to operator locus 2. positively - by cAMP- CAP binding upstream from promoter Mutations in binding of repressor protein will prevent repression of lac operon genes in absence of lactose -> increased trx of genes in lactose deiciency media -> presence of glucose will prevent maximal trx activity a. mutations that prevent cAMP binding to CAP will decreae trx bc it is a positive regulator f

1888 A child who has had nothing to eat for 24 hours appears listeless and has hepatomegaly. He has severely low glucose, no detection of acetoacetate and slightly elevated AST/ALT. Pt begins seizing shortly after arrive in emergency dpt. Which enzyme is deficiency? a.acetyl coA carboxylase b. acid alpha glucosidase c. acyl coA dehydrogenase d. glucose 6 phosphatase`

acyl coA dehydrogenase Pt has hypoketotic hypglycemia - this indicates a defect in FA beta ox. 2 causes: 1. primary carnitine deficiency - cannot carry acyl-coA into the mitochondria -muscle weakness, cardiomyopathy, elevated muscle triglycerides 2. MCAD deficiency - -seizures -sudden death - hepatomegaly Trx: acoid prolonged fasting and supplemental glucose during illness a. acetyl coA carboxylase - FA synthesis first step - supressed dring prolong fasting b.acid alpha glucosidase: Pompe disease - lack of glycogen breakdon from lysosomes - no impairment in ketone formation though c. glucose 6 phosphatase: Von Gierke disease - severe hypoglycemia during fastine due to lack of glycoegenolysis + gng -> both ketone formation is retained

What is DNA glycosylase used for?

base excision repair - removes N base from sugar phosphate backbone - endonuclase comletes remainder of repair

2042 Mutation in non coding DNa seq is beleived to affect expression of gene coding for specific fetal enzyme. Liver and bone marrow cells from fetus and parents are obtained. Which is best method to derermie i gene is being transcribed in cultures of isolated cells? a. northern blot b. western blot e. ELISA

best way to determine if gene is underoging transcriptino is detect mRNA -> northern blot

Cri du chat presentation?

cause: 5p deletion Weak, cat like cry + hypotonia, failure to thrive, developemntal delay, microcephaly, low set ears, hyper telorism and broad nasal bridge + cardiac anomalies

1071 5 day old newborn has epsiodes of emesis. Fewer wet diapers over last 2 days. Tachycardia, tachypnea, hypotension. Icteric, lethargic, sunken fontanelle, dry membranes, hepatomegal. Blood culture and abx started - culture shows gram neg rods. Bloom shows leukocytosis with bandemia. Serum shows hypoglycemia and elevated transaminases. Ammonia level is normal. Planced on special formula and improves. Which step in metabolism is impaired? b. galactose -> galacitol c. galactose -> galactose 1 P d. galactose 1 P -> glucose 1 P e. glucose 1 P -> glucose 6 P

galactose 1 P -> glucose 1 P Galactosemia - deficiency of galactose 1 P uridyltransferase (GALT) or defeect in UDP glucose -> UDP galactose by UDP galactose 4 epimerase - inheritance: AR - clinical: 1. vomiting and lethargy after breastfeeding de to accumulation of toxic galactose 1 P 2. liver dysfcx due to toxic galactose 1 P (transaminits, hyperbilirubinemia, hypoglycemia) and renal dysfucntin (hyperchloremic, metabolic acidosis, aminoacudira) 3. predisposition to E coli sepsis (due to galactose deficiency -> immune system dysfunction) 4. infantile cataracts due to galactitol accumulation 5. intellectual disapoligy 6. phosphate depletion - trx: eclude galactose and lactose (galactose and glucose) from diet Pnemonic: FAB GUT - fructose is to aldolase B as galactose is to uridyltransferase b. galactose -> galacitol by aldose rectuase - can lead to galactitol accumulation and cataracts but no other symptoms c. galactose -> galactose 1 P by galactokinase (GALK) - less severe galactosemia + cataract formation - liver and renal functions are preserved bc galactose 1 P does not accumulate e. glucose 1 P -> glucose 6 P by phosphoglucomutase FA 80

1866 27 yo man is brought to ED due to confusion. Roomate says he has been binge drinking for 5 days and had very little to eat. PMH is sig for alcohol related seizures 1 year ago. Had been sover until 2 weeks ago when he started drinkingagain. Glucoe is 35 and strongly positive for ketones. Suppression of process is cause of hypoglycemia? a. gng b. glyocogenolysis c. insulin clearance

gluconeogensis FA 72 Ethanol metabolzied by alcohol dehydrogenase and aldehyde dehyogenase -> reduces NAD+ to NADH and increases the NADH/NAD+ ration - inhibits all other pathways rewuiring NAD+ including rxns of gng - lactate cannot be conerted to pyrivate -> rxn is driven from pyrvate to lacctate - also inhibits the conversion of malate to oxaloacetate -> intermediate in gng Ethanol has no effect on insulin clearance Excess NADH inhibits FFA ox. -> diverts FFA away from lipolysis to formation of triglycerides - contribues to hepatic steatosis in alcoholic patients but does not cause hypoglycemia

Primary ciliary dyskinesia

inheritance: AR Poor mucociliary clearance in resp. tract, middle ear, and repro organs - affected pts have recurrent sinopulm infectinos in childhood and decreased fertility in adulthood - no viral or opportunistic infections

Functions of TNF-alpha

leukocyte migration, PMN and MO function,granuloma integrity, systemic inflammatory response, regulates apoptosis TNF-alpha inhibitors used in psoriasis, Crohn's and RA

8482 24 yo man comes to ED complaining of abdominal pain, vomiting and severe watery diarrhea. Recently returned from camping trip and admits to eating wild mushroms. He is ill appearing and jaundiced with hepatomegalyand elevated AST ALT and bilirubin. Synthesis of which is directly inhibited by responsible toxic? a. DNA b. mRNA c. protein d. ribosomal RNA e. tRNA

mRNA Anatoxins in mushrooms (Amanita phalloides, death cap) -> absorbed in GI tract -> transported to liver via portal circulation where active transported by organic anion transporting polypep (OATP) and sodium taurochlorate co contractors (NTCP) concentrate toxin within liver cells -> bind got DNA dependent RNA polymerase type 2 and stop mRNA synthesis -> apoptosis Other organs with rapid cell turnover are also affected by amatoxin poisoning - GI tract, PCT renal cells clinical: abdominal pain, vomiting, severe cholera like diarrhea that may be mucousy and bloody, acute hepatic or renal falure Dx: alpha amanitin in urine

11918 Researcher stdudying pathways that contribute to obesity feds in animals given high carb and high protein diet. Beta ox of FAs is inhibited within these cells as a result of the diet. Increase in which substance is most likely responsible for the observed effect? a. carnitine b. citrate c. malonyl coA e. NADPH

malonul coA - rate limiting step in FA synthesis - primary regulator Well fed state -> ATP abundance -> hepatocytes inhibit isocitrate dehydrogenase -> high levels of citrate in mitochondria -> transferred to cytosol via citrate shuttle and cleaved by ATP citrate lyase to form aceyl coA -> conversion to malonyl coA - de novo FA synthesis RLS -> FA synthase catalzyes condensation of malonyl coA with acetyl coA to create 4 C molecule that will undergo subsequent condensation reactions to form 16 C FA Beta Ox takes place in mt matric - impelermable to Fa acids due to neg charge - carnitine carrier must be used to shuttle them into matrix -> prevents transfer of acyl groups into mt - inhibitory action functions to prevent breakdown of newly synthesized FAs

vit E tox

necrotizing entercolitis, hemorrhagic stroke in adults

What does pyruvate kinase deficiency present with?

normal: generates ATP through conversion of PEP -> pyruvate inheritance: AR prx: congenital hemolytic anemia due to impaired glycolytic ATP generation

997 A man stranded for 2 days without food has blood glucose of 78. Which biochemical reaction is most likely responsible for maintaining this patient's current blood glucose levels? a. acetoacetyl coA -> 3 hydroxy 3 methylglutaryl coA b. acetyl coA -> palmitic acid c. glycogen -> glucose 1 phosphate e. oxaloacetate -> PEP

oxaloacetate -> PEP First comitted step is biotin dependent carboxylation to oxaloacetate y mt pyruvate carboxylase -> then to PEP by PEPCK -> work together to bypass pyruvate kinase aa. acetoacetyl coA -> 3 hydroxy 3 methylglutaryl coA occurs n ketosis b. acetyl coA -> palmitic acid: in fasting state you would have FA breakdown not synthesis -> gycerol and FAs c. not glycogenolysis which would be within the first 12-18 hours of fasting and then are depleted

When there are mutliple phenotypes as a result of 1 gene mutation:

pleitrophy (vs polygenism)

What enzyme is required for the initial step in gng and what is the reactino?

pyruvate carboxylase pyruate -> OAA cofactor needed : biotin