Biochem Q's

Question AnswerIn the chromatin structure, which histones form theoctamer, and which ties the nucleosome beadstogether in a string?

octamer

What amino acid makes up most of the octamer lysine and arginineWhich type of chromatin is condensed,transcriptionally inactive, sterically inaccessible? heterochromatin

Which type of chromatin is less condensed,transcriptionally active, sterically accesible euchromatin

What does PURe As Gold and CUT The Py standfor purines

How many rings do purines have 2 ringsHow many rings do pyrimidines have 1 ringHow does cytosine become uracil deaminationWhat polar group does guanine have, and whatnon polar group does thymine have ketone, methyl

Which bond is stronger AT or CG and why? Whatis the laboratory consequence of this? CG- 3 > AT-2 - More CG content, melting point goes up

What 3 amino acids are necessary for purinesynthesis glycine, aspartate, glutamine

What makes up a nucleoside base + riboseWhat makes up a nucleotide base + ribose + phosphate (3' -5') phosphodiester bondWhat are purines made from IMP precursorWhat are pyrimidines made from orotate precursor, with PRPP added laterWhat is made fir rNucleotides ordeoxyrNucleotides and what enzyme is necessaryto convert one to the next

ribos first then deoxyribos with ribonucleotide reductase

What two pathways is carbomoyl phosphateinvolved in, and what enzyme deficiency leads to abuild of carbamoyl phosphate leading to whatelement in pyrimidine synthesis

de novo pyrimidine synthesis and urea, ornithinetranscarbamoyl def in the urea cycle leads to a build ofCP, then converted to orotic acid in pyrimidine synthesispathway

Name 5 drugs that interfere with nucleotidesynthesis

hydroxyurea - inhibits ribonucleotide reductase, 6 MP -blocks de novo purine synthesis, 5 FU inhibits thymidilatesynthase, MTX - inhibits DHFR, Trimethroprin inhibitsbacterial DHFR

Inhibition of thymidilate synthase and and DHFRlead to decrease in what substance dTMP

Which step in the de novo purine and pyrimidinesynthesis pathway requires just aspartate orotic acid to UMP

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Which step in the de novo purine and pyrimidinesynthesis pathway requires aspartate, glycine,glutamine and THF

Ribose 5-P to PRPP

An inability to convert orotic acid to UMP would becaused by a deficiency either of which twoenzymes

orotic acid phosphoribosyltransferase or orotidine 5'-phosphate decarboxylase

How is orotic aciduria inherited AR

What are the findings in orotic aciduria inc orotic acid in urine, megaloblastic anemia (does notcorrect with B12 or folate), failure to thrive

What lab value can distinguish orotic aciduria fromornithine transcarbamoylase def? OTC has hyperammonemia, orotic aciduira does not

What is the treatment for orotic aciduria oral uridine administrationWhat does Adenosine deaminase deficiencycause a build up of, and what does that lead to?

excess ATP, dATP, feeback inhibits ribonucleotidereductase, no DNA synthesis

Adenosine deaminase deficiency is an importantcause of what immunodeficiency? dec DNA, dec lymphos leads to SCID

Leysh-Nyhan syndrome is a defect in whichenzyme and what are the biochemical results

HGPRT, defective purine salvage, excess uric acidproduction

What are the findings in Lesch-Nyhan retardation, self mutilation, aggression, hyperuricemia,gout, choreoathetosis

How is Lesch Neyhan inherited X-linked recessiveWhat enzyme converts adenine to AMP APRT + PRPPWhat step of uric acid synthesis does xanthineoxidase catalyze hypoxanthine to xanthing and xanthine to uric acid

What reaction does adenosine deaminasenormally catalyze adenosine to inosine

What does an umabiguous genetic code refer to each codon specifies only 1 amino acidWhat does degenerate/rundant genetic code referto more than 1 codon may code for the same amino acid

What is the exception to genetic redundancy methionine encode by only 1 codon (AUG)What does commaless, nonoverlapping geneticcode refer to

read from a fixed starting point as a continuous sequenceof bases

What does universal genetic code refer to andwhat are some exception

genetic code is conserved throughout evolution, exceptfor mito, archaebacteria, mycoplasma, and some yeast

What is a silent mutation same AA, often base change in 3rd position of codon(tRNA wobble)

What is a missense mutation changed AA (convservative - new AA is similar inchemical structure)

What is a nonsense mutation change resulting in early stop codon

What is a frame shiftchange resulting in misreading of all nucleotidesdownstream, usually resulting in a truncated nonfxnalprotein

What is the order of severity for the different types nonsense > missense > silent

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of mutationsEukaryotic and prokaryotic DNA synthesis is blankand involves both blank and blank strands

semiconservative, continuous and discontinuous strands(okazaki fragments)

For eukaryotes, where does replication begin? consesus sequenec of base pairs

What is the origin of replication particular sequence of DNA where replicatino begins -may be single of multiple

Describe the replication fork Y shaped region along the DNA template where leadingnad lagging strands are synthesized

What does helicase do unwinds DNA template at replcation forkWhat do the single stranded binding proteins do prevent strands from reannealing

What do DNA topoisomerases do creat a nick in the helix to relieave supercoils createdduring replication

What does primase do makes RNA primer on which DNA poly III can initiatereplication

What does DNA poly III do?

prokaryotic only - elongates leading strand by addingdeoxnucTIDE to the 3' end. Elongates lagging stranduntil it reaches primer of preceeding fragment. 3' to 5'exonuclease activity "proofreads" each added nucTIDE

What does DNA poly I do? prokaryotic only - degrades RNA primer and fills in thegap with DNA

What does DNA ligase do seals.How do fluoroquinolones work inhibit DNA gyrase specific for prokaryotic topoisomeraseIn which single strand DNA repair mechanism dospecific endonucleases release the oligonucTIDEcontaining bases and DNA poly and ligase fill andreseal, and what disease occures when this ismutated

nucleotide excision repair - xeroderma pigmentosum;unable to repair thymidine dimers caused by UV light

In base excision repaire, what recognizes andremoves damaged bases and what cuts the DNAto remove the empty sugar

specific glycosylases, AP endonuclease

In mismatch repair, which strand is recognized andin what hereditary syndrome is this defective unmethylated, newly synthesized, HNPCC

Is there any requirement for homology in NHEJ no - its non homologousIn what direction are DNA and RNA synthesized 5' to 3'Which carbon bears the triphosphate and theenergy source for bond formation 5' of the incoming nucleotide

What is the target of the 3' hydroxyl attack The triphosphate bondIn which direction is protein synthesized N to CWhat is the most abundant type of RNA rRNAWhat is the longest time of RNA and shortest mRNA, tRNAWhat does the start codon code for in eukaryotesand prokaryotes eu - methionine, pro - formyl-methionine

What are the mRNA stop codons UGA, UAA and UAG

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Which part of the DNA binds RNA polymerase andmultiple other TFs upstream from gene locus promotor - TATA box, and CAAT box, AT rich

What stretch of DNA that alters gene expressionby binding of transcription factors enhancers

This is the site where negative regulators bind silencersIn eukaryotes, what does RNA poly I make rRNAIn eukaryotes, what does RNA poly II make mRNAIn eukaryotes, what does RNA poly III make tRNAWhich RNA poly opens DNA at promotor site RNA poly IIRNA poly can't proofread, but what can it do initiate chainsIn prokaryotes, what does makes the differenttypes of RNA 1 kind with multiple subunits

Why does alpha amanitin cause liver failure andwhere is it found

inhibits RNA polymerase II, found in death capmushrooms

What 3 steps in RNA processing occur aftertranscription

1- capping on 5' (7-methyguanosine) 2 - polyadenylationon 3' end 3 - splicing out of introns

What is the initial transcript called and what is thecapped and tailed transcript called

initial is heterogenous nuclear RNA, the capped andtailed is called mRNA

Which enzyme involved in RNA synthesis does notrequire a template poly A polymerase - signal is AAUAA

What kind of RNA is transported out of the nucleus only processed RNAWhat does the primary transcript combine with toform the spliceosome snRNPs and other proteins

What shape does the RNA generate duringsplicing and why?

lariat shape in order and remove intron precisely and join2 exons

Which aspect of the spliceosome do patients withlupus make antibodies against snRNPs

What part of the pre mRNA contains the actualgenetic information coding for protein exons

How many nucTIDEs is a tRNA and what does thesecondary sturcture form 75 to 90, cloverleaf

Which end of the tRNA is the amino acid bound to 3' end (with CCA)What does aminoacyl tRNA synthetase do the AAbefore and after it binds to tRNA, and whathappens if it's the wrong the match

scrutinizes, hydrolyzes the bond

What does a mischarge tRNA do reads usual codon but inserts wrong AA

How do tetracyclines work bind 30s subunit preventing attachment of aminoacyl-tRNA

Accurate base pairing is required only in the firsttwo nucleotide positions of an mRNA codon, soconds differeing in the 3rd position may code forthe same tRNA/AA due to degenerate geneticcode

wobble

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What initiates protein synthesis

GTP hydrolysis, initiation factors assemble 40Sribosomal subunit with initiator tRNA and are releasedwith mRNA and ribosomal subunit assemble with thecomplex

What happens in elongation of protein synthesis

Aminoacyl-tRNA binds A site, ribosomal rRNA catalyzespeptide bond formation, transfers growing peptide to AAin A site, ribosome advances 3 nucTIDE toward 3' end ofRNA, moving peptidyl RNA to P side

What happens in termination of proteins synthesis stop codon is recognized by release factor, andcompleted protein is released from ribosome

What ribosomes do eukaryotes have 40, 60, 80What ribosomes do prokaryotes have 30, 50, 70What is the energy source for tRNA actication(charging) ATP

What is the energy source for translocation GTP

How do aminoglycosides work by inhibiting formation of the initiation complex and causemisreading of mRNA

How does chloramphenicol work inhibits 50S peptidyltransferaseHow do macrolides and clindamycin work binds 50S, blocking translocation

What is trimming removal of N or C termal propeptides from zymogens togenerate mature proteins

What are covalent alterations phosphorylation, glycosylation, hydroxylation

What is proteasomal degredation attachment of ubiquitin to defective proteins tag them forbreakdown

What are CDKs cyclin dependent kinases;constitutive and inactive

What are cyclins regulatory proteins that control cell cycle events; phasespecific; activate CDKs

What are cyclin-CDK complexes must be both activated and inactivated for cell cycle toprogress

Which tumor suppresors inhibit G1 to Sprogression, where mutations result inunrestrained growth

Rb and p53

How do permanent cells grow and regenerate andwhat are examples of permanent cells

remain in G0, regenerate from stem cells, neurons,skeletal/cardiac muscle, RBCs

How do stable (quiescent) cells grow andregenerate and what are examples

enter G1 from G0 when stimulated, hepatocytes andlymphocytes

How do labile celss grow and regenerate and whatare examples

never go to G0, divide rapidly with a short G1, bonemarrow, gut epi, skin, hair follicles

Where are the secretory proteins made and N-linked oligosaccharide addtions put on proteins RER

Where are cytosolic and organellar proteins made free ribosomesWhat is the RER called in neurons and what ismade there Nissl body, enzyme and NTs

mucus secreting globlet cells and antibody secreting

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What two cells are particularly rich in RER plasma cells

What happens at the smooth ER site of steroid synthesis and detoxification of drugs andpoisons

Which cells are rich in smooth ER liver hepatocytes and steroid producing cells of theadrenal cortex

The golgi apparatus fxns as a distribution centerbetween what organelles in the cell and what doesit process

for proteins and lipids from ER to plasma membrane,lysosomes and secretory vesicles

What does the golgi apparatus do on asparagine modifies N-oligosaccharidesWhat does the golgi add to serine and threonineresidues O-oligosaccharaides

What does the addition of mannose-6 phosphatedo targets the proteins for lysosome

What does the golgi assemble proteoglycans from core proteinswhat does the golgi do to sugars in proteoglycansand of selected tyrosine on proteins sulfation

What is I cell diseaseinherited lysosomal storage disorder; failure of addition ofmannose 6 phosphate to lysosomal proteins, enzymessecreted outside of cell instead of lysosomes

What are the clinical features of I cell diesasecoarse facial features, clouded corneas, restricted jointmovements, high plasma levels of lysosomal enzymes,often fatal in childhood

What two proteins make up microtubules and howare they arranged alpha and beta tubulin, dimers have two GTP bound

In which structures do you find microtubules flagella, cilia, mitotic spindlesHow do microtubules grow and collapse grows slowly, collapses quicklyWhich direction does dynein go post to negWhich direction does kinesin go neg to posWhich antihelminthe drugs work on microtubules mebendazole/thiabendazoleWhich antifungal drugs work on microtubules griseofulvinWhich anticancer drugs work on microtubules vincritsine/vinblastineWhich anti breast cancer drugs work onmicortubules paclitaxel

Which anti gout drugs work on microtubules colchicine

What is chediak higashimicrotuble polymerization defect causing a dec inphagocytosis results in recurrent pyogenic infections,partial albinism, and peripheral neuropathy

Describe the structure of cilia 9+2 arrangement of microtubules

What is axonemal dynein ATPase that links peripheral 9 doublets and causesbending of cilium by differential sliding of doublets

What is kartageners syndromeimmotile cilia due to dynein arm defect, male and femailinfertile, bronchiectasis, recurrent sinusitis, associatedwith situs inversus

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cytoskeletal elements in micorvilli, musclecontracting fibers, cytokenesis, adherens jxns actin and myosin

cytoskeletal elements associated with cilia,flagella, mitotic spindle, neurones and centrioles microtubules

cytoskeletal elements associated with vimenentin,desmin, cytokeratin, glial fibrillary acid protiens(GFAP), neurofilaments

intermediate filaments

What does high cholesterol or long saturated fattyacid content do to the melting temperature andfluidity

inc melt, dec fluidity

What does the vimentin stain for connective tissueWhat does desmin stain for muscleWhat does cytokeratin stain for epithelial cellswhat does GFAP stain for neuralgiaWhat do neurofilaments stain for neurons

Describe the location and fxn of the Na/K ATPase plasma membrane, 3Na out, 2K in, ATP on cytoplasmicside

How does ouabain work inhibits the Na/K pump by binding the K side

How do cardia glycosides workdirectly inhibit the Na/K pump which leads to indirectinhibition of Na/Ca exchange, inc calcium inside the cell,inc cardiac contractility

What is the most abundant protein in the body collagen

Type I collagen Bone, skin, tendon, dentin, fascia, cornea, late woundrepair

Type II collagen cartilage, hyaline, vitreous body, nucleus pulposus

Type III collagen reticulin - skin, blood vessels, uterus, fetal tissue,granulation tissue

Type IV collagen basement membrane or basal laminaType I bone bONEType II cartilage carTWOlageType IV BM 4 under the floorWhat happens in the first stage of collagensynthesis, and where does it happen

RER - translation of alpha chains, usually Gly-X-Ypolypeptide (preprocollagen)

What residues are hydroxylated in step 2 ofcollagen synthesis, and what does this require proline and lysine, vit C

What does glycosylation of pro alpha chian yieldand what is the structure procollagen, triple helix of 3 alpha collagen chains

In what cell is collagen synthesis initiated fibroblastOutside the fibroblast what part of procollagen iscleaved and what is it transformed into terminal regions, tropocollagen

How are the many staggered tropocollagenmolecules reinforced

covalent cross-linking by lysyl oxidase to make collagenfibrils

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What does Ehlers Danlos cause and why faulty collagen synthesis, hyperextensible skin, tendencyto bleed, easy bruising, hypermobile joints

What collagen type is most frequently affected inehlers danlos and what are common complications III, joint dislocation, anuerysms, organ rupture

What does osteogenesis imperfecta causes andwhy

brittle bone disease, most commonly lead AD with abnltype I collagen causing multiple fractures with minimaltrauma, blue sclerae due to translucency of connectivetissue over the choroid, hearing loss, dentalimperfections due to lack of dentin

Which kind of osteogenesis imperfecta is fata inutero or in neonatal period type II

What does Alports syndrome cause and whyprogressive hreditary nephritis and deafness, associatedwith occular disturbances - due to abnl type IV collagen,usually x-linked recessive

Type IV collagen is an important structuralcomponenet of the BM for which 3 organs kidney, ears, eyes

Where do you find elastin and what does it do lungs, large arteries, elastic ligaments, vocal cords,ligamenta flava - stretch.

Which amino acids are elastin rich in proline and glycine (non glycosylated forms)Why enzyme breaks down elastin and whatenzyme inhibits it elastase, inhibited by alpha1 antitrypsin

What is the structure of elastin tropoelastin with fibrillin scafoldingWhat causes Marfan syndrome defect in fibrillinWhat enzyme def can cause emphysema alpha1 antitrypsinWhat lab procedure is used to amplify desiredfragment of DNA and what are the 3 steps PCR, denaturation, annealing, elongation

What does a southern blot use as its sample DNAWhat does a northern blot use as its sample RNAWhat does a western blot use for its sample proteinWhat lab technique is use to profile geneexpression levels of thousands of genessimultaneously to study certain diseases andtreatments

microarrays

What is the smallest mutation a mircoarray candetect SNP

What does the ELISA test for antigen - antibody reactivity - can look for antigen orantibody in patients blood

Fluorescent DNA or RNA probe binds to specificgene of interest - used for specific localization ofgenes and direct visualization of anomalies, likemicrodeletions, at molecular level

FISH

What is DNA cloning and how do you do it?

production of a recombinant DNA molecule that is selfperpetuating, plasmids, selection, restriction enzymecleavage, tissue mRNA with reverse transcriptase to

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make cDNA

What are the two transgenic strategies in mice

constitutive - random insertion of gene into mousegenome and conditional - targeted insertion or deletion ofgene through homologous recombination with mousegene

antbiotic controlled promoter to inducibllymanipulate genes at specific developmental points cre-lox system

What is RNAi used for dsRNA promotes degradation of target mRNA knockingdown gene expression

metaphse chromosomes are stained, ordered andnumbered according to morphology, size, armlength ratio, banding pattern

karyotyping

What tissue samples are used for karyotyping blood, bone marrown, amniotic fluid, placental tissueWhat is codominance and give an example neither of 2 alleles is dominant, blood groupsWhat is variable expression and what is anexample

nature and severity of phenotype vary from 1 individual toanother, NF type 1

What is incomplete penetrence and give anexample

not all individuals with a mutant genotype show themutant phenotype

What is pleiotropy and given an example1 gene had >1 effect on an individuals phenotype, PKUcauses many seemingly unrelated symptoms rangingfrom mental retardation to hair/skin changes

What is imprinting and give an exampledifferences in phenotype depend on whether themutation is of maternal or paternal origin, prader-willi andangelman's syndrome

What is anticipation and give an example severity of disease worsens or age of onset of disease isearlier in succeeding generations, huntingtons

What is loss of heterozygosity and give anexample

if pt inherits or develops a mutation in a tumor suppresorgene, the complementary allele must be deleted/mutatedbefore cancer develops- not true of oncogenes,retinoblastoma

what is dominant negative mutation and give anexample

exerts a dominant effect, a heterozygote produces anonfxnal altered protein that also prevents the normalgene from functioning, mutation of Tx factor its allostericsite, nonfxning mutant can still bind DNA, preventing wildtype Tx from binding

What is linkage disequilibriumtendency for certain alleles at 2 linked loci to occurtogether more often than expected by chance - varies isdifferent populations

What is mosaicism and give an example

occurs when cells in the body have different geneticmakeup, can be germline mosaic, which may produce adisease that is not carried by parents somatic cells -lyonization-random X inactivation in females

What is locus heterogeneity and give an examplemutations at different loci can produce the samephenotype, marfans, MEN 2B, homocystinuria; all causemarfinoid habitus, also albinism

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What is heteroplasmy presence of both nl and mutated mtDNA resulting inmitochondrial inherited disease

What is uniparental disomy offspring receives 2 copies of a chromosome from 1parent and no copies from the other parent

What is the Hardy Weinberg disease prevalenceequation p2 +2pq+ q2

What is the hardy weinberg allele prevalence p+qWhat is the hardy weinber heterozygoteprevalence 2pq

What is the prevalence of an X-linked recessivedisease in males and in females q, q2

What are the 4 assumption of the Hardy Weinberglaw

no mutation occuring at the locus, no selection for anygenotypes at the locus, completely random mating, nomigration

Gene imprinting implies that how many alleles areactive at a single locus one

If two alleles are present, but the active allele isdeleted, what happens disease

What are the characteristics of prader willisyndrome how does it occur

mental retardation, hyperphagia, obesity, hypogonadism,hypotonia - deletion of normally active paternal allele onchromosome 15

What are the characteristics of angelmanssyndrome and how does it occur

mental retardation, seizures, ataxia, inappropriatelaughter - deletion of normally active maternal allele

characterize autosomal domint inheritance many generations, both male and female affected - oftenpleiotropic, can present clinically after puberty

characterize autosomal recessive inheritance1/4 of offspring from 2 carrier parents are affected, oftenenzyme def, usually only seen in 1 generation - oftenmore sever than AD, presents in childhood

characterize x linked recessive

sons of heterozygous mothers have 1/2 half chance ofbeing affected - no male to male transmission, and oftenmore severe in males, heterozygous females may beaffected

characterize x linked dominanttransmitted through both parents, affected mother mayhave affected children, affected father will have affectedchildren

What bone disorder has x linked dominantinheritance

hypophophatemia rickets - vit D resistant ricketts, incwasting of phosphate in proximal tubule, rickets likepresentation

characterize mitochondrial inheritance transmitted only through mother, all offspring of affectedfemales may show signs of disease

Give an example of a mitochondrial inheriteddisease

lebers hereditary optic neuropathy - degeneration ofretinal ganglion cells and axons - leads to acute loss ofcentral vision. Mitochondrial myopathies

cell signaling defect of fibroblast growth factor(FGF) receptor 3, results in dwarfism, short limbs, achondroplasia

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head/trunk nl size, associated with advancedpaternal agebilateral, massive enlargement of of kidneys due tomultiple large cysts ADPKD

How does patients present with ADPKD flank pain, hematuria, HTN, progressive renal failure90% of ADPKD cases are due to a mutation inwhat gene APKD1 on chromosome 16

ADPKD is associated with what additionalconditions

polycystic liver disease, berry aneurysm, mitral valveprolapse

colon becomes covered witih adenomatous polypsafter puberty, progresses to colon cancer unlessresected

FAP

FAP is due to deletion on what gene on whatchromosome APC on chromosome 5

elevated LDL due to defective or absent LDLreceptor - heterozygotes have cholesterol ~300,homozygotes ~700

familial hypercholesterolemia, hyperlipidemia type IIA

What are the complications/signs of familialhypercholesterolemia

sever atherosclerotic disease early in life, and tendonxanthomas on the achilles, MI may develop before 20

telangiectasia, recrrent epistaxis, skindiscolorations, AVMs

hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu syndrome)

spheroid RBCs due to spectrin or ankyrin defect,hemolytic anemia, inc MHCH, splenectomy iscurative

hereditary spherocytosis

depression, progressive dementia, choreiformmovements, caudate atrophy and dec levels ofGABA and ACH in the brain

Huntingtons

What trinucleotide repeat in Huntingtons and whatchromosome is it found on CAG, 4

fibrillin defect leading to connective tissue disorderaffecting skeleton, heart, and eyes marfans

what findings are associated with marfans tall with long extremeties, pectus excavatum,hyperextensive joints, arachnodactyly

Describe the pathophys of the aorta in a pt withmarfans, and the eyes

cystic medial necrosis of aorta leading to aorticincompetence and dissecting aortic aneurysms, floppymitral valve, subluxation of lenses

several distinct syndromes characterized byfamilial tumors of endocrine glands includingpancreas, parathyroid, pituitary, thryoid andadrenal medulla - disorders and gene association

MEN - 2A and 2B with ret gene

café au lait spots, neural tumors, lisch nodules,skeletal disorders, optic pathway gliomas neurofibromatosis type 1 (von Recklinghausens disease)

What chromosome is the NF gene on 17, 17 letters in von Recklinghausenbilateral acoustic schwannomas, juvenile cataracts NF2 on chromosome 22

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facial lesions, hypopigmented "ash leaf spots,"cortical and retinal hamartomas, seizures, mentalretardation, renal cysts, renal angiomyolipomas,cardiac rhabdomyomas, inc risk of astrocytomas

tuberous sclerosis

deletion of VHL gene on chromosome 3 leading tohemangioblastomas of retina/cerebellum/medullabilateral RCC - dz and overexpression product

von hippel lindau, 3

What do albinism, ARPKD, CF, glycogen storagediseases, hemochromatosis,mucopolysaccharidoses (except Hunters) PKU,sickle cell, sphingolipodoses (except Fabrys)thalassemias have in common

autosomal recessive diseases

CF, is AR deletion in what gene on whatchromosome resulting in a deletion inf what CFTR gene, 7, Phe 508

What does the CFTR channel do in the lungs, GItract and skin active secretion in lungs and GI, reabsorbs in skin

What does a defective Cl channel do secretion of abnl thick mucus that plugs lungs, pancreas,liver

recurrent pulmonary infxns in CF are due to whatorganisms pseudomonas and s aureus

What are the results of pancreatic insuff in CF malabsorption and steatorrhea (ADEK)

What are the results of CF on male fertility males are infertile due to bilateral absence of vasdeferens

How do you diagnose CFTR inc Cl- in sweatWhat does the mutation in the gene cause inprotein synthesis

abnormal protein folding, degradation before reachingcell surface

What is the TX for CF and what does it do N-acteylcysteine, cleave disulfide bonds within mucusglycoproteins

Name as many x-linked recessive disorders as youcan

bruton's agammaglobulinemia, wiskott-aldrich, fabrysdisease, G6PD def, ocular albinism, Lesch-Nyhansyndrome, Duchenne and Becker Muscular Dystrophy,hunter's syndrome, hemophilia A and B

What leads to the deletion of the dystrophin genein duchenne's muscular dystrophy x linked frame shif mutation

what does the deletion of the dystrophin gene leadto accelearted muscle breakdown

What is pseudohypertrophy in the calf a result of,and what are the cardiac manifestations fibrofatty replacement of muscle, cardiac myopathy

What is Gowers maneuver assistance of upper extremities to stand upWhat is the mutation in beckers musculardystrophy, what is the severity and time of onset mutated dystrophin gene, less severe, adolescence

What is the physiologic role of dystrophin anchor muscle fibers, primarily in skeletal and cardiacmuscle

What is used to diagnose muscular dystrophies inc CPK and muscle biopsy

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what gene is implicated in fragile X syndrome, andwhat is the mutation

FMR1 gene, methylation, associated with chromosomalbreakage

What are the physical findings of fragile xsyndrome

mental retardation, macro-orchidism, long face with largejaw, large everted ears, autism, and mitral valve prolapse

What is the trinucleotide repeat in fragile X CGGtrinucleotide repeat for huntingtons CAGtrinucleotide repeat fo myotonic dystrophy CTGnucleotide repeat for fragile x CGGnucleotide repeat for fredreich's ataxia GAA

What are the findings in Down's syndrome

mental retardation, flat facies, prominent epicanthal folds,simian crease, gap between 1st 2 toes, duodenal atresia,congenital heart disease (ASD), inc risk of ALL andAlzheimers

What causes Down syndromemeiotic nondisjunction of homologous chromosomes(associated with advanced maternal age) leading totrisomy 21

A small proportion of Down syndrome is due towhat two genetic events robertsonian translocation and mosaicism

What are the fetal screening measures for Down dec AFP, inc betahCGH, dec estradiol, inc inhibin - incnuchal translucency on US

What causes Edwards syndrome and what is it

trisomy 18, severe mental retardation, rocker bottom feet,micrognathia, low set ears, clenched hands, prominentocciput, congenital heart disease, death usually withinthe first year

What causes patau's syndrome and what is it

trisomy 13, severe mental retardation, rocker bottom feet,micophthlamia, microcephaly, cleft lip/palate,holoprosencephaly, polydactyly, congenital heartdisease, death usually within the first year

Describe robertsonian translocation nonreciprocal chromosomal translocation that commonlyinvolves chromosome pairs 13, 14, 15, 21, 22

Do balanced translocations cause abnl phenotype no

What are the results of unbalanced translocation miscarriage, stillbirth, chromosomal imbalance (down,patau)

congenital microdeletion of short arm ofchromosome 5 with microcephaly, moderate tosevere mental retardation, high pitchedcrying/meying, epicanthal folds, cardiac abnl

cri du chat

congenital microdeletion of long arm of chromosoe7 with findings of elfin facies, mental retardation,hypercalcemia, well developed verbal skills,extreme friendliness with strangers, cardiovascularproblems

williams syndrome

What does CATCH 22 stand for and what causesis

aberrant 3rd and 4th branchial arches causing 22q11deletion - cleft palate, abnl facies, thymic dysplasia,cardiac defects, hypocalcemia secondary to parathyroid

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aplasiaWhat defects characterize DiGeorge syndrome thymic, parathyroid and cardiacWhat defects characterize velocardiofacialsyndrome palate, facial and cardiac defects

What are the fat soluble vitamins and what doestheir absorption depend on

ADEK, dependent on gut (ileum) and pancreas -accumulate in fat and can cause toxicity

Broadly, what can cause fat-soluble vitamindeficiencies

malapsorption syndromes like sprue or CF or mineral oilintake

What are the water soluble vitamins, which onesare stored

B(1, 2, 3, 5, 6, 12) C, biotin and folate (B12 and folateare stored)

What do B-complex vitamin deficiencies oftenresult in dermatitis, glossitis, and diarrhea

What are the functinos of vitamin A

antioxidant, constituent of visual pigment, essential for nldifferntiation of epithelial cells into specialized tissue(pancreatic cells, mucus secreting cells) used to treatmeasles

What are the symptoms of vit A def night blindness, dry skin

What are the symptoms of vit A excess athralgias, fatigue, headaches, skin changes, sore throat,alopecia

What are the teratogenic effects of vit A and whattest must be ordered before starting a woman onisotreitinoin for severe acne

cleft palate, cardiac abnl, pregs test

What is Retin A used topically for wrinkles and acneWhere is vit A found in the diet liver and leafy veggies

What is the name and function of vit B1

thiamine, in thiamine pyrophosphate a cofactor forpyruvate dehydrogenase (glycolysis), alpha ketoglutaratedehydrogenase (TCA cycle), transketolase (HMP shunt),and branched-chain AA dehydrogenase

What is the results of vit B1 defimpaired glucose breakdown leading to ATP depletion;highly affected aerobic tissues like brain and heartaffected first

What 3 syndromes are associated with vit B1 def wernicke-korsakoff, dry and wet beriberi

What is the wernicke-korsakoff clinical picture confusion, opthalmoplegia, ataxia, confabulation,personality changes and memory loss

What neuroanatomical strutures are injured inwernicke-korsakoff medial dorsal nucleus of thalamus, mamillary bodies

What happens with dry beriberi polyneuritis, symmetrical muscle wasting

What happens with wet beriberi high output cardiac failure, dilated cardiomyopathy,edema

What is the name and function of vit B2 riboflavin, cofactor in oxidation and reduction (FAD andFMN are derived from riboflavin)

What happens in vit B2 def cheilosis - inflammation of lips, scaling and fissures at thecorner of the mouth, corneal vascularizationniacin, constituent of NAD and NADP, derived from

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What is the name is fxn of vit B3 tryptophanSynthesis of vit B3 requires what other vitamin B6What does vit B3 def result in glossitis - severe

what disease can cause pellagrahartnup disease - dec tryptophan absoprtion, malignantcarcinoid syndrome (inc tryptopha metabolism) and INH(dec vit B6)

What can excess vit B3 cause facial flushingWhat can vit B3 be used to treat hyperlipidemia

What is the name and fxn of vit B5 pantothenate, essential component of CoA, a cofactor foracyl transfers and fatty acid synthase

What is the result of vit B5 def dermatitis, enteritis, alopecia, adrenal insuff

What is the function and name of vit B6

pyroxidine, converted to pyroxidine phosphate a cofactorused in transamination, decarboxylation, glycogenphosphorylase, cystathionine synthesis and hemesynthesis - required for synthesis of niacin andtryptophan

What is the result of vit B5 defconvulsions, hyperirritability, peripheral neuropathy,deficiency inducible by INH and oral contraceptives,sideroblastic anemais

What is the name and fxn of vit B12 cobalamin - cofactor of homocysteine andmethyltransferase, methylmalonyl CoA mutase

Where is vit B12 found animal products, synthesized only by microorganisms,large reserve pool, mainly in liver

What happens in a B12 def

macrocytic, megaloblastic anemia, hypersegmentedPMNs, neurologic symptoms, (parasthesias, subacutecombined degeneration) due to abnl myelin, prolongedbecomes irreversible

What causes B12 defmalabsorption (sprue, enteritis) lack of intrinsic factorfrom pernicious anemia, gastric bypass surgery orabsence of terminal ileum as in Crohns

Infection with what organism can cause B12 def diphyllobothrium latumWhat test is used for B12 def Schilling test

What is the function of folic acidconverted to THF, a coenzyme for one-carbontransfer/methylation reactions, important for synthesis ofnitrogenous bases in DNA and RNA

What is the main source of folate foliage, small reserve in liver, eat green leaves

What happens in folate def macrocytic, megaloblastic anemia, no neurologic sx, mostcommon vit def in the US, seen in EtOH and pregs

What drugs can cause folate def phenytoin, MTX, and sulfonamidesGiving folate during early pregnancy is importantto prevent what birth defects neural tube

What components come together to make S-adenosyl methionine ATP and methionine

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What does SAM do transfers methyl unitsWhat is regeneration of methionine depedent on B12 and folateWhat catacholamine step is SAM required for conversion of NE to epi

What is the function of biotincofactor of carboxyltion enzymes: pyruvate carboxylase,acetate-CoA carboxylase, and propionyl-CoAcarboxylase

What substance in egg whites binds biotin Avidinpyruvate carboxylase catalyzes what rxn pyruvate to oxaloacetate (3C to 4C)Acetyl-CoA carboxylase catalyzes what rxn acetyl-CoA to malonyl-CoA (2C to 3C)What rxn does propionyl-CoA carboxylasecatalyze propionyl-CoA to methylmalonyl-CoA (3C to 4C)

What does biotin def cause dermatitis, alopecia, enteritisWhat causes biotin def antibiotic use or excessive ingestion of raw eggsWhat are the names and sources of the two typesof vit D found in nature D2

How is vit D stored 25OHD3What is the active form of vit D 1,25 OH2 D3

What is the fxn of vit D inc intestinal absorption fo calcium and phosphate, incbone resorption

What happens in vit D defrickets in kids -bending bones, osteomalacia in adults,hypocalcemia tetany, breast milk has dec vit D(supplement in dark skinned patients)

What happens in vit D excesshypercalciuria, loss of appetite, stupor, seen insarcoidosis from activation fo vit D by epithelioidmacrophage

What are the function of vit C

antioxidant, facilitates iron absorption by keeping iron inthe Fe2+ reduced state, necessary for hydroxylation ofproline and lysine collagen bridges, necessary fordopamine beta hydroxylase which converts DA to NE

What does vit C def cause scurvy - swollen gums, bruising, hemarthrosis, anemia,poor wound healing, weakened immune response

What is the fxn of vit E antioxidant, protects RBCs and membrances from freeradical damage

What does vit E def cause inc fragility of RBC, hemolytic anemia, muscle weakness,posterior column and spinocerebellar tract demyelination

What is the fxn of vit Kgamma carboxylation of glutamic acid residues onvarious proteins concerned with blood clotting,synthesized in intestinal flora

What clotting factors require vit K II, VII, IX, X (1972) protein C and S

What happens in vit K defneonatal hemorrhage with inc PT and PTT, but nlbleeding time, can also occur after prolonged use ofbroad spectrum Abx

How does warfarin work vit K antagonist

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What is the function of Zinc essential for the activity of over 100+ enzymes, importantin the formatio of zinc fingers,

What happens in zinc def delayed wound healing, hypogonadism, dec in adult hair,dysguesia, anosmia, may predispose to EtOH cirrhosis

What two enzymes are involved in EtOHmetabolism EtOH dehydrogenase and acetaldehyde dehydrogenase

Where is EtOH dehydrogenase located cytosolWhere is acetaldehyde located mitochondriaWhat is the limiting reagent in EtOH metabolism NAD+What order kinetics does EtOH dehydrogenasehave zero

what does fomepizole do inhibits EtOH dehydrogenase and is an antidote formethanol and ethylene glycol poisoning

What is disulfiram used for inhibits acetaldehyde dehydrogenase and contributes tohangover symptoms

how does ethanol induce hypoglycemia

inc NADH/NAD ratio in liver, causing diversion ofpyruvate to lactate and OAA to malate, inhibitinggluconeogenesis and stimulating fatty acid synthesis.Leads to hypoglycemia and hepatic fatty liver changeseen in chronic EtOH users

protein malnutrition resulting in skin lesions,edema and liver malfxn kwashiorkor - small child with swollen belly

energy malnutrition resulting in tissues and musclewasting, loss of subQ fat, variable edema marasmus - muscle wasting

What metabolic rxns occur in the mitochondria fatty acid oxidation, acetyl-Coa production, TCA cycle,OXPHOS

What metabolic rxns occur in the cytoplasm glycolysis, fatty acid synthesis, HMP shunt, proteinsynthesis (RER), steroid synthesis (SER)

What metabolic rxns occur in both the cytoplasmand mitochondria

heme synthesis, urea cycle and gluconeogenesis -HUGs take two

what does a kinase do uses ATP to add high energy phophate group ontosubstrate

What does a phosphorylase do adds an inorganic phosphate onto substrate withoutusing ATP

what does a phosphatase do removes phosphate group from substratewhat does a dehydrogenase do oxidizes substratewhat does a carboxylase do adds 2 carbon with the help of biotinWhat is the rate determining enzyme (RDE) ofglycolysis phosphofructokinase 1

What is the RDE of gluconeogenesis fructose 1,6 bisphosphateWhat is the RDE of TCA cycle isocitrate dehydrogenaseWhat is the RDE of glycogen synthesis glycogen synthaseWhat is the RDE of glycogenolysis glycogen phosphorylase

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What is the RDE of the HMP shunt glucose 6 phosphate dehydrogenase (G6PD)What is the RDE of de novo pyrimidine synthesis carbomoyl phosphate synthetase IIWhat is the RDE of de novo purine synthesis glutamine PRPP amidotransferaseWhat is the RDE of the urea cycle carbomoyl phosphate synthetase IWhat is the RDE of fatty acid synthesis Acetyl-CoA carboxylase (ACC)What is the RDE of fatty acid oxidation carnitine acyltransferase IWhat is the RDE of ketogenesis HMG-CoA synthaseWhat is the RDE of cholesterol synthesis HMG-CoA reductaseHow many ATP are created by aerobicmetabolism of glucose in the heart and liver viawhat shuttle

32, malate aspartate shuttle

How many ATP are created by aerobicmetobolism of glucose in muslce via what shuttle 30, glycerol-3-phosphate shuttle

How many ATP are produced by anearobicglycolysis per molecule of glucose two

How is ATP used by the cell ATP hyrdolysis couple to energetically unfavorable rxnsWhat is the activated carrier for phosphoryl ATPWhat is the activated carrier for electrons NADH, NADPH, FADH2What is the activated carrier for Acyl coenzyme A, lipoamideWhat is the activated carrier for Co2 biotinWhat is the activated carrier for 1 carbon units THFsWhat is the activated carrier for methyl groups SAMWhat is the activated carrier for aldehyddes TTP

What is NAD+ generally used for catabolic processes to carry reducing equivalents awayas NADH

What is NADPH used for anabolic processes as a supply of reducing equivalentsWhat produces NADPH HMP shunt

NADPH are used in what 4 things anabolic processes like steroid and fatty acid synthesis,respiratory burst, P-450, glutathione reductase

phosphorylation of glucose to yield glucose 6phosphate serves as the 1st step of what rxns andwhat enzymes catalyze it

glycolysis and the glycogen synthesis in the liver -hexokinase or glucokinase

Where is hexokinase found, what is its Km andVmax and what uninduces it

ubiquitous, low Km, high affinity, low capacity low Vmax,uninduced by insulin

Where is glucokinase found, what are the Km andVmax, and what induces it

liver and beta cells of pancreas, low affinity, high Km,high capacity, high Vmax, induced by insulin

What feedback inhibits hexokinase glucose-6 phosphate

What fxn does glucokinase serve in the liver phosphorylation excess glucose to sequester it, liverbecomes blood glucose buffer

What are the reactants for glycolysis glucose, 2Pi, 2ADP, 2NAD+What are the products for glycolysis 2 pyruvate, 2ATP, 2NADH, 2H+, 2H2O

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What two rxns in in glycolysis require ATP glucose to G-6P, hexokinase and fructose-6P to fructose1,6 BP phosphofructokinase-1

What substances inhibit phosphofructokinase-1 ATP, citrateWhat substances induce phosphofructokinase AMP, fructose 2,6 BP

What rxn creates ATP phosphenolpyruvate to pyruvate catalyzed by pyruvatekinase

What inhibits pyruvate kinase ATP and alanineWhat induces pyruvate kinase F16BPWhat enzyme catalyzes the rxn from pyrvuate toAcetyl-CoA and what inhibits it pyruvate dehydrogenase, ATP, NADH, acetyl-CoA

In which state is FBPase-2 active fastingIn which state is PFK-2 active fedWhat regulates whether FBPase-2 or PFK-2 isactive protein kinase A

What is the pathway in the fasting state leading toinc FBPase-2 and dec PFK-2 inc glucagon, inc cAMP, inc PKA

What is the pathway in the fed state leading to decFBPase-2 and inc PFK-2 inc insulin, dec cAMP, dec PKA

The pyruvate dehydorgenase complex serves inwhat reaction: reactants pyruvate, NAD+, CoA

The pyruvate dehydrogenase complex serves inwhat reaction: products Acetly-CoA, CO2, NADH

What co-factors are required for the pyruvateddehydrogenase complex

pyrophosphate (B1, thiamine, TPP) FAD (B2, riboflavin),NAD (B3, niacin), CoA (B5 pantothenate), lipoic acid

What activates the pyruvate dehydrogenasecomplex exercise: inc NAD/NADH, inc ADP, inc Ca

What other complex is similar to the pyruvatedehydrogenase complex in that it has the sameco-factors and generates succinyl-CoA

alpha-ketoglutarate dehydrogenase complex

What does arsenic do and what are th results ofpoisoning

inhibits lipoic acid, vomiting, rice water stools, garlicbreath

What does a pyruvate dehydrogenase deficiencylead to and what are the findings

backup of substrate (pyruvate and alanine) resulting inlactic acidosis, congenital or acquired from thiamine defin EtOH, neuro defects

What is the TX for pyruvate dehydrogenasedeficiency

inc intake of ketogenic nutrients, high in fact content orinc lysine or leucine

What are the only purely ketogenic amino acids Lysine and leucineOf the four possible fates for pyruvate, which onecarries amino groups to liver from muscle alanine

Of the four possible fates for pyruvate, which onecan replenish TCA cycle or be used ingluconeogenesis

Oxalacetate

Of the four possible fates for pyruvate, which oneis a transition from glycolysis to TCA cycle Acetyl-CoA

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Of the four possible fates for pyruvate, which endsanaerobic glycolysis as in RBCs, leukocytes,kidney medulla, lens, testes and cornea

Lactate

What does the TCA cycle produce per 1 acetylCoA 3 NADH, 1 FADH2, 2 CO2, 1 GTP

What does Citrate Is Krebs starting substrate formaking oxaloacetate

citrate, isocitrate, alpha ketoglutarate, succinyl-CoA,succinate, fumarate, malate, oxaleoacetate

How doe NADH electrons from glycolysis and theTCA cycle enter the mitochondiria

malate-aspartate shuttle or the glycerol 3 phosphateshuttle

What does the passage of electrons result in thatwhen coupled to OXPHOS drives the productionof ATP

proton gradient

Where are FADH2 electrons transferred to comlex IIWhat substances directly inhibit electron transportchain rotenone, CN-, antimycin A, CO

Wgat substances directly inhibit mitochondrialATPase, causing an inc in proton gradient, no ATPbecause pump is stopped

oligomycin

What are uncoupling agentsinc permeability of membrane causing a dec in protongradient and inc in O2 consumption - ATP synthesisstops, but electron transport continues to produce heat

What substances are uncouling agents 2,4 DNP, aspirinWhat are the irreversible enzymes ofgluconeogenesis

pyruvate carboxylase, PEP carboxykinase, fructose 1,6biphosphatase, glucose 6 phosphatase

Where is pyruvate carboxylase found, what does itdo, what does it require amd what activates it

in mitochondria, pyruvate to oxaloacetate, requires biotin,ATP, activated by acetyl coA

Where is PEP carboxykinase found, what does itdo, and what does it require

in cytosol, oxaloacetate to phosphenolpyruvate, requiresGTP

Where is fructose 1,6 bisphosphatase found andwhat does it do cytosol, F 1,6 BP to fructose 6 Phosphate

Where is glucose 6 phosphatase found and whatdoes it do in ER, glucose 6-P to glucose

Where does gluconeogenesis primarily happenand what are other sites where the enzymes arelocated

liver, also in kidney and gut epithelium

What do def in in enzymes of gluconeogenesiscause hypoglycemia

Why can't muscle produce in gluconeogenesis lacks glucose 6 phophataseHow do odd chain fatty acids participate ingluconeogenesis

via 1 proprionyl-CoA which can enter the TCA assuccinyl-CoA and undergo gluconeogenesis

Why can't even chain fatty acids produce newglucose they yield only acetyl-CoA equivalents

What is the purpose of the HMP shuntprovide a source of NADPH from an abundantly availableglucose 6P, create ribose for nucleotide synthesis and

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glycolytic intermediatesWhat are the 2 distinct phases of the HMP shuntand how many ATP are used and produced oxidative and nonoxidative, no ATP produced or used

Which phase of the HMP shunt is reversible andwhich is irreversible oxidative is irreversible

What happens on the oxidative arm of the HMPshunt and what is the key enzyme

glucose 6P to CO2, 2NADPH, ribulose 5P, G6PD, ratelimiting step

What happens on the nonoxidative arm of theHMP shunt and what is the key enzyme andcofactor

ribulose 5P to ribose 5P, G3P and F6P, transketolaseand B1

What does NADPH oxidase deficiency result inand why

chronic granulomatous disease, no respiatory burst, noformatino of ROS

What enzyme turns ROS to H2O2 superoxide dismutaseWhat enzyme adds Cl- to the H202 to makesbleach myeloperoxidase

In what cells do the respiratory burst occur PMNsWhat substance inside the cell serves to oxidizeglutatione peroxide

What substance inside the cell reduces glutatione NADPHWhat substance inside the cells replenishesNADPH G6PD

Patients with chronic granulomatous disease areat increased risk of infection from which kind oforganisms

catalase positive (catalase neg produce H2O2 the cellcan use) like S. aureus or aspergillus

What is NADPH's role inside RBCs keep glutathione reduced so it can detoxify free radicalsand peroxides

What does a decrease in decrease in NADPH leadto and why

poor defense from oxidizing agents, fava beans,sulfonamides, primaquine, antituberclosis drugs leadig tohemolytic anemia.

What other inflammatory process can induce ahemolytic anemia in NADPH defieicnt patients

infection, free radicals generated by inflammatoryresponse

Why is G6PD def more common among patientsof african decent protective against malaria

What are Heinz bodies oxidized hemoglobin precipiated within RBCs

What are bite cells and when do you see them result from phagocytic removal of heinz bodies my macs- G6PD def

benign asymptomatic condition with elevatedlevels of fructose in urine and blood, dz andenzyme

essential fructosuria - fructokinase AR

What is the defect in fructose intolerance and whatdoes it cause

aldolase B, AR, fructose 1P accumulates causing a decin availabel phosphate which inhibts glycogenolysis andgluconeogenesis leading to hypoglycemia, cirrhosis,jaundice and vomiting

What enzyme does fructose metabolism bypass to PFK - rate limiting enzyme

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reach glycolysisWhat are possilbe presentation for galactokinasedef failure to track objects or develop a social smile

What substance accumulates in galactokinase defand what is the clinical picture

galactitol, galactose appears in blood and urine, cancause infantile cataracta - AR

What enzyme results in classic galactosemia andwhat is the clinical

absence of galactose 1 phosphate uridyltransferase,accumulation of toxic substances leads to failure tothrive, jaundice, hepatomegaly, infantile cataracts,mental retardation

In addition to fructose and galactose, what sugardsshould be excluded from the diets of patients withdisorders of fructose or galactose metabolism

sucrose

What is sorbitol, how and why is it made alcohol version of glucose, can trap glucose in cell,aldose reductase

What sugar is sorbitol converted to and via whatenzyme, and what can happen in cells lacking thisenzyme

fructose via sorbitol dehydrogenase, inc sorbitol leadingto osmotic damage as in cataracts, retinopathy,peripheral neuropathy as in diabetes

What tissues have both enzymes of sorbitolmetabolism liver, ovaries, seminal vesicles

What tissues have only aldose reductase schwann cells, lens, retina, kidneys

What does lactase deficiency cause loss of brush border enzyme causing bloating, cramps,osmotic diarrhea

Who typically has lactase def African Americans and AsiansWhat form of amino acids are found in proteins L formWhat are the glucogenic essential amino acids met, val, arg hisWhat are the glucogenic/ketogenic amino acids Ile, phe, thr, trpWhat are the purely ketogenic amino acids leu, lysWhich are the acidic amino acids Asp and Glu

Which are the basic amino acids arg, lys, his, arg is most basic, has has no charge at bodypH

What two amino acids are required druing periodsof growth and why

arg and his inc in histones which bind negatively chargedDNA

What does amino acid catabolsim results in theformation of what

common metabolites like pyruvate and acetyl CoA andexcess NH4+ converted to urea and exreted

What step begins the urea cycle and what is theenzyme needed, where does it happen

CO2 + NH4 needs carbamoyl phosphate synthase I, inthe mitochondria

When does aspartate enter the urea cycle after citrulineWhat is the composition of urea and where doeach part derive from NH2-(C

How is ammonium transported from muscle to theliver for urea cycle

passed to glutamate, then to alanine enters blood, entersliver, coverted to pyruvate and transfers ammonium backto glutamate which gives it to the urea cycle

What happens in hyperammonemiadepletes alpha-ketoglutarate leading to inhibition of TCAcycle - tremor slurring of speech, somnolence, vomiting,

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cerebral edema, blurring of vision

What is the TX for hyper ammonemialimit protein diet, benzoate or phenylbutarate (both bindamino acids leading to excretion) can decrease ammonialevels

What is the most common urea cycle disorder andwhat is the mode of inheritance?

ornithin transcarbamoylase def - x linked recesssive,other urea cycle enzymes defs are autosommalrecessive

How does OTC def present

evident in first few days of life, can present last onest,excess carbamoyl phosphate converted to orotic acid,orotic acid in blood and urine, dec BUN and symptoms ofhyerpammonemia

What is the amino acid precursor forcatecholamines phenylalanine

What is the amino acid precuros for niacin andserotonin/melatonin tryptophan

What is the amino acid precursor for histamine histidineWhat is the amino acid precursor for porphyrin andheme glycine

What is the amino acid precuror for creatine, ureaand nitric oxide arginine

What is the amino acid precursor for GABA andglutathione glutamate

What enzyme converts phenylalanine to tyrosin phenylalanine hydroxylaseWhat converts tyrosine to DOPA tryosine hydroxylaseWhat converts DOPA to dopamine dopa decarboxylaseWhat converts dopamine to NE dopamine beta hydroxylaseWhat converts NE to epi phenylethamolamine N methyl transferaseWhat is the breakdown product of dopamine HVAWhat is the breakdown product of NE VMAWhat is the breakdown product of epi metanephrinedecreases in what substances can cause PKU phenylalanine hydroxylase, tetrahydrobiopterin cofactorWhat enzyme becomes essential in PKU tyrosineWhat does inc phenylalanine lead to phenylketones in urine

What are the findings in PKU mental retardation, growth retardation, seizures, fair skin,eczema, musty body odor

What is the TX for PKU dec phenylalanine (contained in aspartame, Nutrasweet)inc tyrosine in diet

What is maternal PKUlack of proper dietary therapy during pregnancy leadingto microcephaly, mental retardation growth retardation,congenital heart defects

What creates the musty body odor in PKU disorder of aromatic amino acid metabolismcongenital deficiency of homogentisic acid oxidasein the degradative pathway of tyrosine to fumarate

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leading to dark connective tissue, brownpigmented sclera, urine turns black on standing -dz and worst complication

alkaptonuria, may have debiliating arthralgias

What are the two possible causes of albinismlack of tyrosinase (no melanin) AR ordefective tyrosinetransporters (less tyrosine) - can results in lack ofmigration of NC cells

Pts with albinism are at inc risk for what cancer skinWhy is albinism inheritnace varialbe due to locus heterogeneity - ocular albinism is x-linked recessive

What are the 3 AR forms of homocystinuriacystathionine synthase def, dec affinity of cystathioninesynthase for pyridoxal phosphate, homocysteinmethyltransferase def

What is the treatment for cystathionine synthasedef dec methionine, inc cystiene, inc B12/folate

What is the treatment for dec affinity ofcystathionine synthase for pyroxidal phosphate inc vit B6

What are the findings with homocystinuria andwhat amino acid is needs to be supplemented

homocystein in ruine, mental retardation, osteoporosis,tall stature, kyphosis, lens subluxation andatherosclerosis leading to stroke and MI, cysteine

What is the defect in cystinuria hereditary defect of renal tubular amino acid transporterfor cystein, ornithine, lysine and arginine in PCT

What is the complication of cystinuria cystine kidney stones, cystine staghorn calculi - cystine ismade of two cysteines connected by disulfide bond

What causes maple syrup urine disease and whatdoes it lead to

dec in alpha ketoacid dehydrogenas leading to blockeddegredation of branches amino acids like Ile, Leu, andVal - severe CNS defects mental retardation and death

What causes Hartnup's disease AR disorder characterized by defective neutral aminoacid transporte on renal and intestinal epith cells

What does hartnups disease cause tryptophan excretion in urine and dec absorption from thegut leading to pellagra

How do glucagon/epi lead to glycogenolysisAdenylyl cycle, inc cAMP, inc PKA, glycogenphosphorylase kinase activated, glycogen phosphoylaseactive, glycolysis

How does insulin inhibit glycogenolysisreceptor tyrosine kinases, protein phosphatase, takesphosphate off glycogen phosphorylase kinaseinactivating it

What else can phosphoylate phosphorylasekinase

Ca/calmodulin in muscle to coordinate with muscleactivity

What kind of branches do glycogen branches have alpha 1,6 and alpha 1,4What happens do glycogen in skeletal muscleduring exercise glycogenolysis to form glucose

What happens to glycogen in the liver stored and undergoes glycogenolysis to maintain bloodsugar at appropriate levels

What enzyme converts glucose 1 p to UDPglucose UDP glucose pyrophosphorylase

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What enzyme degrades a small amount ofglycogen in lysosomes alpha 1,4 glucosidase

What liberates glucose from glucose 6 P glucose 6 phosphataseWhat converts limit dextran to glucose debranching enzymeVery Poor Carbohydrate Metabolism stands for 4of the glycogen storage diseases, what are thy Von Gierke's, Pompe, Cori, McArdle

Severe fasting hypoglycemia, inc glycogenstorage in liver, inc blood lactate, hepatomegaly -dz and def enzyme

von gierkes, glucose 6 phosphatase

cardiomegaly, systemic findings leading to earlydeath - dz and enzyme

pompe's lysosomal alpha 1,4 glucosidase (acid maltase)(pompe trashes the pump; heart, liver, muscle)

Milder form of type I with nl blood lactate levels -dz and enzyme

cori's, debranching enzyme alpha 1,6 glucosidase,gluconeogenesis intact

inc glycogen in muscle but can't break it down,painful muscle cramps, myglobinuria withstrenuous exercise - dz and enzyme

mcardle's, skeletal muscle glycogen posphorylase

peripheral neuropathy of hands/feet,angiokeratomas, CV/renal disease - dz, defenzyme, acc substrate, inherit

fabrys, alpha galactosidase A, ceramide trihexoside, XR

hepatosplenomegaly, aseptic necrosis of femur,bone crisis, MACS that look like crumpled tissuepaper

gaucher's, beta glucocerebrosidase, glucocerebrosie, AR

progressive neurodegeneration,hepatosplenomegaly, cherry red spot on macula,foam cells

neimann-pick, sphingomyelinase, sphingomyelin, AR

progressive neurodegeneration, developmentaldelay, cherry red spot on macula, lysosomes withonion skin, NO hepatosplenomegaly

Tay-Sachs, hexosaminidase A, GM2 ganglioside, AR

peripheral neuropathy, developmental delay, opticatrophy, glopoid cells krabbes, galactocerebrosidase, galactocerebroside, AR

central and peripheral demyelination with ataxiaand dementia

metachromatic leukodystrophy, arylsulfatase A,cerebroside sulfate AR

developmental delay, gargoylism, airwayobstruction, corneal clouding, hepatosplenomegaly

hurlers syndrome, alpha L iduronidase, heparansulfate/dermatan sulfate, AR

Mild Hurlurs + aggressive behavior no cornealclouding

Hunters, iduronate sulfatase, heparan sulfate/dermatansulfate, XR

What shuttle is used in fatty acid degredation andwhat does it move and from where to where carnitine shuttle, acyl-coa from cyto to mito

What inhibits the carnitine shuttle malonyl coa

What happens in carnitine definability to transport LCFAs into mitochondria results intoxic accumulation causing weakness, hypotonia,hyperketotic hyperglycemia

What shuttle is involved in fatty acid synthesis andwhat does it move from where to where citrate, acetyl coa from mito to cyto

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What does beta oxidation do and where does itoccur breaks down acyl-coa to acetyl coa groups in mito

what happens in acyl coa dehyrdogenase def inc dicarboxylic acids, dec in glucose and ketonesWhat does acetyl-CoA become before becomingpalmitate malonyl coa (+ biotin

What enzymes metabolize fatty acids and aminoacids acetoacetate and beta hydroxybutyrate

What occurs to oxaloacetate in starvation andDKA

depleted for gluconeogenesis staling the TCA cycle andshunting glucose and FFA to production of ketone bodies

What happens to oxaloacetate in alcholismexcess NADH shunts oxaloacetate to malate(backwards) stalling the TCA and shunting glucose andFFA to ketone body production

What are ketone bodies made from, where arethey metabolized and how are they excreted

HMG-CoA, brain to 2 molecules of acetyl-Coa, excretedin urine

in a 100 meter sprint where does energy comefrom stored ATP, creatine phosphate, anaerobic glycolysis

In a 1000 meter run, where does energy comefrom same as sprint + OXPHOS

in a marathon where does energy come from glycogen and FFA oxidation; glucose conserved for finalsprinting

What are the priorities for the body in fasting andstarvation

supply sufficient glucose to brain and RBCs and topreserve protein

What is the energy source in the fed state rightafter a meal glycolysis and aerobic respiration

What is the source of energy in the fasting statebetween meals

hepatic glycogenolysis >> hepatic gluconeogenesis >adipose release of FFA

What are the blood glucose levels maintained byfor days 1-3

hepatic glycogenolysis, adipose tissue release of FFA,muslce and liver FFA, hepatic gluconeogenesis fromperipheral tissue lactate and alanine and from adiposetissue glycerol and proprionyl-coA (odd chain FFA)

What is the energy source after day 3 of starvation

adipse tissue stores, keton bodies become the mainsource of energy fo the brain and heart, after these aredepleted, vital protein degradation accelerates, leading toorgan failure and death

When are glycogen reserves depleted after day 11 g of protein or cabrohydrate ?kcalI g fat ? KcalWhat is the rate limiting enzyme in cholesterolsynthesis HMG-CoA (HMG-CoA to mevalonate

What enzyme esterifies 2/3 of plasma cholesterol LCAT (lecithin cholesterol acyltransferase)What does lipoprotein lipase do degredation of TG circulating in chylomicrons and VLDLsWhat does pancreatic lipase do degredation of dietary TG in small intestineWhat does hepatic TG lipase do degradation of TG remaining in IDLWhat does hormone sensitive lipase do degradation of TG stored in adipocytes

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What CETP do transfers cholesterol from mature HDL to VLDL, IDL andLDL (cholesterol ester transfer protein)

What does apoA 1 do activates LCATWhat does apoB100 do binds to LDL receptor, mediates VLDL secretionWhat does apoCII do cofactor for LPLWhat does apoB48 do mediates chylomicron secretionWhat does apoE do mediates extra remnant take upDelivers dietary TGs to peripheral tissues, deliverscholesterol to liver in the form of remnants, mostlydepleted of TGs, secreted by intestinal epith cells

chylomicrons

What apolipoproteins are on chylomicrons b48, AIV, CII, Edelivers hepatic TGs to peripheral tissue, secretedby liver VLDL

What apolipoprotiens are on VLDL B-100, CII and EFormed and degradation of VLDL, delivers TGsand cholesterol to liver where they are degradedto LDL

IDL

what apolipoproteins are on IDL B100 and EDelivers hepatic cholesterol to peripheral tissues,formed by LPL modification of VLDL in theperipheral tissue, taken up by target cells via RME

LDL

What apolipoprotein is on LDL B100Mediates reverse cholesterol transport fromperiphery to liver, acts as respository for apoC anapoE, secreted from both liver and small intestine

HDL

What is the defect in I- hyperchylomicronemiaLPL def, or altered apoCII, elevated TG and cholesterol,causes pancreatitis, hepatosplenomegaly anderuptive/pruritic xannthomas - no risk of atherosclerosis

What is the defect in II A familialhypercholesterolemia

AD absent of dec LDL receptors causes acceleratedatherosclerosis, achilles xanthomas and corneal arcus,increase LDL and elecated cholesterol

what is the defectin IV - hypertriglyceridemia hepatic overproduction of VLDL causing pancreatitis,elvelated TGs and VLDL

How does abetalipoproteinemia present and whatis the defect

early in life, AR, inability to synthesize lipoproteins due todef in apoB100 and B48 - intestinal biopsy showsaccumulation within enterocytes due to inability to exportabsorbed lipid as chylomicrons - failure to thrive,steatorrhea, acanthocytosis, ata

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