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Biochem Q's
Question Answer In the chromatin structure, which histones form the octamer, and which ties the nucleosome beads octamer together in a string? What amino acid makes up most of the octamer Which type of chromatin is condensed, transcriptionally inactive, sterically inaccessible? Which type of chromatin is less condensed, transcriptionally active, sterically accesible lysine and arginine heterochromatin euchromatin

What does PURe As Gold and CUT The Py stand purines for How many rings do purines have How many rings do pyrimidines have How does cytosine become uracil What polar group does guanine have, and what non polar group does thymine have Which bond is stronger AT or CG and why? What is the laboratory consequence of this? What 3 amino acids are necessary for purine synthesis What makes up a nucleoside What makes up a nucleotide What are purines made from What are pyrimidines made from 2 rings 1 ring deamination ketone, methyl CG- 3 > AT-2 - More CG content, melting point goes up glycine, aspartate, glutamine base + ribose base + ribose + phosphate (3' -5') phosphodiester bond IMP precursor orotate precursor, with PRPP added later

What is made fir rNucleotides or deoxyrNucleotides and what enzyme is necessary ribos first then deoxyribos with ribonucleotide reductase to convert one to the next What two pathways is carbomoyl phosphate involved in, and what enzyme deficiency leads to a build of carbamoyl phosphate leading to what element in pyrimidine synthesis Name 5 drugs that interfere with nucleotide synthesis Inhibition of thymidilate synthase and and DHFR lead to decrease in what substance Which step in the de novo purine and pyrimidine synthesis pathway requires just aspartate de novo pyrimidine synthesis and urea, ornithine transcarbamoyl def in the urea cycle leads to a build of CP, then converted to orotic acid in pyrimidine synthesis pathway hydroxyurea - inhibits ribonucleotide reductase, 6 MP blocks de novo purine synthesis, 5 FU inhibits thymidilate synthase, MTX - inhibits DHFR, Trimethroprin inhibits bacterial DHFR dTMP orotic acid to UMP
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YKS Which step in the de novo purine and pyrimidine synthesis pathway requires aspartate, glycine, glutamine and THF

Ribose 5-P to PRPP

An inability to convert orotic acid to UMP would be orotic acid phosphoribosyltransferase or orotidine 5'caused by a deficiency either of which two phosphate decarboxylase enzymes How is orotic aciduria inherited What are the findings in orotic aciduria AR inc orotic acid in urine, megaloblastic anemia (does not correct with B12 or folate), failure to thrive

What lab value can distinguish orotic aciduria from OTC has hyperammonemia, orotic aciduira does not ornithine transcarbamoylase def? What is the treatment for orotic aciduria What does Adenosine deaminase deficiency cause a build up of, and what does that lead to? Adenosine deaminase deficiency is an important cause of what immunodeficiency? Leysh-Nyhan syndrome is a defect in which enzyme and what are the biochemical results What are the findings in Lesch-Nyhan How is Lesch Neyhan inherited What enzyme converts adenine to AMP What step of uric acid synthesis does xanthine oxidase catalyze What reaction does adenosine deaminase normally catalyze What does an umabiguous genetic code refer to oral uridine administration excess ATP, dATP, feeback inhibits ribonucleotide reductase, no DNA synthesis dec DNA, dec lymphos leads to SCID HGPRT, defective purine salvage, excess uric acid production retardation, self mutilation, aggression, hyperuricemia, gout, choreoathetosis X-linked recessive APRT + PRPP hypoxanthine to xanthing and xanthine to uric acid adenosine to inosine each codon specifies only 1 amino acid

What does degenerate/rundant genetic code refer more than 1 codon may code for the same amino acid to What is the exception to genetic redundancy What does commaless, nonoverlapping genetic code refer to What does universal genetic code refer to and what are some exception What is a silent mutation What is a missense mutation What is a nonsense mutation What is a frame shift What is the order of severity for the different types methionine encode by only 1 codon (AUG) read from a fixed starting point as a continuous sequence of bases genetic code is conserved throughout evolution, except for mito, archaebacteria, mycoplasma, and some yeast same AA, often base change in 3rd position of codon (tRNA wobble) changed AA (convservative - new AA is similar in chemical structure) change resulting in early stop codon change resulting in misreading of all nucleotides downstream, usually resulting in a truncated nonfxnal protein nonsense > missense > silent
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YKS of mutations

Eukaryotic and prokaryotic DNA synthesis is blank semiconservative, continuous and discontinuous strands and involves both blank and blank strands (okazaki fragments) For eukaryotes, where does replication begin? What is the origin of replication Describe the replication fork What does helicase do What do the single stranded binding proteins do What do DNA topoisomerases do What does primase do consesus sequenec of base pairs particular sequence of DNA where replicatino begins may be single of multiple Y shaped region along the DNA template where leading nad lagging strands are synthesized unwinds DNA template at replcation fork prevent strands from reannealing creat a nick in the helix to relieave supercoils created during replication makes RNA primer on which DNA poly III can initiate replication prokaryotic only - elongates leading strand by adding deoxnucTIDE to the 3' end. Elongates lagging strand until it reaches primer of preceeding fragment. 3' to 5' exonuclease activity "proofreads" each added nucTIDE prokaryotic only - degrades RNA primer and fills in the gap with DNA seals. inhibit DNA gyrase specific for prokaryotic topoisomerase nucleotide excision repair - xeroderma pigmentosum; unable to repair thymidine dimers caused by UV light

What does DNA poly III do?

What does DNA poly I do? What does DNA ligase do How do fluoroquinolones work In which single strand DNA repair mechanism do specific endonucleases release the oligonucTIDE containing bases and DNA poly and ligase fill and reseal, and what disease occures when this is mutated In base excision repaire, what recognizes and removes damaged bases and what cuts the DNA to remove the empty sugar

specific glycosylases, AP endonuclease

In mismatch repair, which strand is recognized and unmethylated, newly synthesized, HNPCC in what hereditary syndrome is this defective Is there any requirement for homology in NHEJ In what direction are DNA and RNA synthesized Which carbon bears the triphosphate and the energy source for bond formation What is the target of the 3' hydroxyl attack In which direction is protein synthesized What is the most abundant type of RNA What is the longest time of RNA and shortest What does the start codon code for in eukaryotes and prokaryotes What are the mRNA stop codons no - its non homologous 5' to 3' 5' of the incoming nucleotide The triphosphate bond N to C rRNA mRNA, tRNA eu - methionine, pro - formyl-methionine UGA, UAA and UAG
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Which partYKS the DNA binds RNA polymerase and of promotor - TATA box, and CAAT box, AT rich multiple other TFs upstream from gene locus What stretch of DNA that alters gene expression by binding of transcription factors This is the site where negative regulators bind In eukaryotes, what does RNA poly I make In eukaryotes, what does RNA poly II make In eukaryotes, what does RNA poly III make Which RNA poly opens DNA at promotor site RNA poly can't proofread, but what can it do In prokaryotes, what does makes the different types of RNA Why does alpha amanitin cause liver failure and where is it found What 3 steps in RNA processing occur after transcription What is the initial transcript called and what is the capped and tailed transcript called enhancers silencers rRNA mRNA tRNA RNA poly II initiate chains 1 kind with multiple subunits inhibits RNA polymerase II, found in death cap mushrooms 1- capping on 5' (7-methyguanosine) 2 - polyadenylation on 3' end 3 - splicing out of introns initial is heterogenous nuclear RNA, the capped and tailed is called mRNA

Which enzyme involved in RNA synthesis does not poly A polymerase - signal is AAUAA require a template What kind of RNA is transported out of the nucleus only processed RNA What does the primary transcript combine with to form the spliceosome What shape does the RNA generate during splicing and why? Which aspect of the spliceosome do patients with lupus make antibodies against What part of the pre mRNA contains the actual genetic information coding for protein snRNPs and other proteins lariat shape in order and remove intron precisely and join 2 exons snRNPs exons

How many nucTIDEs is a tRNA and what does the 75 to 90, cloverleaf secondary sturcture form Which end of the tRNA is the amino acid bound to 3' end (with CCA) What does aminoacyl tRNA synthetase do the AA before and after it binds to tRNA, and what scrutinizes, hydrolyzes the bond happens if it's the wrong the match What does a mischarge tRNA do How do tetracyclines work Accurate base pairing is required only in the first two nucleotide positions of an mRNA codon, so conds differeing in the 3rd position may code for the same tRNA/AA due to degenerate genetic code reads usual codon but inserts wrong AA bind 30s subunit preventing attachment of aminoacyltRNA

wobble

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What initiates protein synthesis

GTP hydrolysis, initiation factors assemble 40S ribosomal subunit with initiator tRNA and are released with mRNA and ribosomal subunit assemble with the complex Aminoacyl-tRNA binds A site, ribosomal rRNA catalyzes peptide bond formation, transfers growing peptide to AA in A site, ribosome advances 3 nucTIDE toward 3' end of RNA, moving peptidyl RNA to P side stop codon is recognized by release factor, and completed protein is released from ribosome 40, 60, 80 30, 50, 70 ATP GTP by inhibiting formation of the initiation complex and cause misreading of mRNA inhibits 50S peptidyltransferase binds 50S, blocking translocation removal of N or C termal propeptides from zymogens to generate mature proteins phosphorylation, glycosylation, hydroxylation attachment of ubiquitin to defective proteins tag them for breakdown cyclin dependent kinases;constitutive and inactive regulatory proteins that control cell cycle events; phase specific; activate CDKs must be both activated and inactivated for cell cycle to progress Rb and p53

What happens in elongation of protein synthesis

What happens in termination of proteins synthesis What ribosomes do eukaryotes have What ribosomes do prokaryotes have What is the energy source for tRNA actication (charging) What is the energy source for translocation How do aminoglycosides work How does chloramphenicol work How do macrolides and clindamycin work What is trimming What are covalent alterations What is proteasomal degredation What are CDKs What are cyclins What are cyclin-CDK complexes Which tumor suppresors inhibit G1 to S progression, where mutations result in unrestrained growth

How do permanent cells grow and regenerate and remain in G0, regenerate from stem cells, neurons, what are examples of permanent cells skeletal/cardiac muscle, RBCs How do stable (quiescent) cells grow and regenerate and what are examples enter G1 from G0 when stimulated, hepatocytes and lymphocytes

How do labile celss grow and regenerate and what never go to G0, divide rapidly with a short G1, bone are examples marrow, gut epi, skin, hair follicles Where are the secretory proteins made and Nlinked oligosaccharide addtions put on proteins What is the RER called in neurons and what is made there RER

Where are cytosolic and organellar proteins made free ribosomes Nissl body, enzyme and NTs mucus secreting globlet cells and antibody secreting
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YKS What two cells are particularly rich in RER

plasma cells site of steroid synthesis and detoxification of drugs and poisons liver hepatocytes and steroid producing cells of the adrenal cortex

What happens at the smooth ER Which cells are rich in smooth ER

The golgi apparatus fxns as a distribution center for proteins and lipids from ER to plasma membrane, between what organelles in the cell and what does lysosomes and secretory vesicles it process What does the golgi apparatus do on asparagine What does the golgi add to serine and threonine residues What does the addition of mannose-6 phosphate do modifies N-oligosaccharides O-oligosaccharaides targets the proteins for lysosome

What does the golgi assemble proteoglycans from core proteins what does the golgi do to sugars in proteoglycans sulfation and of selected tyrosine on proteins What is I cell disease inherited lysosomal storage disorder; failure of addition of mannose 6 phosphate to lysosomal proteins, enzymes secreted outside of cell instead of lysosomes coarse facial features, clouded corneas, restricted joint movements, high plasma levels of lysosomal enzymes, often fatal in childhood

What are the clinical features of I cell diesase

What two proteins make up microtubules and how alpha and beta tubulin, dimers have two GTP bound are they arranged In which structures do you find microtubules How do microtubules grow and collapse Which direction does dynein go Which direction does kinesin go Which antihelminthe drugs work on microtubules Which antifungal drugs work on microtubules Which anticancer drugs work on microtubules Which anti breast cancer drugs work on micortubules Which anti gout drugs work on microtubules What is chediak higashi Describe the structure of cilia What is axonemal dynein What is kartageners syndrome flagella, cilia, mitotic spindles grows slowly, collapses quickly post to neg neg to pos mebendazole/thiabendazole griseofulvin vincritsine/vinblastine paclitaxel colchicine microtuble polymerization defect causing a dec in phagocytosis results in recurrent pyogenic infections, partial albinism, and peripheral neuropathy 9+2 arrangement of microtubules ATPase that links peripheral 9 doublets and causes bending of cilium by differential sliding of doublets immotile cilia due to dynein arm defect, male and femail infertile, bronchiectasis, recurrent sinusitis, associated with situs inversus
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cytoskeletal elements in micorvilli, muscle contracting fibers, cytokenesis, adherens jxns cytoskeletal elements associated with cilia, flagella, mitotic spindle, neurones and centrioles

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actin and myosin microtubules

cytoskeletal elements associated with vimenentin, desmin, cytokeratin, glial fibrillary acid protiens intermediate filaments (GFAP), neurofilaments What does high cholesterol or long saturated fatty acid content do to the melting temperature and inc melt, dec fluidity fluidity What does the vimentin stain for What does desmin stain for What does cytokeratin stain for what does GFAP stain for What do neurofilaments stain for Describe the location and fxn of the Na/K ATPase How does ouabain work How do cardia glycosides work What is the most abundant protein in the body Type I collagen Type II collagen Type III collagen Type IV collagen Type I bone Type II cartilage Type IV BM What happens in the first stage of collagen synthesis, and where does it happen What residues are hydroxylated in step 2 of collagen synthesis, and what does this require What does glycosylation of pro alpha chian yield and what is the structure In what cell is collagen synthesis initiated Outside the fibroblast what part of procollagen is cleaved and what is it transformed into How are the many staggered tropocollagen molecules reinforced connective tissue muscle epithelial cells neuralgia neurons plasma membrane, 3Na out, 2K in, ATP on cytoplasmic side inhibits the Na/K pump by binding the K side directly inhibit the Na/K pump which leads to indirect inhibition of Na/Ca exchange, inc calcium inside the cell, inc cardiac contractility collagen Bone, skin, tendon, dentin, fascia, cornea, late wound repair cartilage, hyaline, vitreous body, nucleus pulposus reticulin - skin, blood vessels, uterus, fetal tissue, granulation tissue basement membrane or basal lamina bONE carTWOlage 4 under the floor RER - translation of alpha chains, usually Gly-X-Y polypeptide (preprocollagen) proline and lysine, vit C procollagen, triple helix of 3 alpha collagen chains fibroblast terminal regions, tropocollagen covalent cross-linking by lysyl oxidase to make collagen fibrils
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What does Ehlers Danlos cause and why

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faulty collagen synthesis, hyperextensible skin, tendency to bleed, easy bruising, hypermobile joints

What collagen type is most frequently affected in III, joint dislocation, anuerysms, organ rupture ehlers danlos and what are common complications What does osteogenesis imperfecta causes and why Which kind of osteogenesis imperfecta is fata in utero or in neonatal period What does Alports syndrome cause and why Type IV collagen is an important structural componenet of the BM for which 3 organs Where do you find elastin and what does it do Which amino acids are elastin rich in Why enzyme breaks down elastin and what enzyme inhibits it What is the structure of elastin What causes Marfan syndrome What enzyme def can cause emphysema What lab procedure is used to amplify desired fragment of DNA and what are the 3 steps What does a southern blot use as its sample What does a northern blot use as its sample What does a western blot use for its sample What lab technique is use to profile gene expression levels of thousands of genes simultaneously to study certain diseases and treatments What is the smallest mutation a mircoarray can detect What does the ELISA test for Fluorescent DNA or RNA probe binds to specific gene of interest - used for specific localization of genes and direct visualization of anomalies, like microdeletions, at molecular level What is DNA cloning and how do you do it? brittle bone disease, most commonly lead AD with abnl type I collagen causing multiple fractures with minimal trauma, blue sclerae due to translucency of connective tissue over the choroid, hearing loss, dental imperfections due to lack of dentin type II progressive hreditary nephritis and deafness, associated with occular disturbances - due to abnl type IV collagen, usually x-linked recessive kidney, ears, eyes lungs, large arteries, elastic ligaments, vocal cords, ligamenta flava - stretch. proline and glycine (non glycosylated forms) elastase, inhibited by alpha1 antitrypsin tropoelastin with fibrillin scafolding defect in fibrillin alpha1 antitrypsin PCR, denaturation, annealing, elongation DNA RNA protein microarrays

SNP antigen - antibody reactivity - can look for antigen or antibody in patients blood FISH production of a recombinant DNA molecule that is self perpetuating, plasmids, selection, restriction enzyme cleavage, tissue mRNA with reverse transcriptase to
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make cDNA constitutive - random insertion of gene into mouse genome and conditional - targeted insertion or deletion of gene through homologous recombination with mouse gene

What are the two transgenic strategies in mice

antbiotic controlled promoter to induciblly cre-lox system manipulate genes at specific developmental points What is RNAi used for dsRNA promotes degradation of target mRNA knocking down gene expression

metaphse chromosomes are stained, ordered and numbered according to morphology, size, arm karyotyping length ratio, banding pattern What tissue samples are used for karyotyping What is codominance and give an example What is variable expression and what is an example What is incomplete penetrence and give an example What is pleiotropy and given an example blood, bone marrown, amniotic fluid, placental tissue neither of 2 alleles is dominant, blood groups nature and severity of phenotype vary from 1 individual to another, NF type 1 not all individuals with a mutant genotype show the mutant phenotype 1 gene had >1 effect on an individuals phenotype, PKU causes many seemingly unrelated symptoms ranging from mental retardation to hair/skin changes differences in phenotype depend on whether the mutation is of maternal or paternal origin, prader-willi and angelman's syndrome severity of disease worsens or age of onset of disease is earlier in succeeding generations, huntingtons if pt inherits or develops a mutation in a tumor suppresor gene, the complementary allele must be deleted/mutated before cancer develops- not true of oncogenes, retinoblastoma exerts a dominant effect, a heterozygote produces a nonfxnal altered protein that also prevents the normal gene from functioning, mutation of Tx factor its allosteric site, nonfxning mutant can still bind DNA, preventing wild type Tx from binding tendency for certain alleles at 2 linked loci to occur together more often than expected by chance - varies is different populations occurs when cells in the body have different genetic makeup, can be germline mosaic, which may produce a disease that is not carried by parents somatic cells lyonization-random X inactivation in females mutations at different loci can produce the same phenotype, marfans, MEN 2B, homocystinuria; all cause marfinoid habitus, also albinism
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What is imprinting and give an example What is anticipation and give an example What is loss of heterozygosity and give an example

what is dominant negative mutation and give an example

What is linkage disequilibrium

What is mosaicism and give an example

What is locus heterogeneity and give an example

What is heteroplasmy What is uniparental disomy What is the Hardy Weinberg disease prevalence equation What is the hardy weinberg allele prevalence What is the hardy weinber heterozygote prevalence What is the prevalence of an X-linked recessive disease in males and in females

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presence of both nl and mutated mtDNA resulting in mitochondrial inherited disease offspring receives 2 copies of a chromosome from 1 parent and no copies from the other parent p2 +2pq+ q2 p+q 2pq q, q2

no mutation occuring at the locus, no selection for any What are the 4 assumption of the Hardy Weinberg genotypes at the locus, completely random mating, no law migration Gene imprinting implies that how many alleles are one active at a single locus If two alleles are present, but the active allele is deleted, what happens What are the characteristics of prader willi syndrome how does it occur What are the characteristics of angelmans syndrome and how does it occur characterize autosomal domint inheritance characterize autosomal recessive inheritance disease mental retardation, hyperphagia, obesity, hypogonadism, hypotonia - deletion of normally active paternal allele on chromosome 15 mental retardation, seizures, ataxia, inappropriate laughter - deletion of normally active maternal allele many generations, both male and female affected - often pleiotropic, can present clinically after puberty 1/4 of offspring from 2 carrier parents are affected, often enzyme def, usually only seen in 1 generation - often more sever than AD, presents in childhood sons of heterozygous mothers have 1/2 half chance of being affected - no male to male transmission, and often more severe in males, heterozygous females may be affected transmitted through both parents, affected mother may have affected children, affected father will have affected children hypophophatemia rickets - vit D resistant ricketts, inc wasting of phosphate in proximal tubule, rickets like presentation transmitted only through mother, all offspring of affected females may show signs of disease lebers hereditary optic neuropathy - degeneration of retinal ganglion cells and axons - leads to acute loss of central vision. Mitochondrial myopathies achondroplasia
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characterize x linked recessive

characterize x linked dominant What bone disorder has x linked dominant inheritance characterize mitochondrial inheritance Give an example of a mitochondrial inherited disease cell signaling defect of fibroblast growth factor (FGF) receptor 3, results in dwarfism, short limbs,

head/trunkYKSsize, associated with advanced nl paternal age bilateral, massive enlargement of of kidneys due to ADPKD multiple large cysts How does patients present with ADPKD 90% of ADPKD cases are due to a mutation in what gene ADPKD is associated with what additional conditions flank pain, hematuria, HTN, progressive renal failure APKD1 on chromosome 16 polycystic liver disease, berry aneurysm, mitral valve prolapse

colon becomes covered witih adenomatous polyps after puberty, progresses to colon cancer unless FAP resected FAP is due to deletion on what gene on what chromosome elevated LDL due to defective or absent LDL receptor - heterozygotes have cholesterol ~300, homozygotes ~700 What are the complications/signs of familial hypercholesterolemia telangiectasia, recrrent epistaxis, skin discolorations, AVMs spheroid RBCs due to spectrin or ankyrin defect, hemolytic anemia, inc MHCH, splenectomy is curative depression, progressive dementia, choreiform movements, caudate atrophy and dec levels of GABA and ACH in the brain APC on chromosome 5 familial hypercholesterolemia, hyperlipidemia type IIA sever atherosclerotic disease early in life, and tendon xanthomas on the achilles, MI may develop before 20 hereditary hemorrhagic telangiectasia (Osler-WeberRendu syndrome) hereditary spherocytosis

Huntingtons

What trinucleotide repeat in Huntingtons and what CAG, 4 chromosome is it found on fibrillin defect leading to connective tissue disorder marfans affecting skeleton, heart, and eyes what findings are associated with marfans Describe the pathophys of the aorta in a pt with marfans, and the eyes several distinct syndromes characterized by familial tumors of endocrine glands including pancreas, parathyroid, pituitary, thryoid and adrenal medulla - disorders and gene association caf au lait spots, neural tumors, lisch nodules, skeletal disorders, optic pathway gliomas What chromosome is the NF gene on tall with long extremeties, pectus excavatum, hyperextensive joints, arachnodactyly cystic medial necrosis of aorta leading to aortic incompetence and dissecting aortic aneurysms, floppy mitral valve, subluxation of lenses MEN - 2A and 2B with ret gene

neurofibromatosis type 1 (von Recklinghausens disease) 17, 17 letters in von Recklinghausen

bilateral acoustic schwannomas, juvenile cataracts NF2 on chromosome 22

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

tuberous sclerosis

deletion of VHL gene on chromosome 3 leading to hemangioblastomas of retina/cerebellum/medulla von hippel lindau, 3 bilateral RCC - dz and overexpression product What do albinism, ARPKD, CF, glycogen storage diseases, hemochromatosis, mucopolysaccharidoses (except Hunters) PKU, sickle cell, sphingolipodoses (except Fabrys) thalassemias have in common CF, is AR deletion in what gene on what chromosome resulting in a deletion inf what What does the CFTR channel do in the lungs, GI tract and skin What does a defective Cl channel do recurrent pulmonary infxns in CF are due to what organisms What are the results of pancreatic insuff in CF What are the results of CF on male fertility How do you diagnose CFTR What does the mutation in the gene cause in protein synthesis What is the TX for CF and what does it do

autosomal recessive diseases

CFTR gene, 7, Phe 508 active secretion in lungs and GI, reabsorbs in skin secretion of abnl thick mucus that plugs lungs, pancreas, liver pseudomonas and s aureus malabsorption and steatorrhea (ADEK) males are infertile due to bilateral absence of vas deferens inc Cl- in sweat abnormal protein folding, degradation before reaching cell surface N-acteylcysteine, cleave disulfide bonds within mucus glycoproteins

bruton's agammaglobulinemia, wiskott-aldrich, fabrys Name as many x-linked recessive disorders as you disease, G6PD def, ocular albinism, Lesch-Nyhan syndrome, Duchenne and Becker Muscular Dystrophy, can hunter's syndrome, hemophilia A and B What leads to the deletion of the dystrophin gene in duchenne's muscular dystrophy x linked frame shif mutation

what does the deletion of the dystrophin gene lead accelearted muscle breakdown to What is pseudohypertrophy in the calf a result of, and what are the cardiac manifestations What is Gowers maneuver What is the mutation in beckers muscular dystrophy, what is the severity and time of onset What is the physiologic role of dystrophin What is used to diagnose muscular dystrophies fibrofatty replacement of muscle, cardiac myopathy assistance of upper extremities to stand up mutated dystrophin gene, less severe, adolescence anchor muscle fibers, primarily in skeletal and cardiac muscle inc CPK and muscle biopsy
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what gene YKSimplicated in fragile X syndrome, and FMR1 gene, methylation, associated with chromosomal is what is the mutation breakage What are the physical findings of fragile x syndrome What is the trinucleotide repeat in fragile X trinucleotide repeat for huntingtons trinucleotide repeat fo myotonic dystrophy nucleotide repeat for fragile x nucleotide repeat for fredreich's ataxia What are the findings in Down's syndrome mental retardation, macro-orchidism, long face with large jaw, large everted ears, autism, and mitral valve prolapse CGG CAG CTG CGG GAA mental retardation, flat facies, prominent epicanthal folds, simian crease, gap between 1st 2 toes, duodenal atresia, congenital heart disease (ASD), inc risk of ALL and Alzheimers meiotic nondisjunction of homologous chromosomes (associated with advanced maternal age) leading to trisomy 21 robertsonian translocation and mosaicism dec AFP, inc betahCGH, dec estradiol, inc inhibin - inc nuchal translucency on US trisomy 18, severe mental retardation, rocker bottom feet, micrognathia, low set ears, clenched hands, prominent occiput, congenital heart disease, death usually within the first year trisomy 13, severe mental retardation, rocker bottom feet, micophthlamia, microcephaly, cleft lip/palate, holoprosencephaly, polydactyly, congenital heart disease, death usually within the first year nonreciprocal chromosomal translocation that commonly involves chromosome pairs 13, 14, 15, 21, 22 miscarriage, stillbirth, chromosomal imbalance (down, patau) cri du chat

What causes Down syndrome A small proportion of Down syndrome is due to what two genetic events What are the fetal screening measures for Down

What causes Edwards syndrome and what is it

What causes patau's syndrome and what is it

Describe robertsonian translocation

Do balanced translocations cause abnl phenotype no What are the results of unbalanced translocation congenital microdeletion of short arm of chromosome 5 with microcephaly, moderate to severe mental retardation, high pitched crying/meying, epicanthal folds, cardiac abnl

congenital microdeletion of long arm of chromosoe 7 with findings of elfin facies, mental retardation, williams syndrome hypercalcemia, well developed verbal skills, extreme friendliness with strangers, cardiovascular problems What does CATCH 22 stand for and what causes is aberrant 3rd and 4th branchial arches causing 22q11 deletion - cleft palate, abnl facies, thymic dysplasia, cardiac defects, hypocalcemia secondary to parathyroid
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aplasia thymic, parathyroid and cardiac palate, facial and cardiac defects ADEK, dependent on gut (ileum) and pancreas accumulate in fat and can cause toxicity malapsorption syndromes like sprue or CF or mineral oil intake B(1, 2, 3, 5, 6, 12) C, biotin and folate (B12 and folate are stored) dermatitis, glossitis, and diarrhea antioxidant, constituent of visual pigment, essential for nl differntiation of epithelial cells into specialized tissue (pancreatic cells, mucus secreting cells) used to treat measles night blindness, dry skin athralgias, fatigue, headaches, skin changes, sore throat, alopecia cleft palate, cardiac abnl, pregs test wrinkles and acne liver and leafy veggies thiamine, in thiamine pyrophosphate a cofactor for pyruvate dehydrogenase (glycolysis), alpha ketoglutarate dehydrogenase (TCA cycle), transketolase (HMP shunt), and branched-chain AA dehydrogenase impaired glucose breakdown leading to ATP depletion; highly affected aerobic tissues like brain and heart affected first wernicke-korsakoff, dry and wet beriberi confusion, opthalmoplegia, ataxia, confabulation, personality changes and memory loss medial dorsal nucleus of thalamus, mamillary bodies polyneuritis, symmetrical muscle wasting high output cardiac failure, dilated cardiomyopathy, edema riboflavin, cofactor in oxidation and reduction (FAD and FMN are derived from riboflavin) cheilosis - inflammation of lips, scaling and fissures at the corner of the mouth, corneal vascularization niacin, constituent of NAD and NADP, derived from
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What defects characterize DiGeorge syndrome What defects characterize velocardiofacial syndrome What are the fat soluble vitamins and what does their absorption depend on Broadly, what can cause fat-soluble vitamin deficiencies What are the water soluble vitamins, which ones are stored What do B-complex vitamin deficiencies often result in What are the functinos of vitamin A What are the symptoms of vit A def What are the symptoms of vit A excess What are the teratogenic effects of vit A and what test must be ordered before starting a woman on isotreitinoin for severe acne What is Retin A used topically for Where is vit A found in the diet What is the name and function of vit B1

What is the results of vit B1 def What 3 syndromes are associated with vit B1 def What is the wernicke-korsakoff clinical picture What neuroanatomical strutures are injured in wernicke-korsakoff What happens with dry beriberi What happens with wet beriberi What is the name and function of vit B2 What happens in vit B2 def

YKS What is the name is fxn of vit B3

tryptophan B6 glossitis - severe hartnup disease - dec tryptophan absoprtion, malignant carcinoid syndrome (inc tryptopha metabolism) and INH (dec vit B6) facial flushing hyperlipidemia pantothenate, essential component of CoA, a cofactor for acyl transfers and fatty acid synthase dermatitis, enteritis, alopecia, adrenal insuff pyroxidine, converted to pyroxidine phosphate a cofactor used in transamination, decarboxylation, glycogen phosphorylase, cystathionine synthesis and heme synthesis - required for synthesis of niacin and tryptophan convulsions, hyperirritability, peripheral neuropathy, deficiency inducible by INH and oral contraceptives, sideroblastic anemais cobalamin - cofactor of homocysteine and methyltransferase, methylmalonyl CoA mutase animal products, synthesized only by microorganisms, large reserve pool, mainly in liver macrocytic, megaloblastic anemia, hypersegmented PMNs, neurologic symptoms, (parasthesias, subacute combined degeneration) due to abnl myelin, prolonged becomes irreversible malabsorption (sprue, enteritis) lack of intrinsic factor from pernicious anemia, gastric bypass surgery or absence of terminal ileum as in Crohns diphyllobothrium latum Schilling test converted to THF, a coenzyme for one-carbon transfer/methylation reactions, important for synthesis of nitrogenous bases in DNA and RNA foliage, small reserve in liver, eat green leaves macrocytic, megaloblastic anemia, no neurologic sx, most common vit def in the US, seen in EtOH and pregs phenytoin, MTX, and sulfonamides neural tube ATP and methionine
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Synthesis of vit B3 requires what other vitamin What does vit B3 def result in what disease can cause pellagra What can excess vit B3 cause What can vit B3 be used to treat What is the name and fxn of vit B5 What is the result of vit B5 def

What is the function and name of vit B6

What is the result of vit B5 def What is the name and fxn of vit B12 Where is vit B12 found

What happens in a B12 def

What causes B12 def Infection with what organism can cause B12 def What test is used for B12 def What is the function of folic acid What is the main source of folate What happens in folate def What drugs can cause folate def Giving folate during early pregnancy is important to prevent what birth defects What components come together to make Sadenosyl methionine

What doesYKS do SAM What is regeneration of methionine depedent on What catacholamine step is SAM required for What is the function of biotin What substance in egg whites binds biotin pyruvate carboxylase catalyzes what rxn Acetyl-CoA carboxylase catalyzes what rxn What rxn does propionyl-CoA carboxylase catalyze What does biotin def cause What causes biotin def

transfers methyl units B12 and folate conversion of NE to epi cofactor of carboxyltion enzymes: pyruvate carboxylase, acetate-CoA carboxylase, and propionyl-CoA carboxylase Avidin pyruvate to oxaloacetate (3C to 4C) acetyl-CoA to malonyl-CoA (2C to 3C) propionyl-CoA to methylmalonyl-CoA (3C to 4C) dermatitis, alopecia, enteritis antibiotic use or excessive ingestion of raw eggs

What are the names and sources of the two types D2 of vit D found in nature How is vit D stored What is the active form of vit D What is the fxn of vit D What happens in vit D def 25OHD3 1,25 OH2 D3 inc intestinal absorption fo calcium and phosphate, inc bone resorption rickets in kids -bending bones, osteomalacia in adults, hypocalcemia tetany, breast milk has dec vit D (supplement in dark skinned patients) hypercalciuria, loss of appetite, stupor, seen in sarcoidosis from activation fo vit D by epithelioid macrophage antioxidant, facilitates iron absorption by keeping iron in the Fe2+ reduced state, necessary for hydroxylation of proline and lysine collagen bridges, necessary for dopamine beta hydroxylase which converts DA to NE scurvy - swollen gums, bruising, hemarthrosis, anemia, poor wound healing, weakened immune response antioxidant, protects RBCs and membrances from free radical damage inc fragility of RBC, hemolytic anemia, muscle weakness, posterior column and spinocerebellar tract demyelination gamma carboxylation of glutamic acid residues on various proteins concerned with blood clotting, synthesized in intestinal flora II, VII, IX, X (1972) protein C and S neonatal hemorrhage with inc PT and PTT, but nl bleeding time, can also occur after prolonged use of broad spectrum Abx vit K antagonist
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What happens in vit D excess

What are the function of vit C

What does vit C def cause What is the fxn of vit E What does vit E def cause What is the fxn of vit K What clotting factors require vit K What happens in vit K def How does warfarin work

What is the function of Zinc What happens in zinc def What two enzymes are involved in EtOH metabolism Where is EtOH dehydrogenase located Where is acetaldehyde located What is the limiting reagent in EtOH metabolism What order kinetics does EtOH dehydrogenase have what does fomepizole do What is disulfiram used for

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essential for the activity of over 100+ enzymes, important in the formatio of zinc fingers, delayed wound healing, hypogonadism, dec in adult hair, dysguesia, anosmia, may predispose to EtOH cirrhosis EtOH dehydrogenase and acetaldehyde dehydrogenase cytosol mitochondria NAD+ zero inhibits EtOH dehydrogenase and is an antidote for methanol and ethylene glycol poisoning inhibits acetaldehyde dehydrogenase and contributes to hangover symptoms inc NADH/NAD ratio in liver, causing diversion of pyruvate to lactate and OAA to malate, inhibiting gluconeogenesis and stimulating fatty acid synthesis. Leads to hypoglycemia and hepatic fatty liver change seen in chronic EtOH users kwashiorkor - small child with swollen belly

how does ethanol induce hypoglycemia

protein malnutrition resulting in skin lesions, edema and liver malfxn

energy malnutrition resulting in tissues and muscle marasmus - muscle wasting wasting, loss of subQ fat, variable edema What metabolic rxns occur in the mitochondria What metabolic rxns occur in the cytoplasm What metabolic rxns occur in both the cytoplasm and mitochondria what does a kinase do What does a phosphorylase do what does a phosphatase do what does a dehydrogenase do what does a carboxylase do What is the rate determining enzyme (RDE) of glycolysis What is the RDE of gluconeogenesis What is the RDE of TCA cycle What is the RDE of glycogen synthesis What is the RDE of glycogenolysis fatty acid oxidation, acetyl-Coa production, TCA cycle, OXPHOS glycolysis, fatty acid synthesis, HMP shunt, protein synthesis (RER), steroid synthesis (SER) heme synthesis, urea cycle and gluconeogenesis HUGs take two uses ATP to add high energy phophate group onto substrate adds an inorganic phosphate onto substrate without using ATP removes phosphate group from substrate oxidizes substrate adds 2 carbon with the help of biotin phosphofructokinase 1 fructose 1,6 bisphosphate isocitrate dehydrogenase glycogen synthase glycogen phosphorylase
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YKS What is the RDE of the HMP shunt

glucose 6 phosphate dehydrogenase (G6PD) carbomoyl phosphate synthetase II glutamine PRPP amidotransferase carbomoyl phosphate synthetase I Acetyl-CoA carboxylase (ACC) carnitine acyltransferase I HMG-CoA synthase HMG-CoA reductase 32, malate aspartate shuttle 30, glycerol-3-phosphate shuttle two ATP hyrdolysis couple to energetically unfavorable rxns ATP NADH, NADPH, FADH2 coenzyme A, lipoamide biotin THFs SAM TTP catabolic processes to carry reducing equivalents away as NADH anabolic processes as a supply of reducing equivalents HMP shunt anabolic processes like steroid and fatty acid synthesis, respiratory burst, P-450, glutathione reductase

What is the RDE of de novo pyrimidine synthesis What is the RDE of de novo purine synthesis What is the RDE of the urea cycle What is the RDE of fatty acid synthesis What is the RDE of fatty acid oxidation What is the RDE of ketogenesis What is the RDE of cholesterol synthesis How many ATP are created by aerobic metabolism of glucose in the heart and liver via what shuttle How many ATP are created by aerobic metobolism of glucose in muslce via what shuttle How many ATP are produced by anearobic glycolysis per molecule of glucose How is ATP used by the cell What is the activated carrier for phosphoryl What is the activated carrier for electrons What is the activated carrier for Acyl What is the activated carrier for Co2 What is the activated carrier for 1 carbon units What is the activated carrier for methyl groups What is the activated carrier for aldehyddes What is NAD+ generally used for What is NADPH used for What produces NADPH NADPH are used in what 4 things

phosphorylation of glucose to yield glucose 6 glycolysis and the glycogen synthesis in the liver phosphate serves as the 1st step of what rxns and hexokinase or glucokinase what enzymes catalyze it Where is hexokinase found, what is its Km and Vmax and what uninduces it ubiquitous, low Km, high affinity, low capacity low Vmax, uninduced by insulin

Where is glucokinase found, what are the Km and liver and beta cells of pancreas, low affinity, high Km, Vmax, and what induces it high capacity, high Vmax, induced by insulin What feedback inhibits hexokinase What fxn does glucokinase serve in the liver What are the reactants for glycolysis What are the products for glycolysis glucose-6 phosphate phosphorylation excess glucose to sequester it, liver becomes blood glucose buffer glucose, 2Pi, 2ADP, 2NAD+ 2 pyruvate, 2ATP, 2NADH, 2H+, 2H2O
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What two rxns in in glycolysis require ATP What substances inhibit phosphofructokinase-1 What substances induce phosphofructokinase What rxn creates ATP What inhibits pyruvate kinase What induces pyruvate kinase What enzyme catalyzes the rxn from pyrvuate to Acetyl-CoA and what inhibits it In which state is FBPase-2 active In which state is PFK-2 active What regulates whether FBPase-2 or PFK-2 is active

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glucose to G-6P, hexokinase and fructose-6P to fructose 1,6 BP phosphofructokinase-1 ATP, citrate AMP, fructose 2,6 BP phosphenolpyruvate to pyruvate catalyzed by pyruvate kinase ATP and alanine F16BP pyruvate dehydrogenase, ATP, NADH, acetyl-CoA fasting fed protein kinase A

What is the pathway in the fasting state leading to inc glucagon, inc cAMP, inc PKA inc FBPase-2 and dec PFK-2 What is the pathway in the fed state leading to dec inc insulin, dec cAMP, dec PKA FBPase-2 and inc PFK-2 The pyruvate dehydorgenase complex serves in what reaction: reactants The pyruvate dehydrogenase complex serves in what reaction: products What co-factors are required for the pyruvated dehydrogenase complex What activates the pyruvate dehydrogenase complex What other complex is similar to the pyruvate dehydrogenase complex in that it has the same co-factors and generates succinyl-CoA What does arsenic do and what are th results of poisoning What does a pyruvate dehydrogenase deficiency lead to and what are the findings What is the TX for pyruvate dehydrogenase deficiency What are the only purely ketogenic amino acids Of the four possible fates for pyruvate, which one carries amino groups to liver from muscle Of the four possible fates for pyruvate, which one can replenish TCA cycle or be used in gluconeogenesis Of the four possible fates for pyruvate, which one is a transition from glycolysis to TCA cycle pyruvate, NAD+, CoA Acetly-CoA, CO2, NADH pyrophosphate (B1, thiamine, TPP) FAD (B2, riboflavin), NAD (B3, niacin), CoA (B5 pantothenate), lipoic acid exercise: inc NAD/NADH, inc ADP, inc Ca alpha-ketoglutarate dehydrogenase complex inhibits lipoic acid, vomiting, rice water stools, garlic breath backup of substrate (pyruvate and alanine) resulting in lactic acidosis, congenital or acquired from thiamine def in EtOH, neuro defects inc intake of ketogenic nutrients, high in fact content or inc lysine or leucine Lysine and leucine alanine Oxalacetate Acetyl-CoA
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Of the four possible fates for pyruvate, which ends anaerobic glycolysis as in RBCs, leukocytes, Lactate kidney medulla, lens, testes and cornea What does the TCA cycle produce per 1 acetyl CoA What does Citrate Is Krebs starting substrate for making oxaloacetate How doe NADH electrons from glycolysis and the TCA cycle enter the mitochondiria What does the passage of electrons result in that when coupled to OXPHOS drives the production of ATP Where are FADH2 electrons transferred to 3 NADH, 1 FADH2, 2 CO2, 1 GTP citrate, isocitrate, alpha ketoglutarate, succinyl-CoA, succinate, fumarate, malate, oxaleoacetate malate-aspartate shuttle or the glycerol 3 phosphate shuttle proton gradient comlex II

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What substances directly inhibit electron transport rotenone, CN-, antimycin A, CO chain Wgat substances directly inhibit mitochondrial ATPase, causing an inc in proton gradient, no ATP oligomycin because pump is stopped What are uncoupling agents What substances are uncouling agents What are the irreversible enzymes of gluconeogenesis inc permeability of membrane causing a dec in proton gradient and inc in O2 consumption - ATP synthesis stops, but electron transport continues to produce heat 2,4 DNP, aspirin pyruvate carboxylase, PEP carboxykinase, fructose 1,6 biphosphatase, glucose 6 phosphatase

Where is pyruvate carboxylase found, what does it in mitochondria, pyruvate to oxaloacetate, requires biotin, do, what does it require amd what activates it ATP, activated by acetyl coA Where is PEP carboxykinase found, what does it do, and what does it require Where is fructose 1,6 bisphosphatase found and what does it do Where is glucose 6 phosphatase found and what does it do Where does gluconeogenesis primarily happen and what are other sites where the enzymes are located What do def in in enzymes of gluconeogenesis cause Why can't muscle produce in gluconeogenesis How do odd chain fatty acids participate in gluconeogenesis Why can't even chain fatty acids produce new glucose What is the purpose of the HMP shunt in cytosol, oxaloacetate to phosphenolpyruvate, requires GTP cytosol, F 1,6 BP to fructose 6 Phosphate in ER, glucose 6-P to glucose liver, also in kidney and gut epithelium hypoglycemia lacks glucose 6 phophatase via 1 proprionyl-CoA which can enter the TCA as succinyl-CoA and undergo gluconeogenesis they yield only acetyl-CoA equivalents provide a source of NADPH from an abundantly available glucose 6P, create ribose for nucleotide synthesis and
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YKS

glycolytic intermediates oxidative and nonoxidative, no ATP produced or used oxidative is irreversible glucose 6P to CO2, 2NADPH, ribulose 5P, G6PD, rate limiting step ribulose 5P to ribose 5P, G3P and F6P, transketolase and B1 chronic granulomatous disease, no respiatory burst, no formatino of ROS superoxide dismutase myeloperoxidase PMNs peroxide

What are the 2 distinct phases of the HMP shunt and how many ATP are used and produced Which phase of the HMP shunt is reversible and which is irreversible What happens on the oxidative arm of the HMP shunt and what is the key enzyme What happens on the nonoxidative arm of the HMP shunt and what is the key enzyme and cofactor What does NADPH oxidase deficiency result in and why What enzyme turns ROS to H2O2 What enzyme adds Cl- to the H202 to makes bleach In what cells do the respiratory burst occur What substance inside the cell serves to oxidize glutatione What substance inside the cells replenishes NADPH Patients with chronic granulomatous disease are at increased risk of infection from which kind of organisms What is NADPH's role inside RBCs

What substance inside the cell reduces glutatione NADPH G6PD catalase positive (catalase neg produce H2O2 the cell can use) like S. aureus or aspergillus keep glutathione reduced so it can detoxify free radicals and peroxides

poor defense from oxidizing agents, fava beans, What does a decrease in decrease in NADPH lead sulfonamides, primaquine, antituberclosis drugs leadig to to and why hemolytic anemia. What other inflammatory process can induce a hemolytic anemia in NADPH defieicnt patients Why is G6PD def more common among patients of african decent What are Heinz bodies What are bite cells and when do you see them benign asymptomatic condition with elevated levels of fructose in urine and blood, dz and enzyme infection, free radicals generated by inflammatory response protective against malaria oxidized hemoglobin precipiated within RBCs result from phagocytic removal of heinz bodies my macs - G6PD def essential fructosuria - fructokinase AR

aldolase B, AR, fructose 1P accumulates causing a dec What is the defect in fructose intolerance and what in availabel phosphate which inhibts glycogenolysis and gluconeogenesis leading to hypoglycemia, cirrhosis, does it cause jaundice and vomiting What enzyme does fructose metabolism bypass to PFK - rate limiting enzyme
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YKS reach glycolysis

What are possilbe presentation for galactokinase def

failure to track objects or develop a social smile

What substance accumulates in galactokinase def galactitol, galactose appears in blood and urine, can and what is the clinical picture cause infantile cataracta - AR What enzyme results in classic galactosemia and what is the clinical absence of galactose 1 phosphate uridyltransferase, accumulation of toxic substances leads to failure to thrive, jaundice, hepatomegaly, infantile cataracts, mental retardation

In addition to fructose and galactose, what sugards should be excluded from the diets of patients with sucrose disorders of fructose or galactose metabolism What is sorbitol, how and why is it made alcohol version of glucose, can trap glucose in cell, aldose reductase

fructose via sorbitol dehydrogenase, inc sorbitol leading What sugar is sorbitol converted to and via what enzyme, and what can happen in cells lacking this to osmotic damage as in cataracts, retinopathy, peripheral neuropathy as in diabetes enzyme What tissues have both enzymes of sorbitol metabolism What tissues have only aldose reductase What does lactase deficiency cause Who typically has lactase def What form of amino acids are found in proteins What are the glucogenic essential amino acids What are the glucogenic/ketogenic amino acids What are the purely ketogenic amino acids Which are the acidic amino acids Which are the basic amino acids liver, ovaries, seminal vesicles schwann cells, lens, retina, kidneys loss of brush border enzyme causing bloating, cramps, osmotic diarrhea African Americans and Asians L form met, val, arg his Ile, phe, thr, trp leu, lys Asp and Glu arg, lys, his, arg is most basic, has has no charge at body pH

What two amino acids are required druing periods arg and his inc in histones which bind negatively charged of growth and why DNA What does amino acid catabolsim results in the formation of what What step begins the urea cycle and what is the enzyme needed, where does it happen When does aspartate enter the urea cycle What is the composition of urea and where do each part derive from common metabolites like pyruvate and acetyl CoA and excess NH4+ converted to urea and exreted CO2 + NH4 needs carbamoyl phosphate synthase I, in the mitochondria after citruline NH2-(C

passed to glutamate, then to alanine enters blood, enters How is ammonium transported from muscle to the liver, coverted to pyruvate and transfers ammonium back liver for urea cycle to glutamate which gives it to the urea cycle What happens in hyperammonemia depletes alpha-ketoglutarate leading to inhibition of TCA cycle - tremor slurring of speech, somnolence, vomiting,
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cerebral edema, blurring of vision limit protein diet, benzoate or phenylbutarate (both bind amino acids leading to excretion) can decrease ammonia levels

What is the TX for hyper ammonemia

ornithin transcarbamoylase def - x linked recesssive, What is the most common urea cycle disorder and other urea cycle enzymes defs are autosommal what is the mode of inheritance? recessive How does OTC def present What is the amino acid precursor for catecholamines What is the amino acid precuros for niacin and serotonin/melatonin What is the amino acid precursor for histamine 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 of hyerpammonemia phenylalanine tryptophan histidine

What is the amino acid precursor for porphyrin and glycine heme What is the amino acid precuror for creatine, urea arginine and nitric oxide What is the amino acid precursor for GABA and glutathione What enzyme converts phenylalanine to tyrosin What converts tyrosine to DOPA What converts DOPA to dopamine What converts dopamine to NE What converts NE to epi What is the breakdown product of dopamine What is the breakdown product of NE What is the breakdown product of epi decreases in what substances can cause PKU What enzyme becomes essential in PKU What does inc phenylalanine lead to What are the findings in PKU What is the TX for PKU What is maternal PKU What creates the musty body odor in PKU congenital deficiency of homogentisic acid oxidase in the degradative pathway of tyrosine to fumarate
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glutamate phenylalanine hydroxylase tryosine hydroxylase dopa decarboxylase dopamine beta hydroxylase phenylethamolamine N methyl transferase HVA VMA metanephrine phenylalanine hydroxylase, tetrahydrobiopterin cofactor tyrosine phenylketones in urine mental retardation, growth retardation, seizures, fair skin, eczema, musty body odor dec phenylalanine (contained in aspartame, Nutrasweet) inc tyrosine in diet lack of proper dietary therapy during pregnancy leading to microcephaly, mental retardation growth retardation, congenital heart defects disorder of aromatic amino acid metabolism

YKS leading to dark connective tissue, brown pigmented sclera, urine turns black on standing dz and worst complication

alkaptonuria, may have debiliating arthralgias

What are the two possible causes of albinism Pts with albinism are at inc risk for what cancer Why is albinism inheritnace varialbe due to What are the 3 AR forms of homocystinuria What is the treatment for cystathionine synthase def What is the treatment for dec affinity of cystathionine synthase for pyroxidal phosphate What are the findings with homocystinuria and what amino acid is needs to be supplemented What is the defect in cystinuria What is the complication of cystinuria

lack of tyrosinase (no melanin) AR ordefective tyrosine transporters (less tyrosine) - can results in lack of migration of NC cells skin locus heterogeneity - ocular albinism is x-linked recessive cystathionine synthase def, dec affinity of cystathionine synthase for pyridoxal phosphate, homocystein methyltransferase def dec methionine, inc cystiene, inc B12/folate inc vit B6 homocystein in ruine, mental retardation, osteoporosis, tall stature, kyphosis, lens subluxation and atherosclerosis leading to stroke and MI, cysteine hereditary defect of renal tubular amino acid transporter for cystein, ornithine, lysine and arginine in PCT cystine kidney stones, cystine staghorn calculi - cystine is made of two cysteines connected by disulfide bond

dec in alpha ketoacid dehydrogenas leading to blocked What causes maple syrup urine disease and what degredation of branches amino acids like Ile, Leu, and does it lead to Val - severe CNS defects mental retardation and death What causes Hartnup's disease What does hartnups disease cause How do glucagon/epi lead to glycogenolysis AR disorder characterized by defective neutral amino acid transporte on renal and intestinal epith cells tryptophan excretion in urine and dec absorption from the gut leading to pellagra Adenylyl cycle, inc cAMP, inc PKA, glycogen phosphorylase kinase activated, glycogen phosphoylase active, glycolysis receptor tyrosine kinases, protein phosphatase, takes phosphate off glycogen phosphorylase kinase inactivating it Ca/calmodulin in muscle to coordinate with muscle activity

How does insulin inhibit glycogenolysis What else can phosphoylate phosphorylase kinase What happens do glycogen in skeletal muscle during exercise What happens to glycogen in the liver What enzyme converts glucose 1 p to UDP glucose

What kind of branches do glycogen branches have alpha 1,6 and alpha 1,4 glycogenolysis to form glucose stored and undergoes glycogenolysis to maintain blood sugar at appropriate levels UDP glucose pyrophosphorylase
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YKS What enzyme degrades a small amount of glycogen in lysosomes

alpha 1,4 glucosidase glucose 6 phosphatase debranching enzyme Von Gierke's, Pompe, Cori, McArdle von gierkes, glucose 6 phosphatase pompe's lysosomal alpha 1,4 glucosidase (acid maltase) (pompe trashes the pump; heart, liver, muscle) cori's, debranching enzyme alpha 1,6 glucosidase, gluconeogenesis intact mcardle's, skeletal muscle glycogen posphorylase

What liberates glucose from glucose 6 P What converts limit dextran to glucose Very Poor Carbohydrate Metabolism stands for 4 of the glycogen storage diseases, what are thy Severe fasting hypoglycemia, inc glycogen storage in liver, inc blood lactate, hepatomegaly dz and def enzyme cardiomegaly, systemic findings leading to early death - dz and enzyme Milder form of type I with nl blood lactate levels dz and enzyme inc glycogen in muscle but can't break it down, painful muscle cramps, myglobinuria with strenuous exercise - dz and enzyme peripheral neuropathy of hands/feet, angiokeratomas, CV/renal disease - dz, def enzyme, acc substrate, inherit hepatosplenomegaly, aseptic necrosis of femur, bone crisis, MACS that look like crumpled tissue paper progressive neurodegeneration, hepatosplenomegaly, cherry red spot on macula, foam cells progressive neurodegeneration, developmental delay, cherry red spot on macula, lysosomes with onion skin, NO hepatosplenomegaly

fabrys, alpha galactosidase A, ceramide trihexoside, XR

gaucher's, beta glucocerebrosidase, glucocerebrosie, AR

neimann-pick, sphingomyelinase, sphingomyelin, AR

Tay-Sachs, hexosaminidase A, GM2 ganglioside, AR

peripheral neuropathy, developmental delay, optic krabbes, galactocerebrosidase, galactocerebroside, AR atrophy, glopoid cells central and peripheral demyelination with ataxia and dementia metachromatic leukodystrophy, arylsulfatase A, cerebroside sulfate AR

developmental delay, gargoylism, airway hurlers syndrome, alpha L iduronidase, heparan obstruction, corneal clouding, hepatosplenomegaly sulfate/dermatan sulfate, AR Mild Hurlurs + aggressive behavior no corneal clouding What shuttle is used in fatty acid degredation and what does it move and from where to where What inhibits the carnitine shuttle What happens in carnitine def Hunters, iduronate sulfatase, heparan sulfate/dermatan sulfate, XR carnitine shuttle, acyl-coa from cyto to mito malonyl coa inability to transport LCFAs into mitochondria results in toxic accumulation causing weakness, hypotonia, hyperketotic hyperglycemia

What shuttle is involved in fatty acid synthesis and citrate, acetyl coa from mito to cyto what does it move from where to where
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What doesYKS oxidation do and where does it beta occur what happens in acyl coa dehyrdogenase def What does acetyl-CoA become before becoming palmitate What enzymes metabolize fatty acids and amino acids What occurs to oxaloacetate in starvation and DKA What happens to oxaloacetate in alcholism What are ketone bodies made from, where are they metabolized and how are they excreted in a 100 meter sprint where does energy come from In a 1000 meter run, where does energy come from in a marathon where does energy come from What are the priorities for the body in fasting and starvation What is the energy source in the fed state right after a meal What is the source of energy in the fasting state between meals What are the blood glucose levels maintained by for days 1-3

breaks down acyl-coa to acetyl coa groups in mito inc dicarboxylic acids, dec in glucose and ketones malonyl coa (+ biotin acetoacetate and beta hydroxybutyrate depleted for gluconeogenesis staling the TCA cycle and shunting glucose and FFA to production of ketone bodies excess NADH shunts oxaloacetate to malate (backwards) stalling the TCA and shunting glucose and FFA to ketone body production HMG-CoA, brain to 2 molecules of acetyl-Coa, excreted in urine stored ATP, creatine phosphate, anaerobic glycolysis same as sprint + OXPHOS glycogen and FFA oxidation; glucose conserved for final sprinting supply sufficient glucose to brain and RBCs and to preserve protein glycolysis and aerobic respiration hepatic glycogenolysis >> hepatic gluconeogenesis > adipose release of FFA hepatic glycogenolysis, adipose tissue release of FFA, muslce and liver FFA, hepatic gluconeogenesis from peripheral tissue lactate and alanine and from adipose tissue glycerol and proprionyl-coA (odd chain FFA)

adipse tissue stores, keton bodies become the main source of energy fo the brain and heart, after these are What is the energy source after day 3 of starvation depleted, vital protein degradation accelerates, leading to organ failure and death When are glycogen reserves depleted 1 g of protein or cabrohydrate I g fat What is the rate limiting enzyme in cholesterol synthesis What enzyme esterifies 2/3 of plasma cholesterol What does lipoprotein lipase do What does pancreatic lipase do What does hepatic TG lipase do What does hormone sensitive lipase do after day 1 ?kcal ? Kcal HMG-CoA (HMG-CoA to mevalonate LCAT (lecithin cholesterol acyltransferase) degredation of TG circulating in chylomicrons and VLDLs degredation of dietary TG in small intestine degradation of TG remaining in IDL degradation of TG stored in adipocytes
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What CETP do What does apoA 1 do What does apoB100 do What does apoCII do What does apoB48 do What does apoE do

transfers cholesterol from mature HDL to VLDL, IDL and LDL (cholesterol ester transfer protein) activates LCAT binds to LDL receptor, mediates VLDL secretion cofactor for LPL mediates chylomicron secretion mediates extra remnant take up

Delivers dietary TGs to peripheral tissues, delivers cholesterol to liver in the form of remnants, mostly chylomicrons depleted of TGs, secreted by intestinal epith cells What apolipoproteins are on chylomicrons b48, AIV, CII, E delivers hepatic TGs to peripheral tissue, secreted VLDL by liver What apolipoprotiens are on VLDL Formed and degradation of VLDL, delivers TGs and cholesterol to liver where they are degraded to LDL what apolipoproteins are on IDL B-100, CII and E IDL B100 and E

Delivers hepatic cholesterol to peripheral tissues, formed by LPL modification of VLDL in the LDL peripheral tissue, taken up by target cells via RME What apolipoprotein is on LDL Mediates reverse cholesterol transport from periphery to liver, acts as respository for apoC an apoE, secreted from both liver and small intestine What is the defect in I- hyperchylomicronemia What is the defect in II A familial hypercholesterolemia what is the defectin IV - hypertriglyceridemia B100 HDL LPL def, or altered apoCII, elevated TG and cholesterol, causes pancreatitis, hepatosplenomegaly and eruptive/pruritic xannthomas - no risk of atherosclerosis AD absent of dec LDL receptors causes accelerated atherosclerosis, achilles xanthomas and corneal arcus, increase LDL and elecated cholesterol hepatic overproduction of VLDL causing pancreatitis, elvelated TGs and VLDL

early in life, AR, inability to synthesize lipoproteins due to def in apoB100 and B48 - intestinal biopsy shows How does abetalipoproteinemia present and what accumulation within enterocytes due to inability to export is the defect absorbed lipid as chylomicrons - failure to thrive, steatorrhea, acanthocytosis, ata

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