Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
209 Cards in this Set
- Front
- Back
|
What is the structure of chromatin?
Which AA's make up histones? |
-DNA + histone octamer (2 set H2A, H2B, H3, H4)
-Connected by H1 string -Histones mainly Lys + Arg |
|
|
Heterochromatin
Euchromatin |
-Condensed, transcriptionally inactive, sterically inaccessible
-Less condensed, transcriptionally active, sterically accessible |
|
|
Purines, structure?
What is needed to make? |
-AG (2 rings for 2 bases)
-Glycine, aspartate, glutamine (GAG) and CO2, N10-fTHF -Adenine has an amine, guanine has a ketone |
|
|
Pyrimidines, structure?
What is needed to make? |
-CUT (1 ring)
-Aspartate, carbamoyl P -Cytosine has amine, uracil has ketone, thymine has methyl added |
|
|
Which AA's needed to make bases?
|
-Glycine, aspartate, glutamine (GAG)
|
|
|
Precursor of purines?
Precursor of pyrimidines? |
-IMP
-Carbamoyl P --> orotic acid + PRPP |
|
|
What enzyme needed to turn ribont's to deoxyribont's?
What drug inhibits? |
-Ribonucleotide reductase
-Hydroxyurea |
|
|
Which 2 pathways is carbamoyl P involved in?
|
-Urea cycle (I) and de novo pyrimidine synthesis (II)
|
|
|
Which pathway is inhibited by...
6-mercaptopurine? 5-fluorouracil? Methotrexate? Trimethoprim? |
6-MP: purine analog activated by HGPRTase, inhibits de novo purine synthesis from IMP
5-FU: pyrimidine analog activated to 5-FdUMP complexes with folate to inhibit thymidylate synthase (no dUMP-->dTMP methyl group transfer) MTX: folate analog inhibits DHF reductase (human) Trimethoprim: folate analog inhibits DHF reductase (bacterial) |
|
|
Ornithine transcarbamoylase def leads to what?
|
-Accumulation of carbamoyl P, which is then converted to orotic acid
-Orotic aciduria + hyperammonemia. UREA CYCLE deficiency! |
|
|
Orotic aciduria - defect, inheritance?
Enzyme def? Findings? Treatment? |
-AR defect in de novo pyrimidine syn. Can't convert orotic acid to UMP.
-Def in orotic acid phosphoribosyltransferase OR oritidine 5'-P decarboxylase. -Orotic aciduria, megaloblastic anemia, FTT. No hyperammonemia because urea cycle is fine! -Tx=oral uridine |
|
|
Adenosine Deaminase Deficiency (purine salvage def)
-Defect? -Findings? -Tx? |
-Cannot convert adenosine to inosine. Build up of ATP and dATP causes feedback inhibition of ribont reductase, preventing syn of other deoxyribont's. No DNA syn.
-Severe lymphocyte depletion (SCID) -Tx=Gene therapy (ADA) |
|
|
Lesch-Nyhan Syndrome (purine salvage def)
-Defect, inheritance? -Findings? |
-X-linked recessive. No HGPRT, cannot convert guanine to GMP or hypoxanthine to IMP. So...gets shunted toward xanthine-->uric acid.
-Severe retardation, self-mut, gout, hyperuricemia, choreoathetosis. |
|
|
-Name 2 fxns of DNA polymerase III? Prokaryotic or eukaryotic?
|
-5'-->3' synthesis of leading and lagging strand, AND 3'-->5' exonuclease proofreading
-Prokaryotic only! |
|
|
-Fxn of DNA polymerase I? Prokaryotic or eukaryotic?
|
-5'-->3' exonuclease (only enzyme that does it this way!), takes out RNA primer on lagging strand and fills in gap
-Prokaryotic only! |
|
|
-Which enzyme do fluoroquinolones inhibit? (floxacins)
|
-DNA gyrase (type of bacterial topoisomerase)
|
|
|
Explain nucleotide excision repair, what enzyme, how work?
Which disease is this fucked up in? |
-Specific endonucleases release damaged oligont's. Then DNA pol and ligase fill in gap.
-Xeroderma pigmentosum |
|
|
Explain base excision repair.
|
-Specific glycosylases only take out the damaged base, not whole nt. Then followed by AP endonuclease, DNA pol, ligase.
|
|
|
-How does mismatch repair work?
-Mutated in what disease? |
-Unmethylated newly syn string recognized, remove mismatch nt, fill/reseal.
-HNPCC (Lynch Syndrome) |
|
|
-How do chain termination drugs work?
|
-Drug with phony 3' group incorporated into growing DNA/RNA chain, but does not have correct 3'-OH needed to attack the 5'-triP on the incoming nt. Chain terminated!
|
|
|
-What are the 3 types of RNA?
-Describe them? -Which enzymes syn in euk? -Which enzymes in prok? |
-rRNA, mRNA, tRNA
-Rampant, Massive, Tiny -RNA polymerase I, II, III (no proofreading ability) -1 RNA pol complex syn all 3 types in prokaryotes |
|
|
-Name the 3 mRNA stop codons?
|
-UGA, UAA, UAG
(U go away, u are away, u are gone) |
|
|
-What do promoters do?
-What base sequences are always in promoters? -What happens when promoter is mutated? |
-Bind TF's and RNA polymerase
-TATA, CAAT (AT rich seqs!) -Severe decrease in gene syn |
|
|
-What does alpha-amanitin do, where is it found?
|
-Death cap mushrooms, inhibits RNA polymerase II. No transcription --> massive liver failure, can't make proteins.
|
|
|
-What are the 3 steps of RNA processing? Where occur?
-What is the polyadenylation signal? What enzyme does it? -What is RNA called before processed? |
-5' cap (7-methyl guanosine), polyadenylation tail, splicing out introns. Occurs in the nucleus.
-AAUAAA. Poly-A polymerase, does not need a template. -Heterogenous nuclear RNA (hnRNA) -->mRNA |
|
|
-What is responsible for pre-mRNA splicing?
-Which disease has antibodies to these? -Which disease is result of wrong alternative splicing? |
-snRNPs and other proteins splice out introns and join 2 exons.
-Lupus (anti-snRNP) -Beta-thal mutations |
|
|
-Where does the AA bind to tRNA molecule? What does this end of tRNA look like?
-What enzyme does this, what energy needed? -What is tRNA wobble? |
-3' end of tRNA opposite the anticodon site. Has CCA and lots of chem modified bases.
-Aminoacyl-tRNA synthetase + ATP. Has proofreading mech. This bond then has E for formation of peptide bond. -Only first 2 bases need to match perfectly. 3rd position can vary (degeneracy of genetic code). |
|
|
-How do aminoglycosides work?
-How do tetracyclines work? |
-Prevent initiation complex of rRNA/initiation factors from forming.
-Bind to 30S ribosomal subunit and prevent binding of aminoacyl-tRNA. |
|
|
Transcription
-Eukaryotic ribosomal subunit? -Prokaryotic ribosomal subunit? -Energy to tRNA charging? -Energy for translocation? -Which site does Met-tRNA bind to? |
-Euk: 40S + 60S = 80s (even)
-Prok: 30S + 50S = 70S (odd) -ATP -GTP -P site. All others enter A site first. |
|
|
-How does chloramphenicol work?
-Macrolides and clindamycin? |
-Inhibits 50S peptidyl transferase
-Bind to the 23srRNA of 50S subunit and prevent translocation |
|
|
-What is trimming?
-What are covalent alterations? |
-Clipping of N or C terminal peptides to activate zymogens
-Hydroxylation, phosphorylation, glycosylation |
|
|
-What are the phases of the cell cycle?
-What controls cell cycle? |
-Interphase (G0/G1, S, G2) and mitosis (PMAT)
-Cyclins, CDK's, tumor sups (p53 and Rb) |
|
|
-Where is Rb and p53 checkpoint?
-How does p53 work? |
-Between G1 and S phase
-p53 inhibits Cdk4 so Rb is not phosphorylated, cell cycle HALT. Gives cell time to repair, if too much damage activates bax for apoptosis. If repaired, Cdk4 can phosphorylate Rb and proceeds. |
|
|
-Permanent cells (G0)
-Stable cells (G0-->G1) -Labile cells (G1 always) |
-Neurons, skeletal/cardiac muscle, RBC
-Endometrium, hepatocytes, lymphocytes -Hair, skin, BM, GI |
|
|
-Fxn of RER?
-Fxn of Nissl Body? -Fxn of free ribosomes? |
-Secretory proteins, N-oligosaccharide addition to proteins
-RER in neuron, makes peptide neurotransmitters and enzymes (ChAT) -Makes cytosolic and organellar proteins |
|
|
-Name 2 cells rich in RER
|
-Plasma cells (ab's) and goblet cells (mucus)
|
|
|
-Fxn of SER?
-Name 2 cells rich in SER |
-Steroid syn and detox of drugs/poisons (p450!)
-Liver hepatocytes and adrenal cortex (zona fasciculata) |
|
|
-Fxn of Golgi apparatus?
|
-Distribution center
-Modify N-oligosac -Add O-oligosac to Ser and Thr -Add Man6P to lysosomal proteins -Add sulfate to Tyr and proteoglycans -Assemble proteoglycans |
|
|
Vesicular Trafficking Proteins
-Retrograde: Golgi-->ER -Anterograde: ER-->cis-Golgi -Trans-golgi--> lysosomes, PM--> endosomes |
-COP I
-COP II -Clathrin (receptor-mediated endocytosis) |
|
|
-What is Inclusion Cell Disease?
-Findings? |
-I cell disease, deficiency of phosphotransferase, can't add Man6P to lysosomal proteins so never get to lysosome, just get exported out of cell into blood. Can't digest stuff in cell so get large inclusions in cytosol.
-Coarse facial features, cloudy cornea, restricted joint mvmt, gingival hypoplasia, high level plasma lysosomal enzymes. Fatal in childhood. |
|
|
-Which E molecule is bound to alpha/beta tubulin dimers?
|
-GTP (2 GTP per dimer)
|
|
|
-Name 5 drugs that act on microtubules?
|
Mebendazole
Griseofulvin Vincristine Paclitaxel Colchicine |
|
|
-What is Chediak-Higashi Syndrome?
-Findings? |
-AR lysosomal transport protein defect and microtubule polym defect that causes poor chemotaxis and poor phagocytosis (bad phagolysosome formation).
-HUGE GRANULES, recurrent pyogenic infxn, partial albinism, peripheral neuropathy |
|
|
-What is the structure of cilia?
-How does it move, what energy? |
-9 microtubule doublets + 2.
-Axonemal dynein arms use ATP to make doublets slide against each other. |
|
|
-What is Kartagener's Syndrome?
-Findings? |
-Dynein arm defect results in immotile cilia.
-Infertility, recurrent sinusitis, bronchiectasis. Assoc with situs inversus. |
|
|
-What are microvilli made of?
-Other fxn of actin and myosin? |
-Actin and myosin
-Muscle contraction, cytokinesis, adherens jxn |
|
|
-MOA of ouabain?
-MOA of cardiac glycosides? |
-Directly binds to K+ site of Na/K ATPase
-Directly inhibits the ATPase activity, leading to indirect inhibition of Na/Ca pump and build up of Ca in cardiac myocytes |
|
|
-What is the most abundant protein in the human body?
-What cell makes, what part of cell? |
-Collagen
-Fibroblasts in ER, then processed outside of cell |
|
|
-Type I collagen (90%)
-Type II -Type III -Type IV |
-Bone, skin, tendon, cornea, dentin, fascia, late wound repair
-Cartilage, viterous body, nucleous pulposus -Skin, blood vessels, uterus, fetal tissue, granulation tissue -Basement membrane |
|
|
-What are the steps of collagen synthesis?
|
1. Synthesis - preprocollagen in ER
2. Hydroxylation of Pro and Lys, needs Vit C in ER 3. Glycosylation of pro-alph Lys and triple helix formation of procollagen in ER 4. Exocytosis of procollagen out of cell 5. Cleavage of terminal regions to tropocollagen 6. Cross-linking of hydroxyLys and Lys residues by lysine oxidase (Cu cofactor) to collagen fibrils |
|
|
-Where is the defect in scurvy?
-Osteogenesis imperfecta? -Ehlers-Danlos? |
-No Vit C, cannot hydroxylate preprocollagen Lys and Pro in ER
-Cannot form triple helix of procollagen in ER after glycosylation, most commonly Type I -Cannot cross-link into collagen fibrils (lysyl oxidase def), most commonly Type III |
|
|
-Ehlers Danlos (inheritance, types)
-Findings -Associations |
-6 diff types, can be AD/AR. Most commonly defect of Type III collagen.
-Easy bruising, stretchy skin, hypermobile jts -Joint dislocation, berry aneurysms, organ rupture |
|
|
-Osteogenesis Imperfecta (inheritance, types)
-Findings (Type 1 OI) |
-Most commonly AD with abnl Type I collagen
-Mult fx, blue sclerae, hearing loss (middle ear bones), bad teeth (dentin) |
|
|
-What is elastin made of? Tropoelastin?
-Where found? -What degrades it? What inhibits this enzyme? |
-Elastin rich in nonglycosylated Gly and Pro. Tropoelastin with fibrillin scaffolding.
-Large arteries, lungs, elastic ligs, vocal cord, ligamenta flava -Elastase, inhibited by alpha1-AT |
|
|
-What is the defect in Marfan's?
-What is the defect in alpha1-AT deficiency? |
-AD defect in fibrillin
-Defect in AAT so no inhibition of elastase, elastin in lungs broken down, emphysema :( |
|
|
-Explain Southern Blotting?
-Northern Blotting? -Western Blotting? (SNW DRP) |
-Gel electrophoresis of DNA, transfer to filter, denature, wash with radio-labeled DNA probe, expose to film
-Radio-labeled DNA probe attaches to RNA -Radio-labeled antibody attaches to protein |
|
|
-What can microarrays be used for?
|
-Profile gene expression levels (RNA or DNA), detect single nt polymorphisms (SNP's)
|
|
|
-Explain the 2 types of ELISA?
|
-Probe patient's blood with test antigen to see if ab present
-Probe patient's blood with test ab to see if ag present |
|
|
-Explain Fluorescence in situ Hybridization?
|
-Fluorescent DNA/RNA probe used to look for specific gene of interest, microdeletions. If gene deleted, will not bind, no light up.
|
|
|
-Explain Cre-lox system?
|
-Inducibly manipulate genes at specific developmental pts by using abx controlled promoter (now can study gene that otherwise causes death in utero)
|
|
|
-Explain RNAi?
|
-dsRNA is made that is complimentary to mRNA of interest. When put into human cells, dsRNA binds and promotes degradation of target mRNA, downreg gene expression.
|
|
|
-What samples can be used for karyotyping?
-What phase are chromosomes in? |
-Blood, BM, amniotic fluid, placenta
-Metaphase |
|
|
-Define pleiotropy
-Example |
-1 mutation causes more than 1 effect on phenotype.
-Ex. PKU causing many seemly unrelated sx in one person. |
|
|
-Define loss of heterozygosity
-Example |
-If pt inherits or acquires mutation in tumor sup gene, must also lose other copy before cancer develops.
-Ex. Rb gene |
|
|
-Define dominant neg mutation
-Example |
-Heterozygote produces nonfxnl altered protein that prevents the normal gene product from fxning.
-Ex. Mutated transcription factor still binds to DNA and prevents good copy from binding. |
|
|
-Define linkage disequilibrium
|
-Tendency of certain alleles at 2 linked loci to occur more often than expected by chance in a population.
|
|
|
-Define locus heterogeneity
-Example (2) |
-Mutations at diff loci all produce the same phenotype.
-Marfan's, MEN2B, homocystinuria all have marfanoid habitus. Albinism. |
|
|
-Define heteroplasmy
|
-Both normal and mutated mtDNA present, resulting in variable expression of mito inherited disease.
|
|
|
-What does the Harvey-Weinberg law assume?
|
-No mutation occurring at locus, no selection for any of genotypes at the locus, random mating, no migration
|
|
|
-Explain imprinting
-Which allele is deleted in Prader-Willi? -Angelman's Syndrome? |
-At single locus, only 1 allele is active and other is methylated. If you delete the copy that is active, you get disease.
-Paternal copy of Chr 15 gene -Maternal copy of Chr 15 gene |
|
|
-Hypophosphatemic rickets- inheritance, defect?
|
-X-linked dominant, phosphate wasting at prox tubule causes rickets-like presentation.
|
|
|
-Leber's Hereditary Optic Neuropathy-inheritance, defect?
|
-Mitochondrial inheritance. Degen of retinal ganglion cells and axons leads to acute loss of central vision.
|
|
|
Achondroplasia
-inheritance, defect |
-AD, FGFR3 inhibits chondrocyte proliferation because mutation makes it constitutively active, no endochondral ossification but membranous ok (big head)
-Assoc with advanced paternal age |
|
|
ADPKD
-inheritance, defect, Chr |
-AD, APKD1 gene on Chr 16 ("polycystic kidney")
|
|
|
Familial Adenomatous Polyposis
-inheritance, defect |
-AD, APC gene tumor sup on Chr 5q ("polyp")
|
|
|
Familial hypercholesteremia (Hyperlipidemia Type IIa)
-inheritance, defect |
-AD, defective/absent LDL receptor
-Heterozygous: total chol 300 -Homozygous: total chol 700 |
|
|
Hereditary Hemorrhagic Telangiectasia (Osler-Weber-Rendu Syndrome)
-inheritance, defect |
-AD, defect in blood vessels
-Recurrent epistaxis, AVM's, telangiectasia, skin discoloration |
|
|
NF Type I (von Recklinghausen's disease)
-inheritance, defect |
-AD, NF1 tumor sup on Chr 17q ("von recklinghausen")
|
|
|
NF Type II
-inheritance, defect |
-AD, NF2 gene tumor sup on Chr 22q
-juvenile cataracts, bilat acoustic schwannomas |
|
|
Tuberous Sclerosis
-inheritance, penetrance and variability? |
-AD, incomplete penetrance and variable presentation
|
|
|
von Hippel-Lindau Disease
-inheritance, defect |
-AD, deletion of VHL gene tumor sup on Chr 3p causes constitutive expression of HIF gene (codes for TF) and activation angiogenic GF's
-cerebellar/retina/medulla hemangiobastomas, bilat RCC in 50% |
|
|
Cystic Fibrosis
-inheritance, defect, chr, MOA -treatment |
-AR, CFTR gene on Chr 7, del of Phe508. Mutation causes protein misfolding that prevents CFTR channel from ever reaching cell surface.
-No secretion of Cl into GI tract or lungs, no resorption of Cl from sweat. -Tx=N-acetylcysteine to hydrolyze disulfide bonds in mucus glycoproteins |
|
|
Duchenne's/Becker's Muscular Dystrophy
-inheritance, defect |
-X-linked recessive, frame shift/mutated DMD gene (longest human gene)
|
|
|
Fragile X Syndrome
-inheritance, defect, why called Fragile X |
-X-linked defect affecting methylation of FMR1 gene
-Triplet repeat (CGG) -called Fragile X because of gap in X chromosome when lymphocytes are grown in folate deficient medium. |
|
|
Triplet Repeat Diseases
-Which ones, what are the repeats? |
-Huntington's (CAG)
-FraGile X (CGG) -MyoTonic Dystrophy (CTG) -Friedrich's AtAaxia (GAA) |
|
|
Cri-du-Chat
-defect -findings |
-Microdeletion of 5p (the whole short arm!)
-MR, microcephaly, high-pitched crying, epicanthal fold, cardiac abnl |
|
|
Williams Syndrome
-defect, what gene does it include -findings |
-Microdeletion of 7q (includes elastin gene)
-elfin, hyperCa (increased sensitivity to Vit D), heart problems, extremely talkative/friendly |
|
|
22q11 deletion syndromes (DiGeorge, Velocardiofacial)
-defect -findings |
-aberrant development of 3rd and 4th branchial pouches
-CATCH-22 (cleft palate, abnl facies, thymic aplasia, cardio, hypocalcemia) |
|
|
B vitamins (1/2/3/5/6/7/12)
-common sx of B vit def? |
B1 = thiamine (TPP)
B2 = riboflavin (FAD, FMN) B3 = niacin (NAD, NADP) B5 = pantothenic acid (CoA) B6 = pyridoxine (PLP) B7 = biotin -Diarrhea, dermatitis, glossitis B12 = cobalamin |
|
|
Vitamin A (retinol)
-source? -fxn? -deficiency? -excess? |
-Liver, leafy vegetables
-Antioxidant, visual pigment, normal diff of epithelial cells into specialized tissue, prevents squamous metaplasia -Night blindness, follicular hyperkeratosis, Bitot's spots in eye -pseudotumor cerebri, arthralgia, fatigue, sore throat, alopecia, skin changes. |
|
|
B1 (thiamine)
-fxn? -def? |
-TPP cofactor for pyruvate DH, alpha-KG DH, transketolase, branched chain AA DH.
-Impaired glycolysis/TCA cycle leads to ATP depletion, brain and heart damage. |
|
|
What part of brain is damaged in Wernicke-Korsakoff Syndrome?
|
-Medial dorsal nuc of thalamus and mammillary bodies.
|
|
|
-Findings in dry beriberi?
-Findings in wet beriberi? |
-Polyneuritis that causes sym muscle wasting.
-Dilated CMP, high output heart failure, edema. |
|
|
B3 (niacin)
-fxn and synthesis? -cause of deficiency, findings? |
-NAD, NADP used in redox rxn. B3=3 ATP. Synthesized from tryptophan using B6.
-corn diet, Hartnup disease, carcinoid syndrome, INH without B6 supplementation. Pellagra. |
|
|
B2 (riboflavin)
-fxn -deficiency |
-FAD and FMN cofactors for redox rxn. B2=2 ATP.
-Cheilosis, corneal vasc "B2, 2 C's, 2 ATP" |
|
|
B5 (pantothenic acid)
-fxn -deficiency |
-CoA cofactor for acyl transfers, component of fatty acid synthase.
-Dermatitis, enteritis, alopecia, adrenal insufficiency. |
|
|
B6 (pyridoxine)
-fxn -causes of deficiency -findings |
-Pyridoxial phosphate cofactor for transamination (ALT/AST), decarboxylation, glycogen phosphorylase, cystathionine syn, heme syn, niacin syn.
-INH, OCP's, goat milk -Sideroblastic anemia, periph neuropathy, convulsions, irritability |
|
|
B12 (cobalamin)
-fxn -deficiency |
-Cofactor for homocysteine methyltransferase (takes the methyl off of folate) and methylmalonyl CoA mutase (odd chain FA metabolism)
-Megalo anemia, subacute combined degeneration, elevated serum homocys and MMA. |
|
|
Folate
-fxn -causes of deficiency -deficiency |
-THF coenzyme for 1C transfers (pyrimidine synthesis!)
-Preg, EtOH, MTX/TMP, phenytoin, valproic acid, goats milk -Megalo anemia, no neuro sx, elevated blood homocys only. |
|
|
-Where are Fe, folate, and B12 absorbed in the GI tract?
-How does phenytoin cause folate def? |
-Duodenum, jejunum, and ileum.
-Inhibits intestinal conjugase so folate cannot be absorbed. |
|
|
S-adenosyl-methionine (SAM)
-how is it made? -name 2 fxns? |
-ATP+methionine = SAM. Needed to transfer methyl.
-Turns methionine back into homocys. -NE-->Epi. |
|
|
Biotin
-fxn -deficiency |
-Cofactor fo carboxylation (pyruvate carboxylase, acetyl-CoA carboxylase, propionyl-CoA carboxylase)
-Rare, caused by avidin in raw eggs/abx. Dermatitis, alopecia, enteritis (rash and go bald) |
|
|
Vitamin C (ascorbic acid)
-fxn -deficiency, excess? |
-Antioxidant, hydroxylation of Lys and Pro in preprocollagen in the ER, facilitates Fe absorption by keeping reduced, conversion of dopamine to NE
-scurvy for deficiency, urate stones for excess |
|
|
-What are the findings of scurvy?
|
-swollen gums, bruising, hemarthrosis, anemia (low Fe), poor wound healing (bad collagen)
|
|
|
Vitamin E
-fxn -deficiency -excess |
-Antioxidant protects Erythrocytes, prevents membrane lipid peroxidation
-Hemolytic anemia (fragile), muscle weakness, DC and spinocerebellar tract degen -decrease syn Vit K dependent clotting factors |
|
|
-What vitamins do bacteria make?
-What enzyme is needed to activate Vit K? What drug targets it? -Why do alcoholics get Vit D def? |
-Vit K and B12
-epoxide reductase, target of warfarin -Alcoholics have increased p450 activity, which increases conversion of Vit D to inactive form. |
|
|
Zinc
-fxn -deficiency |
-Needed as cofactor for metalloenzymes, zinc fingers
-Delayed wound healing, perioral rash, dysgeusia, anosmia, hypogonadism, decreased adult hair. -May predispose to EtOH cirrhosis. -Acrodermatits enteropathica = AR zinc def |
|
|
-What 2 enzymes are needed for EtOH metabolism? End product?
-What is the limiting reagent? |
-Alcohol DH and acetaldehyde DH. End product acetate.
-NAD+ |
|
|
-How does EtOH cause lactic acidosis, hypoglycemia, and fatty liver?
|
-Increased NADH/NAD ratio shunts pyruvate to lactate, oxaloacetate to malate. No gluconeo (hypoglycemia), so shifts to FA syn (fatty liver).
|
|
|
-Findings of Kwashiorkor?
-Findings of Marasmus? |
-Insuff protein intake so no syn of albumin (edema) or VLDL (hepatomeg), anemia, skin lesions
-Insuff E intake causes muscle wasting, loss of subq fat |
|
|
-What processes occur in mito?
|
Acetyl-CoA syn
TCA cycle FA oxidation Oxidative phosphorylation |
|
|
-What processes occur in cytosol?
|
Glycolysis
Glycogen syn/breakdown FA syn HMP shunt Protein/steroid syn (RER/SER) De novo pyrimidine/purine syn |
|
|
-Which processes occur in both cytosol and mito?
|
EtOH metabolism
Heme synthesis Urea cycle Gluconeogenesis (HUGs take 2) |
|
|
-What does a phosphorylase do?
-Dehydrogenase? |
-Add P without using ATP (as opposed to kinase)
-Oxidize |
|
|
Rate lim step of....
-glycolysis -gluconeo -TCA cycle |
-phosphofructokinase-1 (PFK1)
-Fructose-1,6-bisphosphatase -Isocitrate DH |
|
|
Rate lim step of...
-Glycogen syn -Glycogenolysis |
-glycogen synthase
-glycogen phosphorylase |
|
|
Rate lim step of...
-HMP shunt -de novo pyrimidine syn -de novo purine syn -Urea cycle |
-G6P dehydrogenase (G6PD)
-carbamoyl phosphatase synthetase II -glutamine-PRPP amidotransferase -Carbamoyl phosphate synthetase I |
|
|
Rate lim step of...
-FA synthesis -FA oxidation -Ketogenesis -Cholesterol syn |
-Acetyl-CoA carboxylase (ACC)
-Carnitine acetyltransferase I -HMG-CoA synthase -HMG-CoA reductase |
|
|
-Which organ produces 30 ATP, via which shuttle?
-Which organs produce 32 ATP, via which shuttle? -What do these shuttles do? |
-Muscle, via glycerol-3-P shuttle
-Heart and liver, via malate-aspartate shuttle -Bring NADH from glycolysis and TCA cycle to mitochondria, funnel to Complex I. |
|
|
-What carries aldehydes?
-1C units? |
-thiamine pyrophosphate (TPP)
-THF |
|
|
-What accepts electrons, what kind of rxn?
-What donates electrons, what kind of rxn? |
-NAD, NADP, FAD. Catabolic processes. Oxidizing agents.
-NADH, NADPH, FADH. Anabolic processes. Reducing agents. |
|
|
-What pathway does NADPH come from?
-What is it used for? |
-HMP Shunt
-Anabolism, resp burst, p450, glutathione reductase |
|
|
-Where is hexokinase found? Affinity, capacity? Feedback inhibition?
|
-Ubiquitous. High affinity (low Km), low capacity (low Vmax), inhibited by G6P.
|
|
|
-Where is glucokinase found? Affinity, capacity? Feedback inhibition?
-Why?? |
-Liver and beta cells of panc. Low affinity (high Km), high capacity (high Vmax), no feedback inhibition.
-Glucokinase is a GLUtton. Phosphorylates all glc to sequester it in the liver and allow to serve as BG buffer. |
|
|
-Which steps of glycolysis require ATP?
-Produce ATP? |
-Hexo/glucokinase, PFK1
-Phosphoglycerate kinase, pyruvate kinase |
|
|
-What does F2,6BP regulate?
-Fasting state triggers what enzyme? -Fed state? |
-Glycolysis vs gluconeogenesis
-high glucagon/cAMP/PKA activates FBPase2 to turn F26BP to F6P for gluconeo. -high insulin/low cAMP/PKA activates PFK2 to turn F6P to F26BP, which gives pos feedback to PFK1 stim glycolysis. |
|
|
-How many enzymes and cofactors in pyruvate DH complex?
-These are same as for what other enzyme? -What activates it? |
-3 enzymes 5 cofactors (TPP, FAD, NAD, CoA, lipoic acid)
-Alpha-KG DH complex in TCA cycle. -Exercise! (Increase ADP, NAD, Ca) |
|
|
-What is the MOA of arsenic?
-Findings? |
-inhibits lipoic acid in pyruvate DH and alpha-KG DH complex
-Garlic breath, rice water stool, vomiting |
|
|
Pyruvate DH deficiency
-Causes -What happens -Findings -Tx |
-Inherited or acquired due to B1 def (EtOH)
-Causes build-up of pyruvate and alanine that is shunted to lactate -Neuro findings, lactic acidosis -Tx=increase ketogenic nutrients (fat) or Lys/Leu |
|
|
-Anaerobic glycolysis is major source of E for which 6 places in body?
|
RBC
WBC renal medulla lens cornea testes |
|
|
-Name 4 fxn of pyruvate metabolism (enzyme)
|
1. Alanine carries amino groups to liver (ALT)
2. Oxaloacetate for gluconeo or TCA cycle (pyruvate carboxylase) 3. Feeds TCA cycle with acetyl-CoA (pyruvate DH) 4. Anaerobic glycolysis (lactate DH) |
|
|
-TCA/Krebs Cycle: name the substrates in order
|
"Citrate Is Krebs' Starting Substrate For Making Malate"
-Citrate, isocitrate, alpha-KG, succinyl-CoA, succinate, fumarate, malate, oxaloacetate |
|
|
-How many NADH, FADH, GTP, CO2 produced by Krebs cycle?
-How many ATP per turn, per glucose? |
-3 NADH, 1 FADH, 1 GTP, 2 CO2
-12 ATP per turn, 24 ATP per glucose |
|
|
-Where does NADH enter electron transport chain?
-FADH? -What comes next along the electron transport chain? |
-Complex I, inner mitochondrial membrane
-Complex II -I, II, CoQ, III, cytochrome c, Complex IV, ATP synthase |
|
|
Ox Phos Poisons!
-Electron transport inhibitors -ATPase inhibitors -Uncoupling agents, MOA |
Electron transport inhibitors: CN, CO, rotenone, antimycinA. Decrease proton gradient, no ATP made.
Direct ATPase inhibitor: Oligomycin. No ATPase, proton gradient builds up, no electron transport. Uncoupling agents: 2,4-DNP, aspirin. ATP syn stops because gradient washed out, but electron transport continues, producing heat. |
|
|
-Name the 4 enzymes of gluconeo?
|
"Pathway Produces Fresh Glucose"
-Pyruvate carboxylase, PEP carboxykinase, F16BPase, glc-6-phosphatase. |
|
|
-Which organs can do gluconeo?
-Why can't muscle do it? -Can odd chain FA do gluconeo? -Can even chain FA? |
-LIVER, kidney, intestinal epithelium.
-No glc-6-phosphatase to turn G6P back into glc -Yes, propionyl-CoA can enter TCA cycle as succinyl-CoA -No, can only turn into acetyl CoA |
|
|
-Name 2 fxns of HMP shunt (pentose phosphate pathway)
-Where does it occur? -Which enzymes are involved? |
-Produce 2 NADPH, make ribose 5-P, no ATP is used!
-Cytosol of FA/steroid synthesizing cells (lactating mammary glands, liver, adrenal cortex) and RBC -G6P DH, transketolases (TPP cofactor) |
|
|
Oxidative/Respiratory Burst
-Cells occurs in? -Steps involved? -Recovery? |
-PMN, macs
-Membrane-bound NADPH oxidase makes superoxide, SOD converts to peroxide, myeloperoxidase makes bleach, KILL SHIT. -Peroxide neutralized by catalase/glutathione peroxidase. Need NADPH from HMP shunt to reduce glutathione again for reuse. |
|
|
-Explain the pathophys of CGD? Enzyme defect?
|
-NADPH oxidase deficiency, cannot make own peroxide into bleach. Can utilize peroxide from bacteria, EXCEPT catalase pos bugs that neutralize peroxide!
|
|
|
-What is the fxn of NADPH?
|
-NADPH keeps glutathione reduced (GSSG-->GSH) so that it can detox free rads and peroxides.
-Also useful for anabolic processes, resp burst, and p450. |
|
|
G6PD Deficiency
-MOA -Precipitants of attack -MCC death |
-No G6PD, so no NADPH to reduce glutathione, so no protection against oxidizing agents.
-Fava beans, sulfa, anti-malaria, anti TB. Infxn due to free rads generated by inflam response that diffuse into RBC. -Infxn because no NADPH for resp burst! |
|
|
Essential Fructosuria
-defect, inheritance |
-AR defect in fructose kinase, no conversion of fructose-->F6P
-Asx, fructose can't enter cells to cause trouble! |
|
|
Fructose Intolerance
-defect, inheritance -findings -tx |
-AR defect in aldolase B, no conversion F1P--> DHAP/glyceraldehyde. Build up of F1P in liver drains all P stores, inhibiting gluconeo and glycogenolysis
-Hypoglycemia, jaundice, cirrhosis, vomit -Tx=no fructose or sucrose |
|
|
Galactokinase Deficiency
-defect, inheritance -findings |
-AR defect galactokinase
-galactilol accumulates causing infantile cataracts (no social smile/object tracking). |
|
|
Galactosemia
-defect, inheritance -findings -tx |
-AR defect in galactose-1P uridyltransferase.
-Infantile cataracts, MR, jaundice, hepatomeg, FTT. -Tx=No galactose or lactose. |
|
|
-Where does sorbitol come from?
-Why does accumulation and osmotic damage happen in some cells? -Which cells lack sorbitol DH? -Which cells have it? |
-Aldolase reductase converts glc to sorbitol to bring into cell.
-Sorbitol builds up in cells without sorbitol DH to turn it into fructose. -Schwann cell, lens/retina, kidney (DM neuropathy, retinopathy, nephropathy) -Liver, ovary, seminal vesicle |
|
|
-Name the essential AA's (glucogenic, both, ketogenic)
|
Glucogenic only: Met, Val, Arg, His
Both: Ile, Phe, Thr, Trp Ketogenic: Leu Lys |
|
|
-Name the acidic AA's
-Name the basic AA's -Which AA's needed for growth? -Which found in histones? |
-Aspartate, glutamate
-Arg, Lys, His -Arg, His -Arg, Lys (pos charge to bind DNA) |
|
|
Urea Cycle
-What's in it? |
"Ordinarily Careless Crappers Are Also Frivolous About Urination"
-Ornithine, carbamoyl P, citrulline, aspartate, argininosuccinate, fumarate, arginine, urea. |
|
|
Urea Cycle
-How does NH4 enter the cycle? -Rate lim step? -What 3 molecules compose urea? |
-CO2+NH4=carbamoyl P
-Carbamoyl P synthetase I -NH2 from NH4, CO2, NH2 from aspartate |
|
|
-What two AA's help to shuttle NH3 from muscle to liver for excretion in urea cycle? Name of this shuttle? Why do you need it?
-What pairs with alanine and glutamate to help shuttle? |
-Alanine and glutamate (Alanine-glucose shuttle). Cannot use AA's as fuel until you take the amino group off, and then it has to be excreted!
Alanine - pyruvate Glutamate - alpha KG |
|
|
Hyperammonemia
-Biochem sequelae -Findings -Tx |
-Accumulation of NH4 depletes alpha-KG, halting TCA cycle.
-Tremor, slurred speech, vomit, cerebral edema, blurred vision -Limit protein, sodium benzoate, phenylbutarate, or lactulose |
|
|
Ornithine Transcarbamoylase Def
-Inheritance -Pathophys -Findings |
-X-linked recessive (unlike other urea cycle defects)
-Build up of carbamoyl P shunted to orotic acid, no urea excretion -high serum orotic acid levels, low BUN, hyperammonemia |
|
|
-What is synthesized from Phe?
-Tryptophan? -Histidine? -Glycine? -Arginine? -Glutamate? |
Phe-->Tyr, Dopa, DA, NE, Epi. Thyroxine and melanin.
Trp-->niacin (B6), serotonin/ melatonin His-->histamine (B6) Gly-->porphyrin/heme (B6) Arg-->Cr, urea, NO Glu-->GABA (B6), glutathione |
|
|
-Breakdown prods of dopamine, NE, Epi?
-Which enzyme makes DA from dopa. cofactor needed? -Which makes NE from DA, cofactor? |
-HVA, VMA, metanephrine
-Dopa decarboxylase, B6 -Dopamine beta-OHase, Vit C |
|
|
Phenylketonuria
-Defect, inheritance -Findings -Tx |
-AR defect in Phe hydroxylase or low THB cofactor.
-MR, seizure, pale skin, eczema, musty body odor. -Tx=no Phe, increase Tyr |
|
|
Maternal PKU
-Findings in infant? |
-Microceph, MR, growth retardation, congenital heart defect
|
|
|
Alkaptonuria (ochronosis)
-Defect, inheritance -Findings -Toxicity of homogentisic acid? |
-AR defect in homogentisic acid oxidase (can't degrade Tyr to fumarate)
-Dark brown/black CT, sclera, urine. -Homogentisic acid toxic to cartilage, may have arthralgia. |
|
|
Albinism
-Defect, inheritance -Findings |
-AR defect in tyrosinase or tyr transporters, failure of neural crest migration
|
|
|
Homocystinuria
-Defect, inheritance -Findings |
-AR defect of homocys methyltransferase, cystathione synthase, or poor affinity of cystathione synthase
-Increased homocys in urine, marfanoid habitus, accel atherosclerosis, increase of methionine -Tx=Decrease Met, increase Cysteine |
|
|
Cystinuria
-Defect, inheritance -Findings -Tx -What is cystine made of? |
-AR defect of PCT transporter of Cys, ornithine, Lys, arginine
-Cystine kidney stones (hexagon) -Tx=acetazolamide to alk urine -Cystine=2 cysteine joined by disulfide bond |
|
|
Maple Syrup Urine Disease
-Defect, inheritance -Findings |
-AR defect in alpha-ketoacid DH blocks degradation of branched AA (Ile, Leu ,Val)
"I Love Vermont maple syrup from branched trees." -Severe MR, death, urine smells like maple syrup. |
|
|
Hartnup Disease
-Defect, inheritance -Findings |
-AR defect in neutral AA transporter on PCT and intestinal epithelial cells
-Loss of tryptophan causes pellagra |
|
|
-Where are the glucagon receptors that regulate glycogen?
-Epi? |
-Glucagon receptors=liver, Epi receptors=liver, muscle.
|
|
|
-What cascade do glucagon and Epi trigger for glycogenolysis?
-What triggers glycogenloysis in exercising muscle? |
-Activate adenylyl cyclase, increase cAMP, activate PKA, activate glycogen phosphorylase kinase, activate glycogen phosphorylase, break down glycogen.
-Ca in muscle binds to calmodulin receptor on glycogen phosphorylase kinase to trigger same cascade. |
|
|
-What cascade does insulin trigger for glycogenloysis?
|
-RTK dimerizes, activates protein phosphatase, inactive glycogen phosphorlyase kinase and glycogen phosphorylase to prevent breakdown.
|
|
|
-How does the body prevent syn and breakdown of glycogen at same time?
|
-When glucagon/epi and PKA activate glycogen phosphorylase, same pathway simultaneously inactives glycogen synthase. Opp for insulin.
|
|
|
-Which 2 places is glycogen stored and for what purpose?
|
-Muscle for energy during exercise, and liver to maintain blood sugar levels.
|
|
|
-What kind of bonds do glycogen linkages and branches have?
|
-Linkage: alpha(1,4)
-Branch: alpha(1,6) |
|
|
-Describe the pathway of glycogen syn/breakdown?
-What enzyme makes UDP-glc? |
-G6P, G1P, UDP-glc, glycogen, branched glycogen, breakdown to limit dextrin, debranch
-UDP-glc pyrophosphorylase |
|
|
-What 2 enzymes can degrade glycogen?
-Name the 4 glycogen storage disease you know? |
-Glycogen phosphorylase and alpha-1,4-glucosidase (small amnt in lysosome)
-"Very Poor Carb Metabolism" Von Gierke, Pompe,Cori, McArdle |
|
|
Von Gierke Disease (Type I)
-Deficiency -Findings |
-Glc-6-phosphatase. No turn G6P to glc.
-SEVERE fasting hypoglycemia (can't do gluconeo!), high blood lactate, lots of glycogen in liver, hepatomeg |
|
|
Pompe's Disease (Type II)
-Deficiency -Findings |
-Lysosomal alpha-1,4-glucosidase
-Cardiomeg, liver/muscle damage "Pompe's trashes the pump" |
|
|
Cori's Disease (Type III)
-Deficiency -Findings |
-Debranching enzyme (alpha-1,6-glucosidase)
-Milder form of Von Gierke's, normal blood lactate. (Still can go from G1P, G6P, glc. Only have build up limit dextrins.) |
|
|
McArdle's Disease (Type V)
-Deficiency -Findings |
-Skeletal muscle glycogen phosphorylase
-LOTS of glycogen trapped in muscle, fatigue and cramping with exercise, myoglobinuria |
|
|
Fabry's Disease
-Inheritance, deficient enzyme, accumulated substrate -Findings |
-X-linked recessive, alpha-galactosidase A, ceramide trihexoside.
-periph neuropathy of hands and feet (burning), angiokeratoma, CV/renal dz |
|
|
Gaucher's Disease (MC)
-Inheritance, deficient enzyme, accumulated substrate -Findings |
-AR, beta-glucocerebrosidase, glucocerebroside.
-HSM, aseptic necrosis of femur, tissue paper macs |
|
|
Niemann-Pick Disease
-Inheritance, deficient enzyme, accumulated substrate -Findings |
-AR, sphingomyelinase, sphingomyelin.
-Cherry red spot, HSM, neurodegen, foam cells |
|
|
Tay-Sachs Disease
-Inheritance, deficient enzyme, accumulated substrate -Findings |
-AR, hexosaminidase A, GM2 ganglioside.
-Cherry red spot, dev delay, neurodegen, startle, onion skin lysosomes, NO HSM |
|
|
Krabbe's Disease
-Inheritance, deficient enzyme, accumulated substrate -Findings |
-AR, Galactocerebrosidase, galactocerebroside
-Globoid cells, periph neuropathy, optic atrophy, dev delay |
|
|
Metachromatic Leukodystrophy
-Inheritance, deficient enzyme, accumulated substrate -Findings |
-AR, arylsulfatase A, cerebroside sulfate.
-Central/periph demyelination with ataxia and dementia |
|
|
Hunter's Syndrome
-Inheritance, deficient enzyme, accumulated substrate -Findings |
-X-linked recessive, iduronate sulfatase, heparan/dermatan sulfate.
-Mild Hurler's with aggressive behavior, no corneal clouding (angry hunter sees clearly) |
|
|
Hurler's Syndrome
-Inheritance, deficient enzyme, accumulated substrate -Findings |
-AR, alpha-L-iduronidase, heparan/dermatan sulfate.
-Gargoylism, airway obstruction, corneal clouding, HSM, dev delay. |
|
|
-Which shuttle is for FA syn? Where occur?
-Which shuttle is for FA oxidation? Where occur? |
-Citrate shuttle (SYNtrate), cytoplasm.
-Carnitine shuttle (CARnage), mito. |
|
|
-Pathway for FA syn?
-Pathway for FA oxidation? |
-Acetyl-CoA, malonyl coA, FA
-FA+CoA, Acyl-CoA, acetyl-CoA after beta-oxidation |
|
|
-What inhibits the carnitine shuttle?
|
-Malonyl CoA (present during syn, so no breakdown and syn and same time)
|
|
|
-What happens in carnitine deficiency?
|
-Can't transport FA into mitos for breakdown, toxic accum. Hypoketotic hypoglycemia, weakness, hypotonia.
|
|
|
-What happen in acyl-CoA DH deficiency?
|
-Impaired beta-oxidation. Can't breakdown acyl-CoA to glc and ketones, increase dicarboxylic acid.
|
|
|
-Where are ketone bodies made?
-What are they made from? -Which organs can use them as fuel? -How are they excreted? |
-Ketone bodies made in liver
-Made from Fatty acids and amino acids, HMG CoA (HMG CoA synthase) -Brain and muscle can utilize -Urinary excretion |
|
|
-Why do you get ketoacidosis in starvation, DKA?
-What about EtOH? |
-Oxaloacetate is shunted out for gluconeo and TCA cycle stalls. SO...glc and FA are shunted toward ketone bodies.
-Excess NADH shunts oxaloacetate back to malate, stalling TCA cycle as above. |
|
|
-Which type of ketone does urine test detect?
|
-Acetoacetate
|
|
|
-Which fuel do you use for sprint?
-Jog? (mins) -Marathon? (hrs) |
-Sprint: stored ATP, creatine P, anaerobic glycolysis
-Jog: above + aerobic -Marathon: glycogen, FA oxidation. Save glc for final sprint. |
|
|
-What fuel do you use during fasting?
|
-Fast: Hepatic glycogenolysis and gluconeo, small amnt FA
|
|
|
-Starvation day 1-3?
|
-hepatic glycogenolysis (day 1)
-FA from adipose -muscle and liver start using FA -hepatic gluconeo from alanine, lactate, glycerol and propionyl-CoA from odd chain FA's |
|
|
-Starvation after day 3?
-How do you die from starvation? |
-Adipose stores. Muscle and liver keep using FA's, brain and heart use ketone bodies.
-After adipose exhausted, start to breakdown vital proteins and die. |
|
|
-What is the rate lim step of cholesterol syn?
-What esterifies 2/3 of plasma cholesterol? |
-HMG-CoA to mevalonate via HMG CoA reductase
-Lecithin-cholesterol acetyl transferase (LCAT) |
|
|
-Fxn of pancreatic lipase?
-Lipoprotein lipase? -Hepatic TG lipase? -Hormone sensitive lipase? |
Pancreatic: Breakdown TG in SI
LPL: Breakdown TG in chylo, VLDL Hepatic TG lipase: Breakdown TG remaining in IDL HS lipase: Breakdown TG stored in adipocytes |
|
|
-Name some lipoproteins?
-What mediates the transfer of cholesterol onto lipoproteins? -What are lipoproteins made of? |
-Chylo, LDL, HDL, VLDL, etc
-CETP -Cholesterol, TG, phospholipid |
|
|
Apolipoprotein Fxns
A-I B-100 C-II B-48 E |
A-I: Activated LCAT
B-100: Binds LDL receptor, mediates VLDL secretion C-II: Cofactor for LPL B-48: Mediates chylomicron secretion E: Mediates Extra (remnant) uptake |
|
|
-What do chylomicrons do?
-Which apolipoproteins assist? |
-TG from food to periph tissue.
-Chylomicron remnants (cholesterol) to liver. -B48, AIV, CII, E |
|
|
-What does VLDL do?
-Which apolipoproteins assist? |
-TG in liver to periph tissue
-B100, CII, E |
|
|
-What does IDL do?
-Which apolipoproteins assist? |
-Leftover from VLDL. Deliver TG and cholesterol to liver, then turned into LDL.
-B100, E |
|
|
-What does LDL do?
-Where/how is it made? -Which apolipoproteins assist? |
-Take cholesterol from liver to periph
-Made from VLDL in periph tissue via lipoprotein lipase. So eating less fats, less VLDL, less LDL! -B100 |
|
|
-What does HDL do?
-Which organs secrete? -Which apolipoproteins assist? |
-Reverse cholesterol transport from periph to liver.
-Repository of apoC and apoE -Secreted by liver and intestine -None |
|
|
Hyperchylomicronemia (Type I)
-Defect -What is elevated in blood -Findings |
-No lipoprotein lipase, or no C-II (cofactor of LPL)
-TG and cholesterol increased -HSM, pancreatitis, xanthomas, NO risk of athero |
|
|
Familial Hypercholestermia (Type IIa)
-Defect -Elevated in blood -Findings |
-AD, Absent/decreased LDL receptor
-LDL and total chol -Accel athero, xanthomas, arcus senilis |
|
|
Familial Hypertriglyceridemia (Type IV)
-Defect -Elevated in blood -Findings |
-Hepatic overprod of VLDL
-Increased TG -Pancreatitis |
|
|
Abetalipoproteinemia
-Defect -Elevated in blood -Findings |
-AR, no apoB48 (chylo uptake) or apoB100 (LDL receptor/VLDL secretion)
-LOW levels of chylo, VLDL, LDL -FTT, steatorrhea, hemolytic anemia (Vit E def), ataxia, night blindness (Vit A def) |
