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FA-2017
Biochem FA-2017
| Question | Answer |
|---|---|
| Purines | Pure As Gold- Arginine + Guanine |
| Pyrimidines | CUT the py- Cytosine + Uracil + Thyamine |
| Differences between carbamoyl phospatase synthetase I and II? | CPS1- location: mitochondria. Pathway: urea. Source of N: ammonia CPS2- location: cytosol. Pathway: de novo synthesis of pyrimidines. Source of N: glutamine |
| Rate limiting enzyme for pyrimidine de novo synthesis | Carbamoyl phosphatase synthethase II |
| Leflunomide MOA | Inhibits dihydroorotate deshydrogenase |
| Enzyme impaired in orotic aciduria? Symptoms | UMP synthase. Hyperamonemia + megaloblastic anemia |
| Hydroxyurea MOA | Ribonucleotide reductase inhibitor |
| 5-FU MOA | Thymidylate synthase inhibitor |
| MTX,TMP, pyrimethamine MOA | Dihydrofolate reductase inhibitor |
| 6-mercaptopurine and azathioprine MOA | Inhibits glutamine PPRP amidotransferase |
| Mycophenolate + rivabirin MOA | Inhibit inosine monophosphate deshydrogenase (IMP) |
| Drugs that inhibit de novo pyrimidin synthesis? | 1. Leflunomide 2. Hydroxyurea 3. 5-FU 4. MTX 5. TMP 6. Pyrimethamine |
| Drugs that inhibit de novo purine synthesis | 1. 6-MP 2. Azathioprine 3. Rivabirin 4. Mycophenolate |
| What enzyme is deficient in SCID? | Adenosine deaminase. Required for purine salvage pathway. |
| Enzyme deficient in Lesch-Nyhan Sx? | HGPRT- defective purine salvage, can't convert guanine/hypoxanthine back into GMP -> all transformed into uric acid |
| Lesch Nyhan Sx findings | HGPRT-hyperuricemia, gout, pissed off (aggression, self- mutilation), retardation, dysTonia + orange "sand" (Na urate crystals) in diaper |
| Helicase | Unwinds DNA template at replication fork |
| DNA topoisomerases | Remove supercoils |
| Primases | Makes an RNA primer |
| DNA polymerase III | Elongates lagging strand. Exonuclease activity proofreading nucleotides |
| DNA polymerase I | Degrades RNA primer, replaces it with DNA |
| DNA ligase | Joins okazaki fragments |
| Telomerase | Eukaryotes only. Avoids loss of genetic material. |
| Inhibit eukaryotic topoisomerase I | Irinotecan/ topotecan |
| Inhibit eukaryotic topoisomerase II | Etoposide/ teniposide |
| Inhibit prokaryotic topoisomerase II + IV | Fluorquinolones |
| Differences between etoposide and fluorquinolones? | Etoposide inhibits eukaryotic topoisomerase II, fluorquinolones inhibit this enzyme in prokaryotes |
| Silent mutation | Nucleotide substitution but codes for same amino acid. Nothing happens |
| Missense mutation | Nucleotide substitution resulting in changed aminoacid. Protein misfunction |
| Nonsense mutation | Nucleotide substitution resulting in early stop codon. Protein doesn't function |
| Stop codons | UAA, UAG, UGA |
| DNA mutation in sickle cell disease? | Missense mutation |
| Frameshift mutation | Deletion or insertion of nucleotides resulting in misreading of all nucleotides downstream. |
| Splice site mutation | Mutation at the splice site results in retained intron in mRNA. |
| DNA mutation in Duchenne musuclar dysthrophy? | Frameshift mutation |
| DNA mutation in Tay Sachs disease? | Frameshift mutation |
| Lac operon | Example of a genetic response to an enviromental change. If glucose is present, E. Coli will use it and transcription of B- galactosidase to metabolize lactose will not take place |
| Conditions for transcription of B-galactosidase to take place in lac operon | CAP present (in situations with low glucose) and repressor absent (in situations with high lactose) |
| Nucleotide excision repair | Endonucleases. Dna polymerase and ligase fill and reseal gaps. Repairs bulky lesions. Occurs in G1 |
| Base excision repair | 1. Glycosylase removes altered base 2. Endonucleases remove nucleotides at 5' end 3. Lyase cleaves 3'end 4. Dna polymerase fills gap 5. Dna ligase seals it. Occurs throughout cell cycle |
| Mismatch repair | Mismatchrd nucleotides are removed. Occurs in G2 |
| Defective nonhomologous end joining results in what diseases | Ataxia telangectasia, fanconi anemia, breast/ovarian ca with BRCA1 mutation |
| DNA repair mechanism defective in xeroderma pigmentosum | Nucleotide excision repair |
| DNA repair mechanism defective in Lynch sx? | Mismatch repair |
| RNA polymerase I | Makes rRNA |
| RNA polymerase II | Makes mRNA |
| RNA polymerase III | Makes tRNA |
| Inhibits RNA polymerase II | Alpha- amanitin found in amanita phalloides. Can cause severe hepatotoxicity |
| Inhibits RNA polymerase in both eukaryotes and prokaryotes | Actinomycin D |
| DNA- dependent RNA polymerase in prokaryotes inhibitor | Rifampin |
| Exons | They contain the actual genetic information coding for protein |
| Introns | Intervening noncoding segments of DNA |
| Steps in protein synthesis | 1. Initiation 2. Elongation 3. Termination |
| What happens in initiation? | Initiation factors help assemble the 40s and 60s subunits |
| What happens in elongation? | 1. Aminoacyl-tRNA binds to A site (if it has methionine it binds directly to P site) 2. rRNA transfers polypeptide to amino acid in A site 3. Ribosome advances moving tRNA to P site. This keeps going until stop codon is reached |
| What happens in termination? | Stop codon is recognized and completed polypeptide is released. |
| Functions of A,P,E sites | A- holds upcoming tRNA P- accommodates growing peptide E- holds empty tRNA as it exits |
| Cells that remain in G0 | Neurons, skeletal and cardiac muscle, RBCs |
| Smooth endoplasmic reticulum function | Steroid synthesis and detoxification |
| Golgi function | Distribution center for proteins and lipids from the ER to the vesicles and plasma membrane. Adds mannose-6-P to proteins for trafficking to lysosomes |
| Enzyme deficient in I-cell disease | N-acetylglucosaminyl-1-Ptransferase. Failure of Golgi to phosphorylate mannose residues. Proteins are secreted extracellularly |
| I-cell disease findings | Coarse facial features, clouded corneas, restricted joint movement, high plasma levels of lysosomal enzymes. Fatal |
| Vesicular trafficking proteins | COP1: retrograde -> Golgi to ER. COP2: anterograde -> ER to Golgi. Clathrin: Golgi to lysosomes |
| Peroxisomal diseases | Zellweger Sx and Refsum disease |
| Zellweger | Hypotonia, seizures, hepatomegaly, early death |
| Refsum disease | Scaly skin, ataxia, cataracts/night blindness, shortening of 4th toe, epiphyseal dysplasia |
| Vimentin- cell type and tumors | Mesenchymal tissue. Sarcomas, endometrial ca, meningioma, renal cell ca |
| Desmin- cell type and tumors | Muscle- rhabdomyosarcoma |
| Cytokeratin- cell type and tumors | Epithelial cells- squamous cell ca |
| GFAP-cell type and tumors | Neuroglia- astrocytoma and glioblastoma |
| Neurofilaments | Neurons- neuroblastoma |
| Drugs that act on microtubles | 1.Mebendazole 2.Griseofulvin 3. Colchicine 4. Vincristine/Vinblastine 5. Paclitaxel |
| Dynein | Retrograde to microtubule |
| Kinesin | Anterograde to microtubule |
| Kartagener sx | Dynein arm defect. Decreased fertility, bronchiectasis, recurrent sinusitis, chronic ear infections, conductive hearing loss, situs inversus |
| Collagen type 1 | Bone, skin, tendon, dentin, fascia, cornea, late wound repair |
| Collagen type 2 | Cartilage, vitreous body, nucleus pulposus |
| Collagen type 3 | Reticulin, blood vessels, uterus, fetal tissue, granulation tissue |
| Collagen type 4 | Basement membrane, basal lamina, lens |
| Collagen defective in Alport Sx | Collageb type 4 |
| Autoantibodies against what type of collagen in Goodpasture | Type 4 |
| Collagen deficient in vascular Ehlers-Danlos Sx | Type 3 |
| Decreased production of what collagen in Osteogenesis Imperfecta | Type 1 |
| Steps in collagen synthesis | 1. Synthesis 2. Hydroxylation 3. Glycosylation 4. Exocytosis 5. Proteolytic processing 6. Cross linking |
| Synthesis- collagen synthesis | Translation of collagen alpha chains (preprocollagen). Uses glycine and proline/lysine |
| Hydroxylation- collagen synthesis | Hydroxylation of proline and lysine. Uses vit C |
| Glycosylation- collagen synthesis | Formation of procollagen, a triple helix |
| Exocytosis-collagen synthesis | Exocytosis of procollagen into extracellular space |
| Proteolytic processing-collagen synthesis | Cleavage of terminal refions of procollagen-> insoluble tropocollagen |
| Disease originating from impaired collagen hydroxylation | Scurvy |
| Disease originating from impaired glycosylation of collagen | Osteogenesis Imperfecta |
| Disease originating from impaired proteolytic processing | Ehlers-Danlos |
| Cross linking-collagen synthesis | Reinforcement of tropocollagen molecules to make collagen fibrils |
| Diseases that originate from impaired cross linking collagen | Ehlers-Danlos and Menkes |
| Osteogenesis Imperfecta- defective genes | COL1A1 and COL1A2 |
| Modes of inheritance- OI | Type I: AD. Type 2: AR |
| Symptoms of OI | 1. Multiple fractures. 2. Blue sclerae 3. Tooth abnornalities (opalescent teeth that wear easily) 4. Hearing loss |
| Types of Ehlers Danlos- can be associated with berry + aortic aneurysm | Hypermobility (most common), classical type (joint +skin- type 5 collagen), vascular type (vascular and organ rupture-type 3 collagen) |
| Menkes disease | XR. Impaired Cu+ absorption due to defective Menkes protein. Decreases activity of lysyl oxidase |
| Symptoms of Menkes | Brittle, kinky hair, growth retardation and hypotonia |
| Where is elastin found | Skin, lungs, large arteries, elastic ligaments, vocal cords, ligamenta flava. |
| What is elastin made of | NONhydroxylated proline, glycine and lysine. |
| What enzyme inhibits elastase | Alpha 1 antitrypsin |
| Gene mutated in Marfans? Defective protein? | FBN1 gene on chromosome 15. Defective fibrillin-forms sheath around elastin |
| Marfan syndrome- symptoms | Tall long extremities, pectus carinatum or excavatum, hypermobile joints, arachnodactyly, cystic medial necrosis of aorta, aortic incompetence, dissecting aortic aneurysms, floppy mitral valve. Subluxation of lenses- upward and temporally. |
| Ocular changes in marfan and homocystinuria | Marfan- lens subluxation upward and temporally. Homocystinuria- downward and inward. |
| Polymerase chain reaction uses | Used to amplify a desired fragment of DNA. |
| Southern blot | DNA sample, DNA probe |
| Northern blot | RNA sample, RNA probe |
| Western blot | Protein sample, antibody probe. Confirmatory test for HIV after + ELISA |
| Southwestern blot | Transcription factors |
| What is Flow cytometry | Cells are tagged with antibodies and then these are tagged with a fluorescent dye |
| What is flow cytometry used for? | Commonly in workup of hematologic abnormalities- PNH, fetal rbcs in mothers blood, immunodeficiencies |
| ELISA-direct | Used to detect the presence of a specific antigen in pts blood sample. |
| ELISA- indirect | Used to detect the presence of a specific antibody in pts blood sample. |
| ELISA used for VIH screening | Direct elisa |
| Fluorescence in situ hybridization | Fluorescent DNA or RNA probe used foe specific location of genes in chromosomes |
| Codominance definition and example | Both alleles contribute to the phenotype of the heterozygote. Blood groups A, B, AB, alpha 1 antitrypsin deficiency |
| Variable expressivity- definition and example | Disease with variable degree of affectation. NF1 |
| Incomplete penetrance- definition and example | Disease but no phenotype at all. BRACA1 gene mutations |
| Pleiotropy- definition and example | One gene contributes to multiple phenotypic effects. PKU |
| Anticipation- definition and example | Increased severity or earlier onset of disease in succeeding generations. Huntington's |
| Mosaicism- definition and example | Genetically distinct cell lines in same individual. McCune-Albright |
| McCune Albright Sx- defect and symptoms | Mutation in G protein signaling. 1. Cafe au lait 2. Fibrous dysplasia 3. One endocrinopathy. Lethal if affects all cells |
| Locus heterogeneity- definitions and example | Mutations at different loci can produce a similae phenotype. Albinism |
| Allelic heterogeneity- definition and example | Different mutations in the same locus produce the same phenotype. B-thalassemia |
| Hardy-Weinberg formulas | 1) p + q = 1. 2) p^2 +2pq + q^2. P^2 = frequency of A. Q^2 = frequency of a |
| Imprinting- definition and examples | At the same loci, only one allele is active; the other is inactive. Deletion of the active allele is disease. Prader-Willi, Angelman. |
| Prader-Willi- symptoms | Paternal gene deleted. Hyperphagia, obesity, intellectual disability, hypogonadism, hypotonia and osteoporosis |
| Angelman syndrome- symptoms | Maternal gene is deleted. Inappropriate laughter, seizures, ataxia and severe intellectual disability |
| X linked dominant- examples | Hypophosphatemic rickets, fragile x, alport sx. |
| Mitochondrial inheritance | Offspring of females may show signs of disease. MELAS- mitochondrial encephalopathy, lactic acidosis and strokes. Biopsy: ragged red fibers. |
| CF- defective gene and chromosome | CFTR that encodes ATP gated Cl channel that secretes Cl in lungs and GI and reabsorbes Cl in sweat glands. Chromosome 15 |
| Dx of CF | >60mEql of CL in sweat. Can have alkalosis + hypokalemia |
| CF symptoms: pulm, GI, newborns, GU | Recurrent pulm infections (aureus-infancy, pseudo-adolescence),chronic bronchitis + bronchiectasis, pancreatic insufficiency, malabsorption, meconium ileus, infertility in men. |
| X linked recessive disorders | 1. Ornithine transcarbamylase deficiency, ocular albinism 2. Fabry 3. Wiskot-Aldrich 4. Hemophilia A/B 5. Lesch Nyhan 6. Duchenne/Becker, 7. Bruton's 8. Hunter Sx. 9. G6PD def |
| Duchenne- absent protein? symptoms? MCC of death? | Dystrophin. Pseudohypertrophy of calf muscles due to fibrofatty replacement of muscle. Dilated cardiomyopathy |
| Duchenne- protein function? Labs? | Dystrophin: anchors actin to transmembrane proteins. Elevated CK and aldolase. |
| How are duchenne and becker different? | Dystrophin is absent in becker while is its partially functional in becker. Becker has onset in adolescence |
| Myotonic type 1 muscular dystrophy- cause + symptoms | CTG trinucleotide repeat. Myotonia, muscle wasting, cataracts, tersticular atrophy, frontal balding, arrhythmia. |
| Fragile X syndrome- gene involved + symptoms | FMR1 gene. Intellectual disability, macroorchidism, large jaw, large everted ears, autism, mitral valve prolapse. |
| Trinucleotide repeats expansion diseases: | Huntingtons (CAG), Myotonic dystrophy (CTG), Friederich Ataxia (GAA) Fragile X Sx (CGG) |
| What are the 3 main causes of Downs? | 1. maternal age: meiotic nondisjunction 2. Robertosnian translocation 3. Mosaicism |
| Downs- quad screen | 1. Decreased AFP 2. Increased BhCG 3. Decreased estriol 4. Increased inhibin A |
| Downs- first trimester US | Increased nuchal translucency, hypoplastic nasal bone, decreased serum PAPP-A |
| Downs- associated pathologies | 1. Duodenal atresia 2. ASD 3. Hirschsprung 4. Alzheimer 5. ALL |
| Edwards Sx- chromosome + symptoms | 18. PRINCE- Prominent occiput, Rocker-bottom feet, Intellectual disability, Nondisjunction, Clenched fists, low set Ears, micrognatia. |
| Edwards Sx- quad screen | 1. Decreased AFP 2. Decreased BhCG 3. Decreased estriol 4. Decreased or normal inhibin A |
| Patau Sx- chromosome + symptoms | 13. Intellectual disability, microphthalmia, microcephaly, cleft lip + palate, holoprosencephaly, polydactyly, cutis aplasia. |
| What diseases have nuchal translucency on US? | 1. Downs 2. Patau 3. Turner |
| Robertsonian translocation-definition | Long arms of 2 acrocentric chromosomes fuse at the centromere and the 2 short arms are lost. |
| Cri-du-chat Sx- chromosome + symptoms | Deletion chr 5. Microcephaly, intellectual disability, high pitch crying, VSD. |
| Williams Sx- chromosome + symptoms | Deletion chr 7. Elfin facies, intellectual disability, hyperCa (increased sensitivity to Vit D), extreme friendliness with strangers |
| 22q11 deletion sx: aberrant development of 3rd and 4th pouches | DiGeorge + Velocardiofacial sx |
| Vit A-functions | Antioxidant, differentiation of epithelial cells into specialized tissue, prevents squamous metaplasia |
| Vit A- uses | Measles, APL (all-trans retinoic acid), Cystic acne (isotretinoin) |
| Vit A- deficiency | Night blindness, xerosis cutis, keratomalacia- Bitot spots. |
| Vit A- excess | Acute- nausea + vertigo + blurred vision. Chronic- alopecia, dry skin, hepatotoxicity, arthralgias, pseudotumor cerebri, teratogenic- cleft palate + CV anomalies |
| Vit D- D2? D3? storage form? active form? | D2-ergocalciferol (plants) D3-cholecalficerol (milk, skin). Storage-25-OH D3 (calcidiol) Active- 1,25 (OH2) D3 (calcitriol) |
| Enzyme used to convert calcidiol to calcitriol? | 1-alpha-hydroxylase |
| Vit D- deficiency | Children-rickets: genu varum. Adults- osteomalacia: bone pain + muscle weakness |
| Vit D- excess | HyperCa, loss of appeptite, stupor. |
| Why does sarcoidosis increase Ca? | Granulomas produce 25- hydroxylase |
| Vit E- function, deficiency | Antioxidant. Hemolytic anemia, acanthocytosis, posterior column + spinocerebellar demyelination. |
| Vit K- function | Activated by epoxide reductase, cofactor for gamma carboxylation of glutamic acid -> Necessary for maturation of clotting factors II, VII, IX, X and proteins C + S. |
| Lab changes in Vit K deficiency | Increased PT + PTT, normal bleeding time. |
| Zinc- function | Important in formation of zinc fingers, essential for carbonic anhydrase |
| Zinc deficiency | Senses: anosmia, dysgeusia, acrodermatitis enterophatica, delayed wound healing. Sexual: hypogonadism, decreased adult hair. May predispose to alcoholic cirrhosis |
| Kwashiorkor- symptoms | Protein malnutrition- MEALS: Malnutrition, Edema, Anemia, Liver (fatty), Skin lesions (hyperkeratosis/hyperpigmentation) |
| Marasmus- symptoms | Caloric malnutrition. Muscle wasting. |
| Vit B1- name + function | Thiamine. Thiamine pyrophosphate (TPP) is a cofactor for: 1. Pyruvate DHNase 2. alpha ketoglutarate DHNase 3. Transketolase 4. Branched-chain ketoacid DHNase. |
| Vit B1 deficiency | Wernicke encephalopathy (ACO(u)te) Ataxia, Confusion, Ophtalmoplegia. Korsakoff (chronic)- Confabulation, personality change, permanent memory loss. |
| What structures are damaged in Wernicke-Korsakoff Sx? | Medial dorsal nucleus of thalamus + mamillary bodies. |
| Dry beriberi (B1 def) | Polyneuritis, symmetrical muscle wasting |
| Wet beriberi (B1 def) | High output cardiac failure (dilated cardiomyopathy), edema. |
| Vit B2- name + function | RiboFlavin. Component of FAD + FMN used as cofactors in redox reactions. (TLC 4 N) |
| Vit B2- deficiency | Cheilosis + Corneal Vascularization (The 2 Cs of B2) |
| Vit B3- name + function | Niacin, constituent of NAD, NADP (TLC 4 N). Used lower levels of VLDL and increase HDL. |
| What vitamin is derived from tryptophan? | B3-niacin |
| Hartup Disease- cause + symptoms | AR. Deficiency of tryptophan transporters in kidney and enterocytes -> no B3 (niacin)- Pellagra (Diarrhea, Dermatitis, Dementia, Death) |
| Vit B3- deficiency | Glossitis. Severe deficiency leads to pellagra: diarrhea, dermatitis, dementia, death) |
| Causes of B3 deficiency | Hartnup disease (low tryptophan), Malignant carcinoid sx (increased tryp metabolism), Isonazid (decreased Vit B6 needed for synthesis of B3). |
| Vit B3- excess symptoms | 1. Facial flushing (induced by prostaglandin, can avoid by taking aspirin 2. HyperGlu 3. HyperUricemia |
| Vitamin B5- name + function | Pantothenic acid, essential component of coenzyme A (used to form Acetyl-Coa) |
| Vit B5 deficiency | Dermatitis, Enteritis, Alopecia, Adrenal insuffiency |
| Vit B6- name + function | Pyridoxine. Converted to pyridoxal phosphate, 1. Used in transamination - ALT + AST 2. Synthesis of heme, niacin, histamine, serotonin, EPI, Nore, Dopa, GABA. |
| Vit B6 deficieny | (Think loss of GABA) Convulsions, hyperirritability, peripheral neuropathy, sideroblastic anemias. |
| Vit B7- name + function | Biotin. Cofactor for carboxylation |
| Vit B7 deficiency + causes | Dermatitis, alopecia, enteritis (like B5). Caused by antibiotic excess or raw egg whites |
| Vit deficiency leading to alopecia + enteritis + dermatitis | Vit B5 + Vit B7. |
| Vit B9- name + function | Folate. Converted to THF, important for synthesis of nitrogenous bases |
| Vit B9 deficiency symptoms + causes | Megaloblastic anemia, PMNs, glossitis, NO neurological symptoms. Caused by phenytoin, sulfas, methotrexate |
| Vit B9 deficiency labs | Increased homocysteine, normal methylmalonic acid. |
| Vit B12- name + function | Cobalamin (uses cobalt). Cofactor for methionine synthase- DNA synthesis |
| What type of patients are prone to Vit B12 def? | Vegans, B12 is found in animal products. |
| Vit B12 deficiency causes | Malarbsorption (sprue, enteritis, diphyllobothrium latum), no intrinsic factor (pernicious anemia, gastric bypass qx), absence of terminal ileum (qx, chrons), vegans. |
| Vit B12 deficiency symptoms | Megaloblastic anemia, PMNs, paresthesias, subactute COMBINED degeneration (dorsal columns + corticospinal + spinocerebellar). |
| Vit B12 deficiency labs | Increased homocysteine and methymalonic acid. |
| Vit C- function | 1. Hydroxylation of proline + lysine 2. Conversion of Dopa-> NE (B-hydroxylase) 3. Antioxidant |
| Vit C deficiency | Scurvy- swollen gums, bruising, petechiae, hemarthrosis, anemia, poor wound healing, corscrew hair. |
| Vit C + Fe association? | Vit C reduces Fe3 to Fe2. Increasing Fe absorption decreases lead absorption. |
| Fomepizole MOA, uses | Inhibits alcohol dehydrogenase. Antidote for methanol + ethylene glycol poisoning. |
| Antidote for methanol + ethylene glycol poisoning | Fomepizole |
| Disulfiram MOA, uses | Inhibits acetaldehyde dehydrogenase. Discouraging drinking |
| End product of ethanol metabolism | Ethanol -> acetaldehyde -> acetate |
| End product of methanol metabolism | Methanol-> formaldehyde -> formic acid |
| End product of ethylenglycol metabolism | Oxalic acid |
| Triad of formaldehyde intoxication (methanol) | 1. CNS depression 2. Acidosis 3. Blindness |
| Triad of oxalic acid intoxication (EG) | 1. CNS depression 2. Acidosis 3. Kidney damage |
| Limiting reagent in ethanol metabolism | NAD+ |
| Ethanol metabolism increases NADH/NAD+ ratio in liver causing? | 1. Pyruvate-> lactic acidosis. 2. Oxalacetate -> fasting hypoGlu 3. Hepatoesteatosis |
| What 3 processes occur in both mitochondria and cytoplasm? | 1. Heme synthesis 2. Urea cycle 3. Gluconeogenesis |
| Glycolysis- rate limiting enzyme | PKF-1 (Phosphofructokinase-1) |
| Gluconeogenesis- rate limiting enzyme | Fructose 1,6 Biphosphatase |
| TCA cycle- rate limiting enzyme | Isocitrate deshydrogenase |
| Glycogenesis- rate limiting enzyme | Glycogen synthase |
| Glycogenolysis- rate limiting enzyme | Glycogen phosphorylase |
| HMP shunt - rate limiting enzyme | Glucose -6-Phosphate deshydrogenase |
| De novo pyrimide synthesis - rate limiting enzyme | Carbamoyl phosphate synthase II |
| De novo purine synthesis - rate limiting enzyme | Glutamine-phosphoribosylpyrophosphate (PRPP) amidotransferase |
| Urea cycle- rate limiting enzyme | Carbamoyl phosphate synthase I |
| Fatty acid synthesis- rate limiting enzyme | Acetyl-CoA carboxylase |
| Fatty acid oxidation- rate limiting enzyme | Carnitine acyltransferase I |
| Ketogenesis - rate limiting enzyme | HMG-CoA Synthase |
| Cholesterol synthesis - rate limiting enzyme | HMG-CoA reductase |
| Glycolysis- regulators | (+) AMP, fructose 2,6BP. (-) ATP, citrate |
| Gluconeogenesis - regulators | (+) ATP, citrate (-) AMP, fructose 2,6 BP |
| Glycogenesis- regulators | (+) Insulin, cortisol (-) Glucagon, Epi |
| Glycogenolysis- regulators | (+) Glucagon, Epi, AMP (-) Insulin, ATP |
| How many ATPs are produced via the malate-aspartate shuttle? and where | 32, liver + heart |
| How many ATPs are produced via the glycerol-3-P shuttle?, where? | 30, muscle |
| How many ATPs does anaerobic glycolysis produce? | 2 |
| What pathway produces NADPH? Vit? | HMP-Shunt, Vit 3 |
| 4 NADPH uses | 1. FA + chol synthesis 2. Oxygen reactive species 3. Cytochrome P-450 system 4. Glutathione reductase to degrade free radicals in RBCs |
| Hexokinase + Glucokinase function | Convert Glu into Glu-6-P to trap it inside cells for glycolysis/glycogenesis |
| Hexokinase vs Glucokinase | [Location: G-liver + pancreas, H-other tissues] [Km + Vmax:G-High, H-Low] [Induced by insulin: G-yes, H-no] |
| End product of glycolysis? | Pyruvate. |
| What enzyme makes fructose 2,6BP in glycolysis? | PKF-2 induced by insulin |
| How does glucagon turn off glycolysis and drive gluconeogenesis? | It activates FBPase-1 which converts Fructose 1,6-BP back to fructose-6-P to be used in gluconeogenesis and also activates Fructose 2,6 BPase to convert fructose 2,6 BP back to fructose-6-P |
| What are the 4 end products of pyruvate? | 1. Acetyl-Coa to be used in TCA cycle 2. Lactate to be used in Cori cycle 3. Oxaloacetate to be used in gluconeogenesis 4. Alanine to transport N |
| What enzyme converts Pyruvate to Acetyl CoA | Pyruvate DHnase |
| What are the cofactors used by pyruvate Dhnase and alpha ketoglutarate Dhnase? | Tender Loving Care For Nancy: 1. Thiamine pyrophosphate (B1). Lipoic acid (inhibited by arsenic) 3. Coenzyme A (B5) 4. FAD (B2) 5. NAD (B3) |
| What cofactor does arsenic inhibit? Characteristic manifestations of arsenic intoxication? | Lipoic Acid. Garlic breath and rice water stools |
| Pyruvate Dhnase deficiency- inheritance mode + symptoms | XR. Acetyl-Coa can't be made, pyruvate gets shunted to other pathways leading to lactic acidosis + neurologic symptoms, increased serum alanine. |
| Pyruvate Dhnase deficiency- treatment | Increase intake of ketogenic nutrients like high fat diet or increased lysine and leucine |
| What is NADH used for from the TCA cycle? | It's used in the ETC to transfer electrons and make ATP |
| What is the electron transport chain? | It's a pathway that uses electrons from the NADH generated by the TCA cycle to move H across the inner mitochondrial membrane to the intermembrane space to create a chemical gradient and then use it to power an ATPase and create ATP. |
| Cofactors used in Complex I? Inhibitors? | NADH. Rotenone, MPP (a derivate from mepiridine), amytal |
| Cofactors used in Complex II? | FADH2. |
| Cofactors used in Complex III? Inhibitors? | Cytochrome c. Antimycin A |
| Inhibitors of Complex IV? | CN, H2S, Azide, CO |
| Inhibitors of ATPase in ETC? | Olygomicin |
| Uncoupling agents- definition + examples | Agents that increase permeability of membrane causing H to move back into the inner mitochondrial membrane, decreasing the chemical gradient and stopping ATP production producing heat. 2,4 DNP, aspirin overdose, thermogenin. |
| Irreversible enzymes in Gluconeogenesis | 1. Pyruvate to Oxalacetate using Pyruvate carboxylase, uses acetyl-Coa 2. Oxalacetate to PEP using PEP carboxykinase 3. Fructose 1,6 BP to Fructose 6 P using Fructose 1,6BPase |
| HMP shunt function | Provides a source of NADPH from glucose 6 P. |
| Sites where the HMP shunt occurs | Lactating mammary glands, liver, adrenal cortex (sites of FA or chol synthesis) and RBCs |
| G6PD deficiency- inheritance + symptoms + histology | XR. Hemolytic anemia (RBCs can't be protected from free radicals. Heinz bodies (denatured Hb) and bite cells (phagocytic removal of heinz bodies) |
| Heinz bodies + bite cells | Seen in G6PD deficiency. Heinz bodies- denatured Hb. Bite cells: phagocytic removal of Heinz bodies |
| Agents that precipitate hemolytic anemia in G6PD deficiency? (6) | 1. Sulfas 2. Primaquine 3. Chloroquine 4. Fava beans 5. Nitrofurantoine 6. Isoniacid |
| Essential fructosuria- enzyme defective + symptoms | AR. Fructokinase. Fructose in blood and urine |
| Fructose intolerance- enzyme deficient + pathogenesis +symptoms | AR. Aldolase B. Fructose 1 P accumulates, most of the P is used to create it so it's lacking in other pathways like gluconeogenesis and glycogenolysis. Hypoglycemia, jaundice, cirrhosis, vomiting. Urine dipstick for glu is - |
| Galactokinase deficiency- symptoms | AR. Infantile cataracts, galactose accumulates and is converted to galactitol |
| Classic galactosemia- enzyme deficient + symptoms | AR. Galactose-1-P-uridyltransferase. Symptoms present when child beings feeding. Failure to thrive, jaundice, hepatomegaly, infantile cataracts, intellectual disability, can predispose to E coli. |
| Lactase deficiency-causes + symptoms + changes in stool and breath | 1. Primary: age dependent decline after childhood 2. Secondary: loss of brush border 3. Congenital deficiency. Stool: decreased pH. Breath: increased H. Osmotic diarrhea, bloating, cramps, flatulence. |
| Essential aminoacids | PVT TIM HLL- Phenylalanine, Valine, Threonine, Trypthophan Isoleucine, Methionine, Histidine, Leucine, Lysine |
| Ketogenic aminoacids | Lysine + Leucine |
| Aminoacids required in periods of growth | Arginine + Histidine |
| Hyperammonemia- causes + pathogenesis + symptoms | Liver disease, Urea cycle enzyme deficiencies. Excess NH3 which depletes alpha ketoglutarate leading to inhibition of TCA cycle. Asterixis, slurring of speach, somnolence, vomiting, cerebral edema, blurred vision |
| How does lactulose improve hyperammonemia | Lactulose acidifies the GI tract and trap NH4 for excretion |
| Hyperammonemia- treatment | Lactulose, Antibiotics and benzoate, phenylacetate or phenylbutyrate. |
| Ornithine transcarbamlylase deficiency- inheritance + symptoms | XR. Increased orotic acid in blood and urine, No megaloblastic anemia |
| Pathway from Ph to Epi | Ph (uses BH4)-> tyrosine (uses BH4)-> Dopa (uses B6) -> Dopamine -(uses Vit C)> NE -(uses SAM)> Epi |
| Enzyme used to convert Ph to Tyrosine, cofactor used | Phenylalanine hydroxylase. BH4 |
| Enzyme used to convert tyrosine to DOPA, cofactor used | Tyrosine hydroxylase. BH4 |
| Enzyme used to convert DOPA to melanin | Tyrosinase |
| PKU (disorder of aromatic amino acid met)- causes, symptoms, inheritance. | AR. Phenylalanine hydroxylase deficiency, BH4 deficiency. Intellectual disability, growth retardation, seizures, eczema, musty body odor. |
| Maternal PKU-causes + symptoms | Lack of proper dietary therapy during pregnancy. In infant: microcephaly, intellectual disability, growth retardation, congenital heart defects. |
| Maple syrup urine disease- causes + symptoms | Decreased branched-chain alpha ketoacid dhnase causing blocked degradation of branched aminoacids (Isoleucine, leucine, valine). Cns defects, intellectual disability, death. |
| What vitamin is deficient in maple syrup urine disease? | B1 |
| Alkaptonuria- causes + inheritance + symptoms | AR. Homogentisate oxidase deficiency in the pathway to degrade tyrosine to fumarate. Black cartilage, sclerae (ochronosis), urine tuns black on prolonged exposure to air, arthralgias. |
| Albinism- causes | Tyrosinase deficiency, DOPA can't be converted to melanin |
| Homocystinuria- causes (3) | 1, Cystathione synthase def 2. Decreased affinity of cystathione synthase for B6 3. Methionine synthase def |
| Homocystinuria- symptoms | HOMOCYstenuria: 1. Increased homocysteine in urine 2. Osteoporosis 3. Marfanoid habitus 4. Ocular changes (downward and inward) 5. CV (stroke + MI) 6. kYphosis, Intellectual disability |
| Cystinuria- causes + symptoms | Hereditary defect of renal PCT and intestinal aminoacid transporter that prevents reabsorption of COLA- cysteine, ornithine, lysine and arginine. Hexagonal cystine stones |
| Cystinuria treatment | Urine alkalinization and chelating agents |
| Metabolites of Dopa, NE and Epi | Dopa-> Homovalinic acid, Ne-> vanillylmandelic acid, Epi -> metanephrine |
| Glycogen synthase-function | Attachment of UDP-Glu to the growing glycogen molecule, Adds alpha 1,4 glycosidic bonds |
| Branching enzyme-function | Makes α1,6 glycosidic linkages which build branches in glycogen. Since glycogen tends to be gigantic, these branches help to keep it somewhat compact. |
| Glycogen phosphorylase- function | Breaks down Alpha 1,4 linkage and cuts the Glu-1-P molecules liberating them. |
| Why can't muscle glycogen be used as a body source of glucose? | Because muscles don't have glu-6-phosphatase to convert glu-6-p back to glucose. |
| Enzyme that breaks alpha 1,6 glycosidic bonds? | Debranching enzyme (alpha 1,6 glucosidase) |
| Von Gierke- enzyme deficient + symptoms | Glu-6-phosphatase. Severe fasting hypoglycemia, increased lactate, TGs, uric acid (gout) + hepatomegaly. |
| Pompe disease- enzyme deficient + types | Lysosomal acid alpha 1,4 glucosidase. Infantile: cardiomegaly, HF, Adult: muscle weakness, diaphragm weakness, resp failure, no cardiac involvement. |
| Cori disease- enzyme deficient + symptoms | Debranching enzyme. Milder form of von Gierke with normal lactate |
| McArdle disease- enzyme deficient + symptoms | Glycogen phosphorylase. Painful muscle cramps, myoglobinuria with strenuous exercise and arrhythmia from electrolyte abnormalities. |
| Tay-Sachs- enzyme deficient + accumulation product + histology | Hexosaminidase A. GM2 ganglioside. Lysosomes with onion skin |
| Tay-Sachs- symptoms | 1. Progressive neurodegeneration 2. Cherry-red spot on macula 3. Developmental delay. No hepatomegaly |
| Fabry disease- enzyme deficient + acummulation product | Alpha galactosidase A. Cermide trihexoside |
| Fabry disease- symptoms | 1. Angiokeratomas 2. Hypohydrosis 3. Peripheral neuropathy |
| Metachromatic leukodystrophy - enzyme + accumulation product + symtomps | Arylsulfatase A. Cerebroside sulfate. Central and peropheral demyelination with ataxia, dementia. |
| Krabbe disease- enzyme + accumulation product + symptoms | Galactocerebrosidase. Galactocerebroside, psychosine. Peripheral neuropathy, destruction of oligodendrocytes, developmental delay, optic atrophy. |
| Gaucher disease- enzyme + accumulation product + histology | Glucocerebrosidase. Glucocerebroside. Lipid laden macrophages resembling crumpled tissue paper |
| Gaucher disease- symptoms | Hepatosplenomegaly, pancytopenia, osteopporosis, avascular necrosis of femur, bone crises. |
| Most common lysosomal storage disease | Gaucher disease |
| Niemann-Pick disease- enzyme + accumulation product + histology | Sphingomyelinase, sphingomyelin. Foam cells-lipid laden macrophages |
| Niemann-Pick dease- symptoms | Progressive neurodegeneration, cherry spot on macula, hepatosplenomegaly |
| Hurler Sx- enzyme + accumulation product + symptoms | Alpha-L-iduronidase. Heparan sulfate, dermatan sulfate. Developmental delay, gargoylism, airway obstruction, corneal clouding, hepatosplenomegaly. |
| Hunter Sx- enzyme + accumulation produc + symptoms | Iduronate sulfatase. Heparan sulfate, dermatan sulfate. Milder Hurler + aggresive behavior and no corneal clouding. |
| Lysosomal diseases associated with Ashkenazi Jews? (3) | 1. Gaucher 2. Niemann-Pick 3. Tay-Sachs |
| Systemic primary carnitine deficiency- pathogenesis + symptoms | Impaired transport of LCFA into mitochondria. Hypoglycemia, weakness, hypotonia |
| Medium chain acyl CoA dhnase deficiency- pathogenesis + symptoms | Decreased breaking down of FA to Acetyl CoA. Vomiting, lethargy, coma, seizures, liver dysfunction, sudden death in children |
| Ketone bodies (3) | acetone, acetoacetate, B-hydroxybutyrate |
| What ketone bodies gives fruity odor | Acetone |
| What ketone body is + in urine? | Acetoacetate |
| Ketone bodies used for energy? | Acetoacetate + B hydroxybutyrate |
| Fed state- processes + hormone | Glycolysis - Insulin |
| Fasting state - processes + hormone | Hepatic glycogenolysis (major), hepatic gluconeogenesis, adipose release of FFA (minor). Glucagon and Epi |
| Starvation 1-3 days. Blood glu is mantained by: | Hepatic glycogenolysis, adipose release of FA, muscle and liver start using FA, hepatic glyconeogenesis |
| Starvation after 3 days. Blood glu is mantained by: | Adopose stores (ketone bodies become the main source of energy for the brain) |
| Lipoprotein lipase- function | Degradation of TGs in chylomicrons and VLDLs |
| Hormone sensitive lipase- function | Degradation of TGs stored in adipocytes |
| LCAT- function | catalyzes esterification of 2/3 plasma chol |
| Chol- function | Cell membraine integrity, bile acid, steroids, vitamin D |
| Chylomicron-function + secreted by | Delivers dietary TGs to peripheral tissues. Intestinal epithelial cells |
| VLDL- function + secreted by | Delivers hepatic TGs to peripheral tissues. Liver |
| IDL- function | Degradation product of VLDL. Delivers TGs and chol to liver |
| LDL- function | Deliver hepatic chol to peripheral tissues. |
| HDL- function | Mediates rever chol transport from periphery to liver. |
| Apolipoprotein E + A function | E: mediates remnant uptake (everything except LDL) A: activates LCAT |
| Apolipoprotein B 48 + B 100 function | B48: mediates chylomicron secretion into lymphatics. B100: binds to LDL receptor |
| Abetalipoproteinemia: Inheritance + pathogenesis + symptoms | AR. Apo B48 + B100 deficiency. Fat malabsorption, failure to thrive, acanthocytosis, retinitis pigmentosa, spinocerebellar degeneration due to vit E def. |
| Hyperchylomicronemia- Inheritance + pathogenesis + symptoms | AR. LPL or ApoC deficiency. Pancreatitis, hepatosplenomegaly, pruritic xanthomas. |
| Hyperchylomicronemia - blood level | Increased chylomicrons, TG, chol |
| Familial hypercholesterolemia- Inheritance + pathogenesis + symptoms | AD. Absent or defective LDL receptors. Atherosclerosis, may have MI <20yo, tendon xanthomas, corneal arcus. |
| Familial hypercholesterolemia - blood level | Chol >300. |
| Dysbetalipoproteinemia- Inheritance, pathogenesis + symptoms | AR. Defective ApoE. Atherosclerosis, tuberoeruptive xanthomas, xanthoma striatum palmare |
| Hypertriglyceridemia- Inheritance, pathogenesis + symptoms | AD. Hepatic overproduction of VLDL. TGs >1000 can cause acute pancreatitis |
| Systemic primary carnitine deficiency- pathogenesis + symptoms | Defect in transport of LCFAs into mitochondria. Weakness, hypotonia, hypoglycemia |
| Medium-chain acyl CoA dhnase deficiency- pathogenesis + symptoms | Decreased ability to break down FA into acetyl-CoA. Vomiting, lethargy, seizures, coma, sudden death in infants or children |
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