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BR-3
Biochemistry
| Question | Answer |
|---|---|
| Rate limiting reaction in cholesterol synthesis | HMG Co-reductase |
| Findings in PKU | mousy odor; tyrosine missing (must be supplied by diet); can diagnose by amniocentesis and finding abnormal gene; Tx = eliminate Phenylalanine from diet (Nutrasweet is aspartate/phenylalanine...can't use it) |
| I cell disease | inability to phosphorylate the mannose residues of potential lysosomal enzymes (they cannot be taken up by lysosomes to degrade complex substrates) |
| Number of glucoses necessary to build palmitic acid a 16 carbon compound | 4 glucoses (each glucose produces 2 acetyl-CoA which contributes 2 carbons each) |
| Insulin lack in DKA | decreased glycolysis, glycogenesis, FA synthesis, storage of fat in adipose |
| Uncoupling agents (ex: alcohol and salicylates) | produces brown fat from increased heat from rxns trying to increase the generation of more protons to make ATP |
| Von Gierke's disease | dec glu-6-phosphate (gluconeogenic enzyme) w/dec in glucose (fasting hypoglycemia) and inc in glucose 6-phosphate w/production of normal glycogen in liver and kidneys; Stimulation Test = glucagon, fructose, etc cannot inc glucose levels d/t lack of enzyme |
| Biochemical processes in both cytosol and mitochondria | urea cycle, heme synthesis, gluconeogenesis |
| Female with pheochromocytoma | consider treating with dietary restriction of phenylalanine (essential AA) and tyrosine (not essential) |
| Pregnant female with PKU | consider treating with dietary changes: low in phenylalanine, high in tyrosine (avoid nutrasweet) |
| Lesch Nyhan | SXR with absent HGPRT (Hypoxanthine guanine phosphoribosyltransferase); self mutilation, hyperuricemia, MR |
| Glucokinase | only in liver; high Vm and high Km; not inhibited by glucose-6-phosphate |
| Hexokinase | in all tissues; inhibited by glucose-6-phosphate; low Vm and low Km |
| Maple syrup urine disease | branched chain amino acids |
| Key enzyme in gluconeogenesis | fructose-1,6-bisphosphatase (catalyzes conversion of fructose-1,6-bisphosphate to fructose-6-phosphate) |
| Locations of glucose-6-phosphatase | gluconeogenic hormone; liver, kidney, intestinal epithelium (not as much); Absent in von-Gierke's dz |
| Carnitine Shuttle | carries even chained fatty acids |
| Malate Shuttle | carries NADH |
| Functions of LDL | vitamin D synthesis, other steroid synthesis, cell membranes, synthesis of bile salts/acids |
| Acetyl CoA uses | FA synthesis, CH synthesis, ketone body synthesis |
| Function of urea cycle | eliminates ammonia |
| Debrancher deficiency | epinephrine given and only small branched chains are found |
| Origin of apolipoprotein 100 | liver |
| Origin of apolipoprotein 48 | intestine |
| Rate limiting step in glycogenolysis | glycogen phosphorylase |
| Reason why liver cannot use ketones for fuel | cannot activate acetoacetate in mitochondria which requires succinyl CoA; (acetoacetate CoA transferase, a thiotransferase enzyme, is needed to convert AcAc into acetoacetyl CoA |
| McArdles disease | abscent muscle phosphorylase; inc glycogen in muscle; no increase in lactic acid after exercise |
| Pregnant woman is a beer drinker, what supplements does she need? | folate (EtOH inc loss of folate in urine/stool); she should probably stop drinking to prevent FAS (iron is NOT affected) |
| Insulin | key hormone in fed state |
| Glucagon | key hormone in fasting state |
| Mannose-6-phophate | involved in transfer of dolichol (lipid) in RER in the synthesis of O-linked glycosides |
| Major source of NADPH | HMP shunt; malate dehydrogenase rxn to a lesser extent; (it supplies reducing equivalents) |
| Mutation changes an amino acid sequence, which one would have the greatest effect on migration in a serum ptn electrophoresis? | one with the most negative charge (most acidic): GLUTAMINE; (the one that would remain closest to the anode (- pole) is the most basic: ARGININE) |
| Mechanism of ketoacidosis in DKA | inc b-oxidation of FAs and production of acetyl-CoA, which is used up by the liver to synthesize ketone bodies |
| Promoter location | on a linear gene drawing with labels, pick the upstream location |
| Energy source for protein synthesis | GTP |
| Isoenzyme with 2 genes, 4 subunits | LDH isoenzymes; 5 isotypes (LLLL, LLLH, LLHH, LHHH, HHHH) |
| Second messengers | atrial natriuretic peptide: cGMP; Insulin: tyrosine kinase, Nicotinic: ion channels |
| Best method for detecting relatedness of a new bacteria | restriction fragment length polymorphism |
| Mutations: silent, missense, nonsense | no change in AA, new AA, early stop codon |
| Frameshift mutation | truncated protein |
| Primase on lagging strand | (single origin of replication w/discontinuous Okazaki fragments) makes RNA primer on which DNA polymerase III can initiate replication (prokaryotic) |
| DNA polymerase III (prokaryotic) | 5' --> 3' synthesis and proofreads with 3' --> 5' exonuclease |
| DNA polymerase I (prokaryotic) | excises RNA primer with 5' --> 3' exonuclease |
| DNA topoisomerases (prokaryotic) | create nick in helix to relieve supercoils |
| RNA polymerase I, II, III (eukaryotes only) | rRNA (most abundant), mRNA (biggest), tRNA (smallest) |
| Start and Stop codons | AUG (methionine (euk) or f-methionine (pro)); UGA (you go away), UAA (you are away), UAG (you are gone) |
| Promoter region vs. enhancer | upstream site (from gene locus) for RNA polymerase/transcription factor binding; versus any location before or within a gene for transcription factors to bind and alter expression |
| Introns vs. exons | introns stay in the nucleus, wheras exons exit and are expressed |
| DNA synthesis can be prevented by nucleoside analogs such as: | Cytosine arabinoside, Zidovudine, and Acyclovir (they are useful in antiviral and anticancer therapy) |
| Streptomycin | binds to 30S subunit and distorts its structure, interfering with the initiation of protein synthesis |
| Tetracyclines | interact with small ribosomal subunits, blocking access of the aminoacyl-tRNA to the mRNA-ribosome complex |
| Puromycin | has structural resemblance to aminoacyl-tRNA and becomes incorporated into the growing peptide chain, causing inhibition of further elongation in both prokaryotes and eukaryotes; acts at "peptidyl-transferase" step |
| Chloramphenicol | inhibits prokaryotic "peptidyltransferase." high levels may also inhibit mitochondrial protein synthesis |
| Clindamycin and Erythromycin | bind irreversibly to a site on teh 50S subunit of the bacterial ribosome, thus inhibiting translocation |
| Diphtheria Toxin | inactivates the eukaryotic elongation factor, eEF-2, thus preventing translocation in the ribosome |
| Regulation of RNA synthesis | Eukaryotes (methylation, amplification, rearrangement); Prokaryotes (operons w/promoter, operator & repressor: inducable lac operon, repressible tryptophan operaon, positive control arabinose operon, catabolite repressor lac operaon if glucose is present) |
| Disulfide bonds | play major role in maintaining tertiary structure of proteins |
| Peptidoglycan cross-linking in bacterial cell wall | disrupted by penicillin and cephalosporins |
| Blots = Snow Drop | Southern = DNA, Northern = RNA, Western = Protein |
| ELISA | tests antibody-antigen reactivity; determines if pt's blood contains either an Ab or Ag of interest; color change occurs if present |
| Autosomal dominant | usu defect in structural gene; often pleiotropic; many generations; male and female affected; presents after puberty; family Hx crucial for Dx |
| Autosomal recessive | usu enzyme deficiencies; 25% of offspring affected usu seen ONLY in 1 generation; more severe than dominant; presents in CHILDHOOD |
| X-linked recessive | sons of hetero moms have 50% chance; NO MALE TO MALE transmission; more severe in males; hetero females possible |
| X-linked dominant | d/t either parent; All female offspring of father affected; ex: hypophosphatemic rickets; every generation affected |
| Mitochondrial inheritance | transmitted only thru mom; all offspring of affected females may show signs of dz; ex: Leber's hereditary optic neuropathy; mitochondrial myopathies |
| Anticipation of genetic trait | severity of dz worsens w/age or onset of dz is earlier in succeeding generations (ex: Huntington's) |
| Loss of genetic heterozygosity | ex: both alleles of a tumor suppressor gene must be mutated for cancer to develop (this is not the case for oncogenes) |
| Dominant negative mutation | exertion of a dominant effect; a heterozygote produces a nonfxnl altered ptn that also prevents the normal gene product from functioning |
| Hardy-Weinberg Law Assumptions for Population Genetics: p2 + 2pq + q2 = 1; p + q = 1 (2pq = heterozygote prevalence) | 1. there is no mutation occuring at the locus; 2. there is no selection for any of the genotypes at the locus; 3. mating is completely random; 4. there is no migration into or out of the population |
| Fabry's lysosomal storage dz | XR; a-galactosidase A deficiency (accumulation of ceramide trihexoside); peripheral neuropathy, angiokeratomas, CV and renal dz; |
| Hunter's lysosomal storage syndrome | XR; Iduronate sulfatase deficiency (accumulation of heparan sulfate, dermatan sulfate); mild hurler's + AGGRESSIVE behavior, NO corneal clouding |
| Hurler's lysosomal storage syndrome | AR; a-L-iduronidase deficiency (accumulation of hepara and dermatan sulfate); DD, GARGOYLISM, airway obstruction, CORNEAL clouding, hepatosplenomegaly |
| Metachromic Leukodystrophy lysosomal storage dz | AR; arylsulfatase A deficiency (accumulation of cerebroside sulfate); central and peripheral DEMYELINATION w/ataxia and dementia |
| Krabbe's lysosomal storage dz | AR; b-galactosidase deficiency (accumulation of galactocerebroside); peripheral neuropathy, DD, optic atrophy |
| Tay-Sach's lysosomal storage dz | AR; hexosaminidase A deficiency (accumulation of GM2 ganglioside); progressive neurodegeneration, DD, CHERRY-RED SPOT, lysozymes with ONION SKIN |
| Niemann-Pick lysosomal storage dz | AR; sphingomyelinase deficiency (accumulation of sphingomyelin); progressive neurodegeneration, heatosplenomegaly, CHERRY-RED SPOT on MACULA |
| Gaucher's lysosomal storage dz | AR; b-glucocerebrosidase deficiency (accumulation of glucocerebroside); hepatosplenomegaly, aseptic necrosis of femur, BONE CRISIS, Gaucher's cells (MQs) |
| Cell cycle | Mitosis is shortest (prophase, metaphase, anaphase, telophase); G1 and Go are variable, but rapidly dividing cells have shorter G1 |
| Competitive inhibition | resembles substrate; no change in Vmax; inc Km (lower affinity for substrate) |
| Noncompetitive inhibition | dec in Vmax; no change in Km |
| Phosphatidylcholine | aka lecithin; component of RBC membranes, myelin, bile and SURFACTANT; also used in esterification of cholesterol |
| Ouabain | inhibits binding to K site of Na-K-ATPase |
| Cardiac glycosides (digoxin, digitoxin) | inhibit Na-K-ATPase causing increased cardiac contractility |
| Na-K-ATPase pump | ATP site on cytoplasmic side, for each ATP consumed, 3 Na go out and 2 K come in; during cycle pump is phosphorylated |
| alpha1 receptor | q G-ptn class; inc vascular smooth muscle contraction |
| alpha 2 receptor | i G-ptn class; dec sympathetic outflow; dec insulin release |
| beta1 receptor | s G-ptn class; inc HR, inc contractility, inc renin release, inc lipolysis, inc aqueous humor formation |
| beta2 receptor | s G-ptn class; vasodilation, bronchodilation, inc glucagon release |
| M1 receptor | q G-ptn class; CNS fxn |
| M2 receptor | i G-ptn class; dec HR |
| M3 receptor | q G-ptn class; inc exocrine gland secretions |
| D1 receptor | s G-ptn class; relaxes renal vascular smooth muscle |
| D2 receptor | i G-ptn class; modulates transmitter release, esp in brain |
| H1 receptor | q G-ptn class; inc nasal and bronchial mucus production, contraction of bronchioles, pruritis, pain |
| H2 receptor | s G-ptn class; inc gastric acid secretions |
| V1 receptor | q G-ptn class; inc vascular smooth muscle contraction |
| V2 receptor | s G-ptn class; inc H20 permeability and reabsorption in collecting tubules of kidney |
| q G-ptn class (a1, M1, M3, H1, V1) | Phospholipase C --> converts lipids to PIP2 --> IP3 and DAG --> inc [Ca]in and PKC |
| s G-ptn class (b1, b2, D1, H2, V2) | Adenylcyclase --> converts ATP to cAMP --> PKA |
| i G-ptn class (a2, M2, D2) | Adenylcyclase --> dec cAMP --> dec PKA |
| Collagen types | I (90%; bone, tendon, skin, fascia, dentin, cornea, late wound repair); II (cartilage, vitreous, nucleus pulposus); III (reticulin; skin, vessels, uterus, fetal, granulation tissue); IV (basment membrane); X (epiphyseal plate) |
| Ehlers-Danlos Syndrome | faulty collagen synthesis; hyperextensible skin and joints, bleeding/bruising; a/w berry aneurysms and variable inheritance patterns |
| Osteogenesis imperfecta | AD; abnml collagen synthesis; multiple fxs, blue sclera; type II is fatal in utero/neonatal period |
| ATP | aerobic metabolism (38 via malate shuttle; 36 via G3P shuttle); Anaerobic glycolysis (produces 2 ATP/glucose) |
| SAM (s-adenosyl-methionine) - the methyl donor of man | transfers methyl units to acceptors in synth of phosphocreatine (a high-energy phosphate active in muscle ATP production); regeneration dependent on B12 |
| ATP is precursor | cAMP via adenylate cyclase |
| GTP is precursor | cGMP via guanylate cyclase |
| Glutamate is precursor | GABA via glutamate decarboxylase (needs B6) |
| Choline is precursor | ACh via choline acetyltransferase (ChAT) |
| Arachidonate is precursor | prostaglandins, thromboxanes, leukotrienes via COX/lipoxygenase |
| Fructose-6-P is precursor | fructose-1,6-bisphosphate via PFK, the rate limiting enzyme of glycolysis |
| 1,3-BPG is precursor | 2,3-BPG via bisphosphoglycerate mutase |
| NADPH uses as electron donor | anabolic processes, respiratory burst (release of reactive oxygen species), P-450 |
| Hexokinase vs Glucokinase | Glucokinase is only in liver (lower affinity (hi Km), but higher capacity (hi Vmax)); Hexokinase is feedback inhibited by G6P (throughout body) |
| Irreversible enzymes in glycolysis | hexokinase/glucokinase (glu-->G6P); PFK (rate-limiting; F6P-->F1,6-BP); Pyruvate Kinase (PEP-->Pyruvate); Pyruvate DH (Pyruvate-->Acetyl-CoA) |
| Hexokinase/glucokinase regulation | inhibited by G6P |
| Regulation of PFK | Inhibited by ATP, Citrate; Activated by: AMP and F-2,6-BP |
| Regulation of Pyruvate Kinase | Inhibited by: ATP and Alanine; Activated by: F-1,6-BP |
| Regulation of Pyruvate DH | Inhibited by: ATP, NADH, Acetyl-CoA |
| Enzyme deficiencies a/w hemolytic anemia (b/c RBCs depend solely on glycolysis since they lack mitochondria) | hexokinase, glucose phosphate isomerase, aldolase, triosephosphate isomerase, phosphate glycerate kinase, enolase, pyruvate kinase |
| Pyruvate DH complex (similar to a-ketoglutarate DH complex) | cofactors: 1st 4 B vitamins + Lipoic Acid (Thiamine/TPP, FAD, NAD, Pantothene-->CoA, Lipoic Acid); activated by exercise which inc NADH, ADP and Ca |
| Pyruvate DH deficiency | causes lactic acidosis and neurologic defects (esp alcoholics w/B1 deficiency); Tx = intake of ketogenic nutrients (high fat; Lysine and Leucine) |
| What is needed to generate glucose from pyruvate? | 6 ATP equivalents |
| What carries amino groups from muscle to liver? | Alanine |
| What can be used to replenish TCA cycle or in Gluconeogenesis? | Oxaloacetate |
| Cori cycle | transfers excess reducing equivalents from RBCs and muscle to liver, allowing muscle to fxn anaerobically, netting 2 ATP |
| TCA Cycle - how many ATP are produced/Acetyl-CoA and per Glucose | 12 ATP/Acetyl-CoA (3 NADH, 1 FADH2, 2 CO2, 1 GTP); 24 ATP/glucose (b/c glu = 2 pyruvates) |
| Intermediates in TCA Cycle: Cindy is Kinky So She Fornicates More Often | Citrate, Isocitrate, a-Ketoclutarate, Succinyl-CoA, Succinate, Fumarate, Malate, Oxaloacetate |
| 1 NADH equals? 1 FADH2 equals? | 3 ATP; 2ATP |
| Electron transport inhibitors | Directly inhibit electron transport, causing dec of proton gradient and block of ATP synthesis: rotenone, antimycin A, CN-, CO ( |
| ATPase Inhibitor | oligomycin; direct inhibition; increases proton gradient, but no ATP is produced d/t hault of electron transport |
| Uncoupling agents | 2,4-DNP; increases permeability of membrane, dec proton gradient and inc O2 consumption; ATP synthesis stops, Electron transport continues |
| Irreversible enzyems in Gluconeogenesis (liver, kidney, intestine; NOT muscle) | "Pathway Produces Fresh Glucose" = Pyruvate carboxylase, PEP carboxykinase, F-1,6-BP, G6Pase; deficiency of any can cause hypoglycemia (ex: G6Pase = von Gierke's dz) |
| Pyruvate carboxylase | located in mitochondria; Pyruvate --> Oxaloacetate; Requires Biotin, ATP; Activated by Acetyl-CoA |
| PEP Carboxykinase | located in cytosol; OAA --> PEP; requires GTP |
| F-1,6-BPase | located in cytosol; F-1,6-BP --> F6P |
| G6Pase | located in cytosol; G6P --> glucose; |
| Pentose Phosphate Pathway (HMP shunt) | located anywhere FA or steroid synthesis occurs; Produces ribose-5-P from G6P for nucleotide synthesis AND NADPH from NADP+ for FA/Steroid biosynthesis (and maintaining reduced glutathione in RBCs) |
| G6P DH deficiency (rate limiting step in PPP pathway/HMP (hexose monophosphate) shunt) | XR; lack of NADPH = inability to reduce glutathione = inability to detoxify free radicals = HEMOLYTIC ANEMIA; more commonly in blacks; Forms Heinze bodies (altered Hb precipitates in RBCs); a/w FAVA beans, sulfonamides, primaquine and anti-TB drugs |
| Fructose Intolerance d/t deficiency of Aldolase B | AR; hypoglycemia, jaundice, cirrhosis d/t: accumulation of fructose-1-phosphate causes dec in available phosphate = inhibition of glycogenolysis and gluconeogenesis; Tx = reduce fructose/sucrose intake |
| Galactosemia d/t absence of Galactose-1-phosphate uridyltransferase | AR; cataracts, hepatosplenomegaly, MR d/t: accumulation of toxins (galactitol); Tx = exclude galatose and lactose from diet |
| Lactase deficiency | age-dependent or hereditary intolerance (Asians/Blacks); bloating, cramping, osmotic diarrhea; Tx = avoid milk or add lactase pills |
| Essential AAs: PriVaTe TIM HALL | Ketogenic (Leu, Lys), Glucogenic/Ketogenic (Ile, Phe, Trp), Glucogenic (Met, Thr, Val, Arg, His); arg/his - required for growth |
| Basic amino acids | Arg and Lys; positively charged, found in high amounts in histones b/c they bind negatively charged DNA |
| Ammonium transport btw liver and muscle | Alanine and Glutamine |
| Urea Cycle | degrades AA to amino grps (makes up 90% of nitrogen in urine); occurs in LIVER; Carbamoyl Phosphate incorporation is the only mitochondrial step (others occur in cytosol) |
| Urea Cycle Intermediates: Ordinarily, Careless Crappers Are Also Frivolous About Urination | Ornithine, Carbamoyl phosphate, Citrulline, Aspartate, Agrininosucinate, Fumarate, Arginine Urea |
| Phenylalanine Derivatives | tyrosine, thyroxine, dopa, dopamine, NE, Epi, Melanin |
| Tryptophan Derivatives | Niacin (NAD+/NADP+), Serotonin, Melatonin |
| Hisidine Derivatives | Histamine |
| Glycine Derivatives | Porphyrin, Heme |
| Arginine Derivatives | Creatine, Urea, Nitric Oxide |
| Phenylketonuria | AR; can't convert Phe to tyrosine d/t lo phenylalanine hydroxylase or cofactor; Tyrosine becomes essential and Phe adds up (excess phenylketones); MR, growth retardation, fair skin, eczema, musty odor; Tx = dec Phe (in nutrasweet), inc Tyrosine |
| Alkaptonuria | deficiency of homogentisic acid oxidase (degradative pathway for tyrosine); Alkapton bodies turn standing urine and CT black; Benign dz, may have arthralgias |
| Albinism | Deficiency of either Tyrosinase (no melanin synth) OR Defective Tyrosine Transporters (dec amts of melanin); Can be d/t lack of neural crest migration; Inc risk of skin cancer |
| Homocystinuria | Defective Cystathione Synthase or Methionine Synthase; Cysteine becomes essential for diet (or inc B6); MR, osteoporosis, tall staure, kyphosis, lens subluxation |
| Cystinuria | common defect in tubular AA transporter for COLA (cystine, ornithine, lysine, arginine); Can case cystine kidney stones; Tx = acetazolamide to alkalinize the urine |
| Maple Syrup Urine Dz | blocked degeneration of branched AA (Ile, Leu, Val = "I love vermont" maple syrup) d/t dec a-ketoacid DH; Inc a-ketoacids in blood cause CNS defects, MR, death; |
| Adenosine Deaminase Deficiency | Purine salvage deficiency; can cause SCID (T and B cell immunodeficiency - bubble boy); Excess ATP and dATP inhibits ribonucleotide reductase; Prevents DNA synthesis and dec lymphocyte count; 1st dz treated by gene therapy |
| Lesch-Nyham Syndrome | XR; LNS - lacks nucleotide salvage (purine) d/t absence of HGPRTase (converts hypoxanthine to IMP and Guanine to GMP); MR, self-mutilation, aggression, gout, choreoathetosis, hyperuricemia |
| FA degradation occurs | where its products will be consumed (in mitochondria); transported into mito via carnitine shuttle (inhibited by cytoplasmic malonyl-CoA) |
| FA synthesis occurs | in cytosol; transported via citrate shuttle |
| Liver: Fed vs Fasting State | In PHasting state, PHosphorylate |
| Type I Glycogen Storage Dz: Von Gierke's | G6Pase deficiency; liver becomes a muscle; severe fasting hypoglycemia; very high glycogen storage in liver |
| Type II Glycogen Storage Dz: Pompe's | Pompe's trashes the Pump (heart, liver, muscle); lysosomal a-1,4-glucosidase def; Cardiomegaly and systemic probs leading to death |
| Type III Glycogen Storage Dz: Cori's | Deficiency of debranching enzyme a-1,6-glucosidase |
| Type IV Glycogen Storage Dz: McArdle's | McArdle's: Muscle; skeletal muscle glycogen phosphorylase deficiency; inc glycogen in muscle but cannot break it down; cramps, myoglobinuria w/strenuous exercise |
| Glycogen Storage Diseases: Very Poor Carbohydrate Metabolism | Von Gierke's, Pompe's, Cori's, McArdle's |
| Ketone Bodies | FA and AA (in liver) ==> acetoacetate + b-hydroxybutryate (used in muscle/brain); found in urine (from HMG-CoA) d/t starvation and DKA; brain makes 2 Acetyl-CoAs from them; fruity breath d/t actone |
| Insulin is not necessary to moves glucose into most cells: BRICK L | Brain, RBCs, intestine, cornea, kidney, liver |
| Insulin | needed for uptake by adipose and skeletal muscle uptake (GLUT4 transporters); GLUT2 receptors are on beta cells of pancreas; it inhibits glucagon release by alpha cells; serum C-peptide isn't present w/exogenous insulin shots |
| Anabolic effects of insulin | inc glucose transport, inc glycogen storage/synthesis, inc TG synthesis/storage, inc Na retention (kidneys), inc ptn synthesis (muscles); phosphorylation (versus dephosphorylation with glucagon) |
| Cholesterol synthesis | rate-limiting step catalyzed by HMG-CoA reductase (conversion of HMG-CoA to mevalonate); 2/3 esterified by LCAT; INIHIBITED by: Lovastatin |
| Lipoprotein Lipase | FA uptake into cells from chylomicrons and VLDLs |
| Hormone sensitive lipase | degradation of stored TGs |
| Major Apolipotroteins | A-I (activates LCAT), B-100 (Binds LDL receptor); C-II (Cofactor for lipoprotein lipase); E (mediates Extra (remnant uptake) |
| Chylomicrons (B, A, C, E) | from intestinal epithelium; delivers dietary TGs to tissues and cholesterol to liver; excess = pancreatitis, lipemia, retinalis, eruptive xanthomas |
| VLDL (B, C, E) | from liver; delivers hepatic TGs to tissues; excess = pancreatitis |
| LDL (B100 mediates binding to cell surface for endocytosis) | delivers hepatic cholesterol to tissues; formed by lipoprotein lipase modification of VLDL in periphery; taken up by target tissues via endocytosis; Excess = xanthomas, atherosclerosis, arcus corneae |
| IDL | formed from degradation of VLDL; delivers TG and cholesterol to Liver to be degraded to LDL |
| HDL (A activates LCAT for cholesterol esterification; CEPT - transfers CE esters to other lipoptn particles) | mediates centripital transport of cholesterol (reverse; from periphery to liver); a repository for apoC and apoE (needed for chylomicron and VLDL metabolism); secreted by LIVER and INTESTINE |
| LDL and HDL carry the most cholesterol, just in different directions | HDL is healthy (periphery to liver); LDL is lousy (liver to periphery) |
| Familial Dyslipidemia Type I: Hyperchylomicronemia | inc chylomicrons; elevated TGs d/t lipoprotein lipase deficiency or altered apoC-II |
| Familial Dyslipidemia Type IIa: Hypercholesterolemia | inc LDL, inc cholesterol d/t dec in LDL receptors |
| Familial Dyslipidemia Type IIb: Combined Hyperlipidemia | inc LDL, VLDL; inc TG and cholesterol; d/t inc hepatic synthesis of VLDL |
| Familial Dyslipidemia Type III: Dysbetalipoproteinemia | inc IDL, VLDL; inc TG and cholesterol; d/t altered apoE |
| Familial Dyslipidemia Type IV: Hypertriglyceridemia | inc VLDL; inc TG; d/t hepatic overproduction of VLDL |
| Familial Dyslipidemia Type V: Mixed Hypertriglyceridemia | inc VLDL and chylomicrons; inc TG and cholesterol; d/t inc production and dec clearance of VLDL and chylomicrons |
| Which metabolic processes occur in the Mitochondria? | FA oxidation (b-oxidation), Acetyl-CoA Production, Krebs Cycle |
| Which metabolic processes occur in the Cytosol? | Glycolysis, FA synthesis, HMP shuttle, Protein Synthesis (RER), Steroid Synthesis (SER) |
| Which metabolic processes occur in both mitochondria and cytosol? | Gluconeogenesis, Urea Cycle, Heme Synthesis |
| Porphyria Symptoms: 5 Ps | Painful abdomen, pink urine, polyneuropathy, psychological disturbances, precipitated by drugs |
| Lead Poisoning Porphyria | inhibits ferrochelatase and ALA dehydrase; Coproporphyrin and ALA accumulate in urine |
| Acute Intermittant Porphyria | Deficiency in uroporphyrinogen I synthetase; Porphobilinogen and delta-ALA accumulate in urine |
| Porphyria Cutanea Tarda | Deficiency in uroporphyrinogen decarboxylase; uroporphyrin accumulates in urine (tea-colored) w/photosensitivity |
| Underproduction of heme produces | microcytic hypochromic anemia |
| Heme catabolism (scavenged from RBC and Fe2+ is reused) | Heme --> biliverdin --> bilirubin (CNS toxic, albumin transport to liver). Liver conjugates bilirubin with glucuronate (excreted in bile); Urobilinogen (intestine intermediate) and Urobilin (excreted in urine) |
| TCA cycle | regulated by Citrate Synthase; Inhibited by ATP and long chain acyl-CoA; Need for ATP drives cycle with supply of NAD+ |
| Glycolysis and Pyruvate Oxidation | Regulatory enzymes (Phospofructokinase-1, Pyruvate DH); Activators (AMP, F2,6-BP in liver, F1,6-BP in muscle; CoA, NAD, ADP, pyruvate); Induced by Insulin/inhibited by glucagon; regulates TCA |
| Inhibitors of Glycolysis/Pyruvate Oxidation | Citrate (FAs, ketone bodies), ATP, cAMP; Acetyl-CoA, NADH, ATP (FAs, ketone bodies); Glucagon |
| Gluconeogenesis | Enzymes (Pyruvate carboxylase, PEP carboxykinase, F1,6-BPase); Activators (acetyl-CoA, cAMP, glucagon, glucocorticoids), Inhibitors (ADP, AMP, F2,6-BP, insulin) |
| Glycogenesis | Major enzyme (Glycogen Synthase); Activators (Insulin); Inhibitor (phosphorylase (liver); cAMP, Ca (muscle), glucagon, epinephrine) |
| Glycogenolysis | Major enzyme (phosphorylase), Activators (cAMP, Ca (muscle), glucagon (liver), epinephrine); Inhibitors (insulin) |
| Pentose phosphate pathway | Major enzyme (G6P DH); Activators (NADP+, Insulin); Inhibitor (NADPH) |
| Lipogenesis | Major enzyme (Acetyl-CoA carboxylase); Activators (Citrate, Insulin); Inhibitors (long-chain acyl-CoA, cAMP, glucagon (liver)) |
| Cholesterol Synthesis | Major enzyme (HMG-CoA reductase); Activator (Insulin); Inhibitor (cholesterol, cAMP, glucagon (liver), drugs (lovastatin)) |
| Hb Structure Regulation (T (taut) versus R (relaxed) forms) | inc Cl, H, CO2, DPG and temp = favors T form and O2 unloading (lower affinity in T form) |
| Methemoglobinemia | oxidized form of hemoglobin (Ferric, Fe3+) that does not bind O2 as readily as reduced Ferrous (Fe2+) form |
| CO2 transport in blood | binds to AA in globin chain, not to heme; binding favors T form which promotes O2 unloading; must be transported from tissues to lungs usu in form of bicarb in plasma |
| Fat soluble vitamins (A vision, D bone/Ca homeostasis, K clotting, E antioxidant) | absorption depends on ileum and pancreas, toxicity d/t accumulation in fat; deficiency common from malabsorption (cystic fibrosis, sprue, mineral oil, steatorrhea) |
| Vitamin B complex deficiencies | a/w dermatitis, glossitis, diarrhea; B12 is the only one that is stored in body (liver) |
| Vitamin A (retinol) function | constituent of visual pigments |
| Vitamin A deficiency and Excess | Night blindness, dry skin, impaired immune response VERSUS Arthralgias, fatigue, HAs, skin changes, sore throat, alopecia |
| Vitamin B1 (thiamine) function | TPP is cofactor for oxidative decarboxylation of a-keto acids (pyruvate/a-ketoglutarate) and for transketolase in HMP shunt |
| Vitamin B1 (thiamine) deficiency | Wernicke-Korsakoff and Ber1-Ber1 (polyneuritis, cardiac pathology, edema; wet = dilated cardiomyopathy) |
| Vitamin B2 (riboflavin) function | cofactor in oxidation and reduction (FADH2); FAD and FMN are derived from riboFlavin (B2 = 2 ATP) |
| Vitamin B2 (riboflavin) Deficiency | the 2 Cs; cheliosis, corneal vascularization, and angular stomatitis |
| Vitamin B3 (niacin) Function | part of NAD+ and NADP+ (used in redox rxns); derived from tryptophan; (B3 = 3ATP) |
| Vitamin B2 (niacin) Deficiency | Pellagra (3 Ds: diarrhea, dementia, dermatitis and beefy glossitis); can be caused by Hartnup dz, malignant carcinoid, and INH |
| Vitamin B5 (pantothenate) Function | Pantothen-A is in Co-A; part of FA synthase; cofactor for acyl transfers |
| Vitamin B5 (pantothenate) Deficiency | Dermatitis, enteritis, alopecia, adrenal inusfficiency |
| Vitamin B6 (pyridoxine) function | Pyridoxal phosphate (PP) a cofactor in transmamination (ex: AST/ALT), decarboxylation and trans-sulfuration |
| Vitamin B6 (pyridoxine) Deficiency | Convulsions, hyperirritability, (deficiency inducible by INH and OCPs) |
| Biotin Function | Cofactor for carboxylations (Pyruvate --> OAA; Acetyl-CoA --> Malonyl-CoA; Proprionyl CoA --> Methylmalonyl-CoA) |
| Biotin Deficiency | Dermatitis, enteritis; caused by Abx and ingestion of raw eggs; "AVIDin in egg whites AVIDly binds Biotin" |
| Folic Acid Function | Coenzyme for 1-carbon transfer; involved in methylation; important for synthesis of nitrogenous bases in DNA and RNA |
| Folic Acid Deficiency | **mc vitamin deficiency in US; macrocytic megaloblastic aneima (no neurologic symptoms like B12 def); sprue; Tx = eat green veggies, not stored well; prevention of neural tube defects; PABA is precursor in bacteria; Sulfa drugs and Dapsone are PABA analog |
| Vitamin B12 (cobalamin) Function | cofactor for homocysteine methylation and methylmalonyl-CoA handling; stored in liver, made only by microbes; found only in animal products |
| Vitamin B12 (cobalamin) Deficiency | Macrocytic, megaloblastic anemia; NEURO symptoms (optic neuropahty, parasthesias), glossitis; d/t malabsorption (sprue, enteritis, Diphyllobothrium latum), pernicious anemia (no intrinsic factor), Crohn's dz (no terminal ileum); Detected by Schilling Test |
| Vitamin C (ascorbic acid) Function | Cross-links collagen; facilitates Fe absorption (maintains Fe2+ reduced form), cofactor for dopamine --> NE conversion |
| Vitamin C (ascorbic Acid) deficiency | Scruvy; sailors |
| Vitamin D Function | inc intestinal absorption of Ca and Phosphate; good for bones; D2 = ergocalciferol (milk); D3 = cholecalciferol (sun-exposed skin); 25-OH D3 = storage form; 1,25(OH)2 D3 = active form |
| Vitamin D Deficiency | Rickets in kids (bending); Osteomalacia in adults (soft bones), hypocalcemic tetany |
| Vitamin D Excess | Hypercalcemia, loss of appetitie, stupor; a/w Sarcoidosis (epithelioid MQs convert Vit D to active form) |
| Vitamin E Function and Deficiency | Antioxidant needed for Erythrocytes; Deficiency = increased fragility of RBCs |
| Vitamin K Function | necessary for carboxylation of glutamate residues on coagulation and clotting ptns (X, IX, II, VII, C and S) |
| Vitamin K Deficiency | neonatal hemorrhage w/inc PT and PTT, but normal bleeding time; can occur after broad spectrum Abx (b/c of death of intestinal flora); antagonized by Warfarin |
| Alcohol Metabolism | NAD+ is limiting reagent; Disulfiram (inhibits acetaldehyde DH; this is a prevention drug so if pt drinks they begin to feel hung over from accumulation of acetaldehyde) |
| Ethanol hypoglycemia | metabolism increases NADH/NAD+ ratio in liver; pyruvate is converted to latate and OAA to malate; this inhibits gluconeogenesis and causes hypoglycemia; it also causes hepatic fatty change (steatosis) in chonic alcoholics d/t shunting away from glycolysis |
| Kwashiorkor | protein malnutrition; skin lesions, edema, liver malfxn (fatty change); little red johnny |
| Marasmus | protein-calorie malnutrition; tissue wasting |
Created by:
bscaryp