Step 1 - Biochem 3

denniskwinn's version from 2015-04-25 15:56


Question Answer
Fat soluble vitaminsAbsorption dependent on gut (ileum) and pancreas, Toxicity more common than for water-soluble vitamins, because these accumulate in fat - malabsorption syndromes (steatorrhea), such as cystic fibrosis and sprue, or mineral oil intake can cause fat-soluble vitamin deficiencies
Vitamin A nameRetinol
Vitamin A functionAntioxidant; constituent of visual pigments (retinal); essential for normal differentiation of epithelial cells into specialized tissue (pancreatic cells, mucus-secreting cells).
Vitamin A deficiency leads toNight blindness, dry skin
Vitamin A excessArthralgias, fatigue , headaches, skin changes, sore throat, alopecia. Teratogenic (cleft palate, cardiac abnormalities ), so a pregnancy test must be done before isotretinoin is prescribed for severe acne.
Vitamin A sourcesLiver and leafy vegetables
Vitamin B1 functionIn thiamine pyrophosphate (TPP), a cofactor for several enzymes: 1. Pyruvate dehydrogenase (glycolysis) 2. a-ketoglutarate dehydrogenase (TCA cycle) 3. Transketolase (HMP shunt) 4. Branched-chain M dehydrogenase
Vitamin B1 namethiamine
Vitamin B1 deficiencyImpaired glucose breakdown→ ATP depletion; highly aerobic tissues (brain and heart) are affected first. Wernicke-Korsakoff syndrome and beriberi. Seen in malnulTition as well as alcoholism (2° to malnutrition and malabsorption).
Dry beriberipolyneuritis symmetrical muscle wasting
Wet beriberihigh-output cardiac failure (dilated cardiomyopathy), edema
Vitamin B2 nameriboflavin
Vitamin B2 functionCofactor in oxidation and reduction (e.g. FADH2) - FAD and FMN are derived from riboflavin - B2-2ATP
Vitamin B2 deficiencyCheilosis (inflammation of lips, scaling and fissures at the corners of the mouth), Corneal vascularization. (the 2 C’s)
Vitamin B3 nameNiacin
Vitamin B3 FunctionConstituent of NAD+, NADP+ (used in redox reactions). Derived from tryptophan - synthesis requires vitamin B6. NAD derived from Niacin (B3= 3ATP)
Vitamin B3 deficiencyGlossitis. Severe deficiency leads to pellagra, which can be caused by Hartnup disease (↓ tryptophan absorption ), malignant carcinoid syndrome (↑ tryptophan metabolism), and INH (↓- vitamin B6). - the 3Ds of pellagra (Diarrhea, Dermatitis, Dementia)
Vitamin B3 excessFacial flushing (due to pharmacologic doses for treatment of hypcrlipidemia).
Vitamin B3 in dietB3 in corn is only absorbable if corn is treated - excess untreated corn can lead to pellagra
Vitamin B5 namePantothenate
Vitamin B5 functionEssential component of CoA (a cofactor for acyl transfers) and fatty acid synthase
Vitamin B5 deficiencyDermatitis, enteritis, alopecia, adrenal insufficiency
Vitamin B6 namepyroxidine
Vitamin B6 functionConverted to pyridoxal phosphate, a cofactor used in transamination (ALT and AST), decarboxylation reactions, glycogen phosphorylase, cystathionine synthesis, and heme synthesis. Required for the synthesis. Required for the synthesis of niacin from tryptophan
Vitamin B6 deficiencyConvulsions, hyperirritability, peripheral neuropathy (deficiency inducible by INH and oral contraceptives), sideroblastic anemias.
Vitamin B12 nameCobalamin
Vitamin B12 FunctionCofactor for homocysteine methyltransferase (transfers CH3 groups as methylcobalamin) and methylmalonyl-CoA mutase.
Vitamin B12 deficiencyMacrocytic, megaloblastic anemia, hypersegmented PMNs neurologic symptoms. Very large reserve pool (several years) stored primarily in the liver - deficiency usually caused by malabsorption, lack of intrinsic factor or absence of terminal ileum (parasthesias, subacute combined degeneration) due to abnormal myelin. Prolonged deficiency leads to irreversible nervous system damage
Vitamin B12 synthesisonly by microorganisms,
B12 deficiency testSchilling test to determine etiology of deficiency -
Folic acid functionConverted to tetrahydrofolate (THF), a coenzyme for 1-carbon transfer/methdation reactions. Important for the syntheSIS of nitrogenous bases in DNA and RNA
Folic acid deficiencyMacrocytic, megaloblastic anemia, no neurologic symptoms (as opposed to vitamin B12 deficiency) - most common vitamin deficiency in the US. Seen in alcoholism and pregnancy. Small reserve pool stored primarily in liver
Drug causes of folate deficiencyphenytoin, sulfonamides, MTX
SAM (S-adenosyl-methionine)Transfers methyl units - required for the conversion of NE to epinepherine- regeneration of methionine (and SAM) is dependent on vitamin B12 and folate -
Biotin functionCofactor for carboxylation enzymes (which add a l-carbon group): 1. pyruvate carboxylase: Pyruvate(3C)→ oxaloacetate (4C) 2. Acetyl-CoA carboxylase: Acetyl-Coa (2C)→ malonyl-CoA (3C) 3. Propionyl-CoA carboxylase: Propionyl-CoA (3C)→ methylmalonyl-CoA (4C)
Biotin deficiencyRelatively rare - dermatitis, alopecia, enteritis - caused by antibiotic use or excessive ingestion of raw eggs (egg whites bind biotin)
Vitamin C (ascorbic acid) functionAntioxidant, also: I . Facilitates iron absorption by keeping Iron in Fe2+ reduced state (more absorbable) 2. Necessary for hydroxylation of proline and lysine in collagen synthesis 3. Necessary for dopamine Beta- hydroxylase which converts dopamine to NE
Vitamin C sourceFound in fruits and vegetables - british sailors carried limes to scurvy (origin of the word “limey”)
Vitamin C deficiencyScurvy - swollen gums, bruising, anemia, poor wound healing
Vitamin D2 nameergocalciferol
Vitamin D2 sourceingested from plants, used as pharmacologic agent
Vitamin D3 namecholcalciferol
Vitamin D3 sourceconsumed in milk, formed in sun exposed skin - also a pharm agent
Vitamin D functionincreases intestinal absorption of calcium and phosphate, increases bone resorption
Vitamin D deficiencyRickets in children (bending bones), osteomalacia in adults (soft bones), hypocalcemic tetany
Vitamin D excessHypercalcemia, hypercalciuria, loss of appetite, stupor, Seen in sarcoidosis (↑ activation of vitamin D by epithelioid macrophages)
Vitamin E functionAntioxidant (protects erythrocytes and membranes from free-radical damage) E is for RBCs
Vitamin E deficiency↑ fragility of erythrocytes (hemolytic anemia), muscle weakness, neurodysfunction
Vitamin K functionCatalyzes gamma carboxylation of glutamic acid residues on various proteins concerned with blood clotting - synthesized by intestinal flora - K for coagulation - factors II,VII, IX, X and C and S - warfarin is a K antagonist
Vitamin K deficiencyNeonatal hemorrhage with ↑PT and ↑aPTT but normal bleeding time (neonates have sterile intestine and are unable to synthesize K) - can also occur after prolonged use of broad-spectrum antibiotics
Zinc functionessential for the activity of 100+ enzymes. Important in the formation of zinc fingers (transcription factor motif) .
Zinc deficiencyDelayed wound healing, hypogonadism, .↓ adult hair (axillary, facial, pubic), dysgeusia, anosmia. May predispose to alcoholic cirrhosis.
Fomepizoleinhibits alcohol dehydrogenase
Disulfiram (antabuse)Inhibits acetaldehyde dehydrogenase
Ethanol metabolismEthanol to Acetaldehyde via Alcohol dehydrogenase in cytosol (requires NAD+) then to Acetate via Acetaldehyde dehydrogenase in mitoch (another NAD+)
Ethanol hypoglycemiaEthanol metabolism i NADH/NAD+ ratio in liver, causing diversion of pyruvate to lactate and OAA to malate, inhibiting gluconcogenesis and stimulating fatty acid synthesis. Leads to hypoglycemia and hepatic fatty changes (hepatocellular steatosis) seen In chronic alcoholics
Kwashiorkorprotein malnutrition resulting in skin lesions, edema, liver malfunction (fatty change due to ↓ apolipoprotein synthesis). Clinical picture is small child with swollen belly - MEAL - malnutrition, Edema, Anemia, Liver (fatty)
Marasmusenergy malnutrition resulting in tissuc and muscle wasting, loss of subcutaneous fat, and variable cdcma - results in Muscle wasting
Kinaseuses ATP to add high-energy phosphate group onto substrate (e.g. , pho phofructokinase)
Phosphorylaseadds inorganic phosphate onto substrate without using ATP (e.g., glycogen phosphorylase)
Phosphataseremoves phosphate group from substrate (e.g.,fructose-1 ,6-bisphosphatase)
Dehydrogenaseoxidizes substrate (e.g., pyruvate dehydrogenase)
Carboxylaseadds 1 carbon with the help of biotin (e.g.,pyruvate carboxylase)
Glycolysis rate determining enzyme Phosphofructokinase-l (PFK-l )
Gluconeogenesis rate determining enzymeFructose-I,6-bisphosphatase
TCA cycle rate determining enzymeIsocitrate dehydrogenase
Glycogen synthesis rate determining enzymeGlycogen synthase
Glycogenolysis rate determining enzymeGlycogen phosphorylase
HMP shunt rate determining enzymeGlucose-6-phosphate dehydrogenase (G6PD)
De novo pyrimidine synthesis rate determining enzymeCarbamoyl phosphate synthetase II
De novo purine synthesis rate determining enzymeGlutamine-PRPP amidotransferase
Urea cycle rate determining enzymeCarbamoyl phosphate synthetase I
Fatty acid synthesis rate determining enzymeAcetyl-CoA carboxylase (ACC)
Fatty acid oxidation rate determining enzymeCarnitine acyltransferase (
Ketogenesis rate determining enzymeHMG-CoA synthase
Cholesterol synthesis rate determining enzymeHMG-CoA reductase
Aerobic metabolism of glucose produces 32 ATP via malate-aspartate shuttle (heart and liver), 30 ATP via glycerol-3-phosphate shuttle (muscle).
Activated phosphoryl carrierATP
Activated e- carriersNADH, NADPH, FADH2
Activated acyl carriersCoenzyme A, Lipoamide
Activated CO2 carriersBiotin
Activated 1-carbon unit carrierSAM
Activated Aldehyde carrierTPP
Universal e- acceptorsNAD+, NADP+, FAD+
NAD+ Universal e- acceptors generally used in catabolic processes to carry reducing equivalents away as NADH.
NADPH Universal e- acceptors used in anabolic processes (steroid and fatty acid synthesis) as a supply of reducing equivalents - anabolic processes, respiratory burst, p450, glutathione reductase
HexokinaseUbiquitous -high affinity, low capacity - uninduced by insulin - Feedback inhibited by G6P
Glucokinasein liver and Beta cells of pancreas - phophorylates excess glucoes to sequester int in the liver- low affinity high capacity - induced by insulin - high Vmax - no direct feedback inhibition
Hexokinase regulationinhibited by glucose 6 phosphate
Phosphofrutcokinase I regulationInhibited by ATP, Citrate, increased by AMP, Fructose 2,6 BP
Pyruvate kinase regulationinhibited by ATP and alanine, increased by fructose 1,6BP
Pyruvate dehydrogenase regulationInhibited by ATP, NADH and acetyl-CoA , activated by exercise
PFK actions during fasting state↑ glucagon→↑cAMP→↑protein kinase A→↑FBPase-2 and ↓PFK-2
PFK actions during fed state↑ insulin→↓cAMP→↓protein kinase A→↓FBPase-2 and ↑PFK2