Biochemistry Day 3
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- Which are the fat-soluble vitamins?
- KADE
- Cystic fibrosis and celiac sprue can lead to deficiencies of which vitamins?
- fat-soluble ones (KADE)
- B-complex deficiencies often results in which 3 signs?
- dermatitis, glossitis, diarrhea
- Name 9 water-soluble vitamins:
- B1, B2, B3, B5, B6, B12, C, biotin, folate
- Where is B12 stored in the body?
- liver
- Vitamin A (retinol) is needed because:
- constituent of visual pigments (retinal)
- VitA deficiency -->
- night blindness, dry skin, dec. immune response
- VitA overdose -->
- arthralgias, fatigue, HA, skin changes, sore throat, alopecia
- Vitamin B1 (thiamine) is needed for:
- thiamine pyrophosphate cofactor for oxidative decarboxylation of a-ketoacids (pyr, aKG), and cofactor in HMP shunt
- Thiamine deficiency -->
-
1) Beriberi
- dry: polyneuritis, muscle wasting
- wet: high output cardiac failure (dilated), edema
2) Wernicke-Korsakoff
- confusion, ophthalmoplegia, ataxia
- memory loss, confabulation, personality change
- periventricular hemorrhage in mamillary bodies - Vitamin B2 (riboflavin) needed for:
- cofactor in oxidation and reduction (FADH2)
- Riboflavin deficiency -->
- angular stomatitis, cheilosis (inflamed cracked lips), corneal vascularization
- Vitamin B3 (niacin) is needed for:
- constituent of NAD & NADP (redox), derived from Tryptophan USING VITB6!!
- Niacin deficiency -->
- pellagra (diarrhea, dermatitis, dementia, glossitis)
- What can cause pellagra, aka niacin deficiency? (3)
-
- Hartnup disease: dec. Trp absorption
- malignant carcinoid syndrome: inc. Trp metabolism
- INH: dec. vitamin B6 - Vitamin B5 (pantothenate) is needed for:
- CoA (cofactor for acyl transfers), fatty acid synthase
- Pantothenate deficiency -->
- dermatitis, enteritis, alopecia, adrenal insufficiency
- Vitamin B6 (pyridoxine) is needed for:
-
converted to pyridoxal phosphate (cofactor in transamination), decarboxylation, and heme synthesis
*recall: homocystinuria! B6 cofactor for cystathionine synthase! - Pyridoxine deficiency -->
- convulsions, hyperirritability, peripheral neuropathy
- Pyridoxine deficiency can be induced by: (2)
-
- INH
- oral contraceptives - Vitamin B12 (cobalamin) is needed for:
- cofactor for homocysteine methylation (to methionine), and methylmalonyl-CoA (to succinyl-CoA)
- Can humans make B12?
- No, it is made only by microorganisms. Found only in animal products.
- Cobalamin deficiency -->
- macrocytic megaloblastic anemia, neurologic sxs (optic, paresthesia, subacute combined degeneration), beefy glossitis
- Name 3 general causes of B12 deficiency:
-
- malabsorption (sprue, D. latum, enteritis)
- pernicious anemia
- no terminal ileum - What is the test to detect B12 deficiency?
- Schilling test
- You see abnormal ___ in B12 deficiency due to dec. methionine or inc. methylmalonic acid.
- myelin
- What is the most common vitamin deficiency in the US?
- folate
- Folate is needed for:
- coenzyme (tetrahydrofolate) for 1-carbon transfer; methylation reactions; nucleotide synthesis
- Folate deficiency -->
- megaloblastic anemia (no neuro sxs)
- What should you eat to get folate?
- green leaves (FOLiage) - and don't overcook!!!
- How do sulfa drugs and dapsone work?
- PABA analogs (PABA is bacterial folate precursor)
- Biotin is needed for: (3)
-
cofactor for carboxylations:
- pyruvate --> oxaloacetate
- acetyl CoA --> malonyl CoA
- proprionyl CoA --> methylmalonyl CoA - Biotin deficiency -->
- dermatitis, enteritis
- What 2 things can cause biotin deficiency?
-
- eat raw eggs
- antibiotic use - Vitamin C (ascorbic acid) is needed for:
- hydroxylation of Pro & Lys in preprocollagen; iron absorption by maintaining Fe2 reduced state (VitC is antioxidant); cofactor for Dopamine --> NE
- VitC deficiency -->
- scurvy: swollen gums, bruising, poor wound healing
- Vitamin D is needed for:
- inc. intestinal absorption of calcium and phosphate
- VitD2 =
- ergocalciferol, in milk
- VitD3 =
- cholecalciferal, formed in sunexposed skin
- What is the active form of VitD3?
-
1,25-(OH)2 D3
(recall: 1-a-hydroxylase in kidney) - VitD deficiency -->
- rickets, osteomalacia, hypocalcemic tetany
- VitD overdose -->
-
hypercalcemia, loss appetite, stupor, seen in SARCOIDOSIS!
(recall: macs make active D3) - Vitamin E is needed for:
- antioxidant protects RBC from hemolysis
- VitE deficiency -->
- fragile RBC
- Vitamin K is needed for:
- catalyzing gamma-carboxylation of glutamate residues on certain clotting factors (II, VII, IX, X, C, S)
- Why can you be VitK deficient after prolonged use of wide spectrum antibiotics?
- VitK made by intestinal flora
- VitK deficiency -->
- neonatal hemorrhage with prolonged PT and PTT (but normal bleeding time)
- Zinc deficiency -->
- delayed wound healing, hypogonadism, dec. adult hair, may predispose to alcoholic cirrhosis
-
Enzymes that catalyze:
ethanol --> acetaldehyde --> acetate
*how many NADH are made? -
alcohol dehydrogenase, acetaldehyde dehydrogenase
*2 NADH made - What is the limiting reagent in ethanol breakdown?
- NAD+
- How does Disulfiram/Antabuse work?
- inhibit acetaldehyde dehydrogenase, so acetaldehyde accumulates and worsens hangover
- Ethanol metabolism ___ the NADH/NAD+ ratio in Liver.
- increases
- With chronic ethanol use, OAA is diverted to making malate and then you can't do ___ which leads to ___.
-
gluconeogenesis
hypoglycemia - Why do chronic alcoholics have fatty livers?
- inc. NADH/NAD+ ratio shunts substrates away from glycolysis toward fatty acid synthesis
-
With inc. NADH/NAD+ ratio from chronic heavy alcohol use:
pyruvate --> ___
OAA --> ___ -
lactate
malate - Kwashiokor =
- protein malnutrition resulting in skin lesions, edema, liver fatty change (think child with swollen belly)
- Marasmus =
- protein-calorie malnutrition resulting in tissue wasting