PCOL826B vitamins WONDRAK.pdf

PCOL826B Vitamins [email protected] 1 for exam - focus on the following: 2 vitamin B3 (niacin/nicotinic acid) vitamin B6 vitamin K Vitamin A vitamin D Cofactors/coenzymes Hormone; nuclear receptor ligand Provitamin Vitamins as essential dietary factors Vitamins as supplements Vitamins as...

PCOL826B Vitamins [email protected] 1 for exam - focus on the following: 2 vitamin B3 (niacin/nicotinic acid) vitamin B6 vitamin K Vitamin A vitamin D Cofactors/coenzymes Hormone; nuclear receptor ligand Provitamin Vitamins as essential dietary factors Vitamins as supplements Vitamins as drugs Vitamin-derived therapeutics (also: from gut microbiome or endogenous sources: skin) 3 Vitamins and Health 4 Multivitamins: The quest for optimal health 5 Recommended dietary allowance Dietary Reference Intake (DRI): Recommended Dietary Allowances (RDA), the daily dietary intake level of a nutrient considered sufficient by the Food and Nutrition Board of the Institute of Medicine of the National Academies (United States) to meet the requirements of 97.5% of healthy individuals in each life-stage and sex group. The definition implies that the intake level would cause a harmful nutrient deficiency in just 2.5%. Tolerable upper intake levels (UL), to caution against excessive intake of nutrients (like vitamin A) that can be harmful in large amounts. This is the highest level of daily nutrient consumption that is considered to be safe for, and cause no side effects in, 97.5% of healthy individuals in each life-stage and sex group. The definition implies that the intake level would cause a harmful nutrient excess in just 2.5%. 6 Avoiding hypovitaminosis; avoiding hypervitaminosis types of vitamins Water soluble: B, C Fat Soluble: A, D, E, K - dietary excess excreted in urine -dietary excess stored in lipophilic compartments Hypo-vitaminosis: vitamin deficiency - pellagra (B3) beriberi (B1) rickets (D3) pernicious anemia (B12) scurvy (C) Hyper-vitaminosis: vitamin toxicity - hypervitaminosis A - hypervitaminosis D - hypervitaminosis E 7 Avoiding hyper-vitaminosis: Daily Tolerable Upper Intake Level The health benefit of vitamins generally follows a biphasic dose-response curve, taking the shape of a bell curve, with the area in the middle being the safe-intake range and the edges representing deficiency and toxicity. For example: Either an excess or deficiency of vitamin A can cause birth defects. Long-term use of betacarotene may increase the risk of lung cancer in people who smoke. 8 Folic Acid (vitamin B9) folic acid, vitamin B9 Folic acid's primary function in the body is as a cofactor to various methyltransferases involved in serine, methionine, thymidine and purine biosynthesis. Anti-folate drugs (e.g. methotrexate) are a class of antimetabolite medications that antagonize the actions of folic acid (vitamin B9). Antifolates inhibit cell division, DNA/RNA synthesis and repair and protein synthesis. 9 An autoimmmune vitamin deficiency: Vitamin B12 deficiency anemia (pernicious anemia), treatable by cyanocobalamine supplementation 10 Vitamin B12 deficiency anemia (pernicious anemia; PA) is a disease in which not enough red blood cells are present due to a lack of vitamin B12. Dietary B12 undergoes intestinal absorption (ileum) after binding to a protein known as ‘intrinsic factor’. Intrinsic factor is produced by parietal cells of the gastric mucosa and the intrinsic factor-B12 complex is absorbed by cubilin receptors on the ileum epithelial cells. B12 deficiency due the absence of intrinsic factor (autoimmune etiology) causes pernicious anemia. Pernicious anemia can be easily treated with either injections of vitamin B12. Often, treatment is lifelong. A life-saving vitamin supplementation: Cyanocobalamine 11 A vitamin questionnaire Consider the list of vitamins shown below and identify the molecular term that best refers to the specific vitamin: 1. Antioxidant 2. Solar light-induced nuclear receptor agonist 3. Component of visual system 4. Naphthoquinone derivative 5. Antagonist of anticoagulant medication 6. Coenzyme function ? 12 vitamin C vitamin D vitamin K vitamin A vitamin B3 vitamin B12 A vitamin questionnaire Consider the list of vitamins shown below and identify the molecular term that best refers to the specific vitamin: 1. Antioxidant 2. Solar light-induced nuclear receptor agonist 3. Component of visual system 4. Naphthoquinone derivative 5. Antagonist of anticoagulant medication 6. Coenzyme function ? vitamin C vitamin D vitamin K vitamin A vitamin B3 vitamin B12 13 Coenzymes: Nonprotein organic molecules (often derived from vitamins) that participate in catalysis by providing functional groups important coenzymes: thiamine pyrophosphate Coenzyme A (CoA) Pyridoxal phosphate Biotin NAD+ etc. Many coenzymes contain molecular components that are derived from vitamins, e.g.: Nicotinic acid (vitamin B3) > NAD+ The coenzyme NAD+ (= nicotinamide adenine dinucleotide) 14 The coenzyme FAD (Flavin adenine dinucleotide) riboflavin FAD (vitamin B2) > FAD reduction of FAD generates FADH2 15 Vitamers example: vitamin B6 B6-vitamers 16 Vitamin B6 and Amino Acid Metabolism: Example: Amino acid decarboxylases B6-dependent decarboxylation DOPA DOPA decarboxylase dopamine B6-dependent decarboxylation tyramine L-tyrosine B6-dependent decarboxylation L-tryptophan tryptamine B6-dependent decarboxylation L-histidine L-histidine decarboxylase histamine 17 Coenzyme function of B-vitamins Vitamin Coenzyme Thiamin (B1) TPP Transketolase Riboflavin (B2) FAD, FMN Electron transfer Niacin (B3) NAD, NADP Electron transfer Pantothenic acid (B5) Co-A Acyl transfer Pyridoxal (B6) Pyridoxal phosphate Biotin (B7) 18 Biochemical or physiological function Pyruvate Dehydrogenase Complex; 2-oxoglutarate (α-ketoglutarate) Dehydrogenase Complex Transamination, decarboxylation, glycogenolysis carboxylation Folic Acid (B9) Methyl H4 folate One carbon transfer Cobalamin (B12) Methylcobalamin Methylation of homocysteine A vitamin questionnaire Consider the list of vitamins shown below and identify the molecular term that best refers to the specific vitamin: 1. Antioxidant 2. Solar light-induced nuclear receptor agonist 3. Component of visual system 4. Naphthoquinone derivative 5. Antagonist of anticoagulant medication 6. Coenzyme function ? vitamin C vitamin D vitamin K vitamin A vitamin B3 vitamin B12 19 An enzyme cascade: The blood coagulation cascade Enzymatic (proteolytic) control of fibrin formation A thrombus (Greek θρόμβος), or blood clot 20 Factors XIa, IXa, VIIa, Xa, and thrombin are serine proteases. Factors VIII and V are cofactors without protease function. Note the positive feedback regulation of thrombin on the activation of proteases earlier in the cascade sequence. Anticoagulant Drugs: Blocking enzymes involved in the coagulation cascade Warfarin, Heparin, & others Heparin Heparin Heparin 21 vitamin K and warfarin: A drug as a vitamin-antagonist Vitamin K is a group of structurally similar, fat-soluble vitamins the human body requires for complete synthesis of certain proteins that are prerequisites for blood coagulation that the body needs for controlling binding of calcium in bones and other tissues. The vitamin K-related modification of the proteins allows them to bind calcium ions, which they cannot do otherwise. Without vitamin K, blood coagulation is seriously impaired, and uncontrolled bleeding occurs. vitamin K1: phylloquinone naphthoquinone naphthalene 1929: ‘Koagulationsvitamin’; ‘coagulation vitamin’. 22 vitamin K: origin, structure and function Apart from dietary intake, bacteria in the gut flora can also convert K1 into vitamin K2. In addition, bacteria typically lengthen the isoprenoid side chain of vitamin K2 to produce a range of vitamin K2 forms, most notably the MK-7 to MK-11 homologues of vitamin K2. Vitamin K1, also known as phylloquinone, is synthesized by plants, and is found in highest amounts in green leafy vegetables because it is directly involved in photosynthesis. 23 INR INR INR: International Normalized Ratio Phylloquinone (K1) or menaquinone (K2) are capable of reversing the anticoagulant activity of the anticoagulant warfarin (CoumadinTM). Supplemental vitamin K reverses the vitamin K deficiency caused by warfarin, and therefore reduces the intended anticoagulant action of warfarin and related drugs. The proper anticoagulant action of the drug is a function of vitamin K intake and drug dose, and due to differing absorption must be individualized for each patient. The action of warfarin and vitamin K both require two to five days after dosing to have maximum effect. 24 A vitamin questionnaire Consider the list of vitamins shown below and identify the molecular term that best refers to the specific vitamin: 1. Antioxidant 2. Solar light-induced nuclear receptor agonist 3. Component of visual system 4. Naphthoquinone derivative 5. Antagonist of anticoagulant medication 6. Coenzyme function ? vitamin C vitamin D vitamin K vitamin A vitamin B3 vitamin B12 25 From b-carotene (provitamin A) to retinal/retinol (vitamin A) retinal cis/trans-photo-isomerization is the molecular basis of photon sensing/vision 26 Retinoic acid: A vitamin A-derived potent RXR (retinoid X receptor) ligand retinoic acid Dietary retinyl esters, retinol, and provitamin A carotenoids (such as β-carotene) are taken into the body. Both all-trans-retinol and β-carotene may be converted enzymatically to all-trans-retinal. The key role of retinoic acid in embryonic development (‘Hox-homeobox gene activation’) mediates the high teratogenicity of retinoid pharmaceuticals, such as isotretinoin used for treatment of cancer and acne. Oral megadoses of pre-formed vitamin A (retinyl palmitate), and retinoic acid itself, also have teratogenic potential by this same mechanism. Vitamin A (by definition all-trans-retinol) may be esterified into retinyl esters and stored. In times of dietary retinoid insufficiency, retinyl ester stores are hydrolyzed to retinol for delivery to peripheral tissues. Retinal either can be enzymatically oxidized to retinoic acid, which regulates transcription of over 500 retinoidresponsive genes, or reduced enzymatically to retinol. When retinoic acid is no longer needed, it is catabolized and eliminated from the body. 27 Vitamin A and retinoic acid: From vitamin to drug 28 Avoiding hyper-vitaminosis: Daily Tolerable Upper Intake Level The health benefit of vitamins generally follows a biphasic dose-response curve, taking the shape of a bell curve, with the area in the middle being the safe-intake range and the edges representing deficiency and toxicity. For example: Either an excess or deficiency of vitamin A can cause birth defects. Long-term use of betacarotene may increase the risk of lung cancer in people who smoke. 29 A vitamin questionnaire Consider the list of vitamins shown below and identify the molecular term that best refers to the specific vitamin: 1. Antioxidant 2. Solar light-induced nuclear receptor agonist 3. Component of visual system 4. Naphthoquinone derivative 5. Antagonist of anticoagulant medication 6. Coenzyme function ? 30 vitamin C vitamin D vitamin K vitamin A vitamin B3 vitamin B12 The ‘solar’ vitamin: cholecalciferol (vitamin D) 31 Cutaneous photochemistry: From 7-dehydrocholesterol to vitamin D3 to calcitriol [a vitamin ?...] 32 A sun exposure-induced hormone controlling a nuclear receptor and transcription factor: VDR (vitamin D receptor) vitamin D-driven gene expression calcium homeostasis bone formation/maintenance cell proliferation tumor suppression 33 exam question Specify the identity of the molecule shown above: A. retinol B. retinal C. retinoic acid D. retinyl ester E. b-carotene 34 exam question 35 exam question 1 2 3 4 Among the molecules shown above select nicotinic acid: A. 1 B. 2 C. 3 D. 4 36 exam question 1 2 3 4 5 6 Among the molecules shown above select provitamin A: A. 1 B. 2 C. 3 D. 4 E. 5 F. 6 37 exam question 1 2 3 4 Among the molecules displayed above select the correct pair of vitamers: A. 1 + 2 B. 1 + 3 C. 2 + 3 D. 1 + 4 E. 1 + 3 38 exam question 1 2 3 4 Among the vitamins displayed above select the one that does not need metabolic activation after dietary uptake. A. 1 B. 2 C. 3 D. 4 39 40