Vitamins

1. Vitamins 1

2. The discovery of the first vitamin was published in 1911 by a Polish biochemist, Casimir Funk. The term vitamine is derived from the words vita (meaning lifegiving) and amine (were originally thought to be amines). Although not all vitamins are amines, they are organic compounds required by humans in small amounts from the diet. Usually only a few milligrams (mg) or micrograms (�g) are needed per day, but these amounts are essential for health. 2

3. Most vitamins cannot be made by the body, so have to be provided by the diet. An exception is vitamin D which can be obtained by the action of sunlight on the skin. Small amounts of a B vitamin (niacin) can be made from the essential amino acid, tryptophan. Vitamin K is formed by bacterial action in the large intestine. 3

4. Vitamins do not contain energy per se, but they help regulate energy process in the body. Vitamins have a variety of functions in the body: some are co-factors in enzyme activity, some are antioxidants (prevent oxygen from doing damage in the body) and one (vitamin D) is a pro-hormone. If insufficient amounts of vitamins are available to the body because of a poor diet or some medical condition (e.g. malabsorption of nutrients), specific symptoms will appear and can develop into a deficiency disease. Vitamin deficiency diseases are rare in the westernized society, but still occur in some parts of the world. Vitamins and minerals are measured in milligrams (mg), micrograms (�g) and international units (IU). 4 deficiency � di�fi�nsideficiency � di�fi�nsi

5. How much of the vitamins do we need? The body requires different amounts of each vitamin because each of them has a different function. People have different requirements too, according to their age, gender, level of activity and state of health. 5

6. Vitamin supplements Although most people are able to meet their requirements for vitamins by eating a varied diet, there are certain groups of the population who have higher than normal requirements, e.g. the sick, those taking certain drugs and pregnant women. Infants and young children are recommended to have supplements of vitamins A and D for at least 2 years. Some women many require additional iron if menstrual losses are high. The evidence for benefits from antioxidant supplementation for athletes is mixed. 6

7. Vitamins have been traditionally grouped into two categories: the fat soluble vitamin (A, D, E, K), and the water soluble vitamins (C, B complex). Originally, vitamins were given letters (A, B, C, etc.) but now are usually referred to by their chemical names, e.g. folate. 7

8. The fat soluble vitamins are stored in the body and their deficiencies are relatively rare. On the other hand, excessive intakes may be toxic. The water soluble vitamins are not stored to any significant extent in the body. Excess supplements of these vitamins are usually excreted in the urine. 8

9. The water soluble vitamins

10. Vitamin C (Ascorbic acid ) Vitamin C is the most famous vitamin. sources: almost exclusively in foods from plant sources (citrus fruits, broccoli, peppers, kiwi, strawberries, potatoes, tomatoes), although fresh milk and liver contain small amounts. RDA: 80 mg one kiwi, small orange or 4 strawberries provides 100% of RDA 10

11. Vitamin C - Ascorbic Acid Structure Metabolism oxidation/reduction dehydroascorbic acid dehydroascorbate reductase glutathione (GSH) glutamate-cysteine-glycine 11

12. ASCORBIC ACID AND DEHYDROASCOBIC ACID

13. Major function in the body helps form collagen helps in growth and repair of body tissue and blood vessels prevents scurvy a strong antioxidant aids in absorption of iron helps regulate the metabolism of cholesterol and amino acids 13

14. Functions of Vitamin C Enhances absorption of iron reduces iron to more absorbable ferrous form chelates with ferrous ion to make it more soluble 14

15. Functions of Vitamin C Hydroxylation of proline and lysine post-translational reaction of procollagen hydroxylated collagen can be cross-linked to triple helix collagen Scurvy - weak collagen 15

16. Functions of Vitamin C Hydroxylation Reactions Involves O2 and metal coenzyme (ferrous, cuprous) Carnitine synthesis Tyrosine synthesis & catabolism 16

17. Functions of Vitamin C Hydroxylation Reactions Synthesis of Neurotransmitters Dopamine Norepinephrine Serotonin Bile acid synthesis 17

18. Functions of Vitamin C Antioxidant Activity Reacts and removes active oxygen species Pro-oxidant Activity Reduces metals to their pro-oxidant forms 18

19. Scurvy Bleeding gums petechiae easy bruising impaired wound healing and bone repair joint pain anemia 19

20. RDA for Vitamin C 10 mg/day prevents scurvy historic RDA�s 45-70 mg (60mg in 1989), 75mg in 2000 prevention of scurvy vs antioxidant effect with supplements? 20

22. Ascorbic acid defiency: scurvy hemorrhage from mucous membranes, mouth and GIT, skin and muscles gingivitis: swelling, tenderness, redness and ulceration of gums loosening or loss of teeth swelling of joints rarefaction of bones and dentine

23. deficiency: weakness, slows wound healing, bleeding gums, scurvy The vitamin can be decreased by cigarette smoking, stressful injuries, stress and oral contraceptives. hypervitaminosis: excessive doses can cause kidney stones and break down red blood cells 23

24. Toxicity of Vitamin C UL adults: 2000mg/d Osmotic diarrhea Oxalate kidney stones Decreases uric acid reabsorption resulting in increased risk of gout Affects diagnostic tests in feces and gout fecal blood urinary glucose 24

25. VITAMIN B COMPLEX Eight vitamins that make up the B Complex of vitamins: B1 - Thiamine B2 - Riboflavin B3 - Niacin B5 - Panthotenic acid B6 - Pyridoxine B7 � Biotin B9 - Folate (folic acid) B12 � (Cobalamin, cyanocobalamin) 25

26. Vitamins B group Vitamin B1 (Thiamine) Vitamin B2 (Riboflavin) Vitamin B3 or Vitamin P or Vitamin PP (Niacin) Vitamin B5 (Pantothenic acid) Vitamin B6 (Pyridoxine and Pyridoxamine) Vitamin B7 or Vitamin H (Biotin) Vitamin B9 or Vitamin M and Vitamin B-c (Folic acid) Vitamin B12 (Cyanocobalamin)

27. Thiamin (Vitamin B1) sources: whole grains, nuts and meat. White and brown flour and many breakfast cereals are usually fortified with thiamin. RDA: 1,5 mg for men, 1,1 mg for women function: Thiamin is needed to release energy from carbohydrate. It is involved in the normal function of the nervous system and the heart. 27

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29. Thiamin Structure pyrimidine ring thiazole ring methyl bridge 29

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31. Conversion of thiamine to TPP

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36. Chemical Characteristics Very labile nutrient Heat stable in crystalline form less stable in solution Alkali - very unstable with heat baking soda 36

37. Chemical Characteristics Sulfites - decomposes B-1 High cooking/processing losses heat leaching 37

38. Absorption of B-1 in duodenum active transport (low thiamin levels) requires sodium and folic acid passive transport (hi B-1 levels) 38

39. Absorption of B-1 phosphorylation to active form inside cells (TPP) transported via portal blood no significant storage, excess to urine 39

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41. Thiamin Deficiency Beri-Beri anorexia, fatigue, depression effects on cardiovascular system nervous system 41

42. Infantile Beri-Beri first 6 months breast milk deficient in B-1 mother w/o symptoms rapid onset cyanosis, tachycardia, labored breathing heart failure and death 42

43. Wet Beri Beri symptoms similar to congestive heart failure Pitting edema - trunk, limbs, face labored breathing, tachycardia rapid deterioration fatal cirulatory collapse responds rapidly to B-1 supplements 43

44. Dry Beri-Beri no edema progressive wasting numbing and weakening of extremities chronic infections 44

45. Thiamine assay biologic assay � in animals � time consuming and costly (curative or protective) microbiologic using bacteria which require thiamine for growth chemical/fluorescent assay � conversion of thiamine to thiochrome by alkaline ferricyanide

46. Assessment of Thiamin Status Urinary thiamin excretion Blood or serum thiamin concentration [pyr + lac] in blood erythrocyte transketolase activity stimulation with B-1 46

47. Lipoic acid lipoic acid is a co-factor found in pyruvate dehydrogenase and a-ketoglutarate dehydrogenase, two multienzymes involved in a-keto acid oxidation lipoic acid functions to couple acyl group transfer and electron transfer during oxidation and decarboxylation of a-ketoacids no evidence exists of a dietary lipoic acid requirement in humans; therefore it is not considered a vitamin

49. Riboflavin (Vitamin B2) sources: milk, eggs, fortified breakfast cereals, liver and green vegetables. RDA: 1,7 mg for men, 1,3 mg for women function: Riboflavin is required to release energy from protein, carbohydrate and fat. It is also involved in the transport and metabolism of iron in the body and is needed for the normal structure and function of mucous membranes and skin. deficiency: Although there is no specific deficiency disease, low intakes lead to dryness and cracking of the skin around the mouth and nose. hypervitaminosis: general lack of toxicity, excess riboflavin is excreted in the urine.

51. Riboflavin vitamin B2, lactoflavin (ovo, hepato, verdo), vitamin G a heterocyclic flavin linked to ribose analogous to the nucleosides in RNA orange-yellow fluorescent compound found in significant quantities in green leafy vegetables, milk and meats heat stable, but easily destroyed by light recommended intake is related to energy intake (kcal) � RDA 1 � 2 mg/day

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58. Riboflavin 2 cofactors are involved: riboflavin phosphate (flavin mononucleotide, FMN) flavin adenine dinucleotide (FAD) involved in the metabolism of carbohydrates, fats and proteins (flavin dehydrogenases/flavoproteins) hydrogen carriers in the respiratory chain

61. Riboflavin

63. Riboflavin

64. Riboflavin Enzymes utilizing riboflavin cofactors: NADH dehydrogenase succinate dehydrogenase d and l-amino acid oxidases pyridoxine-5-phosphate oxidase glutathione reductase xanthine oxidase In some enzymes, the cofactor is covalently bonded to an amino acid (dehydrogenases)

65. Dehydrogenase reaction

66. Amino acid oxidases

67. Xanthine oxidase

68. Fatty acyl-CoA desaturase

69. Riboflavin deficiency seldom seen in industrialized societies deficiency when seen: cheilosis (vertical fissure in the lips) angular stomatitis (craks in the corner of the mouth) glossitis photophobia seborrheic dermatitis normochromic normocytic anemia usually encountered along with pellagra (niacin deficiency) newborns treated for hyperbilirubinemia by phototherapy (riboflavin is unstable to light)

70. Niacin Structure Nicotinic Acid = Niacin Nicotinamide = Niacinamide 70

71. Niacin (nicotinic acid, B 3) sources: Niacin is found in most foods, although meat is the major source. It can also be made by the body from the amino acid tryptophan. RDA: 19 mg for men, 15 mg for women function: It is required for the release of energy from food, for the normal structure of the skin and mucous membranes and for normal functioning of the nervous system. 71

72. deficiency: a disease called pellagra (symptoms: high sensitivity to sunlight, aggression, dermatitis, red skin lesions, insomnia...) Nicotinic acid is sometimes prescribed by doctors (as a drug) to treat high blood lipid levels, i.e. hyperlipidaemia (excess fat in the blood). hypervitaminosis: rare, headache, nausea, burning and itching skin 72

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75. Cofactor Forms of Niacin Nicotinamide Adenine Dinucleotide NAD nicotinamide-ribose-PP-ribose-adenine Nicotinamide Adenine Dinucleotide Phosphate NADP nicotinamide-ribose-PP-(ribose-P)-adenine 75

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78. Chemical Characteristics of Niacin relatively stable to light heat oxidation alkali major losses due to leaching 78

79. Digestion and Absorption of Dietary Niacin Coenzyme form in food hydrolysis in small intestine to free vitamin absorbed in duodenum nicotinic acid protein bound in corn requires alkali treatment (lime) to release niacin 79

80. Metabolism of B-3 conversion of free vitamin to coenzyme in all cells no storage excesses metabolized in liver to variety of chemicals metabolites excreted in urine 80

81. Synthesis of B-3 from Tryptophan pathway requires B-6 (also B2) 60 mg of TRY required to make 1 mg B-3 corn is low in both B-3 and TRY 81

82. Biochemical Functions of B-3 Oxidation-Reduction Reactions (NAD/NADH Dehydrogenases Electron Transport System Involved in energy production 82

83. Biochemical Functions of B-3 Synthetic Pathways (NADPH) FA synthesis Cholesterol synthesis Purine & Pyrimidine synthesis 83

84. Cofactor Forms of Niacin Nicotinamide Adenine Dinucleotide NAD nicotinamide-ribose-PP-ribose-adenine Nicotinamide Adenine Dinucleotide Phosphate NADP nicotinamide-ribose-PP-(ribose-P)-adenine 84

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86. Deficiency of B-3 Pellegra (fig 4-18) Dermatitis scaly dermatitis, sun exposed Dementia confused, disoriented Diarrhea irritation/inflammation of mucous membranes 86

87. Assessment of B-3 Status Urinary excretion of niacin metabolites N-methyl nicotinamide 2-pyridone 87

88. Niacin Toxicity 1-3g/day for treatment of hypercholesterolemia increases histamine release skin flushing increase risk of peptic ulcers liver injury time release forms greater risk of liver injury 88

89. Pantothenic acid (Vitamin B 5) sources: beef liver, lean meats, milk, eggs, legumes, whole grain products, most vegetables A recent study also suggests that gut bacteria in humans can generate pantothenic acid RDA: 4�7 mg 89

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91. Vitamin B5(Pantothenic acid) It is a peptide substance composed of Pantoic acid and b-Alanine. It can be present as the Calcium salt or the Alcohol �Pantothenol�.

92. Pantothenic acid (vitamin B5)

93. Pantothenic acid a yellow viscous oil (free acid) stable to moist heat (not to dry heat) and to oxidizing and reducing agents hydrolyzed in acid or alkaline medium sources (numerous): liver, kidney, eggs, lean beef, milk, molasses, cabbage, cauliflower, broccoli, peanuts, sweet potatoes, kale (derive its name from everywhere)

94. Pantothenic acid serves in its activated form as the cofactor for coenzyme A (CoA) and the acyl carrier protein (ACP) first phosphorylated by ATP to 4�-phosphopantothenate next is the formation of 4�-phosphopantetheine by addition of cysteine and decarboxylation adenylation by ATP forms dephospho-CoA phosphorylation to the 3�-OH of the ribose generates CoA (coenzyme A)

96. Coenzyme A performs a vital role by transporting acetyl groups from one substrate to another the key to this action is the reactive thioester bond in the acetyl form of CoA the thioester bond is stable enough that it can survive inside the cell, but unstable enough that acetyl-CoA can readily transfer the acetyl group to another molecule

97. Example of an acetylation reaction

98. Pantothenic acid Deficiency: rats graying of hair/fur in black rats dermatitis inflammation of nasal mucosa hemorrhage of adrenal cortex humans has not been encountered or extremely rare difficult to induce with either synthetic diets and/or with antagonists (omega-methylpantothenic acid

99. Pantothenic acid vague symptoms in human deficiency: numbness and tingling in feet �burning foot� fatigue GIT disturbances available pharmaceutically as calcium pantothenate (d-isomer) and as racemic mixture 5 - 7 mg/day appear to prevent signs of deficiency appears to be non-toxic (up to 10-20 gm have been tolerated)

100. Pyridoxine (Vitamin B6) Vitamin B6 comprising 3 forms � pyridoxine, pyridoxal and pyridoxamine. sources: is found in a variety of foods: beef, fish and poultry are rich sources. It also occurs in eggs, whole-grains and some vegetables. RDA: 2 mg for men, 1,6 mg for women 100

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106. Pyridoxine (vitamin B6)

107. Other forms of B-6

108. Pyridoxine widespread occurrence pyridoxine: mostly in vegetable products pyridoxal and pyridoxamine: mostly in animal products pyridoxine is stable in acid solution, but unstable in neutral or alkaline solutions (destroyed by light)

109. Pyridoxal phosphate pyridoxine is converted to pyridoxal phophate by phosphorylation and oxidation to the aldehyde pyridoxal phosphate is then attached to the holoenzyme via a covalent bond to a lysine residue (a Schiff�s base) the Schiff�s base bond is readily broken and reformed this reversibility is very important in the biochemical action of this cofactor

110. Pyridoxal phosphate Biochemical functions: Decarboxylation of amino acids Transaminase reactions Racemization reactions Aldol cleavage reactions Transulfuration reactions Conversion of tryptophan to niacin Conversion of linoleic acid into arachidonic acid (prostaglandin precursor) Formation of sphingolipids

111. Important transaminases ALT ( alanine aminotransferase) formerly known as SGPT (serum glutamate pyruvate transaminase) alanine + alpha-ketoglutarate = pyruvate + glutamate increased serum level in liver injury

112. Important transaminases AST (aspartate aminotransferase) formerly known as SGOT (serum glutamate oxaloacetate transaminase) aspartate + alpha-ketoglutarate = oxaloacetate + glutamate elevated when heart and/or liver are damaged

113. Important decarboxylases

114. Mechanism for transamination reaction

115. Pyridoxine deficiency: difficult to produce in humans may be accomplished artificially with a pyridoxine antagonist (deoxypyridoxine) symptoms include: nausea and vomiting, seborrheic dermatitis, depression and confusion, mucous membrane lesions, peripheral neuritis, anemia

116. Pyridoxine antagonists

117. Biotin (Vitamin B 7 or H) sources: meats, legumes, milk, egg yolk, whole grain products, most vegetables RDA: 300 �g function: It is a coenzyme in the metabolism of carbohydrates, fats, and protein. deficiency: rare, fatigue, nausea, skin rashes hypervitaminosis: general lack of toxicity Biotin supplements are often recommended as a natural product to counteract the problem of hair loss. 117

118. Biotin

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120. Biotin an imidazole sulfur containing compound sometimes referred to as vitamin B7 or vitamin H widely distributed in foods (liver, kidney, milk, molasses) a large portion of the daily need of biotin is met by synthesis by intestinal bacteria deficiency is usually the result of a defect in utilization rather than simple dietary deficiency

121. Reactions involving biotin enzymes

122. Biotin like lipoic acid, biotin is converted to its coenzyme form (called biotinyllysine or biocytin) by formation of a covalent amide bond to the nitrogen of a lysine residue like lipoic acid it performs a highly specialized function : adds a carboxyl group to substrates

123. Biotin deficiency: quite uncommon can be induced by feeding raw egg white (avidin) avidin is a protein which binds tighly with biotin (MW 70,000) symptoms are: anorexia, nausea, muscle pain, fine scaly desquamation of the skin requirements: 150 � 200 mcg/day therapeutic use: in babies with infantile seborrhea (cradle cap) and Leiner�s disease

124. Folate (vitamin B 9) Folic acid is the synthetic form of the vitamin and the most stable. It is used in supplements and for food fortification. Various folates are found in both plant and animal foods. sources: liver, yeast extract, orange juice and green leafy vegetables. Various foods, e.g. breakfast cereals and bread may be fortified with folic acid. 124

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127. Folic Acid / Folacin Structure pteridine ring - PABA - glutamate Stability very sensitive to heat easily oxidized leached 127

128. FOLIC ACID absorbed by both active and passive transport on the average we absorb 50 -200ug per day (about 10 -25% of dietary intake) storage is in the form of 5-methyl THF (5 -20 mg) found in green vegetable, dietary yeasts, liver, kidney bacteria synthesize their own folic acid (dihydropteroate synthetase)

129. Digestion & Absorption dietary form: polyglutamyl folate glutamate gamma linked folate absorbed as monoglutamate (free folate) dietary supplement: free folate 129

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131. Folate Metabolism Intestinal Cells folate reduced to tetrahydrofolate folate reductase inhibited by methotrexate (chemotheraputic drug) methylated to N5-methyl-THF primary blood form 131

132. Folate Functions Single carbon metabolism 132

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134. Folic acid Biochemical functions one carbon fragment transfer (formyl, methyl, hydroxymethyl) conversion of homocysteine to methionine conversion of serine to glycine synthesis of thymidylic acid synthesis of purines (de novo) histdine metabolism synthesis of glycine

137. Deficiency of folic acid abnormal metabolism of folates folic acid antagonists (dihydrofolate reductase inhibibitors - methotrexate, pyrimethamine, trimethoprim) enzyme deficiency vitamin B12 deficiency oral contraceptives increased requirement pregnancy, infancy

138. Folate Functions Interconversion of serine and glycine ser + THF <---> gly + 5,10-Me-THF Degradation of histidine his->->->formiminoglutamate(FIGLU) FIGLU+THF -> glu + 5-forminino-THF histidine load test Functional test for folate status 138

139. Folate Functions Purine and Pyrimidine Synthesis dUMP + 5,10-Me-THF -> dTMP + THF Methionine Synthesis homocysteine + 5-Me-THF -> MET + THF MET as a methyl donor for choline synthesis 139

140. Folate Deficiency Megaloblastic Anemia decreased DNA synthesis failure of bone marrow cells to divide normal protein synthesis results in large immature RBC�s contrast with microcytic hypochromic anemia 140

141. Deficiency of folic acid Inadequate intake defective absorption (most common) sprue gastric resection and intestinal disorders acute and chronic alcoholism drugs (anticonvulsants and oral contraceptives) pregnancy pellagra

142. Folate and Neural Tube Defects Defects in formation of neural tube (brain & spinal cord) First two months gestation Anencephaly absence of cerebral hemispheres 142

143. Folate and Neural Tube Defects Spina bifida defective closure of vertebral column spinal cord protrusion from spinal column results in damage to spinal cord lower limb and hip paralysis rectal and bladder problems 143

144. NTD Prevalence US: 4000 live births with NTDs/yr 1/1000 pregnancies World: 400,000 live births with NTDs/yr 144

145. Cyanocobalamin (Vitamin B12) sources: Dietary intake is exclusively from animal sources, e.g. milk, meat and eggs (and fortified foods). Although some bacteria can make vitamin B12, it is probably not in a form that can be used by the body. Fortified breakfast cereals can be a useful source of this vitamin. 145 virtually (ve:celi) � prakticky, fakticky neurological � njuere�lod�ikl paralysis � pe�relesisvirtually (ve:celi) � prakticky, fakticky neurological � njuere�lod�ikl paralysis � pe�relesis

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147. Vitamin B-12 Structure cobalamine methyl cobalamine transport and coenzyme form adenosyl cobalamine storage and coenzyme form 147

150. Vitamin B12 the corrin ring is similar to the porphyrin ring system found in hemoglobin except that in corrin 2 of the pyrroles are linked directly (without methylene bridges) the cobalt is coordinated to the 4 pyrrole nitrogens one of the axial cobalt ligands is a nitrogen of the dimethylbenzimidazole group the other axial ligand may be CN, OH, CH3 or the 5�-carbon of a 5�-deoxyadenosyl group

152. Vitamin B12 synthesized by bacteria only red in color, levorotatory and stable to heat commercially available either as cyano or hydroxocobalamin stored in the liver as the coenzyme absorbed only in the presence of the intrinsic factor (a glycoprotein released by parietal cells) transported to tissues via transcobalamin II present in foods such as liver, fish, eggs, milk absent in vegetables and fruits

153. Vitamin B12 by far the most complex vitamin in structure made up of a planar corrin ring (4 pyrroles) the only vitamin that possesses a metal ion (cobalt) as part of its structure the major cofactor form of B12 is adenosylcobalamin or 5�-deoxyadenosylcobalamin small amounts of methylcobalamin also occur (intermediate in methyl transfer reactions)

154. Vitamin B12 biochemical functions (mediated by coenzymes) mutase reaction (rearrangement reaction methylmalonyl CoA to succinyl CoA (lipid metabolism) methylation reactions uracil to thymine homocysteine to methionine aminoethanol to choline activation of amino acids for protein synthesis ribonucleotides to deoxyribonucleotides for DNA synthesis in certain bacteria

155. Causes of B12 deficiency Pernicious anemia (autoimmune gastritis against parietal cells - loss of intrinsic factor) rarely due dietary deficiency oral contaceptive drugs intestinal parasite gastrectomy chronic gastritis Schilling test

156. Manifestation of B12 deficiency macrocytic megaloblastic anemia spinal cord degeneration (irreversible) this cannot be treated with folic acid!!

157. Digestion & Absorption of B12 Intrinsic Factor gastric glycoprotein binds with B12 in small intestine IF-B12 complex binds to B12receptor in ileum for absorption B12 absorption requires functioning stomach, pancreas, and ileum 157

158. Shilling Test for Malabsorption Saturation of B12 by injection Oral administration of radiolabeled B12 free B12 IF-B12 Measure urinary excretion of labeled B12 158

159. The fat soluble vitamins

160. Vitamin A (Retinol) Retinol and beta�carotene preformed vitamin A. Beta carotene can be converted to retinol in the body; 6mg of beta carotene is equivalent to 1mg of retinol. sources: Retinol is found in liver, whole milk, cheese and butter. Carotenes are found in milk, carrots, dark green leafy vegetables and orange coloured fruits, e.g. mango and apricots. The law states that margarine must be fortified with vitamin A (and vitamin D). 160

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162. Major function in the body vital to good vision prevents night blindness antioxidant necessary for healthy skin, hair growth keeps mucous membranes healthy promotes bone development 162

163. Vitamin A is stored in the body in relatively large amounts, and thus deficiencies are rare. deficiency: night blindness, intestinal infections, impaired growth hypervitaminosis: nausea, headache, fatigue, liver and spleen damage, skin peeling, risk of birth defect It is for this reason that women who are pregnant, or who might become pregnant, are advised not to take vitamin A supplements unless they are advised to do so by a health professional. Liver and liver products may contain a large amount of vitamin A, so these should also be avoided. 163

164. Vitamin A Exits in 3 forms: all trans-retinol long chain fatty acyl ester of retinol (main storage form) retinal (the active form in the retina) retinoic acid is also considered to be physiologically active provitamin A or carotene can be converted to retinol in vivo

167. Vitamin A Diseases of deficiency: Nigh blindness and xerophthalmia (dry eye) Skin disorders Lack of growth Hypervitaminosis: A serious potential problem (CNS disorders; birth defects)

168. Vision and the role of vitamin A photoreception is the function of 2 specialized cell types: rods and cones both types of cells contain a photosensitive compound called opsin in rod cells opsin is called scotopsin and the receptor is called rhodopsin or visual purple rhodopsin is a receptor in the membrane of the rod cell; it is a complex between scotopsin and 11-cis retinal

169. Vision and the role of vitamin A intracellularly, rhodopsin is coupled to a G-protein called transducin when rhodopsin is exposed to light, it is bleached releasing the 11-cis-retinal from opsin absorption of photons by 11-cis-retinal triggers the conversion to all-trans-retinal (one important conformational intermediate is metarhodopsin II); also there is a change in conformation of the photoreceptor

170. Vision and the role of vitamin A these transformations activate a phosphodiesterase (which hydrolyzes c-GMP to GMP) c-GMP is necessary to maintain the Na+ channels in the rods in the open conformation with a decrease in c-GMP, there occurs a closure of the Na+ channels, which leads to hyperpolarization of the rod cells with concomittant propagation of nerve impulses to the brain

173. Additional role of retinol retinol also functions in the synthesis of certain glycoproteins and mucopolysaccharides necessary for mucous production and normal growth regulation this is accomplished by phosphorylation of retinol to retinyl phosphate which then functions similarly to dolichol phosphate

175. Vitamin D (Cholecalciferol) Vitamin D is found in foods in two main forms, mostly as cholecalciferol and in small amounts as ergocalciferol. The physiologically active form is calcitriol, which is the hormone of this vitamin. The ultraviolet rays from sunshine convert a compound found in the skin into cholecalciferol which is released into the blood and is eventually converted by the liver and kidneys into active hormone calcitriol. In this form it works as a hormone in controlling the amount of calcium absorbed by the intestine. It is also essential for the absorption of phosphorus and for normal bone mineralization and structure. 175

176. sources: fish liver oils, eggs, tuna, salmon, fortified foods like dairy products and margarine, and some breakfast cereals, action of sunlight on the skin = deficiencies are unusual RDA (cholecalciferol): 10 micrograms or 400 IU one glass of milk provides 25% of RDA one tin of sardines provides 100% of RDA 176

177. Vitamin D There are 2 major precursor forms: 7-dehydrocholesterol ergosterol UV irradiation affords cholecalciferol (vitamin D3) and ergocalciferol (vitamin D2) Discovery: 1890 � sunlight prevents rickets 1924 � Steanbock and Hess found that irradiating certain foods produced vitamin D2 1970 � hormonally active form of vitamin D discovered

178. Vitamin D RDA � 20 mg (required in minute amounts) disease of deficiency: rickets Malformation of bones � due to improper bone mineralization Hypervitaminosis Toxic dose only 10X higher than the RDA Causes hypercalcemia � can lead to cardiac arrest vitamin D is not a vitamin (or a cofactor) � it is a steroid hormone

181. Major function in the body acts as a hormone to increase intestinal absorption of calcium promote bone and tooth formation prevents rickets in children and osteomalacia in adults 181

182. Biological functions Calcium homeostasis � it is critical for the body to maintain the proper calcium level in the blood stream Intestinal calcium absorption: acts as a signal to tell intestinal cells to take up more calcium from the gut Bone calcium mobilization Signals osteoclast (bone cells) to release calcium into the blood stream in response to low calcium levels

183. deficiency: rickets in children and osteomalatia in adults, Deficiencies are rare. Some groups of people (e.g. older adults, and children) are at risk of vitamin D deficiency because of low vitamin D intake from food and/or inadequate exposure of skin to sunshine. hypervitaminosis: loss of appetite, nausea, joint pains, loss of muscle tone, damage to soft tissues such as the kidney, heart, and blood vessels due to deposits of calcium. In general, vitamin D supplement are not recommended. 183 rickets � rikits osteomalatia - ostieumalei�ierickets � rikits osteomalatia - ostieumalei�ie

185. Vitamin E (alpha-tocopherol) Vitamin E is a group of compounds called tocopherols and tocotrienols, of which alpha tocopherol is the most active. sources: vegetable oils, margarine, green leafy vegetables, wheat germ, whole grain products, egg yolks RDA (tocopherol): 10 mg for men, and 8 mg for women one tablespoon of margarine provides 74% of RDA 185

186. Major function in the body helps breakdown polyunsaturated fats antioxidant, protect cells against oxidative damage by free radicals, for example oxidation of the lipids in the cell membranes plays a role in aging, sexual performance, or prevention of cancer and/or heart disease 186

187. deficiency: disruption of red blood cell membranes, anemia Deficiencies are extremely rare. hypervitaminosis: headache, fatigue, diarrhea, general lack of toxicity with doses up to 400 mg Vitamin E is one of the most popular nutrient supplements. There are many health claims for supplementation � slowing of the aging process or an improvement in sexual potency. 187

188. Vitamin K (phylloquinone) Vitamin K is found in foods from both plant and animal sources and is also made by bacteria in the gut. sources: beef liver, eggs, spinach, cauliflower, broccoli, tomatoes RDA: 80 �g for men, 65 �g for women 188

189. Major function in the body essential for clotting of blood (vitamin K is named antihemorrhagic vitamin) normal bone structure 189

190. Vitamin K the coagulation vitamin exists in 2 forms: plant origin: phylloquinone or vit K1 bacterial origin: menaquinones or vit K2 also certain synthetic quinones have vitamin K activity menadione (vitamin K3) menadiol sodium phosphate (vitamin K4)

195. deficiency: increased bleeding and hemorrhage Deficiency states are rare, they may occur in some individuals when antibiotic medications kill the intestinal bacteria that produce the vitamin. hypervitaminosis: thrombosis, vomiting 195

196. Vitamin E alpha (E1), beta (E2) and gamma(E3) tocopherol sources: plant oils (corn, peanut, wheat germ), green leafy vegetables, meat, eggs value resides in the antioxidant properties of vitamin E (may prevent the formation of peroxides)

197. Vitamin E Estimated requirements: 5 mg/day + 0.6 mg/day of unstaurated fat Biological function � antioxidant for fatty acids Acts like vitamin C; prevents lipid peroxidation and/or damage to cells by lipid hydroperoxides

198. Uses for vitamin E hemolytic anemia in premature infants, unresponsive to B12, Fe and folic acid macrocytic megaloblastic anemia seen in children with severe protein-calorie malnutrition

199. ALPHA TOCOPHEROL