Biochemistry of Vitamins for Medical Students-Rajendra

Biochemistry of Vitamins for Medical Students-Rajendra

1. VITAMINS ; Chemistry and Beyond Rajendra Dev Bhatt Assistant Professor / C linical Biochemist Dhulikhel Hospital-Kathmandu University Hospital

2. VITAMINS Chemically unrelated organic nutrients Classified by their biological and chemical activity and not by their structure Cannot be synthesized in sufficient quantities In our body Used in many chemical reactions in the body Unlike organic food, they do not enter into tissue structures nor are they converted to energy Unlike hormones which are endogenous, they are exogenous

3. Vitamins are defined as "small organic molecules present in diet which are required in small amounts. " Most of the vitamins are not synthesized in the body and hence they must be supplied in the diet . However few vitamins are synthesized in the body. Though most of them are present in diet as such some are present as precursors . The precursor forms of vitamins are called as provitamins . In the body these provitamins are converted to vitamins.

4. History of vitamins : The story of vitamin dates back to 18 th century. Sailors of this period knew that eating of liver cures a disease called night blindness and Eating of lemons cures another disease called scurvy. Also cod liver oil cures a disease called rickets In 1912, Sir H.G. Hopkins first identified Vitamins in MILK and named it as Accessory factors. Funk named the accessory factors as Vitamins (Vital amines).

5. Criteria for Vitamins Cannot be synthesized in ample amounts in the body Chronic deficiency is likely to cause physical symptoms Symptoms will disappear once the vitamin level in the body is restored Deficiency can cause permanent damage 13 compounds meet the above criteria

6. BIOLOGICAL IMPORTANCE 1. Vitamins are essential f or growth, m a i n ten a n c e a n d reproduction. However, the y are not used f or e n e rg y production. Fat soluble vitamins are required for normal colour vision, blood clotting, bone formation and maintenance of membrane structure. Most of the water soluble vitamins function as coenzymes or prosthetic groups of several enzymes involved in carbohydrate, lipid and amino acid metabolism etc. Vitamins A and D act as steroid hormones. Deficiency of fat soluble vitamins produce night blindness, skeletal deformation, haemorrhages and hemolysis.

7. BIOLOGICAL IMPORTANCE (Cont..) Deficiency of water soluble vitamins produce beriberi, glossitis, pellagra, microcytic anaemia, megaloblastic anaemia and scurvy. Some vitamin analogs are used as drugs. For example folic acid analogs are used as anticancer agents and antibiotics. Moderate consumption of some vitamins is found to decrease occurrence or severity of some diseases. For example carotenes, Vitamin E and Vitamin D consumption at moderate evel reduces incidence of cancer and cardiovascular diseases.

8. Classification of Vitamins Vitamins are divided into two groups. fat soluble vitamins water soluble vitamins. Fat Soluble Vitamins They are vitamins A, D, E and K. They have some common properties. They are: Fat soluble. Require bile salts for absorption. Stored in liver. Stable to normal cooking conditions. Excreted in feces.

9. Water Soluble Vitamins: They are members of vitamin B complex and Vitamin C. Their common properties are Water solubility. Except Vitamin B 12 others are not stored. Unstable to normal cooking conditions. Excreted in urine.

10. VI T AMINS CLASSIFICATION

11. VI T AMINS FAT-SOLUBLE VITAMINS WATER-SOLUBLE VITAMINS Apolar or hydrophobic Polar Require normal fat absorption Does not require normal fat absorption Stored in the liver or adipose tissue No stable storage form (except vitamin B-12) Transported in the blood by lipoproteins or specific binding proteins Does not need protein transporters Less prone to deficiency More prone to deficiency manifestations Prone to toxicity Less prone to toxicity Excreted thr o u gh feces Excreted mainly thr ough urine

12. Absorption and Storage Water-soluble vitamins Absorbed with water and enter directly into the blood stream Most absorbed in the duodenum and jejunum Most are not stored in the body Excess intake excreted through the urine Important to consume adequate amounts daily Fat-soluble vitamins Are absorbed in the duodenum Storage Vitamin A is mainly stored in the liver Vitamins K and E are partially stored in the liver Vitamin D is mainly stored in the fat and muscle tissue Can build up in body to point of toxicity

13. Digesting and Absorbing Vitamins

14. THIA M I NE B1 Chemistry

15. THIA M I NE B1 Chemistry Methylated pyrimidine ring bonded thr o u gh a methylene linkage to a thiazole ring

16. THIAMINE B1 Definition Anti-neuritic vitamin Anti-beriberi vitamin Co-enzyme form: Thiamine pyrophosphate (TPP) Thiamine co-carboxylase Thiamine diphosphate

17. THIA M I NE B1

18. THIA M I NE B1 Properties

19. THIAMINE B1 Metabolic Role Energy-releasing Has a central role in carbohydrate metabolism Half-life is 9-18 days Sources: Meat/fish Beans, Nuts, Yeast What flour, unpolished rice Liver, meat, eggs

20. THIA M I NE B1 Metabolic Roles Co-enzyme in the decarboxylation of: Pyruvate Alpha- k e t oglu t a r at e Keto acids from branch-chain amino acids

21. THIA M I NE B1 Metabolic Roles Thiamine triphosphate (TTP) nerve tissue metabolism and conduction Synthesis of neu r o t r ansmi t t e r s (Ach) Regulates nerve- impulse transmission

22. THIA M I NE B1 Metabolic Roles Central role of thiamine diphosphate

23. THIA M I NE B1 Metabolic Roles

24. THIAMINE B1 Deficiency May occur in the following conditions: When the energy intake is mostly from rice Ingestion of foods containing anti- thiamine factors. Pregnancy and Lactation Persons who do hard physical labor

25. THIAMINE B1 D e fici e n c y 4 Types of Beriberi Dry (peripheral neuritis) Wet (cardiac mani f e s t a tions) Cerebral ( W e r n i c k e - K o r sa k o f f syndrome) Infantile

26. THIA M I NE B1 Deficiency Dry Beriberi Loss of appetite Weight loss Muscle-wasting Peripheral neuritis with numbness Tingling sensations in the lower legs and feet Ataxic gait

27. THIA M I NE B1 D e fici e n c y Wet Beriberi Vasodilatation, tachycardia, wide pulse pressure, sweating , warm skin lactic acidosis Heart Failure Orthopnea Pulmonary and peripheral edema Vaasodilatation Shock

28. THIA M I NE B1 D e fici e n c y Cerebral Beriberi Occurs in alcoholics who consume less food Intelligence disturbance Ataxia Double vision Nystagmus Progresses to Wernicke- Korsakoff psychosis

29. THIA M I NE B1 Deficiency Soshin Beriberi More rapid form of wet beriberi Acute fulminant CV beriberi Cyanosis of hands and feet, tachycardia, distended neck veins, anxiety Rapid deterioration follows inability of heart muscle to satisfy body’s demands because of its own injury

30. THIA M I NE B1 Deficiency

31. THIA M I NE B1 Deficiency Infantile Beriberi Due to low thiamine content of breast milk Anorexia Trachycardia Vomiting Convulsions Edema

32. RIBOFLAVIN B2 Definition I Function Synonyms : Vitamin B2, Vitamin G, Lactoflavin Chemistry: Consists of heterocyclic isoalloxazine ring attached to a sugar alcohol, robitol

33. RIBOFLAVIN B2 Definition I Function Co-enzyme forms: FMN Flavin mononucleotide FAD Flavin adenine dinucleotide

34. RIBO F L A V IN B2 Properties Colored, flourescent pigment Widely used as food additive Heat stable but decomposes in the presence of visible light

35. RIBOFLAVIN B2 D e finit i o n I Fu nction RDA : Adults: 2.0 mg/day Children: 1.2 mg/day Pregnant/lactating: 2.0 mg/day Sources: Milk - 1 quart = 1.7 mg

36. RIBO F L A V IN B2 Physiologic Roles Act as prosthetic group of flavoproteins Act as co-enzyme for hydrogen transfer

37. RIBO F L A V IN B2 Metabolic Roles Flavoproteins: Enzymes involved in oxidation – reduction reactions FAD is required as coenzyme for: Pyruvate dehydrogenase Carbohydrate breakdown Succinate dehydrogenase Krebs cycle Glycerol 3-phosphate dehydrogenase Triglyceride synthesis phospholipid synthesis Acyl-CoA dehydrogenase Fatty acid breakdown Glutathione reductase Anti-oxidation

38. RIBO F L A V IN B2 Metabolic Roles Flavoproteins: Enzymes involved in oxidation – reduction reactions FMN is required for: L-amino acid oxidase Cytochrome C reductase

39. Substrate Enzyme Product Hypoxanthine + O 2 + H 2 O Xanthine Oxidase Xanthine + H 2 O 2 Xanthine + O 2 + H 2 O Xanthine Oxidase Urate + H 2 O 2 Succinate Succinate DH Fumarate Glycerophosphate Glycerophosphate DH Dihydroxyacetone-PO 4 Flavoproteins in electron transport chain Glutathione reductase – for assaying riboflavin status Part of pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase complexes RIBO F L A V IN B2 Metabolic Roles REACTIONS WHERE FAD IS NEEDED AS COENZYME

40. RIBOFLAVIN B2 Deficiency Causes: Malnutrition Malabsorption Anorexia Chronic alcoholism Assay for Riboflavin status: Erythrocyte GSH reductase activity

41. RIBOFLAVIN B2 Deficiency Ariboflavinosis Manifestations: Epithelial changes in the oral cavity Cheilosis or perleche – fissuring of lips Glossitis- Magenta tongue Corneal Vascularization Seborrheic Dermatitis Photophobia

42. A RIBOFLAVIN B2 D e fici e n c y Angular stomatitis

43. Gloss i tis RIBO F L A V IN B2 D e fi c i e n c y

44. NIACIN B3 Definition I Function SYNONYMS Vitamin B3, Nicotinic acid, pellagra preventive ( PP ) factor Nicotinamide, niacinamide CO-ENZYME FORMS Oxidized = NAD and NADP Reduced= NADH AND NADPH

45. NI A CI N B3 Definition I Fu nction Sources: Tryptophan can be converted to NAD 60mg Trp = 1 mg niacin Milk and eggs rich in tryptophan

46. NI A CI N B3 Definition I Fu nction RDA: Adults: 16-20 mg/day Children: 9-16 mg/day Infants: 5-8 mg/day

47. NI A CI N B3 Coenzymes

48. NI A CI N B3 Coenzymes

49. Examples of Reactions Utilizing NAD and NADP Substrate Enzyme Product Lactate Pyruvate Lactate DH Malate Oxaloacetate Malate DH Hydroxybutyrate Acetoacetate Beta-OH- butyrate DH Glucose Gluconate Glucose DH Isocitrate Alpha-ketoglutarate Isocitrate DH Glutamate Alpha-ketoglutarate + Ammonia Glutamate DH

50. NIACIN B3 Deficiency CLINICAL EFFECTS: Pellagra “rough skin” – 3D’s Dermatitis –skin exposed to sunlight Casal’s necklace Gloves and stockings lesions Diarrhea Dementia Stomatitis, magenta tongue Severe cases, GIT hemorrhagic * ineffective repair and regeneration of epithelial cells

51. NI A CI N B3 D e fici e n c y Dermatitis of Pellagra Casal’s Necklace

52. NI A CI N B3 D e ficiency Dermatitis of Pellagra Gloves and stocking appearance

53. NI A CI N B3 Excess Toxicity 1-6 grams ( hyperlipidemia) Dilatation of blood vessels Flushing Skin irritation Liver damage

54. Some times it is Not strictly considered as vitamin. Although the body cannot make vitamin B-3 , it can convert an amino acid called tryptophan into vitamin B-3.

55. P YRI D O XI NE B6 D e fi n iti o n I Fu nct i on SYNONYMS: Amino acid metabolism vitamin Rat anti-dermatitis factor Adermin (essential for AA and Carbohydrate metabolism) Rat anti-pellagra factor CO-ENZYME FORMS: Pyridoxal phosphate and pyridoxinamine phosphate Major excretory product: 4-Pyridoxic acid

56. PYRIDOXINE B6 Definition I Function FUNCTION Precursor of pyridoxal phosphate Coenzyme for several enzymes for AMINO ACID METABOLISM DEFICIENCY Intake of Isoniazid

57. P YRI D O XI NE B6 Definition I Fu nct i on Sources: Whole grain & legumes Poultry & Fish Potatoes Organ meats Eggs RDA: Adults: 2.2 mg/day Children: 1.2 mg/day Infants: 3.0 mg/day

58. P YRI D O XI NE B6 Food Sources RDA: Roughly proportional to the protein content of the diet 0.02 mg/g of protein intake 1.5-2.0 mg/day for normal adult Increased during pregnancy and lactation

59. P YRI D O XI NE B6 Definition I Fu nction

60. P YRI D O XI NE B6 D e fi n iti o n I Fu nct i on Physiological importance: Amino acid metabolism Synthesis of ceramide Synthesis of the neurotransmitters serotonin, dopamine, epinephrine, norepinephrine & GABA . Synthesis of the histamine. Synthesis of porphyrins Glycogenolysis - phosphorylase

61. P YRI D O XI NE B6 D e fi n iti o n I Fu nct i on Co-enzyme in protein metabolism Decarboxylation Conversion of 3-hydroxykynurenine to 3-OH-anthranilic acid Conversion of Tryptophan to serotonin Deamination – serine and threonine Transamination – acts as an amino group carrier

62. P YRI D O XI NE B6 Definition I Fu nction

63. P YRI D O XI NE B6 Definition I Function Co-enzyme in protein metabolism Trans-sulfuration transfer of sulfur from methionine to serine to form cysteine Conversion of cysteine to pyruvate via cysteine desulfhydrase Interconversion of glycine and serine Decarboxylation of alpha-amino-beta-ketoadipic acid to delta- aminolevulinic acid

64. P YRI D O XI NE B6 Definition I Function Co-enzyme in carbohydrate and fat metabolism Conversion of Linoleic to Arachidonic acid Cofactor in the activity of phosphorylase Cofactor in the metabolism of unsaturated fatty acids and cholesterol Synthesis of sphingolipids necessary for myelin formation

65. P YRI D O XI NE B6 Definition I Fu nction Enzymes : Amino transferases amino acid breakdown Glycogen phosphorylase glycogen breakdown Serine dehydratase feeding serine's breakdown product to gluconeogenesis Aminolevulinic acid synthase porphyrin synthesis

66. P YRI D O XI NE B6 Definition I Function Essential for the maintenance of the integrity of : Neuronal tissues Production of anti-bodies Bone development

67. PLP PLP PLP PLP

68. P YRI D O XI NE B6 Deficiency Clinical features: Epileptiform seizures in infants Pellagra-like skin lesions GIT involvement- distention, vomiting , diarrhea Anemia- hypochromic and microcytic

69. P YRI D O XI NE B6 Biochemistry Important biochemical finding in Vitamin B6 deficiency: Increased excretion of urinary oxalates Mechanism: decreased conversion of glycine glyoxalate broken down to oxalic acid increased possibility of forming oxalate stones

70. PANTOTHENIC ACID D e finit i on SYNONYMS: “everywhere vitamin” Filtrate factor ROYAL JELLY

71. PANTOTHENIC ACID F u n c tion FUNCTION Component of Coenzyme A RDA: Adults: 5-10 mg/day Children: 4-5 mg/day Infants: 1-2 mg/day

72. PANTOTHENIC ACID F u n c tion Substrate Enzyme Product Pyruvate + CoASH Pyruvate DH complex Acetyl CoA α-ketoglutarate- CoASH Alpha-KG DH complex Succinyl CoA Fattyl acid + CoASH Thiokinase Acetyl-CoA Ketoacyl CoA + CoASH Thiolase Acyl CoA + Acetyl CoA Detoxification of benzoic acid Synthesis of bile salts

73. PANTOTHENIC ACID F u n c tion As Acetyl CoA Combines with oxaloacetic acid to form citric acid – first step in the Kreb’s cycle Combines with choline to form acetylcholine Combines with sulfonamide drugs to facilitate their excretion Precursor of cholesterol / steroid hormones Activation of some amino acids : valine, leucine and isoleucine Essential function in lipid metabolism

74. PANTOTHENIC ACID Function As Succiny CoA Involved in heme biosynthesis As Acyl Carrier Protein Involved in fatty acid biosynthesis Extra-mitochondrial lipogenesis

75. Acetyl CoA

76. PANTOTHENIC ACID D e ficiency Rare because: Very widespread in natural foods Most symptoms are vague and mimic those of other B vitamin deficiencies

77. BIOTIN B7 Definition SYNONYMS: Vitamin B7; anti-egg white injury factor CHARACTERISTICS: Widely distributed in natural foods From synthesis of bacteria - deficiency is caused by defects in utilization and not dietary Long-term antibiotic treatment or excessive consumption of raw egg

78. BI O TI N B7 Definition AVIDIN – a protein in raw egg white which combines very tightly with biotin, preventing its absorption

79. BI O TI N B7 Function FUNCTION Coenzymes for carboxylation reactions Carrier of activated carbon dioxide FOOD SOURCES Almost all foods, liver, milk, egg yolk 400 µg/day DEFICIENCY Uncommon Raw egg avidin prevents absorption of Biotin

80. BI O TI N B7

81. Function CARBOXYLATION REACTIONS: BI O TI N B7 Substrate Enzyme Product Acetyl CoA Malonyl CoA acetyl CoA ca r b o xylase Propionyl CoA Propionyl CoA carboxylase Met h ylmal o n yl CoA Pyruvate pyruvate c a rb o xylase Oxaloacetic acid

82. Biotin Biotin

83. BIOTIN B7 Deficiency Man (rare) Fine scaly skin desquamation (peeling) Anorexia ( lack or loss of appetite for food) Nausea Lassitude ( lack of energy) Muscle pains Depression Alopecia (baldness) Graying of hair

84. FOLIC ACID B9 Facts SYNONYMS: Vit B9, Folate, Folacin, PGA (Pteroylglutamic acid) FUNCTION One-Carbon metabolism Essential in biosynthesis of thymidine, AA, and purine

85. FOLIC ACID B9 Facts FOOD SOURCES Green leafy vegetables, liver, lima beans, whole grain cereals DEFICIENCY Growth failure Megaloblastic anemia Neural tube defects

86. F OLI C A CI D B9 Structure

87. F OLI C A CI D B9 F u n c tions – Carrier of one-carbon group moieties. Form Formula Name Most reduced CH 3 Methyl Intermediate CH 2 Methylene Most oxidized CHO Formyl CHNH Formimino CH= methenyl

88. F OLI C A CI D B9 F or m s Form Decription N5-methyl- THFA Most prevalent form transported in the blood N5, N10-methylene THFA Provides methyl group in the formation of thymidylate for DNA synthesis and erythrocyte formation N10 formy; THFA Provides C atom that becomes C2 of purine nucleus N5-formimino THFA Histidine catabolism N10-hydroyxymethyl THFA Thymine synthesis

89. F OLI C A CI D B9 F u n c tion

90. F OLI C A CI D B9 F u n c tion 400 ug folate supplement

91. F OLI C A CI D B9 Deficiency Blood Cell Macrocytic Anemia- impaired production Blood Cell Microcytic Anemia Results when RBC are unable to divide…

92. VITAMIN B12 D e finit i on SYNONYMS: Antipernicious anemia vitamin Cobalamin Extrinsic Factor of Castle Erythrocyte Maturation Factor CHEMISTRY:

93. VITAMIN B12 Chem i s t r y Consists of: 1. Corrin ring system - central portion of the molecule: similar to a porphyrin ring 5,6-dimethylbenzimidazole riboside Aminopropanolol Propionic acid Cobalt-occupies the center of the corrin ring system 1 5 4 3 2

94. VITAMIN B12 F u n c tion FUNCTION Synthesis of methionine Isomerization of methylmalonyl CoA

95. VITAMIN B12 F u n c tion – Involved in the rearrangement of methylmalonyl CoA to succinyl CoA by methylmalonyl CoA isomerase Involved in the transfer of a methyl group from methylTHFA to homocysteine to form methionine .

96. VITAMIN B12 Sources І Deficiency FOOD SOURCES Synthesized by microorganisms in the bacterial flora Liver, whole milk, eggs fresh shrimp, pork, chicken RDA Children: 2ug/day Adults 3 ug/day Pregnancy and lactation: 4 ug/day DEFICIENCY Abnormal fatty acid synthesis Cell membrane defects/Neurological abnormalities Pernicious anemia

97. VITAMIN B12 F or m s Forms Content Cobalamin Without cyanide Cyanocobalamin with cyanide group Hydroxocobalamin with hydroxyl group, more active in enzyme systems; retained longer in the body Methylcobalamin major form in the plasma 5’-deoxyadenosyl cobalamin readily binds to plasma-binding proteins

98. VITAMIN B12 Deficiency Causes: Chronic dietary deficiency of vitamin B-12 . Poor absorption due to lack of intrinsic factor . Presence of antibodies to the intrinsic factor in the gastric juice. Lack of secretion of intrinsic factor (due to gastric mucosal cell atrophy or due to total gastrectomy. Extensive resection of the small intestines. Increased requirements as in pregnancy.

99. VITAMIN B12 Deficiency Clinical effects: “Pernicious Anemia” No healthy RBC Characterized by: Megaloblastic or macrocytic anemia. Lesions of the nervous system Mucosal atrophy and inflammation of the tongue (glossitis), mouth (stomatitis) and pharynx (pharyngitis)

100. ASCORBIC ACID (Vitamin C) Facts Anti-scorbutic vitamin Very sensitive to oxidation Rapidly destroyed by alkalies Freezing has no deleterious effect Strong reducing agent Drying vegetables usually results in loss of vitamin C .

101. ASCORBIC ACID F acts Sources: Citrus fruits Tomatoes Strawberries Green vegetables Guava fruit Green pepper RDA: Adults: 60 mg/day Children: 40 mg/day

102. ASCORBIC ACID F acts

103. ASCORBIC ACID Metabolic roles Hydroxylation of Proline and Lysine in collagen formation. Hydroxylation of tryptophan Synthesis of no r ephinep hrine Tyrosine metabolism Hydroxylation of steroids in the adrenal cortex Serves as a reductant of ferric to ferrous ion Involved in the conversion of folic acid to active THFA Involved in the hydroxylation of cholesterol to cholic acid Acts as regulator of cholesterol metabolism

104. ASCORBIC ACID Function Major function of vitamin C – coenzyme in the formation of tissue collagen or intracellular cement substance

105. ASCORBIC ACID Function Major function of vitamin C – coenzyme in the formation of tissue collagen or intracellular cement substance

106. ASCORBIC ACID D e fici e n c y Spongy gums Poor wound healing

107. ASCORBIC ACID D e fici e n c y Splinter hemorrhages in nails subcutaneous hemorrhages

108. ASCORBIC ACID Deficiency swelling at the ends of long bones

109. FAT-SOLUBLE VITAMINS Structure Vitamin A Vitamin D Vitamin K Vitamin E retinol, B-carotenes cholecalciferol phylloquinones, menaquinones tocopherols

110. VITAMIN A R e tinol Structure Retinol and retinoic acid – act like steroid hormones Retinalehyde is a component of Rhodposin Retinoic acid participates in glycoprotein synthesis

111. VITAMIN A Retinol F u nction Provitamin - β carotene FUNCTION Maintenance of reproduction Maintenance of vision Promotion of growth Gene expression Treatment of psoriasis, acne, cancers FOOD SOURCES Liver, kidney, cream, butter, egg yolk Yellow and dark green vegetables

112.    Dietary Vitamin A, from animal sources is available in the form of Retinyl esters, which is hydrolyzed to retinol and fatty acid by pancreatic hydrolases The absorption of retinol requires the presence of bile salts In the intestinal cells, retinol is esterified back and secreted with chylomicrons

113. • The liver contains approximately 90% of the vitamin A reserves and secretes vitamin A in the form of retinol, which is bound to retinol- binding protein . • • The retinol-binding protein complex interacts with a second protein, Transthyretin . This trimolecular complex functions to prevent vitamin A from being filtered by the kidney glomerulus, to protect the body against the toxicity of retinol and to allow retinol to be taken up by specific cell-surface receptors that recognize retinol-binding protein.

114. • In the retina, retinaldehyde functions as the prosthetic group of the light-sensitive opsin proteins, forming Rhodopsin (in rods) and iodopsin (in cones). • • • Any one cone cell contains only one type of opsin, and is sensitive to only one color. The absorption of light by Rhodopsin causes isomerization of the retinaldehyde from 11- cis to all- trans , and a conformational change in opsin. This results in the release of retinaldehyde from the protein, and the initiation of a nerve impulse.

115.   The formation of the initial excited form of Rhodopsin, bathorhodopsin, occurs within pico - seconds of illumination. There are then a series of conformational changes leading to the formation of metarhodopsin II, which initiates a guanine nucleotide amplification cascade and then a nerve impulse.

116.  The final step is hydrolysis to release all- trans -retinaldehyde and opsin.   The key to initiation of the visual cycle is the availability of 11- cis -retinaldehyde, and hence vitamin A. In deficiency, both the time taken to adapt to darkness and the ability to see in poor light are impaired.

117. VITAMIN D Facts FUNCTION 1,25-dihydrocholecalciferol- a steroid hormone Stimulates gene expression or repress gene transcription Regulates plasma levels of calcium and phosphorus

118. Vitamin D Synthesis Vitamin D in reality is a hormone and is a metabolic product of the cholesterol biosynthetic pathway Vitamin D 3 , a cholecalciferol is synthesized de novo by the exposure of skin to sunlight that converts 7-dehydrocholesterol to vitamin D 3 Vitamin D3 is then converted in liver , to 25-hydroxycholecalciferol (25-OH- D 3 ) by the enzyme 25-hydroxylase - still an inactive form 25-OH- D 3 is the blood test used to assess adequacy of vitamin D stores in the body In the kidney , renal 1 α -hydroxylase hydrolyses 25-OH- D 3 to form 1,25-dihydroxycholecalciferol (1,25-[OH]2- D 3 ) – the biologically active form (PTH stimulates this enzyme)

119. Vitamin D from diet Vitamin D is relatively rare in most typical foods. The only common dietary source of vitamin D are multivitamins , supplements and vitamin D fortified milk. Cod liver oil is also a source of vitamin D

120. Vitamin D

121. The actions of Vitamin D 1. Enhances calcium absorption from the intestine 2. Facilitates calcium reabsorption in the kidney 3. Increases bone calcification and mineralization 4. In excess, mobilizes bone calcium and phosphate.

122. VITAMIN D A c tion Response to low plasma calcium

123. VITAMIN D Deficiency DEFICIENCY Rickets Osteomalacia (demineralization of bone) TOXICITY Most toxic of all vitamins Deposition of calcium in organs and arteries, kidney stones

124. Vitamin K Three compounds have the biological activity of vitamin K Phylloquinone (Vitamin K1), the normal dietary source, found in green vegetables Menaquinones (vitamin K2), synthesized by intestinal bacteria , with differing lengths of side chain; and Menadione and menadiol diacetate , synthetic compounds that can be metabolized to phylloquinone.

125. Dietary Sources Green leafy vegetables such as kale and spinach, Margarine and liver. Vegetable oils and particularly olive, canola, and soybean oils. Some amount is contributed by intestinal bacteria 6

126. Absorption, Transportation and Storage Absorption takes place in small intestine in the presence of bile salts . The transportation from intestine is carried out through chylomicrons . Storage occurs in liver and from liver transportation to peripheral cells is carried out bound with beta lipoproteins (VLDL). 131

127. Recommended daily allowance (RDA) The average daily allowance is 50-120 mcg/day. Requirement increases in – Liver disorders Patients on prolonged antibiotic therapy, and Orlistat (weight loss medication)

128. Functions of Vitamin K Coagulation Bone Synthesis Prevention of athe r oscle r os i s 133

129. Vitamin K deficiency Vitamin K de f ic i en c y Dietary de f i c ie n c y Fat malabsorption Surgical i n t e r v ent i o n s of intestine Chronic liver diseases Prolonged intake of ant i b i o ti c s

130. Chemical nature: Vitamin E is chemically known as tocopherol (Greek: tocos= childbirth , piro= to bear and ol= alcohol ) An alcohol was capable to prevent reproductive failure in animals Hence it is known as anti-sterility vitamin Chemistry: Vitamin E is the name given to group of tocopherols and tocotrienols

131. About 8 tocopherols have been identified Alpha- tocopherol is most active The tocopherols are derivatives of 6-hydroxy chromane (tocol) ring with isoprenoid side chain The antioxidant property is due to the chromane ring

132. ABSO R PTION Vitamin E is absorbed along with fat in the upper small intestine Mechanism: Vitamin E combines with Bile salts (micelles) to form mixed micelle and taken up by the mucosal cell In the mucosal cell, it is incorporated into chylomicrons

133. Biochemical functions Vitamin E is essential for membrane structure and integrity of the cell , hence it is membrane antioxident It prevents the peroxidation of PUFA It protects the RBC from hemolysis by oxidizing agents (H 2 O 2 ) It is associated with reproductive function and prevents sterility

134. Vitamin E preserves and maintains germinal epithelium of gonads for proper reproductive function It increases the synthesis of heme by enhancing the activity of enzyme – δ aminolevulinic acid (ALA) synthase and ALA dehydratase It is required for cellular respiration –through ETC (Stabilize coenzyme Q) Vitamin E prevents the oxidation of Vitamin A and carotenes 9. Vitamin E prevents oxidation of LDL, Oxidized LDL promotes heart diseases

135. Males Females Pregnancy Lactation -10 mg/day - 8 mg/day 10 mg/day 12 mg/day 15 mg of vitamin E is equivalent to 33 IU Pharmacological dose is 200-400 IU/day Sources: Rich sources are vegetable oils Includes germ oil, sunflower oil, corn oil and margarine

136. VI T A M I NS Definition I Fu nction VITAMIN FUNCTIONS DEFICIENCY DISEASE A Retinol, β-carotene Visual pigments in the retina; regulation of gene expression and cell differentiation; Antioxidant Night blindness, xerophthalmia; keratinization of skin D Calciferol Maintenance of calcium balance; enhances intestinal absorption of Ca++ and mobilized biomineral Rickets = poor mineralization of bones; Osteomalacia = bone demineralization E T o c oph e r o l s T o c ot r i e n o l s Antioxidant, especially in cell membranes Extremely rare - serious neurologic dysfunction K P h y ll oquinone Mena q uinone Coenzyme in formation of γ- carboxyglutamate in enzymes of blood clotting and bone matrix Impaired blood clotting, hemorrhagic disease

137. VI T A M I NS Definition I Fu nction VITAMIN FUNCTIONS DEFICIENCY DISEASE B1 Thiamin Coenzyme in pyruvate and α- ketoglutarate DH, and transketolase; poorly defined function in nerve conduction Peripheral nerve damage (beriberi) or CNS lesions (Wernicke-Korsakoff syndrome) B2 Riboflavin Coenzyme in redox reactions; prosthetic group of flavoproteins Lesions of corner of mouth, lips and tongue, seborrheic dermatitis B3 Niacin Nicotinic acid Nicotinamide Coenzyme in redox reactions; functional part of NAD and NADP Pellagra- photosensitive dermatitis, depressive psychosis Energy-Releasing

138. VI T A M I NS Definition I Fu nction Energy-Releasing VITAMIN FUNCTIONS DEFICIENCY DISEASE Pantothenic Acid Functional part of CoA and acyl carrier protein: fatty acid synthesis and metabolism Biotin Coenzyme in carboxylation reactions in gluconeogenesis and fatty acid synthesis Impaired fat and CHO metabolism, dermatitis

139. VI T A M I NS Definition I Fu nction VITAMIN FUNCTIONS DEFICIENCY DISEASE Folic acid Coenzyme in transfer of one- carbon fragments Megaloblastic anemia B12 Cobalamin Coenzyme in transfer of one- carbon fragments and metabolism of folic acid Pernicious anemia = megaloblastic anemia with degeneration of the spinal cord H ema t opo e i t i c

140. VI T A M I NS Definition I Fu nction VITAMIN FUNCTIONS DEFICIENCY DISEASE B6 Pyridoxine Pyridoxal Pyr i d ox am i ne Coenzyme in transamination & decarboxylation of AA and glycogen phosphorylase; role in steroid hormone action Disorders of AA metabolism, convulsions C Ascorbic Acid Coenzyme in hydroxylation of proline and lysine in collagen synthesis; antioxidant; enhances iron absorption Scurvy- impaired wound healing, loss of dental cement, subcutaneous hemorrhage Other functions

141. VI T A M I NS Definition I Fu nction w