Vitamins PDF

 VITAMINS ♦ Definition and classification with examples. ♦ Vitamin A and D: Sources, chemical nature, coenzyme, RDA, deficiency ♦ Vitamin E and K: Sources, chemical nature, coenzyme, RDA, deficiency ♦ Vitamin C: Sources, chemical nature, coenzyme, RDA,...

 VITAMINS ♦ Definition and classification with examples. ♦ Vitamin A and D: Sources, chemical nature, coenzyme, RDA, deficiency ♦ Vitamin E and K: Sources, chemical nature, coenzyme, RDA, deficiency ♦ Vitamin C: Sources, chemical nature, coenzyme, RDA, deficiency ♦ Vitamin B: Sources, chemical nature, coenzyme, RDA, deficiency  VITAMINS Vitamins are organic compounds required in diet in small amounts for normal biological function and maintenance for optimum growth and health of organism. ◊ E.coli does not require any vitamin, as it can synthesize all of them. ◊ During evolution of organisms, the ability to synthesize vitamins was lost. Hence, the higher organisms have to obtain them from diet. ◊ Since, the vitamins are required in small amounts, so their degradation is relatively slow. ◊ Hopkins coined the term accessory factors to the unknown and essential nutrients present in the natural foods. ◊ Funk (1913) isolated an amine from rice. He gave the term vitamine (Greek: vita-life) to the accessory factors which were amines. ◊ In 1915 by McCollum and Davis introduced A, B and C categories of vitamins. CLASSIFICATION: Vitamins are classified broadly as Fat soluble and water soluble. Vitamins Fat Soluble Vitamin Water soluble vitamin Vitamin A Vitamin D Vitamin E Non B-complex B-complex Vitamin K Vitamin C B1 (Thiamine) B7 (Biotin) B2 (Riboflavin) B9 (Folic acid) B3 (Niacin) B12 (Cyanocobalamin) B5 (Pantothenic acid) B6 (Pyridoxin) ◊ Fat soluble vitamins are stored in liver and adipose tissue. They are not readily excreted in urine. ◊ All fat soluble vitamins are made up of isoprene units. ◊ Water soluble vitamins are heterogenous compounds since they differ chemically from each other and are readily excreted in urine. ◊ Water soluble vitamins are not stored in body in large quantities (except B12), so they must be supplied in diet. ◊ Most of the water soluble vitamins functions through their respective coenzymes. Vitamin K itself acts as coenzyme. ◊ The term ‘Vitamers’ represents chemically similar substances of vitamin activity. E.g., Retinol & retinal (Vitamin A), Pyridoxin and pyridoxal (Vitamin B6). ❑ VITAMIN A: Fat soluble vitamin found mainly in animal origin foods in the form of retinol but its provitamin is also found in plants in the form of carotene (β-carotene). Recommended daily allowance: In the form of retinol is 800-1000 µg/day or as β-carotene is 4800-6000 µg/day in adult women and men respectively. The requirement increases in pregnant or lactating women. Sources: animal sources (Egg, milk, fish, cheese, butter, liver, kidney etc.), plant sources (Carrots, spinach, pumpkin, mango, papaya etc.) Deficiency diseases: This may be due to inadequate dietary intake, impaired intestinal absorption or reduced storage in liver. 1. Night blindness (Nyctalopia): Difficulty to see in dim light or at night. Prolonged deficiency irreversibly damages visual cells. 2. Xeropthalmia: Dryness of conjunctiva or cornea of eye. In certain areas of conjunctiva, white triangular plaques are seen, known as Bitot’s spots. 3. Keratomalacia: Complete blindness due to persistent xeropthalmia. 4. Effect on growth, reproduction, skin and epithelial tissues. Also associated with the formation of urinary stones and decrease in plasma level of retinol binding protein (RBP). Note: Excessive consumption of vitamin A leads to toxicity known as hypervitaminosis A. Its symptoms includes dermatitis, decalcification of bones, loss of weight, irritability, loss of hair, joint pain etc. *Normal serum vitamin level: 20-50 µg/dl of blood. Chemical nature: The term retinoid is used for all natural and synthetic forms of vitamin A. 1. Retinol (Vitamin A alcohol): Primary alcohol containing β-ionone ring. Its side chain has two isoprenoid units with four double bonds and one hydroxyl group. Retinol is present in animal tissues as retinyl ester with long chain fatty acids. 2. Β-Carotene (Provitamin A): It has 1/6th vitamin A activity compared to retinol and found in plant foods only. It has four isoprenoid units with 8 double bonds and two β-ionone ring. 3. Retinal (aldehyde vitamin A): Aldehyde form of retinol obtained by its oxidation. Retinal and retinol are interconvertible. 4. Retinoic acid (Acid vitamin A): Produced by oxidation of retinal. It is non-convertible. *Retinol, retinal and retinoic acid are regarded as vitamers of vitamin A.  Absorption and transport of vitamin A: Dietary retinyl esters are hydrolyzed hydrolases in the intestine, releasing retinol and free fatty acids. Carotenes are hydrolyzed by β-carotene 15-15′ dioxygenase of intestinal cells to release 2 moles of retinal which is reduced to retinol. In the intestinal mucosal cells, retinol is re-esterified to long chain fatty acids present in chylomicrons and transferred to the lymph. The retinol esters of chylomicrons are taken up by the liver and stored. Vitamin A is released from the liver as free retinol when needed. Retinol is transported in the circulation by the plasma retinol binding protein. Role of vitamin A in vision was first explained by George Wald through a cyclic process known as Rhodopsin cycle/Wald’s cycle. Rhodopsin is conjugated protein present in rods. Rods and cones are two types of cells present in retina of eye responsible for dim light vision and bright light color vision respectively. Biochemical functions: o Necessary for vision, proper growth and differentiation of cells as retinol and retinoic acid regulates protein synthesis. o Helps in reproduction as retinol acts like steroid hormone and regulates gene expression. o Helps in maintenance of epithelial cells as retinol and retinoic acid are required to prevent keratin synthesis (responsible for horny surface). o Vitamin A is considered to be essential for the maintenance of proper immune system to fight against various infections. o Carotenoids (most important β-carotene) function as antioxidants and reduce the risk of cancers. β-Carotene is found to be beneficial to prevent heart attacks. ❑ VITAMIN D: Fat soluble vitamin which resembles sterols in structure and functions like hormone. Hess (1924) reported that irradiation with ultraviolet light induced antirachitic activity in some foods. Vitamin D was isolated by Angus (1931) who named it calciferol. Vitamin D exists in two forms D2 (Ergocalciferol) and D3 (Cholecalciferol). Recommended daily allowance: The daily requirement of vitamin D is 400 International Units or 10 mg of cholecalciferol. In countries with good sunlight (like India), the RDA for vitamin D is 200 IU (or 5 mg cholecalciferol). Sources: Good sources includes fatty fish, fish liver oils, egg yolk etc. Vitamin D can also be provided to the body in three ways like Exposure of skin to sunlight for synthesis of vitamin D, Consumption of natural foods or by irradiating foods (like yeast) that contain precursors of vitamin D and fortification (adding vitamins to food items) of foods (milk, butter etc.). Normal range of vitamin D in blood plasma: 30-40 mg/ml of blood. Vitamin D in the form of 25-hydroxy cholecalciferol is employed in plasma to elevate vitamin D deficiency. Deficiency diseases: 1. Rickets: mainly occurs in children, characterized by bone deformities due to incomplete mineralization, resulting in soft bones and delay in teeth formation. The weight bearing bones are bent to form bow legs. 2. Osteomalacia: also known as adult rickets. Demineralization of bones occur increasing susceptibility to fracture. 3. Renal rickets: due to decreased synthesis of calcitriol. Mainly seen in patients with chronic renal failure. It can be treated by administration of calcitriol. Note: In rickets, plasma level of calcitriol is decreased and alkaline phosphatase activity is elevated. Alkaline phosphatase is concerned with the process of bone formation. Hypervitaminosis D: Symptoms include demineralization of bones and increased calcium absorption from intestine leading to elevated calcium in plasma (hypercalcemia). Note: High consumption of vitamin D is toxic but exposure to sunlight does not cause toxicity. This is due to limited capacity of body to form vitamin in skin.  Chemical nature: Vitamin D has two forms: Ergocalciferol (D2) and Cholecalciferol (D3). o Ergocalciferol is formed from ergosterol and is present in plants. Cholecalciferol is formed from cholesterol and present mainly in animals. o Both the sterols are similar in structure except that ergocalciferol has an additional methyl group and a double bond. o Ergocalciferol and cholecalciferol are sources for vitamin D activity and are referred to as provitamins. o Vitamin D is regarded as sun-shine vitamin. o During cholesterol biosynthesis, 7-dehydrocholesterol is formed as an intermediate. On exposure to sunlight, 7-dehydrocholesterol is converted to cholecalciferol in the skin. o Vitamin D is absorbed in the small intestine for which bile is essential. o Vitamin D enters the circulation bound to plasma α2-globulin and is distributed throughout the body. o Liver and other tissues store small amounts of vitamin D. o Biologically active form of vitamin D is calcitriol (1,25-DHCC). It regulates the plasma levels of calcium and phosphate. Calcitriol acts at 3 different levels (intestine, kidney and bone) to maintain plasma calcium (normal 9–11 mg/dl). Biochemical Functions: o Calcitriol increases intestinal absorption of calcium and phosphate. o Calcitriol is essential for bone formation. The bone is an important reservoir of calcium and phosphate. o Calcitriol is also involved in minimizing the excretion of calcium and phosphate through the kidney, by decreasing their excretion and enhancing reabsorption. ❑ VITAMIN E: Fat soluble vitamin. Also known as tocopherols/tocotrienols is a naturally occurring anti-oxidant. It is essential for normal reproduction, hence known as anti-sterility vitamin. Sources: Vegetable oils are rich sources of vitamin E like wheat germ oil, cotton seed oil, peanut oil, corn oil, sunflower oil etc. Also present in milk, butter and eggs. Recommended daily allowance: 10 mg (15 IU) of α-tocopherol from men and 8mg (12 IU) for women is recommended. Intake of vitamin E is directly related to the consumption of polyunsaturated fatty acid (PUFA). Vitamin E supplemented diet is recommended for pregnant and lactating women. Deficiency diseases: o In many animals, the deficiency is associated with sterility, generative changes in muscles, megaloblastic anaemia and changes in CNS. o Severe symptoms of vit. E deficiency is not seen in humans except increased fragility of erythrocytes and minor neurological symptoms. Note: Among fat soluble vitamins, vitamin E is least toxic. Chemical nature: Vitamin E is considered as group of compounds like tocopherols and tocotrienols. o About 8 tocopherols (vitamers of vitamin E) have been identified as α, β, γ, δ etc. Among these α-tocopherol is most active. o Tocopherols are derivatives of 6-hydroxy chromane ring (tocol ring) with 3 units of isoprenoid side chain. o The anti-oxidant property is due to hydroxyl group of chromane ring. o Vitamin E is absorbed along with fats in small intestine. Bile salts are necessary for its absorption. o It is stored in adipose tissue, liver and muscles. o The plasma level of tocopherol is less than 1mg/dl of blood.  Biochemical Functions: Most of the functions of vitamin E is related to its anti-oxidant property. o It prevents non-enzymatic oxidation of various components of cell. o It is essential for membrane structure and integrity of cell, hence regarded as membrane anti-oxidant. o It protects RBC from haemolysis by oxidizing agents like H2O2. o It is closely associated with reproductive function and prevents sterility (by maintaining germinal epithelium of gonads). o It increases the synthesis of heme by enhancing the activity of enzymes. o Vitamin E prevents the oxidation of vitamin A and carotenes. o Vitamin E is essential for proper absorption of amino acids from intestine. o It is involved in synthesis of nucleic acids. o It protects liver from damaged by toxic compounds like carbon tetrachloride. o It protects polyunsaturated fatty acid (PUFA) from peroxidation reaction. It acts as scavenger to protect PUFA from free radicals and itself gets oxidised by them. o Vitamin E is lipophilic in character and found in association with lipo-proteins, fatty deposits and cell membrane. o Vitamin E prevents oxidation of LDL. Oxidised LDL promotes heart disease. ❑ VITAMIN K: Fat soluble vitamin with specific coenzyme function. It is required for the production of blood clotting factors, essential for coagulation. It is found in two forms K1 (Phylloquinone: in plant source), K2 (Menaquinone: in animal source) and K3 (Menadione: synthetic form). Sources: Plant sources are cabbage, cauliflower, tomatoes, alfa-alfa, spinach and other green vegetables. Animal sources are egg yolk, meat, liver, cheese and diary products. Recommended daily allowance: 70-100 µg/day for adults. This is half of the total requirement of the body per day. The remaining half of vitamin K is synthesised in the body by intestinal bacteria.  Deficiency diseases: It is uncommon because half of the body’s requirements is fulfilled by its synthesis by intestinal bacteria. But o Deficiency may occur due to faulty absorption, loss of vitamin in to faeces or administration of antibiotics which kills intestinal bacteria. o Deficiency leads to lack of prothrombin in circulation which is responsible factor for blood clotting. This increases blood clotting time. Note: Hypervitaminosis K: It can cause haemolytic anaemia and jaundice, particularly in infants. The toxic effect is due to increased breakdown of RBC. Heparin (bis-hydroxy coumarin) is an anti-coagulant and acts as antagonists to vitamin K. Salicylates (Warfarin) and dicumarol also acts as antagonists. Chemical nature: o All vitamin K are naphthoquinone derivatives. o Isoprenoid side chains are present in vitamin K1 and K2. o All three vitamins are stable to heat but their activity may be lost by oxidizing agents, irradiation, strong alkali and acids. ❑ VITAMIN C (ASCORBIC ACID): It is water soluble, versatile vitamin and plays an important role in human health and disease. Sources: Citrus fruits, goose berry (amla), guava, green vegetables (Cabbage, spinach), tomato etc. Recommended daily allowance: 40-50 mg/day for adults. This requirement increases 20-40% for women during pregnancy and lactation. Deficiency diseases: o Scurvy: characterised by spongy and sore gums, loose teeth, anaemia, swollen joints, delayed wound healing etc. o Osteoporosis:, haemorrhage, disturbances in hormonal function of adrenal cortex and gonads. o Impairment in synthesis of collagen. o Infantile scurvy (Barlow’s disease): occurs in infants aged 6-12 months. o Anti-oxidant property of vitamin C is also disturbed. Note: Hypervitaminosis C: Vitamin C is not found to be toxic yet but the oxidised form of vitamin C (dehydroascorbic acid) is toxic. Also, oxalate is a major metabolite of vitamin C is involved in the formation of kidney stones. Chemical nature: o Ascorbic acid is a hexose derivative and closely resembles monosaccharides in structure. o Acidic property of vitamin C is due to enolic hydroxyl group. o It is strong reducing agents, so it readily undergoes oxidation to form dehydroascorbic acid (reversible). o Dextro-ascorbic acid is inactive in nature. o Oxidation of ascorbic acid is rapid in presence of copper. So, vitamin C becomes inactive when food is prepared in copper vessels. Absorption and metabolism: Vitamin C is rapidly absorbed from the intestine. It is not stored in the body to a significant extent. Ascorbic acid is excreted in urine as such, or as its metabolites- diketogulonic acid and oxalic acid  Biochemical Functions: o It is an strong anti-oxidant. o Vitamin C increases synthesis of immunoglobulins (anti-bodies) and increases phagocytic action of leucocytes. o Maintains normal connective tissue (collagen formation) and wound healing process. o Also helps in bone formation. o Helps in iron and hemoglobin metabolism (increases iron absorption). o Helps in metabolism of amino acid. o Needed for the formation of tetrahydrofolate (THF) from folic acid, which in association with ascorbic acid is involved in maturation of erythrocytes. o Vitamin C is necessary for hydroxylation reaction in the synthesis of corticosteroid hormone. o Vitamin C has preventive action on cataract and chronic diseases like cancer and heart disease.  VITAMIN B-COMPLEX ❑ VITAMIN B1 (THIAMINE): It is water soluble vitamin with specific co-enzyme, thiamine pyrophosphate (TPP) which is mostly associated with carbohydrate metabolism. Sources: Plant sources includes Cereals, pulses, oil seeds, nuts and yeast. Mostly concentrated in outer layer of cereals. Animal sources are pork, liver, kidney, heart, milk etc. Since thiamine is water soluble, it is extracted in to water during cooking process. Such water should not be discarded. Recommended daily allowance: 1-1.5 mg/day for adults. 0.7-1.2 mg/day in children. 2 mg/day in old age or pregnant women. Deficiency diseases: o Beri-beri: Specially in people consuming polished rice. Symptoms include loss of appetite, weakness, constipation, nausea, mental depression etc. o Infantile beri-beri: Infants born to mothers suffering from thiamine deficiency. o Carbohydrate metabolism is impaired. o Impairment in nerve impulse transmission. Note: Wet beri-beri (cardiovascular): Symptoms include edema of legs and face, breathlessness and palpitation. Dry beri-beri (neurological): muscles becomes weak and walking becomes difficult. Chemical nature: o Thiamine contains pyrimidine ring and a thiazole ring held by a methylene bridge. o Thiamine is the only natural compound with thiazole ring. o The –OH group of thiamine is esterified with 2 moles of phosphate to form coenzyme TPP. o Pyrithiamine and oxythiamine are anti-metabolites of thiamine.  Biochemical functions of thiamine: o The coenzyme TPP or co-carboxylase is associated with carbohydrate metabolism during energy releasing reactions in Citric acid cycle, HMP shunt, oxidative decarboxylation reaction etc. o TPP plays an important role in transmission of nerve impulse. It is required for the synthesis of acetycholine. ❑ VITAMIN B2 (RIBOFLAVIN): It is a water soluble vitamin which takes part in various oxidation reduction reactions. Sources: Plant sources includes cereals, fruits, vegetables etc. (moderate sources) Animal sources includes milk, dairy products, meat, egg, liver, kidney etc. (rich sources) Recommended daily allowance: 1.2-1.7 mg/day for adults. Deficiency disease: o Cheilosis: Fissures at corners of mouth. o Glossitis: Smooth and purplish tongue. o Dermatitis: inflamed skin. Chemical Nature: o Contains 6,7-dimethyl isoalloxazine (a heterocyclic 3 ring structure) attached to D-ribitol by a nitrogen atom. o Ribitol is an open chain form of sugar ribose having aldehyde group reduced to alcohol. o Riboflavin is stable to heat but sensitive to light. o When exposed to UV-rays of sunlight, it is converted to lumiflavin which exhibits yellow florescence. Biochemical functions: o The coenzymes FAD (flavin adenine dinucleotide) and FMN (flavin mononucleotide) participates in many redox reactions. o Both the coenzymes are associated with certain enzymes involved in metabolism of carbohydrate, lipid, protein and purine. ❑ VITAMIN B3 (NIACIN OR NICOTINIC ACID): Also known as pellagra preventive factor (pp-factor). Coenzymes of niacin are NAD+ and NADP+. Sources: Plant sources includes, whole grains, pulses like nuts, beans, cereals etc are rich sources. Animal sources includes liver, kidney, milk, fish, egg etc. are moderate sources. Recommended daily allowance: 15-20 mg/day for adults. 10-15 mg/day for children. Note: The amino acid tryptophan can also form coenzymes of niacin in the body. The essential amino acid tryptophan can serve as a precursor for the synthesis of nicotinamide coenzymes. 60 mg of tryptophan is equivalent to 1 mg of niacin (ratio 60:1) for the synthesis of nicotinamide coenzymes. Tryptophan can replace niacin to an extent of 10% for the synthesis of coenzymes. Deficiency diseases: o Pellagra: symptoms include three Ds i.e. dermatitis, diarrhoea and dementia. This disease involves skin, gastrointestinal tract and central nervous system. If not treated, this may rarely lead to death. Dermatitis is seen on areas of skin exposed to sunlight. Diarrhoea is characterised by loose stools with blood and mucus. Dementia is associated with degeneration of nervous tissue with symptoms like poor memory and insomnia. Therapeutic uses: 2-4 gm/day (200 times of RDA) results in a number of biochemical effects in the body like it inhibits lipolysis of adipose tissue and decreases circulating free fatty acid and the serum level of LDL, VLDL, triacylglycerol and cholesterol are lowered. Toxicity of niacin: o Megadose of niacin are useful for the treatment of hyperlipidemia. o Glycogen and fat reserves of skeletal and cardiac muscle decreases. o Increased level of glucose and uric acid in circulation. o Prolong use of niacin results in liver damage due to increased serum levels of certain enzymes.  Chemical nature: o Niacin is pyridine derivative. Structurally it is pyridine 3-carboxylic acid. o The amide form of niacin is known as nicotinamide or niacinamide. o NAD+ (Nicotinamide adenine dinucleotide) and NADP+ (Nicotinamide adenine dinucleotide phosphate) are coenzymes of niacin. o 60 mg of tryptophan is equivalent to 1 mg if niacin. o In the structure of coenzymes, nitrogen atom of nicotinamide carries a positive charge (due to formation of extra bond, N is in quaternary state). Hence, the coenzymes have one positive charge. Biochemical functions: o The coenzymes are involved in variety of redox reactions. So, a large number of enzymes belonging to oxido- reductases are dependent on NAD+ and NADP+. o Both coenzymes participates in almost all metabolism like carbohydrate, lipid, protein etc. o NADH is oxidized in electron transport chain to generate ATP. o NADPH is also important for many biosynthetic reactions. o The coenzymes have ability to accept hydride (H-) ion and undergo reductions in various biochemical reactions. ❑ VITAMIN B5 (PANTOTHENIC ACID): It is water soluble vitamin and was also known as chick anti-dermatitis factor/Filtrate factor. Its role as coenzyme A is also widespread. Sources: Plant sources include whole grains and some green vegetables. Animal sources include beef, chicken, organi meats etc. Recommended daily allowance: 4-5 mg/day for adults. 1.5-2 mg/day for children. Deficiency: It is rare, except in people with severe malnutrition. Symptoms include numbness, burning pf hands & feet, headache, fatigue, irritability, restlessness, disturbed sleep and GI disturbances. Chemical nature: Pantothenic acid consists of two components, pantoic acid and β-alanine held togather by peptide linkage. Molecular formula C9H17NO5. Biochemical Functions: o To treat hyperlipidaemia by taking B5 supplements. o A form of pantothenic acid, pantetheine reduces lipid levels when in large amounts. o Main function is synthesis of coenzyme A and acyl carrier protein. o CoA is essential for fatty acid synthesis and degradation, transfer of acetyl and acyl groups. o The main role of Acyl carrier protein is fatty acid synthesis. Toxicity: There is no reported toxicity in humans. Sometimes large doses supplements (10mg/day) develop mild diarrhea and gastrointestinal distress. ❑ VITAMIN B6 (PYRIDOXIN): Water soluble vitamin and is collectively used to represent 3 compounds: pyridoxin, pyridoxal and pyridoxamine. Sources: Plant sources includes wheat, corn, cabbage, roots and tubers. Animal sources include egg yolk, fish, milk, meat etc. Recommended daily allowance: 1.5-2mg/day for adults. Deficiency: o Neurological symptoms such as depression, irritability, nervousness and mental confusion are seen. o Convulsions and peripheral neuropathy are observed in severe deficiency. o Reduction in heme production may be seen. o Consumption of several drugs like isoniazid and penicillamine cause B6 deficiency. Toxicity: o 2.5 gm/day of vitamin B6 cause pre-menstrual syndrome in women. o 200 mg/day may cause neurological damage. Chemical nature: o Vitamin B6 compounds are pyridine derivatives. o Vitamers of vitamin B6 differ from each other in the structure of functional group attached to 4th carbon in the pyridine ring. o Pyridoxin is a primary alcohol, pyridoxal is an aldehyde and pyridoxamine is an amine. o Pyridoxine is mainly present in plants while pyridoxal and pyridoxamine are found in animal foods.  Biochemical functions: o Pyridoxal phosphate (PLP) is involved in transamination reaction, converting amino-acids to keto-acids. o PLP also helps on decarboxylation process. o PLP is required for the synthesis of α-amino levulinic acid which is precursor for heme synthesis. o PLP also helps in the synthesis of niacin coenzymes from tryptophan. o PLP plays an important role in metabolism of Sulphur containing amino acids. o PLP is needed for the absorption of amino acids from intestine. o Serine is synthesized from glycine by PLP dependent enzyme. o Adequate intake of B6 is useful to prevent urinary stone formation. ❑ VITAMIN B7 (BIOTIN): It is water soluble, sulphur containing B-complex vitamin, which was formerly known as Vitamin H or anti-egg white injury factor. It itself acts as coenzyme in various carboxylation reactions. Sources: Liver, kidney, egg yolk, milk, tomatoes etc. are rich sources. Recommended daily allowance: 20-30 µg/day for adults. It is also synthesized by intestinal bacteria but its contribution in the body is not clearly known. Deficiency diseases: Its deficiency is not very common but in some cases, symptoms include o Anaemia, loss of appetite, nausea, dermatitis, glossitis etc. o Deficiency may be due to destruction of intestinal flora due to prolonged use of anti-biotics or high consumption of raw eggs. The raw eggs contains a glycoprotein (avidin), which tightly binds with biotin and blocks its absorption from intestine. Note: Biotin sulphonic acid and desthiobiotin are antagonists of biotin. Chemical Nature: Heterocyclic sulphur containing mono-carboxylic acid. It contains imidazole and thiophene rings. Biocytin is regarded as coenzyme of biotin.  Biochemical functions: o Serves as carrier of CO2 in carboxylation reaction. o Biotin helps in gluconeogenesis and citric acid cycle. o Biotin is needed for the synthesis of fatty acids from acetyl CoA. o Biotin is involved in cell cycle regulation. o It is also helpful in metabolism of leucine. ❑ VITAMIN B9 (FOLIC ACID): A water soluble vitamin required for one-carbon metabolism and also required for the synthesis of certain amino acids, purine and the pyrimidine thymine. Sources: Green leafy vegetables are rich sources. Whole grains, liver, kidney, yeast and eggs are also good sources. Recommended daily allowance: 200 µg/day for adults. Deficiency diseases: It is the most common vitamin deficiency may be due to inadequate dietary intake, defective absorption or use of anti-convulsant drugs. o In folic acid deficiency, decreased production of purines is observed which impairs DNA synthesis. o In pregnant women, it may cause neural defects in the foetus. Chemical nature: o Folic acid consists of three components-pteridine ring, p-aminobenzoic acid (PABA) and glutamic acid. o Folic acid is found in multiple forms with variable number of glutamic acid residue (1-7). But it mostly has one glutamic acid residue and is known as pteroyl-glutamic acid (PGA). o The active form of glutamic acid is tetrahydrofolate (THF). It is synthesized from folic acid by the enzyme dihydrofolate reductase.  Biochemical functions: o THF is the coenzyme of folic acid and is actively involved in one carbon metabolism. o Because of one carbon metabolism, many important compounds are synthesized like purines, pyrimidines, glycine etc. Hence, THF is indirectly involved in the synthesis of purine, pyrimidines and some amino acids. o N-formyl methionine, the initiator of protein biosynthesis is also formed in one carbon metabolism by THF. ❑ VITAMIN B12 (COBALAMIN): It is a water soluble vitamin which is synthesized by micro-organism, only by anaerobic bacteria. Sources: Liver, kidney, milk, curd, eggs etc are rich sources. o Curd is better than milk due to the synthesis of B12 by lactobacillus. o Vitamin B12 is not found in plant products. o Intestinal bacteria also synthesize vitamin B12. Recommended daily allowance: 1-2 µg/day for adults. 0.5-1.5 µg/day for children. 3 µg/day for pregnant women. Deficiency diseases: o Pernicious anemia: Low hemoglobin, decreased erythrocytes etc. o Autoimmune destruction of gastric parietal cells that secrete intrinsic factor. In the absence of intrinsic factor, vitamin B12 is not absorbed. o Dietary deficiency of vitamin B12 is seen in strict vegetarians. o Partial or complete gastrectomy leads to decreased intrinsic factor and hence Vitamin B12. o Insufficient production of intrinsic factor/gastric HCL in older people also leads to deficiency of Vitamin B12. Functions: o Synthesis of methionine from homocysteine with the help of enzyme methionine synthase. o Also helps in formation of succinyl CoA.  Chemical nature: o The empirical formula of vitamin B12 is C63H90N14O14PCo. o The structure of cobalamin consists of corrin ring with a central cobalt atom. o The cobalt atom has a substituent group. This may be cyanide (cyano-cobalamin) or hydroxyl (hydroxy- cobalamin) or nitrite (nitro-cobalamin). o There are two coenzymes of vitamin B12: 5’-deoxyadenosyl cobalamin and methyl-cobalamin. Vitamin like compounds/accessory factors: o Choline: It is trimethyl hydroxy ethanolamine. It is synthesized in the body from serine. Also obtained from dietary sources like milk, eggs, liver, cereals etc. Functions: » Choline as a component of phospholipids is involved in membrane structure and lipid transport. » Prevents accumulation of fat in liver (lipotropic factor). » Due to presence of three methyl group, it is actively involved in one carbon metabolism. » Choline is the precursor for the synthesis of acetyl choline. o Inositol: It is hexahydroxy cyclohexane. Functions: » Required for the synthesis of lipositol, which is a constituent of cell membrane. » Also acts as lipotropic factor (along with choline). » Acts as second messenger for some hormones. » Its concentration in heart muscle is high. o Lipoic acid: Sulfur containing fatty acid. It is fat as well as water soluble. Functions: » Involved in decarboxylation reactions along with vitamins. » It reduces face radicals in brain that contribute to Alzheimer’s disease. » Reduces insulin resistance. » May be useful in prevention of stroke and myocardial infraction. o Para-amino benzoic acid (PABA): Structural constituents of folic acid. It may be regarded as vitamin other than vitamin. Functions: » PABA is synthesized by bacteria and is essential for their growth. » Sulfonilamide is structural analogue of PABA. It competes with PABA and acts as bacteriostatic agent. o Bioflavonoids: It is a type of flavonoids isolated from lemon peel, responsible for maintainance of normal capillary permeability. Functions: » They acts as anti-oxidants and protects ascorbic acid from being destroyed. » They are used to correct vascular abnormality in humans. » Found in peel and pulp of citrus fruits and tobacco leaves. o Anti-vitamins: Antagonists to the action of vitamins. E.g., Dicumarol, warfarin, isoniazid, sulphonilamide, thiaminase, deoxy-pyridoxin etc. END