Vitamins PDF

Vitamins Vitamins are a group of organic nutrients, required in small quantities for a variety of biochemical functions that, generally, cannot be synthesized by the body and must therefore be supplied in the diet. The lipid-soluble vitamins are hydrophobic compounds that can be absorbed efficien...

Vitamins Vitamins are a group of organic nutrients, required in small quantities for a variety of biochemical functions that, generally, cannot be synthesized by the body and must therefore be supplied in the diet. The lipid-soluble vitamins are hydrophobic compounds that can be absorbed efficiently only when there is normal fat absorption. Like other lipids, they are transported in the blood in lipoproteins or attached to specific binding proteins. They have diverse functions; vitamin A, vision and cell differentiation; vitamin D, calcium and phosphate metabolism, and cell differentiation; vitamin E, anti-oxidant; vitamin K, blood clotting. As well as dietary inadequacy, conditions affecting the digestion and absorption of the lipid- soluble vitamins, such as steatorrhea and disorders of the biliary system, can all lead to deficiency syndromes including, - night blindness and xerophthalmia (vitamin A); - rickets in young children and osteomalacia in adults (vitamin D); - neurologic disorders and hemolytic anemia of the newborn (vitamin E); - hemorrhagic disease of the newborn (vitamin K). Toxicity can result from excessive intake of vitamins A and D. Vitamin A and the carotenes (many of which are precursors of vitamin A), and vitamin E are antioxidants and have possible roles in prevention of atherosclerosis and cancer. Vitamin A Retinoids comprise retinol, retinaldehyde, and retinoic acid (preformed vitamin A, found only in foods of animal origin); Carotenoids, found in plants, are composed of carotenes and related compounds; Many are precursors of vitamin A, as they can be cleaved to yield retinaldehyde, then retinol and retinoic acid -Carotene and other provitamin A carotenoids are cleaved in the intestinal mucosa by carotene dioxygenase, yielding retinaldehyde, which is reduced to retinol, esterified and secreted in chylomicrons together with esters formed from dietary retinol. Rhodopsin, the visual pigment of the rod cells in the retina, consists of 11-cis retinal specifically bound to the protein opsin. When rhodopsin is exposed to light, a series of photochemical isomerizations occurs, which results in the bleaching of the visual pigment and release of all-trans retinal and opsin. This process triggers a nerve impulse that is transmitted by the optic nerve to the brain. Regeneration of rhodopsin requires isomerization of all-trans retinal back to 11-cis retinal. All-trans retinal, after being released from rhodopsin, is reduced to all-trans retinol, esterfied, and isomerized to 11-cis retinol that is oxidized to 11-cis retinal. The latter combines with opsin to form rhodopsin, thus completing the cycle. Similar reactions are responsible for color vision in the cone cells. A major role of vitamin A is in the control of cell differentiation and turnover. All-trans -retinoic acid and 9-cis retinoic acid regulate growth, development, and tissue differentiation; they have different actions in different tissues. Like the thyroid and steroid hormones and vitamin D, retinoic acid binds to nuclear receptors that bind to response elements of DNA and regulate the transcription of specific genes Deficiency Vitamin A deficiency is the most important preventable cause of blindness. The earliest sign of deficiency is a loss of sensitivity to green light, followed by impairment to adapt to dim light, followed by night blindness. More prolonged deficiency leads to xerophthalmia: keratinization of the cornea and blindness. Vitamin A also has an important role in differentiation of immune system cells, and even mild deficiency leads to increased susceptibility to infectious diseases. Also, the synthesis of retinol binding protein is reduced in response to infection (it is a negative acute phase protein ), decreasing the circulating concentration of the vitamin, and further impairing immune responses. There is only a limited capacity to metabolize vitamin A, and excessive intakes lead to accumulation beyond the capacity of binding proteins, so that unbound vitamin A causes tissue damage. Symptoms of toxicity affect; the central nervous system (headache, nausea, ataxia, and anorexia, all associated with increased cerebrospinal fluid pressure); the liver (hepatomegaly with histologic changes and hyperlipidemia); calcium homeostasis (thickening of the long bones, hypercalcemia, and the skin (excessive dryness). calcification of soft tissues); Vitamin D Its main function is in the regulation of calcium absorption and homeostasis; most of its actions are mediated by way of nuclear receptors that regulate gene expression. It also has a role in regulating cell proliferation and differentiation. There is evidence that intakes considerably higher than are required to maintain calcium homeostasis reduce the risk of insulin resistance, obesity and the metabolic syndrome, as well as various cancers. Deficiency, leading to rickets in children and osteomalacia in adults, continues to be a problem in northern latitudes, where sunlight exposure is inadequate. Diet: Ergocalciferol (vitamin D2), found in plants, and cholecalciferol (vitamin D3), found in animal tissues, are sources of preformed vitamin D activity. Endogenous Source: 7-Dehydrocholesterol, an intermediate in cholesterol synthesis, is converted to cholecalciferol in the dermis and epidermis of humans exposed to sunlight. Preformed vitamin D is a dietary requirement only in individuals with limited exposure to sunlight. Vitamins D2 and D3 are not biologically active, but are converted in vivo to the active form of the D vitamin by two sequential hydroxylation reactions. The first hydroxylation occurs at the 25-position, and is catalyzed by a specific hydroxylase in the liver. The product of the reaction, 25-hydroxy cholecalciferol is the predominant form of vitamin D in the plasma and the major storage form of the vitamin. 25-OH-D3 is further hydroxylated at the 1 position by 25- hydroxy cholecalciferol 1-hydroxylase found primarily in the kidney, resulting in the formation of 1,25-diOH-D3 (calcitriol) The main function of vitamin D is in the control of calcium homeostasis, and in turn, vitamin D metabolism is regulated by factors that respond to plasma concentrations of calcium and phosphate. Calcitriol acts to reduce its own synthesis by inducing the 24-hydroxylase and repressing the 1-hydroxylase in the kidney. The principal function of vitamin D is to maintain the plasma calcium concentration. Calcitriol achieves this in three ways: It increases intestinal absorption of calcium; it reduces excretion of calcium (by stimulating resorption in the distal renal tubules); it mobilizes bone mineral Deficiency In the vitamin D deficiency disease rickets, the bones of children are undermineralized as a result of poor absorption of calcium. Osteomalacia in adults results from the demineralization of bone, especially in women who have little exposure to sunlight, especially after several pregnancies. Although vitamin D is essential for prevention and treatment of osteomalacia in the elderly, there is little evidence that it is beneficial in treating osteoporosis. Some infants are sensitive to intakes of vitamin D, resulting in an elevated plasma concentration of calcium. This can lead to contraction of blood vessels, high blood pressure, and calcinosis —the calcification of soft tissues. Although excess dietary vitamin D is toxic, excessive exposure to sunlight does not lead to vitamin D poisoning, because there is a limited capacity to form the precursor, 7- dehydrocholesterol, and prolonged exposure of previtamin D to sunlight leads to formation of inactive compounds. Vitamin E It acts as a lipid-soluble antioxidant in cell membranes, where many of its functions can be provided by synthetic antioxidants Is important in maintaining the fluidity of cell membranes. It also has a (relatively poorly defined) role in cell signaling. Vitamin E is the generic descriptor for two families of compounds, the tocopherols and the tocotrienols. The main function of vitamin E is as a chain-breaking, free-radical-trapping antioxidant in cell membranes and plasma lipoproteins by reacting with the lipid peroxide radicals formed by peroxidation of polyunsaturated fatty acids. The tocopheroxyl radical product is relatively unreactive, and ultimately forms nonradical compounds. Commonly, the tocopheroxyl radical is reduced back to tocopherol by reaction with vitamin C from plasma. The resultant monodehydroascorbate radical then undergoes enzymic or nonenzymic reaction to yield ascorbate and dehydroascorbate, neither of which is a radical. Deficiency Dietary deficiency of vitamin E in humans is unknown, although patients with severe fat malabsorption, cystic fibrosis, and some forms of chronic liver disease suffer deficiency because they are unable to absorb the vitamin or transport it, exhibiting nerve and muscle membrane damage. Premature infants are born with inadequate reserves of the vitamin. The erythrocyte membranes are abnormally fragile as a result of peroxidation, leading to hemolytic anemia. Vitamin K Vitamin K is the cofactor for the carboxylation of glutamate residues in the post-synthetic modification of proteins to form the unusual amino acid -carboxyglutamate. Prothrombin and several other proteins of the blood clotting system (Factors VII, IX, and X, and proteins C and S) each contain -carboxyglutamate residues. -Carboxyglutamate chelates calcium ions, and so permits the binding of the blood clotting proteins to membranes. In vitamin K deficiency, or in the presence of warfarin, an abnormal precursor of prothrombin (preprothrombin) containing little or no -carboxyglutamate, and incapable of chelating calcium, is released into the circulation. The water-soluble vitamins are composed of the B vitamins and vitamin C; They function mainly as enzyme cofactors. Deficiency of a single vitamin of the B complex is rare, since poor diets are most often associated with multiple deficiency states. Nevertheless, specific syndromes are characteristic of deficiencies of individual vitamins, beriberi (thiamin); cheilosis, glossitis, seborrhea (riboflavin); pellagra (niacin); megaloblastic anemia, methylmalonic aciduria, and pernicious anemia (vitamin B12); megaloblastic anemia (folic acid); scurvy (vitamin C). Vitamin B1 Thiamin has a central role in energy-yielding metabolism, and especially the metabolism of carbohydrates. Thiamin diphosphate is the coenzyme for three multi-enzyme complexes that catalyze oxidative decarboxylation reactions: Vitamin B1 Thiamin diphosphate is the coenzyme for three multi-enzyme complexes that catalyze oxidative decarboxylation reactions: pyruvate dehydrogenase in carbohydrate metabolism; -ketoglutarate dehydrogenase in the citric acid cycle; and the branched-chain keto-acid dehydrogenase involved in the metabolism of leucine, isoleucine, and valine Deficiency Thiamin deficiency can result in: a chronic peripheral neuritis, beriberi, which may or may not be associated with heart failure and edema. General symptoms include; loss of appetite and overall lassitude, digestive irregularities, and a feeling of numbness and weakness in the limbs and extremities In dry beriberi, there is a gradual degeneration of the long nerves, first of the legs and then of the arms, with associated atrophy of muscle and loss of reflexes. In wet beriberi, a more acute form, there is edema resulting largely from cardiac failure and poor circulation Deficiency Wernicke encephalopathy with Korsakoff psychosis, which is associated especially with alcohol and narcotic abuse. The syndrome is actually two separate conditions that can occur at the same time, Wernicke’s disease (WD) and Korsakoff syndrome. Usually, people get the symptoms of WD first. WD is also known as Wernicke’s encephalopathy. Symptoms of WKS may include confusion, changes to the eyes and vision, or exaggerated storytelling, among others. Alcoholism, or chronic alcohol misuse, is the most common cause of WKS. WKS can also be linked to diet deficiencies or other medical conditions that impair the absorption of vitamin B1. Deficiency The role of thiamin diphosphate in pyruvate dehydrogenase means that in deficiency there is impaired conversion of pyruvate to acetyl CoA. In subjects on a relatively high carbohydrate diet, this results in increased plasma concentrations of lactate and pyruvate, which may cause life-threatening lactic acidosis. Vitamin B2 Riboflavin provides the reactive moieties of the coenzymes flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD). FMN is formed by ATP-dependent phosphorylation of riboflavin, whereas FAD is synthesized by further reaction with ATP in which its AMP moiety is transferred to FMN. The main dietary sources of riboflavin are milk and dairy products. In addition, because of its intense yellow color, riboflavin is widely used as a food additive. Vitamin B2 Riboflavin functions as the precursor or building block for two coenzymes (dihydrolipoyl dehydrogenase [glycation] & succinate dehydrogenase [TCA cycle]) that are important in energy production. Deficiency Although riboflavin is centrally involved in lipid and carbohydrate metabolism, and deficiency occurs in many countries, it is not fatal, because there is very efficient conservation of tissue riboflavin. Riboflavin released by the catabolism of enzymes is rapidly incorporated into newly synthesized enzymes. Riboflavin nutritional status is assessed by measurement of the activation of erythrocyte glutathione reductase by FAD added in vitro. Vitamin B3 Niacin was discovered as a nutrient during studies of pellagra. It is not strictly a vitamin since it can be synthesized in the body from the essential amino acid tryptophan. Two compounds, nicotinic acid and nicotinamide, have the biologic activity of niacin; its metabolic function is as the nicotinamide ring of the coenzymes NAD and NADP in oxidation/reduction reactions. In addition to its coenzyme role, NAD is the source of ADP-ribose for the ADP-ribosylation of proteins and polyADP-ribosylation of nucleoproteins involved in the DNA repair mechanism. Deficiency Pellagra is characterized by a photosensitive dermatitis. As the condition progresses, there is dementia and possibly diarrhea. Untreated pellagra is fatal. Although the nutritional etiology of pellagra is well established, and tryptophan or niacin prevents or cures the disease, additional factors, including deficiency of riboflavin or vitamin B6 , both of which are required for synthesis of nicotinamide from tryptophan, may be important. In most outbreaks of pellagra, twice as many women as men are affected, probably the result of inhibition of tryptophan metabolism by estrogen metabolites. Vitamin B6 Six compounds have vitamin B6 activity: pyridoxine, pyridoxal, pyridoxamine, and their 5'- phosphates. The active coenzyme is pyridoxal 5'-phosphate. Some 80% of the body's total vitamin B6 is pyridoxal phosphate in muscle, mostly associated with glycogen phosphorylase. This is not available in deficiency, but is released in starvation, when glycogen reserves become depleted, and is then available, especially in liver and kidney, to meet increased requirement for gluconeogenesis from amino acids. Pyridoxal phosphate is a coenzyme for many enzymes involved in amino acid metabolism, especially transamination and decarboxylation. It is also the cofactor of glycogen phosphorylase, where the phosphate group is catalytically important. In addition, B6 is important in steroid hormone action. Pyridoxal phosphate removes the hormone- receptor complex from DNA binding, terminating the action of the hormones. Deficiency Although clinical deficiency disease is rare, there is evidence that a significant proportion of the population have marginal vitamin B6 status. Moderate deficiency results in abnormalities of Tryptophan and methionine metabolism. Increased sensitivity to steroid hormone action may be important in the development of hormone-dependent cancer of the breast, uterus, and prostate, and vitamin B6 status may affect the prognosis. Biotin The structures of biotin, biocytin, and carboxybiotin (the active metabolic intermediate), Biotin is widely distributed in many foods as biocytin ( -amino-biotinyllysine), which is released on proteolysis. It is synthesized by intestinal flora. Deficiency is unknown, except among people maintained for many months on total parenteral nutrition, and a very small number who eat abnormally large amounts of uncooked egg white, which contains avidin, a protein that binds biotin and renders it unavailable for absorption. Biotin functions to transfer carbon dioxide in a small number of reactions: acetyl-CoA carboxylase, pyruvate carboxylase, propionyl-CoA carboxylase, and methylcrotonyl-CoA carboxylase. Biotin also has a role in regulation of the cell cycle. Panthotenic acid Pantothenic acid has a central role in acyl group metabolism when acting as the pantetheine functional moiety of coenzyme A or acyl carrier protein (ACP). The pantetheine moiety is formed after combination of pantothenate with cysteine, which provides the–SH prosthetic group of CoA and ACP. CoA takes part in reactions of the citric acid cycle, fatty acid oxidation, acetylations and cholesterol synthesis. ACP participates in fatty acid synthesis. The vitamin is widely distributed in all food-stuffs, and deficiency has not been unequivocally reported in humans except in specific depletion studies. Vitamin B12 The term "vitamin B12 " is used as a generic descriptor for the cobalamins —those corrinoids (cobalt- containing compounds possessing the corrin ring) having the biologic activity of the vitamin. Some corrinoids that are growth factors for microorganisms. Although it is synthesized exclusively by microorganisms, for practical purposes vitamin B12 is found only in foods of animal origin, there being no plant sources of this vitamin. This means that strict vegetarians (vegans) are at risk of developing B12 deficiency. The small amounts of the vitamin formed by bacteria on the surface of fruits may be adequate to meet requirements, but supplements of vitamin B12 made by bacterial fermentation are available. Methylmalonyl CoA mutase, leucine aminomutase, and methionine synthase are vitamin B12–dependent enzymes Pernicious anemia arises when vitamin B12 deficiency impairs the metabolism of folic acid, leading to functional folate deficiency that disturbs erythropoiesis, causing immature precursors of erythrocytes to be released into the circulation (megaloblastic anemia). The most common cause of pernicious anemia is failure of the absorption of vitamin B12 rather than dietary deficiency. Folic Acid The active form of folic acid (pteroyl glutamate) is tetrahydrofolate. The folates in foods may have up to seven additional glutamate residues linked by -peptide bonds. In addition, all of the one-carbon substituted folates may also be present in foods. Tetrahydrofolate can carry one-carbon fragments attached to N -5 (formyl, formimino, or methyl groups), N -10 (formyl) or bridging N -5–N -10 (methylene or methenyl groups). When acting as a methyl donor, S -adenosyl methionine forms homocysteine, which may be remethylated by methyl-tetrahydrofolate catalyzed by methionine synthase, a vitamin B12 –dependent enzyme. As the reduction of methylene-tetrahydrofolate to methyl-tetrahydrofolate is irreversible and the major source of tetrahydrofolate for tissues is methyl-tetrahydrofolate, the role of methionine synthase is vital, and provides a link between the functions of folate and vitamin B12. Impairment of methionine synthase in vitamin B12 deficiency results in the accumulation of methyltetrahydrofolate—the "folate trap." There is therefore functional deficiency of folate, secondary to the deficiency of vitamin B12 Deficiency of folic acid itself or deficiency of vitamin B12 , which leads to functional folic acid deficiency, affects cells that are dividing rapidly because they have a large requirement for thymidine for DNA synthesis. Clinically, this affects the bone marrow, leading to megaloblastic anemia. Vitamin C Vitamin C is a vitamin for humans and other primates, the guinea pig, bats, passeriform birds, and most fishes and invertebrates; other animals synthesize it as an intermediate in the uronic acid pathway of glucose metabolism. In those species for which it is a vitamin, there is a block in the pathway as a result of absence of gulonolactone oxidase. Both ascorbic acid and dehydroascorbic acid have vitamin activity. Ascorbic acid has specific roles in the copper-containing hydroxylases and the -ketoglutarate-linked iron containing hydroxylases. In addition, it has a number of nonenzymic effects as a result of its action as a reducing agent and oxygen radical quencher. Dopamine -hydroxylase is a copper-containing enzyme involved in the synthesis of the catecholamines (norepinephrine and epinephrine), from tyrosine in the adrenal medulla and central nervous system. During hydroxylation the Cu+ is oxidized to Cu2+ ; reduction back to Cu+ specifically requires ascorbate, which is oxidized to monodehydroascorbate. Deficiency Signs of vitamin C deficiency include skin changes, fragility of blood capillaries, tooth loss, and bone fracture, many of which can be attributed to deficient collagen synthesis. At intakes above about 100 mg/day, the body's capacity to metabolize vitamin C is saturated, and any further intake is excreted in the urine. However, in addition to its other roles, vitamin C enhances the absorption of iron, and this depends on the presence of the vitamin in the gut. Therefore, increased intakes may be beneficial. There is very little good evidence that high doses of vitamin C prevent the common cold, although they may reduce the duration and severity of symptoms.