Addition to oxygen, water, proteins, fats, carbohydrates and inorganic salts, a number of organic compounds are also necessary for the life, growth and health of animals including man. These compounds are known as the accessory dietary factors or vitamins and are only necessary in very small amounts.
The absence of vitamins results in deficiency diseases. Vitamins are necessary because all vitamins cannot be synthesized inside the body by animals including man.
Definition: Vitamins are defined as organic compound occurring in natural food either as such as or as utilizable precursors which are required in minute amount for normal growth, maintenance and reproduction.
The absence of these results in deficiency diseases. Most of the vitamins are supplied by the diet; very few vitamins which are synthesized in the intestine belong to the vitamins ‘B’ group.
The term vitamin was derived from ‘vitamine’, a combination word from vital and amine, because it was suggested that the organic micronutrient food factors which prevented beriberi and perhaps other similar dietary-deficiency diseases, might be chemical amines. This proved incorrect for the micronutrient class, and the word was shortened. Today, a chemical compound is called a vitamin when it cannot be synthesized in sufficient quantities by an organism, and must be obtained from the diet. For example, ascorbic acid (vitamin C) is a vitamin for humans, but not for most other animals, and biotin and vitamin D are required in the human diet only in certain circumstances. The term vitamin does not include other essential nutrients such as dietary minerals, essential fatty acids or essential amino acids, nor does it encompass the large number of other nutrients that promote health but are otherwise required less often.
Vitamins are classified by their biological and chemical activity, not their structure. Thus, each ‘vitamin’ refers to a number of vitamer compounds that show the biological activity associated with a particular vitamin. Such a set of chemicals are grouped under an alphabetized vitamin ‘generic descriptor’ title, such as ‘vitamin A’, which includes the compounds retinal, retinol and four known carotenoids. Vitamers by definition are convertible to the active form of the vitamin in the body, and are sometimes inter-convertible to one another, as well.
Table 6.1 Fat Soluble Vitamins
Vitamins have diverse biochemical functions. Some have hormone-like functions as regulators of mineral metabolism (e.g. vitamin D), or regulators of cell and tissue growth and differentiation (e.g. some forms of vitamin A). Others functions as antioxidants (e.g. vitamin E and sometimes vitamin C). The largest numbers of vitamins (e.g. B complex vitamins) function as precursors for enzyme cofactors, that help enzymes in their work as catalyzts in metabolism. In this role, vitamins may be tightly bound to enzymes as part of prosthetic groups: for example, biotin is part of enzymes involved in making fatty acids. Alternately, vitamins may also be less tightly bound to enzyme catalyzts as coenzymes, detachable molecules which function to carry chemical groups or electrons between molecules. For example, folic acid carries various forms of carbon group methyl, formyl and methylene-in the cell. Although these roles in assisting enzyme-substrate reactions are vitamins’ best-known function, the other vitamin functions are equally important.
Until the 1900s, vitamins were obtained solely through food intake, and changes in diet (which, for example, could occur during a particular growing season) can alter the types and amounts of vitamins ingested. Vitamins have been produced as commodity chemicals and made widely available as inexpensive pills for several decades, allowing supplementation of the dietary intake.
Table 6.2 Water Soluble Vitamins
Vitamins are classified as either water-soluble or fat soluble. In humans, there are 13 vitamins: 4 fat-soluble (A, D, E and K) and 9 water-soluble (8 B group of vitamins and vitamin C) that are important. Many types of water-soluble vitamins are synthesized by bacteria.
Fat-soluble vitamins are absorbed through the intestinal tract with the help of lipids (fats). Because they are more likely to accumulate in the body, they are more likely to lead to hypervitaminosis than are water-soluble vitamins. Fat-soluble vitamin regulation is of particular significance in cystic fibrosis.
Fat soluble in non-polar organic solvents, that is, water soluble vitamins are extract from food with aqueous solvents.
Fat soluble vitamins are A, D, E and K. Water-soluble vitamins are vitamin B complex and vitamin C. Fat soluble vitamins are non-polar, hydrophobic molecules. They have isoprene derivatives. They are stored in liver, bile salts and fats are essential for their absorption and normally, not excreted in urine.
Water-soluble vitamins are soluble in water, they are easily absorbed except vitamin B12 ; they are not stored in the body they are excreted in the urine
A number of naturally occurring pigments can be converted into Vitamin A [Retinol] by animal tissue. These pigments known as the carotenoid pigments are found primarily in green leaves and yellow vegetables. A number of carotenoid pigments of plant act as precursors of vitamin A. Animal can consume these pigments and bring chemical alteration in them to produce vitamin A.
McCollum and Davis in 1915 announced that ether extracts of butter or of egg yolk contain some organic complex essential for continued growth of rats on the diets employed. This substance was termed ‘fat soluble A’ by McCollum and now, of course, is known as vitamin A. Xerophthalmia in rats was shown to be due to a deficiency of ‘fat soluble A’ by McCollum and Simmonds in 1917.
Structure and Properties of Vitamin A
β-Carotene is a symmetrical molecule containing two β-ionone rings connected by a carbon chain. It has the following structure shown in Figure 6.1. The two rings in β-Carotene are marked as A and B rings. The formula of α-Carotene can be indicated by showing the difference in the B ring of this pigment compared to the B ring of β-Carotene. The remainder of the molecule is the same. Since the A ring in these pigment is a β-ionone ring, these compounds are vitamin A precursors.
The central double bond of β-Carotene can be oxidized, and after scission at that point it is theoretically possible that two molecule of vitamin A result. Other carotene such as α and γ carotene (Figure 6.1), cannot yield more than one molecule of the vitamin on oxidative scission. This is because a α-ionone ring is an essential part of the vitamin A molecule (vitamin A1) and β-carotene contains two such rings, α- and γ- carotene each have but one β-ionone ring. The second ring in these two pigments varies in structure, and there is no vitamin A activity associated with this part of the molecule after oxidation at the central double bond.
Table 6.3 Water Soluble Vitamins (All Water Soluble Vitamins are Soluble in Hydrophilic Environment)
Vitamin A1 (retinol1), C20H29OH and Vitamin A2 (retinol2) C20H27OH, are alcohols with the accompanying structures. The structure of vitamin A1 differ from the structure of vitamin A2, vitamin A2 contains one more double bond in the ring.
Vitamin A is soluble in fat solvents and insoluble in water. It is viscous, colourless oil or pale yellowish substance. Heat stable in absence of air. Vitamin A can be destroyed on exposure to air or ultra-violet rays.
Coenzyme Activity: Vitamin A has no coenzyme activity.
Physiological Functions of Vitamin A and Carotenoids
Role of Vitamin A in Vision: Wald described in vitro synthesis of rhodopsin in a system containing (i) vitamin A, the precursor of retinene; (ii) opsin, the protein of rhodopsin and (iii) liver alcohol dehydrogenase, which bring about oxidation of vitamin A to retinene.
Table 6.4 Fat Soluble Vitamins (All Fat Soluble Vitamins are Soluble in Hydrophobic Environment)
Figure 6.1 Structure of Carotenes
Vitamin A as well as the retinenes exists in various cis-trans isomeric forms due to the conjugated double bonds. Only one isomer, the neo-b or 11-cis retinene, unites with opsin to form rhodopsin. Neo-b vitamin A was synthesized and converted into neo-b retinene. The aldehyde condenses with opsin to form rhodopsin, thereby establishing the physiological activity of the 11-cis isomer.
Rhodopsin has light absorbing property due to polyene group of 11-cis retinal.
When light falls on, rhodopsin splits into opsin and all trans retinal. All trans retinal may be isomerized to its 11-cis isomer in the presence of blue light but in the eye this isomerization is not significant. All the trans retinol from the blood can be converted to all trans retinal by retinene reductase by making use of NAD+ and all trans retinal then can be isomerized to its cis isomer.
All trans retinol from blood can be first isomerized to 11-cis retinol. All 11-cis retinol then can be converted to 11-cis retinal by retinol dehydrogenase in the presence of co-enzyme NADP+. Thus, the visual process involves continual removal of the active retinol from the blood into retinal (Figure 6.2).
Figure 6.2 The Rhodopsin Cycle
Cardiovascular Disease Prevention
Carotenoids may play a role in preventing cardiovascular disease in persons at high risk, possibly linked to carotenoids antioxidant capability.
Coupled with usability to aid immune system activity, vitamin A may be valuable to in the fight against cancer.
Absorption of Vitamin A
The dietary intake of vitamin A in the form of vitamin A esters are hydrolyzed in the lumen of the intestine by the enzyme lipase in the presence of bile salts and fats. The vitamin and the carotene are taken up by the intestinal mucosa where vitamin is esterified and carotene is converted first to retinal and than to retinol by retinol dehydrogenase (this enzyme present in the liver serum). These esters which are not the precursors of vitamin A are absorbed and enter the intestinal lymphatics and finally to circulation in the form of chylomicrons. In the blood, the vitamin esters are attached to β-lipoprotein and are taken up by the liver. The vitamin is then released as retinol-binding protein for use anywhere required.
95 per cent of vitamin A in the form of esters is stored in the liver. Small amount of vitamin A is also present in other tissues, for example, lactating breast, adrenals, lungs and intestine.
Sources of Vitamin A
Plant Sources: All leafy green vegetables which supply pro vitamin A (Carotene) in the diet. All pigmented vegetables and fruits, for example, carrots, papayas, tomatoes, sweet potatoes, pumpkins and apricots.
Animal Sources: Many marine fish oils, especially the liver oils of Soupfin shark, lingcod, haliput and sword fish.
|During pregnancy and lactation||6000–8000 I.U.|
|1 I.U.||0.3 μg of retinol|
|0.6 μg of β-carotene|
|Normal concentration of Vitamin A in blood||24-60 I.U./dl or 0.84-2.10 μmol/l.|
Deficiency of Vitamin A
- Eyes: There are various eye conditions due to deficiency of vitamin A. Night blindness or nyctalopia, is one of the early symptoms of vitamin A deficiency. In more severe cases of deficiency of vitamin A in children resulting to xerosis and keratomalacia. The eyelids stick together as a result of a purulent discharge. Small ulcers may appear on the cornea. Xerophthalmia with resulting blindness is common in the poor children due to deficiency of vitamin A.
- Bones and Teeth: The bone growth is impaired due to deficiency of vitamin A. Teeth are derived from epithelial tissue, and so it is logical to expect a correlation between dietary vitamin A and tooth development.
- Skin: Deficiency of vitamin A has been associated with specific skin lesions. The deficiency leads to dryness and roughness of the skin.
- Urolithiasis: This is the condition in which urinary calculi are present and is known as urolithiasis. The calculi were composed of calcium phosphate, the deficiency of vitamin A allows keratinization of the genitourinary tract epithelium followed by bacterial invasion and alkalinuria.
- Carbohydrate Metabolism: Vitamin A has a specific function in the carbohydrate metabolism. Vitamin A plays a role in glucose synthesis from triose molecule.
Hypervitaminosis of Vitamin A
Excess vitamin A intake in human leads to number of symptoms like headache, nausea, vomiting and drowsiness.
Vitamin D is a group of fat-soluble secosteroids, the two major physiologically relevant forms of which are vitamin D2 (ergocalciferol) and vitamin D3 (cholecalciferol). Vitamin D without a subscript refers to either D2 or D3 or both. Vitamin D is produced in the skin of vertebrates after exposure to ultraviolet B light, and occurs naturally in a small range of foods. In some countries, staples such as milk, flour and margarine are artificially fortified with vitamin D, and it is also available as a supplement in pill form.
Vitamin D discovered by Elmer McCollum in 1922. McCollum and co-workers demonstrated that cod liver oil contains a specific substance concerned with calcium deposition in rachitic rats. In 1924, Steenbock and co-workers and Hess reported that the irradiation of certain foods with uv (ultraviolet) light endowed them with antirachitic (Vitamin D) activity. Angus and co-workers in 1931 isolated crystalline vitamin D. Vitamin D was obtained upon ultraviolet irradiation of ergosterol, this was named calciferol and is referred as vitamin D2.
Structure and Properties of Vitamin D
Ergosterol occurs in plants and 7-dehydrocholesterol occurs in animals. Ergosterol is unsaturated and contains extra methyl group in its side chain than 7-dehydrocholesterol. Ultraviolet rays from sunlight cleaves B ring of both compounds. Ergocalciferiol (Vitamin D2) is formed in plants and cholecalciferol (Vitamin D3) is formed upon exposure of skin to sunlight. Both vitamin D2 and vitamin D3 are of equal potency giving rise to D2 calcitriol and D3 calcitriol. As far as nutrition is concerned, vitamin D2 and vitamin D3 are important. The structure of Ergocalciferiol (Vitamin D2) is the same as that of cholecalciferol (Vitamin D3) except that the side chain on position 17 is that of cholesterol. Vitamin D2 has extra double bond and extra methyl group in the side chain as compare to vitamin D3 (Figure 6.3). Ergosterol does not absorb visible light but does absorb various wavelengths in the uv spectrum. The absorption maxima are at 260, 270, 282 and 293.5 mμ.
When ergosterol dissolved in alcohol, benzene, ether, etc., is irradiated with ultraviolet light, a series of photochemical reactions takes place. Pro vitamin D3 are synthesized in the body of man and other mammals. This is then activated in the skin by sunlight or ultraviolet rays and carried to various organs in the body for utilization or storage in the liver.
Properties: Soluble in fat solvents but insoluble in water, heat stable, white crystalline material, ordinary boiling does not destroy it.
Physiological and Biochemical Function
Vitamin D3 when given to rachitic animals increases the permeability of the intestinal mucosa cells to calcium ion, apparently by changing the character of the plasma membrane to calcium permeation. It has been shown that vitamin D3 induces the appearance of a specific Calcium binding Protein (CaBP) in the intestinal mucosa of a number of animals. This protein has been isolated and purified; it has a molecular weight of 24,000 daltons and binds one atom of calcium per molecule of protein.
Figure 6.3 Activation of Pro vitamins of the Vitamin Group
Vitamin D behaves more like a hormone than as the cofactor of an enzyme. That is, its effect is in controlling the production of a specific calcium binding protein rather than influencing directly the activity of a specific enzyme.
Vitamin D has no co-enzyme activity.
- Vitamin D is readily absorbed in the small intestine.
- Since they are fat soluble, their absorption is enhanced by factor's which favour fat absorption such as sufficient quantity of bile salt.
Vitamin D is stored largely in liver, kidney Intestine, adrenal's and bones. A small amount of vitamin D is also excreted in bile but is partly reabsorbed in the intestine.
Liver of fish is a rich sources of vitamin D. Vitamin D is present in egg, butter and milk. The cheapest source is sunlight which forms vitamin D3 from 7-dehydrocholesterol in the skin.
|Infants and children||400 I.U.|
|Women during pregnancy and Lactation||400 I.U.|
Normal Concentration of Vitamin D in Blood
Deficiency of Vitamin D
Bow legs, knock knees, due to deficiency of vitamin D. The ankle knees, wrists, elbow are swollen due to swelling of epiphyseal cartilages. Without adequate calcium and phosphorous deposition during synthesis, bones, weaken and bow under pressure this disease is known as rickets in children and osteomalacia in adults (soft bones). It results from inefficient calcium absorption in the intestine or pure conservation of calcium by the kidney.
Hypervitaminosis of Vitamin D
Vitamin D brings about increased absorption of Ca (calcium) and P (phosphorous) from the intestine and does increased blood levels of these minerals. Hypervitaminosis D leads to anorexia, thirst, constipation and polyuria.
Vitamin E is a generic term for tocopherols and tocotrienols. Vitamin E is a family of α, β, γ and δ (respectively: alpha, beta, gamma and delta) tocopherols and corresponding four tocotrienols. Vitamin E is a fat-soluble antioxidant that stops the production of reactive oxygen species formed when fat undergoes oxidation. Of these, α-tocopherol (also written as alpha-tocopherol) has been most studied as it has the highest bioavailability. Mattill and Conklin reported that natural foods contain material specifically concerned with reproduction. They indicated that rats fed on a milk diet supplemented with yeast (B vitamins) and iron, were unable to bear young ones. In 1922, Bishop and Evans announced the existence of a factor X in certain foods and indicated the necessity of the substance in the diet for normal rat reproduction.
Structure and Properties of Tocopherol
Different Forms of Tocopherols: Vitamin E exists in eight different forms, four tocopherols and four tocotrienols. All feature a chromanal ring, with a hydroxyl group that can donate a hydrogen atom to reduce free radicals and a hydrophobic side chain which allows for penetration into biological membranes.
Both the tocopherols and tocotrienols occur in α, β, γ and δ forms, determined by the number of methyl groups on the chromanol ring. The α-tocopherol is most highly methylated. α-tocopherol 5,7,8 trimethyl-tocol (3-methyls groups at 5,7 and 8 carbon in the chromanol ring), (Figure 6.4) β-tocopherol 5,8 dimethyl-tocol (methyl group at 5 and 8 carbon in the chromanol ring), γ-tocopherol 7,8 dimethyl-tocol (methyl group at 7 and 8 carbon in the chromanol ring), δ-tocopherol 8-methyl-tocol (methyl group at 8 carbon in the chromanol ring). The tocotrienols have the same methyl structure at the ring and the same Greek letter-methyl-notation, but differ from the analogous tocopherols by the presence of three double bonds in the hydrophobic side chain. Each form has slightly different biological activity.
Figure 6.4 α-tocopherol Form of Vitamin E
α-tocopherol: α-tocopherol (5,7,8-trimethyl-tocol) is the most important lipid-soluble antioxidant and that it protects cell membranes from oxidation by reacting with lipid radicals produced in the lipid peroxidation chain reaction. This would remove the free radical intermediates and prevent the oxidation reaction from continuing. The oxidized α-tocopherol radicals produced in this process may be recycled back to the active reduced form through reduction by other antioxidants, such as ascorbate, retinol or ubiquinol. However, the importances of the antioxidant properties of this molecule at the concentrations present in the body are not clear and it is possible that the reason why vitamin E is required in the diet is unrelated to its ability to act as an antioxidant. Other forms of vitamin E have their own unique properties. For example, γ-tocopherol (also written as gamma-tocopherol) is a nucleophile that can react with electrophilic mutagens.
Physiological and Biochemical Function
Characteristic symptoms of a vitaminosis E vary with the animal species. In mature female rats, reproductive failure occurs. They may be pregnant but the foetus may die during the pregnancy and are absorbed from the uterus. With the male rat germinal tissue degenerates. With rabbits and guinea pigs acute muscular dystrophy results; in chickens vascular abnormalities occur. In humans, no well-defined syndrome of vitamin E deficiency has been detected. The most prominent effect that tocopherol has is in, in vitro systems is as a strong antioxidant activity. It has been suggested that the biochemical activity of tocopherol is its capacity to protect sensitive mitochondrial systems from irreversible inhibition by lipid peroxidase. Thus, in mitochondria prepared from tocopherol-deficient animals, there is a profound deterioration of mitochondrial activity because of hematin-catalyzed peroxidation of highly unsaturated fatty acids normally present in these particles.
Absorption and Storage
- It is absorbed in the intestine in the presence of bile salts.
- It is stored in the liver (mitochondria; microsomes) and fatty tissues.
- It is present in high concentration in the adrenals, the pituitary, the uterus and the testes.
In general, food sources with the highest concentrations of vitamin E are vegetable oils, followed by nuts and seeds including whole grains. Vitamin E originally extracted from wheat germ oil, most natural vitamin E supplements are now derived from vegetable oils, usually soybean oil.
Vitamin E Content per 100 g of Source include
Wheat germ oil (215.4 mg), Sunflower oil (55.8 mg), Almond oil (39.2 mg), Sunflower seed (35.17 mg), Almond (26.2 mg), Hazelnut (26.0 mg), Walnut oil (20.0 mg), Peanut oil (17.2 mg), Olive oil (12.0 mg), Poppy seed oil (11.4 mg), Peanut (9.0 mg), Pollard (2.4 mg), Maize (2.0 mg), Poppy seed (1.8 mg), Asparagus (1.5 mg), Oats (1.5 mg), Chestnut (1.2 mg), Coconut (1.0 mg), Tomatoes (0.9 mg), Walnut (0.7 mg), Carrots (0.6 mg), Goat's milk (0.1 mg).
A 100 g serving of certain fortified breakfast cereals may contain 24 mg (or more) vitamin E. The proportion of vitamin E to other tocopherols in a nutrient source varies greatly. For example, the tocopherol content is 96 per cent vitamin E in almonds and 9 per cent vitamin E in poppy seeds.
Recommended Daily Amount (RDA) for a 25-year old male for Vitamin E is 15 mg/day. The dietary reference intake (DRI) for vitamin E is based on the α-tocopherol form because it is the most active form as originally tested.
Vitamin E deficiency causes neurological problems due to poor nerve conduction. These include neuromuscular problems such as spinocerebellar ataxia and myopathies. Deficiency can also cause anaemia, due to oxidative damage to red blood cells.
Hypervitaminosis of Vitamin E
Few adverse effects of vitamin E have been reported if 80 times of the recommended intake has given, then it leads to increase congestive heart failure.
Vitamin K (K from ‘Koagulations-Vitamin’) denotes a group of lipophilic, hydrophobic vitamins that are needed for the post-translational modification of certain proteins, mostly required for blood coagulation, but also a number of other proteins which chelate calcium ion, and are involved in bone and other tissue metabolism. Chemically they are 2-methyl-1, 4-naphthoquinone derivatives.
Vitamin K1 is also known as phylloquinone or phytomenadione (also called phytonadione). Vitamin K2 (menaquinone, menatetrenone) is normally produced by bacteria in the large intestine, and dietary deficiency is extremely rare unless the intestines are heavily damaged, are unable to absorb the molecule or are subject to decreased production by normal flora, as seen in broad spectrum antibiotic use. There are three synthetic forms of vitamin K, vitamins K3, K4 and K5 which are used in many areas including the pet food industry (vitamin K3) and to inhibit fungal growth (vitamin K5).
In 1935, Almguist and Stakstav reported that fish meal was an excellent source of antihemorrhagic factor or vitamin K. They also showed that in alfalfa the factor was localized in the unsaponifiable fraction of the ether extract.
Dam, Karrer and their co-workers isolated the vitamin from alfalfa in 1939. In 1939, Doisy associates isolated the factor from both alfalfa and fish meal. The vitamin K was chemically different from the product obtained from fish meal. The vitamin K isolated from alfalfa is designated as vitamin K1 and vitamin K which was isolated from fish meal is designated as vitamin K2. Vitamin K1 is also known as phylloquinone or phytomenadione or phytomadione. Vitamin K2 is also known as menaquinone or menatetrenone.
Structure and Properties of Vitamin K
All members of vitamin K group share a methylated naphthoquinone ring structure and vary in the aliphatic side chain present at carbon number 3 of the nathoquinone ring. Vitamin K1 is 2-methyl-3-phytyo-1, 4-nathoquinone (phylloquinone) found in plants, has four isoprene units in its side chain one of which is unsaturated. Vitamin K2 (menaquinone) found in animals, contain in its side chain 6-isoprene units, each with a double bond. The side chain of vitamin K1 has phytol radical and the vitamin K2 side chain has difarnesyl radical. It is generally accepted that the naphthoquinone is the functional group, so that the mechanism of action is similar for all K vitamins. Substantial differences may be expected with respect to intestinal absorption, transport, tissue distribution and bio-availability. These differences are caused by the different lipophilicity of the various side chains. The two forms of vitamin K are derivatives of quinones and differ from each other in the composition of their side chain at carbon 3 of naphthoquinone ring (Figure 6.5).
Vitamin K has no co-enzyme activity.
Physiological and Biochemical Function
Vitamin K is involved in the carboxylation of certain glutamate residues in proteins to form γ-carboxyglutamate residues (abbreviated Gla-residues) (Figure 6.6). The modified residues are often (but not always) situated within specific protein domains called Gla domains. Gla-residues are usually involved in binding calcium. The Gla-residues are essential for the biological activity of all known Gla-proteins.
Figure 6.5 Structure of Vitamin K1 and K2
Figure 6.6 Vitamin K Acts as Cofactor of the Carboxylase that forms γ-carboxyglutamate Residues in Precursor Proteins
γ-carboxyglutamate residues now provide calcium binding sites in N-terminal position. This brings together activated factor and accelerin close to the phospholipid membrane of platelets. This enhances blood coagulation.
- Bone metabolism: Osteocalcin, also called bone Gla-protein (BGP), and matrix gla protein (MGP).
- Vitamin K acts as a cofactor of carboxylase that forms γ-carboxyglutamate residues in precursor proteins.
Bile salts help in absorption of vitamin K. The absorption is interrupted leading to haemorrhage in jaundice and other liver diseases when the bile secretion is very less.
It is present in significant amount in blood stream. Vitamin K stored in liver and in all other tissues in small amount. The faeces contain large amount of vitamin K which is produced by the bacterial flora, for example, E.coli.
Vitamin K1 is found chiefly in leafy green vegetables such as spinach, swiss chard and Brassica (e.g. cabbage, kale, cauliflower, broccoli and brussels sprouts); some fruits such as avocado and kiwifruit are also high in vitamin K.
It is believed that phylloquinone's tight binding to the thylakoid membranes in the chloroplasts is the reason behind the poor bioavailability of vitamin K in green plants. For example, cooked spinach has a 4 per cent bioavailability of phylloquinone. However, when one adds butter to the spinach, the bioavailability increases to 13 per cent due to the increased solubility of vitamin K in fat.
The US Dietary Reference Intake (DRI) for an Adequate Intake (AI) of vitamin K for a 25-year old male is 120 micrograms/day. The adequate intake (AI) of this phytonutrient for adult women is 90 micrograms/day, for infants is 10–20 micrograms/day, for children and adolescents 15–100 micrograms/day.
The deficiency of vitamin K leads to lowering of prothrombin level and increased clotting of blood, may leads to hemorrhagic conditions.
Vitamin K deficiency is caused by pancreatic dysfunction, biliary disease, atrophy of the intestinal mucosa. Sterilization of the large intestine by antibiotics can result in deficiency when dietary intake is limited. Osteoporosis and coronary heart disease are strongly associated with lower levels of K2 (menaquinone). Menaquinone is not inhibited by salicylates as happens with K1, so menaquinone supplementation can alleviate the chronic vitamin K deficiency caused by long-term aspirin use.
Hypervitaminosis of Vitamin K
Administration of too large doses of vitamin K (30 mg /per day for 3 days) to infants has been shown to produced hyper-bilirubinemia in some cases. There is no known toxicity associated with high doses of the phylloquinone (Vitamin K1) or menaquinone (Vitamin K2). The synthetic form of vitamin K, vitamin K3 (menadione) large doses have been shown to cause allergic reactions, hemolytic anaemia and cytotoxicity in liver cells.
IUPAC name 2-3-(4-amino- 2-methyl- pyrimidin- 5-yl) methyl-4-methyl- thiazol- 5-yl ethanol
Thiamine (pronounced ‘THIGH-a-min’) and named as the ‘thio-vitamine’ (thio means ‘sulphur-containing vitamin’) is a water-soluble vitamin of the B complex. First named aneurin for the detrimental neurological effects of its lack in the diet, it was eventually assigned the generic descriptor name vitamin B1. Its phosphate derivatives are involved in many cellular processes. The best characterized form is thiamine pyrophosphate (TPP), a coenzyme in the catabolism of sugars and amino acids. In yeast, TPP is also required in the first step of alcoholic fermentation.
Thiamine is synthesized in bacteria, fungi and plants. Animals must cover all their needs from their food and insufficient intake results in a disease called beriberi affecting the peripheral nervous system (polyneuritis) and/or the cardiovascular system, with fatal outcome if not cured by thiamine administration. In less severe deficiency, non-specific signs include malaise, weight loss, irritability and confusion.
Structure and Properties of Thiamine
Soon after the purification and crystallization of thiamine, it was evident that a pyrimidine nucleus was a part of the molecule and that there also was present a substituted thiazole ring. In the synthesis of Williams and co-workers, the substituted pyrimidine (2-methyl-5-bromomethyl-6-aminopyrimidine hydrobromide) was reacted with 4 methyl-5-β-hydroxyethylthiazole to yield the bromide-hydrobromide of the vitamin. The naturally occurring thiamine is a chloride-hydrochloride.
Thiamine is a colourless compound with a chemical formula C12H17N4OS. Its structure contains a pyrimidine ring and a thiazole ring linked by a methylene bridge. Thiamine is soluble in water, methanol, and glycerol and practically insoluble in acetone, ether, chloroform and benzene. It is stable at acidic pH, it is destroyed at elevated temperatures unless the pH is low. In alkaline solution, complete destruction of thiamine results from boiling for short periods. At a pH of 3.5 boiling results in little destruction. Thiamine is unstable to heat, but stable during cold storage. It is unstable when exposed to ultraviolet light and γ irradiation. In yeast, autoclaving at 120°C for short periods does not destroy the vitamin, but after 2 or 3 hours nearly complete destruction is achieved.
The structure of thiamine as a free base as shown in Figure 6.7. The naturally occurring molecule and the synthetic vitamin contain a hydrochloride on the amino group and a chloride ion neutralizing the positive charge on the nitrogen atom of the thiazole ring.
Figure 6.7 Structure of Thiamine Free Base
Some other foods rich in thiamine are oatmeal, flax and sunflower seeds, brown rice, whole grain rye, asparagus, kale, cauliflower, potatoes, oranges, liver (beef, pork and chicken) and eggs.
Thiamine hydrochloride (Betaxin) is a (when by itself) white, crystalline hygroscopic food-additive used to add a brothy/meaty flavour to gravies or soups.
It is difficult to fix a single requirement of vitamin B1. The requirement is increased when metabolism is elevated as in fever, hyperthyroidism, increased muscular activity, pregnancy and lactation. Fat and protein reduce while carbohydrate increases the daily requirement of the vitamin. Some of the thiamine is synthesized by the bacteria in the intestine. Deficiencies of the vitamin occur not only by poor dietary intake but also in persons suffering from organic diseases.
|Adults (males)||1.2–1.5 mg|
|Adult (female)||1.0–1.1 mg|
|Pregnant women||1.3–1.5 mg|
|Lactating women||1.3–1.5 mg|
Absorption and Transport
Thiamine is released by the action of phosphatase and pyrophosphatase in the upper small intestine. At low concentrations, the process is carrier mediated and at higher concentrations, absorption occurs via passive diffusion. Active transport is greatest in the jejunum and ileum (it is inhibited by alcohol consumption and by folic deficiency). Decline in thiamine absorption occurs at intakes above 5mg. The cells of the intestinal mucosa have thiamine pyrophosphokinase activity, but it is unclear whether the enzyme is linked to active absorption. The majority of thiamine present in the intestine is in the pyrophosphorylated form ThDP, but when thiamine arrives on the serosal side of the intestine it is often in the free form. The uptake of thiamine by the mucosal cell is likely coupled in some way to its phosphorylation/ dephosphorylation. On the serosal side of the intestine, evidence has shown that discharge of the vitamin by those cells is dependent on Na+-dependent ATPase.
Excess thiamine administered is not stored in the tissues. A part of the excess thiamine is excreted in urine and some of it is destroyed.
Well-known syndromes caused by thiamine deficiency include beriberi and Wernicke-Korsakoff syndrome, diseases also common with chronic alcoholism. Beriberi is a neurological and cardiovascular disease. The three major forms of the disorder are dry beriberi, wet beriberi and infantile beriberi.
Reference daily intake of Thiamine is 1.4mg/day. However, tests on volunteers at daily doses of about 50 mg have claimed an increase in mental acuity. There are no reports available of adverse effects from consumption of excess thiamine by ingestion of food and supplements. Because the data is inadequate for a quantitative risk assessment, no tolerable upper intake level (UL) can be derived for thiamine.
Riboflavin also known as vitamin B2, is an easily absorbed micronutrient with a key role in maintaining health in humans and animals. It is the central component of the cofactors FAD and FMN, and is therefore required by all flavoproteins. As such, vitamin B2 is required for a wide variety of cellular processes. Like the other B vitamins, it plays a key role in energy metabolism and for the metabolism of fats, ketone bodies, carbohydrates and proteins. Milk, cheese, leafy green vegetables, liver, kidneys, legumes, tomatoes, yeast, mushrooms and almonds are good sources of vitamin B2, but exposure to light destroys riboflavin. The name ‘riboflavin’ comes from ‘ribose’ (the sugar which forms part of its structure) and ‘flavin’, the ring-moiety which imparts the yellow colour to the oxidized molecule (from Latin flavus, ‘yellow’). Riboflavin is best known visually as the vitamin which imparts the orange colour to solid B-vitamin preparations and the yellow colour to vitamin supplement solutions.
In 1932, Warburg and Christian isolated a yellow respiratory ferment (Warburg's yellow enzyme), from bottom yeast. This was later separated into a protein fraction and a small pigment molecule (riboflavin), neither of which alone possessed enzyme activity. Pure riboflavin was isolated from milk and other foods in 1933 by Kuhn and co-workers.
Structure and Properties of Riboflavin
FMN and FAD function as coenzymes for a wide variety of oxidative enzymes and remain bound to the enzymes during the oxidation–reduction reactions. Flavins can act as oxidizing agents because of their ability to accept a pair of hydrogen atoms. Reduction of isoalloxazine ring (FAD, FMN oxidized form) yields the reduced forms of the flavoproteins (FMNH2 and FADH2).
D in the chemical name of riboflavin indicates that the ribityl group is related to the D series of sugars. The one prime (1′) indicates attachment of the ribityl group at the first carbon atom and the 9 that this attachment is to position 9 of the isoalloxazine ring system (Figure 6.8). A number of syntheses are available for the dimethyl compound.
It is difficult to incorporate riboflavin into many liquid products because it has poor solubility in water. Hence, the requirement for riboflavin-5′-phosphate is a more expensive but more soluble form of riboflavin.
Riboflavin is generally stable during the heat processing and normal cooking of foods if light is excluded. The alkaline conditions in which riboflavin is unstable are rarely encountered in foodstuffs. Riboflavin degradation in milk can occur slowly in dark during storage in the refrigerator.
Riboflavin is yellow or yellow–orange in colour and in addition to being used as a food colouring, it is also used to fortify some foods. It is used in baby foods, breakfast cereals, pastas, sauces, processed cheese, fruit drinks, vitamin-enriched milk products and some energy drinks. Regarding occurrence and sources of vitamin B2, Yeast extract is considered to be exceptionally rich in vitamin B2, and liver and kidney are also rich sources. Wheat bran, eggs, meat, milk and cheese are important sources in diets containing these foods.
Figure 6.8 Riboflavin 6,7-dimethyl-9-(D-1′-ribityl)-isoalloxazine
Riboflavin is found naturally in asparagus, bananas, persimmons, okra, chard, cottage cheese, milk, yoghurt, meat, eggs, fish and green beans. Riboflavin is destroyed by exposure to ultraviolet light, so milk sold in transparent (glass/plastic) bottles will likely contain less riboflavin than milk sold in opaque containers.
For adults, a minimum intake of 1.2 mg for persons whose caloric intake may be >2,000 Kcal. The current requirement for Riboflavin for adult men and women are 1.3 mg/day and 1.1 mg/day, respectively; the estimated average requirement for adult men and women are 1.1 mg and 0.9 mg, respectively. Recommendations for daily riboflavin intake increase with pregnancy and lactation to 1.4 mg and 1.6 mg, respectively (1in advanced). For infants, the RDA is 0.3–0.4 mg/day and for children, it is 0.6–0.9 mg/day.
Absorption and Storage
This vitamin is phosphorylated in the intestinal mucosa during absorption. It is absorbed from the small intestine through the portal vein and is passed to all tissues being stored in the body. The major part is excreted in urine and a small part is metabolized in the body.
Deficiency of Riboflavin
In humans, signs and symptoms of riboflavin deficiency (ariboflavinosis) include cracked and red lips, inflammation of the lining of mouth and tongue, mouth ulcers, cracks at the corners of the mouth (angular cheilitis) and a sore throat. A deficiency may also cause dry and scaling skin, fluid in the mucous membranes and iron-deficiency anaemia. The eyes may also become bloodshot, itchy, watery and sensitive to bright light.
Niacin, also known as vitamin B3 or nicotinic acid, is an organic compound with the formula C5H4NCO2H. This colourless, water-soluble solid is a derivative of pyridine, with a carboxyl group (COOH) at the 3-position. Other forms of vitamin B3 include the corresponding amide, nicotinamide (‘niacinamide’), where the carboxyl group has been replaced by a carboxamide group (CONH2), as well as more complex amides and a variety of esters. The terms niacin, nicotinamide and vitamin B3 are often used interchangeably to refer to any member of this family of compounds, since they have the same biochemical activity. Nicotinamide does not reduce cholesterol or cause flushing. Nicotinamide may be toxic to the liver at doses exceeding 3g/day for adults. Niacin is a precursor to NADH, NAD +, NADP +and NADPH, which play essential metabolic roles in living cells. Niacin is involved in both DNA repair, and the production of steroid hormones in the adrenal gland. Niacin deficiency leads to disease pellagra.
In 1935, Warburg and Christian showed that nicotinic acid amide (niaciamide) is an essential constituent of a coenzyme concerned in hydrogen transport (oxidation-reduction system).
Niacin is referred to as Vitamin B3 because it was the third of the B vitamins to be discovered. It has historically been referred to as ‘vitamin PP’ or ‘vitamin P-P’.
Structure and Properties of Niacin
Niacin or nicotinic acid is pyridine 3-carboxylic acid (Figure 6.9). Niacinamide or nicotinic acid amide is the acid amide. Niacin is readily prepared by oxidation of nicotine with strong oxidizing agents, such as permanganate or fuming nitric acid. Many other compounds, such as 3-ethylpyridine, can be oxidized to nicotinic acid. A synthesis from pyridine involves sulfonation of pyridine, distillation of the sodium salt of the 3-pyridine sulfonic acid with KCN to give the nitrile, and saponification of nicotinonitrile to yield nicotinic acid. Bromination of pyridine previous to sulfonation markedly increased the yield.
Food Sources: Niacin is found in variety of foods including liver, chicken, beef, fish, cereal, peanuts and legumes and is also synthesized from tryptophan, which is found in meat, dairy and eggs.
Animal Products: Liver, heart and kidney, chicken, beef, fish: tuna, salmon, milk and eggs.
Fruits and Vegetables: Avocados, dates, tomatoes, leaf vegetables, broccoli, carrots, sweet potatoes and asparagus
Seeds: Nuts, whole grain products, legumes and saltbush seeds.
Fungi: Mushrooms, brewer's yeast
Others: Vegemite (from spent brewer's yeast)
The recommended daily allowance of niacin is 212 mg/day for children, 14 mg/day for women, 16 mg/day for men, and 18 mg/day for pregnant or breast-feeding women. The upper limit for adult men and women is 35 mg/day.
Figure 6.9 Structure of Niacin
Absorption and Storage
Nicotinic acid and nicotinamide are absorbed from the intestine through the portal vein into the general circulation. Excess nicotinic acid is not stored in the body. The majority of the excess nicotinic acid is excreted in urine in the form of N-methylnicotinamide, 6-pyridone of N-methylnicotinamide, N-methylnicotinic acid and the glycine conjugates of these methyl derivatives. Methylation takes place in the liver. Methionine is the principal source of these methyl groups.
Severe deficiency of niacin in the diet causes the disease pellagra. Pellagra is characterized by diarrhoea, dermatitis and dementia as well as ‘necklace’ lesions on the lower neck, hyperpigmentation, thickening of the skin, inflammation of the mouth and tongue, digestive disturbances, amnesia, delirium and eventually death, if left untreated. Common psychiatric symptoms of niacin deficiency include irritability, poor concentration, anxiety, fatigue, restlessness, apathy and depression.
Toxicity of Vitamin
Pharmacological doses of niacin (1.5–6 g per day) often lead to side-effects that can include dermatological complaints such as skin flushing and itching, dry skin, skin rashes including acanthosis nigricans. Gastrointestinal complaints, such as dyspepsia (indigestion) and liver toxicity (fulminant hepatic failure) have also been reported. Side effects of hyperglycemia, cardiac arrhythmias and ‘birth defects in experimental animals’ have also been reported.
Pantothenic acid, also called vitamin B5 (α B vitamin), is a water-soluble vitamin required to sustain life (essential nutrient). Pantothenic acid is needed to form coenzyme-A (CoA) and is critical in the metabolism and synthesis of carbohydrates, proteins and fats. Its name is derived from the Greek pantothen meaning ‘from everywhere’ and small quantities of pantothenic acid are found in nearly every food, with high amounts in whole-grain cereals, legumes, eggs, meat and royal jelly. It is commonly found as its alcohol analogue, the provitamin panthenol and as calcium pantothenate. Pantothenic acid is an ingredient in some hair and skin care products. The substance that acted as a growth factor for yeasts and other microorganisms, the widespread distribution of this substance was demonstrated in 1933 by Williams and co-workers. This substance was given the name pantothenic acid by Williams and co-workers.
Structure and Properties of Pantothenic Acid
Pantothenic acid chemically, is α, γ-dihydroxy-β-β-dimethylbutyryl-β′alanide. The molecule is perhaps more easily comprehended if it is thought of as a dihydroxydimethylbutyric acid in peptide bond formation with β-alanine. The β′ indicates that the amino group is on the βcarbon atom rather than on the α carbon, as found in ordinary alanine (Figure 6.10). Many synthesis of pantothenic acid have been developed. The direct condensation of β-alanine with the lactone of the substituted butyric acid gives excellent yields and the desired product is obtained directly. The synthesis of calcium pantothenate was reported by Kagan and co-workers in high yield and in a high state of purity.
Small quantities of pantothenic acid are found in most foods. The major food source of pantothenic acid is in meats, although the concentration found in food animals’ muscles is only about half that in humans’ muscles. Whole grains are another good source of the vitamin, but milling often removes much of the pantothenic acid, as it is found in the outer layers of whole grains. Vegetables, such as broccoli and avocados, also have an abundance of the acid. In animal feeds, the most important sources of the vitamin are rice, wheat brans, alfalfa, peanut meal, molasses, yeasts and condensed fish solutions. The most significant sources of pantothenic acid in nature are coldwater fish ovaries and royal jelly.
Figure 6.10 Pantothenic Acid
Pantothenate in the form of 4′ phosphopantetheine is considered to be the more active form of the vitamin in the body; however, any derivative must be broken down to pantothenic acid before absorption. 10 mg of calcium pantothenate is equivalent to 9.2 mg of pantothenic acid.
Adults men and women
Within most foods, pantothenic acid is in the form of CoA or Acyl Carrier Protein (ACP). In order for the intestinal cells to absorb this vitamin, it must be converted into free pantothenic acid. Within the lumen of the intestine, CoA and ACP are hydrolyzed into 4′-phosphopantetheine. 4′-phosphopantetheine is then dephosphorylated into pantetheine. Pantetheinase, an intestinal enzyme, then hydrolyses pantetheine into free pantothenic acid.
Free pantothenic acid is absorbed into intestinal cells via a saturable, sodium-dependent active transport system. At high levels of intake, when this mechanism is saturated, some pantothenic acid may also be absorbed via passive diffusion. However, as intake increases 10-fold, absorption rate decreases to 10 per cent.
Symptoms of deficiency are similar to other vitamin B deficiencies. There is impaired energy production, due to low CoA levels, which could cause symptoms of irritability, fatigue and apathy. Acetylcholine synthesis is also impaired, therefore, neurological symptoms can also appear in deficiency. They include numbness, paresthesia and muscle cramps.
Deficiency symptoms in other non-ruminant animals include disorders of the nervous, gastrointestinal and immune systems, reduced growth rate, decreased food intake, skin lesions and changes in hair coat, alterations in lipid and carbohydrate metabolism.
Toxicity of pantothenic acid is unlikely. In fact, no tolerable upper level intake (UL) has been established for the vitamin. Large doses of the vitamin, when ingested, have no reported side-effects and massive doses (e.g., 10 g/day) may only yield mild intestinal distress and diarrhoea at worst.
There are also no adverse reactions known following parenteral or topical application of the vitamin. However, a large doses of vitamin B5 (e.g., 5–9 gram) is known to cause nausea and a lack of energy.
Pyridoxine is one of the compounds that can be called vitamin B6, along with pyridoxal and pyridoxamine. It differs from pyridoxamine by the substituent at the ‘4’ position. It is often used as ‘pyridoxine hydrochloride’.
The discovery of pyridoxine unrevealed the complex nature of the B vitamin. Vitamin B6 was given other names like rat acrodynia factor, rat antidermatitis factor and vitamin H.
Structure and Properties of Pyridoxine
It is based on a pyridine ring, with hydroxyl, methyl and hydroxymethyl substituents. It is converted to the biologically active form pyridoxal 5-phosphate.
Pyridoxine is a basic substance. The colourless crystals melt at 160°C. The compounds are soluble in alcohol and water, but only slightly soluble in ether or chloroform. The vitamin is generally used as the hydrochloride salt which melts at 260°C to 280°C with some decomposition. The salt is highly soluble in water at pH about 3, less soluble in alcohol and insoluble in ether. The vitamin shows marked absorption in the ultraviolet range.
The structure of pyridoxine and some related compounds are shown in Figure 6.11.
Function of Pyridoxine
Pyridoxine assists in the balancing of sodium and potassium as well as promoting red blood cell production. It is linked to cardiovascular health by decreasing the formation of homocysteine. Pyridoxine may help balance hormonal changes in women and aid the immune system. Lack of pyridoxine may cause anaemia, nerve damage, seizures, skin problems and sores in the mouth.
It is required for the production of the monoamine neurotransmitters serotonin, dopamine, norepinephrine and epinephrine, as it is the precursor to pyridoxal phosphate: cofactor for the enzyme aromatic amino acid decarboxylase. This enzyme is responsible for converting the precursors 5-hydroxytryptophan (5-HTP) into serotonin and levodopa (L-DOPA) into dopamine, noradrenaline and adrenaline. As such it has been implicated in the treatment of depression and anxiety.
A very good source of pyridoxine is dragon fruit from South East Asia. Most people get their supply of this vitamin from either milk or meat products. Pyridoxine is not normally found in plants. This vitamin is made by certain bacteria. Some vegetarians may get adequate pyridoxine simply from eating plants that have traces of soil (like potato skins).
Figure 6.11 Pyridoxine
Vitamin B6 can be compounded into a variety of different dosage forms. It can be used orally as a tablet, capsule or solution. It can also be used as a nasal spray or for injection when in its solution form. Vitamin B6 is usually safe, at intakes up to 200 mg per day in adults.
Absorption and Storage
It is readily absorbed from the small intestine. The excess amount if ingested is not stored in the body but is excreted in urine.
The early descriptions of a pyridoxine deficiency in rats was one of multiple deficiency; other unknown factors were absent from the synthetic diets. At present, there is recognized specific syndrome representing pyridoxine want in rats. This includes acrodynia or a typical dermatitis which is generally symmetrical and affects the paws and various parts of the head. Seborrheic lesions are frequent. Edema of the connective tissue layer of the skin is thought to be characteristic. Loss of muscle tonus was observed after long-continued deprivation in rats.
Vitamin B6 can cause neurological disorders, such as loss of sensation in legs and imbalance, when taken in high doses (more than 200 mg/ per day) over a long period of time. Vitamin B6 toxicity can damage sensory nerves, leading to numbness in the hands and feet as well as difficulty walking. Symptoms of a pyridoxine overdose may include poor coordination, staggering, numbness, decreased sensation to touch, temperature, and vibration and tiredness for up to several years.
It is given to patients taking isoniazid to combat the toxic side-effects of the drug. Pyridoxine is given 10–50 mg/day to patients on INH (Isoniazid) to prevent peripheral neuropathy and CNS effects that are associated with the use of isoniazid. It is also essential for patients with the extremely rare pyridoxine-dependent epilepsy, thought to be caused by mutations in the ALDH7A1 gene.
IUPAC Name of Biotin is 2'-keto-3, 4-imidazolido-2-tetrahydrothiophene-n-valeric Acid
Biotin is a water-soluble B-complex vitamin which is made up an ureido (tetrahydroimidizalone) ring fused with a tetrahydrothiophene ring. A valeric acid substituent is attached to one of the carbon atoms of the tetrahydrothiophene ring (Figure 6.12). Biotin is a coenzyme in the metabolism of fatty acids and leucine and it plays a role in gluconeogenesis.
Biotin is necessary for cell growth, production of fatty acids, and the metabolism of fats and amino acids. It plays a role in the citric acid cycle, which is the process by which biochemical energy is generated during aerobic respiration. Biotin not only assists in various metabolic reactions, but also helps to transfer carbon dioxide. Biotin may also be helpful in maintaining a steady blood sugar level. Biotin is often recommended for strengthening hair and nails. Consequently, it is added in many cosmetics and health products for the hair and skin, though it cannot be absorbed through the hair or skin itself. Biotin deficiency is rare, as intestinal bacteria generally produce an excess of the body's recommended daily requirement.
In 1916, the toxicity of diet high in egg white was observed. Later, Boas in 1927 described egg white injury in the rats fed diets containing raw egg white as the source of protein.
Figure 6.12 Structure of Biotin
Structure and Properties of Biotin
Biotin (d or natural isomer) is a monocarboxylic acid, only slightly soluble in water (0.03 to 0.04g per 100ml at 25°C and 1g per 100ml at 100°C) and alcohol (0.06g per 100ml at 25°C). Salts of the acid are quite soluble; the sodium salt can be prepared in 20 per cent aqueous solution. The free acid is practically insoluble in acetone and ether. The colourless crystalline needles melt at 231°C to 232°C. Water solutions (pH 4-9) are stable at 100°C, and the dry material is both thermostable and photostable. The vitamin is destroyed by acids and alkalies only on rigorous treatment and by oxidizing agents such as peroxide and permanganate.
The specific rotation, [α] 26/D, is 91.0° in 0.1 N NaOH and it shows maximum absorption in the ultraviolet at 234nm.
Biocytin is a term designating a bound form of biotin first isolated from yeast by Wright and co-workers. It was identified as ε-N-biotinyl-lysine and later synthesized. It occurs in plant and animal tissues also. The synthetic material reacts in the same way as naturally occurring biocytin with respect to microbiological activity, combination with avidin hydrolysis rates, infrared absorption and other criteria. In biocytin, the ε-amino group of lysine and the carboxyl of biotin are combined in a manner similar to that in a peptide bond. Another bound form of the vitamin-soluble bound biotin-contained in peptic digests of hog liver and other tissues was found to be convertible to free biotin by an enzyme from liver named biotinidase.
A deficiency of pyruvate carboxylase can cause lactic acidosis as a result of lactate build up. Normally, excess pyruvate is shunted into gluconeogenesis via conversion of pyruvate into oxaloacetate, but because of the enzyme deficiency, excess pyruvate is converted into lactate instead. As a key role of gluconeogenesis is in the maintenance of blood sugar, deficiency of pyruvate carboxylase can also lead to hypoglycemia.
Sources of Biotin
Biotin is consumed from a wide range of food sources in the diet, however, there are few particularly rich sources. Foods with relatively high biotin content include egg yolk, liver and some vegetables. The dietary biotin intake in Western populations has been estimated to be 35 to 70 μg/d (143287 nmol/d).
Biotin is also available from supplements. The synthetic process uses fumaric acid as a starting material and is identical to the natural product.
Since intestinal bacteria and diets supply biotin in adequate amounts the deficiency of this vitamin in human beings is rare.
Factors that Affect Biotin Requirements
In alcoholics, low levels of biotin has been found. Also, relatively low levels of biotin have been reported in the urine or plasma of patients who have had partial gastrectomy or who have other causes of achlorhydria, burn patients, epileptics, elderly individuals and athletes. Pregnancy and lactation may be associated with an increased demand for biotin. In pregnancy, this may be due to a possible acceleration of biotin catabolism, whereas in lactation, the higher demand has yet to be elucidated.
Absorption and Storage
Biotin is readily absorbed from the small intestine through the portal vein into the general circulation. Excess of the requirement is not stored in the body but is mostly excreted in the urine.
Biotin deficiency is relatively rare and mild, and can be addressed with supplementation. Such deficiency can be caused by the excessive consumption of raw egg whites (20 eggs/day would be required to induce it), which contain high levels of the protein avidin, which binds biotin strongly. Avidin is deactivated by cooking, while the biotin remains intact.
Symptoms of Overt Biotin Deficiency include
- Hair loss (alopecia)
- Dermatitis in the form of a scaly red rash around the eyes, nose, mouth and genital area.
- Neurological symptoms in adults such as depression, lethargy, hallucination and numbness and tingling of the extremities.
Folic acid and folate as well as pteroyl-L-glutamic acid and pteroyl-L-glutamate, are forms of the water-soluble vitamin B9. Folic acid is itself not biologically active, but its biological importance is due to tetrahydrofolate and other derivatives after its conversion to dihydrofolic acid in the liver.
Vitamin B9 (folic acid and folate inclusive) is essential to numerous bodily functions ranging from nucleotide biosynthesis to the remethylation of homocysteine. The human body needs folate to synthesize DNA, repair DNA and methylate DNA, as well as to act as a cofactor in biological reactions involving folate. It is especially important during periods of rapid cell division and growth. Both children and adults require folic acid to produce healthy red blood cells and prevent anaemia. Folate and folic acid derive their names from the Latin word folium (which means ‘leaf’). Leafy vegetables are a principal source, although in Western diets fortified cereals and bread may be a larger dietary source.
Lucy Wills in 1931 led to the identification of folate as the nutrient needed to prevent anaemia during pregnancy. Dr. Wills demonstrated that anaemia could be reversed with brewer's yeast. In the 1920s, scientists believed that folate deficiency and anaemia were the same condition. Folate was identified as the corrective substance in brewer's yeast in the late 1930s and was first isolated in and extracted from spinach leaves by Mitchell and others in 1941. Bob Stokstad isolated the pure crystalline form in 1943, and was able to determine its chemical structure.
Structure and Properties of Folic Acid
Folic acid (folacin, pteroylglutamic acid) is a compound made up of the Pteridine nucleus, P-aminobenzoic acid and glutamic acid (Figure 6.13). There are at least three nutritionally important and chemically related compounds which occur in natural products belonging to the folic acid group. The various vitamins of B9 group differ from each other in the number of glutamic acid groups present; the additional glutamic acid group being conjugated in peptide linkages. For example, folic acid contains one glutamic acid groups fermentation Lactobacillus casei factor three and Bc conjugate seven glutamic acid groups. The conjugates (i.e., compounds having more than one glutamic acid groups in the molecule) are ineffective for some species as these species do not possess the enzyme conjugase which is necessary for the release of free vitamin. Citrivorum factor, however, differs from other vitamins of B9 group in the structure of one of the rings of the pterin moiety.
The naturally occurring enzyme, vitamin Bc conjugase, hydrolyzes folic acid-like compounds with several glutamic acid residues to pteroyglutamic acid and glutamic acid. This enzyme is widely distributed in animal tissues and may be of importance in converting pteroylglutamates to PGA, although pteroylglutamic acid, pteroyltriglutamic acid and pteroylheptaglutamic acid are active as hematopoietic agents for man.
Two diglutamic acid derivatives have been synthesized. Pteroyl-a-glutamylglutamic acid (Diopterin) is inactive for L.casei and Streptococcus faecalis R (Rhizopterin) but active in the types of human blood discrasias. Folic acid is water soluble it is stable to at neutral pH. Its activity is not lost if heated at 120°C for 30 min at neutral pH.
Leafy vegetables such as spinach, asparagus, turnip greens, romaine lettuces, dried or fresh beans and peas, beer, fortified grain products (pasta, cereal, bread), sunflower seeds and certain other fruits (orange juice, canned pineapple juice, cantaloupe, honeydew melon, grapefruit juice, banana, raspberry, grapefruit, strawberry) and vegetables (beets, broccoli, corn, tomato juice, vegetable juice, brussels sprouts, bok choy) are rich source of folate. Liver and liver products also contain high amounts of folate, as does baker's yeast. Some breakfast cereals (ready-to-eat and others) are fortified with 25 to 100 per cent of the recommended dietary allowance (RDA) of folic acid. Folic acid is naturally found in food is susceptible to degradation in high heat, UV and is soluble in water. It is heat labile in acidic environments and may also be subject to oxidation.
Figure 6.13 Ptero Glutamic Acid (PGA): Folic Acid
Because of the difference in bioavailability between supplemented folic acid and the different forms of folate found in food, the dietary folate equivalent system was established. 1 DFE is defined as 1¼g (microgram) of dietary folate, or 0.6 μg of folic acid supplement.
Absorption and Transport
Absorption of folic acid takes place along the whole length of the mucosa of the small intestine. Monoglutamates are produced from polyglutamates which is ingested within the intestinal mucosa and dihydrofolates are further reduced to tetrahydrofolates by folic acid reductases. The tetrahydrofolates are then converted to methyltetrahydrofolate which enter the portal blood to be transported to the liver. The vitamin then appears in the systemic circulation to supply the tissue. The vitamin is transported to the plasma as methyltetrahydrofolate bound to protein. The folate level of plasma obtained from umbilical cord blood is about three times that of the maternal plasma.
Deficiency Leads to Health Issues
Human Reproduction: Folic acid is an important nutrient for women who may become pregnant, because a woman's blood levels of folate fall during pregnancy due to an increased maternal RBC synthesis in the first half of the pregnancy and foetal demands in the second half. The first 4 weeks of pregnancy (when most women do not even realize they are pregnant) require folic acid for proper development of the brain, skull and spinal cord.
Heart Disease: Deficiency of folate leads to (13,500 deaths occur annually) coronary artery . The risk of ischemic heart disease and stroke has been reduced by 15 per cent since folate fortification regulations were enforced.
Stroke: Folic acid appears to reduce the risk of stroke.
Cancer: Folate deficiency decreases intracellular S-adenosylmethionine (SAM) which inhibits cytosine methylation in DNA, activates proto-oncogenes, induces malignant transformations, causes DNA precursor imbalances, misincorporates uracil into DNA, and promotes chromosome breakage; all of these mechanisms increase the risk of prostate cancer development.
Antifolates: Folate is important for cells and tissues that rapidly divide. Cancer cells divide rapidly, and drugs that interfere with folate metabolism are used to treat cancer. The antifolate methotrexate is a drug often used to treat cancer because it inhibits the production of the active form of THF from the inactive dihydrofolate (DHF).
Obesity: Folic acid increases lipolysis in adipocytes and may have a role in the prevention of obesity and type 2 diabetes. This mechanism involves the adrenoceptors in the abdominal adipocytes.
Depression: Some evidence links a shortage of folate with depression. There is some limited evidence from randomized controlled trials that using folic acid in addition to antidepressants.
IUPAC name of Vitamin B12 is α-(5, 6-dimethylbenzimidazolyl) cobamidcyanide
Vitamin B12 is a class of chemically related compounds all of which have vitamin activity. It is structurally the most complicated vitamin and it contains the biochemically rare element—cobalt. Biosynthesis of the basic structure of the vitamin can only be accomplished by bacteria and algae but conversion between different forms of the vitamin can be accomplished in the human body. A common synthetic form of the vitamin, cyanocobalamin, does not occur in nature, but is used in many pharmaceuticals and supplements and as a food additive, due to its stability and lower cost. In the body, it is converted to the physiological forms, methylcobalamin and adenosylcobalamin, leaving behind the cyanide. More recently, hydroxocobalamin (a form produced by bacteria), methylcobalamin and adenosylcobalamin can also be found in more expensive pharmacological products and food supplements.
The name vitamin B12, known as vitamin B12 (commonly B12) or also cyanocobalamin generally refers to all forms of the vitamin. Some medical practitioners have suggested that its use be split into two different categories, however.
In a broad sense, B12 refers to a group of cobalt-containing vitamer compounds known as cobalamins; these include cyanocobalamin (an artefact formed as a result of the use of cyanide in the purification procedure), hydroxocobalamin (another medicinal form, produced by bacteria) and finally, the two naturally occurring cofactor forms of B12 in the human body: 5′-deoxyadenosylcobalamin (adenosylcobalaminAdo B12), the cofactor of Methylmalonyl Coenzyme A mutase (MUT), and methylcobalamin (Me B12), the cofactor of 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR).
Pseudo—B12 refers to B12—like substances which are found in certain organisms, including Spirulina (a cyanobacterium) and some algae.
The antipernicious anaemia factor of liver extract was isolated in 1948 by Rickes and co-workers. Various workers had been studying the same or a similar substance found in other material. The ‘animal proteins factor’, which promotes the growth of animals on diets containing vegetable proteins and is found in such materials as fish solubles and cow manure, is similar to the factor isolated from liver extract. The name B12 was given to the vitamin.
Vitamin B12 is a collection of cobalt and corrin ring molecules which are defined by their particular vitamin function in the body. All of the substrate cobalt-corrin molecules from which B12 is made must be synthesized by bacteria. However, after this synthesis is complete, the body has a limited power to convert any form of B12 to another, by means of enzymatically removing certain prosthetic chemical groups from the cobalt atom. The various forms (vitamers) of B12 are all deeply red coloured, due to the colour of the cobalt–corrin complex.
B12 is the most chemically complex of all the vitamins. The structure of B12 is based on a corrin ring, which is similar to the porphyrin ring found in heme, chlorophyll and cytochrome. The central metal ion is cobalt. Four of the six coordination sites are provided by the corrin ring and a fifth by a dimethylbenzimidazole group. The sixth coordination site, the centre of reactivity, is variable, being a cyano group (-CN), a hydroxyl group (-OH), a methyl group (-CH3) or a 5′-deoxyadenosyl group (here the C5′ atom of the deoxyribose forms the covalent bond with Co), respectively, to yield the four B12 forms mentioned above (Figure 6.14). Historically, the covalent C-Co bond is one of first examples of carbon-metal bonds to be discovered in biology. The hydrogenases and by necessity, enzymes associated with cobalt utilization, involve metal-carbon bonds.
Cyanocobalamin is one such ‘vitamer’ in this B complex, because it can be metabolized in the body to an active co-enzyme form. However, the cyanocobalamin form of B12 does not occur in nature normally, but is a byproduct of the fact that other forms of B12 are avid binders of cyanide (-CN) which they pick up in the process of activated charcoal purification of the vitamin after it is made by bacteria in the commercial process. Since the cyanocobalamin form of B12 is easy to crystallize and is not sensitive to air-oxidation, it is typically used as a form of B12 for food additives and in many common multivitamins. However, this form is not perfectly synonymous with B12, in as much as a number of substances (vitamers) have B12 vitamin activity and can properly be labelled vitamin B12, and cyanocobalamin is but one of them. (Thus, all cyanocobalamin is vitamin B12, but not all vitamin B12 is cyanocobalamin).
Figure 6.14 Vitamin B12; Cyanocobalamin
Hydroxocobalamin is another form of B12 commonly encountered in pharmacology, but which is not normally present in the human body. Hydroxocobalamin is sometimes denonoted B12. This form of B12 is the form produced by bacteria, and is what is converted to cyanocobalamin in the commercial charcoal filtration step of production. Hydroxocobalamin has an avid affinity for cyanide ion and has been used as an antidote to cyanide poisoning. It is supplied typically in water solution for injection. Hydroxocobalamin is thought to be converted to the active enzymic forms of B12 more easily than cyanocobalamin, and since it is little more expensive than cyanocobalamin, and has longer retention times in the body, has been used for vitamin replacement in situations where added reassurance of activity is desired. Intramuscular administration of hydroxocobalamin is also the preferred treatment for pediatric patients with intrinsic cobalamin metabolic diseases, for vitamin B12 deficient patients with tobacco amblyopia (which is thought to perhaps have a component of cyanide poisoning from cyanide in cigarette smoke); and for treatment of patients with pernicious anaemia who have optic neuropathy.
Properties of Vitamin B12
Cyanocoblamin crystals are tasteless and odourless. One gram dissolves in about 80 ml of water at room temperature, forming a neutral solution. The pure material is quite soluble in alcohol and insoluble in ether and acetone. In aqueous solution, crystalline cyanocobalamin has three absorption maxima at 278nm, 361nm and 550nm, with extinction coefficients of 115, 107 and 64, respectively. It is remarkable that cobalamin contains about 4.35 per cent cobalt. The molecular weight is 1355.
Cyanocobalamin has a net charge of one. The cobalt has a coordination number of 6. It has one coordinate linked cyanide group, one coordinate pyrrole nitrogen, and a coordinate link to a nitrogen of the 5, 6-dimethylbenzimidazole moiety. Other B12 active compounds are known in which the cyanide radical is replaced by various groups forming other cobalamins, such as hydroxycobalamin, chlorocobalamin, nitrocobalamin and thiocyanatocobalamin. Treatment with cyanide converts these molecules into cyanocobalamin.
The similarity of the cyanocobalamin molecule and the porphyrins is of interest. In B12, two pyrrole rings are joints directly rather than through the methene (–CH=) bridge as in other porphyrins.
Vitamin B12 Deficiency
Vitamin B12 deficiency has the following pathomorphology and symptoms:
Clinical Symptoms: The main syndrome of vitamin B12 deficiency is Biermer's disease (pernicious anaemia). It is characterized by a triad of symptoms:
- Anaemia with bone marrow promegaloblastosis (megaloblastic anaemia).
- Gastrointestinal symptoms.
- Neurological symptoms.
Each of these symptoms can occur either alone or together. The neurological complex, defined as myelosis funicularis, consists of the following symptoms:
- Impaired perception of deep touch, pressure and vibration, abolishment of sense of touch, very annoying and persistent paresthesias.
- Ataxia of dorsal cord type.
- Decrease or abolishment of deep muscle-tendon reflexes.
- Pathological reflexes—Babinski, Rossolimo and others, also severe paresis.
Ultimately, animals must obtain vitamin B12 directly or indirectly from bacteria, and these bacteria may inhabit a section of the gut which is posterior to the section where B12 is absorbed. Thus, herbivorous animals must either obtain B12 from bacteria in their rumens, or (if fermenting plant material in the hindgut) by reingestion of cecotrope faeces.
Vitamin B12 is found in foods that come from animals, including fish and shellfish, meat (especially liver), poultry, eggs, milk and milk products. 3 ounces of beef, 2.4 µg, or 40 per cent of one's DV (daily value); one slice of liver 47.9 µg or 780 per cent of DV; and 3 ounces of molluscs 84.1 µg, or 1,400 per cent of DV.
The dietary reference intake for an adult ranges from 2 to 3 µg (micrograms) per day. Vitamin B12 is believed to be safe when used orally in amounts that do not exceed the recommended dietary allowance (RDA). The RDA for vitamin B12 in pregnant women is 2.6 µg per day and 2.8 µg during lactation periods. There is insufficient reliable information available about the safety of consuming greater amounts of vitamin B12 during pregnancy.
Vitamin B12 supplements in theory should be avoided in people sensitive or allergic to cobalamin, cobalt or any other product ingredients. However, direct allergy to a vitamin or nutrient is extremely rare and if reported, other causes should be sought.
Castle and others, some years ago, suggested that in pernicious anaemia, there is a deficiency of an intrinsic factor (stomach factor) and an extrinsic factor (food factor). The two factors were thought to react to form something required for the maturation of red blood cells. The extrinsic factor (EF) of Castle is now established to be vitamin B12. The intrinsic factor, a low-molecular-weight mucoprotein, normally occurs in gastric juice; and pernicious anaemia is due to a lack of this substance, since B12 is not absorbed in its absence. The mechanism by which intrinsic factor brings about absorption is still not clear.
However, it has been proposed that IF removes the vitamin from natural protein complexes with animal proteins. It also brings about absorption of the vitamin into the mucosal cells with the aid of an intestinal juice factor called releasing factor. Herbert studied the source of this factor in rats and found it to be in the proximal end of the small intestine. It is known that IF has a high degree of specificity. Fortunately, hog and human IF have similar actions in humans. In very large doses B12 is absorbed in humans without IF, but not with doses found in ordinary diets. Small doses parenterally are highly effective in deficiency states.
After absorption into the blood, B12 is bound to plasma proteins and may circulate to the sites of activity. That portion converted into coenzymes is stored principally in the liver. Small amounts of B12 occur in blood of normal individuals. The variations are wide, but around 100 mg to several 100 mg per ml of blood have been found and a tenth or less of these amounts in pernicious anaemia patients. The stools of pernicious anaemia patients contain large amounts of the vitamin after oral administration if no intrinsic factor is given.
(IUPAC) name 2-oxo-L-threo-hexono-1, 4-lactone-2,3-enediol:
Vitamin C or L-ascorbic acid or L-ascorbate is an essential nutrient for humans and certain other animal species, in which it functions as a vitamin. In living organisms, ascorbate is an anti-oxidant, since it protects the body against oxidative stress. It is also a cofactor in at least eight enzymatic reactions, including several collagen synthesis reactions that cause the most severe symptoms of scurvy when they are dysfunctional. In animals, these reactions are especially important in wound-healing and in preventing bleeding from capillaries.
Ascorbate (an ion of ascorbic acid) is required for a range of essential metabolic reactions in all
animals and plants. It is made internally by almost all organisms; notable mammalian group exceptions are most or all of the order chiroptera (bats), and one of the two major primate suborders, the Anthropoidea (Haplorrhini) (tarsiers, monkeys and apes, including human beings). Ascorbic acid is also not synthesized by guinea pigs and some species of birds and fish. All species that do not synthesize ascorbate require it in the diet. Deficiency in this vitamin causes the disease scurvy in humans. It is also widely used as a food additive.
In 1932, Waugh and King reported that the vitamin C isolated by them from lemon juice and the reducing heuronic acid studied by others were identical because of the similarity in many chemical and physical properties as well as in biological potency in protecting guinea pigs against scurvy.
Structure and Properties of Ascorbic Acid
The strong reducing property of vitamin C depends on the loss of hydrogen atoms from the hydroxyls on the double-bonded (endiol) carbons. Pure vitamin C is a white crystalline odourless substance with a sour (acid) taste. It melts at 190°C–192°C, and in the crystalline form it is stable for years. It is insoluble in most organic solvents, although a 2 per cent solution can be made in alcohol. In water, the vitamin is soluble to the extent of 1 g in 3 ml. A dilute solution of vitamin C has a pH of about 3. The acidity is due to ionization of the enol group on carbon atom 3.
Ascorbic acid forms salts of several metals. Ascorbic acid takes up iodine at the double bond can be reduced here by hydrogenation. Oxidation of ascorbic acid yields dehydroascorbic acid. This is a freely reversible reaction. H2S, among other things, may be used to reduce the oxidized form in the laboratory. The dehydro form, except in rather acid solution, undergoes hydrolysis at the lactone ring with the formation of diketogulonic acid and oxalic acid. The reverse of this reaction does not proceed in the body but can be brought about in the laboratory (Figure 6.15).
The greater stability of ascorbic acid solution depends on the decreased tendency towards hydrolysis of the lactone ring with decreasing pH. In alkaline solution, the hydrolysis is fairly rapid and such solutions lose vitamin activity in a short period of time. The oxidation of ascorbic acid in vitro is catalyzed by various substances. The copper ion is quite active and, of course, the plant ascorbic acid oxidase (a copper-protein enzyme) is highly active. With the increasing pH rate of destructive oxidation is greater. This type of oxidation involves molecular oxygen, and, consequently, in processing vitamin C-containing foods, such as orange juice, the removal of oxygen by nitrogen or CO2 result in decreased losses of the vitamin during canning or other processing. Low-temperature storage of vegetables before processing, though usually impractical, and a quick preheating (blanching) just previous to canning or freezing also aid in decreasing ascorbic acid destruction.
Figure 6.15 Oxidation of Ascorbic Acid Yields Dehydroascorbic Acid. This is a Reversible Reaction. The Dehydro form Undergoes Hydrolysis at the Lactone Ring with the Formation of Diketogulonic Acid
Ascorbic acid is well known for its antioxidant activity. Ascorbate acts as a reducing agent to reverse oxidation in aqueous solution. When there are more free radicals (reactive oxygen species) in the human body than antioxidants, the condition is called oxidative stress.
The richest natural sources are fruits and vegetables and of those, the Kakadu plum and the camu camu fruit contain the highest concentration of the vitamin. It is also present in some cuts of meat, especially liver. Vitamin C is the most widely taken nutritional supplement and is available in a variety of forms, including tablets, drink mixes, crystals in capsules or naked crystals.
Amount (mg/100g): Kakadu plum 3100, Camu Camu 2800, Rose hip 2000, Acerola1600, Seabuckthorn 695, Jujube 500, Indian gooseberry 445, Papaya 60, Strawberry 60, Orange 50, Kale 41, Lemon 40, Melon, cantaloupe 40, Cauliflower 40, Garlic 31, Grapefruit 30, Grape 10, Apricot 10, Plum 10, Watermelon 10, Banana 9, Carrot 9, Avocado 8, Crabapple 8, Persimmon fresh 7, Cherry 7 and Peach 7.
The following information shows the relative abundance of vitamin C in various foods of animal origin, given in milligram of vitamin C per 100 grams of food:
Amount (mg/100g): Calf liver (raw) 36, Beef liver (raw) 31, Oysters (raw) 30, Cod roe (fried) 26, Pork liver (raw) 23, Lamb brain (boiled) 17, Chicken liver (fried) 13, Lamb liver (fried) 12.
|Pregnant women||60 mg|
|Lactating women||80 mg|
Absorption and Storage
Ascorbic acid is readily absorbed from the small intestine peritoneum and subcutaneous tissues. It passes through the portal vein to the general circulation and to all tissues. It is supplied to the placental barrier readily. The placenta is also able to concentrate this vitamin. It is not stored in any particular organ and is distributed throughout the body. Each organ or tissue has an optimal saturation level of ascorbic acid. Excessive intake of ascorbic acid does not increase the saturation level but the excess is excreted in the urine.
Scurvy is an avitaminosis resulting from lack of vitamin C, since without this vitamin, the synthesized collagen is too unstable to perform its function. Scurvy leads to the formation of liver spots on the skin, spongy gums and bleeding from all mucous membranes. The spots are most abundant on the thighs and legs, and a person with the ailment looks pale, feels depressed and is partially immobilized.
Vitamin C Hypervitaminosis
Higher vitamin C intake reduces serum uric acid levels, and is associated with lower incidence of gout. Relatively large doses of vitamin C may cause indigestion, particularly when taken on an empty stomach. When taken in large doses, vitamin C causes nausea, vomiting, diarrhoea, flushing of the face, headache, fatigue and disturbed sleep. The main toxic reactions in the infants are skin rashes.
Minerals are essential parts of all cells. They form the major parts of the hard tissues of the body, are necessary to muscle contraction and nervous conduction, are integral parts of the organismal and cellular respiration systems, are essential to enzyme function and are necessary to the maintenance of water and acid base balance in the body. Minerals must be replaced daily as they are lost in the excreta (sweat, tears, urine, faeces). Daily requirements are greater for children, pregnant women and under certain pathological conditions.
Mineral requirements of the human can be roughly classified into macrominerals and micro or trace minerals based on the amounts required in the diet. Kinds of Minerals: Minerals may be divided into two groups.
- Macro minerals: The minerals, which are required in amounts greater than 100 mg/day.
- Micro minerals: The minerals, which are required in amounts less than 100 mg/day.
- Calcium: Milk, egg, leafy green vegetable, fish, meat soybeans, etc. Formation of bones and teeth structure. Activates ATP during muscular contraction, helps in blood clotting and capillary permeability.
- Phosphorus: Milk, peas, meat, fish, eggs, cottage cheese, almonds, wheat germ, soybeans, black beans, etc. Synthesis of nucleic acid, ATP and some protein. Helps in calcification of bones, maintain buffer system in body and bone formation.
- Magnesium: Magnesium supplements are available as several salts (chloride, gluconate, lactate, sulphate and oxide) and are used to treat people with magnesium deficiency due to poor nutrition, restricted diet, alcoholism or magnesium-depleting drugs. Many antacids or laxatives also contain magnesium.
- Sodium: Table salt, eggs, meat, milk, cheese, butter, margarine, bacon, etc., form part of tissue fluids inducing blood, involves kidney functioning and transmission of nervous impulses, acid–base balance in body.
- Potassium: Spinach, butter, beans, oranges, milk, peas, meat, fruits, nuts and vegetables. Potassium is essential to energy metabolism and to glycogen and protein synthesis.
- Iron: Liver, eggs, meat, dark and green vegetables, lentils, potatoes, soybeans, chick peas, black beans, spinach, etc., forms part of haemoglobin, helps in electron transport in biochemical reactions.
- Zinc: Most foods; CO2 transport in vertebrate blood.
- Iodine: Seafood's, such as fish, shellfish and fish oil. Vegetables, spinach, fruits and cereals.
- Chromium: Chromium found in whole grains, egg yolks, brewer's yeast, liver, meats and nuts. It is an essential trace element that is needed for carbohydrate, fat and nucleic acid (DNA or RNA) metabolism.
- Cobalt: Liver and red meat; Red bloods cell development.
- Copper: Most foods; Melanin production.
- Manganese: Vegetables and most other foods; Bone development (a growth factor.
- Molybdenum: Most foods; Hydrolysis of peptide bonds in protein digestion.
- Selenium: Foods containing selenium include meat, poultry, grains and seafood. Some reports have suggested that selenium may protect against certain types of cancer.
- Fluorine: Water, milk, etc. needed for strong enamel on teeth, as calcium deposits in bone.
Calcium in the body must be tightly controlled because it is necessary for cell function such as blood clotting, muscle contraction, enzyme reactions, cellular communication and skin differentiation. It also gives bones and teeth their strength. In fact, the hardest substance in the human body, tooth enamel, is 95 per cent calcium. Calcium is rather deficient in the environment. The body has developed special mechanisms to extract calcium from dietary sources. Normal adults adapt to decreased calcium intake by increasing the fraction of dietary calcium absorbed, but absorption is impaired by ageing. Some 30–60 per cent of dietary intake is normally absorbed. Several hormones are involved in calcium metabolism. Two protein hormones, parathyroid hormone and calcitonin, and a derivative of Vitamin D act to make sure that body optimally assimilates dietary calcium.
A deficiency of calcium results in rickets in children and osteomalacia, both of which display a lack of bone mineralization. Calcium deficiency may also contribute to osteoporosis. Low levels of calcium in the blood can cause tetany, which is characterized by tremor, seizures, muscle cramps, abnormal nerve sensation and shortness of breath.
Toxicity is rare except in certain diseases involving vitamin D or the parathyroid gland.
Dietary sources of calcium are mostly from the dairy foods. However, meat, some beans, seafood and green leafy vegetables contain substantial amounts of calcium. 72 per cent of the calcium available from dietary sources is from the dairy group. Unless an individual has an adverse reaction to milk's components (e.g., lactose intolerance) milk consumption is encouraged.
RDA of calcium is at least 1100mg/day for adult women and1600 mg/day for those age 11 to 24 and for pregnant or breastfeeding women.
Phosphorus is present in the body as inorganic phosphate or phosphate esters, and has many biological roles. Like calcium, the active form of vitamin D regulates phosphorus absorption. It is important for carbohydrate metabolism, cell membrane structure, transport processes, muscle function and energy storage. Energy is stored in the form of adenosine triphosphate (ATP) which is used to fuel many biological processes. Phosphorus is present in nucleic acids and as a structural component of bones and teeth. The phosphate buffer system is important in maintaining the narrow pH range that is necessary for life.
Sources of Phosphorus: Milk, peas, meat, fish, eggs, cottage, cheese, almonds, wheat germ, soybeans, black beans, etc.
The widespread abundance of phosphorus in food makes a deficiency uncommon except in certain diseases. With excessive intake of aluminium, calcium or magnesium containing antacids or laxatives, a phosphate deficiency can occur because these substances prevent phosphate from being absorbed from the intestine.
Phosphorus containing laxatives are often used before surgery or x-ray of the intestines. Sodium phosphate increases the amount of water in the bowel that then stimulates bowel stretch receptors and increases muscle contractions of the intestines. Given as an enema, sodium phosphate primarily promotes evacuation of the colon.
The RDA of phosphorus for males and females over 18 years is 700 mg.
At high doses it may cause nausea, diarrhoea, cramps, muscle paralysis, mental confusion, high blood pressure and abnormal heart rhythms. High levels of phosphate in the blood can cause precipitation of calcium as calcium phosphate in places other than bone and result in low levels of calcium in the blood.
Many cola drinks contain a high amount of phosphate and high consumption of these drinks can result in high phosphate and low calcium in the blood. People with osteoporosis are advised to limit their consumption of these beverages due to their effect on calcium balance.
Magnesium works in conjunction with many enzymes that are involved in energy metabolism, protein synthesis and nucleic acid synthesis. Magnesium supplements are available as several salts (chloride, gluconate, lactate, sulphate and oxide) and are used to treat people with magnesium deficiency due to poor nutrition, restricted diet, alcoholism or magnesium-depleting drugs. Many antacids or laxatives also contain magnesium. It is sometimes given during pregnancy to control eclamptic seizures and to inhibit uterine motility during premature labour.
Large doses can lower blood pressure and cause depression of the central nervous system. Recently magnesium supplements have gained popularity for several unapproved uses. Many patients with migraine headaches have been found to have low levels of magnesium ions. Magnesium supplements appear to decrease the incidence of migraine attacks in certain people. Oral magnesium may be helpful in preventing premenstrual or menstrual migraines. It may also minimize premenstrual mood changes and fluid retention. When used under medical supervision, magnesium may be used to treat cluster migraines. Magnesium supplements should only be used under medical supervision in the presence of heart disease or kidney impairment.
A deficiency of magnesium is rare. Drugs that cause potassium depletion, such as certain diuretics, may also cause low magnesium levels. A deficiency can occur in diabetics, alcoholics and in the presence of gastrointestinal disorders where absorption is impaired, such as prolonged diarrhoea. Magnesium appears to be involved in the regulation of calcium levels; therefore if magnesium levels are low, calcium levels may also be low and unresponsive to treatment unless magnesium levels are corrected. Signs of a deficiency include loss of appetite, irritability, disorientation, convulsions and abnormal behaviour.
The RDA of magnesium for males 31 years and older is 420 mg; for women 31 years and older, 320 mg; for pregnant women 19–30 years, 350 mg; and for lactating women 19–30 years, 310 mg.
Sodium acts to maintain the normal hydration state of the bodily fluids. Sodium ions are found primarily in the plasma and fluid surrounding cells while potassium is found within cells. These ions affect the movement of water in an out of cells. Sodium ions balanced by other ions are necessary to normal cell function in all tissues of the body. Sodium, chloride and potassium concentrations are tightly controlled by osmoreceptors within the brain and the hormones ADH and aldosterone. These ions can be resorbed from or excreted in the urine, sweat, tears as needed.
Sodium Sources: Table salt, eggs, meat, milk, cheese, butter, margarine, bacon, etc.
One to 2 grams of sodium is found in the normal diet. We require an intake of about 4–6 grams each day. Because sodium is added to many foods during processing as a flavour enhancer, intakes in the United States, are often in excess of the requirement.
Sodium in high doses may be involved in hypertension in some individuals.
Potassium is essential to energy metabolism and to glycogen and protein synthesis. Because of its role in neuromuscular conduction, high or low levels of potassium can be life-threatening. Potassium involves in transmission of nervous impulses, chemical reactions and acid–base balance in the body.
- Low levels of potassium: (hypokalemia) results in cardiac arrhythmias, muscle weakness, sodium loss in the urine, alterations in acid–base balance and the inefficient use of carbohydrate.
- High levels of potassium: (hyperkalemia) requires immediate medical attention because the heart may fail to beat normally or at all.
- Sources of Potassium: Spinach, butter, beans, oranges, milk, peas, meat, fruits, nuts and vegetables.
Essential trace elements range from metals to non-metals. What makes them essential is their variable oxidation state. They are important parts of oxidative-reduction enzymes in the body. They also have roles in transport proteins, cofactors, and detoxification and defence. Trace elements are carried bound to transport proteins in the blood. Because they are generally toxic when in free form, they are transported in bound form since entry to exit within the body.
Iron is important in the transportation of oxygen from the lungs by way of the blood stream to the tissues. It is present in the red blood cell protein, haemoglobin. A similar protein in muscle, myoglobin, also contains iron and stores oxygen for use during muscle contraction. Iron is found in the portion of the cell involved in energy production and as a cofactor for several enzymes.
Iron deficiency generally occurs during the growth period or when intake fails to replace iron loss that is associated with blood loss. When iron stores are depleted and there is inadequate production of heme (the portion of haemoglobin associated with the iron), the red blood cells become small (microcytic) and have decreased capacity to carry oxygen. There is also a drop in iron-containing enzymes that are important in cellular metabolism. This results in decreased work capacity, fatigue and altered behaviour such as irritability.
Toxicity: Iron poisoning is the most common cause of death resulting from poisoning in children. Supplemental iron can cause gastric irritation, abdominal pain, constipation, diarrhoea, nausea and vomiting. Certain antacids may decrease the absorption of iron supplements.
The RDA for iron in males over 19 years is 10 mg; for females of 11–50 years, 15 mg; for females over 51 years, 10 mg; for pregnant females, 30 mg; and for lactating females, 15 mg. Not all forms of iron are the same: 1 gram of ferrous gluconate=120 mg elemental iron; 1 gram ferrous sulphate=200 mg elemental iron; and 1 gram of ferrous fumarate=330 mg elemental iron.
Zinc is important in growth, appetite, development of the testicles, skin integrity, mental activity, wound healing and proper functioning of the immune system. Zinc is a cofactor for many enzymes, which means that zinc is necessary for the proper functioning of these enzymes. These enzymes participate in the metabolism of carbohydrates, lipids, proteins and nucleic acids (such as DNA). Zinc is involved in the functioning of the immune system and in the expression of genetic information. Zinc is present in bone and is involved in the regulation of bone calcification. It is also present in members of a class of proteins called the metallothioneins that are believed to provide antioxidant protection by scavenging free radicals.
The RDA of zinc for males 11 years and older is 15 mg; for females 11 years and older, 12 mg; for pregnant females, 15 mg; for lactating females during the first 6 months, 19 mg; and during the second 6 months, 16 mg.
A zinc deficiency may be associated with diets high in unrefined cereal and unleavened bread or diseases of the intestine such Crohn's disease, alcoholism or pregnancy.
Toxicity from zinc supplements can cause flu-like symptoms, fever, epigastric pain, fatigue, vomiting, dehydration, anaemia, depressed immune function and decrease in the ‘good’ form of cholesterol. Excessive zinc interferes with the function of copper and iron.
Iodine is absorbed well, circulates both free and bound, and is sequestered in the thyroid gland where it is incorporated into the thyroid hormones, triiodothyronine (T3) and thyroxine (T4). These hormones are important in regulating the basal metabolic rate (associated with energy production) of adults, and the growth and development of children. Iodine is sometimes used to help thin secretions from the lung in order to help expel the secretions. It is used on the skin as an antiseptic, although it may stain the skin, irritate tissues and cause sensitization in some people.
Deficiency: Deficiency is manifest by a decreased metabolic rate, lethargy and obesity. A prolonged deficiency of iodine causes the thyroid gland to increase in size such that a large nodule referred to as goitre, protrudes from the neck. In many countries, inorganic iodides are added to table salt to prevent the deficiency. Iodine deficiency in infants and children results in mental retardation. Inadequate maternal intake causes a deficiency in the foetus and newborn. Early recognition of the syndrome is key to minimizing mental retardation. Some plants produce goitrogens (cabbage, plantain). These substances fool the thyroid and inhibit the synthesis of the thyroid hormones. Arsenic can also inhibit the synthesis of thyroid hormones by interfering with normal thyroid function.
Toxicity: High doses of iodides (the salts of iodine) inhibit thyroid hormone synthesis and release. As lack of iodine leads to symptoms of thyroid deficiency, so do excessive doses of iodides. It is sometimes used to treat hyperthyroidism. With prolonged excessive intake, a goitre can occur. Sometimes a large dose of iodides is given before thyroid surgery to shrink the size of the thyroid gland.
Some people are hypersensitive to iodine and this can lead to skin rashes, mucous membrane ulcers, fever, ‘iodism’ (metallic taste, gastric irritation, burning mouth and throat, sore teeth and gums, symptoms of a head cold), and swelling in the neck area. Iodine supplements can cause acne.
The RDA for iodide in males and females over 12 years is 150 mg; for pregnant females, 175 mg; and for lactating females, 200 mg. The content of iodide in iodized table salt is 76 mg/g of salt; therefore with an average use of 3.4 g per day, approximately 200 mg of iodide is consumed.
Chromium is an essential trace element that is needed for carbohydrate, fat and nucleic acid (DNA or RNA) metabolism. Main sources in the diet include whole grains, egg yolks, brewer's yeast, liver, meats and nuts.
Chromium deficiency is usually only seen in adults eating highly refined foods. With a chromium deficiency, blood sugar levels are generally high. There may also be abnormalities of nerve stimulation of the extremities (arms, hands, legs and feet) and alterations of brain tissue. There are some people with type 2 (non-insulin dependent) diabetes that appear to have improved blood sugar control with chromium supplementation, but this is not seen in all diabetics. Chromium is part of the glucose tolerance factor (GTF) that is required for insulin action, however more thorough studies need to be conducted before supplementation in diabetics becomes a general recommendation. There is no scientific basis for the use of chromium supplements by athletes to increase muscle mass or to reduce body fat. Chromium supplements may lower cholesterol and triglycerides in people with diabetes as well as with non-diabetics, but it may take months before this result is seen and the effect may not be substantial. Chromium appears to affect some of the enzymes that regulate cholesterol synthesis. The mechanism by which chromium participates in proper nerve function is not well understood.
The RDA is 50 to 200 micrograms.
Toxicity: Not many side-effects have been reported from the use of chromium supplements unless excessive doses are taken. This has resulted in liver and kidney failure, anaemia, muscle breakdown and abnormalities in blood clotting. People with impaired kidney function should seek medical advice before taking supplements.
Cobalt has a central action in vitamin B12 function. Meats provide cobalt as a component of vitamin B12. If the vitamin B12 requirement is met, then the cobalt requirement is met. It is not known if cobalt has other functions. An RDA has not been established. Cobalt can be toxic to humans because it is not regulated at the point of absorption.
Excess cobalt can cause polycythemia (increased red blood cells), bone marrow hyperplasia, pancreatic failure or congestive heart failure. At large doses, it also interferes with the absorption of iron.
Copper is incorporated into many enzymes and is necessary for their actions. For example, the copper containing ceruloplasmin is involved in the transport of iron in the blood to places where haemoglobin synthesis occurs. Another enzyme is involved in maintaining connective tissue integrity, and in copper deficiency, defective bone matrix and osteoporosis may occur.
Deficiency: Although a deficiency is rare, it can occur in people with prolonged diarrhoea or other disorders of intestinal absorption. It can also occur in the presence of high dose zinc supplementation. Signs of a deficiency include anaemia, a decrease in certain white blood cells, skeletal demineralization, loss of hair colour and skin pallor. Children with copper deficiencies may experience ruptured blood vessels, central nervous system abnormalities, growth retardation and poor temperature regulation.
Toxicity:Excessive doses of copper can cause diarrhoea, epigastric pain and discomfort, blood in the urine, liver damage, low blood pressure and vomiting. No RDA has been established for copper.
Two diseases are associated with abnormal copper metabolism: Wilson's disease is marked by high levels of copper, especially in the brain, liver, kidney and eye; Menke's kinky hair syndrome results from defective transport of copper into the blood of male infants and are associated with retarded growth and a kinky appearance of the hair.
Manganese assists in the activity of many enzymes, including some involved in lipid, protein and carbohydrate metabolism.
Deficiency:Manganese deficiency has not been well documented in humans. A few people on manganese deficient diets showed signs of elevated calcium and phosphorus, suggesting that dissolution of bone to release manganese stores may also release calcium and phosphorus into the blood. As such, it is speculated that a manganese deficiency may be a contributing factor for osteoporosis. In animals, the deficiency has been associated with abnormal reproductive ability, growth retardation, birth defects, abnormal formation of bone and cartilage, dermatitis and impaired glucose handling.
Toxicity: Chronic poisoning from manganese inhalation by miners has caused dementia, psychiatric disorders similar to schizophrenia, and neurological changes resembling Parkinson's disease. Iron and manganese affect the absorption of each other. Chronic liver disease can cause manganese accumulation and toxicity. No RDA has been established for manganese.
Molybdenum is part of the molecular structure of several enzymes. One of these enzymes is involved in the formation of sulphate. Under normal circumstances, there have been no reports of molybdenum deficiency. Molybdenum deficiency leads to headache, irritability; lethargy and coma have occurred but have been rapidly reversed upon addition of molybdenum. An excess of molybdenum interferes with copper and iron absorption. No RDA has been established for this element.
Selenium is an essential non-metallic element. Foods containing selenium include meat, poultry, grains and seafood. Some reports have suggested that selenium may protect against certain types of cancer, but large trials in humans are needed to support this. Selenium is important for the function of several proteins. One of these is glutathione peroxidase, an enzyme that prevents oxidative damage to cells from a variety of peroxides. Selenium also appears to bind to some minerals such as arsenic and mercury and decrease their toxicity.
Deficiency: Although selenium deficiency is uncommon in the United States, low levels in the body may be associated with acute illness. Symptoms of selenium deficiency include muscle weakness and pain, inflammation of the muscles, fragile red blood cells, degeneration of the pancreas and abnormal colouration. There have also been associations of selenium deficiency with several diseases affecting the heart muscle, but a protective effect against heart disease has not been proven. In geographic areas where selenium is deficient in the soil and therefore in food, human deficiencies have been reported to cause dilation of the heart and congestive heart failure.
Toxicity: Side effects with high doses of selenium supplements include hair and nail loss, skin lesions, fatigue, irritability, liver and kidney damage, nausea, vomiting and abnormal blood clotting. Animals in the west grazing on plants that have accumulated selenium show acute or chronis selenium poisoning. Chronic selenium toxicity (alkaline disease) is characterized by muscle degeneration, rough coat, laboured breathing and cardiovascular failure. Acute selenium toxicity (blind staggers) manifests as weight loss, anorexia, excessive salivation, jaundice or necrosis of the heart and liver.
For cancer prevention, a typical dose of selenium is 200 micrograms per day. The RDA for women over 19 years is 55 micrograms; for pregnant women, 65 micrograms; for lactating women, 75 micrograms; and for men over 19 years, 70 micrograms.
Fluoride may not actually function as an essential trace element but it has beneficial effects on skeletal and dental health. Fluoride assists in the prevention of tooth decay. It works by increasing the tooth resistance to acid, promoting remineralization and inhibiting the process by which bacteria promote cavities. There is also evidence that fluoride helps protect against osteoporosis. It is associated with a decrease in bone demineralization. Fluoridation of the water supply is an effective method for providing fluoride. Oral supplements are available for people that do not have access to fluoridated water. Although there is no RDA for fluoride, the protective effect of fluoride for teeth occurs at an intake of 1.5 mg/day or more for adults. Intakes over 2.5 mg/day in children may cause mottling of the teeth.
Toxicity: Acute toxicity has occurred by ingestion of household products containing high levels of fluoride such as certain insecticides. The mechanism of fluoride toxicity is conversion in the stomach to hydrofluoric acid. Gastrointestinal symptoms predominate and include nausea, vomiting, diarrhoea and abdominal pain. Chronic ingestion of high amounts of fluoride during tooth development results in dental fluorosis and mottling of teeth. It can also result in increased density and calcification of bone and in severe cases is referred to as crippling skeletal fluorosis.
- Give the chemistry, functions and deficiency manifestations of vitamin A.
- Mention the sources of vitamin A. Describe the function and effects of deficiency of vitamin A. What is the daily requirement?
- Describe briefly the chemical nature, action in the body, dietary sources and nutritional importance of vitamin A.
- Name the fat-soluble vitamins, their occurrence, daily adult requirements and their importance to the body.
- Give a brief account of the chemistry, sources, daily requirement and deficiency states of thiamine. Describe the mechanism of the action.
- Describe briefly the chemical nature, mode of action, dietary sources and nutritional importance of thiamine.
- Describe the chemistry, sources, daily requirement and metabolic functions of
- niacin. Mention the diseases caused by their deficiency in diet.
- What is riboflavin? Discuss its metabolic role in the body and the deficiency symptoms.
- What are vitamins? Describe the functions and properties of any two vitamins of B-complex group.
- Mention the sources of vitamin B12 and the effect of its deficiency. Describe the metabolic functions of vitamin B12.
- Describe the sources, requirements, functions and deficiency manifestations of vitamin C.
- Describe the metabolism of calcium in the body.
- Describe the sources, requirements and physiological functions of calcium.
- What part does calcium play in bodily functions? How is the level of calcium in the blood regulated?
- Mention the sources of iron in our diet. Describe the mechanism of iron absorption. Mention how iron is transported and stored in our body.
- State briefly the sources of iron in our diet. Mention the functions of iron in the body. Discuss the metabolism of iron.
- Discuss the metabolism of sodium in the body.
- State how copper is metabolized in the body.
- Write notes on:
- Function of manganese in the body
- Iron and its significance
- Function of zinc
- Function of fluorine
Multiple Choice Questions
- Zinc is a constituent of
- Carbonic anhydrase
- Malate dehydrogenase
- Haemoglobin formation needs both
- Iron and zinc
- Iron and calcium
- Iron and copper
- Iron and magnesium
- Calcium is required for the activation of the enzyme
- Isocitrate dehydrogenase
- Succinate thiokinase
- The absorption of calcium is increased by the dietary higher levels of
- Vitamin A
- Calcium absorption is interfered by
- Fatty acids
- Amino acids
- Vitamin D
- Vitamin B12
- The percentage of calcium in milligram in nonionized form is about
- Retinal is reduced to retinol by retinene reductase in presence of the coenzyme
- NADH+ H +
- Retinol exists as an ester with higher fatty acids in the
- All of the above.
- Retinol is transported to the blood as retinol attached to
- Carotenes are transported with the
- In the blood, the vitamin esters are attached to
- The preformed vitamin A is supplied by foods such as
- Fish liver oil
- All of the above
- Lumirhodopsin is stable only at a temperature below
- The normal concentration of vitamin A in blood in I.U./dl.
- The activity of tocopherols is destroyed by
- All of the above
- Some tocopherols are
- Terpenoid in structure
- Dionol in structure
- Isoprenoid in structure
- Farnesyl in structure
- Vitamin E is stored in
- Both of the above
- None of the above
- Vitamin E protects the polyunsaturated fatty acids from oxidation by moleculer oxygen in the formation of
- All of the above
- Vitamin K2 was originally isolated from
- Putrid fish meal
- Vitamin K regulates the synthesis of blood clotting factors
- All of the above
- Vitamin C is required in the metabolism of
- Both of the above
- None of the above
- Thiamine is also said to be
- Antiberiberi substance
- Antineuritic vitamin
- All of the above
- Lipoic acid is also termed as
- Thioctic acid
- Acetate replacement factor
- All of the above
- Folic acid is also termed as
- SLR factor
- Pteroyl- glutamic acid
- Liver lactobacillus casei factor
- All of the above
- Thiamine is oxidized to thiochrome in alkaline solution by
- Potassium permanganate
- Potassium ferricyanide
- Potassium dichromate
- Potassium chlorate
- Riboflavin in alkaline solution when exposed to ultra violet light is converted into lumiflavin which in ultra-violet light has a
- Greenish yellow fluorescence
- Bluish yellow fluorescence
- Reddish yellow fluorescence
- Light yellow fluorescence
- FMN is a constituent of the
- Warburg yellow enzyme
- Cytochrome C reductase
- L amino acid dehydrogenase
- All of the above
- Niacin is present in the maize in the form of
- Nicotinic acid is essential for the normal functioning of
- Intestinal tract
- Nervous system
- All of the above
- Pyridoxine produces a coloured compound with
- 2:6 dichloroquinone chlorimide
- 2:6 dichloroquinone
- 2:4 nitroquinone
- All of the above
- Pyridoxal phosphate is involved in the desulphuration of
- Both of the above
- None of the above
- Pentothenic acid deficiency causes
- All of the above
- Pantothenic acid exists in the tissues as
- Coenzyme A
- Pantoic acid
- Folic acid coenzymes take part in the synthesis of
- Both of the above
- None of the above