This article throws light upon the fourteen main types of vitamins. They are: 1. Fat Soluble Vitamins 2. Vitamin K 3. Vitamin E 4. Vitamin D 5. Riboflavin/B2 6. Thiamine 7. Vitamin C/Ascorbic Acid 8. Biotin 9. Pantothenic Acid 10. Niacin 11. Choline 12. Folic Acid 13. Vitamin B12/CyanacobaIamin 14. Vitamin B6/Pyridoxine.
Type # 1. Fat Soluble Vitamins:
Vitamin A (Chemistry & Salient Features):
(i) It is fat soluble, long chain unsaturated alcohol with double bonds (five in A1 and six in A2).
(ii) It is found as carotenoids in plant, a precursor of vitamin A.
(iii) The β-carotene molecule having two β-ionone ring linked through a polyene chain, when cleaved from middle double bond, (by β-carotene-15, 15′ di-oxygenase) yields 2 retinal, the aldehyde form of vitamin A.
(iv) Retinal, in presence of retinene reductase and NADH + H+ yields corresponding retinol.
(v) Trans forms are more active biologically in comparison to cis form.
(vi) Rat, pig, goat, sheep, rabbit, buffalo, dog and Holestein Frissian (HF) cow cleaves virtually all carotenoid in intestine.
(vii) Human, cattle (other than HF), horses and carps absorb significant amount of carotenoids for storage in liver and adipose tissues. That is why milk fat is yellowish in cattle (except HF) and white in buffaloes and HF.
(viii) 3-dehydroretinol (A2) is 40% potent with respect to retinal (A1).
(ix) β-carotene has highest vitamin A activity.
(x) β -carotene and vitamin E acts a antioxidant at lower and higher O2 concentration respectively, may be a reason of its anti-carcinogenic property.
(xi) Mammals and marine fish have vitamin A1, while common fresh water fish have vitamin A2.
(xii) Retinol, retinal and retinoic acid has – OH, – CHO and – COOH at 15 C of polyene chain respectively.
(xiii) Vitamin E prevents oxidative destruction of vitamin A.
(xiv) The site of making carotene to active form (retinol) in liver in human but intestinal wall play a major role in goat, pig, rat, sheep, rabbit and chicken complemented by liver.
(xv) Retina contains rode’s which facilitate visual activity in dim light/in night and cones for bright light vision and colour accommodation.
(xvi) Hyper-polarisation of rod membrane causes initiation of receptor potential.
Photolysis of rhodopsin results into:
1. Closure of Na+ channel (Cytosolic Ca++ ↑ or ↓ in CGMP)
2. Na+ permeability reduces.
3. Hyperpolarization of rod membrane.
4. Change in configuration by 5°.
5. Visual signal from rods.
(xvii) Rhodopsin is a conjugated protein (opsin + 11-cis-retinal). Its light absorbing (photo- sensitivity) is due to polyene group of 11-cis-retinal.
(xviii) Vitamin A has no enzymatic activity.
Five Distinct Functions of Vitamin A:
1. Normal vision
2. Maintenance of epithelial integrity
3. Reproductive function
4. Re-modelling of bones
5. Immune competency
Deficiency of Vitamin A:
(i) Xerophthalamia Keratomalacia
(ii) Follicular conjunctivitis
(iii) Keratomalacia
(iv) Nyctalopia
(v) Follicular hyperkeratosis of skin.
(vi) Keratinizing metaplasia of epithelium of nose respiratory mucosa, oesophagus, genitourinary tract.
(vii) Urolithiasis
(viii) Faulty remodeling of bones.
(ix) Foramina of nerve passage fails to enlarge result in to distortion, herniation, degeneration of nerves.
When plasma vitamin A concentration is less than 20 µg (calves) to 40 µg/dl (cattle) and < 10 µg/dl in pigs is considered deficiency.
Unit:
International unit (IU)
1 IU = 0.3 µg trans-retinol
= 0.344 µg trans-retinyl acetate
= 0.66 µg trans-retinyl palmitate
= 0.60 µg carotene
Recommended dose is 1000-2000 IU daily.
Preparations:
(i) Natural fish oil.
(ii) Synthetic ester of acetate, propionate, palmitate.
(iii) Multivitamin oral or injectable preparations.
(iv) Retinyl esters coated with gelatin and anti-oxidants.
Type # 2. Vitamin K:
Dam in 1934 termed it for the first letter of danish word “Koagulation”.
Chemistry:
(i) Vitamin K is the derivative of naphthoquinone. When it contains saturated isoprene unit called phylloquinone (plant origin). When each isoprene unit consists of double bond, called menaquinone obtained from bacteria.
(ii) No. of isoprene unit may vary.
(iii) Biological activity of vitamin K depends upon the ring or menadione not synthesized by animal body.
(iv) Vitamin K is fat soluble (except) few synthetic water soluble forms) and heat stable yellow oil, although it can loose property when exposed to moisture, heat, light, transition metals and unsaturated fat.
Absorption:
(i) Microflora of rumen, caecum and large intestine synthesize vitamin K, although in non-ruminants the absorption is limited. Quick passage of ingesta as in poultry limits the synthesis as well as absorption therefore dietary supplementation is necessary.
(ii) Liver can modify isoprene units.
(iii) Vitamin K require dietary fat, bile and pancreatic secretion for absorption, similar to other fat soluble vitamins.
(iv) Liver concentrates but can’t retain for long, gets it distributed to tissues excreted rapidly after glucuronidation.
(v) The microbial synthesis of vitamin K reduces on continuous therapy with sulfa drug/antibiotics.
Metabolic/Physiological Function:
(i) The precursor of coagulative proteins factors II, VII, IX & X are synthesized by liver, activated by incorporation of CO2 in to glutamic acid residue including osteocalcin required for normal bone formation.
(ii) Vitamin K enhances the biosynthesis of factor II, VII, IX and X in liver.
(iii) Vitamin K dependent blood clotting factors in the absence of vitamin K remains inactive precursor & proteins in liver.
Deficiency:
Impaired homeostasis, uncontrolled haemorrhage i.e. echymoses, epistaxis, hematurea, gastrointestinal bleeding etc.
Dietary Requirement:
(i) It ranges from 0.05 to 2 mg/kg of diet.
(ii) Pregnancy, lactation, growing stage needs more vitamins.
(iii) Abnormal fat digestion, biliary obstruction, inflammatory bowel disease impair absorption can cause deficiency.
Assessment of Status:
It can be done by:
1. Estimating prothrombin time.
2. Blood vitamin K concentration.
3. Coagulation time (prolonged in deficiency).
Preparation:
(i) Single or part of multivitamin, oral or parenteral preparation is available.
(ii) Chemically stabilized forms should be preferred to overcome oxidative instability.
Sources:
(i) Green part of plant (Menadione bisulfite & Menadione de-methyl pyrimidinol bisulfite).
(ii) Liver and fish meal, fish oil.
(iii) Dehydrated alfalfa leaf meal.
Toxicity:
(i) Approximately 500 to 1000 times to nutritional requirement produces hemolytic anemia, hyperbilirubinemia, haemoglobinurea.
(ii) MLD for single parenteral injection of menadione in chicks, dogs, rabbits, mice, rats is 75-200 mg/kg body weight.
(iii) Horse —2.1-8.3 mg/kg body weight menadione bisulfite causes acute renal failure.
(iv) Aqueous solution of free dl-a-tocopherol are best absorbed following parenteral injection.
(v) Chemically stabilized form of tocopherol with polyethylene glycol or tocopheryl esters of acetate succinate or nicotinate are good for feed supplementation.
(vi) Compared to vitamin A or D, E is relatively non-toxic.
(vii) In vitamin E deficiency state vitamin E @ 25 IU/kg body weight is recommended for parenteral administration or 40 IU/kg body wt. for oral administration in domestic animals.
(viii) Injectable preparations of vitamin E is combined with Se in the ratio of 10: 1.
(ix) Hypervitaminosis can result when doses 100 times to nutritional requirement; induce coagulation defects, abnormal calcification etc.
Type # 3. Vitamin E:
(i) Evans and Bishop isolated it from wheat germ oil termed vitamin E and Tocopherol.
(ii) Vitamin E is also known as anti-sterility vitamin.
(iii) There are 8 structural isomers, vary by number of methyl group in 6-OH- chroman nucleus and degree of unsaturation of the isoprene side chain.
(iv) Tocopherol has saturated side chain but tocotrienol contain unsaturated side chain.
(v) Tocopherol are redox agent which under certain circumstances act as antioxidant, quenches free radicals.
(vi) Vitamin E gets oxidized when exposed to heat, moisture, rancid fat or transition metal.
(vii) α-tocopherol acetate is common dietry supplement.
(viii) Absorption, fate and excretion of vitamin E is similar to other fat soluble vitamins.
(ix) Metabolic product of vitamin E is tocopheronic acid and lactone, are excreted in urine.
Metabolic Function:
(i) Tocopherol is interwoven with long chain fatty acid in lipid bilayer of cell membrane.
(ii) The cellular integrity is highly vulnerable to free radical.
(iii) Free radical can initiate the vicious circle i.e. peroxides can yield two free radical, each can again give rise to another set of free radicals and so on.
(iv) Antioxidants (tocopherol) contribute hydrogen, rearrange electrons of free radical inactivated form, thus prevents the vicious chain reaction, ultimately protects the enzyme system and cell membrane as for RBC, capillary integrity and nutritional muscular dystrophy.
(v) The free radical quenching of tocopherol is supplemented by selenium of enzyme glutathione peroxidase.
(vi) Liver is the store house for tocopherol and glutathione peroxidase (along with its selenium).
(vii) Glutathione peroxidase and or vitamin E convert hydrogen peroxidase to water and organic peroxide into alcohol.
(viii) α-d-tocopherol is the main naturally occurring compound possesses vitamin E activity followed by dl-α-tocopherol, α-β-tocopherol and d-α- tocopherol.
(ix) Vitamin E has a role in mitogen stimulated lymphocyte proliferation, cell mediated toxicity and natural Killer Cell’s activity.
(x) Vitamin E and Se play important role in normal reproductive function to reduce retention of placenta, metritis, cystic ovaries etc.
(xi) Antioxidants help in prostaglandin biosynthesis and blood coagulation.
(xii) Dietary vitamin E supplementation enhances secondary humoral immune response.
(xiii) Se and vitamin E can ameliorate each others deficiency symptoms.
Deficiency:
Common in young growing animals.
(i) Nutritional muscular dystrophy/white muscle disease characterized by generalized weakness, stiffness, motor disturbances and heart failure in rats, rabbits, poultry, dogs and other domestic animals.
(ii) Reproduction-Mid gestational resorption of fetus in rodent.
(iii) Mulberry heart disease i.e. Hepatosis dietetica in pigs.
(iv) Encephalomalacia in poultry.
(v) Degenerative myeloencephalopathy.
Deficiency:
Plasma tocopherol 0.5-1.0 µg/ml or less is considered deficiency in most species.
Unit:
IU = 1 mg of dl-α-tocopheryl acetate
= 1.49 mg of da-tocopherol
= 1.36 mg of da-tocopheryl acetate
= 1.21 mg of da-tocopheryl-succinate
Dietary Requirement:
(i) Requirement is higher in pregnancy, lactation and rapid growth.
(ii) Transition elements (Fe, Zn, Cu, Mn) oxidize vitamin E, not to be mixed with vitamin E preparation.
(iii) Vitamin C protects vitamin E from oxidative damage.
(iv) Unsaturated fat content of feed may affect stability of vitamin E.
Type # 4. Vitamin D:
(i) Ergocalciferol or D2 from plant, cholecalciferol or D3 of animal origin are considered vitamin D.
(ii) “Ultraviolet exposure was efficacious in curing rickets” observed by Hess and Weinstock; Steenbock and Black (1924).
(iii) Mc Collum and others (1922) discovered vitamin D.
(iv) D3 has 2-30 times more biological activity in comparison to D2.
(v) Mellanby and Huldschinsky (1919) observed that addition of cod liver oil or exposure to sun prevented and cured the disease ricket.
(vi) Green fodder need proper exposure for conversion of ergosterol into ergocholecalciferol (D2), over exposure may yield undesirable products.
(vii) Vitamin D is vulnerable to oxidation by:
1. Light
2. Rancid fat
3. Heat
4. Moisture
5. Transition metals.
(viii) Vitamin D is unstable but lipid soluble. Water soluble crystalline form and nuorinated side chain of 1, 25 (OH)2 D are stable for longer duration.
Hormonal Nature:
(i) Synthesized in skin, transported in blood to target tissue, activated by highly regulated enzymes.
(ii) Active form i.e. calcitriol binds to specific receptors in target tissue.
(iii) The receptor for calcitriol is from steroid and thyroid hormone receptor super gene family.
(iv) Receptor hormone complex initiates transcription, produce calcium binding proteins, facilitates uptake of calcium from intestinal lumen and also in loop of henle under PTH and calcitriol interaction.
(v) Calcitriol or 1, 25 (OH)2 D is necessary for normal lysyl oxidase activity and collagen cross linking of matrix and normal mineralization of organic matrix.
(vi) Vitamin D (calcitriol) interacts with PTH in resorption, re-modelling of bone and calcium-phosphorus homeostasis.
(vii) Calcitriol promote monocyte differentiation into macrophages and enhances the chemo- tactic and bactericidal function of neutrophil and macrophages.
Metabolic Function of Vitamin D:
(i) Regulation of PTH secretion.
(ii) Homeostatic control of Ca & P metabolism.
(iii) Absorption of Ca++& Pi from intestine.
(iv) Renal excretion control for Ca++ & Pi.
(v) Bone re-modelling and mineralization.
(vi) Immune system regulation.
Storage of vitamin D is not in appreciable amount in most animals.
Egg shell thickness reduces in vitamin D and consequent Ca & P deficiency, due to mandibular anomalies, chicks fail to crack the shell.
Blood level of 25 OH D/calciferol indicates dietary intake and uv exposure where as 1, 25 (OH)2 D level indicate both supply and renal activation capacity.
Deficiency:
(i) Rickets of weight bearing bones in growing animals.
(ii) Osteomalacia through mobilization of Ca++ and Pi in adult.
(iii) Milk fever in high yielder cows due to excessive drainage of calcium in milk. It can be infused with calcium salt.
(iv) Massive doses of vitamin D before parturition can prevent this condition.
(v) Feeding of calcium deficient diet for last two weeks before calving can help by increasing its absorption from intestine.
Major Therapeutic uses of Vitamin D:
(i) Prophylaxis and cure of nutritional rickets.
(ii) Metabolic rickets and osteomalacia.
(iii) Treatment of hypoparathyroidism.
(iv) Prevention and treatment of osteoporosis.
(v) Cholecalciferol as rodenticides.
Dietry requirement, indication and use:
(i) Healthy animals with proper sun exposure don’t require any supplementation.
(ii) Body coat, thickness affects uv penetration.
(iii) Vitamin D should be administered in protective coating (gelatin, resin and antioxidant) in feed supplements.
(iv) Dietry requirement range between 125-1000 IU per kg of diet.
(v) IU = 0.025 µg of vitamin D2/D3 similar in activity in human and animals.
(vi) D3 is ten times more active with respect to chicks (one chick unit = 0.025 µg of vitamin D2).
Hypervitaminosis/Toxicity:
(i) Due to consumption of certain plant i.e. Cestrum diurnum and Solanum spp. contain toxic concentration of 1, 25 (OH)2 D as a glycoside.
(ii) MLD for cholecalciferol is 44 mg/kg b.wt. for rodent and 88 mg/kg body wt. for dog.
(iii) Interfere with metabolism of other fat soluble vitamin i.e. A, E & K.
(iv) Dystrophic mineralization of soft tissue.
(v) Hypercalcemia may cause vasoconstriction and ischemic tissue damage, cardiac arrhythmia and neurologic disturbances.
Preparations:
(i) Chemically stabilized form of vitamin D for feed supplement i.e. gelatin and antioxidants coated forms.
(ii) Injectable and oral preparation singly or as multivitamin.
Type # 5. Riboflavin/B2:
(i) Warburg & Christian (1932) mentioned it as old yellow (respiratory) enzyme.
(ii) Wagner and Jauregg isolated B2 from egg white.
(iii) Kuhn et. al. and Karrer et. al. (1934-35) identified chemical structure of riboflavin, later synthesized.
Chemical Structure:
Riboflavin consists of a dimethyl isoalloxazine ring having ribose side chain as free alcohol. Other form of riboflavin are Flavine mononucleotide. (FMN) and Flavine adenine dinucleotide (FAD), act as coenzyme in important metabolic function/reactions.
Digestion, Absorption and Fate:
(i) Diet contains riboflavin in its phosphorylated form, gets hydrolysed to riboflavin before being absorbed.
(ii) Riboflavin is absorbed by active transport normally, albeit higher concentration facilitate passive diffusion.
(iii) Once absorbed, riboflavin is again phosphorylated (FMN) transported albumin bound to liver through circulating blood.
(iv) Hepatocytes converts FMN to FAD, stocked to a limited extent for lean period.
(v) These coenzyme (FMN, FAD) undergo hydrolysis yield free riboflavin, excreted through kidney & bile. Riboflavin doesn’t undergo any metabolic destruction.
(vi) Oestrogen induced riboflavin binding protein has been mentioned in rats for placental transfer to fetus or to eggs in chicken.
Metabolic/Physiological Function:
Flavin mono nucleotide and Flavin adenine dinucleotide are the main functional entity of riboflavin which play active role in oxidation of substrate (i.e. carbohydrates, lipid and amino acids) to generate ATP via electron transport system.
Antimetabolites:
(i) When ribose is substituted by other pentoses, the activity of riboflavin reduces.
(ii) Hexoses in place of ribose yield antivitamins.
(iii) Change in methyl groups position produces antivitamin.
Deficiency:
(i) Dermatitis, loss of hair, loss of appetite, lens opacities, muscle weakness, ataxia are common deficiency symptoms.
(ii) Deficiency damages sciatic and brachial nerves produces paralysis in chicken called curled toe paralysis.
Requirement:
(i) It ranges between 1.8-4 mg/kg of diet for all non-ruminants.
(ii) Ruminants do not need riboflavin as ruminal microflora fulfills the requirement.
Toxicity:
(i) Common in lab animals manifested as reproductive abnormalities and death.
(ii) Upper safe limit is 10-20 times and possibly 100 times to the nutritional requirements.
Type # 6. Thiamine:
Eijkman (1897) cured polyneuritis/ beriberi in birds and human by administering rice polishings in ration.
Admiral Takaki (1880) added greens against beriberi for his navy men.
Funk’s active factor i.e. ‘Vitamin’ later vitamins was termed vitamin B1.
Jansen and Donath (1926) isolated B1 in crystalline form later stated as thiamine by Council of Pharmacy and Chemistry.
Chemical Properties:
1. Highly water soluble, destroyed by cooking.
2. Mono-nitrate salts of thiamine is more stable with respect to hydrochloride salt.
3. It consists of one pyrimidine and one thiazole ring linked by methylene.
Metabolic/Physiological Function:
(i) Thiamine pyrophosphate (TPP) is the active form of thiamine, plays important role as coenzyme in carbohydrate metabolism.
(ii) It functions as coenzyme co-carboxylase for oxidative decarboxylation of pyruvate and α-keto-gutarate (keto acids) to acetyl coenzyme A and succinyl coenzyme A respectively. These coenzymes further enter into TCA cycle.
(iii) TPP plays important role in HMP/PPP pathway, ribonucleotide synthesis, NADP and NADH.
(iv) It is required for synthesis of cholesterol and fatty acid due to which thiamine can affect neural membrane synthesis and thereby integrity and can cause peripheral neuritis.
(v) Thiamine is necessary for Ach synthesis.
(vi) Metabolically active organs (liver, kidney, heart and brain) maintain higher level of B1, but can’t store except in pigs muscle.
Absorption and Fate:
(i) The absorption of thiamine normally is carrier mediated, although significant passive diffusion supervene at higher concentration.
(ii) Excretion depends upon intake. Higher quantity saturates tissues first and excess appear in urine as thiamine or pyrimidine.
(iii) At recommended dietry requirement (0.8-2 mg/kg of diet) it rarely appear in urine.
Antimetabolites/Anti-vitamines and Deficiency:
(i) Neopyrithiamine, pyrithiamine and oxythiamine are antimetabolites of thiamine.
(ii) Pyrithiamine interferes with phosphorylation of thiamine.
(iii) Oxythiamine when phosphorylated, competes with TPP for the enzyme.
(iv) Thiaminases found in Some microbes, fishes and some plants are of two types. One cleaves the thiazole ring, thus destroys thiamine, other exchanges thiazole ring for nicotinic for picolinic acid and form antivitamin.
(v) Bracken fern contains thiaminases, result into poisoning in horses and other non-ruminants herbivorous.
(vi) Carnivorous develop paralysis (chastek paralysis) due to deficiency of thiamine, as it is destroyed when fed upon raw fish or its viscera having thiaminases.
(vii) Increased thiaminase activity in rumen may predispose thiamine deficiency among ruminants.
(viii) Amprolium, the coccidiostat in higher dose may pose thiamine deficiency among poultry.
(ix) High sulfur feeding can predispose thiamine deficiency in cattle.
Dietry Requirement:
(i) It ranges from 0.8 to 2 mg/kg of diet for most birds and animals.
(ii) Ruminants doesn’t require any supplementation normally.
(iii) Coprophagy helps rabbits.
(iv) Beyond gastrointestinal diseases, stress reduces thiamine utilization.
(v) Thiamine may help in lead toxicity.
Thiamine may be toxic at the dose 1000 times to the nutritional requirement.
Type # 7. Vitamin C/Ascorbic Acid:
(i) Isolated and termed as hexuronic acid by Szent & Gyorgy in 1928.
(ii) Waugh & King (1931) isolated vitamin C in crystalline form from lemon juice.
(iii) Its antiscurbutic property lead to the term ascorbic acid.
(iv) Two separate team i.e. Haworth et. al. and Reichstein et. al. separately reported synthesis of vitamin C in 1933.
(v) Chemical structure was reported by Haworth and associates in 1933.
Chemistry:
Ascorbic acid is a six carbon ketolactone related to hexoses, can be reversibly oxidized to another biologically active form i.e. ascorbone or L- dehydroascorbic acid; although L-ascorbic acid dominates in all tissues over ascorbone.
Absorption:
It is actively absorbed in small intestine depending upon sodium dependent active transport process. The absorption is saturable and dose dependent i.e. higher intake reduces absorption. Each organ/ tissue has its saturation limit.
Surplus is excreted as such or as metabolite i.e. oxalic acid, ascorbate- 2-sulfate, dehydroascorbic acid. Ascorbic acid is present in all tissues but not stored in any specific organ although pituitary, adrenal gland and healing wound contains highest concentration.
Physiological/Metabolic Function:
Ascorbic acid is required for:
(i) Enzymatic hydroxylation of proline and lysine for collagen synthesis.
(ii) Synthesis of carnitine from lysine and methionine along with ferrous ion.
(iii) Hydroxylation of steroid in adrenal cortex.
(iv) Absorption of calcium and non-heme iron from gut (dietry vitamin C).
(v) Free radical scavenging.
(vi) Metabolism of tyrosine, phenyl alanine and tryptophan.
(vii) Cementing substances of capillaries, dentine fibrils and collagen of connective tissues which overcome capillary fragility, weak bones and slow healing of wound.
Deficiency:
Deficiency of vitamin C leads to scurvy which affect intercellular matrix, bone, dentine, cartilages and connective tissues, which may lead to
(i) Fragile and swollen long bones.
(ii) Bleeding gums and loosening of teeth.
(iii) Vulnerable to infections.
(iv) Poor healing of wound.
(v) Internal bleeding/haemorrhage.
(vi) Anaemia.
Most mammals do contain L-gulono-y-lactone oxidase activity which converts the gulonolactone to ascorbic acid present in domestic animals, poultry and absent in human, monkey, guinea pigs and some bats. This is why domestic animals do not need any supplementation as such except some time in young calves.
Type # 8. Biotin:
1. Kogl and Tonnis (1936) isolated biotin in crystalline form from egg yolk.
2. de Vigneaud (1942) presented the structural formula and later synthesized.
3. Avidin (biotin antagonist) was isolated from egg white in 1940 by Eakin and associates.
Chemical Structure:
It is 2-keto-3, 4-imidazilido-2-tetrahydrothiophene valeric acid with sulfur in a thioether linkage. Out of eight isomers only d-biotin meets the properties of vitamins.
Digestion, Absorption and Fate:
(i) Avidin binds biotin and render it unavailable to raw egg consumers. Cooking destroys biotin binding capacity of avidin.
(ii) Unbound natural biotin is easily digested, absorption is carrier mediated seek presence of sodium ions, transported free in blood plasma to tissues.
(iii) Biotin is excreted as sulfoxide or sulfone or bisnorbiotin along with free biotin.
Metabolic/Physiological Function:
1. It acts as a cofactor for carboxylation of enzymes, facilitates the fixation of CO2 in to organic molecules i.e. pyruvate, Acetyl CoA, propionyl CoA and β-methyl crotonyl CoA. Biotin is important for synthesis of arachidonic acid, metabolism of carbohydrate, lipid and degradation of some amino acids.
Deficiency:
Deficiency is rare in ruminants and horses.
1. Cats and dogs may show weight loss, inappetance, dermatitis and alopecia.
2. Swine may develop anorexia, poor growth and problems of dermis i.e. dermatitis, dryness, roughness, ulceration, stomatitis, cracking of sole, hoof tops etc.
3. Reduced growth rate, dermatitis, hyperkeratosis brittle and broken feather, chondrodystrophy and perosis are common in poultry.
4. Antimicrobials (sulfa drugs) may interfere with the synthesis of biotin in small intestine and predispose deficiency. Coprophagy as in rabbits help.
5. Requirement range from 100-300 µ gm./kg of diet in domestic animals.
Type # 9. Pantothenic Acid:
Chemistry:
It is an amide include pantoic acid and β-alanine present in CoA and acyl carrier protein.
It is easily destroyed by heat and alkali.
Metabolic/Physiological Function:
1. Following phosphorylation and addition of cysteine, adenine and ribose, pantothenic acid yields CoA.
2. Cysteine adds sulfhydryl group, the active site.
3. CoA facilitate enzymes catalysed reactions forms acetyl CoA with acetic acid which facilitate entry of carbon skeleton into TCA cycle, synthesis of fatty acid, cholesterol, acetyl choline, gluconeogenesis, steroid synthesis, ketone body metabolism etc. Thus play important role in intermediary metabolism.
Absorption:
As CoA it gets hydrolysed by alkaline phosphatase in small intestine, diffuses and/or taken up actively, transported, as pantothenic acid in plasma and as CoA in RBC to tissues.
Deficiency:
(i) Ruminants and horses gut microflora are of great help and, therefore deficiency seldom appear.
(ii) Growing calves develop anorexia, poor growth, diarrhoea, rough hair coat, scaly dermatitis near eye and muzzle.
(iii) Pigs develop goose stepping i.e. slow progressive tremor, spasticity due to demyelinization of nerve of dorsal root. Other manifestation like anorexia, retarded or stunted growth, dermatitis, reduced antibody response are common to growing calves, dogs etc.
(iv) Birds egg production and hatchebility gets reduced.
Requirement:
Ranges between 8-16 mg/kg of feed in most animals and birds. 1 gm. pantothenic acid is equivalent to 1.087 gm. of calcium pantothenate a common supplement added in animal feed. Pantothenic acid is widely distributed in plants and animals, although yeast is commercial source.
Anti vitamins – ω-methyl pantothenic acid
– Pantonyl taurine
Type # 10. Niacin:
(i) Prepared chemically — Hubner (1867).
(ii) Experimental model of black tongue (in dog) was produced by Goldberger (1916).
(iii) Goldberger and Tanner shown that tryptophan could cure human pellagra, later found that tryptophan gets converted to nicotinic acid.
(iv) Elvehjem and associates (1937) shown that inacin can cure black tongue.
(v) To avoid confusion with alkaloid nicotine, nicotinic acid was termed as niacin.
Chemistry:
1. It is a derivative of pyrimidine i.e.
3-pyridinamide is a niacin amide and
3-pyridine carboxylic acid is nicotinic acid.
2. It is found as nicotine adenine dinucleotide (NAD) and nicotine adenine dinucleotide phosphate (NADP) in animals.
Digestion and Absorption:
(i) Niacin is common as niacinogen in feed i.e. associated with polysaccharide, peptide/glycopeptide.
(ii) This complex form is of little use to ruminal microflora and not available to non-ruminants.
(iii) Natural unbound niacin is easily digested and absorbed from stomach and small intestine.
(iv) Nicotinamide is hydrolysed in small intestine to nicotinic acid, absorbed by active transport as well as passive diffusion, back to amide form in enterocytes.
(v) Niacin is associated to RBC for its transport.
(vi) Tryptophan is the precursor of niacin in most animals depending upon their conversion efficiency. Rats are quite efficient, where as cats are not, needs direct supplementation.
(vii) Human need 60 mg of tryptophan to 1 mg of niacin, 30 is to one in rats and 45 is to one in birds.
(viii) The level of niacin in organs is directly related to its metabolic activity although not stored.
Metaboliq/Physiological Function:
(i) The metabolic activity of niacin depends upon its coenzyme forms (NAD & NADP).
(ii) These coenzymes are required for glycolysis, TCA cycle, glycerol synthesis and break down, fatty acid synthesis and break down, steroid synthesis and breakdown and synthesis of amino acid.
Antivitamins:
(i) 3-acetyl pyridine
(ii) Pyridine sulfonic acid.
Fate:
The major metabolic product of niacin excreted in urine is as:
(i) N-methyl-nicotinamide (non-ruminants).
(ii) Nicotinuric acid (ruminants).
(iii) Nicotinamide conjugated with ornithine before excretion in birds.
Deficiency:
(i) Metabolic disorder-primarily affects skin and digestive system. The symptoms include inappetance, poor growth, stomatitis, vomiting diarrhea, exploitative dermatitis and alopecia in pigs.
(ii) Ruminants are benefitted in growth, lactation, ketosis by niacin supplementation, although deficiency as such seldom appear.
(iii) Horses-Niacin deficiency is uncommon.
(iv) Dogs develop signs of black tongue i.e. anorexia, depression, weight loss, cheilosis, glossitis, gingivitis, bloody diarrhoea and death ultimately.
(v) Bowing of legs and thickening of hock joint are common in poultry along with typical signs of black tongue.
Preparations:
Available as yeast extracts in oral and injectable, singly or as multivitamin.
Toxicity:
(i) High niacin intake increases the activity of mixed function oxidase and other xenobiotic metabolizing enzymes, thus may affect metabolism of drugs as well as toxicants.
(ii) Ten to thousand times of requirement is considered toxic depending upon species.
Requirement:
It depends upon species and varies from 10-70 mg/kg diet in animals and birds.
The conversion efficiency of different species from tryptophan to niacin affects the normal dietry requirement.
Type # 11. Choline:
1. Strecker isolated choline in 1849 although Best and associates established its nutritional significance.
2. Choline is non-vitamin but an essential component for life; required in higher amount than vitamins. The deficiency signs/symptoms are similar to vitamins, reasons its consideration as vitamins.
Chemistry:
It is hydroxy ethyl trimethyl-ammonium hydroxide, a strong base, colourless crystalline water soluble compound.
Digestion:
Normally feed contains higher content of choline in the form of lecithin, half of which is absorbed intact from small intestine into lymph, rest is hydrolysed and absorbed by passive and/or active transport mode in ileum.
Metabolic/Physiological Function:
(i) Being a constituent of phospholipid (lecithin), it is an integral structural- component of cell membrane.
(ii) Choline forms acetyl choline in presence of acetyl CoA and enzyme choline acetylase.
(iii) Choline is oxydized to betaine which facilitate formation of methionine by trans-methylation of homocysteine.
(iv) Being lipotropic, it prevents accumulation of fat in liver. Other lipotropic agents are inositol, methionine, vitamin B12 and folic acid.
(v) It plays important role in the synthesis of autocoid PAF.
Deficiency:
(i) Ruminants and horses seldom develop choline deficiency albeit milk yield of lactating cows increase on choline supplementation.
(ii) In pigs, choline deficiency is manifested as reduced weight gain, faulty conformation, reproductive failure and lipidosis of liver.
(iii) Growing piglets develop “Spraddled leg conformation.”
(iv) Egg production reduces in poultry along with stunted growth, fatty liver and perosis.
Requirement:
It ranges from 400-1900 mg/kg of diet in most domestic animals depending upon species and stage of life cycle.
Type # 12. Folic Acid:
1. It was prepared in pure crystalline form by Mitchell (1944), Later Angier et. al. confirmed its chemical structure in 1946.
Chemical Structure:
1. It is made up of a pteridine nucleus, p-amino benzoic acid and glutamic acid.
2. It is heat stable at neutral pH.
3. Glutamic acid residue may vary.
4. It is ubiquitous in plants and animals as polyglutamic acid and tetrahydrofolic acid derivatives.
Digestion, Absorption and Excretion:
1. Folic acid is present in feed in the polyglutamate form. It is hydrolysed to mono-glutamate, absorbed in intestine by active transport.
i. Polyglutamate (methyl tetrahydrofolate) form is reconstructed, transported through blood taken up by peripheral tissues and stored.
ii. All these processes right from absorption of folic acid to reconstruction, transportation to tissues is facilitated by folacin binding protein.
iii. Liver stores over 50% folic acid in the form of N5 methyl-tetrahydrofolic acid which when needed may be released by the liver and transported to the tissues.
iv. The metabolites of folic acid with pteridine nucleus is excreted via urine.
Physiological/Metabolic Functions:
1. Tetrahydrofolic acid (THFA) is concerned with two types of reactions.
i. Transfer of one carbon unit-transfer of one carbon unit/moiety i.e. methyl group is concerned with synthesis of methionine, serine-thymidine and purine bases.
ii. Hydroxylation reaction-In presence of THFA, phenylalanine, tyrosine and tryptophan forms norepinephrine and serotonin.
Folic Acid Antagonists:
(i) Aminopteridine (4-amino folic acid) is the most potent competitive inhibitor of folic acid. Another is amethopteridine (4-amino-10 methyl folic acid).
(ii) Antimicrobial Sulfonamides are PABA analogue competitively inhibit synthesis of folic acid in microorganism. Similarly folate antagonist from moldy feed may block microbial folic acid synthesis in intestine.
Deficiency:
(i) Rare in horses and ruminants as gut microflora can synthesize enough folate to fulfill the requirement.
(ii) Pigs may develop deficiency on prolonged sulfa drug treatment manifested by macrocytic anaemia, leukopenia, diarrhoea and reduced growth rate.
(iii) In dogs, cats folate deficiency results in inappetance, weight-loss, anaemia, leukopenia and glossitis.
(iv) In poultry, it is manifested by megaloblastic anaemia, poor growth, poor feather development, depigmentation of feather, perosis, reduced egg production, hatchability and spastic cervical paralysis.
(v) Requirement ranges between 0.26 to 1 mg per kg of diet for animal and poultry.
Type # 13. Vitamin B12/CyanacobaIamin:
Smith & Parker and Rickes et. al. separately isolated vitamin B12. The structure was established in 1956.
Chemical Structure:
The molecule of B12 consists of a corrin ring system, having a central cobalt atom linked to nitrogen of tetrapyrrole rings. Below the plane of corrin ring system, 5, 6 dimethyl benzimidazoe riboside is linked to central cobalt atom at one end and ribose at other through phosphate and amino propranol to the side chain on ring d of tetrapyrrole nucleus. The functional group determines the form of B12 i.e. nitrocobalamine (nitrate) cyanacobalamin (cyanide) hydroxylcobalamine (hydroxyl).
Digestion, Absorption and Excretion:
Gastric acidity facilitates release of B12 from protein bound form of feed. The absorption of B12 depends upon its binding to intrinsic factor (a mucopolysaccharide released from perital cells of gastric mucosa) under the influence of trypsin in ileum. Two moles of vitamin B12 combine with one mole of intrinsic factor. The absorption of vitamin B12 is carrier mediated, having specific receptor on microvilli of enterocytes.
Further it is transported to portal blood, then bound to a specific protein synthesized by liver called transcobalamin, which facilitates the transport and storage of vit. B12. As an exception to other water soluble vitamins, it is stored in liver having half life of one month. It is excreted in bile and reabsorbed by enterohepatic circulation in the case of deficient intake other wise leaves the body in faeces.
Metabolic/Physiological Function:
1. Vitamin B12 in the form of coenzyme (5′-de-oxy-adenosyl cobalamin) for methyl malonyl CoA mutase enzyme catalyses conversion of propionate (of VFA in ruminants) to succinyl CoA. So, in B12 deficiency, VFA’s utilization reduces.
2. Other coenzyme form is methyl cobalamin. It methylate homocysteine to methionine.
3. B12 play very important role in the development of RBC beyond megaloblast stage along with folic acid.
4. It is involved in the maintenance of sulfhydryl group and biosynthesis of proteins.
Requirement:
It is a vitamin of animal origin so feed prepared strictly of plant material needs supplementation. It ranges from 3-50 µg/kg of diet for non-ruminants.
Even ruminal microflora seek cobalt for synthesis which otherwise may be manifested as deficiency symptoms i.e. anorexia, anemia etc.
Type # 14. Vitamin B6/Pyridoxine:
It includes three biologically active forms differ by their functional groups.
1. Pyrrdoxol, an alcohol
2. Pyridoxal, an aldehyde
3. Pyridoxamine, the amine.
All these three possess the same biological properties undergoes conversion in the liver to pyridoxal 5′-phosphate, the active form of vitamin.
When X is CH2OH – Pyridoxol
CHO – Pridoxal
CH2 NH2 – Pyridoxamine
Antivitamin/Antimetabolites:
1. 4-de-oxy-pyridoxine
2. Isoniazid
3. Hydralazine
4. Cycloserine
5. Levodopa
6. Pencillamine
Digestion, Absorption & Fate:
Natural, unbound B6 is easily digested and absorbed. Phosphorylated B6 undergo hydrolysis, by passive absorption, transported to liver, undergo activation (phosphorylation) with the help of niacin (NADP) and riboflavin dependent enzymes. Oxidation of pyridoxal to 4-pyridoxic acid which is excreted with some unchanged vitamin B6.
Physiological/Metabolic Function:
(i) Pyridoxal phosphate is metabolically active derivative of pyridoxine which facilitate co-decarboxylation, deamination, transsulfuration, desulfuration etc. It also function as coenzyme for Kynureninase in the synthesis of niacin from tryptophan.
(ii) Pyridoxal phosphate facilitate synthesis of porphyrin, heme nuclei, serotonin, γ-amino- butyric acid and catecholamines.
Deficiency:
(i) The microflora of gut cover up the requirement of horses and ruminants.
(ii) Calves, cats and dogs may develop deficiency manifested by anorexia, poor growth, vomiting, visual impairment, microcytic hypochromic anemia, nervous disorder due to demyelinization of peripheral nerves.
(iii) Cats and dogs may develop ataxia, convulsion cardiomyopathy, renal lesion and nephrolithiasis.
(iv) Poultry develop trembling, stiff and jerky movement and convulsion.
Requirement ranges from 1-6 mg/kg of diet, albeit normal diet contain adequate active content of B6, therefore doesn’t need any supplementation.