BIOLOGICAL ROLE OF VITAMIN-A1. Retinol and retinoic acid have role in normal reproduction2. Retinal has a role in visual cycle3. Retinoic acid has a role in glycoprotein synthesis4. Roll in MPS synthesis5. Vitamin-A is needed for mitochondrial membrane function
6. Anti cancer role: β-carotene is an antioxidant and trap peroxy free radicals in tissues at low partial pressure of O 27. Role in reproduction8. Bone and teeth formation is slow
BIOCHEMICAL ACTIONS OF CHOLECALCIFEROL1. Vitamin-D promotes absorption of Ca ++ and P by the intestine. It stimulates the synthesis of a specific Ca++ binding protein by intestinal epithelium.2. Vitamin-D induces the synthesis of specific Ca++ binding protein in bones3. Vitamin-D regulates the Ca++ level by reabsorbing Ca++ through the kidney
4. Vitamin-D promotes mineralization of bones through deposition of Ca++ and P in growing bones.5. Vitamin-D increases the reabsorption of PO4 through renal tubules.6. Vitamin-D acts as coenzyme for alkaline phosphatase7. Vitamin-D is responsible for enameling of the teeth. Its deficiency leads to irregular and rough teeth
8. Vitamin-D promotes growth in general and is essential for normal health. BMR is decreased in vitamin-D deficiency. The deficiency of vitamin-D leads to the repeated attacks of respiratory diseases.
BIOCHEMICAL ACTIONS OF VITAMIN-E1. Antioxidant role: Vitamin-E is the most potent natural antioxidant.2. Removal of Free radicals: Vitamin-E removes free radicals, prevents their peroxidative effects on unsaturated lipids of membrane and thus maintains integrity of membranes.
3. Protective role: i. Vitamin-E prevents massive hepatic necrosis produced on diet deficient in sulphur containing aminoacids.4. Role in reproduction: It is required for normal reproduction, muscle integrity and for resistance of erythrocytes to hemolysis.5. Role in Heme Synthesis: Vitamin-E also takes part in the synthesis of heme. Vitamin-E induces enzymes ALA-synthase and ALA-dehydratase.
6. A derivative of vitamin-E is said to be necessary for the synthesis of CoQ which is the component of mitochondrial electron transport chain.
BIOLOGICAL ACTIONS OF VITAMIN-K1. Vitamin-K is needed for formation of proconvertin: It is needed for the formation of prothrombin. Deficiency of vitamin K decreases proconvertin level in blood.2. Vitamin-K modifies prothrombin: Vitamin-K is a coenzyme in modification of prothrombin to thrombin.
3. Vitamin-K modifies other clotting factors also: Vitamin K is needed for maintenance of normal levels of blood clotting factors II, VII, IX and X. All these factors are synthesized in the liver in their zymogen forms. Their conversion to biologically active forms depends upon vitamin K. The activation involves carboxylation of glutamyl residues in the molecules of these factors (including prothrombin also) to form dicarboxylic glutamyl residue.
4. Vitamin-K is needed for carboxylation of glutamyl residue of Ca++ binding transport between the flavin coenzyme and the cytochrome system.
FACTORS CAUSING VITAMIN-K DEFICIENCY:• Surgical removal of intestine:• Liquid paraffin:• Antibiotic therapy for a long time:• Vitamin-K antagonists: Heparin and warfarin
BIOCHEMICAL FUNCTIONS: THIAMINE• TPP [cocaroxylase] being an essential part of the decarboxylating dehydrogenases acts as a cofactor in many important reactions in carbohydrate metabolism i.e., dehydrogenase [PDH] complex and α-ketoglutarate dehydrogenase [αKGDH] complexi. Oxidative Decarboxylation of α-ketoacids
ii. Conversion of α-Ketoglutarate to succinyl- SCoAiii. TPP acts as coenzyme in reactions catalyzed by transketolaseiv. Tryptophan metabolism: Tryptophan pyrrolaseTryptophan N-formylkynurenine O2
v. TPP is a coenzyme for mitochondrial branched chain α-ketoacid dehydrogenases [decarboxylases] which oxidatively decarboxylate α-ketoacids formed in the catabolsim of valine, leucine and isoleucline.vi. In the nervous system: TPP is a cofactor for the synthesis of acetylcholine.vii. TPP also acts as a coenzyme [co- carboxylase] for pyruvate carboxylase in yeast for non-oxidative decaroxylation of pyruvate to acetaldehyde.
BIOCHEMICAL FUNCTIONS OF RIBOFLAVIN:A- Biochemical role of FMN as a coenzyme1. FMN as a part of redox potential2. FMN is a coenzyme for L-amino acid oxidases:3. FMN being a part of Cut. C reductase4. FMN also accepts 2H+ from NADH+H+5. FMN is a coenzyme for Warburg’s yellow enzyme [a component of respiratory chain]
B- FAD is a coenzyme for the following enzyme:Like FMN, FAD is also is a part of mitochondrial respiratory chain1. D-aminoacid oxidases: The enzymes catalyze reaction similar to L-aminoacid oxidases but with FAD as coenzyme.2. Aldehyde oxidase3. Acyl-CoA dehydrogenase of the β oxidation of fatty acids
4. Succinate dehydrogenase, an enzyme of citric acids cycle and converts succinate to fumarate in mitochondria5. Xanthine oxidase present in milk, small intestine, kidney and liver has Mo as its activator ion converts urine bases to uric acid6. Glucose oxidase prepared from fungi7. Glycine oxidase which oxidatively deaminates glycine to glyoxylic acid and ammonia
NIACIN NAD+ and NADH are coenzymes of niacin:A- NAD+ containing dehydrogenases are:1. Isocitrate dehydrogenase of mitochondrial origin.2. Alcohol dehydrogenase3. Lactate dehydrogenase4. Malate dehydrogenase of citric acid cycle. Malate Oxaloacetate
5. Glyceraldehyde-3-P dehyrogenase of glycolysis6. Pyrurate dehydrogenase complex7. α-ketoglutarate dehydrogenase of citric acid cycle.8. β-hydroxy fatty acyl-coA dehydrogenase of β-oxidation of fatty acids
B- NADP+ containing dehydrogenases are:1. Isocitrate dehydrogenase of extra mitochondrial origin.2. Glucose-6-phosphate dehydrogenase of HMP-shunt3. β-ketoacyl reductase in the fatty acid synthesis4. HMG-CoA reductase in cholesterol synthesis HMG-CoA → Mevalonate
5. Enoyl reductase of fatty acid synthase complex
BIOCHEMICAL ACTIONS: PANTO THENIC ACID1. Formation of active acetate [Acetyl-CoA]: CoA-SH2. Formation of acetyl-ACP and malonyl- ACP3. Role in oxidation of fatty acids, formation of fats and phospholipids:
4. Heme Synthesis: Ative succinate [succinyl-CoA] is product of oxidative decarboxylation of α-oxoglutarate in TCA cycle. Succinyl-CoA and glycine is needed for the synthesis of heme.
BIOCHEMICAL FUNTIONS OF PYRIDOXINE:1. As co-transaminase: It acts as a coenzyme in transamination reactions. GOT [AST] and GPT [ALT] are transaminases which need PLP as coenzyme for their actions2. As co-decarboxylase: It also functions as a coenzyme in non-oxidative decarboxylation of some aminoacids or their derivatives.
Tyrosine Tyramine + CO2Histidine Histamine + CO23. As Ala-synthase: in the synthesis of δ- aminolevulinic acid which is an intermediate in heme synthesis4. As coenzyme in the conversion of tryptophan to niacin.5. Interconversion of glycine and serine by hydroxymethyl transferase.
6. In transulphuration reactions, where transfer of-SH group takes place, B 6 is needed.7. In synthesis of sphingosine8. Intramitochondrial fatty acid synthesis9. Intestinal absorption of aminoacids10. Transport of K+. B6 is reported to promote transport of K+ across the membrane.
11. Synthesis of CoA-SH from pantothenic acid needs B6. in B6 deficiency CoA level of the liver is decreased.12. B6 acts as a coenzyme for glycine Synthase.
BIOCHEMICAL FUNCTIONS OF BIOTINBiotin is a prosthetic group of some enzymes catalyzing CO2 transfer or CO2 fixation reactions.1. Formation of malonyl-CoA from acety- CoA and CO22. Pyruvate carboxylase Reaction: Here pyruvate forms oxaloacetate.
3. Formation of carbamoyl-PO4: NH3, CO2 and ATP requires biotin to form carbamyl-PO4 in presence of carbamyl- PO4 synthetase.4. Formation of β-methylglutaconyl-CoA from β-methylcrotonyl-CoA. It is an intermediate reaction in leucine metabolism
5. Biotin influences other enzyme systems e.g. succinate dehydrogenase, decarboxylase and aminoacid deaminases. Here CO2 is used for the formation of aspartic acid, serine and threonine.6. Propionyl-CoA carboxylase reaction requires biotin ATPPropionyl-CoA+CO2 → Methylmalonyl-CoA ADP+Pi
COENZYME FORMS OF FOLIC ACID:1. Tetrahydrofolic acid, FH4:2. Folinic acid:3. Rhizopterin:
METABOLIC ROLE (ONE CARBON METABOLISM):FH4 is the coenzyme form of folic acid and it acts as coenzyme in transfer and utilization of one carbon moiety [C1]One Carbon Donor and Acceptor Compounds:
One carbon donor group One carbon acceptor groupFormimino group of N-formyl methionine offormimino glu [from his]. transfer-RNA.Methyl group of methionine. Glycine to form serine.Methyl group of methionine. Glycine to form serine.Methyl group of thymine. Uracil to form thymine.β-carbon of serine. Ethanolamine to form choline.Gly, trp, ALA and acetone, Positions 2 and 8 of purin ring. Histidine synthesis.
FOLATE ANTAGONISTS:1. SULFONAMIDES2. TRIMETHOPRIM:3. PYRIMETHAMINE:4. AMINOPTERIN AND AMETHOPTERIN:
BIOCHEMICAL FUNCTIONS OF B121. Methylmalonyl-CoA-isomerase: It catalyzes the reaction using B12 as a coenzymeMethylmalonyl-CoA → succinyl-CoA2. Methionine synthase or homocysteine methyl transferase requires B12 as coenzyme:
3. Conversion of Ribonucleotide to deoxyribonucleotide also needs B12. It is important in the synthesis of DNA hence deficiency of B12 leads to the defective synthesis of DNA.4. Role as Hemopoietic Factor: Like folic acid, vitamin B12 is also concerned with hemopoiesis and is needed for maturation of RBCs.
5. Abnormal Homocysteine Level: In vitamin B12 deficiency, Homocysteine Conversion to methionine a block so that homocysteine is accumulated, leading to homocystienuria. Homocysteine level in blood is related with myocardial infarction. So1, B12 is protective against cardiac disease.
Demyelination and Neurological Deficits: In B12 deficiency, methylation of phosphatidyl ethanolamine to phosphatidyl choline is not adequate. This leads to deficient formationOf myelin sheaths of nerves, demyelination and neurological lesions.
CAUSES OF B12 DEFICIENCY:1. Nutritional B12 deficiency.2. Decrease in absorption due to non- availability of absorptive sufface caused by gastrectomy, resection of ileum, blind loop syndrome.3. Elderly people are unable to absorb B 12
4. Addisonian anemia is pernicious [fatal] without any remedy. It is manifested in persons 40 years of age. It is an autoimmune disease and antibodies are formed against IF. The deficiency of IF leads to defective absorption of B12.5. Atrophy of gastric epithelium: It leads to decreased IF and decreased absorption of B12.
6. Drugs: Some drugs interfere with absorption of B12. These are phenphormin, cholchicine, neomycine, ethanol and KCl.7. Increased requirement of B12 in pregnancy is common cause for vitamin B12 deficiency.
BIOCHEMICAL FUNCTIONS OF ASCORBIC ACID:1. Vitamin C acts as a reducing agent:2. The oxidation of p-hydroxphenyl pyruvate to homogentisate in the metabolism of tyrosine needs the presence of vitamin V and Cu+23. Role in iron absorption: Ascorbic acid present in food reduces the inorganic Fe + ++ (ic) to Fe++ (ous) form.
4. Vitamin-C acts as a coenzyme for hydroxylases. Hydroxylation reactions are involved in the synthesis of collagen and other compounds:5. Formation of carnitine in liver by hydroxylation of γ-butyrobetaine involves vitamin-C, α-ketoglutarate, Fe++ and a dioxygenase.6. Vitamin-C required for the normal function of adrenal cortex.
7. The formation of FH4 from folate needs vitamin-C. Tetrahydrofolate [FH4] is a coenzyme from of folate.8. Ascorbic acid is necessary for the formation of tissue ferritin.9. Vitamin C is needed for the functional activity of fibroblast, osteoblast, and consequently for the synthesis of MPS of connective tissues, osteoid tissues, dentine tissues and intracellular substance involved in the cementing of capillaries.