Vitamin I: Water Soluble Vitamins PDF

FACULTY OF MEDICINE MHBH HUMAN BODY IN HEALTH VITAMIN I: WATER SOLUBLE VITAMINS ASSOC. PROF. DR. CHIN JIN HAN [email protected] Biochemistry WATER SOLUBLE VITAMINS Learning Outcomes On completion of this topic, you should be able to: 1. Distinguish between water sol...

FACULTY OF MEDICINE MHBH HUMAN BODY IN HEALTH VITAMIN I: WATER SOLUBLE VITAMINS ASSOC. PROF. DR. CHIN JIN HAN [email protected] Biochemistry WATER SOLUBLE VITAMINS Learning Outcomes On completion of this topic, you should be able to: 1. Distinguish between water soluble and fat soluble vitamins. 2. Explain the source of water soluble vitamins in diets. 3. Explain the synthesis of water soluble vitamins. 4. Discuss the importance of water soluble vitamins in human. 5. Explain avitaminosis Biochemistry WATER SOLUBLE VITAMINS Classification of Vitamins  Importance of Ascorbic acid (Vit. C) The active form of vitamin C is L-ascorbic acid. 1. Reducing Agent To reduce O2, nitrate, and cytochromes. Maintain the metal cofactor in reduce state: Prolyl hydroxylase (iron-containing) in the reduction of proline to hydroxyproline in collagen. 4 α-hydroxylase (copper-containing) in the formation of norepinephrine, bile acid & etc. Importance of Ascorbic Acid 2. Antioxidant Directly, by reaction with aqueous peroxyl radicals. Indirectly, by restoring the antioxidant properties of fat-soluble vitamin E. 5 Deficiency of Ascorbic Acid Clinical ascorbate deficiency (as in scurvy) is the first manifested in the connective tissue of the mouth with loose teeth and bleeding gums. Wound repair (requiring synthesis of fresh collagen) is slow. 6 Importance of Thiamine (Vit. B1) Thiamine pyrophosphate (TPP) plays an essential role as coenzyme in oxidative decarboxylation reactions, which result in the loss of carbon dioxide and transketolase in the hexose monophosphate pathway. Thiamin diphosphate has a central role in energy-yielding metabolism; pyruvate dehydrogenase in the metabolism of carbohydrates. The requirement of thiamine is 7 increased along with higher intake of carbohydrates. Disorder of Thiamine The classic disorder of thiamine is beri-beri, a condition characterised by polyneuropathy (including sensory loss), muscle wasting, exhaustion and cardiac failure. Thiamine deficiency will lead to incomplete glucose utilisation and impaired synthesis of myelin (the fatty sheath around peripheral nerves) which is necessary for normal nerve conduction velocity. 8 Importance of Riboflavin (Vit. B2) Riboflavin is converted to its active coenzymes forms, i.e. flavine adenine dinucleotide (FAD) and flavine adenine mononucleotide (FMN). Flavin coenyzmes are electron carries in redox reactions. Both are important in redox reactions of Kreb’s cycle. 9 Riboflavin Deficiency Symptoms of deficiency include angular stomatitis (cracks at the corner of the mouth), glossitis (inflammation of the tongue) and other ocular symptoms include burning and itching of the eyes and possible corneal vascularisation. However, natural deficiency of riboflavin alone in human is uncommon because riboflavin could be synthesised by the 10 intestinal flora. Important of Niacin (Vit. B3) Niacin is required for biosynthesis of the coenzyme, nicotinamide adenine dinucleotides (NAD+) and nicotinamide adenine dinucleotide phosphate (NADP+). Niacin can be synthesised in the body from tryptophan. It has been suggested that a high protein diet may enable the synthesis of adequate levels even in the absence of dietary niacin. 11 Niacin Deficiency  The classical niacin deficiency syndrome is pellagra while the symptoms are diarrhoea, dermatitis and dementia.  The disease is sometimes seen in maize eating populations as not only is niacin deficit in this food but such niacin as in present is bound in the nonbioavailable form niacin called niacytin. 12 Importance of Pantothenic Acid (Vit B5) Pantothenic acid is necessary for the synthesis of coenzyme A (CoA), a vital carrier of small acyl groups. Coenzyme A is an important components of fatty acid synthase complex. The important CoA derivatives are acetyl-CoA, succinyl-CoA and HMG- CoA. However, there is no clinically 13 deficiency syndrome has ever been demonstrated. Importance of Vitamin B6  Vitamin B6 consists of three substituted pyridines: i. Pyridoxal (Food obtained from animals) ii. Pyridoxine (Plants) iii. Pyridoxamine (Foods obtained from animals)  Pyridoxal phosphate (PLP) is important in amino acid metabolism as coenzyme to carrier of amino groups via transamination and decarboxylation of amino acids.  Aminolevulinic acid (ALA) synthase, the 14 key enzyme in haem synthesis is PLP dependent enzyme. Vit B6 Deficiency  The requirement for this vitamin is around 1-2 mg daily.  A high protein diet thus requires a higher daily intake of pyridoxal.  Hypochromic microcytic aneamia may occur due to inhibition of haem biosynthesis. ** Large doses (>10 g daily) may lead to sensory neuropathy and it is generally recommended that daily doses should not exceed 200 mg. 15 Cobalamin (Vit. B12) Vitamin B12 is exclusively synthesised by microorganisms. The intestinal absorption of cobalamin requires its binding to a specific glycoprotein secreted by the parietal cells of the stomach and known as intrinsic factor. Strict vegetarians usually have an inadequate supply of the Vitamin B12. 16 Importance of Vitamin B12 Cobalamin acts as coenzyme to recycle the active form of folate after it has delivered its methyl groups to the developing nucleic acid. Cobalamin acts as coenzyme in the metabolism of amino acids and fatty acids with odd number of carbon atom. 17 Vit. B12 Deficiency Symptoms of cobalamin deficiency are thus similar to those folate deficiency. Reduced cobalamin levels are usually associated with pernicious anaemia, a form of megaloblastic anaemia. Pernicious anaemia is usually a result of reduced secretion of intrinsic factor and is associated with reduced acid secretion by the stomach. 18 Importance of Folate (Folic Acid) Folate derivatives function as carriers of single carbon units for the synthesis of purine and pyrimidine components of nucleotides and hence of nucleic acid. Nucleic acid synthesis is essential to all dividing cells. Therefore, reduced folate activity will reduce the rate at which cells can reproduce. 19 Folate Deficiency Deficiency of folate can lead to macrocytic (large cells) and megaloblastic aneamias. Folate plays an essential role in the early development of nervous system and the importance of adequate dietary folate to prevent neural tube defects in the foetus. Folate antagonists (such as methotrexate) compete with folate for binding to the enzymes of nucleic acid synthesis and reduce the rate of cell division in rapidly growing tumours and 20 cancers. Importance of Biotin Biotin is important as a component of enzyme complexes which catalyses carboxylation reactions in which either carbon dioxide or carboxylic acid groups are added to another molecules: Pyruvate carboxylase is an important enzyme in gluconeogenesis. Acetyl-CoA carboxylase is the rate limiting step in fatty acid 21 biosynthesis.  Biotin Deficiency Biotin deficiency can be induced by a diet rich in uncooked egg white which contains a biotin- binding protein, avidin. No well defined syndrome has been described in adults as the normal bacterial flora of the gut will provide adequate quantities of biotin. Deficiency states have been identified in infants and young children and the respond well to oral biotin therapy. 22 Biochemistry VITAMIN I: WATER SOLUBLE VITAMINS Summary of the Importance of Water Soluble Vitamins Vitamin Importance Thiamin (B1) Oxidative decarboxylation and transketolation Riboflavin (B2) In the form of FMN & FAD for oxidoreductase Niacin (B3) NAD & NADP for oxidoreductase Pantothenic acid (B5) Coenzyme A (Co-A) and acyl carrier protein Pyridoxal phosphate (B6) Aminotransferase of amino acids metabolism Biotin Carboxylase Conversion of methylmalonyl-CoA to succinyl -CoA, methy-tetrahydrofolate to Cobalamin (B12) THF (Folate Cycle) Ascorbic acid (Vit C) Maintains many metal cofactors in the reduced state Folic acid One-carbon residue for nucleic acid synthesis BIOCHEMISTRY VITAMIN I: WATER SOLUBLE VITAMINS References Text Book 1. Kennelly PJ, Botham KM, McGuinness O, Rodwell VW, Weil PA (2022). Harper’s Illustrated Biochemistry. 32nd Edition. McGraw Hill, Boston. References: 1. Lieberman M & Peet A (2022). Marks’ Basic Medical Biochemistry: A Clinical Approach. 6th Edition. Lippincott, Williams and Wilkins. 2. Emine E. Abali, Susan D. Cline, et al. (2021). Lippincott’s Illustrated Reviews, Biochemistry. 8th Edition. Lippincott, Williams and Wilkins.