Biological active form is Thiamine pyrophosphate (TPP). Acts as a coenzyme in several metabolic reactions. * Acts as coenzyme to the enzyme pyruvate dehydrogenase complex (PDH) which conves pyruvic acid to acetyl-CoA (oxidative decarboxylation) Pyruvate PDH TPP Acetyl-CoA * Similarly acts as a coenzyme to a-oxoglutarate dehydrogenase complex and conves a-oxoglutarate to succinyl-CoA (oxidative decarboxylation). a-oxoglutarate dehydrogenase a-Oxoglutarate TPP Succinyl-CoA * TPP also acts as a coenzyme with the enzyme Transketolase in transmetallation reaction in HMP pathway of glucose metabolism. Transketolase Ribose-5-P + xylulose-5-P TPP Sedoheptulose-7-P + Glyceraldehyde-3-P *B1 is also required in amino acid Tryptophan metabolism for the activity of the enzyme Tryptophan pyrrolase. * Also acts as a coenzyme for mitochondrial branched-chain a-ketoacid decarboxylase which catalyses oxidative decarboxylation of branched-chain a-ketoacids formed in the catabolism of valine, Leucine and Iso-leucine. TPP binds with and decarboxylates this branched-chain a-ketoacids and transfers the resulting activated -CHO groups to alipoic acid. * TPP acts as the coenzyme (Co-carboxylase) of pyruvate carboxylase in yeasts for the non-oxidative decarboxylation of pyruvate to acetaldehyde. * The coenzymes NAD+ and NADP+ operate as hydrogen and electron transfer agents by viue of reversible oxidation and reduction. The mechanism of the transfer of Hydrogen from a metabolite to oxidised NAD+, thus completing the oxidation of the metabolite and the formation of reduced NAD (NADH + H+) is shown in box. Reduction of NAD+ occurs in para position; one H loses an electron and enters the medium as H+. * Function of NADP+ is similar to that of NAD+ in hydrogen and electron transpo. The two coenzymes are interconveible. The impoant enzymes to which NAD+ and NADP+ act as coenzyme Biotin is the prosthetic group of ceain enzymes that catalyse CO2-transfer reaction (CO2-fixation reaction). In biologic system, biotin functions as the coenzyme for the enzyme called carboxylases, which catalyse the CO2-fixation (Carboxylation). In this process, Biotin is first conveed to carboxybiotin complex by reaction with HCO3- and ATP. "CO2-biotin complex'' is the source of "active" CO2 which is transferred to the substrate, CO2 becomes attached to the biotin Metabolic Role of Cobamide Coenzymes * Methyl malonyl-CoA to succinyl-CoA conversion: Vitamin B12 is required as a coenzyme for the conversion of L-methyl malonyl CoA to succinyl-CoA. The reaction is catalyzed by the enzyme isomerase. B12 L-Methyl Malonyl-CoA ________________ Succinyl-CoA Isomerase Normal healthy individuals excrete less than <2 mg/day which is not detectable. Note: In B12 deficiency: Methylmalonic acid accumulates and excretion of methylmalonic acid in urine is increased. Methylmalonic aciduria is a sensitive index for B12 deficiency. * Methylation of Homocysteine to Methionine: This requires tetrahydrofolate (F.H4) as a -CH3 carrier. * Methylation of pyrimidine ring to form thymine. * Conversion of Ribonucleotides to deoxyribonucleotides: It is of impoance in DNA synthesis. B12 Ribonucleotides __________________ DeoxyribonucleotidesRef: MN Chatterjea Textbook of Medical Biochemistry, 8th edition, page no: 178, 183, 190, 198