CHAPTER 4: The Importance of Vitamins in Biochemistry and Disease as Illustrated by Thiamine Diphosphate (ThDP) Dependent Enzymes

Thiamine diphosphate (ThDP), the biologically active form of thiamine (vitamin B₁), functions as a cofactor in enzymes that catalyse various essential reactions in metabolic pathways. The ThDP-dependent enzymes are ubiquitously present in all organisms and generally catalyse oxidative conversion or the nonoxidative transfer of 2-keto acids. The first essential activation step common in all ThDP-dependent enzymes is the formation of ThDP ylide. The ThDP ylide is a C2 ionized state of the thiazolium ring that attacks the substrate carbonyl group. Pyruvate decarboxylase, pyruvate oxidase, pyruvate:ferredoxin oxidoreductase and pyruvate dehydrogenase catalyse different reactions after the decarboxylation of pyruvate. Transketolase catalyses transfer of a two-carbon fragment between sugar phosphates, whereas phosphoketolase catalyses phosphorolytic cleavage of sugar phosphates. The ThDP-dependent enzymes are classified into five families.