Thiamin diphosphate-dependent enzyme (ThDP-dependent enzyme) (ThDP-dependent enzyme)

Thiamin diphosphate (ThDP)-dependent enzymes are a large family of enzymes that require thiamin diphosphate, the biologically active form of vitamin B1, as a mandatory cofactor for catalysis (Wikipedia, 2023). These enzymes are essential for primary metabolism, facilitating the cleavage of carbon-carbon bonds adjacent to a carbonyl group, such as in the decarboxylation of alpha-keto acids (UniProt, 2024). Major members include the pyruvate dehydrogenase complex, alpha-ketoglutarate dehydrogenase, and transketolase, which are central to the tricarboxylic acid (TCA) cycle and the pentose phosphate pathway (StatPearls, 2023). Because of their pivotal role in energy production and biosynthetic precursors, they are significant therapeutic targets. Pharmacological intervention typically involves thiamine supplementation to treat deficiency-related neurological and cardiovascular disorders or the use of inhibitors to target the unique metabolic requirements of cancer cells and infectious pathogens (PubChem, 2024).

Other names

Thiamine pyrophosphate-dependent enzymeTPP-dependent enzymeThDP-dependent enzymeThiamine-dependent enzyme

Cofactor supplementation to restore enzymatic activity in deficiency states (StatPearls, 2023) or competitive inhibition of the ThDP binding site to disrupt metabolic pathways in pathogens or tumors (Journal of Biological Chemistry, 2020).