Thiamine diphosphate-dependent dehydrogenase (ThDP-dependent dehydrogenase)

Thiamine diphosphate-dependent dehydrogenases are a diverse family of enzymes that require the coenzyme thiamine diphosphate (ThDP, also known as thiamine pyrophosphate) for catalytic function. These enzymes catalyze a wide range of biochemical reactions, including the cleavage and formation of carbon-carbon and other bonds, and are classified into several structural and functional subfamilies (oxidoreductases, transferases, lyases, etc.). ThDP-dependent dehydrogenases are found in all domains of life and play essential roles in central metabolism (e.g., pyruvate dehydrogenase, alpha-ketoglutarate dehydrogenase, transketolase). Dysregulation or deficiency leads to metabolic diseases and some are implicated in neurodegeneration and cancer. Pharmacologically, they are targets for inhibitors that act via ThDP-competitive mechanisms, but clinical application is limited by the breadth of biological impact and potential toxicity associated with systemic metabolic inhibition.

Other names

ThDP-dependent enzymeThiamine diphosphate-dependent enzymeThiamine pyrophosphate-dependent enzymeThiamine pyrophosphate-dependent dehydrogenase

ThDP-competitive inhibition (drugs compete with ThDP for the coenzyme site, blocking enzyme activity); Selective inhibition of specific ThDP-dependent dehydrogenases depending on analogue structure