Thiamin pyrophosphate-dependent enzyme

Thiamin pyrophosphate-dependent enzymes are a broad, structurally related class of enzymes that require thiamin pyrophosphate (also known as thiamine diphosphate, TPP, or ThDP) as an essential cofactor for their catalytic activity[1][2][3][4][7][8][9]. These enzymes are central to major metabolic pathways, especially the decarboxylation of alpha-keto acids and the transfer of two-carbon units in carbohydrate and amino acid metabolism[2][4][6][8]. Major human examples include pyruvate dehydrogenase complex, alpha-ketoglutarate dehydrogenase complex, branched-chain alpha-keto acid dehydrogenase complex, and transketolase[2][4][7][8][9]. They are crucial for processes ranging from energy production to biosynthesis of nucleic acids and neurotransmitters[2][4][6][8]. Several synthetic and natural analogs, such as oxythiamine and pyrithiamine, can act as inhibitors, making this enzyme family both a metabolic vulnerability and a potential therapeutic or research target[8]. The classification "Thiamin pyrophosphate-dependent enzyme" refers to a large enzyme class—a molecular family, not a specific protein or single therapeutic target, so precise therapeutic targeting must specify a member enzyme (e.g., "Pyruvate dehydrogenase" or "Transketolase").

Other names

ThDP-dependent enzymeTPP-dependent enzymeThiamine diphosphate-dependent enzymeThiamine-dependent enzyme

Competitive inhibition of active site; Inhibition of coenzyme binding; Disruption of thiamine transport or phosphorylation