Thiamine pyrophosphate-dependent metabolic enzymes (TPP-dependent enzymes)

Thiamine pyrophosphate (TPP)-dependent metabolic enzymes are a diverse group of enzymes that utilize thiamine pyrophosphate (the active form of Vitamin B1) as an essential cofactor to catalyze the cleavage of carbon-carbon bonds adjacent to a carbonyl group (PubMed: 24533648). Key members include the pyruvate dehydrogenase complex (PDC), alpha-ketoglutarate dehydrogenase (KGDH), branched-chain alpha-keto acid dehydrogenase (BCKDH), and transketolase (TKT). These enzymes play critical roles in central energy metabolism, the citric acid cycle, and the pentose phosphate pathway, facilitating the conversion of nutrients into cellular energy and biosynthetic precursors (StatPearls: NBK537204). Dysregulation or deficiency of these enzymes is linked to metabolic disorders like maple syrup urine disease and neurological conditions such as Wernicke-Korsakoff syndrome (NIH: NBK1144). In oncology, certain TPP-dependent enzymes like transketolase-like 1 (TKTL1) are often upregulated in tumors to support the Warburg effect, making them potential targets for cancer therapy (PubMed: 28811344). Additionally, because many pathogens rely on unique TPP-dependent pathways, these enzymes are explored as targets for antimicrobial and antiparasitic drugs.

Other names

Thiamin diphosphate-dependent enzymesThDP-dependent enzymesTPP-dependent enzymesThiamine-dependent enzymes

These enzymes are targeted primarily through cofactor supplementation to restore metabolic function or through competitive inhibition of the TPP-binding site to disrupt metabolic pathways in cancer cells or pathogens.