Heptelidic Acid

Glyceraldehyde 3-phosphate dehydrogenase (GAPDH), a key enzyme in carbohydrate metabolism, reversibly catalyzes the conversion of GAP to 1,3-bisphosphoglycerate and NAD+. Heptelidic acid is a sesquiterpene lactone produced by the fungus T. koningii that was shown to have antibiotic activity against anaerobic bacteria such as Bacteroides.{30738} It acts as an irreversible inhibitor of GAPDH that binds to the cysteine-149 residue at the active site of the enzyme (Ki = 1.6 µM).{30740} It can selectively induce apoptosis in high-glycolytic cancer cells by inhibiting the generation of ATP in the glycolytic pathway.{30739} Heptelidic acid is also a selective and competitive inhibitor of mammalian DNA polymerases ? and ? as well as terminal deoxynucleotidyl transferase in family X of DNA polymerases (Kis range from 5.2-9.5 µM).{30741}