Inhibition of mammalian pyruvate dehydrogenase complex by metabolites of 3-mercaptopropanoic acid.
3-Mercaptopropanoyl-CoA and S-acetyl-3-mercaptopropanoyl-CoA, physiological metabolites of the known convulsant 3-mercaptopropanoic acid, were found to be inhibitors of purified pyruvate dehydrogenase complex from porcine and bovine heart. Under optimal conditions, 50% inhibition was obtained at 12.6 microM 3-mercaptopropanoyl-CoA or 5 microM S-acetyl-3-mercaptopropanoyl-CoA. The inhibition caused by S-acetyl-3-mercaptopropanoyl-CoA was irreversible. Maximal inhibition of the complex was observed when it was preincubated with the inhibitor under conditions which promote reduction of the endogenous lipoate.
D015097:3-Mercaptopropionic Acid / Q000031:analogs & derivatives; D000107:Acetylation; D000214:Acyl Coenzyme A / Q000494:pharmacology*; D000818:Animals; D002417:Cattle; D007700:Kinetics; D009206:Myocardium / Q000201:enzymology; D011768:Pyruvate Dehydrogenase Complex / Q000037:antagonists & inhibitors* / Q000302:isolation & purification; D013552:Swine
C045680:3-mercaptopropionyl-coenzyme A; D000214:Acyl Coenzyme A; D011768:Pyruvate Dehydrogenase Complex; C053050:S-acetyl-3-mercaptopropanoyl-coenzyme A; D015097:3-Mercaptopropionic Acid