The interaction of mitochondrial transhydrogenase with derivatives of coenzyme A.
The 2,4-dinitrophenyl derivative of dephospho-CoA and the 7-nitrobenzofurazan-4-yl derivative of CoA are competitive inhibitors (Ki 3 microM and 2.6 microM respectively) of mitochondrial transhydrogenase with regard to NAD+ and NADPH respectively. The 7-nitrobenzofurazan-4-yl derivative of dephospho-CoA is a competitive inhibitor with regard to both transhydrogenase substrates with the same Ki equal to 0.3 microM. The pattern of transhydrogenase inhibition with the 7-nitrobenzofurazan-4-yl derivative of dephospho-CoA indicates that one molecule of the inhibitor binds simultaneously to both the NADP(H) and the NAD(H) binding sites of the enzyme. This result is evidence of the short distance between the NADP(H) and the NAD(H) binding sites.
D000818:Animals; D002417:Cattle; D003065:Coenzyme A / Q000031:analogs & derivatives* / Q000494:pharmacology; D007700:Kinetics; D008929:Mitochondria, Heart / Q000201:enzymology*; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism*; D009250:NADP Transhydrogenases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013329:Structure-Activity Relationship
D009247:NADH, NADPH Oxidoreductases; D009250:NADP Transhydrogenases; D003065:Coenzyme A