[Characteristics of thiamine thiazolone diphosphate-induced inhibition of a pyruvate dehydrogenase complex in vitro and in intact mitochondria].
Thiamine thiazolone diphosphate (TTPP) was capable of penetrating through the mitochondrial membrane and of inhibiting the pyruvate dehydrogenase complex (PDC) in intact mitochondria. TTPP depressed the activity of mammalian PDC in a mixed manner (Ki = 5.10(-8) M) and yeast pyruvate decarboxylase (Ki = 5.10(-6) M) via a competitive mechanism with respect to thiamine diphosphate. It was shown that decarboxylation of pyruvate in intact and disrupted mitochondria of rat liver and brain is less inhibited by TTPP than the overall activity of PDC determined by the formation of acetyl-CoA. It was assumed that TTPP as a transition state analog participates only in oxidative reactions (but not in simple decarboxylation of pyruvate).
D000302:Adrenal Cortex / Q000201:enzymology; D000818:Animals; D001921:Brain / Q000201:enzymology; D002417:Cattle; D055598:Chemical Phenomena; D002621:Chemistry; D066298:In Vitro Techniques; D007700:Kinetics; D008928:Mitochondria / Q000201:enzymology*; D008930:Mitochondria, Liver / Q000201:enzymology; D011768:Pyruvate Dehydrogenase Complex / Q000037:antagonists & inhibitors*; D051381:Rats; D013835:Thiamine Pyrophosphate / Q000031:analogs & derivatives* / Q000494:pharmacology
D011768:Pyruvate Dehydrogenase Complex; C014222:thiamine thiazolone pyrophosphate; D013835:Thiamine Pyrophosphate
Osobennosti ingibirovaniia tiamintiazolondifosfatom piruvatdegidrogenaznogo kompleksa in vitro i v sostave intaktnykh mitokhondriĭ.