[Interaction of mitochondrial succinate:ubiquinone reductase with thenoyltrifluoroacetone and carboxin].
Thenoyltrifluoroacetone (TTA) and carboxin inhibit soluble ubiquinone-deficient succinate: ubiquinone reductase according to the mixed type (with respect to added Q2) inhibition. pattern. The Ki values for the inhibitors are mutually dependent, thus indicating the presence of a single binding site for both TTA and carboxin. The enolic form of TTA was shown to be the species interacting with the enzyme. Carboxin prevents the alkali-induced inactivation of the membrane-bound succinate dehydrogenase without having any effect on the reconstitution of succinate: ubiquinone reductase from the soluble dehydrogenase and b-c1 complex. The reduction of the respiratory chain by succinate protects succinate dehydrogenase against inactivation (solubilization) by alkali; under these conditions, carboxin does not affect the inactivation process. The cumulative data suggest that the degree of the mutual mobility of the succinate dehydrogenase smaller subunit and ubiquinone reactivity-conferring protein (QPs) is a prerequisite for the catalytic mechanism of succinate: ubiquinone reductase. A mechanism of the enzyme inhibition by TTA and carboxin is proposed, which consists in non-covalent cross-linking of the subunits by the inhibitors.
D000813:Anilides / Q000494:pharmacology*; D000818:Animals; D002261:Carboxin / Q000494:pharmacology*; D002417:Cattle; D042963:Electron Transport Complex II; D007425:Intracellular Membranes / Q000201:enzymology; D007700:Kinetics; D046911:Macromolecular Substances; D008560:Membrane Fluidity; D008929:Mitochondria, Heart / Q000201:enzymology*; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors*; D010088:Oxidoreductases / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D013385:Succinate Dehydrogenase / Q000037:antagonists & inhibitors*; D013804:Thenoyltrifluoroacetone / Q000494:pharmacology*; D013876:Thiophenes / Q000494:pharmacology*
D000813:Anilides; D046911:Macromolecular Substances; D009097:Multienzyme Complexes; D013876:Thiophenes; D013804:Thenoyltrifluoroacetone; D002261:Carboxin; D010088:Oxidoreductases; D042963:Electron Transport Complex II; D013385:Succinate Dehydrogenase
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