New evidence for the multiplicity of ubiquinone- and inhibitor-binding sites in the mitochondrial complex I.
Determination of the number of ubiquinone- and inhibitor-binding sites in the mitochondrial complex I (NADH:ubiquinone oxidoreductase) is a controversial question with a direct implication for elaborating a suitable model to explain the bioenergetic mechanism of this complicated enzyme. We have used combinations of both selective inhibitors and common ubiquinone-like substrates to demonstrate the multiplicity of the reaction centers in the complex I in contrast with competition studies that have suggested the existence of a unique binding site for ubiquinone. Our results provide new evidence for the existence of at least two freely exchangeable ubiquinone-binding sites with different specificity for substrates, as well as for a different kinetic interaction of inhibitors with the enzyme.
Tormo
J R
JR
Department de Farmacologia, Facultat de Farmàcia, Universitat de València, Burjassot, Spain.
Estornell
E
E
D000818:Animals; D001665:Binding Sites; D002417:Cattle; D042967:Electron Transport Complex I; D004734:Energy Metabolism; D066298:In Vitro Techniques; D007700:Kinetics; D008929:Mitochondria, Heart / Q000201:enzymology; D008954:Models, Biological; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism*; D013367:Submitochondrial Particles / Q000201:enzymology; D013379:Substrate Specificity; D014451:Ubiquinone / Q000378:metabolism*
D014451:Ubiquinone; D009247:NADH, NADPH Oxidoreductases; D042967:Electron Transport Complex I