A novel strong competitive inhibitor of complex I.
Alkaline incubation of NADH results in the formation of a very potent inhibitor of complex I (NADH:ubiquinone oxidoreductase). Mass spectroscopy (molecular mass equal to 696) and absorption spectroscopy suggest that the inhibitor is derived from attachment of two oxygen atoms to the nicotinamide moiety of NADH. The inhibitor is competitive with respect to NADH with a K(i) of about 10(-8)M. The inhibitor efficiently suppresses NADH-oxidase, NADH-artificial acceptor reductase, and NADH-quinone reductase reactions catalyzed by submitochondrial particles, as well as the reactions catalyzed by either isolated complex I or the three subunit flavoprotein fragment of complex I.
Kotlyar
Alexander B
AB
Molecular Biology Division (151-S), VA Medical Center, 4150 Clement Street, San Francisco, CA 94121, USA. s2shak@post.tau.ac.il
Karliner
Joel S
JS
Cecchini
Gary
G
D000818:Animals; D042967:Electron Transport Complex I / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D013058:Mass Spectrometry; D008929:Mitochondria, Heart / Q000201:enzymology; D015394:Molecular Structure; D009243:NAD / Q000737:chemistry* / Q000378:metabolism; D010084:Oxidation-Reduction; D051381:Rats
D009243:NAD; D042967:Electron Transport Complex I