title: A novel strong competitive inhibitor of complex I.
abstract: 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.
authors.affiliation: Molecular Biology Division (151-S), VA Medical Center, 4150 Clement Street, San Francisco, CA 94121, USA. s2shak@post.tau.ac.il
authors.forename: Alexander B
authors.initials: AB
authors.lastname: Kotlyar
authors.forename: Joel S
authors.initials: JS
authors.lastname: Karliner
authors.forename: Gary
authors.initials: G
authors.lastname: Cecchini
mesh_terms: 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
chemical_list: D009243:NAD; D042967:Electron Transport Complex I