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A novel strong competitive inhibitor of complex I
Author(s) -
Kotlyar Alexander B.,
Karliner Joel S.,
Cecchini Gary
Publication year - 2005
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2005.07.076
Subject(s) - flavoprotein , chemistry , oxidoreductase , submitochondrial particle , nad+ kinase , nadh dehydrogenase , stereochemistry , moiety , reductase , nicotinamide , electron transport chain , dicoumarol , protein subunit , enzyme , biochemistry , gene
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.