A novel strong competitive inhibitor of complex I

Alexander B Kotlyar; Joel S Karliner; Gary Cecchini

doi:10.1016/j.febslet.2005.07.076

A novel strong competitive inhibitor of complex I

FEBS Lett. 2005 Aug 29;579(21):4861-6. doi: 10.1016/j.febslet.2005.07.076.

Authors

Alexander B Kotlyar¹, Joel S Karliner, Gary Cecchini

Affiliation

¹ Molecular Biology Division (151-S), VA Medical Center, 4150 Clement Street, San Francisco, CA 94121, USA. s2shak@post.tau.ac.il

PMID: 16107251
DOI: 10.1016/j.febslet.2005.07.076

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.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Animals
Electron Transport Complex I / antagonists & inhibitors*
Electron Transport Complex I / metabolism
Hydrogen-Ion Concentration
Mass Spectrometry
Mitochondria, Heart / enzymology
Molecular Structure
NAD / chemistry*
NAD / metabolism
Oxidation-Reduction
Rats

Substances

NAD
Electron Transport Complex I