A ternary mechanism for NADH oxidation by positively charged electron acceptors, catalyzed at the flavin site in respiratory complex I

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• 作者：James A. Birrell¹ ; ^a ; Martin S. King¹ ; ^a ; Judy Hirst ; ^a ; ^{jh@mrc-mbu.cam.ac.uk"" rel=""nofollow}
• 关键词：Hexaammineruthenium(III) ; Mitochondria ; NADH ; ubiquinone oxidoreductase ; Oxidative stress ; Paraquat ; Ternary reaction
• 刊名：FEBS Letters
• 出版年：2011
• 出版时间：21 July 2011
• 年：2011
• 卷：585
• 期：14
• 页码：2318-2322
• 全文大小：851 K

文摘

The flavin mononucleotide in complex I (NADH:ubiquinone oxidoreductase) catalyzes NADH oxidation, O₂ reduction to superoxide, and the reduction of several ‘artificial’ electron acceptors. Here, we show that the positively-charged electron acceptors paraquat and hexaammineruthenium(III) react with the nucleotide-bound reduced flavin in complex I, by an unusual ternary mechanism. NADH, ATP, ADP and ADP-ribose stimulate the reactions, indicating that the positively-charged acceptors interact with their negatively-charged phosphates. Our mechanism for paraquat reduction defines a new mechanism for superoxide production by complex I (by redox cycling); in contrast to direct O₂ reduction the rate is stimulated, not inhibited, by high NADH concentrations.