title: A ternary mechanism for NADH oxidation by positively charged electron acceptors, catalyzed at the flavin site in respiratory complex I.
abstract: The flavin mononucleotide in complex I (NADH:ubiquinone oxidoreductase) catalyzes NADH oxidation, O(2) 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 O(2) reduction the rate is stimulated, not inhibited, by high NADH concentrations.
authors.affiliation: Medical Research Council Mitochondrial Biology Unit, Wellcome Trust/MRC Building, Cambridge, UK.
authors.forename: James A
authors.initials: JA
authors.lastname: Birrell
authors.forename: Martin S
authors.initials: MS
authors.lastname: King
authors.forename: Judy
authors.initials: J
authors.lastname: Hirst
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism; D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002417:Cattle; D042967:Electron Transport Complex I / Q000378:metabolism*; D004583:Electrons; D005415:Flavins / Q000737:chemistry* / Q000378:metabolism; D006540:Herbicides / Q000737:chemistry / Q000378:metabolism; D008929:Mitochondria, Heart / Q000737:chemistry / Q000378:metabolism; D009243:NAD / Q000737:chemistry* / Q000378:metabolism; D010084:Oxidation-Reduction; D010269:Paraquat / Q000737:chemistry / Q000378:metabolism; D017975:Ruthenium Compounds / Q000737:chemistry / Q000378:metabolism
chemical_list: D005415:Flavins; D006540:Herbicides; D017975:Ruthenium Compounds; D009243:NAD; C031584:hexammineruthenium; D000246:Adenosine Diphosphate Ribose; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D042967:Electron Transport Complex I; D010269:Paraquat