What are the sources of hydrogen peroxide production by heart mitochondria?
Coupled rat heart mitochondria produce externally hydrogen peroxide at the rates which correspond to about 0.8 and 0.3% of the total oxygen consumption at State 4 with succinate and glutamate plus malate as the respiratory substrates, respectively. Stimulation of the respiratory activities by ADP (State 4-State 3 transition) decreases the succinate- and glutamate plus malate-supported H2O2 production 8- and 1.3-times, respectively. NH4+ strongly stimulates hydrogen peroxide formation with either substrate without any effect on State 4 and/or State 3 respiration. Rotenone-treated, alamethicin-permeabilized mitochondria catalyze NADH-supported H2O2 production at a rate about 10-fold higher than that seen in intact mitochondria under optimal (State 4 succinate-supported respiration in the presence of ammonium chloride) conditions. NADH-supported hydrogen peroxide production by the rotenone-treated mitochondria devoid of a permeability barrier for H2O2 diffusion by alamethicin treatment are only partially (approximately 50%) sensitive to the Complex I NADH binding site-specific inhibitor, NADH-OH. The residual activity is strongly (approximately 6-fold) stimulated by ammonium chloride. NAD+ inhibits both Complex I-mediated and ammonium-stimulated H2O2 production. In the absence of stimulatory ammonium about half of the total NADH-supported hydrogen peroxide production is catalyzed by Complex I. In the presence of ammonium about 90% of the total hydrogen peroxide production is catalyzed by matrix located, ammonium-dependent enzyme(s).
Grivennikova
Vera G
VG
Department of Biochemistry, School of Biology, Moscow State University, Moscow 119991, Russian Federation.
Kareyeva
Alexandra V
AV
Vinogradov
Andrei D
AD
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D042967:Electron Transport Complex I / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism*; D066298:In Vitro Techniques; D008293:Malates / Q000378:metabolism; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism; D009243:NAD / Q000378:metabolism; D010084:Oxidation-Reduction; D010101:Oxygen Consumption; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology; D051381:Rats; D019802:Succinic Acid / Q000378:metabolism
D008293:Malates; D024101:Mitochondrial Proteins; D000644:Quaternary Ammonium Compounds; D009243:NAD; D018698:Glutamic Acid; D000244:Adenosine Diphosphate; C030298:malic acid; D019802:Succinic Acid; D006861:Hydrogen Peroxide; D042967:Electron Transport Complex I