Pathways of hydrogen peroxide generation in guinea pig cerebral cortex mitochondria.
The production of H2O2 by brain mitochondria was monitored employing a new technique based on the horseradish peroxidase dependent oxidation of acetylated ferrocytochrome c. It was shown that brain mitochondria release H2O2 by an intermediate autooxidation at the QH2-cytochrome c oxidoreductase level (induced by antimycin A and inhibited by myxothiazol). With both succinate and pyruvate plus malate this H2O2 release is inhibited at high substrate concentrations. With pyruvate plus malate a second source of H2O2 could be detected, apparently from autoxidation at the NADH dehydrogenase level. With alpha-glycerophosphate some H2O2 derives from autooxidation at the alpha-glycerophosphate dehydrogenase. The NADH dehydrogenase dependent, but not the QH2-cytochrome c oxidoreductase dependent H2O2 was significantly stimulated upon depletion of the mitochondrial glutathione.
Zoccarato
F
F
Department of Biological Chemistry, University of Padova, Italy.
Cavallini
L
L
Deana
R
R
Alexandre
A
A
D000818:Animals; D000968:Antimycin A / Q000494:pharmacology; D002540:Cerebral Cortex / Q000648:ultrastructure*; D005979:Glutathione Peroxidase / Q000378:metabolism; D006168:Guinea Pigs; D006735:Horseradish Peroxidase / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism*; D008293:Malates / Q000494:pharmacology; D008689:Methacrylates; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D009245:NADH Dehydrogenase / Q000378:metabolism; D011773:Pyruvates / Q000494:pharmacology; D019289:Pyruvic Acid; D013844:Thiazoles / Q000494:pharmacology
D008293:Malates; D008689:Methacrylates; D011773:Pyruvates; D013844:Thiazoles; D000968:Antimycin A; C030517:myxothiazol; C030298:malic acid; D019289:Pyruvic Acid; D006861:Hydrogen Peroxide; D006735:Horseradish Peroxidase; D005979:Glutathione Peroxidase; D009245:NADH Dehydrogenase