摘要 : In brain mitochondria succinate activates H_2O_2 release, concentration dependently (starting at 15 μM), and in the presence of NAD dependent substrates (glutamate, pyruvate, β-hydroxybutyrate). We report that TCA cycle metabolite... 展开 In brain mitochondria succinate activates H_2O_2 release, concentration dependently (starting at 15 μM), and in the presence of NAD dependent substrates (glutamate, pyruvate, β-hydroxybutyrate). We report that TCA cycle metabolites (citrate, isocitrate, α-ketoglutarate, fumarate, malate) individually and quickly inhibit H_2O_2 release. When they are present together at physiological concentration (0.2, 0.01, 0.15, 0.12, 0.2 mM respectively) they decrease H_2O_2 production by over 60% at 0.1-0.2 mM succinate. The degree of inhibition depends on the concentration of each metabolite. Acetoacetate is a strong inhibitor of H_2O_2 release, starting at 10 μM and acting quickly. It potentiates the inhibition induced by TCA cycle metabolites. The action of acetoacetate is partially removed by β-hydroxybutyrate. Removal is minimal at 0.1 mM acetoacetate, and is higher at 0.5 mM acetoacetate. We conclude that several inhibitors of H_2O_2 release act jointly and concentration dependently to rapidly set the required level of H _2O_2 generation at each succinate concentration. 收起