The reaction of superoxide with reduced glutathione

Superoxide, generated by a xanthine oxidase/hypoxanthine system, reacts with reduced glutathione (GSH) to cause an increase in oxygen consumption and oxidized glutathione (GSSG) formation, both of which are fully inhibited by superoxide dismutase. In this study we have shown that little, if any, of the additional oxygen consumed is converted to hydrogen peroxide. We have confirmed that approximately 90% of the GSH is oxidized to GSSG, the remainder being converted to the sulfonic acid. Approximately 1.2 mol of GSSG was formed for each additional mole of oxygen consumed in the presence of GSH. The efficiency of the reaction increased with increasing GSH concentration (1-8 mM), pH, and pO2 and with decreasing superoxide generation rate. The results are consistent with a superoxide-dependent chain that does not produce hydrogen peroxide and that is terminated primarily by superoxide dismutation. We propose that this occurs via an initial reaction of superoxide with GSH to produce a sulfinyl radical rather than hydrogen transfer to give the thiyl radical. Our data suggest a rate constant for the superoxide/GSH reaction in the 10(2)-10(3) M-1s-1 range. GSH at the millimolar concentrations found intracellular should react with superoxide, but because superoxide is regenerated, it will not be an effective scavenger. Physiologically, superoxide dismutase is required to prevent chain oxidation of GSH.