Copper-catalyzed autoxidations of GSH and L-ascorbic acid: mutual inhibition of the respective oxidations by their coexistence

Glutathione (GSH) is known to inhibit copper-catalyzed autoxidation of L-ascorbic acid (AA); in this study, AA was found to conversely inhibit copper-catalyzed autoxidation of GSH. To elucidate the mechanism of the mutual inhibition of the autoxidations of these two reducing substances in their coexistence, we have kinetically investigated these phenomena. The study of the former phenomenon revealed that GSH forms a 1:1 chelate with Cu⁺ and thereby prevents the autoxidation of AA. By the analysis of the latter phenomenon, it was postulated that the inhibition of GSH oxidation by AA is due to rapid reduction of thiyl radical of GSH by AA rather than competition of AA with GSH in the reduction of Cu²⁺. The effect of GSH on the formation of hydroxyl radical by the copper-catalyzed autoxidation of AA was also studied and it was found that the hydroxyl radical formation was delayed dose-dependently by GSH with time lags comparable to those of the oxidation of AA. Because there are several lines of evidence that redox-active copper ions are released from tissues under pathological conditions, it is possible that such copper ions coexist with AA and GSH in vivo, and in such a situation, GSH may exert an inhibitory effect on the hydroxyl radical formation caused by the autoxidation of AA.