MECHANISM OF COPPER-CATALYZED OXIDATION OF GLUTATHIONE

The mechanism of copper-catalyzed glutathione oxidation was investigat ed using oxygen consumption, thiol depletion, spectroscopy and hydroxy l radical detection. The mechanism of oxidation has kinetics which app ear biphasic. During the first reaction phase a stoichiometric amount of oxygen is consumed (1 mole oxygen per 4 moles thiol) with minimal ( OH)-O-. production. In the second reaction phase, additional (excess) oxygen is consumed at an increased rate and with significant hydrogen peroxide and (OH)-O-. production. The kinetic and spectroscopic data s uggest that copper forms a catalytic complex with glutathione (1 mole copper per 2 moles glutathione). Our proposed reaction mechanism assum es two parallel processes (superoxide-dependent and peroxide-dependent ) for the first reaction phase and superoxide-independent for the seco nd phase. Our current results indicate that glutathione, usually consi dered as an antioxidant, can act as prooxidant at physiological condit ions and therefore can participate in cellular radical damage.