Copper, zinc superoxide dismutase and H2O2 -: Effects of bicarbonate on inactivation and oxidations of NADPH and urate, and on consumption of H2O2

Copper,zinc superoxide dismutase (Cu,Zn-SOD) catalyzes the HCO3--dependent oxidation of diverse substrates. The mechanism of these oxidations involves the generation of a strong oxidant, derived from H2O2, at the active site copper. This bound oxidant then oxidizes HCO3- to a strong and diffusible oxidant, presumably the carbonate anion radical that leaves the active site and then oxidizes the diverse substrates. Cu,Zn-SOD is also subject to inactivation by H2O2. It is now demonstrated that the rates of HCO3--dependent oxidations of NADPH and urate exceed the rate of inactivation of the enzyme by similar to100-fold. Cu,Zn-SOD is also seen to catalyze a HCO3-. dependent consumption of the H2O2 and that HCO3- does not protect Cu,Zn-SOD against inactivation by H2O2. A scheme of reactions is offered in explanation of these observations.