Superoxide-dependent and ascorbate-dependent formation of hydroxyl radicals in the presence of copper salts: A physiologically significant reaction?

Copper (Cu2+) ions at physiological concentrations can promote the formation of hydroxyl radical (OH.) or a species of equivalent reactivity. The reaction requires H2O2 and a reducing agent. Reduction of Cu2+ can be achieved by superoxide ion generated by a mixture of hypoxanthine and xanthine oxidase or added directly as its potassium salt. Reduction of Cu2+ can also be achieved by ascorbic acid. Hence both O2 .−-dependent and ascorbate-dependent formation of OH. from H2O2 in the presence of Cu2+ can be observed. Only the former reaction is significantly inhibited by superoxide dismutase. The binding of Cu2+ to histidine or albumin at physiological concentrations decreases the formation of OH. radicals in free solution in the presence of either ascorbate or an O2 .−-generating system. It is suggested that OH. is still formed but reacts immediately with the binding molecule.