Superoxide modulates the oxidation and nitrosation of thiols by nitric oxide-derived reactive intermediates. Chemical aspects involved in the balance between oxidative and nitrosative stress

Thiol-containing proteins are key to numerous cellular processes, and their functions can be modified by thiol nitrosation or oxidation. Nitrosation reactions are quenched by O₂/^-·, while the oxidation chemistry mediated by peroxynitrite is quenched by excess flux of either NO or O₂/^- ·. A solution of glutathione (GSH), a model thiol-containing tripeptide, exclusively yielded S-nitrosoglutathione when exposed to the NO donor, Et₂NN(O)NONa. However, when xanthine oxidase was added to the same mixture, the yield of S-nitrosoglutathione dramatically decreased as the activity of xanthine oxidase increased, such that there was a 95% reduction in nitrosation when the fluxes of NO and O₂/^-· were nearly equivalent. The presence of superoxide dismutase reversed O₂/^-·-mediated inhibition, while catalase had no effect. Increasing the flux of O₂/^-· yielded oxidized glutathione (GSSG), peaking when the flux of NO and O₂/^-· were approximately equivalent. The results suggest that oxidation and nitrosation of thiols by superoxide and NO are determined by their relative fluxes and may have physiological significance.