SUPEROXIDE AS AN INTRACELLULAR RADICAL SINK

A pathway is proposed for superoxide to act as a sink for intracellularly generated radicals. A variety of radicals, either directly or via reduced glutathione (GSH) as an intermediate, can transfer their unpaired electron to oxygen to give superoxide. It is proposed that in a cellular environment, superoxide can undergo chain reactions involving GSH with or without another redox cycling agent, converting GSH to oxidized glutathione (GSSG) and oxygen to hydrogen peroxide far in excess of the initial radical. This places an oxidative stress on the cell, depleting reducing equivalents and energy reserves. Superoxide dismutase is necessary to prevent this oxidative stress, as well as any direct damage by superoxide. Through this metabolic pathway, GSH and superoxide dismutase can be linked in antioxidant function, and superoxide dismutase, by reacting with superoxide, can provide general protection against radical reactions in the cell. The pathway also provides a mechanism for superoxide and superoxide dismutase to influence the redox state of the cell and regulate functions that are under redox control.