Superoxide and iron: Partners in crime

Superoxide (O-2(-)) poses multiple threats, which are diminished by a famil y of metalloenzymes, the superoxide dismutases. Among the damaging effects of O-2(-) are direct oxidation of low-molecular-weight reductants; inactiva tion of a select group of enzymes; and reaction with NO to yield the strong oxidant, peroxynitrite, Of even greater import is the ability of O-2(-) to univalently oxidize the [4 Fe-4 S] clusters of dehydratases, which causes release of iron. The "free" iron, which is kept reduced by cellular reducta nts, then reduces hydroperoxides to hydroxyl or alkoxyl radicals. Because t he "free" iron will preferentially bind to anionic polymers, such as nuclei c acids, or to anionic surfaces, such as cell membranes, these radicals wil l be generated adjacent to these vital targets and will preferentially atta ck them. O-2(-) and iron can thus be viewed as partners in crime, and recip rocal regulatory effects between iron and O-2(-) may be anticipated, These are discussed.