Superoxide and Iron: Partners in Crime

Abstract Superoxide (O2 ) poses multiple threats, which are diminished by a family of metalloenzymes, the superoxide dismutases. Among the damaging effects of O are direct oxidation of low‐molecular2 weight reductants; inactivation 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 to univalently oxidize the [4 Fe2 4 S] clusters of dehydratases, which causes release of iron. The “free” iron, which is kept reduced by cellular reductants, then reduces hydroperoxides to hydroxyl or alkoxyl radicals. Because the “free” iron will preferentially bind to anionic polymers, such as nucleic acids, or to anionic surfaces, such as cell membranes, these radicals will be generated adjacent to these vital targets and will preferentially attack them. O and iron can thus be viewed as part2 ners in crime, and reciprocal regulatory effects between iron and O2 may be anticipated. These are discussed.