Many faces of superoxide dismutase, originally known as erythrocuprein

Superoxide dismutase (SOD), discovered in 1969 by Fridovich, was found to be identical with the ubiquitous copper protein, erythrocuprein, originally described by Keilin. SOD had great influence in the studies on oxygen radicals and toxicity. New reactions, now identified with this protein, expand its potential beyond dismutation of superoxide. By virtue of being a copper protein with accessible metal centre, the SOD protein shows efficient reversible electron transfer with superoxide $(O^{-\bullet}_ 2)$. So do others in addition to $O^{-\bullet}_ 2$. Utilizing this potential, SOD can nullify autoxidation by dismutating the two radical products formed in the first step of electron transfer. This brings out a true antioxidant function of SOD of saving catechol, thiol and other compounds from autoxidation loss. Among the emerging novel functions, two examples are outstanding. First is the protection against autoxidative inactivation of calcineurin (a protein phosphatase) by the native SOD protein, but not its mutant forms. Second is the ability of exogenously added native SOD as well as metalfree protein (with no possibility of dismutation activity) to regulate an intracellular enzyme, HMGCoA reductase, and thereby cholesterol biogenesis. A quantum jump has been made in understanding the versatility of the SOD protein in cell functions by the discovery of mutants in the neurodegenerative disease, familial amyotrophic lateral sclerosis. These mutant proteins retain the dismutase activity to varying degree (like isoenzymes), have changes in structure and folding and an increased tendency to form aggregates and insoluble complexes, and assume activities that are toxic.