SUPEROXIDE RADICAL AND SUPEROXIDE DISMUTASES

O-2(-) oxidizes the [4Fe-4S] clusters of dehydratases, such as aconitase, causing- inactivation and release of Fe(II), which may then reduce H2O2 to OH- +OH .. SODs inhibit such HO . production by scavenging O-2(-), but Cu, ZnSODs, by virtue of a nonspecific peroxidase activity, may peroxidize spin trapping agents and thus give the appearance of catalyzing OH . production from H2O2. There is a glycosylated, tetrameric Cu, ZnSOD in the extracellular space that binds to acidic glycosamino-glycans. It minimizes the reaction of O-2(-) with NO. E. coli, and other gram negative microorganisms, contain a periplasmic Cu, ZnSOD that may serve to protect against extracellular O-2(-). Mn(III) complexes of multidentate macrocyclic nitrogenous ligands catalyze the dismutation of O-2(-) and are being explored as potential pharmaceutical agents. SOD-null mutants have been prepared to reveal the biological effects of O-2(-). SodA, sodB E. coli exhibit dioxygen-dependent auxotrophies and enhanced mutagenesis, reflecting O-2(-)-sensitive biosynthetic pathways and DNA damage. Yeast, lacking either Cu, ZnSOD or MnSOD, are oxygen intolerant, and the double mutant was hypermutable and defective in sporulation and exhibited requirements for methionine and lysine. A Cu, ZnSOD-null Drosophila exhibited a shortened lifespan.