The familial amyotrophic lateral sclerosis-associated amino acid substitutions E100G, G93A, and G93R do not influence the rate of inactivation of copper- and zinc-containing superoxide dismutase by H2O2.
Inactivation of copper- and zinc-containing superoxide dismutase (Cu,ZnSOD) by H2O2 is the consequence of several sequential reactions: reduction of the active site Cu(II) to Cu(I) by H2O2; oxidation of the Cu(I) by a second H2O2, thus generating a powerful oxidant, which may be Cu(I)O or Cu(II)OH or Cu(III); and finally oxidation of one of the histidines in the ligand field, causing loss of SOD activity. Three familial amyotrophic lateral sclerosis (FALS)-associated mutant Cu,ZnSODs, i.e., E100G, G93A, and G93R, did not differ from the control enzyme in susceptibility to inactivation by H2O2. It thus appears that an increased peroxidase activity of the FALS-associated Cu,ZnSOD variants might not be a factor in the development of this disease. This leaves the loss of Zn, and the consequent increase in peroxidase activity, or in nitration activity, as a viable explanation (J. P. Crow et al., 1997, J. Neurochem. 69, 1936-1944), among other possibilities.
Liochev
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Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA.
Chen
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Hallewell
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Fridovich
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I
D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics*; D004795:Enzyme Stability / Q000235:genetics; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D007700:Kinetics; D008667:Metalloproteins / Q000378:metabolism; D009154:Mutation / Q000235:genetics*; D010544:Peroxidases / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics*; D014527:Uric Acid / Q000494:pharmacology
D008667:Metalloproteins; D014527:Uric Acid; D006861:Hydrogen Peroxide; D010544:Peroxidases; D013482:Superoxide Dismutase