CUZN-SUPEROXIDE DISMUTASE, EXTRACELLULAR-SUPEROXIDE DISMUTASE, AND GLUTATHIONE-PEROXIDASE IN BLOOD FROM INDIVIDUALS HOMOZYGOUS FOR ASP(90)ALA CUZN-SUPEROXIDE DISMUTASE MUTATION

The Asp(90)Ala CuZn-superoxide dismutase mutation is associated with a myotrophic lateral sclerosis (ALS) in both home-and heterozygous form, We analyzed antioxidant enzymes in blood from 44 individuals homozygo us and 114 individuals heterozygous for the Asp(90)Ala mutation as wel l as 66 blood relatives carrying the wild-type allele only. Erythrocyt e CuZn-superoxide dismutase activity was reduced by 9% in the homozygo us individuals, confirming previous findings on a smaller cohort. The specific activity of Asp(90)Ala mutant CuZn-superoxide dismutase in er ythrocytes was equal to that of isolated mutant enzyme and slightly hi gher than that of isolated wild-type enzyme. There was no evidence for the presence of inactive mutant molecules in erythrocytes, and the lo wer activity is due to the occurrence of fewer active molecules. There were no significant differences between the groups in plasma extracel lular superoxide dismutase content, and the erythrocyte glutathione pe roxidase activities were virtually identical. Also, there were no diff erences in these parameters between homozygous individuals with or wit hout ALS. There was no evidence for any association with ALS of a poly morphic extracellular superoxide dismutase mutation, Arg(213)Gly. The absence of response of the blood antioxidant enzymes to the Asp(90)Ala CuZn-superoxide dismutase mutation does not support the theory that t he ALS-linked CuZn-superoxide dismutase mutations cause disease by inc reased oxidant stress.