Since 1–2% of the red cell’s oxyhemoglobin undergoes spontaneous heterolytic dissociation into metHb and superoxide every day, and superoxide is readily converted to H2O2 by superoxide dismutase, the red cell is unavoidably exposed to high levels of reactive oxygen species (ROS). We have used a series of gene-disrupted mice to examine the oxidative defenses of the red cell. Work with glutathione peroxidase deficient [GSHPx(−/−)] red cells has been reported earlier. We here add results with red cells from mice that were catalase deficient (−/−), catalase heterozygotes (+/−), double knockouts [GSHPx(−/−) and catalase (−/−)], or peroxiredoxin II deficient. Catalase(−/−) cells were readily oxidized by exogenous H2O2, as monitored by methemoglobin formation, but no methemoglobin was formed when these cells were exposed to organic peroxides. Catalase heterozygotes were not distinguishable from wild type cells in these assays. This is consistent with the clinical finding that partial catalase deficiency is a benign condition. Red cells lacking both GSHPx and catalase exhibited more metHb formation in response to an H2O2 generating system than did either single knockout, indicating that both enzymes contribute to the defense against exogenous H2O2. Adding catalase deficiency to GSHPx deficiency did not increase Hb oxidation by organic peroxides. With peroxiredoxin-deficient cells, PrxII(−/−), preliminary results found an increased flux of the endogenously generated H2O2 through catalase, which could be detected using 3-amino-1,2,4-triazole (3-AT) inhibition. Earlier work (
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