Peroxiredoxin-2 (Prdx2), a potent peroxide reductant, is the third most abundant 
protein in the erythrocyte and might be expected to play a major role in the 
cell's oxidative defenses. However, in this study, experiments with erythrocytes 
from mice with a disrupted Prdx2 gene found that the cells were not more 
sensitive to exogenous H(2)O(2) or organic peroxides than wild type. 
Intraerythrocytic H(2)O(2) was increased, however, indicating an important role 
for Prdx2 in detoxifying endogenously generated H(2)O(2). These results are 
consistent with proposals that red cell Prdx2 acts stoichiometrically, not 
catalytically, in reducing peroxides. Additional experiments with mice with 
disrupted catalase or glutathione peroxidase (Gpx1) genes showed that Gpx1 is 
the only erythrocyte enzyme that reduces organic peroxides. Catalase(-/-) cells 
were readily oxidized by exogenous H(2)O(2). Cells lacking both catalase and 
Gpx1 were more sensitive to exogenous H(2)O(2) than cells lacking only catalase. 
A kinetic model proposed earlier to rationalize results with Gpx1(-/-) 
erythrocytes also fits the data with Prdx2(-/-) cells and indicates that 
although Gpx1 and Prdx2 both participate in removing endogenous H(2)O(2), Prdx2 
plays a larger role. Although the rate of H(2)O(2) production in the red cell is 
quite low, Prdx2-deficient mice are anemic, suggesting an important role in 
erythropoiesis.