FIG. 1.

Typical 2-Cys peroxiredoxin catalytic cycle and hyperoxidation. Low levels of H₂O₂ are reduced by Prx through a pair of essential Cys residues, Cys-S_PH and Cys-S_RH. The sulfenic acid intermediate (Cys-S_POH) reacts with the Cys-S_RH residue to form an intermolecular disulfide bond, which is subsequently reduced by thioredoxin. During this process, the Prx molecules alternate between dimeric and decameric states. The reduced, decameric form of the protein is the most reactive with H₂O₂ (51, 73, 75). As the level of H₂O₂ increases, eukaryotic Prxs can react with a second H₂O₂ molecule to form the sulfinic acid form (CysS_PO₂^-) and, as a result, are inactivated. This hyperoxidation stabilizes the decameric state of the Prx molecule and can lead to the formation of filamentous and spherical, high-molecular-weight species; depicted schematically here. The molecular details of these interactions are unknown. Further oxidation of the Prx molecule to the Cys sulfonic acid form (CysS_PO₃^2-) can occur. Srx, however, can only reduce the CysS_PO₂^- moiety.