Characterization of three isoforms of mammalian peroxiredoxin that reduce peroxides in the presence of thioredoxin.

A peroxidase from yeast that reduces H2O2 with the use of electrons provided by thioredoxin (Trx) together with homologs from a wide variety of species constitute the peroxiredoxin (Prx) family of proteins. Twelve mammalian Prx members have been previously identified in association with various cellular functions apparently unrelated to peroxidase activity. These mammalian proteins have now been divided into three distinct types, Prx I, II, and III, on the basis of their deduced amino acid sequences and immunological reactivity. With the use of recombinant proteins, Prx I, II, and III have now been shown to possess peroxidase activity and to rely on Trx as a source of reducing equivalents. None of the three proteins exhibited peroxidase activity in the presence of glutaredoxin. All three enzymes showed similar kinetic properties: the Vmax was 6-13 micromol/min per mg at 37 degrees C, the Km for Trx was 3-6 microM, and the Km for H2O2 was < 20 microM. Immunoblot analysis of various rat tissues and cultured cells indicated that most cell types contain the three Prx isoforms, the sum of which amounts to approximately 1-10 microg per milligram of soluble protein. Prx I and II are cytosolic proteins, whereas Prx IlI is localized in mitochondria. These results suggest that, together with glutathione peroxidase and catalase, Prx enzymes likely play an important role in eliminating peroxides generated during metabolism as well as during stimulation of cell surface receptors.