The biochemistry of selenium and the glutathione system

In the context of defense against pro-oxidants, selenium and the glutathion e (GSH) system play key functions. Major roles of GSH include direct interc eption of pro-oxidants, as well as a reduction of other antioxidants from t heir oxidized forms. Furthermore, GSH has ancillary functions, such as meta bolism, cell signaling, and protein interactions, that can also mediate def ense against oxidants. Protection by selenium in the mammalian cell is medi ated by selenol-aminoacids, either as selenocysteine or selenomethionine. T he active site of the potent glutathione peroxidases (GPx) contains selenoc ysteine residues. Furthermore, other selenoproteins (e.g. selenoprotein P a nd thioredoxin reductase) also have been shown to possess antioxidant prope rties. Synthetic organoselenium compounds (e.g. ebselen) have also shown pr omise as pharmacologic antioxidants in in vivo models of tissue damage due to oxidative stress. The specific function of selenoproteins and organosele nium compounds in defense against peroxynitrite, by reduction of this poten t oxidizing and nitrating species to nitrite, is also discussed. (C) 2001 E lsevier Science B.V. All rights reserved.