Some Functions of the Essential Trace Element, Selenium

In recent years there have been impressive increases in information concerning selenium biochemistry. After the initial discoveries that bacteria (Pinsent, 1954) and animals (Patterson et al., 1957; Schwarz and Foltz, 1957) require this trace element, almost 20 years elapsed before selenium was demonstrated to be an essential component of a mammalian enzyme, glutathione peroxidase,(Flohe et al., 1973; Rotruck et al., 1973) and a protein component of the Clostridial glycine reductase complex (Turner and Stadtman, 1973). Selenocysteine was determined to be the chemical form of selenium present in glycine reductase (Cone et al., 1976). Other prokaryotic selenoenzymes, several formate dehydrogenases (Stadtman, 1979, 1980a, 1980b, 1990 and 1996), a hydrogenase of Methanococcus vannielii (Yamazaki, 1982) and a clostridial nicotinic acid hydroxylase (Dilworth, 1982) were discovered. Mammalian glutathione peroxidase isoenzymes (Ursini et al., 1995) and selenoprotein P, a glycoprotein of unknown function, were isolated (Hill et al., 1991). Selenoprotein P is unusual in that it contains 10 selenocysteine residues in the polypeptide chain. Selenoprotein W, a 10 kDa muscle protein of unknown function was purified from normal muscle and partially characterized (Vendeland et al., 1993; Vendeland et al., 1995). The function of selenoprotein W is unknown but the occurrence of the selenocysteine residue in a Cys-x-x-Secys motif is suggestive of a redox role. The importance of selenium in mammalian physiology was magnified by the discovery of its occurrence in a 5' deiodinase that converts the prothyroid hormone, tetraiodothyronine, to the active hormone, 3,5,3'-tri-iodothyronine (Berry et al., 1991) and this established a direct role of selenium in eukaryotic developmental processes. Several years after the identification of selenocysteine in selenoproteins this unusual amino acid was shown to be inserted cotranslationally. An in-frame TGA codon was