New biologic functions — Selenium-dependent nucleic acids and proteins

Abstract

Selenium occurs normally in living things as a highly specific component of certain enzymes and amino acid transfer nucleic acids (tRNAs). In bacteria, biosynthesis of essential selenoenzymes has been shown to be unaffected by wide variations in sulfur levels. The naturally occurrring selenoenzymes so far identified from bacterial sources include glycine reductase, certain formate dehydrogenases, a hydrogenase, nicotinic acid hydroxylase, xanthine dehydrogenase and thiolase. The selenoenzyme, glutathione peroxidase, and three other selenoproteins of unknown function have been isolated from animals. In certain enzymes, e.g. glycine reductase, formate dehydrogenase, hydrogenase and glutathione peroxidase, the chemical form of selenium has been identified as selenocysteine. One enzyme, a bacterial thiolase, contains selenomethionine rather than selenocysteine. A labile, unidentified form of selenium is present in nicotinic acid hydroxylase, and by inference, xanthine dehydrogenase. The seleno-tRNAs serve as examples of a different type of biological macromolecule that is specifically modified with selenium. The major seleno-tRNAs in Clostridium sticklandii and Escherichia coli have been identified as glutamate and lysine isoaccepting species. The selenium-modified nucleoside is 5-methyl-aminomethyl-2-selenouridine (mnm 5Se 2U), which is the chemical analog of 5-methylaminomethyl-2-thiouridine, a previously identified minor base of E. coli tRNA 2 Glu. The seleno-tRNA Glu of C. sticklandii contains one gram atom of Se per mole of biologically active tRNA. Loss of Se from the modified nucleoside, mnm 5Se 2U, in this tRNA results in concomitant loss of glutamate charging activity suggesting that selenium is essential for interaction of the synthetase and its cognate tRNA.