Molecular biology of selenium with implications for its metabolism.
Selenium has a highly specific metabolism centered around its incorporation as selenocysteine into selenoproteins. An outline of this metabolism has emerged from recent molecular biological and biochemical studies of bacteria and animals. A unique tRNA, designated tRNA[Ser]Sec, is charged with L-serine, which is then converted through at least two steps to selenocysteine. With the aid of a unique translation factor, the selenocysteinyl-tRNA[Ser]Sec recognizes specific UGA codons in mRNA to insert selenocysteine into the primary structure of selenoproteins. Turnover of selenoproteins presumably liberates selenocysteine which is toxic in its free form. Selenocysteine beta-lyase catabolizes free selenocysteine and makes its selenium available for reuse. Proteins contain almost all the selenium in animals. Of the known selenoproteins, the glutathione peroxidases contain the most selenium. Cellular and plasma glutathione peroxidases are products of different genes but have 44% identity of amino acid sequence. There is evidence for other proteins of this family. Selenoprotein P is an unrelated protein with multiple selenocysteines in its primary structure. It contains most of the selenium in rat plasma. Studies of the regulation of cellular glutathione peroxidase by selenium have yielded conflicting results, but there is a strong suggestion that mRNA levels of the rodent liver glutathione peroxidase decrease in selenium deficiency. This could be a mechanism for directing selenium to the synthesis of other selenoproteins. Although present knowledge allows construction of an outline of selenium metabolism, several steps have not been characterized and little is known about mechanisms of its regulation.
Burk
R F
RF
Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232.
D000818:Animals; D003545:Cysteine / Q000031:analogs & derivatives / Q000235:genetics; D011506:Proteins / Q000235:genetics; D012643:Selenium / Q000378:metabolism*; D017279:Selenocysteine; D051149:Selenoprotein P; D051140:Selenoproteins
D011506:Proteins; D051149:Selenoprotein P; D051140:Selenoproteins; D017279:Selenocysteine; D012643:Selenium; D003545:Cysteine