Abstract
Selenium is an essential trace element for mammals, birds, and some bacteria. Its remarkable biological effects in eukaryotes may be related to unique functions of various selenoproteins. A^<75>Se-labeled protein was purified from a human lung adenocarcinoma cell line, NCI-H441 . A homodimer of 57-kDa subunits contained selenium in the form of selenocysteine. The selenoprotein contained FAD as a prosthetic group and catalyzes NADPH-dependent reduction of insulin in the presence of thioredoxin. The subunit composition and catalytic properties were identical to those of mammalian thioredoxin reductase (TrxR). This was the first report on the biochemical relevance between selenium and Trx-mediated metabolic regulation. Interestingly, human lung adenocarcinoma cells produced the selenoenzyme TrxR over hundred times that of normal mammalian cells. A Iabile selenium donor compound monoselenophosphate, required for selenoprotein biosynthesis, is synthesized from selenide and ATP by selenophosphate synthetase (SPS).
