Biochemistry of selenium: A brief overview

Abstract

The chemistry of Se suggests that, in biological systems, it is most likely present as the selenol (selenomercaptan) R-SeH, or, as the Se ether analogous to sulfur in the amino acid methionine. Selenols are stronger acids than mercaptans and, at physiological pH, exist mainly in anionic form (R-Se −) whereas the sulfhydryl group exists mainly in the protonated form. The anionic form of the selenohydryl group is a good nucleophile as well as a good leaving group. Also, it binds metals strongly, which is the principle behind the use of Se compounds for heavy metal detoxification. Conversely, metal ions can strip Se from organoselenium compounds and Hg, Cd, Pb, and Cu are highly effective in this capacity. In vivo, Se compounds tend to undergo reduction in contrast to sulfur compounds which are acquired in reduced form and generally undergo oxidation. Biosynthesis of methylated Se compounds, yielding dimethyl selenide, dimethyl diselenide, or trimethyl selenonium ion, appears to be the major pathway of Se metabolism/detoxification in animals. The highest activity of the pathway has been found in liver and kidney followed by lung, skeletal muscle, spleen, and heart. Selenium (Se) appears to be incorporated into proteins via post transcriptional modification of polypeptides. Six proteins that incorporate/require Se have been isolated: Se-dependent glutathione peroxidase (GSH-Px), the selenoprotein of muscle, selenoflagellin, Se-transport protein, and the bacterial enzymes formate dehydrogenase and glycin reductase. There is evidence also that Se is an essential component of nicotinic acid hydroxylase, xanthine dehydrogenase, and a bacterial thiolase. As an integral part of Se-dependent GSH-Px, Se has been reported to play a key role in the cellular antioxidant defense mechanism and modulation of the arachidonic acid cascade. Selenium deficiency has been implicated as a factor in a number of diseases affecting humans and animals of economic importance. Also, Se has been reported to enhance both the humoral and cellular immune responses and to possess anticarcinogenic activity.