Role of Selenium in the Enzymatic Reduction of Hydroperoxides

Abstract

Selenium-mediated catalysis in the enzymatic reduction of hydroperoxides is reviewed. Out of the growing number of mammalian selenoproteins four are peroxidases. Their common catalytic mechanism involves redox shuttling of a selenocysteine residue in the active site, where it forms a characteristic catalytic triad with hydrogen-bonded tryptophan and glutamine residues. These peroxidases differ in tissue distribution, substrate specificity, regulation, responsiveness to selenium restriction, and likely in their biological role. Cytosolic glutathione peroxidase, which predominates in balancing hydroperoxide toxicity, rapidly declines in selenium deficiency. Its activity can therefore be taken as a sensitive indicator of the selenium status. Indirectly, selenium can be involved in peroxide reduction by proteins formerly known as antioxidant proteins and now named peroxiredoxins. They reduce hydroperoxides by means of a particularly reactive cysteine residue. Some members of this protein family proved to be thioredoxin-dependent peroxidases. In mammals the regeneration of reduced thioredoxin depends on the selenoprotein thioredoxin reductase. Selenium supplementation proved mandatory in areas severely deficient in this trace element and may be considered reasonable also in asymptomatic moderate selenium deficiency whenever clinical conditions known to cause oxidative stress have to be anticipated.