Thiol cofactors for selenoenzymes and their synthetic mimics

Abstract

The importance of selenium as an essential trace element is now well recognized. In proteins, the redox-active selenium moiety is incorporated as selenocysteine (Sec), the 21st amino acid. In mammals, selenium exerts its redox activities through several selenocysteine-containing enzymes, which include glutathione peroxidase (GPx), iodothyronine deiodinase (ID), and thioredoxin reductase (TrxR). Although these enzymes have Sec in their active sites, they catalyze completely different reactions and their substrate specificity and cofactor or co-substrate systems are significantly different. The antioxidant enzyme GPx uses the tripeptide glutathione (GSH) for the catalytic reduction of hydrogen peroxide and organic peroxides, whereas the larger and more advanced mammalian TrxRs have cysteine moieties in different subunits and prefer to utilize these internal cysteines as thiol cofactors for their catalytic activity. On the other hand, the nature of in vivo cofactor for the deiodinating enzyme ID is not known, although the use of thiols as reducing agents has been well-documented. Recent studies suggest that molecular recognition and effective binding of the thiol cofactors at the active site of the selenoenzymes and their mimics play crucial roles in the catalytic activity. The aim of this perspective is to present an overview of the thiol cofactor systems used by different selenoenzymes and their mimics.

Nuclear blebbing of biologically active organoselenium compound towards human cervical cancer cell (HeLa): In vitro DNA/HSA binding, cleavage and cell imaging studies

“…Upon increasing concentration of the 1, the emission band at 591 nm was quenched up to 44.71%, of the initial fluorescence intensity accompanied by red shift of 22 nm. The observed decrease in the fluorescence intensity with a strong red shift clearly indicates that the EB molecule was displaced by the 1 from their DNA binding sites [25].…”

Epoxidation of cyclooctene and cyclohexene with hydrogen peroxide catalyzed by bis[3,5-bis(trifluoromethyl)-diphenyl] diselenide: Recyclable catalyst-containing phases through the use of glycerol-derived solvents

“…But there are other many applications for selenium, for instance organoselenium ligands have been used for metal-catalyzed processes [34], it has been recently included in polyoxometalates to generate a new active catalyst for the epoxidation of olefins [35], or some selenium derivatives have potential as efficient mimetics for selenoenzymes [36].…”

Correlations between daily weight gain, lipid peroxidation and glutathione status of liver and kidney in different pig genotypes

“…It is well known that the primary site of GSH synthesis is the liver (Shi et al 1996) therefore it has better antioxidant defence as compared to kidney. Daily weight gain also showed positive correlation with GSH content, the co-substrate of GPx (Sarma & Mugesh 2008), in Középtiszai hybrid, which had the highest daily weight gain among the hybrids investigated. Activity of GPx, part of the antioxidant defence system, was not significantly lower in the other hybrids with lower weight gain, which result is partly in agreement with a previous research, which showed a negative correlation between weight gain and GPx activity in pig (Lingaas et al 1991).…”