Enzymes selenium-dependent glutathione

Hu, M.-L., Dillard, C.J. and Tappel, A.L. (1988) Aurofhioglucose effect on sulfhydryls and glutathione-metabolizing enzymes in vivo inhibition of selenium-dependent glutathione peroxidase. Research Communications in Chemical Pathology and Pharmacology, 59,... 

All selenium-containing proteins and enzymes in animals, microorganisms and plants incorporate selenocysteine non-specifically105 or as part of Se-dependent antioxidant enzymes such as glutathione peroxidase, (EC 1.11.1.9) which has a Se-cysteine residue in its active site.116 120 An active form of Se, selenophosphate, is produced by selenophosphate synthetase in several bacteria. This active form is required for the production of Secys-tRNA, a precursor for Se-cysteine.121 In a similar vein, a Se-containing modified-tRNA nucleoside, 5-methylaminomethyl-2-selenouridine, encodes a selenouridine synthase which replaces sulfur in tRNA with selenium.122... 

Glutathione peroxidase is a selenium-dependent enzyme, which rapidly detoxifies hydrogen peroxide and various hydroperoxides. Suttorp et al. [67] showed that the impairment of glutathione cycle resulted in an increase in the injury of pulmonary artery endothelial cells. Glutathione cycle protected against endothelial cell injury induced by 15-HPETE, an arachi-donate metabolite produced by 15-lipoxygenase-catalyzed oxidation [68]. 

This selenium-dependent enzyme [EC 1.11.1.9] catalyzes the reaction of two molecules of glutathione with hydrogen peroxide to produce glutathione disulfide and two water molecules. Hydrogen peroxide can be replaced by steroid and lipid hydroperoxides, albeit not as effectively (nevertheless, this enzyme is not identical with phospholipid-hydroperoxide glutathione peroxidase [EC 1.11.1.12]). However, the hydroperoxy products formed by the action of lipoxygenase [EC 1.13.11.12] are not substrates. 

Considerable interest was generated when it was shown that substantial GSHPx activity exists in liver of selenium-depleted rats when LOOH is used as substrate but not H2O2 [20]. The enzyme was subsequently shown to be identical to a member of the glutathione-S-transferase family of enzymes [20,21,48], The enzyme was for a time called selenium-independent , or non-selenium dependent GSHPx and this nomenclature, which is confusing, has persisted in the literature. The role of GSH-S-transferases in the overall protection of cells against the harmful potential of LOOH has not been determined but it undoubtedly must form part of that protective mechanism. 

As shown in Fig. 15.1, snperoxide dismntase (SOD) dismutes superoxide anions to hydrogen peroxide, which is safely converted to water and molecular oxygen by catalase. Furthermore, hydrogen peroxide is disposed of by cytosohc glutathione peroxidase, a selenium-dependent enzyme that provides a major route for elimination. 

Glutathione peroxidase a selenium dependent enzyme that catalyzes the CSH-mediated conversion of hydroperoxides to water or alcohol... 

One way that selenium appears to act is as a non-specific stimulant of immune competent tissues and cells contributing to its anti-inflammatory, immunopotentiation and carcinostatic attributes. Additional data suggests other effects of Se upon cells of the immune system perhaps independent of GSHPx activity such as ubiquinone biosynthesis, (Coenz3one Q 10) which in turn affects host-defense mechanisms (Frost, 1975). A third possibility to explain the effects attributed to Se above is to propose that increases in levels of the selenium dependent enzyme glutathione peroxidase and perhaps other specific selenium-dependent functions in lymphocytes and macrophages is the reason for immunoenhancement. This subject has been addressed by Schauzer (1979) and is amplified here by the author. 

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