Selenium-Dependent Glutathione Peroxidase

Glutathione-peroxidase (GSH-Pxase) is an enzyme found in erythroqrtes and other tissues that has an essential selenocysteine residue involved in the catalytic decomposition of reactive oxygen species. In the erythrocyte, hydrogen peroxide is the principle reactive oxygen species available. 

This type of in vitro study is relevant because it mimics likely physiological conditions. Red cells contain 1-2 mM GSH so the formation of glutathione complexes would be a likely consequence when auranofin metabolites enter red cells [112, 113]. Compared with typical in vivo gold concentrations of 10-15 pM observed in patients, the Ki values for the four gold complexes are less than anticipated. This indicates that chrysotherapy can greatly depress GSH-Pxase activity in vivo so the normal cellular redox balance would be displaced, favoring the accumulation of H2O2 and possibly GSH [3, 79, 114]. 

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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,... 

Also, selenium-dependent glutathione peroxidase activity has been shown to be reduced in selenium-deficient rats (C. Reddy, ( li). Selenium appears to inhibit both the initiation and promotion phases of carcinogenesis (Milner,... 

Although glutathione is specifically decreased in kwashiorkor, blood levels of selenium-dependent glutathione peroxidase (a scavenger of peroxides) and vitamins A, C, and E (all members of the antioxidant machinery) are lower in both kwashiorkor and marasmus (Ashour et al., 1999). Why then are marasmic children, also deficient in some antioxidants, spared the oxidative stress Does a weakened antioxidant defense manifest as a serious threat only in the presence of pro-oxidant activities of the type encountered in kwashiorkor What is a possible trigger for the increase in free radicals, and how might this account for some of the phenotypic alterations in kwashiorkor ... 

Cohen, HJ Stanford University Relationship of the synthesis and secretion of an extracellular selenium dependent glutathione peroxidase to changes in renal function CRISP 2001... 

Burk RF. Selenium-dependent glutathione peroxidases. In Guengerich FP, editor. Biotransformation, Vol. 3, Comprehensive Toxicology, first ed. Elsevier Science, Oxford 1997. p 229-242. 

Lewis CD, Laemmli UK (1982) Higher order metaphase chromosome structure evidence for metalloprotein interactions. Cell 29 171-181 Li NQ, Reddy PS, Thyagaraju K, Reddy AP, Hsu BL, Scholz RW, Tu CP, Reddy CC (1990) Elevation of rat liver mRNA for selenium-dependent glutathione peroxidase by selenium deficiency. J Biol Chem 265 108-113 McArdle HJ, Mercer JF, Sargeson AM, Danks DM (1990) Effects of cellular copper content on copper uptake and metallothionein and ceruloplasmin mRNA levels in mouse hepatocytes. J Nutr 120 1370-1375... 

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