Selenium glutathione peroxidase

The most clearly documented role lor selenium is as a necessary component of glutathione peroxidase. Selenium is also involved in the functions of additional enzymes, e.g.. type I iodoihvronine deiodinase. leukocyte acid phosphatase, and glucuronidases. A role for selenium in electron transfer has been suggested as has involvement in nonheme iron proteins. Selenium and vitamin b appear to be necessary lor proper functioning of lysosomal membranes. A role for selenium in metabolism of thyroid hormone has been continued. 

Determination of the effective functioning of particular enzymes or metabolic pathways potentially may be useful in demonstrating adequacy of provision. Enzymes in plasma that may be helpful in this regard are glutathione peroxidase as an index of selenium status, and red cell enzymes, such as transketolase (thiamine), glutathione reductase (riboflavin) or transaminase (pyridoxine), or glutathione peroxidase (selenium) are all widely used. Methyltetrahydrofolate reductase is involved in metabolism of homocysteine, hence assessment of plasma homocysteine is a useful measure of... 

Enzymes often need for their activity the presence of a non-protein portion, which may be closely combined with the protein, in which case it is called a prosthetic group, or more loosely associated, in which case it is a coenzyme. Certain metals may be combined with the enzyme such as copper in ascorbic oxidase and selenium in glutathione peroxidase. Often the presence of other metals in solution, such as magnesium, are necessary for the action of particular enzymes. 

Fig. 7. The glutathione peroxidase (a selenium enzyme) system where GSH = A -(A -L-7-giutamyi -L-cysteinyi )giycine and G—S—S—G, the disulfide.

In 1956 selenium was identified (123) as an essential micronutrient iu nutrition. In conjunction with vitamin E, selenium is effective iu the prevention of muscular dystrophy iu animals. Sodium selenite is adrninistered to prevent exudative diathesis iu chicks, a condition iu which fluid leaks out of the tissues white muscle disease iu sheep and infertility iu ewes (see Eeed ADDITIVES). Selenium lessens the iacidence of pneumonia iu lambs and of premature, weak, and stillborn calves controls hepatosis dietetica iu pigs and decreases muscular inflammation iu horses. White muscle disease, widespread iu sheep and cattle of the selenium-deficient areas of New Zealand and the United States, is insignificant iu high selenium soil areas. The supplementation of animal feeds with selenium was approved by the U.S. EDA iu 1974 (see Eeed additives). Much of selenium s metaboHc activity results from its involvement iu the selenoproteia enzyme, glutathione peroxidase. 

Figure 20-3. Role of the pentose phosphate pathway in the glutathione peroxidase reaction of erythrocytes. (G-S-S-G, oxidized glutathione G-SH, reduced glutathione Se, selenium cofactor.)...

Chaudiere, J. and Tappel, A.L. (1984) Interaction of gold(I) with the active site of selenium-glutathione peroxidase. Journal of Inorganic Biochemistry, 20, 313—325. 

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,... 

Roberts, J. and Shaw, C.F. Ill (1998) Inhibition of erythrocyte selenium-glutathione peroxidase by auranofin analogs and metabolites. Biochemical Pharmacology, 55, 1291-1299. 

Roberts,J.(1993)Thekineticpropertiesof Au(I) drug binding to serum albumin and selenium-glutathione peroxidase and their significance for rheumatoid arthritis. Ph.D. thesis, University-Milwaukee. 

Situnayake et al., 1991). No correlation between disease activity and serum vitamin E concentrations was found, but it was su ested that such patients might suffer a reduced antioxidant capacity. However, it is conceivable that a decreased serum antioxidant status is a primary event in the evolution of RA. Recent studies (Heliovaara etal., 1994) have demonstrated that lowered levels of vitamin E, /3-carotene and selenium (required for glutathione peroxidase) together may be a risk fector for subsequent development of RA. 

There is very little evidence relating to the role of ROMs in cholestatic liver disease. Serum selenium and glutathione peroxidase activity are decreased in humans with intrahepatic cholestasis of pregnancy (Kauppila et al., 1987). Low levels of vitamin E have been reported in patients with primary biliary cirrhosis, and in children with Alagille s syndrome or biliary atresia (Knight et al., 1986 Jeffrey etal., 1987 Lemonnier etal., 1987 Babin etal., 1988 Kaplan et al., 1988 Sokol etal., 1989). Serum levels of Mn-SOD are increased in patients with all stages of primary biliary cirrhosis compared with patients with other forms of chronic liver disease, although whether this causes or results from the disease process is unclear (Ono etal., 1991). 

Kauppila, A., Korpela, H., Makila, U-M. and Yrjanheikki, E. (1987). Low serum selenium concentration and glutathione peroxidase activity in intrahepatic cholestasis of pregnancy. Br. Med. J. 294, 150-152. 

Ward, K.P., Arthur, J.R., Russell, G. and Aggett, P.J. (1984). Blood selenium content and glutathione peroxidase activity in children with cystic fibrosis, coeliac disease, asthma and epilepsy. Eur. J. Paediatr. 142, 21-24. 

Selenium is required, but levels must fall into a narrow window. Both deficiency and toxicity symptoms occur. The element is also used therapeutically in cancer treatment. It is the co-factor of the enzyme glutathione peroxidase which is thought to play an important role in oxygen toxicity. The determination of Se in blood or serum is not easy, as many incorrect, inaccurate and imprecise methods have been published (Magee and James 1994). A suggested procedure for Se in body fluids is based on GF-AAS (Thomassen et al. 1994)- For tissues SS-AAS may be used (Fler-ber 1994a). Recent developments by Turner et al. (1999) show that LC-ICP-MS is sensitive and reproducible at low levels. 

P9. Perona, G., Guidi, G. C., Piga, A., Cellerino, R., Milani, G., Colautti, P., Moschini, G., and Stievano, B. M Neonatal erythrocyte glutathione peroxidase deficiency as a consequence of selenium imbalance during pregnancy. Br. J. Haematol. 42,567-574 (1979). 

Other non-metals became oxidised, such as selenium to selenate, and this element became a detoxifying agent, used in destroying peroxides, e.g. in glutathione peroxidase, as well as a hydrogen transfer centre. 

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]. 

Selenium is essential for many species including man, on account of its presence in a number of enzymes, notably glutathione peroxidase, an important antioxidant enzyme. It is incorporated into selenoenzymes in the form of selenocysteine. 

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