Glutathion peroxidase

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. 

Glutathione peroxidase [9013-66-5] oxidizes glutathione, and helps to remove inorganic and organic hydroperoxides (221] It exhibits antiinflammatory activity in experimental uveitis of rats (234). 

The increased concentrations of K, Ca, Fe, Br, Se and Rb in infarction and scar areas are observed for patient with the recent infarction. For the patients with old infarction the levels of these elements are decreased in the same areas. This reflects the intensity of metabolic processes in the pathological area of myocardium. Additionally, the elevated levels of Se was find out in myocardium of right ventricle in both patients, that may be caused by the increasing the activity of the glutathione peroxidase enzyme. 

Two classes of antioxidants are known the low-molecular weight compounds (tocopherols, ascorbate, -carotene, glutathione, uric acid and etc.) and the proteins (albumin, transferrin, caeruloplasmin, ferritin, etc.) including antioxidant enzymes (e.g. superoxide dismutase, catalase, glutathione peroxidase). 

Organoselenium compounds in particular, once ingested, are slowly released over prolonged periods and result in foul-smelling breath and perspiration. The element is also highly toxic towards grazing sheep, cattle and other animals, and, at concentrations above about 5 ppm, causes severe disorders. Despite this, Se was found (in 1957) to play an essential dietary role in animals and also in humans — it is required in the formation of the enzyme glutathione peroxidase which is involved in fat metabolism. It has also been found that the Incidence of kwashiorkor (severe protein malnutrition) in children is associated with inadequate uptake of Se, and it may well be involved in protection... 

Polidoro G, Dillio C, Arduini A, et al. 1982. Glutathione peroxidase and glutathione S-transferase activities in human fetal tissues. Inability of acidic forms of glutathione S-transferase to catalyze the reduction of organic hydroperoxides. Biochem Int 4 637-645. 

THE PENTOSE PHOSPHATE PATHWAY GLUTATHIONE PEROXIDASE PROTECT ERYTHROCYTES AGAINST HEMOLYSIS... 

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.)...

In erythrocytes, the pathway has a major function in preventing hemolysis by providing NADPH to maintain glutathione in the reduced state as the substrate for glutathione peroxidase. 

The red cell contains a battery of cytosolic enzymes, such as superoxide dismutase, catalase, and glutathione peroxidase, to dispose of powerful oxidants generated during its metabolism. 

It participates in the decomposition of potentially toxic hydrogen peroxide in the reaction catalyzed by glutathione peroxidase (Ghapter 20). 

Figure 15.11 Possible scheme for the formation of free radicals from the metabolism of dopamine. Normally hydrogen peroxide formed from the deamination of DA is detoxified to H2O along with the production of oxidised glutathione (GSSG) from its reduced form (GSH), by glutathione peroxidase. This reaction is restricted in the brain, however, because of low levels of the peroxidase. By contrast the formation of the reactive OH-radical (toxification) is enhanced in the substantia nigra because of its high levels of active iron and the low concentration of transferin to bind it. This potential toxic process could be enhanced by extra DA formed from levodopa in the therapy of PD (see Olanow 1993 and Olanow et al. 1998)...

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. 

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. 

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