Glutathione peroxidase enzyme

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. 

A wide variety of interactions of selenium with essential and nonessential elements, vitamins, xenobiotics, and sulfur-containing amino acids have been demonstrated in numerous studies. Selenium has been reported to reduce the toxicity of many metals including mercury, cadmium, lead, silver, and to some extent, copper (Frost 1972). Most forms of selenium and arsenic interact to reduce the toxicity of both elements (Levander 1977). Because of selenium s role in the antioxidant glutathione peroxidase enzymes, selenium also reduces the toxicity of metals in vitamin E-deficient animals (Diplock et al. 1967). 

A cofactor (/.e. the key of enzyme activity) of the glutathione peroxidase enzyme is the element selenium. The enzyme contains cysteine residues in which sulfur is replaced by selenium. A deficiency of this element causes insufficient enzyme activity, so selenium is often considered as an antioxidant, although it has no such direct effect. 

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. 

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... 

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. 

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. 

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,... 

Reduction by available peroxidase enzymes, e.g. glutathione peroxidase ... 

The free-radical defence mechanisms utilized by the brain are similar to those found in other tissues. The enzymes SOD, catalase, glutathione peroxidase, and the typical radical scavengers, ascorbate, vitamin E and vitamin A are present in the brain, as they are in peripheral tissues. However, the brain may actually be slightly deficient in some of these defence mechanisms when compared to the amounts present in other tissues. 

Furthermore, depletion of hepatic GSH induced chemically or by fasting augmented hepatic I/R-induced enzyme release and promoted lipid peroxidation (Jennische, 1984 Stein et al., 1991) Benoit et al. (1992) have used portacaval-shunted rats as a model of chronic hepatic ischaemia, and were able to show decreases in total levels of SOD and xanthine dehydrogenase, but no significant change in catalase or glutathione peroxidase. 

Reduced scavenger capacity is deduced from studies demonstrating low plasma and cellular levels of antioxidants such as glutathione, vitamin E, thiols, magnesium and ascorbic acid, as well as reduced levels of scavenger enzymes such as neutrophil glutathione peroxidase and red cell superoxide dismutase (Lyons, 1991 Sinclair /., 1992). 

Thiols are also important protection against lipid peroxidation. Glutathione (7-Glu-Cys-Gly) is used by several glutathione-dependent enzymes such as free-radical reductase (converts vitamin E radical to vitamin E), glutathione peroxidase (reduces hydrogen peroxide and lipid hydroperoxides to water and to the lipid alcohol, respectively), and others. In addition, the thiol group of many proteins is essential for function. Oxidation of the thiol of calcium ATPases impairs function and leads to increased intracellular calcium. Thiol derivatives such as the ovothiols (l-methyl-4-mercaptohistidines) (Shapiro, 1991) have been explored as therapeutics. 

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. 

Garlic s proven mechanisms of action include (a) inhibition of platelet function, (b) increased levels of two antioxidant enzymes, catalase and glutathione peroxidase, and (c) inhibition of thiol enzymes such as coenzyme A and HMG coenzyme A reductase. Garlic s anti-hyperlipidemic effects are believed to be in part due to the HMG coenzyme A reductase inhibition since prescription medications for hyperlipidemia have that mechanism of action (statins). It is unknown whether garlic would have the same drug interactions, side effects, and need for precautions as the statins. 

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