A glutathione peroxidase

Jiang D., Akopian G., Ho Y. S., Walsh J. P, and Andersen J. K. (2000). Chronic brain oxidation in a glutathione peroxidase knockout mouse model results in increased resistance to induced epileptic seizures. Exp. Neurol. 164 257-268. 

Liu, J. Luo, G. Gao, S. Zhang, K. Chen, X. Shen, J. Generation of a glutathione peroxidase-like mimic using bioimprinting and chemical mutation. Chem. Commun. 1999 (2), 199-200. 

The finding that the endoperoxides caused platelet aggregation made it of interest to study the transformations of arachidonic acid in suspensions of human platelets. Two pathways were identified [16]. The initial reaction of one of them was catalyzed by fatty acid cyclooxygenase and led to the formation of three major end-products, i.e. 12L-hydroxy-5,8,10-heptadecatrienoic acid (HHT), malondialdehyde, and a novel hemiacetal derivative named thromboxane 82 (TXBj). The other pathway consisted of conversion of arachidonic acid into 12L-hydroperoxy-5,8,10,14-eicosatetraenoic acid (12-HPETE) by a novel lipoxygenase. The hydroperoxide was subsequently converted into a stable end-product, 12L-hydroxy-5,8,10,14-eicosatetraenoic acid (12-HETE) by a glutathione peroxidase [16,17]. 

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. 

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. 

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. 

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,... 

In the previous section, we have described some of the mechanisms that may lead to the fijrmation of lipid hydroperoxides or peroxyl radicals in lipids. If the peroxyl radical is formed, then this will lead to propagation if no chain-breaking antioxidants are present (Scheme 2.1). However, in many biological situations chain-breaking antioxidants are present, for example, in LDL, and these will terminate the peroxyl radical and are consumed in the process. This will concomitandy increase the size of the peroxide pool in the membrane or lipoprotein. Such peroxides may be metabolized by the glutathione peroxidases in a cellular environment but are probably more stable in the plasma comjxutment. In the next section, the promotion of lipid peroxidation if the lipid peroxides encounter a transition metal will be considered. 

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. 

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. 

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