Glutathione reductase EC

How the stereospecificity arises (a) Reactions involving flavin coenzymes (i) Glutathione reductase (EC 1.6.4.2) 

A groove (Fig. 13) divides the subunit into two lobes. In a derivative made for crystallographic purposes using NaAu(CN)2, the gold was in a pocket close to the isoalloxazine (Fig. 13). The nicotinamide ring of NADPH is thought to be located in this pocket [60]. The p-hydroxybenzoate binds (hydroxyl inwards, carboxyl towards 

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III. Glutathione reductase (EC 1.6.4.2) It is a flavoprotein that catalyzes the NADPH-dependent reduction of oxidized glutathione (GSSG) to glutathione (GSH). This enzyme is essential for the GSH redox cycle which maintains adequate levels of reduced cellular GSH. A high GSH/GSSG ratio is essential for protection against oxidative stress. 

Figure 7.5. Reaction of glutathione peroxidase (EC 1.11.1.19) and glutathione reductase (EC 1.6.4.2). Relative molecular masses (Mr) glutathione, 307.3 and oxidized glutathione, 612.6.

Prentice AM and Bates CJ (1981a) A biochemical evaluation of the erythrocyte glutathione reductase (EC 1.6.4.2) test for riboflavin status. 1. Rate and specificity of response in acute deficiency. British Journal of Nutrition 45,37-52. 

Glutathione reductase (EC 1.8.1.7 formerly EC 1.6.4.2 GSR) links the glutathione pathway to the hexose monophosphate pathway through the reversible oxidation and reduction of NADP. Flavin adenine dinucleotide (FAD) is necessary as a cofactor. The enzyme maintains high levels of reduced glutathione in the cell. Two isoforms exist, a mitochondrial and cytoplasmic form, produced by alternative initiation. The molecule is a homodimer, linked by a disulfide bridge. Each subunit (522 amino acids 56kDa) is divided into four domains of which domains one and two bind FAD and NADPH, respectively and domain four forms the interface. ... 

Fig. 10. Hydrogen donor systems for ribonucleotide reduction. Enzyme reactions are I thioredoxin reductase (EC 1.6.4.5) II ribonucleotide reductase (EC 1.17.4) III glutathione reductase (EC 1.6.4.2). GSH, GSSG reduced and oxidized glutathione NADPH, NADP reduced and oxidized nicotinamide adenine dinucleotide phosphate coenzymes. The hydrogen transfer chain is continued in Fig. II...

GSH is maintained in the reduced state by the NAD(P)H-dependent, flavin-containing glutathione reductase (EC 1.6.4.2 2 identical subunits, Mr depending on the source 100000-125000) and serves as prophylaxis against oxidative stress. Inhibitors of glutathione reductase are under consideration as anti-malarial drugs GSH can also be regenerated by L- ascorbic acid ... 

Viologen-acrylamide copolymers have been used in a similar manner to entrap enzymes and carry out direct reduction of the active site by bound viologen moieties. In these studies the polymer was reduced chemically rather than electrochemically, but there appears no reason in principle why this same chemistry could not be carried out on an electrode. These viologen-acrylamide copolymers have been shown to reduce nitrate reductase (EC 1.9.6.l/ and glutathione reductase (EC 1.6.4.2). 2 >... 

Increased oxidative stress in the RAW 264.7 macrophage cell line is partially mediated via the S-nitrosothiol-induced inhibition of glutathione reductase (EC 1.6.4.2) (Butzer et al. 1999). Fujii et al. (2000) isolated a cDNA for rat glutathione reductase and constructed a baculovirus system to produce recombinant glutathione reductase on a large scale. NO donors (S-nitrosoglutathione, SIN-1, and S-nitroso-N-acetyl-D,L-penicillamine) inhibited the enzymatic activities of purified glutathione reductase. 

Subchronic exposure to MnCb for 7 days (total dose 1750 pmol/kg) by means of mini-osmotic pumps inplanted s.c. produced significant reduction in GSH-peroxidase (EC 1.11.1.9) activity in the cytosol and mitochondrial fractions of the whole rat brain and the striatum (Liccione and Maines 1988). The decrease in GSH-peroxidase was most pronounced in the mitochondrial fraction of the striatum where the activity was reduced to 35 % of the control. Catalase (EC 1.11.1.6) activity was also decreased in the striatum of rats treated with Mn but not in the whole brain. GSH content was markedly depleted (20 % of the control) in the striatum, although only modestly decreased in the whole brain (80% of the control). The treatment of rats with Mn also decreased the activity of oxidised glutathione reductase (EC 1.6.4.2) the same treatment increased the activity of y-glutamyltranspeptidase (EC 2.3.2.2). The activity of y-glutamylcysteine synthetase was not altered by Mn. 

While Kish et al. (1986) did not find any increase in the activity of glutathione peroxidase, Lovell etal. (1995) reported increased activities of glutathione peroxidase (EC 1.11.1.9), glutathione reductase (EC 1.6.4.2) and catalase (EC 1.11.1.6). Gsell et al. (1995) rather found decreased catalase activity in brains of patients with Alzheimer s disease. The findings on the expression and activity of super-oxide dismutase in brains of patients with Alzheimer s disease are also highly controversial (Mar-KLUND et al. 1985, Balasz and Leon 1994, Gsell et al. 1995, Lovell et al. 1995) that may be due to the post mortem delay. 

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