Glutathione disulfide

This thiol-disulfide interconversion is a key part of numerous biological processes. WeTJ see in Chapter 26, for instance, that disulfide formation is involved in defining the structure and three-dimensional conformations of proteins, where disulfide "bridges" often form cross-links between q steine amino acid units in the protein chains. Disulfide formation is also involved in the process by which cells protect themselves from oxidative degradation. A cellular component called glutathione removes potentially harmful oxidants and is itself oxidized to glutathione disulfide in the process. Reduction back to the thiol requires the coenzyme flavin adenine dinucleotide (reduced), abbreviated FADH2. 

MRP2 (ABCC2) LTC4, bilirubin-glucuronide, estradiol 17 3-glucuronide, dianionic bile salts, anionic conjugates, glutathione disulfide, and others... 

Savas, M.M., Petering, D.H. and Shaw, C.F. Ill (1993)Theoxidationofrabbitliver metallothionein-11 by 5,5 -dithiobis (2-nitrobenzoic acid) and glutathione disulfide. Journal of Inorganic Biochemistry, 52, 235—249. 

Kondo, T., Miyamoto, K., Gasa, S., Taniguchi, N. and Kawakami, Y. (1989). Purification and characterization of glutathione disulfide-stimulated Mg -ATPase from human erythrocytes. Biochem. Biophys. Res. Commun. 162, 1-8. 

Bilzer, M. and Lauterburg, B.H. (1991). Effects of hypoch-lorous acid and chloramines on vascular resistance, cell integrity, and biliary glutathione disulfide in the perfused rat liver modulation by glutathione. J. Hepatol. 13, 84-89. 

Jaeschke, H. (1990). Glutathione disulfide formation and oxidant stress during acetaminophen-induced hepatotoxicity in mice in vivo-, the protective effect of allopurinol. J. Pharmacol Exp. Ther. 255, 935-941. 

Monostori P, Wittmann G, Karg E, Turi S (2009) Determination of glutathione and glutathione disulfide in biological samples an in-dept review. J Chromatogr B 877 3331-3346... 

The presence at the BBB of members of the multidrug resistance-associated protein (MRPs) family, whose members preferentially transport anionic compounds, is still controversial. The seven members of the MRP family belong, like P-gp, to the ATP-binding cassette (ABC) protein superfamily. Mrpl has been found at the BBB in isolated rat brain capillaries, primary cultures of brain capillary endothelial cells and in immortalized capillary endothelial cells, but not in human brain capillaries [59]. Another member, MRP2 has been found at the luminal membrane of the brain endothelial cells [60]. However, further studies are required to show that there are MRP transporters at the BBB (Figure 15.5). As for P-gp, a functional Mrpl was found in primary cultured rat astrocytes [56] and it has been shown to take part in the release of glutathione disulfide from brain astrocytes under oxidative stress [61]. 

Fig. 2 Possible mechanisms by which nanoparticles cause toxicity inside cells. GSH glutathione, GSSG glutathione disulfide, MDA malondialdehyde, NFkB nuclear factor kappa B, Nrf2 nuclear factor-erythroid 2-related factor 2, ROS reactive oxygen species...

Metallothioneins (MT) are unique 7-kDa proteins containing 20 cysteine molecules bounded to seven zinc atoms, which form two clusters with bridging or terminal cysteine thiolates. A main function of MT is to serve as a source for the distribution of zinc in cells, and this function is connected with the MT redox activity, which is responsible for the regulation of binding and release of zinc. It has been shown that the release of zinc is stimulated by MT oxidation in the reaction with glutathione disulfide or other biological disulfides [334]. MT redox properties led to a suggestion that MT may possesses antioxidant activity. The mechanism of MT antioxidant activity is of a special interest in connection with the possible antioxidant effects of zinc. (Zinc can be substituted in MT by some other metals such as copper or cadmium, but Ca MT and Cu MT exhibit manly prooxidant activity.)... 

The use of GSNO in vasodilator research is particularly unsafe as the effect of copper ions, as determined by in vitro studies, is much more complex than with SNAP. Briefly, Cu(I) ions complex not only with GSNO but also with glutathione disulfide (a reaction product) and this means that the concentration of Cu(l) ions falls as the reaction proceeds, killing the reaction when all the Cu(I) ions have been complexed [22]. The absence of any observed effect when GSNO is used as a vasodilator may be due to removal of copper ions by complexation with glutathione disulfide. 

The exact nature of the NO-releasing reaction and the other products of reaction in mammalian tissue are still unclear. The matter has been discussed by a number of authors and a reductive mechanism in rat hepatocytes and human erythrocytes has been suggested in the presence of NADH and NADPH. Nitroprusside can pass through cell membranes and so there is no intrinsic difficulty with this suggestion. There is direct evidence from spin echo NMR studies to show the conversion, by nitroprusside, of glutathione into glutathione disulfide within erythrocytes [49]. 

N. S. Kosower and E. M. Kosower, The glutathione-glutathione disulfide system, Free Radicals Biol. 2, 55-84 (1976). 

Direct evidence of the reaction of PAN with sulfhydryl compounds has since been obtained (PAN at 115 ppm for 1-10 min). - In the reaction with glutathione, the major products are oxidized glutathione (disulfide) and 5-acetylglutathione. Other sulfhydryl compounds (e.g., coenzyme A, lipoic acid, and cysteine) yield only oxidation products, with no evidence of 5-acetylation. However, acetylation reactions have been observed with alcohols and amines. Sulfur compounds other than thiols can undergo oxidation by PAN methionine is converted to methionine sulfoxide, and oxidized lipoic acid (disulfide) is converted to sulfoxide. 

This enzyme [EC 1.8.5.1], also known as glutathioneide-hydroascorbate oxidoreductase, catalyzes the reaction of two molecules of glutathione with dehydroascorbate to produce glutathione disulfide and ascorbate. 

This selenium-dependent enzyme [EC 1.11.1.9] catalyzes the reaction of two molecules of glutathione with hydrogen peroxide to produce glutathione disulfide and two water molecules. Hydrogen peroxide can be replaced by steroid and lipid hydroperoxides, albeit not as effectively (nevertheless, this enzyme is not identical with phospholipid-hydroperoxide glutathione peroxidase [EC 1.11.1.12]). However, the hydroperoxy products formed by the action of lipoxygenase [EC 1.13.11.12] are not substrates. 

This EAD-dependent enzyme [EC 1.6.4.2] catalyzes the reaction of NADPH with glutathione disulfide to produce NADP+ and two glutathione molecules. The enzyme activity is dependent on a redox-active disulfide group in each of the active sites. 

Transport Studies with Intact Cells Transport of glutathione, glutathione disulfide, and glutathione conjugates across the hepato-cyte plasma membrane, 173, 523 Ca fluxes and phosphoinosi-... 

GSSG Glutathione disulfide (sometimes referred to as oxidized glutathione) kb Kilobase pair... 

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