Glutathione disulfides

Schafer FQ, Buettner GR. (2001) Redox environment of the cell as viewed through the redox state of the glutathione disulfide/glutathione couple. Free Radic Biol Med 30 1191-1212. 

Schafer, F.Q. Buettner, G.R. (2001). Redox Environment of the Cell as Viewed Through the Redox State of the Glutathione Disulfide/Glutathione Couple. Free Radicals in Biology and Medicine, Vol. 30, No. 11, 0une 2001), pp. 1191-1212, ISSN 0891-5849... 

Diallyl sulfide -Diallyl disulfide -Diallyl trisulfide Dimethyl sulfides Disulfides Glutathione Methionine Methyl sulfides Propenylsulfides Pseudoscordinine... 

Disulfides. As shown in Figure 4, the and h-chains of insulin are connected by two disulfide bridges and there is an intrachain cycHc disulfide link on the -chain (see Insulin and other antidiabetic drugs). Vasopressin [9034-50-8] and oxytocin [50-56-6] also contain disulfide links (48). Oxidation of thiols to disulfides and reduction of the latter back to thiols are quite common and important in biological systems, eg, cysteine to cystine or reduced Hpoic acid to oxidized Hpoic acid. Many enzymes depend on free SH groups for activation—deactivation reactions. The oxidation—reduction of glutathione (Glu-Cys-Gly) depends on the sulfhydryl group from cysteine. 

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.

Cysteine [52-90 ] is a thiol-bearing amino acid which is readily isolated from the hydrolysis of protein. There ate only small amounts of cysteine and its disulfide, cystine, in living tissue (7). Glutathione [70-18-8] contains a mercaptomethyl group, HSCH2, and is a commonly found tripeptide in plants and animals. Coenzyme A [85-61-0] is another naturally occurring thiol that plays a central role in the synthesis and degradation of fatty acids. 

All mammalian cells contain a thiol called glutathione. Glutathione protects the cell by scavenging harmful oxidants. It reacts with these oxidants by forming a disulfide, which is eventually converted back to glutathione. 

Thiazolidines have been prepared from )3-aminothiols—for example, cysteine— to protect the -SH and -NH groups during syntheses of peptides, including glutathione. Thiazolidines are oxidized to symmetrical disulfides with iodine they do not react with thiocyanogen in a neutral solution. ... 

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...

Immobilized dihydrolipoamide (thioctic acid) (Gorecki and Patchornick, 1973 Gorecki and Patchornick, 1975) and immobilized N-acetyl-homocysteine thiolactone (Eldjarn and Jellum, 1963 Jellum, 1964) are the two most commonly used immobilized disulfide reductants. In addition, immobilized TCEP provides a reducing matrix that is free of thiols (Thermo Fisher). Such immobilized reductants successfully can be used to reduce many types of biological disulfides, including small molecules like oxidized glutathione and bovine insulin. They... 

The iodoacetyl group of both isomers reacts with sulfhydryls under slightly alkaline conditions to yield stable thioether linkages (Figure 9.7). They do not react with unreduced disulfides in cystine residues or with oxidized glutathione (Gorman et al., 1987). The thioether bonds will be hydrolyzed under conditions necessary for complete protein hydrolysis prior to amino acid analysis. 

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