Glutathione-mediated

The degradation of isoprene by Rhodococcus sp. strain AD45 involves a glutathione-mediated reaction (van Hylckama Vlieg et al. 2000) and is noted again in Chapter 7, Part 1. 

The degradation of vinyl chloride and ethene has been examined in Mycobacterium sp. strain JS 60 (Coleman and Spain 2003) and in Nocardioides sp. strain JS614 (Mattes et al. 2005). For both substrates, the initially formed epoxides underwent reaction with reduced coenzyme M and, after dehydrogenation and formation of the coenzyme A esters, reductive loss of coenzyme M acetate resulted in the production of 5-acetyl-coenzyme A. The reductive fission is formally analogous to that in the glutathione-mediated reaction. 

Nucleophilic displacement including hydroxylation, hydrolysis, and glutathione-mediated reactions... 

Glutathione-Mediated and Other Reactions Involving Nucleophilic Sulfur... 

Hong R, Han G, Fernandez JM et al (2006) Glutathione-mediated drug release using monolayer protected nanoparticle carriers. J Am Chem Soc 128 1078-1079... 

Ozawa N, Guengerich FP. 1983. Evidence for formation of an S-[2(N -guanyl]ethyl) glutathione adduct in glutathione-mediated binding of the carcinogen 1,2-dibromoethane to DNA. Proc Natl Acad Sci USA 80 5266-5270. 

Figure 4.64 Glutathione-mediated activation of 1, 2-dibromoethane. The addition of glutathione is catalyzed by glutathione transferase. Loss of bromide from the glutathione conjugate gives rise to an episulfonium ion. This can react with bases such as guanine in DNA.

Weber, G.L., Steenwyk, R.C., Nelson, S.D. Pearson, PG. (1995) Identification of V-acetyl-cysteine conjugates of l,2-dibromo-3-chloropropane evidence for cytochrome P450 and glutathione mediated bioactivation pathways. Chem. Res. Toxicol., 8, 560-573... 

A. Structure of glutathione (G-SH). [Note Glutamate is linked to cysteine through a y-carboxyl, rather than an a-carboxyl.] B. Glutathione-mediated reduction of hydrogen peroxide by NADPH. 

Dixon, D. P., Cummins, I., Cole, D. J., and Edwards, E. 1998. Glutathione-mediated detoxification systems in plants. Curr. Opin. Plant Biol. 1, 258-266... 

Famin, O. Krugliak, M. Ginsburg, H. Kinetics of inhibition of glutathione-mediated degradation of ferriprotoporphyrin IX by antimalarial drugs. Biochem. Pharmacol, 1999, 58(1) 59-68. 

Roth RA and Dahm LJ (1997) Neutrophil- and glutathione-mediated hepatotoxicity of alpha-naphthyliso-thiocyanate. Drug Metabolism Reviews 29(1-2) 153-165. 

Defatting creates cell necrosis. Nematocides also reduce cell P450 content. Sulphyril, but not glutathione, mediates toxic effects. Biotransformation (hydrolysis and oxidation) is via the mercapturic acid route, producing a-chlorohydrin and a-bromohy-drin, two antifertility agents. Further oxidation of these substances may produce oxalic acid, which causes liver and kidney damage. 

Sharma, K.G., Kaur, R., and Bachhawat, A.K. (2003) The glutathione-mediated detoxification pathway in yeast an analysis using the red pigment that accumulates in certain adenine biosynthetic mutants of yeasts reveals the involvement of novel genes. Archives of Microbiology. 180. 108-117. 

K19. Kraus, P., Noack, G., and Portig, J., Biodegradation of alpha-hexachlorocyclohexane II. Glutathione-mediated conversion to hydrophilic substance by particulate fi actions of rat liver and by homogenates of various rat organs. Naunyn-Schmiedeberg s Arch. Pharmacol. 279, 199-202 (1973). 

Nock BA, Maine T, Yannoukakos D et al (1999) Glutathione-mediated metabolism of technetium-99m SNS/S mixed ligand complexes a proposed mechanism of brain retention. J Med Chem 42 1066-1075... 

Interaction of marine isonitriles derivatives with heme was shown to inhibit the transformation of heme into / -hematin and then hemozoin, a polymer produced by Plasmodium in order to neutralize the toxic (detergent-like) free heme produced in the food vacuole. In addition, isonitriles were shown to prevent both the peroxidative and glutathione-mediated destruction of heme under conditions that mimic the environment within the malaria parasite. In summary, isonitriles, similarly to quinoline antimalarials [38], exert their antiplasmodial activity by preventing heme detoxification. 

Another pos.sible phase II reaction with the OP insccti-cide.s is a glutathione-mediated dealkylation, which is most likely with the methoxy compounds (Suitatos, 1992). However, although theoretically possible, the relevance of this reaction in vivo is not clear. 

Glutathione-mediated disulphide reductions whether enzyme mediated or spontaneous probably proceed through an intermediate mixed disulphide via a thiolate displacement mechanism. 

R. Hong et al., Glutathione-mediated delivery and release using monolayer protected nanoparticle carriers. Journal of the American Chemical Society, 128(4), 1078-1079 (2006). 

Cui, Y., Dong, FL, Cai, X, Wang, D., and Li, Y. (2012) Mesoporous silica nanoparticles capped with disulfide-linked PEG gatekeepers for glutathione-mediated controlled release. ACS Appl. Mater. Interfaces, 4 (6), 3177-3183. 

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