With glutathione

Recognition of the thio group s key role in biochemistry has led to studies of l,4-ben2oquinone with glutathione, a tripeptide 7-Glu-Cys-Gly (GSH). The cross-oxidation of the initial addition product by excess quinone leads, under physiological conditions, to all three isomeric products (46), ie, the 2,3-and 2,6-isomers as well as the 2,5-disubstituted l,4-ben2oquinone shown. 

As the above mentioned studies with high supplementation dosages exemplarily show, there is no known toxicity for phylloquinone (vitamin Kl), although allergic reactions are possible. This is NOT true for menadione (vitamin K3) that can interfere with glutathione, a natural antioxidant, resulting in oxidative stress and cell membrane damage. Injections of menadione in infants led to jaundice and hemolytic anemia and therefore should not be used for the treatment of vitamin K deficiency. 

Oakley AJ, Lo Bello M, Battistoni A, Ricci G, Rossjohn J, Villar HO, et al. The structures of human glutathione transferase Pl-1 in complex with glutathione and various inhibitors at high resolution. J Mol Biol 1997 274 84-100. 

Plasmid- ortransposon-mediated resistance occurs by inactivation ofthe antibiotic. Fosfomycin is combined with glutathione intracellularly to produce a compound lacking in antibacterial activity. The gene encoding the enzyme catalysing this reaction has been designated/or-r. 

HONG w K and wu x (2000) Dietary intake of isothiocyanates evidence of a joint effect with glutathione S-transferase polymorphisms in lung cancer risk . Cancer Epidemiol Biomarkers Prev, 9 1017-20. 

Kessi J, KW Hanselmann (2004) Similarities between the abiotic reduction of selenite with glutathione and the dissimilatory reaction mediated by Rhodospirillum rubrum and Escherichia coli. J Biol Chem 279 50662-50669. 

Coles, B., Wilson, I. and Wardman, P. (1988). The spontaneous and enzymatic reaction of N-acetyl-/>-benzoquinone imine with glutathione, a stopped flow kinetic study. Arch. Biochem. Biophys. 264, 253-260. 

Fig. 5 Human corneal endothelium following 3-hour perfusion with glutathione bicarbonated Ringer s solution (a) scanning electron micrograph (1950 x ) (b) transmission electron micrograph (8450 x ). (Courtesy of H. Edelhauser.)... 

As noted above, MDA is a potent stimulator of monoamine release (see Table 7.1), and recent reports indicate that a number of MDMA metabolites are bioactive. For example, Forsling et al.61 showed that the metabolite 4-hydroxy-3-methoxymethamphetamine (HMMA) is more potent than MDMA as a stimulator of vasopressin secretion from rat posterior pituitaries in vitro. The neuroendocrine effects produced by in vivo administration of MDMA metabolites have not been examined. Monks et al.62 demonstrated that catechol metabolites of MDMA and MDA, namely, 3,4-dihydroxymethamphetamine (HHMA) and 3,4-dihydroxyamphetamine (HHA), exhibit neurotoxic properties when oxidized and conjugated with glutathione. Further characterization of the biological effects of MDMA metabolites is an important area of research. 

Alternatively, acrylonitrile is metabolized to 2-cyanoethylene oxide by the microsomal enzyme system. 2-Cyanoethylene oxide can react directly with tissue macromolecules or it can be further metabolized to oxidation products that release cyanide. Cyanide is converted to thiocyanate and excreted in the urine. 2-Cyanoethylene oxide is also conjugated with glutathione and metabolized to 2- hydroxyethylmercapturic acid which is excreted in the urine. 

Guengerich FP, Geiger LE, Hogy LL, et al. 1981. In vitro metabolism of acrylonitrile to 2-cyanoethylene oxide, reaction with glutathione, and irreversible binding to proteins and nucleic acids. Cancer Res 41 4925-4933. 

Aliosman, F., Caughlan, J., and Gray, G.S. (1989) Diseased DNA intrastrand cross-linking and cytotoxicity induced in human brain tumor cells by 1,3-fcis(2-chlorocthyl)-1 -nitrosourea after in vitro reaction with glutathione. Cancer Res. 49, 5954. 

Very interesting mechanism of the enhanced glutathione antioxidant activity in the presence of SOD was offered by Winterbourn [227]. She pointed out that the interaction of all free radicals with glutathione resulted in the formation of superoxide as the only final active species a free radical sink. Therefore, the mixture of glutathione together with SOD may be considered as a universal scavenger of free radicals of any structure. 

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.)... 

Retention of radiocopper injected into humans is high only 10% is excreted within 72 h in urine and feces, and 50% in four weeks (Aaseth and Norseth 1986). Most (72%) of the unabsorbed copper is excreted in the feces primarily by way of the biliary duct, the salivary glands, or the intestinal mucosa a minor portion is excreted by way of sweat and menses (Schroeder et al. 1966 USEPA 1980 ATSDR 1990). In mammals, copper is excreted mainly via the bile in association with glutathione or unidentified high-molecular-weight molecules. However, the transport mechanisms of copper from liver cells into bile are essentially unknown (Aaseth and Norseth 1986). In rats, biliary excretion of copper is increased by increased flow of bile, increased body temperature, or administration of adrenal steroids (Sugawara et al. 1994). 

In the rusty crayfish (Orconectes rusticus), toxicity of copper at high concentrations is due to the coagulatory action on cellular proteins and to interference with respiratory processes at low concentrations, copper causes degenerative changes in certain tissues and interferes with glutathione equilibrium (Hubschman 1967). Larvae of the red crayfish (Procambarus clarkii) exposed to copper as embryos are less sensitive than those exposed after hatching, suggesting acclimatization (Rice and Harrison 1983). 

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