Properties of GSH

Misonidazole [27 l-methoxy-3-(2-nitroimidazol-l-yl)-2-propanol] and the model compound l-methyl-2-nitroimidazole have been used as radiosensitizers in the treatment of certain types of human tumors. One important property of these compounds is that they are more toxic to hypoxic cells than to aerobic cells, indicating that reductive metabolism of the drug is involved in the toxicity. Results of a number of studies suggest that intracellular thiols play a significant role in the hypoxic cell toxicity, and it was found that reduction products formed stable thio ethers with GSH (for literature see References 181-183). The reaction mechanism of thio ether formation has not been fully established. It has been suggested that the 4-electron reduction product was involved in thio ether formation181,184,185, and that the hydroxylamine rather than the nitroso derivative was the reactant. On the other hand, an intermediate nitroso derivative is expected to give a sulfenamide cation (see Scheme 1) which easily allows thio ether formation. 

The excessive replacement of Met by SeMet lowers the protein stability in vitro, but not necessarily in vivo. At the low levels of SeMet normally present in culture media, the substitution of Met by the more oxygen-sensitive SeMet is unlikely to affect the properties of enzymes in an adverse manner. Moreover, since methionine selenoxide is readily converted back to SeMet on reaction with biogenic thiols such as GSH, a mechanism of repair of this type of oxidative damage is available. The reversibility of SeMet oxidation in the... 

Additionally, Pt nanoclusters were synthesized with glutathione as a ligand. Upon rednction of a preformed Pt(II)GSH complex, nanoparticulate material of Pt -(GSH) was formed. These nanoparticles had an average diameter of 17.0 6.2 nm and demonstrated no plasmon absorbance due to the electronic and dielectric properties of the metal. Powder XRD analysis confirmed a face-centered cubic lattice stmcture for the material. ... 

Ebselen (2-phenyl-1,2-benzisoselenazol-3(2//)-one), 4 and some of its derivatives mimic the action of GSH-Px.The sulfur analogue is completely inactive, an observation which highlights the importance of selenium in this redox chemistry. Ebselen has also been shown to be a nitric oxide synthase (NOS) inhibitor,to induce cytokines such as interferons, tumour necrosis factor, interleukin-2 and gratunocytemacrophage colony stimulating factor. These properties combined with Ebselen s low toxicity have led to interest in its therapeutic potential for a number of diseases.5... 

Recently a microsomal GSH S-transferase has been characterized in rat liver, which has the distinctive property of being activated by N-ethylmalelmlde ( ). The existence of this GSH S-transferase in fish species is not documented, although one study with pike liver microsomes showed that there was no N-ethylmalelmide-... 

Glutathione S-transferase enzymes have been detected In a variety of different plant species (24,76.64.97.101.107-110). Howevei, detailed enzyme studies have been limited to corn (24.76, J09., 12 ) and pea (. JOT., 110). The foliar tissue of corn contains a GST Isozyme that appears rather unique In Its ability to catalyze the conjugation of various 2-chloro-s-trlazlnes with GSH (78). The molecular weight and other properties of this Isozyme are similar to those reported for many mammalian GST Isozymes however, the pH optimum of this Isozyme for atrazine Is somewhat lower than that reported for many GST Isozymes (, 78,J09.). When corn Is treated with R-25788, a second Isozyme Is Induced ( ). The Induced Isozyme Is very effective In catalyzing the GSH conjugation of an a-chloroacetamlde herbicide (alachlor), but It was not assayed with atrazine ( ). 

Many organisms contain multiple forms of GSH S-transferase, but the isoenzymes of mammalian liver have been the most extensively studied (37). These abundant enzymes are characterized by distinct but overlapping substrate specificities that account for the liver s capacity to conjugate a structurally diverse group of chemicals. Based on primary structure, physicochemical properties and catalytic specificities, mammalian GSH S-transferases have been assigned to one of three classes (a, or n) that correspond three major gene families (43). The catalytically active enzymes exist as binary combinations of either identical (homodimer) or certain combinations of non-identical subunits (heterodimer) but heterodimers do not form between subunits of different classes (43). 

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