Glutathione thiyl radical

The key to hexavalent chromium s mutagenicity and possible carcinogenicity is the abiHty of this oxidation state to penetrate the cell membrane. The Cr(VI) Species promotes DNA strand breaks and initiates DNA—DNA and DNA-protein cross-links both in cell cultures and in vivo (105,112,128—130). The mechanism of this genotoxic interaction may be the intercellular reduction of Cr(VI) in close proximity to the nuclear membrane. When in vitro reductions of hexavalent chromium are performed by glutathione, the formation of Cr(V) and glutathione thiyl radicals are observed, and these are beHeved to be responsible for the formation of the DNA cross-links (112). 

Carbon monoxide has been used to scavenge OH fonned from the ozonolysis of alkenes. The CO2 tints generated was detected by FTIR spectroscopy and the "OH yields for individual reactions were calculated.239 The significance of the OH-induced intramolecular transformation of glutathione thiyl radicals to a-aminoalkyl radicals has been discussed with respect to its biological implications.240 The kinetics and mechanism of the process indicated that it could be a significant pathway for the selfremoval of glutathione thiyl radicals in vivo. 

Grierson L, Hildenbrand K, Bothe E (1992) Intramolecular transformation reaction of the glutathione thiyl radical into a non-sulphur-centered radical a pulse radiolysis and EPR study. Int J Radiat Biol 62 265-277... 

Zhao R, Lind J,Merenyi G, EriksonTE(1997) Significance of the intramolecular transformation of glutathione thiyl radicals to a-aminoalkyl radicals. Thermochemical and biological implications. J Chem Soc Perkin Trans 2 569-574... 

Aiyar J, Borges K, Floyd RA, et al. 1989. Role of chromium(V), glutathione thiyl radical and hydroxyl radical intermediates in chromium(VI)-induced DNA damage. Toxicol Environ Chem 22 135-148. 

Made) E, Wardman P. (2007) The oxidizing power of the glutathione thiyl radical as measured by its electrode potential at physiological pH. Arch Biochem Biophys 462 94-102. 

Glutathione thiyl radicals (GS ) can be produced e.g. when radicals from oxidable drugs redox cycle (ScHREiBER et al. 1989), or in the repair of oxidative stress (O Brien 1988) and radiation damage (Quintiliani et al. 1977). 

The reaction of P-CAR with thiyl (RS ) and thiyl sulfonyl (RS()2 ) radicals have both been reported using pulse radiolysis (Everett et al. 1995, 1996). It was found that radical addition to P-CAR occurred and that p-CAR scavenges the thiyl radical, including that derived from glutathione, only via this mechanism, whereas it reacts with thiyl sulfonyl radicals by electron transfer as well. 

Rauk A, Armstrong DA, Berges J (2001) Glutathione radical intramolecular H abstraction by thiyl radical. Can J Chem 79 405-417... 

Sevilla MD, Becker D, Yan M (1990a) The formation and structure of the sulfoxyl radicals RSO, RSOO, RSCV, and RS0200 from the reaction of cysteine, glutathione and penicillamine thiyl radicals with molecular oxygen. Int J Radiat Biol 57 65-81... 

The free thiol group of cysteine readily undergoes reversible oxidation to form a disulphide via a thiyl radical, which can be repaired in the presence of a thiol donor such as glutathione. This is important during reversible cellular signalling processes. Further oxidation leads irreversibly to cysteic acid [96]. Oxidation of the single amino acid cysteine is also complicated by the observation that the product may be a composite mixed disulphide formed between other thiol-containing molecules. 

The chemical properties of these free radicals were studied in small molecules such as dithiothreitol, lipoamide and glutathione etc... (For reviews see 7, 132). The thiyl radical is oxidizing (table 5). However, it is in tautomeric equilibrium with a carbon-centered free radical (49, 133) formed through base-catalyzed intramolecular rearrangement. This latter form is a reductant (49) and its fate is unknown. Thiyl radicals are also formed in proteins. They are somewhat uneasy to visualize because of their low extinction coefficient (table 3). In addition when they are formed by one-electron oxidation, tyrosinyl radicals are also created and thus thiyl radicals are hidden by their strong absorption (134, 135). However they may be observed when formed by reduction (37). 

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