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The main fragmentation process of \u03b3\u2010glutamyl compounds, whether in the thiol, disulfide, thioether or metal\u2010bis\u2010thiolate form, is the loss of the \u03b3\u2010glutamyl residue, a process which ERMS data showed to be hardly influenced by the sulfur substitution. However, loss of the \u03b3\u2010glutamyl residue from the <jats:italic>mono\u2010S<\/jats:italic>\u2010glutathionyl\u2010mercury (II) cation is a much more energetic process, possibly pointing at a strong coordination of the carboxylic group to the metal. Moreover, loss of neutral mercury from ions containing the \u03b3\u2010glutamyl residue to yield a sulfenium cation was a much more energetic process than those not containing them, suggesting that the redox potential of the thiol\/disulfide system plays a role in the formal reduction of the mercury dication in the gas phase. Occurrence of complementary sulfenium and protonated thiol fragments in the spectra of protonated disulfides of the glutathione metaboloma mirrors the thiol\/disulfide redox process of biological importance. The intensity ratio of the fragments is proportional to the reduction potential in solution of the corresponding redox pairs. This finding has allowed the calculation of the previously unreported reduction potentials for the disulfide\/thiol pair of cysteinylglycine, thereby confirming the decomposition scheme of bis\u2010 and <jats:italic>mono\u2010S<\/jats:italic>\u2010glutathionyl\u2010mercury (II) ions. Finally, on the sole basis of the mass spectrometric fragmentation of the glutathione\u2013mercury conjugates, and supported by independent literature evidence, an unprecedented mechanism for mercury ion\u2010induced cellular oxidative stress could be proposed, based on the depletion of the glutathione pool by a catalytic mechanism acting on the metal (II)\u2013thiol conjugates and involving as a necessary step the enzymatic removal of the glutamic acid residue to yield a mercury (II)\u2013cysteinyl\u2010glycine conjugate capable of regenerating neutral mercury through the oxidation of glutathione thiols to the corresponding disulfides. Copyright \u00a9 2006 John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/jms.1143","type":"journal-article","created":{"date-parts":[[2006,11,29]],"date-time":"2006-11-29T17:59:07Z","timestamp":1164823147000},"page":"1578-1593","source":"Crossref","is-referenced-by-count":19,"title":["A study of the glutathione metaboloma peptides by energy\u2010resolved mass spectrometry as a tool to investigate into the interference of toxic heavy metals with their metabolic processes"],"prefix":"10.1002","volume":"41","author":[{"given":"Federico Maria","family":"Rubino","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco","family":"Pitton","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabri","family":"Brambilla","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio","family":"Colombi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2006,11,29]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-2952(02)01172-3"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-2952(02)01176-0"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2003.12.126"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-2952(02)01173-5"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-2952(02)01560-5"},{"key":"e_1_2_6_7_2","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1016\/S0006-2952(02)01175-9","article-title":"Glutathionylation of proteins by glutathione disulfide S\u2010oxide","volume":"64","author":"Kuo\u2010Ping H","year":"2002","journal-title":"Biochem. 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