Publication Details

Category Text Publication
Reference Category Journals
DOI 10.1021/acs.est.6b04981
Title (Primary) Glutathione adduct patterns of Michael-acceptor carbonyls
Author Slawik, C.; Rickmeyer, C.; Brehm, M.; Böhme, A.; Schüürmann, G.
Journal Environmental Science & Technology
Year 2017
Department OEC
Volume 51
Issue 7
Page From 4018
Page To 4026
Language englisch
UFZ wide themes RU3;
Abstract Glutathione (GSH) has so far been considered to facilitate detoxification of soft organic electrophiles through covalent binding at its cysteine (Cys) thiol group, followed by stepwise catalyzed degradation and eventual elimination along the mercapturic acid pathway. Here we show that in contrast to expectation from HSAB theory, Michael-acceptor ketones, aldehydes and esters may form also single, double and triple adducts with GSH involving β-carbon attack at the much harder N-terminus of the γ-glutamyl (Glu) unit of GSH. In particular, formation of the GSH-N single adduct contradicts the traditional view that S alkylation always forms the initial reaction of GSH with Michael-acceptor carbonyls. To this end, chemoassay analyses of the adduct formation of GSH with nine α,β-unsaturated carbonyls employing high performance liquid chromatography and tandem mass spectrometry have been performed. Besides enriching the GSH adductome and potential biomarker applications, electrophilic N-terminus functionalization is likely to impair GSH homeostasis substantially through blocking the γ-glutamyl transferase catalysis of the first breakdown step of modified GSH, and thus its timely reconstitution. The discussion includes a comparison with cyclic adducts of GSH and furan metabolites as reported in literature, and quantum chemically calculated thermodynamics of hard–hard, hard–soft, and soft–soft adducts.
Persistent UFZ Identifier
Slawik, C., Rickmeyer, C., Brehm, M., Böhme, A., Schüürmann, G. (2017):
Glutathione adduct patterns of Michael-acceptor carbonyls
Environ. Sci. Technol. 51 (7), 4018 - 4026