Journal article
Nonenzymatic displacement of chlorine and formation of free radicals upon the reaction of glutathione with PCB quinones
Proceedings of the National Academy of Sciences - PNAS, Vol.106(24), pp.9725-9730
06/16/2009
DOI: 10.1073/pnas.0810352106
PMCID: PMC2689812
PMID: 19497881
Abstract
The reactions of glutathione (GSH) with polychlorinated biphenyl (PCB) quinones having different degrees of chlorination on the quinone ring were examined. EPR spectroscopy and MS revealed 2 types of reactions yielding different products: (
i
) a nonenzymatic, nucleophilic displacement of chlorine on the quinone ring yielding a glutathiylated conjugated quinone and (
ii
) Michael addition of GSH to the quinone, a 2-electron reduction, yielding a glutathiylated conjugated hydroquinone. The p
K
a
of parent hydroquinone decreased by 1 unit as the degree of chlorination increased. This resulted in a corresponding increase in the oxidizability of these chlorinated hydroquinones. The reaction with oxygen appears to be first-order each in ionized hydroquinone and dioxygen, yielding hydrogen peroxide stoichiometrically. The generation of semiquinone radicals, superoxide, and hydroxyl radicals was observed by EPR; however, the mechanisms and yields vary depending on the degree of the chlorination of hydroquinone/quinone and the presence or absence of GSH. Our discovery that chlorinated quinones undergo a rapid, nonenzymatic dechlorination upon reaction with GSH opens a different view on mechanisms of metabolism and the toxicity of this class of compounds.
Details
- Title: Subtitle
- Nonenzymatic displacement of chlorine and formation of free radicals upon the reaction of glutathione with PCB quinones
- Creators
- Yang Song - Free Radical and Radiation Biology Program and Electron Spin Resonance Facility, University of Iowa, Iowa City, IA 52242-1101Brett A Wagner - Free Radical and Radiation Biology Program and Electron Spin Resonance Facility, University of Iowa, Iowa City, IA 52242-1101Jordan R Witmer - Free Radical and Radiation Biology Program and Electron Spin Resonance Facility, University of Iowa, Iowa City, IA 52242-1101Hans-Joachim Lehmler - Interdisciplinary Graduate Program in Human Toxicology, University of Iowa, 100 Oakdale Campus, 124 IREH, Iowa City, IA 52242-5000; andGarry R Buettner - Interdisciplinary Graduate Program in Human Toxicology, University of Iowa, 100 Oakdale Campus, 124 IREH, Iowa City, IA 52242-5000; and
- Resource Type
- Journal article
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, Vol.106(24), pp.9725-9730
- DOI
- 10.1073/pnas.0810352106
- PMID
- 19497881
- PMCID
- PMC2689812
- NLM abbreviation
- Proc Natl Acad Sci U S A
- ISSN
- 0027-8424
- eISSN
- 1091-6490
- Publisher
- National Academy of Sciences
- Language
- English
- Date published
- 06/16/2009
- Academic Unit
- Occupational and Environmental Health; Iowa Neuroscience Institute; Radiation Oncology; Iowa Superfund Research Program
- Record Identifier
- 9984001096802771
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