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Human class Mu glutathione transferases, in particular isoenzyme M2-2,catalyze detoxication of the dopamine metabolite aminochrome
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Biochemistry and Organic Chemistry.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Organic Pharmaceutical Chemistry.
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1997 (English)In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 272, no 9, 5727-5731 p.Article in journal (Refereed) Published
Abstract [en]

Human glutathione transferases (GSTs) were shown to catalyze the reductive glutathione conjugation of aminochrome (2, 3-dihydroindole-5,6-dione). The class Mu enzyme GST M2-2 displayed the highest specific activity (148 micromol/min/mg), whereas GSTs A1-1, A2-2, M1-1, M3-3, and P1-1 had markedly lower activities (<1 micromol/min/mg). The product of the conjugation, with a UV spectrum exhibiting absorption peaks at 277 and 295 nm, was 4-S-glutathionyl-5,6-dihydroxyindoline as determined by NMR spectroscopy. In contrast to reduced forms of aminochrome (leucoaminochrome and o-semiquinone), 4-S-glutathionyl-5, 6-dihydroxyindoline was stable in the presence of molecular oxygen, superoxide radicals, and hydrogen peroxide. However, the strongly oxidizing complex of Mn3+ and pyrophosphate oxidizes 4-S-glutathionyl-5,6-dihydroxyindoline to 4-S-glutathionylaminochrome, a new quinone derivative with an absorption peak at 620 nm. GST M2-2 (and to a lower degree, GST M1-1) prevents the formation of reactive oxygen species linked to one-electron reduction of aminochrome catalyzed by NADPH-cytochrome P450 reductase. The results suggest that the reductive conjugation of aminochrome catalyzed by GSTs, in particular GST M2-2, is an important cellular antioxidant activity preventing the formation of o-semiquinone and thereby the generation of reactive oxygen species.

Place, publisher, year, edition, pages
1997. Vol. 272, no 9, 5727-5731 p.
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Natural Sciences Pharmaceutical Sciences
URN: urn:nbn:se:uu:diva-50864DOI: 10.1074/jbc.272.9.5727ISI: A1997WK74700052PubMedID: 9038184OAI: oai:DiVA.org:uu-50864DiVA: diva2:78773
Available from: 2008-10-17 Created: 2008-10-17 Last updated: 2010-11-16Bibliographically approved

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Widersten, Mikael
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