HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Segura-Aguilar, J. Articles by Mannervik, B. Search for Related Content PubMed PubMed Citation Articles by Segura-Aguilar, J. Articles by Mannervik, B. Social Bookmarking                      What's this?

Volume 272, Number 9, Issue of February 28, 1997 pp. 5727-5731
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.

---

Human Class Mu Glutathione Transferases, in Particular Isoenzyme M2-2, Catalyze Detoxication of the Dopamine Metabolite Aminochrome

(Received for publication, October 1, 1996, and in revised form, November 20, 1996)

Juan Segura-Aguilar , Sofia Baez ^¶ , Mikael Widersten , Christopher J. Welch ^** and Bengt Mannervik

From the  Division of Biochemistry, Department of Pharmaceutical Bioscience, the  Department of Biochemistry, and the ^** Division of Organic Pharmaceutical Chemistry, Biomedical Center, Uppsala University, S-751 23 Uppsala and the ^¶ Unit of Biochemical Toxicology, Wallenberg Laboratory, Stockholm University, S-106 91 Stockholm, Sweden

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 µmol/min/mg), whereas GSTs A1-1, A2-2, M1-1, M3-3, and P1-1 had markedly lower activities (<1 µmol/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.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				K. Bjork, S. T. Saarikoski, C. Arlinde, L. Kovanen, D. Osei-Hyiaman, M. Ubaldi, M. Reimers, P. Hyytia, M. Heilig, and W. H. Sommer Glutathione-S-transferase expression in the brain: possible role in ethanol preference and longevity FASEB J, September 1, 2006; 20(11): 1826 - 1835. [Abstract] [Full Text] [PDF]

				K. S. Zafar, D. Siegel, and D. Ross A Potential Role for Cyclized Quinones Derived from Dopamine, DOPA, and 3,4-Dihydroxyphenylacetic Acid in Proteasomal Inhibition Mol. Pharmacol., September 1, 2006; 70(3): 1079 - 1086. [Abstract] [Full Text] [PDF]

				M. A. Norrgard, Y. Ivarsson, K. Tars, and B. Mannervik Alternative mutations of a positively selected residue elicit gain or loss of functionalities in enzyme evolution PNAS, March 28, 2006; 103(13): 4876 - 4881. [Abstract] [Full Text] [PDF]

				G. L. David, I. Romieu, J. J. Sienra-Monge, W. J. Collins, M. Ramirez-Aguilar, B. E. del Rio-Navarro, N. I. Reyes-Ruiz, R. W. Morris, J. M. Marzec, and S. J. London Nicotinamide Adenine Dinucleotide (Phosphate) Reduced:Quinone Oxidoreductase and Glutathione S-Transferase M1 Polymorphisms and Childhood Asthma Am. J. Respir. Crit. Care Med., November 15, 2003; 168(10): 1199 - 1204. [Abstract] [Full Text] [PDF]

				P. Talalay and J. W. Fahey Phytochemicals from Cruciferous Plants Protect against Cancer by Modulating Carcinogen Metabolism J. Nutr., November 1, 2001; 131(11): 3027S - 3033. [Abstract] [Full Text] [PDF]

				J. Matsunaga, D. Sinha, L. Pannell, C. Santis, F. Solano, G. J. Wistow, and V. J. Hearing Enzyme Activity of Macrophage Migration Inhibitory Factor toward Oxidized Catecholamines J. Biol. Chem., February 5, 1999; 274(6): 3268 - 3271. [Abstract] [Full Text] [PDF]

				P. L. Pettersson and B. Mannervik The Role of Glutathione in the Isomerization of Delta 5-Androstene- 3,17-dione Catalyzed by Human Glutathione Transferase A1-1 J. Biol. Chem., April 6, 2001; 276(15): 11698 - 11704. [Abstract] [Full Text] [PDF]