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Glutathione (GSH) conjugates with dopamine (DA)-derived quinones to form reactive or non-reactive GSH-conjugates

Zhidong Zhou¹ and Tit Meng Lim¹

Correspondence: (Login to view email address)

1. National University of Singapore, Department of Biological Science

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Document Type:

Manuscript

Date:

Received 21 March 2009 11:03 UTC; Posted 23 March 2009

Subjects:

Biotechnology, Chemistry, Neuroscience, Pharmacology

Tags:

• glutathione,
• dopamine
• quinone,
• conjugates,
• HPLC,
• ESI-MS,
• Parkinson’s
• disease

Abstract:

In this study we demonstrate for the first time that GSH could rapidly conjugate with dopamine (DA)-derived DA-o-quinones without enzymatic catalysis to form short-lived intermediate GSH-conjugates (2-S-GSH-DA-o-quinone and 5-S-GSH-DA-o-quinone). These intermediate GSH-conjugates are unstable and would finally form reactive or non-reactive GSH-conjugates dependent on ambient reductive forces. Under insufficient reductive forces, the intermediate GSH-conjugates could cyclize spontaneously to form reactive 7-S-GSH-aminochrome (7-S-GSH-AM). The 7-S-GSH-AM is so reactive that it could further react with another GSH to form 4,7-bi-GSH-5,6-dihydroindole. Its reactivity could also abrogate tyrosinase activity in solutions. In addition, the 7-S-GSH-AM could further undergo internal rearrangement to form non-reactive 7-S-GSH-5,6-dihydroindole. From these novel findings, we propose two detrimental positive feedback loops involving accelerated DA oxidation, increased GSH consumption and impaired GSH detoxification efficiency, as the underlying chemical explanation for dopaminergic neuron degeneration in Parkinson's disease.

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This document is licensed to the public under the Creative Commons Attribution 3.0 License

How to cite this document:

Zhou, Zhidong and Lim, Tit Meng. Glutathione (GSH) conjugates with dopamine (DA)-derived quinones to form reactive or non-reactive GSH-conjugates. Available from Nature Precedings <http://hdl.handle.net/10101/npre.2009.2963.1> (2009)

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