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Title: Glutathione conjugates with dopamine-derived quinones to form reactive or non-reactive glutathione-conjugates
Authors: Zhou, Z.D. 
Lim, T.M. 
Keywords: Dopamine oxidation
Dopamine quinone
Glutathione (GSH)
GSH detoxification efficiency
Intermediate GSH-conjugates
Parkinson's disease
Issue Date: Nov-2010
Citation: Zhou, Z.D., Lim, T.M. (2010-11). Glutathione conjugates with dopamine-derived quinones to form reactive or non-reactive glutathione-conjugates. Neurochemical Research 35 (11) : 1805-1818. ScholarBank@NUS Repository.
Abstract: In this study we demonstrate for the first time that short-lived intermediate glutathione (GSH) conjugates (5-S-GSH-DA-o-quinone and 2-S-GSH-DA-o-quinone) must have first formed when GSH reacted with dopamine (DA)-derived DA-o-quinones without enzymatic catalysis in solutions. These intermediate GSH-conjugates are unstable and would finally transform into reactive or non-reactive GSH-conjugates dependent on ambient reductive forces. We demonstrated that, under sufficient reductive force, the intermediate GSH-conjugates could be reduced and transform into non-reactive 5-S-GSH-DA and 2-S-GSH-DA. However, 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 and toxic that it could further conjugate with another GSH to form non-reactive 4,7-bi-GSH-5,6-dihydroindole in solutions. Furthermore 7-S-GSH-AM could abrogate tyrosinase activity rapidly and even inhibit proteasome activity in solutions. However, 7-S-GSH-AM could undergo automatically internal rearrangement and transform into non-reactive 7-S-GSH-5,6-dihydroindole if it had not conjugated with GSH. Therefore, insufficient ambient reductive force, such as decreased GSH concentration, could lead to decreased GSH detoxification efficiency for toxic DA quinones. Based on findings in this study, we propose two potential detrimental positive feedback loops involving accelerated DA oxidation, increased GSH consumption and impaired GSH detoxification efficiency, as the potential underlying chemical explanation for dopaminergic neuron degeneration in Parkinson's disease. © 2010 Springer Science+Business Media, LLC.
Source Title: Neurochemical Research
ISSN: 03643190
DOI: 10.1007/s11064-010-0247-7
Appears in Collections:Staff Publications

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