L-DOPA-quinone inactivates tryptophan hydroxylase and converts the enzyme to a redox-cycling quinoprotein.
Tryptophan hydroxylase, the initial and rate limiting enzyme in the biosynthesis of serotonin (5-HT), is inactivated by the quinone of L-DOPA. L-DOPA itself has no effect on enzyme activity. The inactivation of tryptophan hydroxylase could be prevented by glutathione (GSH), dithiothreitol, cysteine, and ascorbic acid but not by scavengers of hydrogen peroxide (catalase), hydroxyl radical (DMSO), or superoxide (superoxide dismutase). All cysteinyl residues within tryptophan hydroxylase are modified after treatment with L-DOPA-quinone as revealed by loss of DTNB-reactivity and formation of cysteinyl-DOPA residues. L-DOPA-quinone also converts tryptophan hydroxylase to a redox-cycling quinoprotein. These results suggest a possible mechanism of 5-HT neuronal damage in Parkinson's Disease by a redox-cycling quinoprotein.
Kuhn
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Cellular and Clinical Neurobiology Program Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, MI 48201, USA. donald.kuhn@wayne.edu
Arthur
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D000975:Antioxidants / Q000494:pharmacology; D016227:Benzoquinones / Q000378:metabolism*; D015153:Blotting, Western; D004591:Electrophoresis, Polyacrylamide Gel; D004789:Enzyme Activation / Q000187:drug effects; D007980:Levodopa / Q000494:pharmacology*; D014442:Monophenol Monooxygenase / Q000494:pharmacology; D009580:Nitroblue Tetrazolium; D010084:Oxidation-Reduction; D019163:Reducing Agents / Q000494:pharmacology; D013194:Staining and Labeling; D013438:Sulfhydryl Compounds / Q000737:chemistry; D014365:Tryptophan Hydroxylase / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*
D000975:Antioxidants; D016227:Benzoquinones; D019163:Reducing Agents; D013438:Sulfhydryl Compounds; D009580:Nitroblue Tetrazolium; C004532:quinone; D007980:Levodopa; D014365:Tryptophan Hydroxylase; D014442:Monophenol Monooxygenase