Characterization of peroxidative oxidation products of dopamine by mass spectrometry.
We characterized three cytotoxic products, namely dopaminochrome (2,3-dihydro-1H-indole-5,6-dione), 2-(3,4-dihydroxyphenyl)-1-nitroethane and 2-(3,4,6-trihydroxyphenyl)-1-nitroethane. The compounds were separated from the incubation of dopamine (3,4-dihydroxyphenethylamine) with horseradish peroxidase which mimics the peroxidative activity of Prostaglandin H synthase. Incubation of 2-(3,4,6-trihydroxyphenyl)-1-nitroethane with NADPH-cytochrome c reductase led to the formation of 6-hydroxydopamine, a known neurotoxin. Several adducts were also isolated in this study. Oxidation of dopamine in the presence of N-acetylcysteine yielded a thioether conjugate namely, 5-S-(N-acetylcysteinyl)-3,4-dihydroxyphenethylamine. Reaction of the partially purified dopaminochrome with N-acetylcysteine permitted the isolation of another thioether conjugate which was tentatively identified as 7-S-(N-acetylcysteinyl)-5,6-dihydroxyindole. We also isolated the one-to-one condensation products of malonaldehyde with dopamine, norepinephrine and serotonin. The identities of these products were established by chemical synthesis and various mass spectrometric techniques.
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Geriatric Research, Education, and Clinical Center, VA Medical Center, St. Louis University School of Medicine, MO 63104.
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White
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Hsu
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D000111:Acetylcysteine / Q000378:metabolism; D004298:Dopamine / Q000737:chemistry* / Q000378:metabolism*; D008401:Gas Chromatography-Mass Spectrometry; D006735:Horseradish Peroxidase / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D013058:Mass Spectrometry / Q000379:methods*; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D010084:Oxidation-Reduction; D016627:Oxidopamine / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism
D012701:Serotonin; D008315:Malondialdehyde; D016627:Oxidopamine; D006861:Hydrogen Peroxide; D006735:Horseradish Peroxidase; D009251:NADPH-Ferrihemoprotein Reductase; D004298:Dopamine; D000111:Acetylcysteine; D009638:Norepinephrine