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.
Geriatric Research, Education, and Clinical Center, VA Medical Center, St. Louis University School of Medicine, MO 63104.
M B
MB
Mattammal
R
R
Strong
E
E
White
F F
FF
Hsu
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