| Abstract
| - In 0.1 M phosphate buffer, pH 7.4, dopamine reacts with glyoxal, a cytotoxic and genotoxicα-oxoaldehyde produced by oxidative degradation of carbohydrates, to give three main products,two of which could be isolated and identified as the isomeric tetrahydrobiisoquinolines 1 and2 by extensive two-dimensional NMR and mass spectrometric analysis. Time course studiesindicated that 1 is the first intermediate in the process and changes slowly to 2 via an unstablespecies that escaped all efforts at isolation and structural identification. Products 1 and 2were detected also among the species formed by the interaction of dopamine with oxidizedcarbohydrates, such as glucose, ribose, and fructose. Mechanistic evidence suggests that theformation of 1 proceeds by an unusual reaction pathway involving intramolecular cyclizationof a double Schiff base intermediate followed by glyoxal-induced oxidation of the resultingoctahydrobiisoquinoline intermediate (4). Subsequent conversion of 1 to 2 would involve acomplex redox mechanism depending on an initial oxidation step. Product 2 was only poorlytoxic to PC12 cells, whereas its methylated derivative 3 was as toxic as salsolinol, an establishedneurotoxin. Overall, these results throw light on a novel pathway of dopamine modification ofpotential relevance to the mechanisms underlying neurodegenerative changes in Parkinson'sdisease and other disorders characterized by a prooxidant state.
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