Newcomer T A, Palmer A M, Rosenberg P A, Aizenman E
Department of Physiology, University of Pittsburgh School of Medicine, Pennsylvania 15261.
J Neurochem. 1993 Sep;61(3):911-20. doi: 10.1111/j.1471-4159.1993.tb03602.x.
2,4,5-Trihydroxyphenylalanine (TOPA) oxidizes in solution to form a quinone derivative that is a non-N-methyl-D-aspartate agonist and neurotoxin. Although pathways have been postulated for the formation of both TOPA and TOPA quinone from closely related catecholamines, the generation of these compounds has not been conclusively demonstrated by analytical techniques. Reverse-phase HPLC with a dual electrode coulometric detector was used to analyze TOPA containing solutions in an effort to rigorously characterize the behavior of this substance under physiological conditions. Electrode potential, buffer system, and methanol concentration were varied to obtain optimal conditions to selectively detect and quantify TOPA and TOPA quinone from closely related catecholamines. TOPA was shown to rapidly autoxidize to TOPA quinone by a process dependent on pH. TOPA was the dominant species at acidic pHs (below 5-6), whereas TOPA quinone was dominant at physiological pHs. This conversion was reversible upon acidification. In addition, we found that 3,4-dihydroxyphenylalanine can autoxidize to form both TOPA and TOPA quinone under physiological conditions. This partial conversion (0.5%) is time dependent and can be substantially decreased (0.2%) in acidic conditions (pH < or = 3). These results suggest that some of the excitatory and excitotoxic properties that some investigators have attributed to DOPA may actually be due to its conversion to TOPA and TOPA quinone.
2,4,5-三羟基苯丙氨酸（TOPA）在溶液中氧化形成一种醌衍生物，该衍生物是一种非N-甲基-D-天冬氨酸受体激动剂和神经毒素。尽管已经提出了从密切相关的儿茶酚胺形成TOPA和TOPA醌的途径，但这些化合物的生成尚未通过分析技术得到确凿证明。使用带有双电极库仑检测器的反相高效液相色谱法分析含TOPA的溶液，以严格表征该物质在生理条件下的行为。改变电极电位、缓冲系统和甲醇浓度以获得最佳条件，以便从密切相关的儿茶酚胺中选择性地检测和定量TOPA和TOPA醌。结果表明，TOPA通过一个依赖于pH的过程迅速自氧化为TOPA醌。在酸性pH值（低于5-6）时TOPA是主要形式，而在生理pH值时TOPA醌是主要形式。酸化后这种转化是可逆的。此外，我们发现3,4-二羟基苯丙氨酸在生理条件下可以自氧化形成TOPA和TOPA醌。这种部分转化（0.5%）是时间依赖性的，在酸性条件（pH≤3）下可以大幅降低（0.2%）。这些结果表明，一些研究人员归因于多巴的某些兴奋性和兴奋毒性特性可能实际上是由于其转化为TOPA和TOPA醌所致。
