Buckman T D, Eiduson S
J Biol Chem. 1985 Oct 5;260(22):11899-902.
The reaction of the neurotoxin MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) with monoamine oxidase from a variety of tissues including rat and monkey brain, bovine liver, and human placenta and platelets was found to yield, as a primary product, a reactive photosensitive substance with an absorbance maximum at 345 nm which is not the cation 1-methyl-4-phenylpyridinium ion previously reported as a monoamine oxidase-MPTP metabolite in vivo and in vitro. Our results suggest that the 1-methyl-4-phenyl-pyridinium ion is probably only generated in subsequent nonenzymatic transformations of this reactive monoamine oxidase metabolite. This substance was found to specifically inactivate the B-form of monoamine oxidase by a photo-induced mechanism and to react directly with NADPH and dopamine. Properties of the metabolite and potential significance of its reactions to MPTP neurotoxicity are discussed.
人们发现神经毒素MPTP（1-甲基-4-苯基-1,2,3,6-四氢吡啶）与来自多种组织（包括大鼠和猴脑、牛肝以及人胎盘和血小板）的单胺氧化酶反应时，会产生一种主要产物，即一种在345nm处有最大吸收峰的反应性光敏物质，该物质并非先前在体内和体外作为单胺氧化酶-MPTP代谢产物报道的阳离子1-甲基-4-苯基吡啶离子。我们的结果表明，1-甲基-4-苯基吡啶离子可能仅在这种反应性单胺氧化酶代谢产物随后的非酶促转化过程中产生。已发现该物质通过光诱导机制特异性地使单胺氧化酶的B型失活，并直接与NADPH和多巴胺发生反应。文中讨论了该代谢产物的性质及其反应对MPTP神经毒性的潜在意义。
