Ansher S S, Cadet J L, Jakoby W B, Baker J K
Biochem Pharmacol. 1986 Oct 1;35(19):3359-63. doi: 10.1016/0006-2952(86)90436-3.
Amine N-methyltransferases in the brains of humans, monkeys, mice, rabbits and rats, as well as two homogeneous enzymes isolated from rabbit liver, are capable of N-methylating 4-phenyl-1,2,3,6-tetrahydropyridine to 1-methyl-4-phenyltetrahydropyridine (MPTP), and 4-phenylpyridine to 1-methyl-4-phenylpyridinium ion (MPP+). The product in each instance is a neurotoxin. The suggestion is offered that the known long half-life of methylpyridinium compounds in brain may be due to limitations in transport of such charged metabolites out of this tissue and to metabolic recycling of the desmethyl species by amine N-methyltransferases. The methylation of pyridines to quaternary amines is suggested as a means by which lipophilic compounds, having gained entrance to the cell, are converted to charged species that efflux much less readily.
人类、猴子、小鼠、兔子和大鼠大脑中的胺N - 甲基转移酶，以及从兔肝脏中分离出的两种均一酶，能够将4 - 苯基 - 1,2,3,6 - 四氢吡啶N - 甲基化为1 - 甲基 - 4 - 苯基四氢吡啶（MPTP），并将4 - 苯基吡啶N - 甲基化为1 - 甲基 - 4 - 苯基吡啶鎓离子（MPP⁺）。在每种情况下，产物都是一种神经毒素。有人提出，大脑中甲基吡啶鎓化合物已知的长半衰期可能是由于此类带电荷代谢物从该组织中转运受限，以及胺N - 甲基转移酶对去甲基化物种的代谢循环。吡啶甲基化为季胺被认为是一种手段，通过这种手段，进入细胞的亲脂性化合物被转化为带电物种，其外排的难度要大得多。
