Damani L A, Shaker M S, Godin C S, Crooks P A, Ansher S S, Jakoby W B
J Pharm Pharmacol. 1986 Jul;38(7):547-50. doi: 10.1111/j.2042-7158.1986.tb04636.x.
The substrate specificity of two homogeneous amine N-methyltransferases from rabbit liver has been demonstrated to extend to the azaheterocycles pyridine, R-(+)-nicotine and S-(-)-nicotine. Both enzymes methylate R-(+)-nicotine at the pyridyl nitrogen to afford the N-methylnicotinium salt, whereas S-(-)-nicotine does not act as a substrate for either enzyme. Surprisingly, R-(+)-nicotine is methylated at either the pyridyl nitrogen, or the pyrrolidine nitrogen, to afford the two isomeric monomethylate nicotinium ions when an enzymic preparation containing both methyl transferase activities was used. Under similar conditions S-(-)-nicotine was methylated only at the pyridyl nitrogen. The production of charged metabolites in-vivo, from the large number of pyridino-compounds that are used as drugs, or are present in the environment, may be of toxicological significance, in view of the reported toxicities of several such quaternary ammonium compounds.
已证明来自兔肝的两种均一胺N-甲基转移酶的底物特异性可扩展至氮杂环吡啶、R-(+)-尼古丁和S-(-)-尼古丁。两种酶均使R-(+)-尼古丁的吡啶氮甲基化，生成N-甲基烟碱盐，而S-(-)-尼古丁对这两种酶都不是底物。令人惊讶的是，当使用含有两种甲基转移酶活性的酶制剂时，R-(+)-尼古丁在吡啶氮或吡咯烷氮处甲基化，生成两种异构的单甲基化烟碱离子。在类似条件下，S-(-)-尼古丁仅在吡啶氮处甲基化。鉴于已报道的几种此类季铵化合物的毒性，大量用作药物或存在于环境中的吡啶基化合物在体内产生带电代谢物可能具有毒理学意义。
