The ability of amine N-methyltransferases from rabbit liver to N-methylate azaheterocycles.
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.
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D066298:In Vitro Techniques; D008099:Liver / Q000201:enzymology*; D008745:Methylation; D008780:Methyltransferases / Q000378:metabolism*; D011817:Rabbits
D008780:Methyltransferases; C045058:azaheterocycle N-methyltransferase