N-methylation and quaternization of pyridine in vitro by rabbit lung, liver and kidney N-methyltransferases: an S-adenosyl-L-methionine-dependent reaction.
The N-methylation of pyridine in vitro, using dialysed and undialysed hepatic, pulmonary, renal and brain preparations from rabbits, is described. Analysis of the quaternary metabolite, N-methylpyridinium ion, was carried out by selective ion-pair extraction and cation-exchange high-performance liquid chromatography (h.p.l.c.) using a u.v. detector, and also by direct cation-exchange h.p.l.c. of incubates containing S-adenosyl-L-[methyl-3H]methionine using a flow-through radioactivity detector. N-Methylation of pyridine could be readily demonstrated with dialysed homogenates, 9000 g and 100 000 g supernatant fractions from lung, kidney and liver, but not with any of the brain preparations. 'Pyridine N-methyltransferase' activity was confined to the tissue cytosol, and this enzyme utilized S-adenosyl-L-methionine as the methyl donor. Since the activity of the 'pyridine N-methyltransferase' in rabbit tissues is increased many fold by dialysis, this enzyme, in common with most other N-methylating enzymes, is subject to inhibition by a low-molecular-weight endogenous substance.
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D007668:Kidney / Q000201:enzymology* / Q000378:metabolism; D008099:Liver / Q000201:enzymology* / Q000378:metabolism; D008168:Lung / Q000201:enzymology* / Q000378:metabolism; D008297:Male; D008745:Methylation; D008780:Methyltransferases / Q000378:metabolism*; D011725:Pyridines / Q000378:metabolism*; D011726:Pyridinium Compounds / Q000378:metabolism; D011817:Rabbits; D012436:S-Adenosylmethionine / Q000378:metabolism
D011725:Pyridines; D011726:Pyridinium Compounds; C014677:1-methylpyridinium; D012436:S-Adenosylmethionine; D008780:Methyltransferases; C023666:pyridine