N-methylation and quaternization of pyridine in vitro by rabbit lung, liver and kidney N-methyltransferases: an S-adenosyl-L-methionine-dependent reaction

Xenobiotica. 1986 Jul;16(7):645-50. doi: 10.3109/00498258609043554.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chromatography, High Pressure Liquid
  • Kidney / enzymology*
  • Kidney / metabolism
  • Liver / enzymology*
  • Liver / metabolism
  • Lung / enzymology*
  • Lung / metabolism
  • Male
  • Methylation
  • Methyltransferases / metabolism*
  • Pyridines / metabolism*
  • Pyridinium Compounds / metabolism
  • Rabbits
  • S-Adenosylmethionine / metabolism

Substances

  • Pyridines
  • Pyridinium Compounds
  • 1-methylpyridinium
  • S-Adenosylmethionine
  • Methyltransferases
  • pyridine