N-Methylation of nicotine enantiomers by human liver cytosol

Abstract Incubation of human liver cytosol with either R-(+)-[3H-N′CH3]nicotine or S-(−)-[3H-N′CH3]nicotine results in the formation of the corresponding N-methyl quaternary ammonium metabolite. A substrate stereoselectivity was observed in that the turnover number for the methylation of the S-(−)-isomer was 0.25 pmol mg 1 protein h−1, whereas that for the R-(+)-isomer was 2.11. The latter substrate exhibited an apparent Km value of 20.1 μM. Nicotine N-methylation appears to be species-dependent, since rat liver homogenates contained no ‘nicotine N-methyl-transferase’ activity, whereas with guinea-pig liver homogenates, a substrate specificity for only R-(+)-nicotine was observed.