N-methylation of nicotine enantiomers by human liver cytosol.
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 microM. Nicotine N-methylation appears to be species-dependent, since rat liver homogenates contained no 'nicotine N-methyltransferase' activity, whereas with guinea-pig liver homogenates, a substrate specificity for only R-(+)-nicotine was observed.
D000818:Animals; D003600:Cytosol / Q000378:metabolism*; D006168:Guinea Pigs; D006801:Humans; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism*; D008297:Male; D008745:Methylation; D009538:Nicotine / Q000378:metabolism* / Q000493:pharmacokinetics; D051381:Rats; D013237:Stereoisomerism
D009538:Nicotine