β-Nicotyrine is an alkaloid metabolite of nicotine as well as a major product of its pyrolysis. It binds comparably to two cytochrome P450 (CYP) isoforms, CYP2A6 and CYP2A13 (Kis = 7.5 and 5.6 μM, respectively), which are prominently involved in the metabolism of xenobiotics in the airways. However, β-nicotyrine appears to more effectively inactivate CYP2A6, leaving only 49% activity after a 10 minute exposure with 20 μM β-nicotyrine, as opposed to 87% remaining activity for CYP2A13 treated identically. Presumably through this effect, β-nicotyrine inhibits DNA strand breaks induced by the genotoxic tobacco metabolite (4-(methylnitrosamino)-1-(2-pyridyl)-1-butanone), which is bioactivated by CYP2A isoforms.
