β-Nicotyrine

β-Nicotyrine is an alkaloid metabolite of nicotine as well as a major product of its pyrolysis.[1],[2] 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.[3] 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.[4] 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.[5]

Reference:
[1]. Swain, M.L., Eisner, A., Woodward, C.F., et al. Ultraviolet absorption spectra of nicotine, nornicotine and some of their derivatives. Journal of the American Chemical Society 71(4), 1341-1345 (1949).
[2]. Clayton, P., Lu, A., and Bishop, L. The pyrolysis of (−)-(S)-nicotine: Racemization and decomposition. Chirality 22(4), 442-446 (2010).
[3]. Stephens, E.S., Walsh, A.A., and Scott, E.E. Evaluation of inhibition selectivity for human cytochrome P450 2A enzymes. Drug Metabolism and Disposition 40(9), 1797-1802 (2012).
[4]. Kramlinger, V.M., von Weymarn, L.B., and Murphy, S.E. Inhibition and inactivation of cytochrome P450 2A6 and cytochrome P450 2A13 by menthofuran, β-nicotyrine and menthol. Chemico-Biological Interactions 197(2-3), 87-92 (2012).
[5]. Ordonez, P., Sierra, A.B., Camacho, O.M., et al. Nicotine, cotinine, and β-nicotyrine inhibit NNK-induced DNA-strand break in the hepatic cell line HepaRG. Toxicol.In Vitro 28(2014), 1329-1337 (2014).