title: Liver and lung microsomal metabolism of the tobacco alkaloid beta-nicotyrine.
abstract: The in vitro metabolic fate of beta-nicotyrine has been examined in rabbit lung and liver microsomal preparations as part of an effort to characterize the formation of potentially reactive metabolic species that may contribute to the toxic properties of tobacco products. HPLC analysis revealed the formation of an unstable metabolite which displayed HPLC-MS/MS characteristics consistent with the structure 1-methyl-5-(3-pyridyl)-3-pyrrolin-2-one. Attempted synthesis of this pyrrolinone, however, resulted in the isolation of the isomeric 1-methyl-5-(3-pyridyl)-2-pyrrolin-2-one. The HPLC, diode array UV, and mass spectral characteristics of this delta 4,5-isomer proved to be identical with those of the metabolite derived from beta-nicotyrine. Studies in D2O suggest that the 2- and 3-pyrrolinones are in equilibrium in aqueous solution. The metabolite undergoes autoxidation, possibly via radical intermediates, to yield 1-methyl-5-(3-pyridyl)-5-hydroxy-3-pyrrolin-2-one.
authors.affiliation: Department of Pharmacology, University of California, San Francisco.
authors.forename: M K
authors.initials: MK
authors.lastname: Shigenaga
authors.forename: B H
authors.initials: BH
authors.lastname: Kim
authors.forename: P
authors.initials: P
authors.lastname: Caldera-Munoz
authors.forename: T
authors.initials: T
authors.lastname: Cairns
authors.forename: P
authors.initials: P
authors.lastname: Jacob
authors.forename: A J
authors.initials: AJ
authors.lastname: Trevor
authors.forename: N
authors.initials: N
authors.lastname: Castagnoli
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D008168:Lung / Q000378:metabolism*; D008297:Male; D008861:Microsomes / Q000378:metabolism*; D008862:Microsomes, Liver / Q000378:metabolism*; D010084:Oxidation-Reduction; D010947:Plants, Toxic; D011725:Pyridines / Q000378:metabolism*; D011817:Rabbits; D013056:Spectrophotometry, Ultraviolet; D014026:Nicotiana
chemical_list: D011725:Pyridines; C008615:alpha-nicotyrine; D003577:Cytochrome P-450 Enzyme System