title: Effects of whole deletion of CYP2A6 on nicotine metabolism in humans.
abstract: We investigated the effects of CYP2A6 genotypes on nicotine metabolism, focused from nicotine to cotinine and its additional 3'-hydroxylating resulted in trans-3'-hydroxycotinine formation. In the subjects genotyped by PCR-RFLP method, one cigarette smoking experiment was performed and urine samples were collected for 24 h. In all subjects who smoked, we detected nicotine, cotinine and trans-3'-hydroxycotinine in urine by GC-MS analysis. In whole deletion of CYP2A6, urinary excretion amounts of cotinine and trans-3'-hydroxycotinine were significantly smaller than those in the wild-type of CYP2A6*1. A lack of CYP2A6 reduces the formation of cotinine and trans-3'-hydroxycotinine, but not entirely reduces the trans-3'-hydroxycotinine formation. Unknown cotinine 3'-hydroxylating activity except CYP2A6 are suspected in humans.
authors.affiliation: Department of Forensic Medicine, Kagawa Medical University, 1750-1, Ikenobe, Miki, Kita, Kagawa 761-0793, Japan.
authors.forename: X
authors.initials: X
authors.lastname: Zhang
authors.forename: K
authors.initials: K
authors.lastname: Ameno
authors.forename: S
authors.initials: S
authors.lastname: Ameno
authors.forename: H
authors.initials: H
authors.lastname: Kinoshita
authors.forename: T
authors.initials: T
authors.lastname: Kubota
authors.forename: M
authors.initials: M
authors.lastname: Kumihashi
authors.forename: J
authors.initials: J
authors.lastname: Mostofa
authors.forename: K
authors.initials: K
authors.lastname: Iwahashi
authors.forename: I
authors.initials: I
authors.lastname: Ijiri
mesh_terms: D001189:Aryl Hydrocarbon Hydroxylases / Q000097:blood / Q000235:genetics*; D003367:Cotinine / Q000031:analogs & derivatives* / Q000652:urine; D065637:Cytochrome P-450 CYP2A6; D008401:Gas Chromatography-Mass Spectrometry; D017353:Gene Deletion; D005838:Genotype; D006720:Homozygote; D006801:Humans; D006899:Mixed Function Oxygenases / Q000097:blood / Q000235:genetics*; D009538:Nicotine / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length
chemical_list: C001381:hydroxycotinine; D009538:Nicotine; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C585710:CYP2A6 protein, human; D065637:Cytochrome P-450 CYP2A6; D003367:Cotinine