Effects of whole deletion of CYP2A6 on nicotine metabolism in humans.
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.
Zhang
X
X
Department of Forensic Medicine, Kagawa Medical University, 1750-1, Ikenobe, Miki, Kita, Kagawa 761-0793, Japan.
Ameno
K
K
Ameno
S
S
Kinoshita
H
H
Kubota
T
T
Kumihashi
M
M
Mostofa
J
J
Iwahashi
K
K
Ijiri
I
I
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
C001381:hydroxycotinine; D009538:Nicotine; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C585710:CYP2A6 protein, human; D065637:Cytochrome P-450 CYP2A6; D003367:Cotinine