Isoflavones inhibit nicotine C-oxidation catalyzed by human CYP2A6.
The inhibitory effects of isoflavones (daidzein, genistein, and glycitein) on human cytochrome P450 (CYP) 2A6 activities were investigated. Daidzein, genistein, and glycitein uncompetitively inhibited nicotine C-oxidation catalyzed by recombinant CYP2A6 expressed in baculovirus-infected insect cells with Ki values of 1.3 +/- 0.3 microM, 0.7 +/- 0.2 microM, and 5.2 +/- 0.8 microM, respectively, but not coumarin 7-hydroxylation. Effects of the intake of soy isoflavones on in vivo nicotine metabolism were investigated with 7 healthy Japanese homozygotes of CYP2A6*1. The cotinine/nicotine ratio of the plasma concentrations 2 hours after chewing 1 piece of nicotine gum under the basal condition (after abstaining from soy foods for 1 week) was 8.8 +/- 2.6 (4.4-11.4). The ratio was significantly (P < .05) reduced to 6.7 +/- 1.6 (4.0-8.2) after consumption of a soy isoflavone supplement (60 mg of total isoflavones/d) for 5 days. The authors found that isoflavone contained in soy products significantly decreased nicotine metabolism.
Nakajima
Miki
M
Drug Metabolism and Toxicology, Division of Pharmaceutical Sciences, Graduate School of Medical Science, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan. nmiki@kenroku.kanazawa-u.ac.jp
Itoh
Masahiro
M
Yamanaka
Hiroyuki
H
Fukami
Tatsuki
T
Tokudome
Shogo
S
Yamamoto
Yasuhiko
Y
Yamamoto
Hiroshi
H
Yokoi
Tsuyoshi
T
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000037:antagonists & inhibitors / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D016367:Baculoviridae; D002638:Chewing Gum; D003367:Cotinine / Q000378:metabolism; D065637:Cytochrome P-450 CYP2A6; D019587:Dietary Supplements; D019833:Genistein / Q000494:pharmacology*; D005838:Genotype; D006720:Homozygote; D006801:Humans; D007313:Insecta / Q000166:cytology; D007529:Isoflavones / Q000494:pharmacology*; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D009538:Nicotine / Q000378:metabolism*; D010084:Oxidation-Reduction / Q000187:drug effects; D010641:Phenotype; D045730:Soy Foods
D002638:Chewing Gum; D007529:Isoflavones; C004742:daidzein; D009538:Nicotine; C086566:glycitein; D019833:Genistein; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C585710:CYP2A6 protein, human; D065637:Cytochrome P-450 CYP2A6; D003367:Cotinine