Effective NADH-Dependent Oxidation of 7β-Hydroxy-Δ^8-tetrahydrocannabinol to the Corresponding Ketone by Japanese Monkey Hepatic Microsomes(Toxicology)
スポンサーリンク
概要
- 論文の詳細を見る
The NADH-dependent activity by hepatic microsomes of Japanese monkeys for 7-oxo-Δ^8-tetrahydrocannabinol (7-oxo-Δ^8-THC) formation from 7β-hydroxy-Δ^8-THC exhibited about 70% of the NADPH-dependent activity (100%) at the substrate concentration of 72.7μ_M, although NADPH was an obligatory cofactor for maximal activity. Both NADH-and NADPH-dependent activities were significantly inhibited by the typical P450 inhibitors, such as SKF525-A and metyrapone. Both activities were almost completely inhibited by the NADPH-P450 reductase inhibitor diphenyliodonium chloride. The ratio of NADH- and NADPH-dependent activities varied significantly according to the substrate concentration. Interestingly, the NADH-dependent activity was higher than that of NADPH at low substrate concentrations of 13-50μ_M. The ratio was also affected by the cofactor concentration. In the reconstituted system of CYP3A8 purified from hepatic microsomes of Japanese monkeys as a major enzyme responsible for the NADPH-dependent oxidation, NADH as well as NADPH could sustain the oxidation of 7β-hydroxy-Δ^8-THC to the corresponding ketone. The NADH-dependent oxidation of 7β-hydroxy-Δ^8-THC by monkey livers is mainly catalyzed by CYP3A8 as well as the NADPH-dependent oxidation. These results indicate that NADH as a cofactor may be also useful for the oxidation of 7β-hydroxy-Δ^8-THC, and that the cofactor requirement for the reaction is varied by the concentrations of substrate and/or cofactor.
- 社団法人日本薬学会の論文
- 2005-04-01
著者
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YAMAMOTO IKUO
Department of Laboratory Medicine, Miyazaki Medical College
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景山 節
京大・霊長類研・生化学
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Yamamoto Ikuo
Department Of Hygienic Chemistry School Of Pharmaceutical Sciences Kyushu University Of Health And W
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Watanabe Kazuhito
Department of Hygienic Chemistry, Faculty of Pharmaceutical Sciences, Hokuriku University
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MATSUNAGA Tamihide
Division of Pharmacy, Shinshu University Hospital
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YAMAMOTO Ikuo
School of Pharmaceutical Sciences, Kyushu University of Health and Welfare
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HIGUCHI Shinsuke
Department of Hygienic Chemistry, Faculty of Pharmaceutical Sciences, Hokuriku University
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KAGEYAMA Takashi
Department of Cellular and Molecular Biology, Primate Research Institute, Kyoto University
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Yamamoto Ikuo
北陸大学 薬 衛化
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Yamamoto Ikuo
Department Of Hygienic Chemistry Faculty Of Pharmaceutical Sciences Hokuriku University
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OHMORI Shigeru
Division of Pharmacy, Shinshu University Hospital
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YAMAMOTO IKUO
Hygienic Chemistry
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Kimura T
Department Of Hygienic Chemistry Faculty Of Pharmaceutical Sciences Hokuriku University
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景山 節
京都大学霊長類研究所人類進化モデル研究センター
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景山 節
京大・霊長研
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Higuchi Shinsuke
Department Of Hygienic Chemistry Faculty Of Pharmaceutical Sciences Hokuriku University
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Watanabe Kazuhito
Department Of Hygienic Chemistry Faculty Of Pharmaceutical Sciences Hokuriku University
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Watanabe Kazuhito
Department Of Chemistry And Chemical Engineering Faculty Of Engineering Yamagata University
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Kimura T
Department Of Medicinal Chemistry Center For Frontier Research In Medicinal Science 21st Century Coe
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Yamamoto I
Hokuriku Univ. Kanazawa Jpn
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Ohmori Shigeru
Division Of Pharmacy Shinshu University Hospital
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Yamamoto I
Hygienic Chemistry
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Matsunaga Tamihide
Division Of Pharmacy Shinshu University Hospital
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Watanabe Kazuhito
Faculty Of Pharmaceutical Sciences Kyushu University
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Yamamoto Ikuo
Hygienic Chemistry School Of Pharmacy Hokuriku University
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Yamamoto Ikuo
Department Of Bioapplied Chemistry Faculty Of Engineering Osaka City University
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Ohmori Shigeru
Dep. Of Pharmacy Shinshu Univ. Hospital
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