Characterization of Microsomal Alcohol Oxygenase Catalyzing the Oxidation of 7-Hydroxy-Δ8-tetrahydrocannabinol to 7-Oxo-Δ8-tetrahydrocannabinol in Rat Liver
Characterization of Microsomal Alcohol Oxygenase Catalyzing the Oxidation of 7-Hydroxy-Δ8-tetrahydrocannabinol to 7-Oxo-Δ8-tetrahydrocannabinol in Rat Liver
复制标题
大鼠肝脏中微粒体醇加氧酶催化 7-羟基-Δ8-四氢大麻酚氧化为 7-Oxo-Δ8-四氢大麻酚的表征
DOI：
--
复制
发表时间：
2000
期刊：
影响因子：
--
通讯作者：
I. Yamamoto
中科院分区：
文献类型：
--
作者：
T. Matsunaga;K. Shibayama;S. Higuchi;Hiroyuki Tanaka;Kazuhito Watanabe;I. Yamamoto
在大鼠肝微粒体中发现7β-羟基-Δ 8-THC形成7-氧代-Δ8-四氢大麻酚（7-oxo-Δ 8-THC）。该酶的活性具有立体选择性，比7α-羟基-Δ8-THC高3倍。雄性动物中7α-和7β-羟基-Δ8-THC氧化为7-氧代-Δ8-THC的活性显著高于雌性动物，地塞米松和苯巴比妥可显著增强该活性，然后抗P450 GPF-B抗体可抑制该活性至对照值的约20%，P450 GPF-B可能是3A亚家族的成员，3A亚家族是豚鼠中负责形成7-氧代-Δ8-THC的主要酶。该抗体还抑制大鼠肝微粒体由Δ8-THC形成7α-和7β-羟基-Δ8-THC和7-氧代-Δ8-THC。结果表明，大鼠肝微粒体7-羟基-Δ8-THC氧化为7-氧代-Δ8-THC的反应存在性别差异，该反应主要由3A亚家族的P450酶催化，P450酶是肝微粒体醇加氧酶的主要酶。
The formation of 7-oxo-Δ8-tetrahydrocannabinol (7-oxo-Δ8-THC) from 7β-hydroxy-Δ8-THC was found in hepatic microsomes of rats. The activity was stereoselective and about 3-fold higher than that from 7α-hydroxy-Δ8-THC. The oxidative activity of 7α- and 7β-hydroxy-Δ8-THC to 7-oxo-Δ8-THC was significantly higher in male than in female, and significantly enhanced by both dexamethasone and phenobarbital, and then inhibited up to about 20% of the control value by antibody against P450GPF-B, presumably a member of the 3A subfamily, a major enzyme responsible for the formation of 7-oxo-Δ8-THC in guinea pigs. This antibody also inhibited the formation of 7α- and 7β-hydroxy-Δ8-THC, and 7-oxo-Δ8-THC from Δ8-THC by hepatic microsomes of rats. These results indicate that there is a sex-related difference in the oxidatio of 7-hydroxy-Δ8-THC to 7-oxo-Δ8-THC and the reaction is mainly catalyzed by P450 enzyme(s) beloging to the 3A subfamily as major enzyme(s) of microsomal alcohol oxygenase in rats.
人肝微粒体 δ1-四氢大麻酚的代谢。
DOI：
--
发表时间：
1992
期刊：
Drug metabolism and disposition: the biological fate of chemicals
影响因子：
--
作者：
Bornheim,LM;Lasker,JM;Raucy,JL
通讯作者：
Raucy,JL