Karara A, Dishman E, Blair I, Falck J R, Capdevila J H
Department of Medicine, Vanderbilt University, Nashville, Tennessee 37232.
J Biol Chem. 1989 Nov 25;264(33):19822-7.
Chiral analysis of the endogenous rat liver epoxyeicosatrienoic acids shows the biosynthesis of 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acids in a 4:1, 2:1, and 3:1 ratio of antipodes, respectively. Animal treatment with phenobarbital results in a 3.7-fold increase in microsomal cytochrome P-450 concentration and a concomitant, regioselective 6.8- and 3.4-fold increase in the liver concentration of 8,9- and 14,15-epoxyeicosatrienoic acids, respectively. Phenobarbital induces the in vivo synthesis of both regioisomers as nearly optically pure enantiomers. These results demonstrate the enzymatic origin of the epoxyeicosatrienoic acids present in rat liver and document a novel metabolic function for cytochrome P-450 in the regio- and enatioselective epoxygenation of endogenous pools of arachidonic acid.
对大鼠肝脏内源性环氧二十碳三烯酸的手性分析表明，8,9 -、11,12 -和14,15 -环氧二十碳三烯酸的生物合成中，对映体的比例分别为4:1、2:1和3:1。用苯巴比妥处理动物会导致微粒体细胞色素P - 450浓度增加3.7倍，同时肝脏中8,9 -和14,15 -环氧二十碳三烯酸的浓度分别有区域选择性地增加6.8倍和3.4倍。苯巴比妥诱导这两种区域异构体在体内合成为几乎光学纯的对映体。这些结果证明了大鼠肝脏中环氧二十碳三烯酸的酶促来源，并证明了细胞色素P - 450在内源性花生四烯酸池的区域和对映体选择性环氧化中的一种新的代谢功能。
