LIVER MICROSOMAL CYTOCHROME-P-450 AND THE OXIDATIVE-METABOLISM OF ARACHIDONIC-ACID
LIVER MICROSOMAL CYTOCHROME-P-450 AND THE OXIDATIVE-METABOLISM OF ARACHIDONIC-ACID
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DOI：
10.1073/pnas.78.9.5362
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发表时间：
1981-01-01
期刊：
影响因子：
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通讯作者：
ESTABROOK, RW
中科院分区：
文献类型：
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作者：
CAPDEVILA, J;CHACOS, N;ESTABROOK, RW
花生四烯酸被大鼠肝微粒体氧化代谢，代谢速率约为。5 nmol/min每毫克蛋白质在25度。这个反应依赖于NADPH和O2的存在。对各种抑制剂的研究表明，膜结合细胞色素P-450在花生四烯酸转化为羟基酸衍生物混合物中的作用。该反应的化学计量符合单加氧酶反应，即每摩尔O2被氧化1mol NADPH，这表明该反应机制不同于脂质过氧化反应。没有证据表明前列腺素样代谢物的形成。形成的一些代谢物的二烯特征表明细胞色素P-450的另一个作用，即参与氢提取反应以激活各种底物。
Arachidonic acid is oxidatively metabolized by rat liver microsomes at a rate of .apprx. 5 nmol/min per mg of protein at 25.degree. C. This reaction is dependent on the presence of NADPH and O2. Studies with various inhibitors indicate a role for membrane-bound cytochrome P-450 in the transformation of arachidonic acid to a mixture of hydroxy acid derivatives. The stoichiometry of the reaction conforms to that of a monooxygenase reaction i.e., 1 mol of NADPH is oxidized per mole of O2 utilized suggesting a reaction mechanism different from that proposed for lipid peroxidation reactions. No evidence for the formation of prostaglandin-like metabolites was obtained. The diene character of some of the metabolites formed suggests another role for cytochrome P-450, i.e., participation in hydrogen abstraction reactions for the activation of various substrates.