Cytochrome P450 and arachidonic acid bioactivation. Molecular and functional properties of the arachidonate monooxygenase.
Cytochrome P450 and arachidonic acid bioactivation. Molecular and functional properties of the arachidonate monooxygenase.
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发表时间：
2000-02
影响因子：
6.5
通讯作者：
J. Capdevila;J. Falck;Raymond C. Harris
中科院分区：
文献类型：
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作者：
J. Capdevila;J. Falck;Raymond C. Harris
体内花生四烯酸环氧化和ω-羟基化的证明确立了细胞色素P450表氧化酶和ω/ω-1羟化酶作为正式代谢途径和作为花生四烯酸代谢级联的成员。与几种细胞色素P450衍生的类花生酸相关的有效生物活性的表征表明这些酶在细胞、器官和身体生理学中具有新的重要功能作用，包括控制血管反应性和全身血压。细胞色素P450生物化学和分子生物学的过去和当前进展促进了负责组织/器官特异性花生四烯酸环氧化和ω/ω-1羟基化的细胞色素P450同种型的表征，并因此促进了cDNA和/或基因特异性功能表型的分析。生理学、生物化学、分子和遗传学方法的联合应用开始为这些酶、其内源性底物和产物的生理学和/或病理生理学意义提供新的见解。
The demonstration of in vivo arachidonic acid epoxidation and omega-hydroxylation established the cytochrome P450 epoxygenase and omega/omega-1 hydroxylase as formal metabolic pathways and as members of the arachidonate metabolic cascade. The characterization of the potent biological activities associated with several of the cytochrome P450-derived eicosanoids suggested new and important functional roles for these enzymes in cellular, organ, and body physiology, including the control of vascular reactivity and systemic blood pressures. Past and current advances in cytochrome P450 biochemistry and molecular biology facilitate the characterization of cytochrome P450 isoforms responsible for tissue/organ specific arachidonic acid epoxidation and omega/omega-1 hydroxylation, and thus, the analysis of cDNA and/or gene specific functional phenotypes. The combined application of physiological, biochemical, molecular, and genetic approaches is beginning to provide new insights into the physiological and/or pathophysiological significance of these enzymes, their endogenous substrates, and products.