Cytochrome P450 ω-Hydroxylases in Inflammation and Cancer.
Cytochrome P450 ω-Hydroxylases in Inflammation and Cancer.
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DOI：
10.1016/bs.apha.2015.05.002
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Rettie AE
中科院分区：
文献类型：
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作者：
Johnson AL;Edson KZ;Totah RA;Rettie AE
细胞色素P450依赖性ω-羟基化是CYP 4家族成员的原型代谢反应，不仅对治疗药物，而且对内源性化合物（主要是脂肪酸）的消除和生物活化都很重要。衍生自花生四烯酸的类二十烷酸是后一类中的关键底物。人CYP 4酶，主要是CYP 4A 11、CYP 4F 2和CYP 4F 3B，在ω位羟基化花生四烯酸以形成20-HETE，其在肿瘤进展以及血管和肾脏中的血管生成和血压调节中具有重要作用。髓样组织中的CYP 4F 3A催化白三烯B4的ω-羟基化为20-羟基白三烯B4，这是一个对炎症反应调节至关重要的失活过程。在这里，我们回顾了酶学，组织分布和底物选择性的人CYP 4 ω-羟化酶及其催化剂的作用，形成和终止的关键类花生酸代谢产物的生物学效应的炎症和癌症的进展。
Cytochrome P450-dependent ω-hydroxylation is a prototypic metabolic reaction of CYP4 family members that is important for the elimination and bioactivation of not only therapeutic drugs, but also endogenous compounds, principally fatty acids. Eicosanoids, derived from arachidonic acid, are key substrates in the latter category. Human CYP4 enzymes, mainly CYP4A11, CYP4F2, and CYP4F3B, hydroxylate arachidonic acid at the omega position to form 20-HETE, which has important effects in tumor progression and on angiogenesis and blood pressure regulation in the vasculature and kidney. CYP4F3A in myeloid tissue catalyzes the ω-hydroxylation of leukotriene B4 to 20-hydroxy leukotriene B4, an inactivation process that is critical for the regulation of the inflammatory response. Here, we review the enzymology, tissue distribution, and substrate selectivity of human CYP4 ω-hydroxylases and their roles as catalysts for the formation and termination of the biological effects of key eicosanoid metabolites in inflammation and cancer progression.