Cytochrome P450 4A fatty acid omega hydroxylases.
Cytochrome P450 4A fatty acid omega hydroxylases.
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DOI：
10.2174/1389200013338423
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发表时间：
2001-08
影响因子：
2.3
通讯作者：
R. Okita;J. Okita
中科院分区：
文献类型：
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作者：
R. Okita;J. Okita
细胞色素P450 4A亚家族是CYP 4家族的18个亚家族之一，目前在9种不同的哺乳动物中由20种单独的形式组成。CYP 4A形式的主要底物是脂肪酸，但最近的研究表明，其他非脂肪酸底物可能被特定的CYP 4A形式代谢。CYP 4A亚家族的生理和代谢功能尚未阐明，但CYP 4A形式在其ω（ω）-碳原子处代谢中链和长链脂肪酸的能力已经引起了极大的兴趣，因为ω-羟基化脂肪酸在细胞信号传导过程中可能具有的作用以及作为脂肪酸代谢的替代途径。许多不同的化合物或生理条件已显示调节肝脏和/或肾脏中CYP 4A形式的表达。几种CYP 4A形式可作为暴露于被归类为过氧化物酶体增殖剂的化合物的标志物。为什么多种CYP 4A形式存在于不同的组织中也有相当大的兴趣。最近在大鼠和人类中的研究表明，除了CYP 4A形式之外，其他CYP 4形式可能负责花生四烯酸代谢为其ω-羟基产物。本文重点综述了近年来对大鼠、兔和人CYP 4A底物特异性的研究，并讨论了CYP 4A介导的脂肪酸羟基化的意义。此外，饮食的影响或新的化合物，已报告调节CYP 4A在大鼠和小鼠的表达将进行讨论。
The Cytochrome P450 4A subfamily is one of eighteen subfamilies in the CYP4 family and presently consists of twenty individual forms in nine different mammalian species. The major substrates for CYP4A forms are fatty acids, but recent studies have shown other non-fatty acid substrates may be metabolized by specific CYP4A forms. The physiological and metabolic functions of the CYP4A subfamily have not been elucidated, but the ability of CYP4A forms to metabolize medium and long chain length fatty acids at their omega (omega)-carbon atom has generated significant interest because of the possible role that omega-hydroxylated fatty acids may have in cell signalling processes and as an alternative pathway for fatty acid metabolism. A number of different compounds or physiological conditions have been shown to regulate the expression of CYP4A forms in liver and/or kidney. Several CYP4A forms may serve as a marker for the exposure to compounds that are classified as peroxisome proliferators. There is also considerable interest why multiple CYP4A forms exist in different tissues. Recent studies in the rat and human indicate that other CYP4 forms besides CYP4A forms may be responsible for the metabolism of arachidonic acid to its omega-hydroxy product. The focus of this review will be to summarize recent studies that have characterized the substrate specificity of rat, rabbit and human CYP4A forms and discuss the significance of CYP4A-mediated hydroxylation of fatty acids. In addition, dietary effects or novel compounds that have been reported to regulate CYP4A expression in the rat and mouse will be discussed.