CYTOCHROME P-450-DEPENDENT OXYGENATION OF ARACHIDONIC-ACID TO HYDROXYICOSATETRAENOIC ACIDS
CYTOCHROME P-450-DEPENDENT OXYGENATION OF ARACHIDONIC-ACID TO HYDROXYICOSATETRAENOIC ACIDS
复制标题
DOI：
10.1073/pnas.79.3.767
复制
发表时间：
1982-01-01
期刊：
影响因子：
--
通讯作者：
ESTABROOK, RW
中科院分区：
文献类型：
--
作者：
CAPDEVILA, J;MARNETT, LJ;ESTABROOK, RW
花生四烯酸被大鼠肝微粒体的 NADPH 依赖性加氧酶氧化成许多含 O2 的产物，这些产物可以通过高压液相色谱法进行解析。其中一些产品经过纯化和表征。它们在光谱的 UV 区域表现出吸光度，在 235 nm 处具有最大值，表明存在共轭二烯官能团。氢化和非氢化代谢物甲酯的三甲基甲硅烷基醚衍生物的质谱分析表明它们是花生四烯酸（羟基二十碳四烯酸（HETE））的9-、11-、12-和15-单羟基衍生物。它们的紫外吸光度和色谱特性表明这些产品具有从其他哺乳动物来源分离的 HETE 的顺式、反式二烯几何特征。这些异构体 HETE 的分离表明细胞色素 P-450 可能在花生四烯酸氧化代谢为生理学和药理学上重要的羟基化不饱和脂肪酸中发挥作用。
Arachidonic acid is oxidized by a NADPH-dependent oxygenase of rat liver microsomes to a number of O2-containing products, which can be resolved by high pressure liquid chromatography. Several of these products were purified and characterized. They exhibit an absorbance in the UV region of the spectrum that has a maximum at 235 nm, indicative of the presence of a conjugated diene function. Mass spectral analysis of the trimethylsilyl ether derivatives of the methyl esters of the hydrogenated and nonhydrogenated metabolites shows that they are the 9-, 11-, 12- and 15-monohydroxy derivatives of arachidonic acid, the hydroxyicosatetraenoic acids (HETE). Their UV absorbance and chromatographic properties suggest that these products possess cis, trans-diene geometry characteristic of HETE isolated from other mammalian sources. The isolation of these isomeric HETE suggests that cytochrome P-450 may play a role in the oxidative metabolism of arachidonic acid to physiologically and pharmacologically important hydroxylated unsaturated fatty acids.