Monolayer autoxidation of arachidonic acid to epoxyeicosatrienoic acids as a model of their potential formation in cell membranes.
Monolayer autoxidation of arachidonic acid to epoxyeicosatrienoic acids as a model of their potential formation in cell membranes.
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DOI：
10.1016/j.jlr.2021.100159
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发表时间：
2022-01
影响因子：
6.5
通讯作者：
Brash AR
中科院分区：
文献类型：
--
作者：
Weiny JA;Boeglin WE;Calcutt MW;Stec DF;Brash AR
鉴于epoxyeicosatrienoic acids（ESTs）在哺乳动物病理生理学中的重要性，可能在细胞中形成这些单环氧化物的非酶途径具有重要意义。在20世纪70年代后期，设计了一种简单的系统，将亚油酸分子排列在二氧化硅上的单层上，并显示出产生单环氧化物作为主要的自氧化产物。在这里，我们研究了这个系统与花生四烯酸和其特征在于的主要产品。通过LC-MS和HPLC-UV检测到的自氧化早期阶段（花生四烯酸的转化率约10%）的主要产物是14，15-、11，12-和8，9-EET，其中5，6-EET主要代表5-δ-内酯-6-羟基二十碳三烯酸酯，如1H-NMR所确定的。结果表明，环氧化合物主要为顺式环氧化物，反式构型较少.在四种氘代溶剂中的1H-NMR分析有助于澄清环氧化物构型。EET在单层中的形成涉及与脂肪酸过氧自由基的分子间反应，产生EET并留下初始的和更具反应性的烷氧基自由基，其进而产生环氧-氢（佩罗）氧化物和其他极性产物。脂肪酸分子的单层排列类似于脂肪酸在细胞膜中的排列，在脂质过氧化的条件下，这种分子间机制可能有助于在生物膜中形成EET。
In light of the importance of epoxyeicosatrienoic acids (EETs) in mammalian pathophysiology, a nonenzymatic route that might form these monoepoxides in cells is of significant interest. In the late 1970s, a simple system of arranging linoleic acid molecules on a monolayer on silica was devised and shown to yield monoepoxides as the main autoxidation products. Here, we investigated this system with arachidonic acid and characterized the primary products. By the early stages of autoxidation (∼10% conversion of arachidonic acid), the major products detected by LC-MS and HPLC-UV were the 14,15-, 11,12-, and 8,9-EETs, with the 5,6-EET mainly represented as the 5-δ-lactone-6-hydroxyeicosatrienoate as established by 1H-NMR. The EETs were mainly the cis epoxides as expected, with minor trans configuration EETs among the products. 1H-NMR analysis in four deuterated solvents helped clarify the epoxide configurations. EET formation in monolayers involves intermolecular reaction with a fatty acid peroxyl radical, producing the EET and leaving an incipient and more reactive alkoxyl radical, which in turn gives rise to epoxy-hydro(pero)xides and other polar products. The monolayer alignment of fatty acid molecules resembles the arrangements of fatty acids in cell membranes and, under conditions of lipid peroxidation, this intermolecular mechanism might contribute to EET formation in biological membranes.
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影响因子：
3.9
作者：
BRASH, AR;BOEGLIN, WE;BLAIR, IA
通讯作者：
BLAIR, IA
影响因子：
4.8
作者：
Graves, Joan P.;Bradbury, J. Alyce;Zeldin, Darryl C.
通讯作者：
Zeldin, Darryl C.
DOI：
10.1016/0006-291x(87)90576-6
发表时间：
1987-07-31
影响因子：
3.1
作者：
CAPDEVILA, JH;KISHORE, V;FALCK, JR
通讯作者：
FALCK, JR
影响因子：
3.6
作者：
Chen, JY;Capdevila, JH;Rosenberg, RL
通讯作者：
Rosenberg, RL
DOI：
10.1152/ajpheart.01267.2010
发表时间：
2011-06-01
影响因子：
4.8
作者：
Jiang, Houli;Quilley, John;Carroll, Mairead A.
通讯作者：
Carroll, Mairead A.