Dix T A, Marnett L J
J Biol Chem. 1985 May 10;260(9):5351-7.
We have carried out a study of the reaction of 13-hydroperoxy-9-cis,11-trans-octadecadienoic acid (linoleic acid hydroperoxide) with hematin. The major products are erythro-11-hydroxy-12,13-epoxy-9-octadecenoic acid, threo-11-hydroxy-12,13-epoxy-9-octadecenoic acid, 9,12,13-trihydroxy-10-octadecenoic acid, 13-keto-9,11-octadecadienoic acid, and 13-hydroxy-9,11-octadecadienoic acid. Several minor products have also been identified, including 9-hydroxy-12,13-epoxyoctadecenoic acid, 11-hydroxy-9,10-epoxy-12-octadecenoic acid, 9-hydroxy-10,12-octadecadienoic acid, and 9-keto-10,12-octadecadienoic acid. Oxygen labeling studies indicate that the observed products arise by at least two pathways. In the major pathway, hematin reduces 13-hydroperoxy-9,11-octadecadienoic acid by one electron to an alkoxyl radical that cyclizes to an adjacent double bond to form an epoxy allylic radical. The allylic radical either couples to the hydroxyl radical coordinated to hematin or diffuses from the solvent cage and couples to O2, forming a peroxyl radical. In the minor pathway, the hydroperoxide is oxidized by one electron to a 13-peroxyl radical that undergoes beta-scission to a pentadienyl radical and O2. Exchange of hydroperoxide-derived O2 for dissolved O2 occurs at this stage followed by coupling of O2 to either terminus of the pentadienyl radical. Both pathways of hydroperoxide metabolism generate significant quantities of peroxyl radicals that epoxidize the isolated double bonds of dihydroaromatic molecules. The products of hydroperoxide reaction with hematin and the oxygen labeling patterns are very similar to the products of unsaturated fatty acid hydroperoxide metabolism by platelets, aorta, and lung. Our results not only provide a mechanism for the formation of a series of mammalian metabolites of linoleic and arachidonic acids but also offer an estimate of the yield of peroxyl radicals generated during the process.
我们开展了一项关于13 - 氢过氧 - 9 - 顺式，11 - 反式 - 十八碳二烯酸（亚油酸氢过氧化物）与血红素反应的研究。主要产物有赤藓糖型11 - 羟基 - 12,13 - 环氧 - 9 - 十八碳烯酸、苏阿糖型11 - 羟基 - 12,13 - 环氧 - 9 - 十八碳烯酸、9,12,13 - 三羟基 - 10 - 十八碳烯酸、13 - 酮基 - 9,11 - 十八碳二烯酸和13 - 羟基 - 9,11 - 十八碳二烯酸。还鉴定出了几种次要产物，包括9 - 羟基 - 12,13 - 环氧十八碳烯酸、11 - 羟基 - 9,10 - 环氧 - 12 - 十八碳烯酸、9 - 羟基 - 10,12 - 十八碳二烯酸和9 - 酮基 - 10,12 - 十八碳二烯酸。氧标记研究表明，观察到的产物至少通过两条途径生成。在主要途径中，血红素将13 - 氢过氧 - 9,11 - 十八碳二烯酸单电子还原为烷氧基自由基，该自由基环化至相邻双键形成环氧烯丙基自由基。烯丙基自由基要么与配位至血红素的羟基自由基偶联，要么从溶剂笼中扩散并与O₂偶联，形成过氧自由基。在次要途径中，氢过氧化物被单电子氧化为13 - 过氧自由基，该自由基发生β - 断裂生成戊二烯基自由基和O₂。在此阶段，氢过氧化物衍生的O₂与溶解的O₂发生交换，随后O₂与戊二烯基自由基的任一末端偶联。氢过氧化物代谢的两条途径都会产生大量过氧自由基，这些自由基会使二氢芳香分子中孤立的双键环氧化。氢过氧化物与血红素反应的产物及氧标记模式与血小板、主动脉和肺中不饱和脂肪酸氢过氧化物代谢的产物非常相似。我们的结果不仅为一系列亚油酸和花生四烯酸的哺乳动物代谢产物的形成提供了一种机制，还对该过程中产生的过氧自由基的产量进行了估计。
