Rao G H, Gerrard J M, Eaton J W, White J G
Prostaglandins Med. 1978 Jul;1(1):55-70. doi: 10.1016/0161-4630(78)90077-0.
Arachidonic acid (AA) is the essential substrate for production of platelet endoperoxides and thromboxanes. Iron or heme is an essential cofactor for the peroxidase, lipoxygenase and cyclo-oxygenase enzymes involved in formation of these products. The present study has examined the direct interactions between iron and arachidonic acid. Iron caused the oxidation of AA into more polar products which could be detected by UV absorbtion at 232 nM or the thiobarbituric acid (TBA) reaction. High pressure liquid chromatography, chem-ionization and electron-impact mass spectrometry and nuclear magnetic resonance spectroscopy suggest that the major product was a hydroperoxide of AA. Ferrous iron (Fe++) and oxygen were absolute requirements. Fe++ was converted to the ferric iron (Fe+++) state during oxidation of AA, but Fe+++ could not substitute for Fe++. No other enzymes, cofactors or ions were involved. Conversion of AA to a hydroperoxide by Fe++ was inhibited by the antioxidant, 2, (3)-Tert-butyl-4-hydroxyanisole, the radical scavenger, nitroblue tetrazolium, and iron chelating agents, including EDTA, imidazole and dihydroxybenzoic acid. The reaction was not affected by superoxide dismutase, catalase or aspirin. These findings and preliminary studies of the Fe++ induced oxidation product of AA as a substrate for prostaglandin synthesis and inhibitor of prostacyclin production indicate the critical role of Fe++ in AA activation.
花生四烯酸（AA）是血小板内过氧化物和血栓烷生成的必需底物。铁或血红素是参与这些产物形成的过氧化物酶、脂氧合酶和环氧化酶的必需辅因子。本研究检测了铁与花生四烯酸之间的直接相互作用。铁导致AA氧化成极性更强的产物，这些产物可通过在232 nM处的紫外吸收或硫代巴比妥酸（TBA）反应检测到。高压液相色谱、化学电离和电子轰击质谱以及核磁共振光谱表明，主要产物是AA的氢过氧化物。亚铁（Fe++）和氧气是绝对必需的。在AA氧化过程中，Fe++转化为三价铁（Fe+++）状态，但Fe+++不能替代Fe++。不涉及其他酶、辅因子或离子。抗氧化剂2,（3）-叔丁基-4-羟基茴香醚、自由基清除剂硝基蓝四唑以及包括EDTA、咪唑和二羟基苯甲酸在内的铁螯合剂可抑制Fe++将AA转化为氢过氧化物的反应。该反应不受超氧化物歧化酶、过氧化氢酶或阿司匹林的影响。这些发现以及对作为前列腺素合成底物和前列环素生成抑制剂的AA的Fe++诱导氧化产物的初步研究表明，Fe++在AA活化中起关键作用。
