Rao G H, Radha E, White J G
Biochem Biophys Res Commun. 1983 Dec 16;117(2):549-55. doi: 10.1016/0006-291x(83)91235-4.
Studies from our laboratory have suggested a role for ferrous iron in the metabolism of arachidonic acid and demonstrated that inhibitors of prostaglandin synthesis exert their effect by complexing with the heme group of cyclooxygenase. Docosahexaenoic acid (DHA) is a potent competitive inhibitor of arachidonic acid metabolism by sheep vesicular gland prostaglandin synthetase. In this study we have evaluated the effect of exogenously added DHA on platelet function and arachidonic acid metabolism. DHA at 150 microM concentration inhibited aggregation of platelets to 450 microM arachidonic acid. At this concentration DHA also inhibited the second wave of the platelet response to the action of agonists such as epinephrine, adenosine diphosphate and thrombin. Inhibition induced by this fatty acid could be overcome by the agonists at higher concentrations. DHA inhibited the conversion of labeled arachidonic acid to thromboxane by intact, washed platelet suspensions. However, platelets in plasma incubated first with DHA then washed and stirred with labeled arachidonate generated as much thromboxane as control platelets. These results suggest that the polyenoic acids, if released in sufficient quantities in the vicinity of cyclooxygenase, could effectively compete for the heme site and inhibit the conversion of arachidonic acid.
我们实验室的研究表明亚铁在花生四烯酸代谢中发挥作用，并证明前列腺素合成抑制剂通过与环氧化酶的血红素基团结合发挥作用。二十二碳六烯酸（DHA）是绵羊精囊前列腺素合成酶对花生四烯酸代谢的一种有效竞争性抑制剂。在本研究中，我们评估了外源性添加DHA对血小板功能和花生四烯酸代谢的影响。浓度为150微摩尔的DHA将血小板对450微摩尔花生四烯酸的聚集抑制至一定程度。在此浓度下，DHA还抑制了血小板对肾上腺素、二磷酸腺苷和凝血酶等激动剂作用的第二波反应。这种脂肪酸诱导的抑制作用可被更高浓度的激动剂克服。DHA抑制完整的、洗涤过的血小板悬液将标记的花生四烯酸转化为血栓素。然而，先与DHA孵育然后洗涤并与标记的花生四烯酸搅拌的血浆中的血小板产生的血栓素与对照血小板一样多。这些结果表明，如果多不饱和脂肪酸在环氧化酶附近大量释放，它们可以有效地竞争血红素位点并抑制花生四烯酸的转化。
