Schneider Claus, Boeglin William E, Yin Huiyong, Stec Donald F, Voehler Markus
Department of Pharmacology, Division of Clinical Pharmacology, 23rd Avenue South at Pierce, Vanderbilt University Medical School, Nashville, Tennessee 37232, USA.
J Am Chem Soc. 2006 Jan 25;128(3):720-1. doi: 10.1021/ja056517y.
5-Lipoxygenase and cyclooxygenase-2 (COX-2) initiate the biosynthesis of distinct families of mediators from arachidonic acid (leukotrienes and prostaglandins, respectively) and are each the target of anti-inflammatory medications. Here we show that the product of 5-lipoxygenase, 5S-hydroxyeicosatetraenoic acid, is selectively and efficiently triply oxygenated by COX-2, implicating a cross-pathway interaction. The product is a unique diendoperoxide, potentially representing the parent compound of a novel group of lipid mediators.
5-脂氧合酶和环氧化酶-2（COX-2）分别启动花生四烯酸生成不同介质家族（分别为白三烯和前列腺素）的生物合成过程，且二者均为抗炎药物的作用靶点。我们在此表明，5-脂氧合酶的产物5S-羟基二十碳四烯酸可被COX-2选择性且高效地进行三次加氧，这意味着存在跨途径相互作用。该产物是一种独特的双环内过氧化物，可能代表一类新型脂质介质的母体化合物。
