The production of the arachidonate metabolite HETE in vascular tissue
The production of the arachidonate metabolite HETE in vascular tissue
复制标题
血管组织中花生四烯酸代谢物 HETE 的产生
作者：
J. Greenwald;J. Bianchine;L. Wong
血小板含有两个酶系统，它们都是花生四烯酸（AA）。首先是一种环加氧酶1，它将AA代谢成生物活性的前列腺素内过氧化物（PGG 2和PGH 2），后者是血小板前列腺素PGE 2、PGF 2 α和血栓烷A2（TxA 2）的前体。第二，将AA代谢成12-L-氢过氧-5，8，10，14-二十碳四烯酸（HPETE）的脂氧合酶1，2。HPETE是一种不稳定的中间体，其在水性环境中被非酶促还原为更稳定的代谢物12-L-羟基-5，8，10，14-二十碳四烯酸（HETE）。HPETE由聚集的血小板大量产生，但其确切的生物学作用尚不清楚。Turner等人3认为HETE可能是中性粒细胞趋化性的介导物。Vane及其同事证明，15-氢过氧-5，8，10，14-二十碳四烯酸4，5以及HPETE是前列环素（PGI 2）的强效抑制剂，PGI 2是血管组织中主要的花生四烯酸代谢物。这些数据表明，HPETE，如果存在于血管组织中，可能作为PGI 2生产的内源性调节剂。利用放射化学技术和质谱，我们现在已经确定了一种脂氧合酶在血管组织（兔主动脉），其中也发生HETE的生物合成。HETE的检测表明脂氧合产物作为PGI 2生物合成的内源性调节剂的潜在作用。
Blood platelets contain two enzyme systems which oxygenate arachidonic acid (AA). First, a cyclooxygenase1 which metabolises AA into the biologically active prostaglandin endoperoxides (PGG2 and PGH2) which are precursors for the platelet prostaglandins PGE2, PGF2α and thromboxane A2 (TxA2). And second, a lipoxygenase that metabolises AA into 12-L-hydroperoxy-5, 8, 10, 14-eicosatetraenoic acid (HPETE)1,2. HPETE is a labile intermediate which is nonenzymatically reduced in aqueous environments to a more stable metabolite, 12-L-hydroxy-5, 8, 10, 14-eicosatetraenoic acid (HETE). HPETE is produced in significant quantities by aggregated platelets, but its exact biological role is not known. Turner et al.3 has suggested that HETE may be a mediator of neutrophil chemotaxis. Vane and coworkers demonstrated that 15-hydroperoxy-5, 8, 10, 14-eicosatetraenoic acid4,5 as well as HPETE were potent inhibitors of prostacyclin (PGI2), the major arachidonate metabolite in vascular tissue. These data suggest that HPETE, if present in vascular tissue, might act as endogenous regulator of PGI2 production. Using radiochemical techniques and mass sspectrometry we have now identified a lipoxygenase enzyme in vascular tissue (rabbit aorta) in which biosynthesis of HETE also occurred. The detection of HETE in this suggests a potential role of the lipoxygenated product as an endogenous regulator of PGI2 biosynthesis.