Arachidonate metabolism via lipoxygenase and 12L-hydroperoxy-5,8,10,14-icosatetraenoic acid peroxidase sensitive to anti-inflammatory drugs.
Arachidonate metabolism via lipoxygenase and 12L-hydroperoxy-5,8,10,14-icosatetraenoic acid peroxidase sensitive to anti-inflammatory drugs.
复制标题
花生四烯酸通过脂氧合酶和 12L-氢过氧-5,8,10,14-二十碳四烯酸过氧化物酶代谢，对抗炎药物敏感。
DOI：
10.1073/pnas.77.1.308
复制
发表时间：
1980
影响因子：
11.1
通讯作者：
P. Cuatrecasas
中科院分区：
文献类型：
--
作者：
M. Siegel;R. McConnell;N. Porter;P. Cuatrecasas
通过脂氧合酶途径对人血小板胞浆中花生四烯酸代谢的酶进行了表征和部分纯化。脂加氧酶的最适pH值为7.3，在花生四烯酸浓度为80 μ m时达到半最大值。这些酶对花生四烯酸酯的氧化被修饰巯基的试剂所抑制。用Sephadex G-150层析和DEAE-Sephadex层析分别检测两种可分离的脂氧合酶活性。其中一个的Mr值明显为100,000。第二种酶表现为Mr为160,000的实体，除了含有脂氧合酶外，还含有催化12l -羟基-5,8,10,14-二十碳四烯酸（HPETE）转化为12l -羟基-5,8,10,14-二十碳四烯酸（HETE）的过氧化物酶活性。阿司匹林、吲哚美辛、水杨酸钠、苯丁酮、布洛芬、萘普生和舒林酸，但对乙酰氨基酚或非那西丁不会导致脂氧合酶途径中HPETE水平升高。HPETE水平的增加是由于这些药物能够直接抑制HPETE向HETE的酶转化。
The enzymes of arachidonate metabolism via the lipoxygenase pathway in human platelet cytosol have been characterized and partially purified. The lipoxygenase activity has a pH optimum of 7.3 and reaches half-maximal activity at an arachidonate concentration of 80 microM. The oxidation of arachidonate by these enzymes is inhibited by reagents that modify sulfhydryl groups. Two separable lipoxygenase activities can be detected by chromatography of platelet cytosol on Sephadex G-150 and of partially purified preparations on DEAE-Sephadex. One of these has an apparent Mr of 100,000. A second enzyme species behaves as a Mr 160,000 entity containing, in addition to lipoxygenase, a peroxidase activity that catalyzes the conversion of 12L-hydroperoxy-5,8,10,14-icosatetraenoic acid (HPETE) to 12L-hydroxy-5,8,10,14-icosatetraenoic acid (HETE). Aspirin, indomethacin, sodium salicylate, phenylbutazone, ibuprofen, naproxen, and sulindac, but not acetaminophen or phenacetin, give rise to increased levels of HPETE in the lipoxygenase pathway. This increase in HPETE levels is the result of the ability of these drugs to inhibit directly the enzymatic conversion of HPETE to HETE.