IDENTIFICATION AND BIOLOGICAL-ACTIVITY OF NOVEL OMEGA-OXIDIZED METABOLITES OF LEUKOTRIENE B4 FROM HUMAN-LEUKOCYTES
IDENTIFICATION AND BIOLOGICAL-ACTIVITY OF NOVEL OMEGA-OXIDIZED METABOLITES OF LEUKOTRIENE B4 FROM HUMAN-LEUKOCYTES
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DOI：
10.1016/0014-5793(81)80676-x
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发表时间：
1981-01-01
期刊：
影响因子：
3.5
通讯作者：
SAMUELSSON, B
中科院分区：
文献类型：
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作者：
HANSSON, G;LINDGREN, JA;SAMUELSSON, B
白三烯构成了一组新的衍生自多不饱和脂肪酸的生物活性化合物[11]。因此，花生四烯酸可以通过脂氧合酶氧化为SS-氢过氧二十碳四烯酸[2]，其进一步转化为不稳定的环氧化物，5，6-氧化-7，9，11，14-二十碳四烯酸（白三烯Aq，LTA 4）[3，4]。通过添加谷胱甘肽将该中间体酶促转化为“过敏性慢反应物质”（SRS-A），LTC 4 [5，6]。大多数SRS-A制剂的生物活性是由于LTC 4和两种代谢产物LTD 4和LTE 4 [7-91]。LTA 4也可以酶促水解成5S，12 R-二羟基-6-顺式，8，10-反式，14-顺式-二十碳四烯酸（LTB 4）[1012]或非酶促水解成异构的5，12-和5，6-二羟基-二十碳四烯酸[131.我们已经报道了一种新的二羟基酸，5S，12 S-二羟基-6-反式，8-顺式，10-反式，14-顺式-二十碳四烯酸（SS，12 SDHETE）在人白细胞制备物中的形成[14]。这种二羟基酸不是通过环氧化物中间体形成的，而是通过花生四烯酸的双重氧化形成的。此外，还鉴别出一种ω-羟基化代谢产物5S，12 S，20-三羟基-6-反式，8-顺式，10-反式，1 LF-顺式-二十碳四烯酸（5S，12 S，20-THETE）。本报告描述了LTB_4，5S，12 R，20-三羟基-6-顺式，10-反式，14-S-二十碳四烯酸（20-OHLTB_4）在人白细胞制剂中的ω-羟基化代谢产物的形成，以及该三羟基酸进一步转化为二羧酸（20-COOH-LTB_4）。此外，还报道了LTB 4、20-OH-LTB 4和20-COOH-LTB 4对豚鼠肺条的生物活性。
The leukotrienes constitute a new group of biologically active compounds derived from polyunsaturated fatty acids [11. Thus, arachidonic acid can be oxygenated by a lipoxygenase to SS-hydroperoxyeicosatetraenoic acid [2], which is further converted to an unstable epoxide, 5, 6-oxido-7, 9, 11, 14-eicosatetraenoic acid (leukotriene Aq, LTA4)[3, 4]. This intermediate is transformed enzymatically by addition of glutathione into a ‘slow-reacting substance of anaphylaxis’(SRS-A), LTC4 [5, 6]. The biological activity of most SRS-A preparations is due to LTC4 and the two metabolites LTD4 and LTE4 [7-91. LTA4 can also be hydrolyzed enzymatically to 5S, 12R-dihydroxy-6-cis, 8, 1O-trans, l4-cis-eicosatetraenoic acid (LTB4)[1 Ol 2] or non-enzymatically to isomeric 5, 12-and 5, 6-dihydroxy-eicosatetraenoic acids [131. We have reported the formation of a novel dihydroxy-acid, 5S, 12S-dihydroxy-6-trans, 8-cis, lO-trans, l4-cis-eicosatetraenoic acid (SS, 12SDHETE), in preparations of human leukocytes [14). This dihydroxy-acid was not formed via an epoxide intermediate, but by a double oxygenation of arachidonic acid. In addition, an w-hydroxylated metabolite, 5S, 12S, 20-trihydroxy-6-trans, 8-cis, lO-trarzs, lLF-cis-eicosatetraenoic acid (5S, 12S, 20-THETE), was identified. This report describes the formation of an w-hydroxylated metabolite of LTB4, 5S, 12R, 20-trihydroxy-6-cis $, lO-trans, l4&s-eicosatetraenoic acid (20-OHLTB4) in human leukocyte preparations and further conversion of this trihydroxy acid to a dicarboxylic acid (20-COOH-LTB4). In addition, the biological activity of LTB4, 20-OH-LTB4 and 20-COOH-LTB4, on guinea pig lung strips is reported.