Phospholipid and fatty acid specificity of endothelial lipase: Potential role of the enzyme in the delivery of docosahexaenoic acid (DHA) to tissues

Phospholipid and fatty acid specificity of endothelial lipase: Potential role of the enzyme in the delivery of docosahexaenoic acid (DHA) to tissues
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DOI:
10.1016/j.bbalip.2007.08.001
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发表时间:
2007-10-01
影响因子:
4.8
通讯作者:
Subbaiah, Papasani V.
Subbaiah, Papasani V.
中科院分区:
生物学2区
文献类型:
--
作者:
Chen, Su;Subbaiah, Papasani V.

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二十二碳六烯酸(DHA;22:6n-3)是几种组织,尤其是大脑正常功能所必需的一种必需脂肪酸。以往的研究表明,溶血磷脂酰胆碱是DHA在脑内的首选载体,但血浆中含有DHA的溶血磷脂的形成途径尚未阐明。我们认为,内皮脂酶(EL)是一种在高密度脂蛋白代谢中起重要作用的磷脂酶A,它可能与血浆中DHA溶血磷脂的生成有关。在这里,我们使用不同极性头基的氚标记磷脂以及富含DHA的天然磷脂来研究EL的底物特异性,以验证这一假说。用重组电致发光对甘油稳定的磷脂进行处理,并用高效液相色谱/电喷雾电离质谱仪对产物进行分析。电致发光以phosphatidylethanolamine>phosphatidylcholine>phosphatidyiserine>phosphatidic酸的顺序显示了极性头基的特异性。在同一类磷脂中,该酶优先选择sn-2位含DHA的物种,而对含醚键的磷脂不起作用。由于已知EL是由血脑屏障的细胞分泌的,我们认为它在DHA溶血磷脂载体进入大脑的过程中起着重要的作用。(C)2007 Elsevier B.V.保留所有权利。
Docosahexaenoic acid (DHA; 22:6 n-3) is an essential fatty acid required for the normal function of several tissues, especially the brain. Previous studies suggested that lysophosphatidylcholine (lysoPC) is a preferred carrier of DHA to the brain, although the pathways of the formation of DHA-containing lysophospholipids in plasma have not been delineated. We propose that endothelial lipase (EL), a phospholipase A, that plays an important role in the metabolism of high density lipoproteins, may be responsible for the generation of DHA lysophospholipids in plasma. Here we studied the substrate specificity of EL using deuterium-labeled phospholipids with different polar head groups, as well as DHA-enriched natural phospholipids to test this hypothesis. Glycerol-stabilized phospholipids were treated with recombinant EL, and the products were analyzed by liquid chromatography/electrospray ionization mass spectrometry. EL showed the polar head group specificity in the order of phosphatidylethanolamine>phosphatidylcholine>phosphatidyiserine>phosphatidic acid. Within the same phospholipid class, the enzyme showed preference for the species containing DHA at the sn-2 position, and was inactive in the hydrolysis of phospholipids containing an ether linkage. Since EL is known to be secreted by the cells of blood-brain barrier, we suggest that it plays an important role in the delivery of DHA lysophospholipid carriers to the brain. (c) 2007 Elsevier B.V. All rights reserved.