期刊
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
卷 1864, 期 6, 页码 772-783出版社
ELSEVIER
DOI: 10.1016/j.bbalip.2018.07.002
关键词
Phospholipase A(2); Lipid mediator; Glycerophospholipid; Arachidonic acid; Docosahexaenoic acid; Transacylase; Monocyte; Macrophage; Inflammation; Innate immunity
资金
- Spanish Ministry of Economy, Industry and Competitiveness [SAF2016-80883-R, SAF2015-73000-EXP]
- Education Department of the Regional Government of Castile and Leon [CSI073U16]
Phospholipase A(2)s are enzymes that hydrolyze the fatty acid at the sn-2 position of the glycerol backbone of membrane glycerophospholipids. Given the asymmetric distribution of fatty acids within phospholipids, where saturated fatty acids tend to be present at the sn-1 position, and polyunsaturated fatty acids such as those of the omega-3 and omega-6 series overwhelmingly localize in the sn-2 position, the phospholipase A(2) reaction is of utmost importance as a regulatory checkpoint for the mobilization of these fatty acids and the subsequent synthesis of proinflammatory omega-6-derived eicosanoids on one hand, and omega-3-derived specialized proresolving mediators on the other. The great variety of phospholipase A(2)s, their differential substrate selectivity under a variety of pathophysiological conditions, as well as the different compartmentalization of each enzyme and accessibility to substrate, render this class of enzymes also key to membrane phospholipid remodeling reactions, and the generation of specific lipid mediators not related with canonical metabolites of omega-6 or omega-3 fatty acids. This review highlights novel findings regarding the selective hydrolysis of phospholipids by phospholipase A(2)s and the influence this may have on the ability of these enzymes to generate distinct lipid mediators with essential functions in biological processes. This brings a new understanding of the cellular roles of these enzymes depending upon activation conditions.
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