title: Secreted Phospholipase A2Specificity on Natural Membrane Phospholipids.
abstract: The secreted phospholipase A2(sPLA2) family contains 10 catalytically active isoforms. Current in vitro biochemical studies have shown that individual sPLA2s have distinct substrate selectivity in terms of the polar head groups or sn-2 fatty acids of their substrate phospholipids. Importantly, transgenic or knockout mice for distinct sPLA2s display nonoverlapping phenotypes, arguing that they do act on different phospholipid substrates and mobilize unique lipid metabolites in vivo. In an effort to comprehensively understand lipid metabolism driven by individual sPLA2s under pathophysiological conditions, we took advantages of mass spectrometric lipidomics technology to monitor the spatiotemporal changes in phospholipids (substrates) and products (fatty acids, lysophospholipids, and their metabolites) in tissues or cells of sPLA2-transgenic or knockout mice. The in vivo lipidomic data were compared with the in vitro activity of recombinant sPLA2s toward phospholipid mixtures extracted from the target tissues, cells, or extracellular membrane components on which sPLA2s may intrinsically act. These approaches reveal that the overall tendency in in vitro assays using natural membranes is recapitulated in several in vivo systems, often with even more selective patterns of hydrolysis. In this chapter, we will summarize current understanding of the in vivo substrate specificity of sPLA2s toward natural membrane phospholipids.
authors.affiliation: Lipid Metabolism Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan; Faculty of Bioscience and Bioindustry, Tokushima University, Tokushima, Japan; PRIME, Japan Agency for Medical Research and Development, Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Yamamoto
authors.affiliation: Lipid Metabolism Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Miki
authors.affiliation: Lipid Metabolism Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Sato
authors.affiliation: Lipid Metabolism Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
authors.forename: R
authors.initials: R
authors.lastname: Murase
authors.affiliation: Lipid Metabolism Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Taketomi
authors.affiliation: Lipid Metabolism Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan; AMED-CREST, Japan Agency for Medical Research and Development, Tokyo, Japan. Electronic address: murakami-mk@igakuken.or.jp.
authors.forename: M
authors.initials: M
authors.lastname: Murakami
mesh_terms: D000273:Adipose Tissue / Q000737:chemistry / Q000201:enzymology; D000818:Animals; D016718:Arachidonic Acid / Q000302:isolation & purification / Q000378:metabolism; D002460:Cell Line; D003106:Colon / Q000737:chemistry / Q000201:enzymology; D004281:Docosahexaenoic Acids / Q000302:isolation & purification / Q000378:metabolism; D004817:Epidermis / Q000737:chemistry / Q000201:enzymology; D006868:Hydrolysis; D007527:Isoenzymes / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D019787:Linoleic Acid / Q000302:isolation & purification / Q000378:metabolism; D050356:Lipid Metabolism / Q000502:physiology*; D008198:Lymph Nodes / Q000737:chemistry / Q000201:enzymology; D008246:Lysophospholipids / Q000302:isolation & purification / Q000378:metabolism; D008297:Male; D008563:Membrane Lipids / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D019301:Oleic Acid / Q000302:isolation & purification / Q000378:metabolism; D009928:Organ Specificity; D054497:Phospholipases A2, Secretory / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism*; D021241:Spectrometry, Mass, Electrospray Ionization; D013094:Spermatozoa / Q000737:chemistry / Q000201:enzymology; D013379:Substrate Specificity
chemical_list: D007527:Isoenzymes; D008246:Lysophospholipids; D008563:Membrane Lipids; D010743:Phospholipids; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid; D019301:Oleic Acid; D019787:Linoleic Acid; D054497:Phospholipases A2, Secretory
keywords: Arachidonic acid; Docosahexaenoic acid; Knockout mouse; Lipidomics; Lysophospholipid; Mass spectrometry; Phospholipid; Polyunsaturated fatty acid; Secreted phospholipase A(2); Transgenic mouse