1-Lysophosphatidylcholine

Class of phospholipids class=skin-invert-image|thumb|right|150px|General chemical structure of 1-lyso-phosphatidylcholines, where R is a variable fatty acyl group 1-Lysophosphatidylcholines (or 1-lysoPC) are a class of phospholipids that are intermediates in the metabolism of lipids. They result from the hydrolysis of an acyl group from the sn-1 position of phosphatidylcholine. They are also called 2-acyl-sn-glycero-3-phosphocholines. The synthesis of phosphatidylcholines with specific fatty acids occurs through the synthesis of 1-lysoPC. The formation of various other lipids generates 1-lysoPC as a by-product. Other synonyms for this class of compounds are 2-acylglycero-3-phosphocholine, 1-lyso-2-acyl-sn-glycero-3-phosphocholine, β-lysophosphatidylcholine, 2-acylglycerophosphocholine, L-1-lysolecithin and 1-lecithin. Chemical properties 1-LysoPC can convert to the structurally similar 2-lysoPC. This happens by the migration of the acyl group from the sn-1 position of the glycerol backbone to the sn-2 position. 1-lysoPC 2-lysoPC reversible 2-Acylglycerin-3-phosphocholin.svg150px 1-Acylglycerin-3-phosphocholin.svg150px The lowest rate of isomerization is at pH 4–5. Starting from either 1-lysoPC or 2-lysoPC, an equilibrium mixture of 90% 2-lysoPC and 10% 1-lysoPC is obtained with a half-time of about 10 minutes under physiological conditions 10600639 10.1042/0264-6021:3450061 1220730 345 Characterization of plasma unsaturated lysophosphatidylcholines in human and rat January 2000 Biochem. J. 61–7 Croset M Brossard N Polette A Lagarde M 1 and about 1 hour under typical laboratory conditions.Plückthun A, Dennis EA Acyl and phosphoryl migration in lysophospholipids: importance in phospholipid synthesis and phospholipase specificity Biochemistry 21 8 1743–50 April 1982 7082643 10.1021/bi00537a007 Thus, unless special care is taken to slow this isomerization reaction, characterization of either of these lipids using laboratory assays that take a significant amount of time is likely to produce results on a mixture of the two lipids. In the fungus 'Penicillium notatum, an enzyme called lysolecithin acylmutase has been reported that can catalyze this isomerization reaction at low pHs at which the uncatalyzed reaction occurs very slowly. Uziel M. Hanahan DJ. An enzyme-catalyzed acyl migration; a lysolecithin migratase J Biol Chem 226 2 789–98 Jun 1957 10.1016/S0021-9258(18)70861-2 13438864 free Metabolic reactions Because 1-lysoPC has a relatively short half-life (see above), it is primarily a metabolic intermediate or side-product in the formation or breakdown of other lipids. As product of reactions 1-LysoPC can be produced from phosphatidylcholine by enzymes having phospholipase A1 activity, that is, enzymes hydrolyzing specifically at the sn-1 position of a phospholipid and releasing a fatty acid. Enzymes having phospholipase B activity hydrolyze both the sn-1 and sn-2 positions, so they produce both 1-lysoPC and 2-lysoPC. In humans, a number of enzymes with phospholipase A1 exist: they include two from the brain (with different optimal pHs), two from the liver (one cytosomal and one membrane-bound) Hawthorne J. N. Ansell G. B. Phospholipids 1982 Elsevier Biomedical Press 17 Amsterdam; New York 978-0-444-80427-3 https://books.google.com/books?id=sqp91vnUnaQC&pg=PA17 and one from the mitochondrion. Badiani K. Page L. Arthur G. Hydrolysis of 2-acyl-sn-glycero-3-phosphocholines in guinea pig heart mitochondria Biochem Cell Biol 68 9 1090–5 Sep 1990 10.1139/o90-163 2257116 phosphatidylcholine(PC) Phosphatidylcholin.svg150px 1-lysoPC 2-Acylglycerin-3-phosphocholin.svg150px fatty acid Carboxylic-acid-skeletal.svg50px phospholipase A1 forward 1-LysoPC can be produced as a by-product of the reaction transferring an acyl group from a phosphatidylcholine to an acceptor molecule, resulting in the formation of an esterified acceptor molecule. In the human, an example of such a transacylation reaction is that catalyzed by the enzyme LRAT that converts an all-trans retinol to an all-trans-retinyl ester. The latter is a storage form of Vitamin A in various tissues, as well as a retinal precursor in the retina (see visual cycle). Ruiz A. Winston A. Lim YH. Gilbert BA. Rando RR. Bok D. Molecular and biochemical characterization of lecithin retinol acyltransferase J Biol Chem 274 6 3834–41 Feb 1999 10.1074/jbc.274.6.3834 9920938 free all-trans-retinol all-trans-Retinol.svg125px dipalmitoyl-PC Dipalmitoyllecithin.svg200px all-trans-retinyl ester Retinyl palmitate.png125px 2-palmitoyl-PC(a 1-lysoPC) 2-Palmitoyllecithin copy.svg150px lecithin retinol acyltransferase forward 1-LysoPC is also a by-product of the reaction in which N-arachidonoyl-1,2-diacyl-glycerol 3-phosphoethanolamine (NAPE) is produced. This is a rate-limiting step for the synthesis of anandamide and related signaling lipids. Two enzymes are known to catalyze this reaction. LRAT-like protein (RLP-1; a product of the gene HRASLS5), catalyzes transfer of an acyl group from phosphatidylcholine (PC) to phosphatidylethanol (PE), resulting in the formation of radioactive NAPE. RLP-1 does not show selectivity with respect to the sn-1 and sn-2 positions of PC as an acyl donor and therefore can generate N-arachidonoyl-PE (an anandamide precursor) from 2-arachidonoyl-PC and PE. There is also a Ca2+-dependent, membrane-associated enzyme (whose gene is currently not known) that is specific for the sn-1-acyl group of PC. Jin XH. Okamoto Y. Morishita J. Tsuboi K. Tonai T. Ueda N. Discovery and characterization of a Ca2+-independent phosphatidylethanolamine N-acyltransferase generating the anandamide precursor and its congeners J Biol Chem 282 6 3614–23 Feb 2007 10.1074/jbc.M606369200 17158102 free Ueda N. Tsuboi K. Uyama T. N-acylethanolamine metabolism with special reference to N-acylethanolamine-hydrolyzing acid amidase (NAAA) Prog Lipid Res 49 4 299–315 Oct 2010 10.1016/j.plipres.2010.02.003 20152858 phosphatidylethanol(PE) Phosphatidylethanolamin.svg 125px PC Phosphatidylcholin.svg150px NAPE N-Arachidonoyl-PE.svg200px 1-lysoPC 2-Acylglycerin-3-phosphocholin.svg 150px LRAT-like protein forward As substrate of reactions 1-lysoPC can be hydrolyzed further by lysophospholipases to lose the remaining fatty acid and yield L-1-glycero-3-phosphocholine. In humans, 1-lysoPC can be hydrolyzed by ten different enzymes:http://metacyc.org/HUMAN/NEW-IMAGE?type=REACTION&object=LYSOPHOSPHOLIPASE-RXN Homo sapiens Reaction: 3.1.1.5 http://www.genome.jp/dbget-bin/www_bget?ec:3.1.1.5 KEGG ENZYME: 3.1.1.5 KEGG: Kyoto Encyclopedia of Genes and Genomes calcium-independent phospholipase A2-gamma (coded by the gene PNPLA8), neuropathy target esterase (PNPLA6), lysophospholipase (PLB1), eosinophil lysophospholipase (CLC), galactoside-binding soluble lectin 13 (LGALS13), Group XV phospholipase A2 (PLA2G15), acyl-protein thioesterase 1 (LYPLA1), lysophospholipase (PLA2G4A), acyl-protein thioesterase 2 (LYPLA2) and PNPLA7 (Some of these enzymes also have phospholipase A2 activity). Other organisms have different numbers of enzymes that catalyze the same chemical reaction. For example the bacterium E. coli has only the gene products of tesA and pldB, while the yeast S. cerevisiae has the gene products of NTE1, PLB2, PLB1 and PLB3. 1-lysoPC 2-Acylglycerin-3-phosphocholin.svg150px Glycerol-3-phosphocholine Glycerin-3-phosphocholin.svg150px Fatty acid Carboxylic-acid-skeletal.svg50px lysophospholipase forward There appear to be at least two enzymes that can produce a phosphatidylcholine molecule from 1-lysoPC. 2-acylglycerophosphocholine O-acyltransferase, an enzyme purified in liver microsomes, catalyzes specifically the acylation of 1-lysoPC with acyl-CoA to create a phosphatidylcholine molecule. Van Den Bosch H. Van Golde MG. Slotboom AJ. Van Deenen LL. The acylation of isomeric monoacyl phosphatidylcholines Biochim Biophys Acta 152 4 694–703 Jul 1968 10.1016/0005-2760(68)90115-x 5660084 This reaction is important for the synthesis of phosphatidylcholine containing specific fatty acids, but are not used for the de-novo synthesis of phosphatidylcholine. Arthur G. Acylation of 2-acyl-glycerophosphocholine in guinea-pig heart microsomal fractions Biochem J 261 2 575–80 Jul 1989 10.1042/bj2610575 2775234 1138863 In contrast to these finding from rat liver microsomes, mammalian acyl transferase from dog lungs was found to exhibit no preference between 1-lyso-2-acyl-phosphatidylcholine and 1-acyl-2-lyso-phosphatidylcholine. http://www.jlr.org/content/12/1/96.long 5542709 Acyl transferase activities in dog lung microsomes 1971-01-01 M. F. Frosolono Journal of Lipid Research 12 1 96–103 Slivka S Charms BL 10.1016/S0022-2275(20)39552-3 free These differences have been attributed to the remodeling of membrane phospholipids in order to regulate membrane fluidity and the accumulation of physiologically important fatty acids such as arachidonic acid. Yamashita A. Sugiura T. Waku K. Acyltransferases and transacylases involved in fatty acid remodeling of phospholipids and metabolism of bioactive lipids in mammalian cells J Biochem 122 1 1–16 Jul 1997 10.1093/oxfordjournals.jbchem.a021715 9276665 free 1-lysoPC 2-Acylglycerin-3-phosphocholin.svg150px acyl-CoA Acyl-CoA2.svg75px PC Phosphatidylcholin.svg150px Glycerol-3-phosphocholine Glycerin-3-phosphocholin.svg150px 2-acylglycerophosphocholineO-acyltransferase forward CoA In humans, triglyceride synthesis occurs through the Kennedy pathway, in which glycerol-3-phosphate is sequentially acylated to produce triacylglycerol. In plants and fungi, however, triacylglycerol synthesis can be catalyzed by phospholipid:diacylglycerol acyltransferase (PDAT). Thus, diacylglycerol is the acceptor of a fatty acid coming from phosphatidylcholine, resulting in the release of a 1-lysoPC. http://fungicyc.broadinstitute.org/PCWC541255/NEW-IMAGE?type=PATHWAY&object=TRIGLSYN-PWY Penicillium chrysogenum Wisconsin 54-1255 Pathway: triacylglycerol biosynthesis FungiCyc - an organism-specific database of metabolic pathways, compounds and reactions 2012-01-10August 2018 InternetArchiveBot yes diacylglycerol Diacylglycerin.svg100px PC Phosphatidylcholin.svg150px triacylglycerol Triacylglycerin.svg100px 1-lysoPC 2-Acylglycerin-3-phosphocholin.svg150px Phospholipid:diacylglycerol acyltransferase forward A rat enzyme was found to transfer the acyl group from 2-lysoPC to 1-lysoPC, producing phosphatidylcholine. Sugimoto H. Yamashita S. Characterization of the transacylase activity of rat liver 60-kDa lysophospholipase-transacylase. Acyl transfer from the sn-2 to the sn-1 position Biochim Biophys Acta 1438 2 264–72 May 1999 10.1016/S1388-1981(99)00059-1 10320809 2-lysoPC 1-Acylglycerin-3-phosphocholin.svg100px 1-lysoPC 2-Acylglycerin-3-phosphocholin.svg100px PC Phosphatidylcholin.svg100px glycerol-3-phosphocholine Glycerin-3-phosphocholin.svg100px lysophospholipase-transacylase forward Transport systems In the human body, 1-lysoPC that is made in the liver is carried by albumin in the blood plasma to various tissues where it is acylated to produce PC molecules with specific acyl groups. In the liver, 1-lysoPC is released by phospholipase A1 and is also formed by hepatic lipase. Albumin-bound 1-lysoPC is an important pathway to access tissue compartments such as the brain, which take up few lipoproteins. Fatty acyl chains delivered by this route can then be acylated into tissue membrane phospholipids. Zhou L. Nilsson A. Sources of eicosanoid precursor fatty acid pools in tissues. J Lipid Res 42 10 1521–42 Oct 2001 10.1016/S0022-2275(20)32206-9 11590208 free Lysophosphatidylcholine processing has been discovered to be an essential component of normal human brain development: those born with genes that prevent adequate uptake suffer from lethal microcephaly.Guemez-Gamboa Alicia N Nguyen Hongbo Yan Inactivating mutations in MFSD2A, required for omega-3 fatty acid transport in brain, cause a lethal microcephaly syndrome. Nature Genetics 10.1038/ng.3311 47 7 809–813 26005868 4547531 2015 MFSD2a has been shown to transport LPC-bound polyunsaturated fatty acids, including DHA and EPA, across the blood-brain and blood-retinal barriers.Nguyen LN Ma D Shui G Wong P Cazenave-Gassiot A Zhang X Wenk MR Goh ELK Silver DL Mfsd2a is a transporter for the essential omega-3 fatty acid docosahexaenoic acid Nature 14 May 2014 509 7501 503–506 10.1038/nature13241 24828044 2014Natur.509..503N 4462512 https://doi.org/10.1038/nature13241 subscription Wong BH Chan JP Cazenave-Gassiot A Poh RW Foo JC Galam DLA Gosh S Nguyen LN Barathi VA Yeo SW Luu CD Wenk MR Silver DL Mfsd2a Is a Transporter for the Essential ω-3 Fatty Acid Docosahexaenoic Acid (DHA) in Eye and Is Important for Photoreceptor Cell Development J Biol Chem 2016 291 20 10501–10514 10.1074/jbc.M116.721340 27008858 4865901 free In the human body, lysoPC (1-lysoPC and 2-lysoPC together) represent 5-20% of all phospholipids in the blood plasma. NELSON AM. Phospholipids and coronary mortality. Use of ratio between phospholipid and cholesterol levels to determine successful treatment. Northwest Med 61 47–52 Jan 1962 14478888 Taking care to control for the chemical isomerization between 1-lysoPC and 2-lysoPC (see above), about half of the lysoPC molecules in plasma have been shown to be in the 1-lysoPC form. Croset M. Brossard N. Polette A. Lagarde M. Characterization of plasma unsaturated lysophosphatidylcholines in human and rat. Biochem J 345 1 61–7 Jan 2000 10.1042/0264-6021:3450061 10600639 1220730 Most (~60%) of the lysoPC is bound to albumin, and the rest is associated with lipoproteins. Of the total (free and esterified form) fatty acids carried by albumin, about one third is in the form of lysoPC. In addition to transport across tissues in the body, there are transport systems within cells to transport 1-lysoPC from where it is synthesized, or where it is delivered from other tissues, to where it is needed. Most organisms have transfer proteins (type IV ATPases) to transport phospholipid across their cell membranes. These proteins are likely to transport 1-lysoPC as well but their substrate specificities have not been established yet. Tanaka K. Fujimura-Kamada K. Yamamoto T. Functions of phospholipid flippases. J Biochem 149 2 131–43 Feb 2011 10.1093/jb/mvq140 21134888 free E. coli and other bacteria have such a transporter protein that is a specialized lysophospholipid transporter (the LplT gene product). It can "flip" 1-lysoPC and the related compound 2-acylglycerophosphoethanolamine from the outer leaflet of the lipid bilayer to inner layer. Harvat EM. Zhang YM. Tran CV. Zhang Z. Frank MW. Rock CO. Saier MH. Lysophospholipid flipping across the Escherichia coli inner membrane catalyzed by a transporter (LplT) belonging to the major facilitator superfamily J Biol Chem 280 12 12028–34 Mar 2005 10.1074/jbc.M414368200 15661733 free Synthesis in the laboratory In the laboratory, a method to prepare relatively pure 1-lysoPC and purify away the reaction side-products is available.Eibl H, Lands WE Phosphorylation of 1-alkenyl-2-acylglycerol and preparation of 2-acylphosphoglycerides Biochemistry 9 2 423–8 January 1970 4983883 10.1021/bi00804a033 References 2 External links 1-LysoPC page at the Chemical Entities of Biological Interest 1-LysoPC page at KEGG Category:Phospholipids