PathwayStep1702 PathwayStep1771 PathwayStep1769 PathwayStep1758 PathwayStep1752 PathwayStep1787 PathwayStep1784 PathwayStep1726 PathwayStep1712 PathwayStep1717 PathwayStep1745 PathwayStep1742 PathwayStep1732 PathwayStep1735 PathwayStep1698 PathwayStep1690 PathwayStep1681 PathwayStep1674 Acyl chain remodelling of PS Synthesis of PS Synthesis of PI Synthesis of PE Acyl chain remodelling of PE Hydrolysis of LPE Synthesis of PC PI and PC transport between ER and Golgi membranes Acyl chain remodelling of PC Hydrolysis of LPC Acyl chain remodeling of DAG and TAG Synthesis of PA Glycerophospholipid biosynthesis Authored: Williams, MG, 2011-09-14 Edited: Williams, MG, 2011-08-12 GENE ONTOLOGYGO:0046474 Glycerophospholipids are important structural and functional components of biological membranes and constituents of serum lipoproteins and the pulmonary surfactant. In addition, glycerophospholipids act as precursors of lipid mediators such as platelet-activating factor and eicosanoids. Cellular membranes contains a distinct composition of various glycerophospholipids such as phosphatidic acid (PA), phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylserine (PS), phosphatidylglycerol (PG), phosphatidylinositol (PI), cardiolipin (CL), lysophosphatidic acid (LPA) and lysobisphosphatidic acid (also known as bis(monoacylglycerol) hydrogen phosphate - BMP). Glycerophospholipids are first formed by the de novo (Kennedy) pathway using fatty acids activated as acyl-CoA donors. However, the acyl groups of glycerophospholipids are highly diverse and distributed in an asymmetric manner. Saturated and monounsaturated fatty acids are usually esterified at the sn-1 position, whereas polyunsaturated acyl groups are esterified at the sn-2 position. Subsequent acyl chain remodeling (Lands cycle) generates the diverse glycerophospholipid composition and asymmetry characteristic of cell membranes. In the de novo pathway of glycerophospholipid biosynthesis, lysophosphatidic acid (LPA) is initially formed from glycerol 3-phosphate (G3P). Next, LPA is converted to PA by a LPA acyltransferase (AGPAT, also known as LPAAT), then PA is metabolized into two types of glycerol derivatives. The first is diacylglycerol (DAG) which is converted to triacylglycerol (TAG), PC, and PE. Subsequently, PS is synthesized from PC or PE. The second is cytidine diphosphate-diacylglycerol (CDP-DAG), which is processed into PI, PG, CL, and BMP. Each glycerophospholipid is involved in acyl chain remodeling via cleavage by phospholipases followed by reacylation by an acyltransferase. Most of the glycerophospholipids are synthesized at the endoplasmic reticulum (ER), however, some, most notably cardiolipin, and BMP are synthesized in the mitochondrial and endosomal membranes respectively. Since the most of the glycerophospholipids are found in all membrane compartments, there must be extensive network of transport of glycerophospholipids from one membrane compartment to another via various mechanisms including diffusion through the cytosol, formation of transportation complexes, and diffusion via membrane contact sites (MCS) (Osman et al. 2011, Lebiedzinska et al. 2009, Lev 2010, Scherer & Schmitz 2011, Orso et al. 2011, Hermansson et al. 2011, Vance & Vance 2008). ISBN978-0-444-53219-0 Pubmed19703651 Pubmed20823909 Pubmed21220505 Pubmed21382416 Pubmed21683693 Pubmed21704024 Reactome Database ID Release 431483206 Reactome, http://www.reactome.org ReactomeREACT_121401 Acyl chain remodeling of CL Synthesis of BMP Acyl chain remodelling of PG Synthesis of CL Acyl chain remodelling of PI Synthesis of PG