Glycerophospholipids

Abstract

Glycerophospholipids are derivatives of sn‐glycero‐3‐phosphoric acid. They contain an O‐acyl or O‐alkyl or O‐alk‐1′‐enyl residue at the sn‐1 position and an O‐acyl residue at the sn‐2 position of the glycerol moiety and are defined on the basis of the substituents on the phosphoric acid at the sn‐3 position. Glycerophospholipids are asymmetrically distributed between the two bilayers membranes, which also contain cholesterol and proteins. Glycerophospholipids not only constitute the backbone of cellular membranes, but also provide the membrane with a suitable environment, fluidity and ion permeability. They are synthesised at the endoplasmic reticulum and are transported to other membranous structures by phospholipid exchange and transfer proteins. Once glycerophospholipids are laid down in a biomembrane, they undergo interconversion reactions. These reactions and activities of phospholipases may be responsible for the turnover, compositional maintenance and rearrangements of glycerophospholipids in membranes. This process results in the modulation of membrane function. Glycerophospholipids are precursors for lipid mediators, which play important roles in internal and external communication and modulate cellular responses. In addition, glycerophospholipids and their lipid mediators may be involved in membrane fusion, apoptosis and regulation of the activities of membrane‐bound enzymes and ion channels.

Key Concepts:

  • Lipid bilayers provide the fundamental architecture of biological membranes, which are made up of lipids (phospholipids, cholesterol and sphingolipids) and proteins.

  • The role of lipids is to provide membranes with integrity and flexibility, whereas embedded proteins in biomembrane are associated with the maintenance of cellular chemical climate.

  • Phospholipids are reservoir for lipid mediators, cholesterol provides flexibility, and sphingolipids and cholesterol are involved in formation of lipid rafts.

  • Lipid mediators not only transduce signals from the cell surface to the interior, but also modulate gene expression, growth, differentiation, adhesion, migration and apoptosis.

  • Arachidonic acid‐derived lipid mediators induce oxidative stress and inflammatory effects.

  • Docosahexaenoic acid‐derived lipid mediators produce antioxidative and anti‐inflammatory effects.

Keywords: glycerophospholipids; signal transduction; PLA2; PLC; PLD; eicosanoids; docosanoids

Figure 1.

Structures of glycerophospholipids found in mammalian tissues. (a) Phosphatidic acid (PtdH), (b) phosphatidylcholine (PtdCho), (c) phosphatidylethanolamine (PtdEtn), (d) phosphatidylserine (PlsSer), (e) plasmalogen (PlsEtn), (f) phosphatidylinositol (PtdIns) and (g) platelet‐activating factor (PAF). Boxed structures represent changes from PtdH.

Figure 2.

Reactions involved in the biosynthesis of glycerophospholipids. Glycerophospholipid‐synthesizing enzymes are located in cytosol, plasma membrane, endoplasmic reticulum and mitochondria. ATP, adenosine triphosphate; ADP, adenosine diphosphate; CTP, cytidine triphosphate; CDP, cytidine diphosphate; CMP, cytidine monophosphate; AdoMet, S‐adenosylmethionine and AdoHcy, S‐adenosylhomocysteine.

Figure 3.

Glycerophospholipid‐derived lipid mediators and their roles in metabolism. Arachidonic acid (ARA); prostaglandins (PGs); Leukotrienes (LTs); Thromboxanes (TXs); lipoxins (LXs); 4‐hydroxynonenal (4‐HNE); reactive oxygen species (ROS); isoprostanes (IsoP); phosphatidic acid (PtdH); lysophosphatidic acid (Lyso‐PtdH); docosahexaenoic acid (DHA); resolvins D (RvDs); protectins (PDs); maresins (MaRs); 4‐hydroxyhexanal (4‐HHE); neuroprostanes (NPs); lyso‐phospholipid (lyso‐PL); and platelet activating factor (PAF).

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References

Allen JA, Halverson‐Tamboli RA and Rasenick MM (2007) Lipid raft microdomains and neurotransmitter signalling. Nature Reviews Neuroscience 8: 128–140.

Banchio C, Schang LM and Vance DE (2004) Phosphorylation of Sp1 by cyclin‐dependent kinase 2 modulates the role of Sp1 in CTP: phosphocholine cytidylyltransferase alpha regulation during the S phase of the cell cycle. Journal of Biological Chemistry 279: 40220–40226.

Bankaitis VA and Grabon A (2011) Phosphatidylinositol synthase and diacylglycerol platforms bust a move. Developmental Cell 21: 810–812.

Birner R and Daum G (2003) Biogenesis and cellular dynamics of aminoglycerophospholipids. International Review of Cytology 225: 273–323.

Bleijerveld OB, Klein W, Vaandrager AB, Helms JB and Houweling M (2004) Control of the CDPethanolamine pathway in mammalian cells: effect of CTP: phosphoethanolamine cytidylyltransferase overexpression and the amount of intracellular diacylglycerol. Biochemical Journal 379: 711–719.

Buratta S, Ferrara G and Mozzi R (2011) Presence of phosphatidylserine synthesizing enzymes in triton insoluble floating fractions from cerebrocortical plasma membranes: do phosphatidylserine synthesizing enzymes in plasma membrane microdomains play a role in signal transduction? Neurochemical Research 36: 774–782.

Carter JM, Demizieux L, Campenot RB, Vance DE and Vance JE (2008) Phosphatidylcholine biosynthesis via CTP: phosphocholine cytidylyltransferase 2 facilitates neurite outgrowth and branching. Journal of Biological Chemistry 283: 202–212.

DeLong CJ, Shen YJ and Thomas MJ and Cui Z (1999) Molecular distinction of phosphatidylcholine synthesis between the CDP‐choline pathway and phosphatidylethanolamine methylation pathway. Journal of Biological Chemistry 274: 29683–29688.

Farooqui AA (2009) Hot Topics in Neural Membrane Lipidology. New York, NY: Springer.

Farooqui AA (2011) Lipid Mediators and Their Metabolism in the Brain. New York, NY: Springer.

Farooqui AA, Farooqui T and Horrocks LA (2008) Metabolism and Functions of Bioactive Ether Lipids in the Brain. New York, NY: Springer.

Farooqui AA, Farooqui T and Horrocks LA (2009) Choline and ethanolamine glycerophospholipids. In: Tettamanti G and Gorracci G (eds) Hand Book of Neurochemistry and Molecular Biology, pp. 21–38. New York, NY: Springer.

Farooqui AA and Horrocks LA (2007) Glycerophospholipids in Brain: Phospholipase A2 in Neurological Disorders. New York, NY: Springer.

Farooqui AA, Horrocks LA and Farooqui T (2000) Deacylation‐reacylation of neural membrane glycerophospholipids, a matter of life and death. Journal of Molecular Neuroscience 14: 123–133.

Farooqui T and Farooqui AA (2012) Perspective and directions for future studies. In: Farooqui T and Farooqui AA (eds) Oxidative Stress in Vertebrate and Invertebrates, pp. 377–384. Hoboken, New Jersey, USA: Wiley‐Blackwell.

Inglis‐Broadgate SL, Ocaka L, Banerjee R et al. (2005) Isolation and characterization of murine Cds (CDP‐diacylglycerol synthase) 1 and 2. Gene 356: 19–31.

Kennedy EP (1986) The biosynthesis of phospholipids. In: Op den Kamp JAF, Roelofsen B and Wirtz KWA (eds) Lipids and Membranes: Past, Present and Future, pp. 171–206. Amsterdam: Elsevier.

Kent C and Carman GM (1999) Interactions among pathways for phosphatidylcholine metabolism, CTP synthesis and secretion through the Golgi apparatus. Trends in Biochemical Sciences 24: 146–150.

Lohner K (1996) Is the high propensity of ethanolamine plasmalogens to form non‐lamellar lipid structures manifested in the properties of biomembranes? Chemistry and Physics of Lipids 81: 167–184.

Paltauf F (1994) Ether lipids in biomembranes. Chemistry and Physics of Lipids 74: 101–139.

Pavlovic Z and Bakovic M (2013) Regulation of phosphatidylethanolamine homeostasis – the critical role of CTP: phosphoethanolamine cytidylyltransferase (Pcyt2). International Journal of Molecular Sciences 14: 2529–2550.

Sarri E, Sicart A, Lázaro‐Diéguez F and Egea G (2011) Phospholipid synthesis participates in the regulation of diacylglycerol required for membrane trafficking at the Golgi complex. Journal of Biological Chemistry 286: 28632–28643.

Snyder F (1995) Platelet‐activating factor: the biosynthetic and catabolic enzymes. Biochemical Journal 305: 689–705.

Tomohiro S, Kawaguti A, Kawabe Y Kitada S and Kuge O (2009) Purification and characterization of human phosphatidylserine synthases 1 and 2. Biochemical Journal 418: 421–429.

Vance JE and Vance DE (2004) Phospholipid biosynthesis in mammalian cells. Biochemistry and Cell Biology 82: 113–128.

Wright MM and McMaster CR (2002) PC and PE synthesis: mixed micellar analysis of the cholinephosphotransferase and ethanolaminephosphotransferase activities of human choline/ethanolamine phosphotransferase 1 (CEPT1). Lipids 37: 663–672.

Further Reading

AlbJG Jr, Kearns MA and Bankaitis VA (1996) Phospholipid metabolism and membrane dynamics. Current Opinion in Cell Biology 8: 534–541.

Araki W and Wurtman RJ (1998) How is membrane phospholipid biosynthesis controlled in neural tissues? Journal of Neuroscience Research 51: 667–674.

Dennis EA, Rhee SG, Billah MM and Hannun YA (1991) Role of phospholipases in generating lipid second messengers in signal transduction. FASEB Journal 5: 2068–2077.

Englund PT (1993) The structure and biosynthesis of glycosylphosphatidylinositol protein anchor. Annual Review of Biochemistry 62: 121–138.

Exton JH (1994) Phosphoinositide phospholipases and G proteins in hormone action. Annual Review of Physiology 56: 349–369.

Moreau P and Cassagne C (1994) Phospholipid trafficking and membrane biogenesis. Biochimica et Biophysica Acta 1197: 257–290.

Umeda M and Emoto K (1999) Membrane phospholipid dynamics during cytokinesis: regulation of actin filament assembly by redistribution of membrane surface phospholipids. Chemistry and Physics of Lipids 101: 81–91.

Zachowski A (1993) Phospholipids in animal eukaryotic membranes: transverse asymmetry and movement. Biochemical Journal 294: 1–14.

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Farooqui, Akhlaq A(Jun 2014) Glycerophospholipids. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0000726.pub3]