Membrane Lipid Biosynthesis

Abstract

Biological membranes consist of a complex array of proteins and lipids that create selective permeability barriers in cells. Another function of membrane lipids is their degradation to generate ‘lipid second messengers’ that can regulate important cellular functions such as cell division and cell death. The major membrane lipids of eukaryotic cells are the glycerophospholipids, the sterols and the sphingolipids. The most abundant glycerophospholipids in eukaryotic cells are phosphatidylcholine and phosphatidylethanolamine, each of which is synthesised by two independent pathways. The glycosphingolipids consist of structures in which ceramide is attached to a variety of oligosaccharide chains to create an enormously diverse class of lipids that are highly enriched on the cell surface. In mammalian cells, cholesterol is the most abundant sterol in membranes, whereas plants and fungi do not contain cholesterol per se but instead contain sterols that are related to cholesterol; prokaryotic membranes do not contain sterols.

Key Concepts:

  • Lipid bilayers provide the fundamental architecture of biological membranes.

  • Cellular phospholipid levels are tightly regulated.

  • Major classes of phospholipids are made by more than one pathway.

  • Acyl chain composition of phospholipids can be modified by deacylation.

  • The cholesterol‐lowering statin drugs regulate cholesterol biosynthesis at the step catalysed by 3‐hydroxy‐3‐methylglutaryl‐CoA reductase.

Keywords: cardiolipin; ceramide; cholesterol; ether lipids; glycosphingolipid; lipid bilayer; phosphatidylcholine; phosphatidylethanolamine; phosphatidylserine; sphingomyelin

Figure 1.

Structures of common glycerophospholipids. (a) For the most abundant diacylglycerophospholipids, phosphatidylcholine and phosphatidylethanolamine, the polar head group X represents choline or ethanolamine, respectively. In other phospholipids (not shown), X can be serine (in phosphatidylserine), inositol (in phosphatidylinositol) or glycerol (in phosphatidylglycerol). Usually, the fatty acyl substituent at position 1 of the glycerol backbone is saturated, whereas that at position 2 contains one or more double bonds. n denotes the number of methylene groups in the fatty acyl chain; usually n=12–20. (b) In the ether‐linked glycerophospholipids, the polar head group X is either choline or ethanolamine. For the plasmanyl series of lipids, an alkyl substituent is attached to position 1 of the glycerol backbone, whereas in the plasmenyl series, there is a vinyl ether linkage at position 1. n denotes the number of methylene groups in the alkyl, alkenyl and acyl chains.

Figure 2.

Structures of some common sphingolipids. All sphingolipids contain a sphingoid base such as sphinganine or sphingosine. Ceramide, which is a basic building block for both sphingomyelin and the more complex glycosphingolipids, is formed by N‐acylation of the sphingoid base with a long‐chain fatty acid, the alkyl chain of which is represented by R. In sphingomyelin, the hydroxyl group at position 1 of ceramide is attached to phosphocholine, whereas in the glycosphingolipids, ceramide is linked to a large variety of different monosaccharides or oligosaccharides.

Figure 3.

Biosynthetic pathways for mammalian phospholipids. The abbreviations used are CDP, cytidine 5′‐diphosphate; cer, ceramide; cho, choline; choP, phosphocholine; CL, cardiolipin; CMP, cytidine 5′‐monophosphate; DG, diacylglycerol; etn, ethanolamine; etnP, phosphoethanolamine; G3P, glycerol‐3‐phosphate; ino, inositol; PA, phosphatidic acid; PC, phosphatidylcholine; PE, phosphatidylethanolamine; PG, phosphatidylglycerol; PI, phosphatidylinositol; PS, phosphatidylserine; ser, serine and SM, sphingomyelin. The enzymes involved are (1) phosphatidic acid phosphatase; (2) choline kinase; (3) CTP:phosphocholine cytidylyltransferase; (4) CDP–choline:1,2‐diacylglycerol cholinephosphotransferase; (5) ethanolamine kinase; (6) CTP:phosphoethanolamine cytidylyltransferase; (7) CDP–ethanolamine:1,2‐diacylglycerol ethanolaminephosphotransferase; (8) phosphatidylethanolamine N‐methyltransferase; (9) phosphatidylserine synthase; (10) phosphatidylserine decarboxylase; (11) phosphatidylinositol synthase; (12) sphingomyelin synthase; (13) CDP–diacylglycerol synthase and (14) cardiolipin synthase.

Figure 4.

Biosynthesis of sphingolipids. The abbreviations used are CMP, cytidine 5′‐monophosphate; CoA, coenzyme A; DG, diacylglycerol; Gal, galactose; Glc, glucose; NeuAc, N‐acetylneuraminic acid; PC, phosphatidylcholine; SM, sphingomyelin and UDP, uridine 5′‐diphosphate.

Figure 5.

Outline of the cholesterol biosynthetic pathway.

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Further Reading

Vance DE and Vance JE (eds) (2008) Biochemistry of Lipids, Lipoproteins and Membranes, 5th edn. Amsterdam: Elsevier Science.

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Vance, Jean E(Sep 2010) Membrane Lipid Biosynthesis. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0001391.pub2]