Many phospholipids are derivatives of phosphatidic acid (Figure 1), in which a glycerol moiety is esterified to a phosphate group and two long-chain fatty acids (glycerophospholipids). Phosphatidic acid is important as an intermediate in the synthesis of triacylglycerols as well as glycerophospholipids but is not found in any great quantity in tissues. Sphingolipids, such as sphingomyelin, in which the phosphate is esterified to sphingosine, a complex amino alcohol (Figure 2), are also important membrane components. Both glycerophospholipids and sphingolipids have two long-chain hydrocarbon tails which are important for their function in forming the lipid bilayer in cell membranes , but in the former both are fatty acid chains while in the latter one is a fatty acid and the second is part of the sphingosine molecule (Figure 3).
Fig1. Phospholipids.The —O shown shaded in phosphatidic acid is substituted by the substituents A-E to form the phospholipids: (A) 3-phosphatidylcholine, (B) 3-phosphatidylethanol amine, (C) 3-phosphatidylserine, (D) 3-phosphatidylinositol, and (E) cardiolipin (diphosphatidylglycerol).
Fig2. A sphingomyelin.
Fig3. Comparison of glycerophospholipid and sphingolipid structures. Both types of phospholipid have two hydrocar bon tails, in glycerophospholipids both are fatty acid chains (a phosphatidylcholine with one saturated and one unsaturated fatty acid is shown) and in sphingolipids one is a fatty acid chain and the other is part of the sphingosine moiety (a sphingomyelin is shown). The two hydrophobic tails and the polar head group are important for the function of these phospholipids in the lipid bilayer in cell membranes .
Phosphatidylcholines (Lecithins) & Sphingomyelins Are Abundant in Cell Membranes
Glycerophospholipids containing choline (see Figure 1), (phosphatidylcholines, commonly called lecithins) are the most abundant phospholipids of the cell membrane and represent a large proportion of the body’s store of choline. Choline is important in nervous transmission, as acetylcholine, and as a store of labile methyl groups. Dipalmitoyl lecithin is a very effective surface-active agent and a major constituent of the surfactant preventing adherence, due to surface tension, of the inner surfaces of the lungs. Its absence from the lungs of premature infants causes respiratory distress syndrome. Most phospholipids have a saturated acyl radical in the sn-1 position but an unsaturated radical in the sn-2 position of glycerol.
Phosphatidylethanolamine (cephalin) and phosphatidylserine (found in most tissues) are also found in cell membranes and differ from phosphatidylcholine only in that ethanolamine or serine, respectively, replaces choline (see Figure 1). Phosphatidylserine also plays a role in apoptosis (programmed cell death).
Sphingomyelins are found in the outer leaflet of the cell membrane lipid bilayer and are particularly abundant in specialized areas of the plasma membrane known as lipid rafts . They are also found in large quantities in the myelin sheath that surrounds nerve fibers and play a role in cell signaling and in apoptosis. Sphingomyelins contain no glycerol, and on hydrolysis they yield a fatty acid, phosphoric acid, choline, and sphingosine (see Figure 2). The com bination of sphingosine plus fatty acid is known as ceramide , a structure also found in the glycosphingolipids.
Phosphatidylinositol Is a Precursor of Second Messengers
The inositol is present in phosphatidylinositol as the stereo isomer, myoinositol (see Figure 1). Phosphorylated phosphatidylinositols (phosphoinositides) are minor components of cell membranes, but play an important part in cell signaling and membrane trafficking. Phosphoinositides may have 1, 2, or 3 phosphate groups attached to the inositol ring. Phosphatidylinositol 4,5-bisphosphate (PIP2 ), for example, is cleaved into diacylglycerol and inositol trisphosphate upon stimulation by a suitable hormone agonist, and both of these act as internal signals or second messengers.
Cardiolipin Is a Major Lipid of Mitochondrial Membranes
Phosphatidic acid is a precursor of phosphatidylglycerol, which in turn gives rise to cardiolipin (see Figure 1). This phospholipid is found only in mitochondria and is essential for the mitochondrial function. Decreased cardiolipin levels or alterations in its structure or metabolism cause mitochondrial dysfunction in aging and in pathologic conditions including heart failure, cancer, and Barth syndrome (a rare genetic dis ease causing cardioskeletal myopathy).
Lysophospholipids Are Intermediates in the Metabolism of Phosphoglycerols
These are glycerophospholipids containing only one acyl radical, for example, lysophosphatidylcholine (lysolecithin) (Figure 4), which is important in the metabolism and interconversion of phospholipids. This compound is also found in oxidized lipoproteins and has been implicated in some of their effects in promoting atherosclerosis.
Fig4. Lysophosphatidylcholine (lysolecithin).
Plasmalogens Occur in Brain & Muscle
These compounds constitute as much as 10 to 30% of the phospholipids of brain and heart. Structurally, the plasmalogens resemble phosphatidylethanolamine but possess an ether link on the sn-1 carbon instead of the ester link found in acylglycerols. Typically, the alkyl radical is an unsaturated alcohol (Figure 5). In some instances, choline, serine, or inositol may be substituted for ethanolamine. Plasmalogens play an important role in the structure of membranes, and are believed to be involved in cell signaling and to act as endogenous antioxidants.
Fig5. Plasmalogen.
