Glycerophospholipids phosphatidylcholine

Our first issue with respect to the lipid bilayer is its composition. This varies from membrane to membrane but generally includes several glycerophospholipids— phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine—as well as... 

FIGURE 8.6 Structures of several glycerophospholipids and space-filling models of phosphatidylcholine, phosphatidylglycerol, and phosphatidylinositol. 

Phospholipids are important constituents of cell membranes and are of two kinds. Glycerophospholipids, such as phosphatidylcholine and phos-phatidylethanolamine, are closely related to fats in that they have a glycerol backbone esterified to two fatty acids (one saturated and one unsaturaled) and to one phosphate ester. Sphingomyelins have the amino alcohol sphingo-sine for their backbone. 

Figure 4.22 (a) Stearic and oleic acid (b) glycerol and a triglyceride (c) the general structure of a glycerophospholipid and (d) the glycerophospholipid l-stearoyl-2-oleoyl-3-phosphatidylcholine. 

Glycerophospholipids are used for membrane synthesis and for producing a hydrophilic surface layer on lipoproteins such as VLDL. In cell membranes, they also serve as a reservoir of second messengers such as diacylglycerol, inositol 1,4,5-triphosphate, and arachidonic acid. Their structure is similar to triglycerides, except that the last fatty acid is replaced by phosphate and a water-soluble group such as choline (phosphatidylcholine, lecithin) or inositol (phosphatidyl-inositol). 

There are few commercial fungicides that have glycerophospholipid biosynthesis inhibition as their mode of action. The validated targets are phosphatidylcholine synthesis and phosphatidylinositol synthesis. 

FIGURE 10-13 The similarities in shape and in molecular structure of phosphatidylcholine (a glycerophospholipid) and sphingomyelin (a sphingolipid) are clear when their space-filling and structural formulas are drawn as here. 

FIGURE 10-15 The specificities of phospholipases. Phospholipases Ai and A2 hydrolyze the ester bonds of intact glycerophospholipids at C-l and C-2 of glycerol, respectively. Phospholipases C and D each split one of the phosphodiester bonds in the head group. Some phospholipases act on only one type of glycerophospholipid, such as phosphatidylinositol 4,5-bisphosphate (shown here) or phosphatidylcholine others are less specific. When one of the fatty acids has been removed by a type A phospholipase, the second fatty acid is cleaved from the molecule by a lysophospholipase (not shown). 

Glycerophospholipids differ in the structure of their head group common gycerophospholipids are phosphatidylethanolamine and phosphatidylcholine. The polar heads of the gycerophospholipids carry electric charges at pH near 7. 

T6. The Action of Phospholipases The venom of the Eastern diamondback rattler and the Indian cobra contains phospholipase A2, which catalyzes the hydrolysis of fatty acids at the C-2 position of glycerophospholipids. The phospholipid breakdown product of this reaction is lysolecithin (lecithin is phosphatidylcholine). At high concentrations, this and other lysophospholipids act as detergents, dissolving the membranes of erythrocytes and lysing the cells. Extensive hemolysis may be life-threatening. 

Definition and example of a glycerophospho-lipid Phospholipids that contain glycerol are called glycerophospholipids or phosphoglyc-erides. All contain phosphatidic acid, the simplest glycerophospholipid. When an alcohol, such as choline, is esterified to phosphatidic acid, the product is phosphatidylcholine. 

The phospholipids in milk are synthesized by the mammary cell via pathways that are common to other mammalian cells. For further information on the synthesis of phospholipids in the mammary cell, see Kinsella and Infante (1978) and Patton and Jensen (1976). The major glycerophospholipids are phosphatidylethanolamine, phosphatidylcholine, phosphatidylserine, and phosphatidylinositol. A more complete composition is given in Table 4.6, Patton and Jensen (1976). The acyl and alkyl compositions will be given later. In milk, the glycerophospholipids are found predominantly in the diacyl form. However, small... 

Glycerophospholipids contain a glycerol skeleton to which two fatty acids are esterified saturated fatty acids occupy mostly sn-position 1, whereas unsaturated fatty acids are mainly present on sn-position 2. The third hydroxyl is linked to a phosphate group to which an organic base is mostly esterified (Fig. 1). The most important components of soybean lecithin are phosphatidylcholine (PC), phosphatidylethanolamine (PE), and phosphatidylinositol (PI). Phosphatidic acid (PA) may become important due to the presence of phospholipase D this enzyme slowly converts PC into PA in vegetable lecithins. Phosphatidylserine (PS), phosphatidylglycerol (PG), and lyso-phosphatidylcholine (LPC) are known as minor components lysophospholipids contain only one acyl group per molecule. Besides, ether phospholipids occur in which one or both fatty acyl... 

The positional distribution of fatty acids in phosphatidylcholine and phosphatidylethanolamine, the major glycerophospholipids, of bovine milk, were investigated by Morrison et al. (1965) and are shown in Table 1.13. Unlike triacylglycerols, phospholipids do not contain short-chain fatty acids (14 0 being the shortest chain fatty acid present at a significant level). This is probably due to differences in the route of synthesis, as most short-chain fatty acids are found at the sn-3 position of triacylglycerols, which in phospholipids is occupied by the phosphate moiety. In phospholipids, the polyunsaturated fatty acids tend to be esterified preferentially at the sn-2 position, while the saturated fatty acids show a preference for the sn-1 position (Table 1.13). For phosphatidylethanolamine, 18 2 and 18 3 are found predominantly at the sn-2 position, while 18 1 is fairly evenly distributed and 16 0 and 18 0 are predominantly at the sn-1 position. In phosphatidylcholine, which is more saturated than phosphatidylethanolamine, the distribution of saturated and unsaturated fatty acids is less distinct between... 

The structure of glycerophospholipids is characterized by a l,2-diacyl-3-phospho-5n-glycerol, or phosphatidyl moiety, and a variable headgroup linked to the phosphate. Major phosphoglycerides found in nature are phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylglycerol (PG), phosphatidylserine, phosphatidylinositol (PI), and diphospha-... 

Phospholipids (Figure 3) are constituents of membranes and are only minor components of oils and fats, sometimes responsible for cloudiness. They are usually removed during degumming, the residue from soybean oil processing being a source of phospholipids used as food emulsifiers. The term lecithin is used very loosely for such material, and it may variously mean phosphatidylcholine, mixed glycerophospholipids, or cmde phospholipid extracts from various sources. Where possible, more specific nomenclature or the source and purity should be used (14). 

Glycerophospholipids which can be analysed in this way [285] include the cephalins (R = ethanolamine), phosphatidylserine [287], phos-phatidylinositol, and phosphatidylcholine. 

Therraodjmamics of phospholipids depend on their molecular structure the conformation and the geometry of the phospholipids polar head, the orientation of the molecular backbone (glycerol in the case of glycerophospholipids) and the acyl-chaiiis orientation. NMR spectroscopy has been used extensively in order to reveal the lipid orientation in membrane structures [20]. NMR experiments have shown that except for phospatidic acid, in all phospholipid crystal structures a part of the sn-2 fatty acyl chain is parallel to the bilaycr surface. In egg phosphatidylcholines for example the averege size of the sn-2 acyl chain is 18 carbons while the sn- fatty acid is 16 carbons long. The final configuration of the two fatty acyl chains extends to the same depth from the bilayer surface and a thermodynamicaly stable conformation of the acyl lipid chains is formed [21]. 

Some commercial preparations of purified sphingomyehnase from B. cereus may be contaminated with phospholipase C. This is irrelevant when the substrate consists of pure sphingomyelin, but when the LUV contain glycerophospholipids, e.g. phosphatidylcholine, contamination is serious because both enzymes will give off the water-soluble end-product phosphorylcholine. In such cases, the assays include o-phenanthroline, a specific inhibitor of phospholipase C that is innocuous for SMase [92-94]. 

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