Phospholipase glycerophospholipids

Most cells continually degrade and replace their membrane lipids. For each hydrolyzable bond in a glycerophospholipid, there is a specific hydrolytic enzyme in the lysosome (Fig. 10-15). Phospholipases of the A type remove one of the two fatty acids, producing a lysophospholipid. (These esterases do not attack the ether link of plasmalogens.) Lysophospholipases remove the remaining fatty acid. 

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). 

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. 

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... 

Farooqui A. A. and Horrocks L. A. (2007b). Glycerophospholipids in the Brain Phospholipases A2 in Neurological Disorders, pp. 1-394. Springer, New York. 

Phospholipase, hydrolyses glycerophospholipids and forms lysophospholipids and arachidonic acid. Regulated by MAP kinase and Ca +... 

The hydrolysis of glycerophospholipids ester bonds are regulated by a group of enzymes namely phospholipases. The site of action of every phospholipase is specific for every enzyme and is of great importance for the biological role of the phospholipids. Phospholipase A2 for example stereospeciftcally catalyzes the hydrolysis of xn-2 acyl ester bond, and plays an important role in the lung inflammation pathogenesis Fig. (5) LU5]. 

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]. 

Myocardial ischemia is accompanied by the release of arachidonic acid and the accumulation of lysophosphatidylcholine and lysophosphatidylethanolamine (cf, Corr et al., 1984). Arachidonic acid is predominantly stored in choline- and ethanolamine-glycerophospholipids in myocardium. Thus, these findings demonstrate that phospholipase A2 is activated during myocardial ischemia. Since lyso-phospholipids are potent amphiphilic compounds which have profound effects on the physical propwties of myocardial sarcolemma, the accumulation of these moieties has also been implicated in arrhythmogenesis. 

The above described pro-apoptotic effects were observed when cells were exposed to chemically defined phospholipids. However, it has to be taken into account that the respective 2-acyl-glycerophospholipids may be subject to hydrolysis by phospholipases inside and outside cells. As a consequence, the apoptotic oxidized phospholipids are degraded leading to harmless compounds or lipids of even higher toxicity. We found that POV-PCand PG-PC were inactivated in serum (Fruhwirth et al., 2006) and that this effect was due to hydrolysis by serum phospholipases since the main degradation product was lysophosphatidylcholine (Bjorkerud and Bjorkerud, 1996 Matsuzawa... 

Phospholipases other than phospholipase C are also stimulated by G proteins. Arachidonic acid, released from phosphatidylcholine, is the major metabolic precursor to eicosanoids. Phospholipase A2, which releases fatty acids from glycerophospholipids, also interacts with G proteins, and phospholipase D (see here) is thought to participate in signal transduction via diacylglycerol formation. In addition, some phospholipases are controlled by Ca. ... 

Phospholipases are enzymes that can catalyze cleavage of acyl or phosphoacyl moieties from glycerophospholipids, as shown in Figure 19.6. Phospholipases are implicated in rearrangement of phospholipids after they have been synthesized and in release of arachidonic acid from glycerophospholipids in eicosanoid metabolism. 

Phospholipase A2 cleaves an acyl group from glycerophospholipids (Figure 19.6) and may be involved in synthesis of lung surfactant, which contains a saturated fatty acid at position 2, unlike normal glycerophospholipids, which contain an unsaturated fatty acid. 

See also Redistribution of Phospholipid Fatty Acids, Phospholipases, Lung Surfactant, Glycerophospholipids, Second Messenger Systems... 

One enzyme capable of removing a fatty acid from a glycerophospholipid is phospholipase A2, one of a class of four enzymes that hydrolyze specific bonds in phospholipids (Figure 19.6). 

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