Phosphatidylcholine degradation

The identity of the moiety (other than glycerol) esterified to the phosphoric group determines the specific phosphoHpid compound. The three most common phosphoHpids in commercial oils are phosphatidylcholine or lecithin [8002-45-5] (3a), phosphatidylethanolamine or cephalin [4537-76-2] (3b), and phosphatidjlinositol [28154-49-7] (3c). These materials are important constituents of plant and animal membranes. The phosphoHpid content of oils varies widely. Laurie oils, such as coconut and palm kernel, contain a few hundredths of a percent. Most oils contain 0.1 to 0.5%. Com and cottonseed oils contain almost 1% whereas soybean oil can vary from 1 to 3% phosphoHpid. Some phosphoHpids, such as dipaLmitoylphosphatidylcholine (R = R = palmitic R" = choline), form bilayer stmetures known as vesicles or Hposomes. The bdayer stmeture can microencapsulate solutes and transport them through systems where they would normally be degraded. This property allows their use in dmg deHvery systems (qv) (8). 

The exact mechanism responsible for the uptake of liposomes by KCs and SECs is not clear. Most studies confirm internalization of whole liposomes in an energy-dependent phagocytic process in which the liposomes are delivered to the lysosomes. The liposomal lipids are completely degraded and the encapsulated solutes released. Neutral liposomes consisting of lipids such as cholesterol and phosphatidylcholine are probably cleared by receptor-mediated mechanisms, due to the adsorption of opsonizing proteins onto the hpid bi-... 

Certain classes of lipids are susceptible to degradation under specific conditions. For example, all ester-linked fatty acids in triacylglycerols, phospholipids, and sterol esters are released by mild acid or alkaline treatment, and somewhat harsher hydrolysis conditions release amide-bound fatty acids from sphingolipids. Enzymes that specifically hydrolyze certain lipids are also useful in the determination of lipid structure. Phospholipases A, C, and D (Fig. 10-15) each split particular bonds in phospholipids and yield products with characteristic solubilities and chromatographic behaviors. Phospholipase C, for example, releases a water-soluble phosphoryl alcohol (such as phosphocholine from phosphatidylcholine) and a chloroform-soluble diacylglycerol, each of which can be characterized separately to determine the structure of the intact phospholipid. The combination of specific hydrolysis with characterization of the products by thin-layer, gas-liquid, or high-performance liquid chromatography often allows determination of a lipid structure. 

Lysophospholipids have been found in butter serum by Cho et al. (1977). They characterized the sn-1 and -2 lysophosphatidylcholines and phosphatidylethanolamines. It is not known if these compounds are products of degradation or remnants of biosynthesis. Cho et al. (1977) searched for, but did not find, another possible product of enzymatic degradation of milk, phosphatidic acid. Phosphatidic acid can be formed by the action of phospholipase D on phosphatidylcholine, for example, but this enzymatic activity was not detected. The compound is also an important intermediate in the biosynthesis of lipids, but the concentration in tissue is always very low. The amount is also low in milk. Cho et al. (1977) found 1.2 and 0.9 (percent of total lipid P) of the lyso compounds above. The quantities of the other phospholipids were phosphatidylethanolamine, 27.3 -choline, 29.1 -serine, 13.4 -inositol, 2.5 and sphingomyelin, 25.6. 

In some cases the functions of phospholipases in cells are purely degradative and result in the release of the phospholipid components (fatty acids, glycerol, phosphate, and head-groups). But in many cases phospholipases have important roles in synthesis and regulation. For example, we have seen how phospholipase A2 catalyzes the first step in the remodeling of phosphatidylcholine to the surfactant... 

Unlike fatty acids, cholesterol is not degraded to yield energy. Instead excess cholesterol is removed from tissues by HDL for delivery to the liver from which it is excreted in the form of bile salts into the intestine. The transfer of cholesterol from extrahepatic tissues to the liver is called reverse cholesterol transport. When HDL is secreted into the plasma from the liver, it has a discoidal shape and is almost devoid of cholesteryl ester. These newly formed HDL particles are good acceptors for cholesterol in the plasma membranes of cells and are converted into spherical particles by the accumulation of cholesteryl ester. The cholesteryl ester is derived from a reaction between cholesterol and phosphatidylcholine on the surface of the HDL particle catalyzed by lecithimcholesterol acyltransferase (LCAT) (fig. 20.17). LCAT is associated with FIDL in plasma and is activated by apoprotein A-I, a component of HDL (see table 20.3). Associated with the LCAT-HDL complex is cholesteryl ester transfer protein, which catalyzes the transfer of cholesteryl esters from HDL to VLDL or LDL. In the steady state, cholesteryl esters that are synthesized by LCAT are transferred to LDL and VLDL and are catabolized as noted earlier. The HDL particles themselves turn over, but how they are degraded is not firmly established. 

Zaccheo, O., Dinsdale, D., Meacock, P.A., Glynn, P. (2004). Neuropathy target esterase and its yeast homologue degrade phosphatidylcholine to glycerophosphocholine in living cells. J. Biol. Chem. 279 24024-33. 

Porn Ml, Ares MP, Slotte JP (1993) Degradation of plasma membrane phosphatidylcholine appears not to affect the cellular cholesterol distribution. J Lipid Res 34 1385—1392... 

Phosphatidylcholine is degraded by phospholipases that cleave preferentially at specific bonds (Chapter 18). Choline released is phosphorylated by choline kinase and reutilized in phosphatidylcholine synthesis. However, in liver mitochondria, choline is also oxidized to betaine (N-trimethylglycine) ... 

Phosphatidylcholines, above all lecithin, occur in millimolar concentrations in serum and bile. Acetylcholine (ACh) occurs in brain and nerve extracts together with its degradation product, choline. 

Figure 33. Arrhenius plots describing the degradation of soybean phosphatidylcholine at three pH values. Phosphatidylcholine concentration 0.05M (Reproduced from Ref. 309 with permission.)...

The phospholipases A2 (PLAjS) were the first of the phospholipases to be recognized. Over a century ago, Bokay (1877-1878) observed that phosphatidylcholine was degraded... 

The catalytic domain The cPLA2 shows lysophospholipase and transacylase activities that are consistent with the formation of an acyl-serine intermediate characteristic of lipases and Ser-228 has been identified as the involved residue. In addition, Asp-549 has been demonstrated to be the second member of the predicted catalytic triad. However, histidine has not been identified as the third member and none of the 19 histidine residues in the protein has been shown to play any catalytic role. At present, a dyad mechanism must be invoked while Arg-200 is in a position to stabilize the oxyanion intermediate. Interestingly, 1-palmitoyl lysophosphatidylcholine is degraded at a rate comparable to that of 2-arachidonoyl phosphatidylcholine, which raises the possibility that the enzyme serves multiple functions in the cell. The other isoenzymes of CPLA2 also have these three conserved active-site residues (R, S, and D). 

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