Choline lysophosphatidylcholine

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. 

The pathway for the synthesis of dipalmitoyl-phos-phatidylcholine is illustrated in figure 19.5. The starting species of phosphatidylcholine is made by the CDP-choline pathway (see fig. 19.4). The fatty acid at the sn-2 position, which is usually unsaturated, is hydrolyzed by phospholi-pase A2, and the lysophosphatidylcholine is reacylated with palmitoyl-CoA. This modification permits alteration of the properties of the phospholipid without resynthesis of the entire molecule, a strategy called remodeling. Deacylation-reacylation of phosphatidylcholine occurs in other tissues and provides an important route for alteration of the fatty acid substituents at both the sn-1 and sn-2 positions. For example, fatty acids at the sn-2 position can be replaced by arachidonic acid, which is stored there until needed for eicosanoid biosynthesis, as we discuss later in this chapter. 

Boggs K. P., Rock C. O., and Jackowski S. (1995). Lysophosphatidylcholine and l-O-octadecyl-2-O- methyl-rac-glycero-3-phosphocholine inhibit the CDP-choline pathway of phosphatidylcholine synthesis at the CTP phosphocholine cytidylyltransferase step. J. Biol. Chem. 270 7757-7764. 

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. 

All of the above SMases are C type SMases that produce Cer and choline phosphate an SMase D (which produces Cer 1-phosphate and choline) is found in the venom of brown recluse spider, Corynebacterium pseudotuberculosis (which commonly infects sheep). Vibrio damsela (an aquatic bacterium that causes wound infections in humans), and the human pathogen Arcanobacterium haemolyticum. The venom SMase D produces much of the tissue damage caused by these organisms (A.P Truett, 1993) by sustained activation of inflammation (S.H. Farsky, 2005). Interestingly, SMase also acts as a lysophosphatidylcholine phosphodiesterase to produce lysophosphatidic acid, another inflammatory mediator (L.A. van Meeteren, 2004). 

DAG produced via the action of PA phosphatase can also be converted to PC by the catalytic action of choline phosphotransferase (CPT). Production of polyunsaturated FAs via the catalytic action of membrane-bound desaturases occurs while monounsaturated FAs are esterifled to the glycerol backbone of PC. The combined forward and reverse reactions catalyzed by lysophosphatidylcholine acyltransferase (LPCAT) are believed to facilitate acyl exchange at the sn-2 position of PC, with the acyl-CoA pool thereby allowing incorporation of polyunsaturated FA into TAG via the acyl-CoA-dependent acyltransferase reactions in the mainstream of TAG biosynthesis. The reverse reaction of CPT to produce DAG provides a second opportunity to introduce polyunsaturated FA into TAG. In addition, phospholipase A2 may catalyze the release of free FA from PC. The liberated FA could be reesterified as acyl-CoA for use in the mainstream of TAG biosynthesis. 

Phosphatidylcholines are the most important fraction of soybean lecithin. Then-content may be increased by transesterihcation with choline hydrochloride, catalyzed by phospholipase D. Phosphatidylcholine content may thus be increased from 30% up to 60 or 70%, or from 75 or 80% to more than 90% (Juneja et ah, 1989). Similarly, phosphatidylserine can be produced from phosphatidylcholine by enzyme-catalyzed inter-esterification (Yaqoob et al., 2001). Another modification of lecithins is the inter-esterihcation of lysophosphatidylcholine with fish PUFA under catalytic action of phospholipase A2 (Na et al., 1990). 

The main absorbed product of phospholipid digestion is monoacyl-phosphatidylcholine (lysophosphatidylcholine). A fatty acid is re-esterified to position 1 to form phosphatidylcholine by an acyl transferase located in the villus tips of the intestinal brush border. The function of this phospholipid will be to stabilize the triacylglycerol-rich particles, or chylomicrons, exported from the cell as described later. It is thought that the phosphatidylcholine used for the synthesis and repair of membranes in the enterocytes (cells with a rapid turnover) is synthesized by the classical CDP-choline pathway (section 7.1) in cells at the villus crypts. 

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