Phosphatidal choline

Gottfried, E. L. and Rapport, M. M. (1962) The biochemistry of plasmalogens I Isolation and characterization of phosphatidal choline, a pure native plasmalogen, J. Biol. Chem. 237, 329-333. 

Plasmalogens are phospholipids containing an a,P-unsaturated ether at C-1. Phosphatidal choline, the plasmalogen corresponding to phosphatidyl choline, is formed by desaturation of a 1-alkyl precursor. 

It is now generally agreed that choline plasmalogen (VII) may be represented by the unsaturated ether structure of Rapport and co-workers (Rapport et al. 1957, Rapport and Franzl 1957a), who suggest that the compound be referred to as phosphatidal choline. 

Lecithin. Lecithin [8002-43-5] (qv) is a mixture of fat-like compounds that includes phosphatidyl choline, phosphatidyl ethanolamines, inositol phosphatides, and other compounds (37). Commercial lecithin was originally obtained from egg yolks, but is now extracted from soybean oil. Lecithin is used in many products, including margarine, chocolate, ice cream, cake batter, and bread. 

Fig. 1. Chemical stmcture of phosphatidylcholine (PC) (1) and other related phosphohpids. R C O represents fatty acid residues. The choline fragment may be replaced by other moieties such as ethanolamine (2) to give phosphatidylethanolamine (PE), inositol (3) to give phosphatidylinositol (PI), serine (4), or glycerol (5). IfH replaces choline, the compound is phosphatidic acid (6). The corresponding lUPAC-lUB names ate (1), l,2-diacyl-t -glyceto(3)phosphocholine (2), l,2-diacyl-t -glyceto(3)phosphoethanolamine (3), 1,2-diacyl-t -glyceto(3)phosphoinositol (4), 1,2-diacyl-t -glyceto(3)phospho-L-serine and (5), l,2-diacyl-t -glyceto(3)phospho(3)-t -glycetol.

Plasmalogens are ether glycerophospholipids in which the alkyl moiety is d5-a,/3-unsaturated (Figure 8.10). Common plasmalogen head groups include choline, ethanolamine, and serine. These lipids are referred to as phosphati-dal choline, phosphatidal ethanolamine, and phosphatidal serine. 

Triacylglycerols and some phosphoglycerols are synthesized by progressive acylation of glycerol 3-phosphate. The pathway bifurcates at phosphatidate, forming inositol phospholipids and cardiolipin on the one hand and triacylglycerol and choline and ethanolamine phospholipids on the other. 

Soya lecithin is a natural product which contains about 34% glycerides (soya oil), 5% sugars, and 61% phosphatides. The phosphatides in turn are comprised of phosphatidyl choline, i.e., chemical lecithin (20%), phosphatidyl ethanolamine (20%), and phosphatidyl inositol (21%). 

The chromatogram of the commercial soya lecithin as shown in Figure 4 suggests a number of components and all subsequent work was done with the ethanol-soluble fraction, i.e., phosphatidyl choline, or the ethanol-insoluble fraction, comprised primarily of other phosphatides. 

Figure 7. Effect of sample size on apparent molecular weight for soya lecithin phosphatide fractions (conditions same as for Figures 5 and 6 (O) ethanol-soluble fraction (phosphatidyl choline), oligomer GPC (%) ethanol-soluble fraction (phosphatidyl choline), "main column (l ) ethanol-insoluble fraction (other phos-p hat ides), "oligomer GPC (A) ethanol-insoluble fraction (other phosphatides),...

Analogues of phosphatidyl ethanolamine, phosphatidyl choline, and phosphatidic acid with pantoic acid skeleton were prepared by phosphorylation with the respective phosphoric mono-, bis-, and tristriazolide [17]... 

The nomenclature for associating individual fatty acid groups with particular phosphodig-lyceride derivatives is straightforward. For instance, a phosphatidic acid (PA) derivative which contains two myristic acid chains is commonly called dimyristoyl phosphatidic acid (DMPA). Likewise, a PC derivative containing two palmitate chains is called dipalmitoyl phosphatidyl choline (DPPC). Other phosphodiglyceride derivatives are similarly named. 

The rate of production of DAG in the cell does not occur linearly with time, but rather it is biphasic. The first peak is rapid and transient and coincides with the formation of IP3 and the release of Ca2+ this DAG is therefore derived from the PI-PLC catalyzed hydrolysis of phosphatidylinositols [1]. There is then an extended period of enhanced DAG production that is now known to be derived from the more abundant phospholipid phosphatidylcholine (PC), which has a different composition of fatty acid side chains [9]. Although DAG may be generated directly from PC through the action of PC-PLC, it can also be formed indirectly from PC. In this pathway, PC is first hydrolyzed by PLD to give choline and phosphatidic acid, which is then converted to DAG by the action of a phos-phatidic acid phosphatase [10,11 ]. 

Phosphatidic acid Phosphatidyl ethanolamine Phosphatidyl serine Phosphatidyl choline Phosphatidyl inositol Sphingomyelin. 

It can be seen from Figure 1 that the choline-containing phospholipids, phosphatidylcholine and sphingomyelin are localized predominantly in the outer monolayer of the plasma membrane. The aminophospholipids, conprising phosphatidylethanolamine and phosphatidylserine, by contrast, are enriched in the cytoplasmic leaflet of the membrane (Bretcher, 1972b Rothman and Lenard, 1977 Op den Kamp, 1979). The transmembrane distribution of the minor membrane lipid components has been determined by reaction with lipid-specific antibodies (Gascard et al, 1991) and lipid hydrolases (Biitikofer et al, 1990). Such studies have shown that phosphatidic acid, phosphatidylinositol and phosphatidylinositol-4,5-fc -phosphate all resemble phosphatidylethanolamine in that about 80% of the phospholipids are localized in the cytoplasmic leaflet of the membrane. 

Achve translocation of phospholipids aaoss the plasma membrane has been demonstrated both from the inner to the outer leaflet and from the outer to the inner leaflet. The translocation processes specifically transport phosphatidyserine and phosphatidylethanolamine from the cytoplasmic to the outer surface of the membrane while choline phosphatides are transported from the outer to the cytoplasmic surface. The rate of translocahon, in general, is greater for the amino phospholipids compared with the choline phospholipids. 

The simplest of the glycerophospholipids is phosphatidic acid, in which phosphate is linked to the third hydroxyl function, forming a phosphate ester. More complex glycerophospholipids are derivatives of phosphatidic acid in which one of several groups is attached commonly choline, ethanolamine, serine, or myo-inositol. Structures are collected in table 19.1. 

The other phospholipids can be derived from phosphatidates (residue = phosphatidyl). Their phosphate residues are esterified with the hydroxyl group of an amino alcohol choline, ethanolamine, or serine) or with the cyclohexane derivative myo-inositol. Phosphatidylcholine is shown here as an example of this type of compound. When two phosphatidyl residues are linked with one glycerol, the result is cardiolipin (not shown), a phospholipid that is characteristic of the inner mitochondrial membrane. Lysophospholipids arise from phospholipids by enzymatic cleavage of an acyl residue. The hemolytic effect of bee and snake venoms is due in part to this reaction. 

Phosphatidylcholine (lecithin) is the most abundant phospholipid in membranes. Phosphatidylethanolamine (cephalin) has an ethanolamine residue instead of choline, and phosphatidylserine has a serine residue. In phosphatidylinositol, phosphatidate is esterified with the sugarlike cyclic polyalcohol myo-inositol. A doubly phosphorylated derivative of this phospholipid, phosphatidylinositol 4,5-bisphosphate, is a special component of membranes, which, by enzymatic cleavage, can give rise to two second messengers, diacylglycerol (DAG) and inositol l,4,5trisphosphate (InsPsi see p.386). 

Transfer of a phosphocholine residue to the free OH group gives rise to phosphatidylcholine (lecithin enzyme l-alkyl-2-acetyl-glycerolcholine phosphotransferase 2.7.8.16). The phosphocholine residue is derived from the precursor CDP-choline (see p. 110). Phos-phatidylethanolamine is similarly formed from CDP-ethanolamine and DAG. By contrast, phosphatidylserine is derived from phosphatidylethanolamine by an exchange of the amino alcohol. Further reactions serve to interconvert the phospholipids—e.g., phosphatidylserine can be converted into phosphatidylethanolamine by decarboxylation, and the latter can then be converted into phosphatidylcholine by methylation with S-adenosyl methionine (not shown see also p. 409). The biosynthesis of phosphatidylino-sitol starts from phosphatidate rather than DAG. 

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