Phosphatidylcholine diacyl

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.

The role of protein kinase C in many neutrophil functions is undisputed and has been recognised for some time. For many years it was believed that the source of DAG, the activator of protein kinase C, was derived from the activity of PLC on membrane phosphatidylinositol lipids. Whilst this enzyme undoubtedly does generate some DAG (which may then activate protein kinase C), there are many reasons to indicate that this enzyme activity is insufficient to account for all the DAG generated by activated neutrophils. More recently, experimental evidence has been provided to show that a third phospholipase (PLD) is involved in neutrophil activation, and that this enzyme is probably responsible for the majority of DAG that is formed during cell stimulation. The most important substrate for PLD is phosphatidylcholine, the major phospholipid found in neutrophil plasma membranes, which accounts for over 40% of the phospholipid pool. The sn-1 position of phosphatidylcholine is either acyl linked or alkyl linked, whereas the sn-2 position is invariably acyl linked. In neutrophils, alkyl-phosphatidylcholine (1-0-alky 1-PC) represents about 40% of the phosphatidylcholine pool (and is also the substrate utilised for PAF formation), whereas the remainder is diacyl-phosphatidylcholine. Both of these types of phosphatidylcholine are substrates for PLD and PLA2. 

The different phosphoglycerides are often named by placing the constituent attached to the phosphate group after phosphatidyl , e.g. phosphatidyl choline (3-in-phosphatidylcholine or l,2-diacyl-sn-glycero-3-phosphoryl-choline). There are many phosphoglycerides because of the possible variation in the fatty acid chains, and when the full chemical structure is known, it should be used (e.g. l-palmitoyl-2-oleoyl-phosphatidylcholine). Nomenclature that entails the use of the DL system should be avoided. 

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... 

Phosphatidylcholine can be formed by two pathways as described on pp. 1198-1199. A third pathway, used by some bacteria, involves a direct one-step reaction of choline with CDP-diacyl-glycerol.359 Write a reasonable chemical mechanism. 

The nomenclature rules just cited for phosphatidylcholine and its analogs also hold for ethanolamine phosphoglycerides. Mixtures of the diacyl, alkenyl acyl, and alkyl ether forms are found, for example, in macrophages and neutrophils but in much different ratios than observed for the choline-containing types (Figure 1-11). Again, only the (diacyl) phosphatidylethanol-amine is found in liver cells. These structures will be discussed in more detail in Chapter 5. 

Exactly the same methodology as applied to analysis of diacylphosphatidyl-choline can be used here. Thin-layer chromatography using several different types of adsorbents will show that usually the alkylacyl derivative will comigrate with the diacyl—as well as the alkenylacyl—phosphatidylcholine counterparts. 

The major (salvage) pathways for the formation of phosphatidylcholine and ethanolamine are illustrated in Figure 19.16. Free (dietary) choline and etha-nolamine are converted to their CDP derivatives, which then react with diacyl-glycerol to form phosphatidylcholine and ethanolamine. In the lungs, another pathway forms dipalmitoyl phosphatidylcholine, a powerful surfactant. Phos-phatidylethanolamine may be methylated by S-adenosylmethionine (SAM see Chapter 20) to yield phosphatidylcholine. The reaction is catalyzed by two enzymes the first methyl group is transferred via phosphatidylethanolamine N-methyltransferase I. The other two methyl groups are transferred by phosphatidylethanolamine N-methyltransferase II. Some authorities believe that the two enzymes are identical. It has also been proposed that methylation of phospha-... 

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-... 

Lecithin is the widely obtained edible byproduct from oil processing. The definition of lecithin varies considerably however, lecithin represents a family of products based on naturally occurring phospholipids and other polar lipids. Most of the commercially available lecithins are obtained from various oilseeds or egg (179). In the scientihc hterature, lecithin stands for a special phospholipid, 1,2-diacyl-j n-glycero-3-phosphatidylcholine or phosphatidylchohne. 

The chemical nomenclature and CAS Registry numbering of lecithin is complex. The commercially available lecithin, used in cosmetics, pharmaceuticals, and food products, is a complex mixture of phospholipids and other materials. However, it may be referred to in some literature sources as l,2-diacyl-s -glycero-3-phosphocholine (trivial chemical name, phosphatidylcholine). This material is the principal constituent of egg lecithin and has the same CAS Registry Number. The name lecithin and the CAS Registry Number above are thus used to refer to both lecithin and phosphatidylcholine in some literature sources. 

B. Phosphatidylcholine (lecithin) may be produced when CDP-choline reacts with a diacyl-glycerol. 

Phosphatidylcholine specific phospholipase C (PLC) can be used for the hydrolysis of PC (and PX) affording natural diacyl glycerol (DAG ) and chohne phosphate (CP) (or corresponding organic phosphate, OP). Transesterification has not been observed with this enzyme. The substrate specificity is less broad than desirable for the synthesis of OP that is otherwise... 

Particulate preparations from higher plants will esterify plant sterols diacyl glycerols are the most effective acyl donors. However in Phycomyces blakesleamis the donor is phosphatidylcholine [5]. 

Lysophosphatidylcholine is a frequent product of oxidized phospholipid hydrolysis and shows structural similarities to its diacyl counterparts containing a short acyl chain in sn-2 position. Therefore, its cellular activities deserve particular attention, especially in the context of its cytotoxicity. The effects of phospholipid oxidation products and lyso-PC depend not only on their concentration but also on the cell type. Lyso-PC containing a long acyl chain in sn- position (e.g. C16 0, C18 0) is an amphiphilic phospholipid that is generated by phospholipase-catalyzed hydrolysis of phosphatidylcholine or extensive oxidation leading to loss of the entire sn-2 acyl chain. Its critical micellar concentration (CMC) is around 50 pM. It is easily taken up into lipid membranes and increases their fluidities . Above the CMC it forms micelles that destroy membrane integrity also by removal of proteins as shown in erythrocytes (Bierbaum et al., 1979 Colics and Chisholm, 2000). Lyso-PC exerts apoptotic effects in rVSMCs at concentrations below its CMC and induces necrotic cell death at concentrations above its CMC (Hsieh et al.,... 

Abbreviations APCI Atmospheric Pressure Chemical Ionization DAG Diacyl-glycerols DE Delayed Extraction DHB 2,5-Dihydroxybenzoic Acid El Electron Impact ESI Electrospray Ionisation FACS Fluorescence-activated cell sorting GC Gas Chromatography HDL High Density Lipoprotein HPLC High-Performance Liquid Chromatography IR Infrared LDL Low Density Lipoprotein LOD Level of Detection LOQ Level of Quantification LPC Lyso-Phosphatidylcholine LPL Lyso-Phospholipid MALDI Matrix-... 

Phospholipase D hydrolyzes the phosphoester bond, primarily of phosphatidylcholine, to form phosphatidic acid or l-alkyl-2-acyl-sn-glycero-3-phosphate when the substrate is an ether phospholipid (Chapter 11). In human neutrophils, the phosphatidic acids produced upon stimulation of the cells by chemotactic peptides and other stimuli are approximately 50% alkylacyl-linked species and 50% diacyl-linked species, reflecting the cellular... 

---