Phosphatidylcholine ethanolamine

Phosphatidylethanolamines, or cephalins (so-called because they were first obtained from brain tissue), can be synthesized by reactions analogous to those of de novo synthesis of phosphatidylcholine. Ethanolamine is first phosphorylated by ATP and ethanolamine kinase to phosphoethanolamine, which then reacts with CTP to form CDP-ethanolamine. CTPrphosphoethanolamine cytidylyltransferase is not located on the endoplasmic reticulum, nor do fatty acids activate it as they do the analogous enzyme of phosphatidylcholine synthesis. Finally, 1,2-diacylglycerol phosphoethanolamine transferase catalyses the reaction of diacylglycerol with CDP-ethanolamine to form phosphatidylethanolamine. 

Figure 1 Hydrolysis of ester linkages in glvcerophospholipids bv phospholipases Ai. A . C and D. The fatty acid at the sn-1-position (Ri) is usually saturated while that at the sn-2-position (R2) is unsaturated. R3 varies in different phospholipids and could be choline (phosphatidylcholine), ethanolamine (phosphatidylethanolamine), serine (phospha-tidylserlne), myoinositol (phosphatidylinositol), myoino-sitol-4-monophosphate (phosphatidylinositol-4-monophosphate) or myoinositol-4,5-blsphosphate (phosphatidylinositol-4,5-bisphosphate). In phosphatidic acid, R3 is a hydrogen atom.

Fatty Fraction VLDL/LDL Triacylglycerols Phosphatidylcholines ethanolamines ... 

Some sustained release of bovine somatotropin was demonstrated fror liposome delivery systems. Egg phosphatidylcholine, ethanolamine an otocopheryl hemisuccinate, and Tris salt vesicles released bovine somato ropin, giving hypophysectomized rat growth for over a week (Janoff et al,... 

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.

Phosphatidylethanolamine synthesis begins with phosphorylation of ethanol-amine to form phosphoethanolamine (Figure 25.19). The next reaction involves transfer of a cytidylyl group from CTP to form CDP-ethanolamine and pyrophosphate. As always, PP, hydrolysis drives this reaction forward. A specific phosphoethanolamine transferase then links phosphoethanolamine to the diacylglycerol backbone. Biosynthesis of phosphatidylcholine is entirely analogous because animals synthesize it directly. All of the choline utilized in this pathway must be acquired from the diet. Yeast, certain bacteria, and animal livers, however, can convert phosphatidylethanolamine to phosphatidylcholine by methylation reactions involving S-adenosylmethionine (see Chapter 26). 

FIGURE 25.19 Diacylglycerol and CDP-diacylglycerol are the principal precursors of glycerolipids in eukaryotes. Phosphatidylethanolamine and phosphatidylcholine are formed by reaction of diacylglycerol with CDP-ethanolamine or CDP-choline, respectively. 

Phosphatidic acid Phosphatidylcholine Phosphatidyl- ethanolamine Phosphatidylserine... 

Hauser, H., Pascher, I., Pearson, R.H. Sundell, S. (1981). Preferred conformation and molecular packing of phosphatidyl ethanolamine and phosphatidylcholine. Biochimica Biophysica Acta, 650, 21-51. 

Phosphatidylethanolamine (cephalin) and ph os-phatidylserine (found in most tissues) differ from phosphatidylcholine only in that ethanolamine or serine, respectively, replaces choline (Figure 14-8). 

Figure 24-2. Biosynthesis of triaq/lglycerol and phospholipids. ( , Monoacylglycerol pathway (D, glycerol phosphate pathway.) Phosphatidylethanolamine may be formed from ethanolamine by a pathway similar to that shown for the formation of phosphatidylcholine from choline.

Ethanolamine Choline HOCH2CH2NHj HOCH2CH2N+(CH3)3 Phosphatidylethanolamine Phosphatidylcholine also called Lecithin PE PC... 

The 31P n.m.r. of phospholipids has been the subject of a number of papers.62-89 These have been primarily aimed at investigating the conformation and motion of phospholipids in bilayers, but information has also been obtained on gel-to-liquid crystal transformations of phospholipids.65-67 A P31 1H nuclear Overhauser effect indicates that there is little tendency for mixed phosphatidylcholine/phosphatidyl-ethanolamine vesicles to segregate in separate domains.68 69 A phosphonium analogue (23) of choline chloride has been prepared and converted chemically into... 

Figure 1. Synthetic pathway for PS and PE in mammalian cells. The major steps occuring in the synthesis and interconversion of PS and PE are shown. The PS synthases condense serine with a phosphatidyl moiety derived from PC and PE. The nascent PS can be converted to PE by decarboxylation. PE can also be formed by transfer of a phosphoethanolamine moiety from CDP-ethanolamine to diacylglycerol via the Kennedy pathway. The abbreviations used are PC, phosphatidylcholine PS, phosphatidylserine PE, phosphatidylethanolamine DG, diacylglycerol PSD, phosphatidylserine decarboxylase PSS, PS synthase.

Figure 2. Effect of Ca-ceramide on phosphatidylcholine and phosphatidylethanolamine synthesis in rat-2 fibroblasts. Cells were treated for 2 h in the absence (open bars) or presence (hatched bars) of 25pM C6-ceramide and the following parameters were determined i) the incorporation of [ H]choline and [ H]ethanolamine into phosphatidylcholine (PC) and phosphatidylethanolamine (PE), respectively (panel A) and in CDP-choline and CDP-ethanolamine, respectively (panel B) and ii) the in vitro activity of choline- and ethanolaminephosphotransferase (CPT and EPT) (panel C).

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. 

Phosphatidylcholine (l Ethanolamine CDP-ethanolamine Phosphatidylethanolamine (l Palmitoyl CoA Phosphatidylserine Sphingosine Serine... 

Tetragonia tetragonoides (Pall.) O. Kuntz. Fan Xing (leaf, stem)60 Phosphatidylcholine, phosphatidyl-ethanolamine, phosphatidyl-serine, phosphatidyl-inositol, tetragonin, trigonelline, choline, adenine.56 A remedy for carcinoma, treat ventriculi, stomach ulcers, leukemia. 

Although the sinusoidal and canalicular surfaces of the liver cell are similar, having phosphatidyl ethanolamine and sphingomyelin in the exterior surface, on the contiguous surface of the liver cell, the exterior layer is almost entirely composed of phosphatidylcholine. 

Plasma membrane lipids are asymmetrically distributed between the two monolayers of the bilayer, although the asymmetry, unlike that of membrane proteins, is not absolute. In the plasma membrane of the erythrocyte, for example, choline-containing lipids (phosphatidylcholine and sphingomyelin) are typically found in the outer (extracellular or exoplasmic) leaflet (Fig. 11-5), whereas phosphatidylserine, phosphatidyl-ethanolamine, and the phosphatidylinositols are much more common in the inner (cytoplasmic) leaflet. Changes in the distribution of lipids between plasma membrane leaflets have biological consequences. For example, only when the phosphatidylserine in the plasma membrane moves into the outer leaflet is a platelet able to play its role in formation of a blood clot. For many other cells types, phosphatidylserine exposure on the outer surface marks a cell for destruction by programmed cell death. 

FIGURE 21-28 Pathway for phosphatidylcholine synthesis from choline in mammals. The same strategy shown here (strategy 2 in Fig. 21-24) is also used for salvaging ethanolamine in phosphatidylethanolamine synthesis. 

Mammalian cells have some pathways similar to those in bacteria, but somewhat different routes for synthesizing phosphatidylcholine and phosphatidylethanolamine. The head-group alcohol (choline or ethanolamine) is activated as the CDP derivative, then condensed with diacylglycerol. Phosphatidylserine is derived only from phosphatidylethanolamine. 

Source of choline and ethanolamine used for phospholipid synthesis Phosphatidylethanolamine (PE) and phosphatidylcholine (PC) are the most abundant phospholipids in most eukaryotic cells. The primary route of their synthesis uses choline and ethanolamine obtained either from the diet or from the turnover of the body s phospholipids. Because the amount of choline the body makes is insufficient for its need, choline is an essential dietary nutrient. 

Fig. 21-5, are also used for formation of both phosphatidylcholine and phosphatidylethanolamine. In both cases, the free base, choline, or ethanolamine180a b is phosphorylated with ATP. Choline phosphate formed in this manner is then converted by reaction with CTP to CDP-choline (Eq. 17-58).181 Phosphatidylcholine is formed from this intermediate1813/b while CDP-ethanolamine is used to form phosphatidylethanolamine (Fig. 21-5). These synthetic reactions occur within cell nuclei as well as on surfaces of cytoplasmic membranes.1810...

Synthesis of most phospholipids starts from glycerol-3-phosphate, which is formed in one step from the central metabolic pathways, and acyl-CoA, which arises in one step from activation of a fatty acid. In two acylation steps the key compound phosphatidic acid is formed. This can be converted to many other lipid compounds as well as CDP-diacylglycerol, which is a key branchpoint intermediate that can be converted to other lipids. Distinct routes to phosphatidylethanolamine and phosphatidylcholine are found in prokaryotes and eukaryotes. The pathway found in eukaryotes starts with transport across the plasma membrane of ethanolamine and/or choline. The modified derivatives of these compounds are directly condensed with diacylglycerol to form the corresponding membrane lipids. Modification of the head-groups or tail-groups on preformed lipids is a common reaction. For example, the ethanolamine of the head-group in phosphatidylethanolamine can be replaced in one step by serine or modified in 3 steps to choline. 

Additional regulation of phosphatidylcholine and phosphatidylethanolamine biosynthesis occurs at the second step in the biosynthetic sequence (see fig. 19.4) where either CDP-choline or CDP-ethanolamine are made. For phosphatidylcholine biosynthesis, the activity of CTP phos-phocholine cytidylyltransferase (which makes CDP-choline) is governed by an unusual mechanism. The enzyme... 

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