Synthesis of Phospholipids

Synthesis of phosphatidylcholine and phosphatidylethanolamine begins with activation of choline (or ethanolamine) with ATP via choline kinase to yield phosphocholine (phosphoethanolamine) + ADP the activated base is transferred via CTP and phosphocholine cytidyl transferase to form CDP-choline (CDP-ethanolamine) and PPi. The base is then transferred to the sn-3 of diacylglycerol via phosphocholine diacylglycerol transferase to yield phosphatidylcholine (phosphatidylethanolamine) + CMP. The cytidyl transferase is believed to be the rate-limiting or regulatory step in the pathway. Phospha-tidylserine is formed by a direct transfer and substitution of serine for ethanolamine in phosphatidylethanolamine. Phosphatidyl serine can be dec-arboxylated to form phosphatidylethanolamine. 

Phosphatidylcholine is preferentially synthesized in lactating mammary tissue (Kinsella, 1973), possibly regulated by the differential activities of choline kinase and ethanolamine kinase. Choline kinase has a lower Km and a higher Vmax with its substrate than does ethanolamine kinase. Also, choline kinase is inhibited slightly by ethanolamine, whereas choline is a potent competitive inhibitor of ethanolamine kinase. Thus, the intracellular concentration of choline probably regulates the synthesis of these two phos-phoglycerides (Infante and Kinsella, 1976). 

Synthesis of phosphatidylinositol follows a slightly different pathway from the other phosphoglycerides. Phosphatidate is activated by CTP-phos-phatidate cytidyl transferase to form CDP-diacylglycerol. Free inositol is then incorporated by CDP-diacylglycerol inositol transferase, with the release of CMP. Phosphatidylinositol usually constitutes less than 5% of total milk phospholipids (Bitman and Wood, 1990). 

The glycerol ethers and plasmalogens are a unique class of phosphoglycerides that contain an ether-linked chain at the sn-1 position. These are formed by the incorporation of acyl CoA at the sn-1 position of dihydroxy-acetone phosphate. The acyl group is then exchanged for a long-chain 

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Ishihara K, Hanyuda H, and Nakabayashi N. Synthesis of phospholipids polymers having a urethane bond in the side chain as coating material on segmented polyurethane and their platelet adhesion resistant properties. Biomaterials, 1995, 16(11), 873-879. 

The mechanisms involved in the establishment of lipid asymmetry are not well understood. The enzymes involved in the synthesis of phospholipids are located on the cytoplasmic side of microsomal membrane vesicles. Translocases (flippases) exist that transfer certain phospholipids (eg, phosphatidylcholine) from the inner to the outer leaflet. Specific proteins that preferentially bind individual phospholipids also appear to be... 

Lipogenesis in liver and possibly adipose tissue, leading to increased synthesis of phospholipids and triacylglycerol. 

Polyunsaturated fatty acids Polyunsaturated fatty acids are provided in the triacylglycer-ols on phospholipids in the feeds. They are required for synthesis of phospholipids, which are required for formation of new membranes in proliferating cells, and as precursors for fat signalling molecules that are important in control of proliferation (see below). 

A summary of some of these processes is as follows synthesis of phospholipids and cholesterol de novo synthesis of ribonucleotides synthesis of RNA de novo synthesis of deoxyribonucleotides regulation of synthesis of deoxyribonucleotides salvage pathways duplication of DNA transcription and translation (polypeptide synthesis). After this series of topics, those of fuels and ATP generation, mitosis and, finally, regulation of the cycle, are described and discussed. 

Example 12 dibenzyl-iV,iSr-diisopropylphosphoroamidite has been applied by Lindberg et al. in the efficient synthesis of phospholipids from glycidol phosphates [39]. 

In the human body choline is needed for the synthesis of phospholipids in cell membranes, methyl metabolism, transmembrane signaling and lipid cholesterol transport and metabolism [169]. It is transported into mammalian cells by a high-affinity sodium-dependent transport system. Intracellular choline is metabolized to phosphorylcholine, the reaction being catalyzed by the enzyme choline... 

Chemicals such as these bind with phospholipids, inhibiting their hydrolysis by phospholipases. They can also interact with phospholipases, thus limiting the ability of the enzyme to metabolize phospholipid. Drugs, which have this structure, may also influence the synthesis of phospholipids. 

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... 

Since the synthesis of glycolipids involves the synthesis of both the lipid and the oligosaccharide portions, we shall also discuss that part of the recorded lipid synthetic work which has involved the use of carbohydrates. In fact, some of the first-recorded applications of carbohydrate molecules as chiral templates are to be found in the lipid field particularly with the use of 1,2 5,6-di-O-isopropylidene-D-mannitol [33] as a precursor of chiral glycerol derivatives for the synthesis of phospholipids and glycolipids based on glycerol and with the use of glucosamine derivatives for the synthesis of phytosphingosines [34] and since this area has not previously been reviewed, it will be treated with a more historical perspective. 

P. Wang, M. Schuster, Y.-F. Wang, and C.-H. Wong, Synthesis of phospholipid-inhibitor conjugates by enzymatic transphosphatidylation with phospholipase D, J. Am. Chem. Soc., 115 (1993) 10487-10491. 

The new 31p-NMR results also allow us to directly establish the specificity of various phospholipases by direct product observation and should also be very useful in regiospecific chemical synthesis of phospholipids. 

New Methods in the Synthesis of Phospholipids and Their Analogs on the Basis of Phosphites and Amidophosphites of Glycerine... 

Despite the negative results of feeding experiments, it is clear that animals require myo-inositol for the synthesis of phospholipids (see p. 175), and, perhaps, for other purposes. Indeed, jra/o-inositol is necessary for the propagation, in culture, of 19 out of 20 lines of normal and malignant human and mouse tissues.122 It thus appears likely that only certain animal... 

The provision of an appropriate fatty acid pool for use in synthesis of phospholipids involves a complex mixture of dietary and biosynthetic effects. To at least some extent, one is what one eats applies in the context of adaptation of lipid-containing structures, a point... 

Figure 26.1. Structure of CDP-Diacylglycerol. A key intermediate in the synthesis of phospholipids consists of phosphatidate and CMP joined by a pyrophosphate linkage. 

The most suitable starting materials, for the total synthesis of phospholipids, are optically active derivatives from glycerol, called chiral C3 building blocks. In addition to proper conhguration, an early differentiation of the hydroxyl groups is also necessary to shorten the process of synthesis (75). 

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