Phospholipids in cells

Choline, a component of the phospholipids in cell membranes, can be prepared by Sn2 reaction of trimethylamine with ethylene oxide. Show the structure of choline, and propose a mechanism for the reaction. 

Michell, R. H. (1975). Inositol phospholipids in cell surface receptor function. Biochim. Biophys. Acta 415, 81-147. 

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... 

Either of two solutions can be used to redissolve the radiolabeled sterols. The first, oil, is simpler to prepare and administer to the mice. However, it is not strictly a physiological representation of dietary cholesterol, which is largely present with phospholipids in cell membranes, and the oikcholesterol ratio is much greater than would occur in most diets. The second solution, a lipid emulsion, is more tedious to prepare and is less stable but is more physiologically accurate. 

As one further explores the chemical and compositional nature of the phospholipids in cells, some very interesting comparisons can be made, admittedly using a broad brush. The distribution of lipids (including cholesterol), human erythrocytes (red blood cells), bovine erythrocytes, and human platelets serve as good examples. This information is provided in Table 1-4. 

While the point was made as to the variability in phospholipid composition in cells, a facet of the data presented in Table 1-4 has titillated the phagocytes of this author for some years. Basically it centers on the quite constant ratio of choline to noncholine phospholipids in cells. This is clearly evident in the data presented in Table 1-5. 

Choline is an essential component of phospholipids - phosphatidylcholine (lecithin) is the major phospholipid in cell membranes and sphingomyelin is important in the nervous system. Acetylcholine is a transmitter in the central and parasympathetic nervous systems and at neuromuscular junctions, and has a role in the regulation of differentiation and development of the nervous system (Biagioni et al., 2000). Acetylcholine is also synthesized in mononuclear lymphocytes, where it has an autocrine or paracrine role in regulating immune function (Fujii and Kawashima, 2001). 

Polyunsaturated fatty acids containing 20 carbons and three to five double bonds (e.g., arachidonic acid) are usually esterified to position 2 of the glycerol moiety of phospholipids in cell membranes. These fatty acids may require dietary linoleic acid (18 2,A9 12), an essential fatty acid, for their synthesis. 

D. Accumulation of gangliosides is not caused by increased synthesis, but rather by decreased degradation in lysosomes. Phospholipase A2 cleaves fatty acids from position 2 of phospholipids in cell membranes. 

Figure 20.4. Molecular models of cutaway structures formed from the lipid-like peptides with negatively charged heads and glycine tails. Each peptide is c. 2 nm in length. (A, C) Peptide vesicle with an area sliced away. (B, D) Peptide tubes. The glycines are packed inside the bilayer away from water, and the aspartic acids are exposed to water, much like other lipids and surfactants. The modeled dimension is 50-100 nm in diameter. Preliminary experiments suggest that the wall thickness may be c. 4-5 nm, implying that the wall may form a double layer, similar to phospholipids in cell membranes.

Application of high pressure (600-900 MPa) resulted in lower texture degradation of mushroom as compared to thermal blanching. However, high-pressure-induced crystallization of phospholipids in cell membrane led to permeabilization of the cell membrane. Due to increased permeability, extracellularly located polyphenoloxidase could better react with phenols and resulted in increased browning... 

The major pathway of phosphatidylcholine (lecithin) synthesis is via preformed choline (Fig. 15.5). Phosphotidylethanolamine can be converted to phosphatidylcholine in a minor pathway by the addition of 3CH3 groups (from methionine). Thus, phosphatidylcholine can be synthesized de novo if choline is not available and there is a source of "CH3" groups. In a major pathway, phosphatidylcholine can also be synthesized more directly starting with choline. Choline can be phosphorylated with ATP to form phosphocholine. Phosphocholine can react, via phosphocholine cytidyltransferase, in the presence of CTP, to form CDP choline + pyrophosphate, which is pulled in the forward direction by hydrolysis of the pyrophosphate. The CDP choline then can react with diacylglycerol to form phosphatidylcholine and CMP. This reaction is catalyzed by the enzyme phosphocholinetransferase. The major role of phospholipids in cell membranes is discussed in Chapter 4. 

A major fate of PA is conversion to DG that can be metabolized to PC, PE, and TG (Fig. 1). Alternatively, PA can react with CTP to form CDP-DG that is utilized for biosynthesis of the inositol phospholipids as well as phosphatidylglycerol (PG) and diphosphatidylglycerol (DPG) (Fig. 1). Inositol is a cyclohexane derivative in which all six carbons contain hydroxyl groups. The most common inositol isoform is myo-inositol but other less abundant inositols with different structures also occur. The first report of an inositol-containing lipid was in 1930 in Mycobacteria which is ironic since inositol lipids are rarely found in bacteria. Brain is the richest source of inositol-containing lipids, as first discovered by Folch and Wooley in 1942. In 1949, Folch described a PI phosphate (PI-P) that was later found to include PI and PI bisphosphate (PI-P2). The chemical structures of PI, PI-P, and PI-P2 were determined by Ballou and co-workers between 1959 and 1961. PI (1.7 pmol/g liver) constitutes -10% of the phospholipids in cells and tissues. PI-P and PI-P2 are present at much lower concentrations (1-3% of PI). In 1958, Agranoff and co-workers first reported the incorporation of [ HJinositol into PI. Subsequently, Paulus and Kennedy showed that CTP was the preferred nucleotide donor. 

The starting point of their biosynthesis is linoleic acid, an essential dietary constituent for Man. This is converted to arachidonic acid (4.68) (a 20-carbon aliphatic acid with four double bonds) which is stored as a phospholipid in cell membranes. From these it is liberated, on demand, by phospholipase A2. Arachidonic acid is further metabolized by two pathways. In the first of these, it... 

After oxygenation, the fate of fatty add epoxides is diverse and varied (Fig. 13.4). EETs may transactivate membrane receptors or directly bind to ion charmels or other proteins to cause biological effects. All four EET regioisomers can be esterified into phospholipids in cell mem-... 

Figure 22.15 Phospholipids in cell membranes. The polar head is represented by a blue sphere, and the nonpolar tails are shown in red. 

The other response to G-protein activation involves phosphatidylinositol, one of the phospholipids in cell membranes (section 4.3.1.2). As shown in Figure 10.9, phosphatidylinositol can undergo two phosphorylations, catalysed by phosphatidylinositol kinase, to yield phosphatidylinositol bisphosphate (PIPj). PIPj is a substrate for phospholipase C, which is activated by the binding of (G-protein a-subunit)—GTE The products of phospholipase C action are inositol trisphosphate (IPj) and diacylglycerol, both of which act as intracellular second messengers. 

PAs are double character molecules whose self-assembling mechanism resembles that of phospholipids in cell membranes. To design a PA, a hydrophobic structural domain— usually in the form of a polymer or alkyl chain, or less frequently, a sequence of nonpolar amino acids—is linked to hydrophilic peptides. 

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