Phosphatidylcholines

Phosphatidylcholines, or lecithins, are zwitterionic over a wide pH range because of the presence of a quaternary ammonium group and a phosphate moiety. Phosphatidylcholines are the most abundant phospholipids in animal tissues and typically contain palmitic, stearic, oleic, linoleic, or arachidonic acid, usually with saturated fatty acids in the sn- position and unsaturated fatty acids at sn-2. 

The de novo pathways for phospholipid synthesis use cytidine triphosphate (CTP) for activation of intermediate species (analogous to the role of UTP in glycogen biosynthesis Chapter 15). The principal pathway of 

Phosphatidylcholine can also be synthesized by the methylation pathway that converts phosphatidylethanolamine to phosphatidylcholine, principally in the liver. The methyl donor is S-adenosylmethionine (Chapter 17). Phosphatidylethanolamine-N-methyltransferase transfers three methyl groups in sequence to produce phosphatidylcholine. The fatty acid components of phosphatidylcholine can then be altered by deacylation-reacylation reactions. 

Phosphatidylcholine is degraded by phospholipases that cleave preferentially at specific bonds (Chapter 18). Choline released is phosphorylated by choline kinase and reutilized in phosphatidylcholine synthesis. However, in liver mitochondria, choline is also oxidized to betaine (N-trimethylglycine)  

Betaine functions as a methyl donor (e.g., in methionine biosynthesis from homocysteine Chapter 17), and it can also be converted to glycine. 

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McConnell et al. [196] and Andelman and co-workers have predicted [197,198] an ordered array of liquid domains in the gas-liquid coexistence regime caused by the dipole moment difference between the phases. These superstructures were observed in monolayers of dipalmitoyl phosphatidylcholine monolayers [170]. 

Fig. VI-6. The force between two crossed cylinders coated with mica and carrying adsorbed bilayers of phosphatidylcholine lipids at 22°C. The solid symbols are for 1.2 mM salt while the open circles are for 10.9 roM salt. The solid curves are the DLVO theoretical calculations. The inset shows the effect of the van der Waals force at small separations the Hamaker constant is estimated from this to be 7 1 x 10 erg. In the absence of salt there is no double-layer force and the adhesive force is -1.0 mN/m. (From Ref. 66.)...

An essential component of cell membranes are the lipids, lecithins, or phosphatidylcholines (PC). The typical ir-a behavior shown in Fig. XV-6 is similar to that for the simple fatty-acid monolayers (see Fig. IV-16) and has been modeled theoretically [36]. Branched hydrocarbons tails tend to expand the mono-layer [38], but generally the phase behavior is described by a fluid-gel transition at the plateau [39] and a semicrystalline phase at low a. As illustrated in Fig. XV-7, the areas of the dense phase may initially be highly branched, but they anneal to a circular shape on recompression [40]. The theoretical evaluation of these shape transitions is discussed in Section IV-4F. 

A study by Bames and co-workers of the equilibrium spreading behavior of dimyristol phosphatidylcholine (DMPC) reconciles the differences between spreading of bulk solids and dispersions of liposomes [41]. This study shows the formation of multibilayers below the monolayer at the air-water interface. An incipient phase separation, undetectable by microscopy, in DMPC-cholesterol... 

Figure Bl.20.11. Force curves of DMPC/DPPE (dimyristoyl phosphatidylcholine and dipalmitoyl phosphatidylethanolainine) bilayers across a solution of PEG at different concentrations. Clearly visible is a concentration-dependent depletion attraction, with pennission from [17],...

Phosphatidylcholine is an important component of cell membranes but cell mem branes are more than simply lipid bilayers Although their composition varies with their source a typical membrane contains about equal amounts of lipid and protein and the amount of cholesterol m the lipid fraction can approximate that of phosphatidylcholine The lipid fraction is responsible for the structure of the membrane Phosphatidyl choline provides the bilayer that is the barrier between what is inside the cell and what IS outside Cholesterol intermingles with the phosphatidylcholine to confer an extra measure of rigidity to the membrane... 

The identity of the moiety (other than glycerol) esterified to the phosphoric group determines the specific phosphoHpid compound. The three most common phosphoHpids in commercial oils are phosphatidylcholine or lecithin [8002-45-5] (3a), phosphatidylethanolamine or cephalin [4537-76-2] (3b), and phosphatidjlinositol [28154-49-7] (3c). These materials are important constituents of plant and animal membranes. The phosphoHpid content of oils varies widely. Laurie oils, such as coconut and palm kernel, contain a few hundredths of a percent. Most oils contain 0.1 to 0.5%. Com and cottonseed oils contain almost 1% whereas soybean oil can vary from 1 to 3% phosphoHpid. Some phosphoHpids, such as dipaLmitoylphosphatidylcholine (R = R = palmitic R" = choline), form bilayer stmetures known as vesicles or Hposomes. The bdayer stmeture can microencapsulate solutes and transport them through systems where they would normally be degraded. This property allows their use in dmg deHvery systems (qv) (8). 

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.

Commercial cmde lecithin is a brown to light yeUow fatty substance with a Hquid to plastic consistency. Its density is 0.97 g/mL (Uquid) and 0.5 g/mL (granule). The color is dependent on its origin, process conditions, and whether it is unbleached, bleached, or filtered. Its consistency is deterrnined chiefly by its oil, free fatty acid, and moisture content. Properly refined lecithin has practically no odor and has a bland taste. It is soluble in aflphatic and aromatic hydrocarbons, including the halogenated hydrocarbons however, it is only partially soluble in aflphatic alcohols (Table 5). Pure phosphatidylcholine is soluble in ethanol. 

Alcohol fractionation redistributes the phosphoHpids according to their respective hydrophilic and lipophilic properties (13). A process to produce fractionated phosphoHpids with a phosphatidylcholine (PC) content of more than 30% and a PC/PE (phosphatidylethanolamine) quotient of ca 4 has been developed. With this process it is possible to produce 1000 t per year. 

To produce highly purified phosphatidylcholine there are two industrial processes batch and continuous. In the batch process for producing phosphatidylcholine fractions with 70—96% PC (Pig. 4) (14,15) deoiled lecithin is blended at 30°C with 30 wt % ethanol, 90 vol %, eventually in the presence of a solubiHzer (for example, mono-, di-, or triglycerides). The ethanol-insoluble fraction is separated and dried. The ethanol-soluble fraction is mixed with aluminum oxide 1 1 and stirred for approximately one hour. After separation, the phosphatidylcholine fraction is concentrated, dried, and packed. 

Pig. 4. Batch process for producing phosphatidylcholine fractions. 1, Ethanol storage tank 2, deoiled lecithin 3, solubiHzer 4, blender 5, film-type evaporator 6, ethanol-insoluble fraction 7, ethanol-soluble fraction 8, aluminum oxide 9, mixer 10, decanter 11, dryer 12, aluminum oxide removal 13, phosphatidylcholine solution 14, circulating evaporator 15, cooler 16, dryer and 17, phosphatidylcholine. 

In the continuous process for producing phosphatidylcholine fractions with 70—96% PC at a capacity of 600 t/yr (Pig. 5) (16), lecithin is continuously extracted with ethanol at 80°C. After separation the ethanol-insoluble fraction is separated. The ethanol-soluble fraction mns into a chromatography column and is eluted with ethanol at 100°C. The phosphatidylcholine solution is concentrated and dried. The pure phosphatidylcholine is separated as dry sticky material. This material can be granulated (17). 

Fig. 5. Continuous process for producing phosphatidylcholine. 1, Lecithin 2, ethanol 3, blender 4, diffuser 5, thin-type evaporator 6, ethanol-insoluble fraction 7, heat exchanger 8, chromatography column (Si02) 9, prestream 10 and 12, phosphatidylcholine solution 11, circulating evaporator 13, dryer ...

Food. Lecithin is a widely used nutritional supplement rich ia polyunsaturated fatty acids, phosphatidylcholine, phosphatidylethanolamine, phosphatidjhnositol, and organically combiaed phosphoms, with emulsifying and antioxidant properties (38). 

A. I. Archakov and K. J. Gundermann, eds.. Phosphatidylcholine on Cell Membranes and Fransport of Cholesterol, wbn-Vedag-Biagen, Rheia, Germany, 1988. 

Acetylcholine Precursors. Early efforts to treat dementia using cholinomimetics focused on choline [62-49-7] (12) supplement therapy (Fig. 3). This therapy, analogous to L-dopa [59-92-7] therapy for Parkinson s disease, is based on the hypothesis that increasing the levels of choline in the brain bolsters acetylcholine (ACh) synthesis and thereby reverses deficits in cholinergic function. In addition, because choline is a precursor of phosphatidylcholine as well as ACh, its supplementation may be neuroprotective in conditions of choline deficit (104). 

A novel approach to the modification of aminoglycoside pharmacokinetics is under investigation (84). Administration of gentamicin encapsulated in egg phosphatidylcholine Hposomes has been found to lead to a longer half-life and much higher spleen and Hver levels for the gentamicin component. This formulation is undergoing clinical study (85). 

In addition to the triglycerides, the four oilseeds also contain phosphatides. For example, soybean oil containing 1.47% phosphatides consists of 48.9% phosphatidylcholine, 27.0% phosphatidylethanolamine, 21.9% phosphatidjlinositol and 2.2% phosphatidic acid (24). Total phosphatides of cottonseed and peanut kernels are estimated to be 1.5—1.9 and 0.8%, respectively (25). 

In nutrition, the most important function of choline appears to be the formation of lecithin (phosphatidylcholine) (2) and other cb oline-containing pho sphohpids. 

Figure 1 Chemical structure and space-filling representation of a phosphatidylcholine, DPPC. Different parts of the molecule are referred to by the labels at the left together the choline and phosphate are referred to as the headgroup, which is zwitteriomc. In the space-filling model, H atoms are white, O and P gray, and C black. (From Ref. 55.)...

We finish this section by comparing our results with NMR and incoherent neutron scattering experiments on water dynamics. Self-diffusion constants on the millisecond time scale have been measured by NMR with the pulsed field gradient spin echo (PFGSE) method. Applying this technique to oriented egg phosphatidylcholine bilayers, Wassail [68] demonstrated that the water motion was highly anisotropic, with diffusion in the plane of the bilayers hundreds of times greater than out of the plane. The anisotropy of... 

Phosphatidylcholine Apply phospholipase C solution as a band, dry, apply sample solution to enzyme band, stop reaction with hydrochloric acid vapor. sn-l,2-Digly-cerides are produced. [43]... 

One important phospholipid is phosphatidylcholine, also called lecithin. Phosphatidylcholine is a mixture of diesters of phosphoric acid. One estei function is derived from a diacylglycerol, whereas the other is a choline [—OCH2CH2N(CH3)3] unit. 

The lipid fraction is responsible for the structure of the membrane. Phosphatidylcholine provides the bilayer that is the banier between what is inside the cell and what is outside. Cholesterol intermingles with the phosphatidylcholine to confer an extra measure of r-igidity to the membrane. 

Phospholipid (Section 26.4) Adiacylglycerol bearing a choline-phosphate head group. Also known as phosphatidylcholine. 

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