Lipids phosphatidylcholine

The squaraine probe 9g was tested for its sensitivity to trace the formation of protein-lipid complexes [57]. The binding of dye 9g to model membranes composed of zwitter-ionic lipid phosphatidylcholine (PC) and its mixtures with anionic lipid cardiolipin (CL) in different molar ratios was found to be controlled mainly by hydrophobic interactions. Lysozyme (Lz) and ribonuclease A (RNase) influenced the association of 9g with lipid vesicles. The magnitude of this effect was much higher... 

Fig. 4.8. (Below) A diagram of the bilipid layer membrane of a vesicle or a cell with (above) a typical lipid, phosphatidylcholine. Large molecules and ions cannot penetrate the membrane as illustrated by the ions surrounding and inside a cell, but the distribution is reversed in vesicles (see Chapter 7). The ions create chemical and electrical field gradients across the membrane.

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. 

Such new RP-HPLC stationary-phase materials have been available for some years (Regis Chemical Company, Morton Grove, IL, USA). These so-called immobilized artificial membrane (IAM) columns consist of lipid molecules covalently bound to propylamine-silica. The unreacted propylamine moieties are end-capped with methylglycolate. The membrane lipid, phosphatidylcholine, possesses polar head groups and two non-polar hydrocarbon chains (C18). One of the alkyl chains is linked to the propylamine-silica surface. 

Bilayer composition can be almost infinitely varied by choice of the constituent lipids. Phosphatidylcholine (PC), a neutral phospholipid, has emerged as the major lipid component used in the preparation of pharmaceutical liposomes. Phosphatidylglycerol and phosphatidylethanolamine are also widely used. Liposomal bilayers may also accommodate sterols, glycolipids, organic acids and bases, hydrophilic polymers, antibodies and other agents, depending on the type of vesicle required. 

It is natural to classify lipids as polar or non-polar according to their interaction with water. Non-polar lipids, for example triglyceride oils, do not form aqueous phases, whereas polar lipids do. Except for cholesterol, membrane-forming lipids form aqueous phases and have polar head groups. Within membranes there are also trace amounts of lipids in membranes that do not interact with water, for example diacylglycerols. The structural formulae of two common membrane lipids, phosphatidylcholine (PC) and phosphatidylethanolamine (PE) are shown above. 

The simplest topic covered in this chapter is that of choline, a compound with a 2-carbon backbone, which occurs in the diet and in the body mainly in the form of the structural lipid phosphatidylcholine. Choline is an issue in the metabolism of other lipids, namely, of phosphatidylserine, phosphatidylethanola-mine, and sphingomyelin. Phosphatidylino-sitol is a lipid that has received enormous attention from cell biologists because of its role in transmitting signals within the cell. Sphingomyelin is a structmal lipid in the plasma membrane, but it has received increased attention because of its role in regulating the growth, differentiation, and death of cells. 

Amphotericin B is complexed with deoxycholate (C-AMB) and marketed as a lyophilized powder (fungizone) containing 50 mg of amphotericin B that forms a colloid in water. Three lipid formulations of amphotericin B are marketed in the U.S. Amphotericin B colloidal dispersion (ABCD, AMPHOTEC, amphocil) contains equimolar amounts of amphotericin B and cholesteryl sulfate. AMBISOME is a small, unilamellar vesicle formulation that combines amphotericin B (50 mg) with 350 mg of lipid (phosphatidylcholine, cholesterol, and distearoylphosphatidylglycerol, in molar ratio of 10 5 4) in an -10% molar ratio. Amphotericin B lipid complex (ABLC, abelcet) contains dimyristoylphosphatidylcholine and dimyristoylphosphatidylglycerol in a 7 3 mixture with -35 mol% of amphotericin B. 

Metabolism of the dietary lipid phosphatidylcholine by gut bacteria generates trimethylamine (TMA), which is then oxidized into trimethylamine N-oxide (TMAO) by hepatic flavin mono-oxygenase (FMO). FMO expression is induced by the BA nuclear receptor FXR, upon stimulation with BA. TMAO is implicated in the formation of atherosclerotic plaque through induction of upregulation of the expression of two macrophage scavenger receptors, CD36 and SR-Al 7° Additionally TMAO were recently shown to inhibit reverse cholesterol transport (RCT),... 

MGD[6]. In Fig. Id this is shown by a decreased flux through the prokaryotic pathway of only 280 fatty acids compared with 390 in the wild type and an increased flux through the eukaryotic pathway. The extrachloroplast lipids-phosphatidylcholine (PC), and phosphatidylethanolamine (PE)- of the fade mutant also show increased levels of 18 1. We did not expect this result since the mutant contains normal activity of the endoplasmic reticulum 18 1 desaturase. While the eukaryotic pathway very probably delivers some 18 1-containing lipids to the chloroplast, any 18 1 reexported to the... 

Efforts to solubilize and isolate the P-450 monoxygenases from the microsomal membranes have been hampered by the facile conversion to a catalytically inactive form, cytochrome P-420. In 1968, however, a successful solubilization of catalytically active P-450 from hepatic microsomes was reported.30, 31 he solubilized system, which effected w-hydroxylation of fatty acids, required three coiq>onents for catalytic activity cytochrome P-450, NADPH-cytochrome c reductase, and a heat-stable, chloroform-soluble factor, the active component of which was identified as the microsomal lipid phosphatidylcholine.32 Further studies with this solubilized and reconstituted system have Indicated that the cytochrome P-450 and P-448 fractions have different catalytic activities 33-35 and that the terminal oxidase activity resides in the b-type cytochrome (P-450 or P-448) fraction rather than the cytochrome c reductase or lipid fractions.33, 36, 37 xhe cytochrome P-450 and P-448 were found to coiq>ete for reductase when present together.38 Cytochrome bs did not appear to be an obligatory component of the reconstituted systera.39 Cytochrome P-450 and P-448 fractions from rat liver were found to contain high levels of an epoxide hydrase, which can convert intermediate oxides to vicinal diols. Further purification has afforded fractions relatively free of cross-contamination of monoxygenase and hydrase enzymes. Recently, differential solubilization of monoxygenase activity towards a Type I substrate (naphthalene) and a Type II substrate (aniline) was... 

The cammon features of plasma lipoprotein structure are shown in Fig. 2. The interior of the lipoproteins contains the neutral lipids, cholesteryl ester and triglyceride. The exterior surface is a monomolecular film of specific proteins, termed apolipopro-teins, and the polar lipids, phosphatidylcholine and cholesterol. One possible arrangement (Edelstein et al., 1979) of the phosphatidylcholine, cholesterol and apolipoprotein A-1 (apoA-1) in HDL the most abundant of the plasma lipoproteins, is illustrated schematically in Fig. 3. In this model, there are no lipid domains in the surface of HDL. The phospholipid molecules are widely dispersed so that intermolecular associations can involve only apoprotein lipid and apoprotein apoprotein interactions. By contrast, with increasing size and a greater proportion of hydrophobic core volume, the structure of the larger lipoproteins more closely re-... 

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