Solubilization of phospholipids

An alternative mechanism for loss of membrane integrity is via the solubilization of phospholipids by thionins." This revised version of the carpet model is based on the observation of a conserved binding site for phospholipids head groups in thionins, their tendency to form oligomers," " and small-angle X-ray scattering... 

Lichtenberg, D., R.J. Robson, and E.A. Dennis. 1983. Solubilization of phospholipids by detergents. Structural and kinetic aspects. Biochim Biophys Acta 737 285. 

Phospholipase A2 Hydrolysis of Phospholipids Use of 31P NMR to Study the Hydrolysis, Acyl Migration, Regiospecific Synthesis, and Solubilization of Phospholipids... 

Lopez, O., de la Maza, A., Coderch, L., Lopez-Iglesias, C., Wehrli E., and Parra, J. L. (1998), Direct formation of mixed micelles in the solubilization of phospholipid liposomes by Triton X-100, FEBS Lett., 426, 314-318. 

Bile salts have proven to act very differently on the intestinal absorption of drugs. In some cases, the drug absorption was reduced due to micelle formation, whereas in other cases, the absorption was enhanced due to intestinal membrane disruption caused by the solubilization of phospholipids or by Ca " " complexation.f" ... 

The polar character of the liposomal core makes the encapsulation of polar drug molecules possible. Amphiphilic and lipophilic molecules are solubilized within the phospholipid bilayer according to their affinity toward the phospholipids. Participation of nonionic surfactants instead of phospholipids in the bilayer formation results in Niosomes . The term sphingosomes is suggested for vesicles from sphingolipids. However, the nomenclature is not consistent, and the term liposomes is used as a general term, although vesicles would be the better choice. 

A further possibility is the formation of liquid crystals on contact with body fluids at the site of application. The initially applied drug solution interacts with body fluids such as plasma, tears, or skin lipids and undergoes a phase transition into a mono-or multiphasic system of liquid crystals (Fig. 15). For example, oily solutions of reverse micellar solutions of phospholipids, which solubilize additional drug, trans-... 

According to Helenius and Simons (30) solubilization of the membrane is preceded by saturation of the bilayer with surfactant. Certainly critical surfactant/phospholipid ratios must be attained before membrane disruption occurs. 

The sample is disrupted completely and distributed over the surface as a function of interactions with the support, the bonded phase, and the tissue matrix components themselves. The solid support acts as an abrasive that promotes sample disruption, whereas the bonded phase acts as a lipophilic, bound solvent that assists in sample disruption and lysis of cell membranes. The MSPD process disrupts cell membranes through solubilization of the component phospholipids and cholesterol into the Cis polymer matrix, with more polar substituents directed outward, perhaps forming a hydrophilic outer surface on the bead. Thus, the process could be viewed as essentially turning the cells inside out and forming an inverted membrane with the polymer bound to the solid support. This process would create a pseudo-ion exchange-reversed-phase for the separation of added components. Therefore, the Cis polymer would be modified by cell membrane phospholipids, interstitial fluid components, intracellular components and cholesterol, and would possess elution properties that would be dependent on the tissue used, the ratio of Cis to tissue employed and the elution profile performed (99-104). 

HDL uptake of unesterified cholesterol Nascent HDL are diskshaped particles containing primarily phospholipid (largely phosphatidylcholine) and apolipoproteins A, C, and E. They are rapidly converted to spherical particles as they accumulate cholesterol (Figure 18.23). [Note HDL particles are excellent acceptors of unesterified cholesterol (both from other lipoproteins particles and from cell membranes) as a result of their high concentration of phospholipids, which are important solubilizers of cholesterol.]... 

Integral proteins are dissolved into the lipid bilayer of the membrane through interactions of the hydrophobic amino acid side chains and fatty acyl groups of phospholipids. In order to remove integral membrane proteins, the membrane must be disrupted by addition of detergents or other chaotropic reagents to solubilize the protein and to prevent aggregation and precipitation of the hydrophobic proteins upon their removal from the membrane. 

Various aspects of the (Ca2+, Mg2+)-ATPase have been reviewed.126 133 It can be isolated in vesicular form from homogenized skeletal muscle. Since it is the major protein component of SR membranes, it can also be isolated fairly easily in relatively pure form. The enzyme has a molecular weight in the range 100 000-120 000, and forms oligomers in the SR membranes, probably tetramers.133 Each subunit is associated with about 30 molecules of phospholipid, which are suggested to form a shell or annulus around the protein. The monomeric subunit has ATPase activity, and remains monomeric throughout the enzyme cycle,136 although the behaviour of the monomer is dependent on the solubilization procedure. 37... 

The solubilization of the lipophilic molecule occurs mostly at the upper part of the GI tract, where pancreatic fluids and biliary lipids (including bile salts, phospholipid and... 

The presence of lipids in the GI tract stimulates gall bladder contracts and biliary and pancreatic secretions, including bile salts, phospholipids, and cholesterol. These products, along with the gastric shear movement, form a crude emulsion, which promotes the solubilization of the coadministered lipophilic drug. Exogenous surface-active agents incorporated into the formulation may further stimulate the solubilization of the lipophilic compound. 

The solubilization phenomenon, which refers to the dissolution of normally insoluble or only slightly soluble compounds in water caused by the addition of surfactants, is one of the most striking effects encountered for surfactant systems. Solubilization is of considerable physico-chemical interst, such as in discussion of the structure and dynamics of micelles and of the mechanism of enzyme catalysis, and has numerous practical applications, such as in detergency, in pharmaceutical preparations and in micellar catalysis. In biology, solubilization phenomena are most significant, e.g., cholesterol solubilization in phospholipid bilayers and fat solubilization in fat digestion and transport. 

We have now extended these studies to synthetic phospholipids that contain short chain fatty acyl groups and which are water soluble, such as dibutyryl and dihexanoyl phosphatidylcholine (PC). These phospholipids are monomeric below their critical micelle concentration (cmc), yet activate the enzyme. In order to carry out kinetic studies, the long chain phospholipid substrate must generally be solubilized by a detergent such as Triton X-100 which serves as an inert matrix. Further understanding of the mechanism of the activation by short-chain phospholipids requires first a quantitation of the solubilization of these compounds by detergent ... 

We found the 31p-NMR chemical shift of monomeric dihexanoyl PC increases upon the addition of the nonionic detergent Triton X-100. This phenomenon was used to quantitate the solubilization of this phospholipid by the detergent micelles as a function of detergent concentration using a simple phase separation model ( 5). Similar studies were carried out on dibutyryl PC. At a phospholipid concentration of 7 mM and 56 mM detergent, 85% of the dihexanoyl PC, but only 3% of the dibutyryl PC was incorporated into the micelles. 

In t Veld, G., De Vrije.T., Driessen, A J.M., Konings, W.N.(1992). Acidic phospholipids are required during solubilization of amino acid transport systems of Lactococcus lactis. Biochim. Biophys. Acta 1104,250-256. 

Unlike TLL, both the active and inactive forms of PLAf showed periods of immobilization at the layer edge with a much longer residence time for iPLAl. Enzymatic activity is thus not a prerequisite for strong enzyme intercalation at the layer edge, but is clearly a prerequisite for efficient desorption of the enzyme. The products of the hydrolysis reaction cause considerable reorganization and solubilization of the phospholipid bilayer, and either effect could trigger the desorption of enzyme. 

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