Bilayers containing cholesterol and

Pitman, M.C., Suits, F., Mackerell, A.D. Jr., Feller, S.E. Molecular-level organization of saturated and polyunsaturated fatty acids in a phosphatidylcholine bilayer containing cholesterol. Biochem. 2004, 43, 15318-28. 

Analysis of the hitherto largest set of drugs by ILC is described in Ref. 27. Interactions with bilayers containing proteins and cholesterol were reported in Refs. 7 and 25. 

The Singer and Nicholson (13) model for the plasma membrane, which now receives much support, is basically a smectic liquid crystal consisting of one bilayer of phospholipid (Figure 4a). The phospholipid bilayer contains cholesterol at a concentration which depends on cell type. Embedded in the lipid liquid crystal he protein molecules. Some of these protein molecules transverse the entire lipid bilayer and communicate both with the inside and the outside of the cells. Some of these may... 

The lipid bilayer is such that the polar heads (often phosphatidylcholine or phosphati-dylethanolamine) of the phospholipids are juxtaposed on the external and internal surfaces of the membrane, causing the ends of the hydrophobic (i.e., long-chained alkyl) portions of the phospholipids to extend inside the membrane. Also contained within the lipid bilayer are cholesterol and other sterols. 

Devadoss etal. (18) have developed a cholesterol oxidase modified electrode that has been used to detect cholesterol in the plasma membranes of Xenopus oocytes. A platinum electrode modified with a lipid bilayer containing cholesterol oxidase (50) is operated in the amperometric mode and placed adjacent to an oocyte (Figure 17.1.3A-B). 

HDL is synthesized and secreted from both liver and intestine (Figure 25—5). However, apo C and apo E are synthesized in the liver and transferred from fiver HDL to intestinal HDL when the latter enters the plasma. A major function of HDL is to act as a repository for the apo C and apo E required in the metabohsm of chylomicrons and VLDL. Nascent HDL consists of discoid phosphohpid bilayers containing apo A and free cholesterol. These hpoproteins are similar to the particles found in the plasma of patients with a deficiency of the plasma enzyme lecithimcholesterol acyltransferase (LCAT) and in the plasma of patients with obstructive jaundice. LCAT—and the LCAT activator apo A-I— bind to the disk, and the surface phosphohpid and free cholesterol are converted into cholesteryl esters and... 

While the fluid mosaic model of membrane stmcture has stood up well to detailed scrutiny, additional features of membrane structure and function are constantly emerging. Two structures of particular current interest, located in surface membranes, are tipid rafts and caveolae. The former are dynamic areas of the exo-plasmic leaflet of the lipid bilayer enriched in cholesterol and sphingolipids they are involved in signal transduction and possibly other processes. Caveolae may derive from lipid rafts. Many if not all of them contain the protein caveolin-1, which may be involved in their formation from rafts. Caveolae are observable by electron microscopy as flask-shaped indentations of the cell membrane. Proteins detected in caveolae include various components of the signal-transduction system (eg, the insutin receptor and some G proteins), the folate receptor, and endothetial nitric oxide synthase (eNOS). Caveolae and lipid rafts are active areas of research, and ideas concerning them and their possible roles in various diseases are rapidly evolving. 

Natural biological membranes consist of lipid bilayers, which typically comprise a complex mixture of phospholipids and sterol, along with embedded or surface associated proteins. The sterol cholesterol is an important component of animal cell membranes, which may consist of up to 50 mol% cholesterol. As cholesterol can significantly modify the bilayer physical properties, such as acyl-chain orientational order, model membranes containing cholesterol have been studied extensively. Spectroscopic and diffraction experiments reveal that cholesterol in a lipid-crystalline bilayer increases the orientational order of the lipid acyl-chains without substantially restricting the mobility of the lipid molecules. Cholesterol thickens a liquid-crystalline bilayer and increases the packing density of lipid acyl-chains in the plane of the bilayer in a way that has been referred to as a condensing effect. 

Zhang, Z., Bhide, S.Y., Berkowitz, M.L. Molecular dynamics simulations of bilayers containing mixtures of sphingomyelin with cholesterol and phosphatidylcholine with cholesterol. J. Phys. Chem. B 2007, 111, 12888-97. 

In contrast to (VIII), biradical (VII) shows a strong concentration, cholesterol- and temperature-dependent spin-spin interaction. Rey and McConnell41 have analyzed these spectra quantitatively when the concentration of (VII) is varied between 0.025 mole % and 2 mole % in bilayer membranes (70 mole % dimyristoylphosphatidylcholine and 30 mole % cholesterol) at 30°C. The surprising result was obtained that all the spectra can be accounted for quantitatively as the superposition of two spectra, a monomer spectrum [one molecule of (VII)] and a hexamer spectrum [a cluster containing six molecules of (VII)]. Representative data are given in Figs. 8 and 9. 

As the final outer stratum comeum is formed the phospholipid bilayer deteriorates and intercellular lipid layers are formed.k l These contain principally ceramides, cholesterol, and free fatty acids. Some sphingolipids are covalently attached to proteins.3... 

The lipid part of the membrane is essentially a two-dimensional liquid in which the other materials are immersed and to which the cytoskeleton is anchored. This last statement is not totally correct, as some membrane bound enzymes require the proximity of particular lipids to function properly and are thus closely bound to them. Simple bilayers formed from lipids in which both hydrocarbon chains are fully saturated can have a highly ordered structure, but for this reason tend to be rigid rather than fluid at physiological temperatures. Natural selection has produced membranes which consist of a mixture of different lipids together with other amphiphilic molecules such as cholesterol and some carboxylic acids. Furthermore, in many naturally occurring lipids, one hydrocarbon chain contains a double bond and is thus kinked. Membranes formed from a mixture of such materials can retain a fluid structure. The temperature at which such membranes operate determines a suitable mixture of lipids so that a fluid but stable structure results at this temperature. It will be seen that the lipid part of a membrane must, apart from its two-dimensional character, be disordered to do its job. However, the membrane bound proteins have a degree of order, as will be discussed below. 

Figure 5 (A) Temperature dependence of the parameter I /If obtained from the spectra of 9-heptadecanone (9HP) incciporated in hydrated DHPC bilayers containing different cholesterol concentrations 0 mol % (+) 8 mol % (o) 29 mol % ) and 45 mol % ( ) (B) Temperature dependence of the symmetric CHj stretching band of DHPC in the same samples described in (A).

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