Cholesterol membrane

In milk fat, cholesterol is associated with Hpoproteins in the milk fat globule. It is also a component of animal membranes and controls rigidity and permeabihty of the membranes. Cholesterol has interesting surface properties and can occur in Hquid crystalline forms. Plants contain sterols such as P-sitosterol [83-46-5] (4b) or stigmasterol [83-48-7] (4c). Their functions in plant metaboHsm are not yet well understood. Analysis of sterols has proven useful for detection of adulteration of edible fats (9). 

Cholesterol is a principal component of animal cell plasma membranes, and much smaller amounts of cholesterol are found in the membranes of intracellular organelles. The relatively rigid fused ring system of cholesterol and the weakly polar alcohol group at the C-3 position have important consequences for the properties of plasma membranes. Cholesterol is also a component of lipoprotein complexes in the blood, and it is one of the constituents oiplaques that form on arterial walls in atherosclerosis. 

The most common sterol in membranes is cholesterol (Chapter 14), which resides mainly in the plasma membranes of mammalian cells but can also be found in lesser quantities in mitochondria, Golgi complexes, and nuclear membranes. Cholesterol intercalates among the phospholipids of the membrane, with its hydroxyl group at the aqueous interface and the remainder of the molecule within the leaflet. Its effect on the fluidity of membranes is discussed subsequently. 

Much of the plasma membrane cholesterol is removed by incubating cells with P-methylcyclodextrin for several hours. Cells remain viable after this treatment but the raft fraction is reduced and it is inferred that the depleted proteins are normally associated with cholesterol-dependent lipid rafts. Some, but not all, glycosylphosphatidylinositol (GPI)-anchored proteins are recovered in the fractions defined by this procedure. 

Allen-Vercoe, E., Waddell, B., Livingstone, S., Deans, J., and DeVinney, R. (2006). Entero-pathogenic Escherichia coli Tir translocation and pedestal formation requires membrane cholesterol in the absence of bundle-forming pili. Cell. Microbiol. 8, 613-624. 

Szebeni J, Hauser H, Eskelson CD, et al. Interaction of hemoglobin derivatives with liposomes. Membrane cholesterol protects against the changes of hemoglobin. Biochemistry 1988 27 6425. 

Figure 5.1 The structure of a glycerophospholipid. A simple diagram showing the charges on the head group. In this struction, palmitic and oleic acids, provide the hydrophobic component of the phospholipids and choline (and four bases) and the phosphate group provide the hydrophilic head. The unsaturated fatty acid, oleic acid, provides a kink in the structure and therefore some flexibility in the membrane structure which allows for fluidity. The more unsaturated the fatty acid, the larger is the kink and hence more fluidity in the membrane. Cholesterol molecules can fill the gaps left by the kink and hence reduce flexibility. Hydroxyl groups on the bases marked are those that form phosphoester links. Choline and inositol may sometimes be deficient in the diet so that they are, possibly, essential micronutrients (Chapter 15).

Steck, T.L., Ye, J., Lange, Y. Probing red cell membrane cholesterol movement with cyclodextrin. Biophys. J. 2002, 83, 2118-25. 

Bastiaanse EM, Jongsma H, van der Laarse A, Takens-Kwak BR Heptanol-induced decrease in cardiac gap jnctional conductance is mediated by a decrease in the fluidity of membranous cholesterol-rich domains. J Membr Biol 1993 136 135-145. 

Another significant component of many liposome preparations is cholesterol. In natural cell membranes, cholesterol makes up about 10—50% of the total lipid on a molar basis. For liposome preparation, it is typical to include a molar ratio of about 50% cholesterol in the total lipid recipe. The addition of cholesterol to phospholipid bilayers alters the properties of the resultant membrane in important ways. As it dissolves in the membrane, cholesterol orients itself with its polar hydroxyl group pointed toward the aqueous outer environment, approximately even, in a three-dimensional sense, with the glyceryl backbone of the bilayer s phosphodiglyceride components (Fig. 337). Structurally, cholesterol is a rigid component in membrane construction, not having the same freedom of movement that the fatty acid tails of... 

Some studies have shown increased risks of violent death and depression in subjects with reduced serum cholesterol concentrations. Serum and membrane cholesterol concentrations, the microviscosity of erythrocyte membranes, and platelet serotonin uptake have been determined in 17 patients with hypercholesterolemia (21). There was a significant increase in serotonin transporter activity only during the first month of simvastatin therapy. This suggests that within this period some patients could be vulnerable to depression, violence, or suicide. This is an important paper, in that it explains why mood disorders are not regularly seen in clinical trials with statins, as has been summarized in a recent review (3). 

Chin, J.H., and D.B. Goldstein. 1997. Membrane disordering action of ethanol Variation with membrane cholesterol content and depth of the spin label probe. Mol Pharmacol 13 435. 

Both suicidal behavior and impulsive aggression have been associated with low levels of brain serotonergic activity [91, 92]. Engelberg suggested that a reduction in serum cholesterol may decrease brain-cell-membrane cholesterol, lower lipid microviscosity, and decrease exposure of protein serotonin receptors on the membrane surface, thus resulting in a poorer uptake of serotonin from the blood and less serotonin entry into brain cells [4]. Other reports have discussed the relationships between cholesterol, serotonin, and depression [6, 93-96]. 

The sterol cholesterol (Fig. 2b) is a major constituent of animal plasma membranes but is absent from prokaryotes. The fused ring system of cholesterol means that it is more rigid than other membrane lipids. As well as being an important component of membranes, cholesterol is the metabolic precursor of the steroid hormones (see Topic K5). Plants contain little cholesterol but have instead a number of other sterols, mainly stigmasterol and P-sitosterol which differ from cholesterol only in their aliphatic side chains. 

The effects of cholesterol and cholesterol-derived oxysterols on adipocyte ghost membrane fluidity has been studied. It has been found that cholesterol and oxysterols interact differently with rat adipocyte membranes. Cholesterol interacts more with phosphatidylcholine located at the outer lipid bilayer whereas, for example, cholestanone seems to interact more with phospholipids located at the inner layer... 

The fluidization and increase in permeability of tumor cell membranes has been reported [43, 44], as well as changes in cellular lipid synthesis during ether phospholipid-induced cytolysis [45]. Direct evidence was found by Diomede et al. [46] and Principe et al. [47] for the importance of the lipid composition of membranes for the sensitivity to antineoplastic ether phospholipids. These authors studied the influence of tumor cell membrane cholesterol content on the sensitivity of leukemic cells [46] and cells derived from three human carcinomas [47] with different rates of cell... 

Annaba F, Sarwar Z, Kumar P, Saksena S, Turner JR, Dudeja PK, Gill RK, Alrefai WA (2007) Modulation of ileal bile acid transporter (ASBT) activity by depletion of plasma membrane cholesterol association with lipid rafts. Am J Physiol Gastrointest Liver Physiol 294 489-497... 

In 1979, Simpson [24] postulated that the outer mitochondrial membrane was the site of action of a labile protein factor, necessary to facilitate the transport of cholesterol, and Privalle et al. [19] provided evidence to support the notion that transference of cholesterol from the outer to the inner membrane required an agent that is cycloheximide dependent. When rats were ether-stressed in vivo and cholesterol SCC was deliberately inhibited, cholesterol accumulated in the adrenal mitochondria, most (90%) of this being associated with the inner membrane cytochrome P-450scc. After administration of aminoglutethimide to rats to block SCC, there was a two-fold increase in inner membrane cholesterol, while cycloheximide abolished this increase. Thus, it appears that cholesterol accumulates in the inner mitochondrial membrane as a result of stress and that transference from outer to inner membrane requires a protein factor. 

Changes in cholesterol content. A third type of intrinsic change involves alteration in the amount of cholesterol in a membrane (Robertson and Hazel, 1997). Cholesterol can be incorporated into a membrane up to an approximately one-to-one ratio with phospholipids. Most membrane-localized cholesterol is found in the plasma membrane. Cholesterol is an amphipathic molecule, that is, different regions of the molecule have affinities for either polar or nonpolar environments (figure 7.19). In a membrane, the flexible alkyl tip of the molecule penetrates into the bilayer the 3-/1-hydroxyl group remains near the surface of the membrane, near the ester linkages between the acyl chains and the glycerol moiety. 

Permeabilizes membranes (cholesterol interaction) [antifungal, haemolytic]... 

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