Plasma membrane cholesterol

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. 

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. 

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... 

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. 

Chen HW. Role of cholesterol metabolism in cell growth. FedProc 1984 43 126-130. Dabrowski MR Peel WE, Thomson AE. Plasma membrane cholesterol regulates human lymphocyte cytotoxic function. Ear J Immunol 1980 10 821-827. Ostaszewski P, Kostiuk S, Balasinska B, Jank M, Papet 1, Glomot F. The leucine metabolite 3-hydroxy-3-methylbutyrate (HMB) modifies protein turnover in muscles of the laboratory rats and domestic chicken in vitro. J Anim PhysiolAnim Nutr (Swiss) 2000 84 1-8. 

The interaction of anandamide with plasma membrane cholesterol may also be linked to the mechanism of anandamide transport through a biological membrane. This issue has been greatly debated. As a lipid, anandamide is probably able to diffuse passively through the... 

Arispe N, DohM. Plasma membrane cholesterol controls the cytotoxicity of Alzheimer s disease AbetaP (1-40) and (1-42) peptides. FASEB J. 2002 16(12) 1526-1536. 

Cholesterol is a widely distributed sterol found free or esterified to fatty acids. It is an important intermediate in the biosynthesis of steroid hormones and the principal component of cell plasma membranes and the membranes of intracellular organelles. 

Lipid rafts are specific subdomains of the plasma membrane that are enriched in cholesterol and sphin-golipids many signaling molecules are apparently concentrated in these subdomains. 

Cholesterol (Figure 14-17) is widely distributed in all cells of the body but particularly in nervous tissue. It is a major constituent of the plasma membrane and of plasma lipoproteins. It is often found as cholesteryl ester, where the hydroxyl group on position 3 is esteri-fied with a long-chain fatty acid. It occurs in animals but not in plants. 

Figure 2S-1. Generalized structure of a plasma lipoprotein. The similarities with the structure of the plasma membrane are to be noted. Small amounts of cholesteryl ester and triacylglycerol are to be found in the surface layer and a little free cholesterol in the core.

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. 

Figure 2.1 Structure of the plasma membrane. The plasma membrane is composed of a bilayer of phospholipid molecules. Associated with this bilayer are intrinsic proteins embedded within and spanning the membrane as well as intrinsic proteins found on the external or internal surface of the membrane. Molecules of cholesterol are found in the inner, nonpolar region of the membrane.

The lipid compositions of plasma membranes, endoplasmic reticulum and Golgi membranes are distinct 26 Cholesterol transport and regulation in the central nervous system is distinct from that of peripheral tissues 26 In adult brain most cholesterol synthesis occurs in astrocytes 26 The astrocytic cholesterol supply to neurons is important for neuronal development and remodeling 27 The structure and roles of membrane microdomains (rafts) in cell membranes are under intensive study but many aspects are still unresolved 28... 

Although apoE HDL particles are formed by astrocytes in vitro, the brain contents of apoE knockout (-/-) were not found to differ in lipid content in comparison to those obtained from normal animals [14]. A probable explanation is that newly synthesized cholesterol can be transported from astrocyte ER to plasma membrane via an alternative route that employs caveolae to form apoAl-HDL [15]. 

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