Cholesterol, in cell membranes

The polyene macrolide filipin was isolated in 1955 from the cell culture filtrates of Sterptomyces filipinensis, and was later shown to be a mixture of four components [36]. Although too toxic for therapeutic use, the filipin complex has found widespread use as a histochemical stain for cholesterol and has even been used to quantitate cholesterol in cell membranes [37]. The flat structure of filipin III, the major component of the filipin complex, was assigned from a series of degradation studies [38]. Rychnovsky completed the structure determination by elucidating the relative and absolute stereochemistry [39]. The total synthesis plan for filipin III relied heavily on the cyanohydrin acetonide methodology discussed above. 

Carr AC, van den Berg JJM, Winterboum CC (1996) Chlorination of Cholesterol in Cell Membranes by Hypochlorous Acid. Arch Biochem Biophys 332 63... 

The cholesterol in cell membranes occurs as free cholesterol, rather than as choJesteryl esters. As illustrated in Figure 6.21, this cholesterol can be removed and transfern to circulating HDLs in a reaction catalyzed by lecithin choLesterol acy(transferase (LCAT). Continued insertion of cholestery l esters into an HDL changes its initial disk shape to a sphere shape. The lipid-poor HDLs (diskshaped HDl. ) account for only a few percent of the HDLs in the bloodstream. 

Problem 19.36. What is the function of cholesterol in cell membranes ... 

Eukaryotes (single cell) Plant-like Fungal-like Animal-like Cholesterol in cell s membrane compartments, nucleus, filaments, Ca2+ signals Photosynthetic, sedentary Dependent on plants, sedentary Dependent on digestion, mobile Use of Cu, Zn... 

Benninger, R. K. P., Onfelt, B., Neil, M. A. A., Davis, D. M. and French, P. M. W. (2005b). Fluorescence imaging of two-photon linear dichroism Cholesterol depletion disrupts molecular orientation in cell membranes. Biophys. J. 88, 609-22. 

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... 

An important question arises about the effects of phospholipid composition and the function of membrane-bound enzymes. The phospholipid composition and cholesterol content in cell membranes of cultured cells can be modified, either by supplementing the medium with specific lipids or by incubation with different types of liposomes. Direct effects of phospholipid structure have been observed on the activity of the Ca2+-ATPase (due to changes in the phosphorylation and nucleotide binding domains) [37]. Evidence of a relationship between lipid structure and membrane functions also comes from studies with the insulin receptor [38]. Lipid alteration had no influence on insulin binding, but modified the kinetics of receptor autophosphorylation. 

Chylomicrons are assembled from dietary triglyceride (containing predominantly the longer-chain fatty adds) and cholesterol esters by intestinal epithelial cells. The core lipid is surrounded by phospholipids similar to those found in cell membranes, which increase the solubility of chylomicrons in lymph and blood. ApoB-48 is attached and required for release from the epithelial cells into the lymphatics. 

In the human body choline is needed for the synthesis of phospholipids in cell membranes, methyl metabolism, transmembrane signaling and lipid cholesterol transport and metabolism [169]. It is transported into mammalian cells by a high-affinity sodium-dependent transport system. Intracellular choline is metabolized to phosphorylcholine, the reaction being catalyzed by the enzyme choline... 

Cholesterol is a soft waxy substance that is a steroidal alcohol or sterol. It is the most abundant steroid in the human body and is a component of every cell. Cholesterol is essential to life and most animals and many plants contain this compound. Cholesterol biosynthesis occurs primarily in the liver, but it may be produced in other organs. A number of other substances are synthesized from cholesterol including vitamin D, steroid hormones (including the sex hormones), and bile salts. Cholesterol resides mainly in cell membranes. 

Receptor desensitisation, initiated by phosphorylation of the receptor, can be subsequently followed by receptor internalisation via multiple methods including clathrin-coated pits and/or lipid rafts/caveolae. Clathrin-coated pits are specialized regions of the cell surface that mediates the internalisation of the most of GPCRs to endosomes. Lipid rafts are planar domains in cell membranes that are enriched in specific lipid and proteins with an high content of cholesterol and glycosphingolipid (Chini and Parenti 2004). Caveolae are flask-shaped invaginations located at or near the plasma membrane and are considered a non-planar subfamily of lipid rafts (Ferguson 2001 Chini and Parenti 2004). 

Either of two solutions can be used to redissolve the radiolabeled sterols. The first, oil, is simpler to prepare and administer to the mice. However, it is not strictly a physiological representation of dietary cholesterol, which is largely present with phospholipids in cell membranes, and the oikcholesterol ratio is much greater than would occur in most diets. The second solution, a lipid emulsion, is more tedious to prepare and is less stable but is more physiologically accurate. 

HDLs are synthesized in the blood and extract cholesterol from cell membranes, converting it into cholesterol esters. Some of the cholesterol esters are then transferred to VLDLs. About half of the VLDLs and all of the HDLs are taken up into the liver cells by receptor-mediated endocytosis and the cholesterol disposed of in the form of bile salts. 

The bulk of our knowledge regarding thermal oxidation has been derived from studies with model systems of fatty acids and their derivatives, or with individual natural oils (2,3,6,12,13,14,15,16). However, in biological systems as complex as food, lipids usually exist in a complicated environment markedly different from that of the single phase model system. In cell membranes, for example, the lipid molecules are highly ordered, relatively restricted in distance and mobility, and closely associated with different neighboring molecules, e.g., other lipids, protein, cholesterol, water, pro- and antioxidants. What influence does such an environment have on the oxidation of the lipids at elevated temperature Even in less organized systems, e.g., depot fat from animal or plant, the lipids... 

The third class of lipids found in stratum corneum extracts is represented by cholesterol and cholesteryl esters. The actual role of cholesterol remains enigmatic, and no clear reason for its role in the barrier function has been proposed so far. However, it is possible that contrary to what is the role in cell membranes where cholesterol increases close packing of phospholipids, it can act as kind of a detergent in lipid bilayers of long-chain, saturated lipids.30,31 This would allow some fraction of the barrier to be in a liquid crystalline state, hence water permeable in spite of the fact that not only ceramides, but also fatty acids found in the barrier are saturated, long-chain species.28,32... 

The degree to which the B-100.E receptors are expressed in various tissues appears to be a function of the requirement of that tissue for cholesterol. Thus, cell membranes from the adrenal cortex and gonads, organs that require cholesterol for the production of steroid hormones, contain many... 

The nascent HDL particles change shape and composition as they acquire additional free cholesterol by passive cellular diffusion of free cholesterol from cell membranes or from other plasma lipoproteins. HDL surface-localized LCAT progressively converts the free cholesterol on the surface of the particles to cholesterol ester, which occupies the core of the lipoprotein particle. This process converts the shape of the HDL particles from discoidal to spherical. The lipid unloading of HDL in the liver follows at least two pathways. In the first route, the cholesterol ester transfer protein (CETP) mediates cholesterol ester transfer from HDL to VLDL and LDL in exchange for triglyceride LDL in turn are taken up by the liver via the LDL receptor. In the second route, HDL binds to the scavenger receptor Bl, and cholesterol esters are selectively taken into the liver cells without internalization of HDL proteins (Fig. 15-2). 

Cholesterol is a basic constituent of cell membranes and is known to affect their properties [10]. Thus experiments with liposomes incorporating varying amounts of cholesterol may simulate the function of cholesterol in cell mem-... 

Cell membrane fluidity is determined by its hpid composition. The cell membrane is rendered more rigid if increased amounts of saturated fatty acids and cholesterol are incorporated into the membrane phospholipids. In contrast, increased incorporation of unsaturated fatty acids into the membrane will make it more fluid. This increase in membrane fluidity has been shown to increase the number of receptors and their affinity to their respective hormones or growth factors. For instance, an increase in the rigidity of the cell membrane reduces the number of insulin receptors and their affinity to insulin that, in turn, could cause insulin resistance. Alternatively, an increase in cell membrane fluidity because of an increase in the unsaturated fatty acid content in the membrane phosphohpids increases the number of insulin receptors and their affinity to insuhn and, thus, decreases insulin resistance (35 2). 

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