Membrane fluidity cholesterol, role

Cholesterol is an important structural component of cellular membranes, where it plays a role in modulating membrane fluidity and phase transitions, and, together with sphingomyelin, forms lipid rafts or caveolae, which are sites where proteins involved in diverse signaling pathways become concentrated. Furthermore, cholesterol is a precursor of oxysterols, steroid hormones, and bile acids. 

Myelin is modified plasma membrane. Myelin of the PNS resembles that of the CNS with respect to lipid composition. There is an enrichment in such specialized lipids as cerebroside and ethanolamine plasmalogen, and the high content of cholesterol plays an important role in control of membrane fluidity. The protein composition of PNS myelin is, however, distinct from that of CNS myelin. A single protein, P0, accounts for half of all protein of PNS myelin. Of the other proteins present, most are expressed in the CNS as well as the PNS but in quantitatively different amounts. Prominent among these proteins are myelin basic proteins and myelin-associated glycoprotein. 

Cholesterol, which is an important constituent of cell membranes, plays an important role in maintaining membrane fluidity. It effectively inhibits the transition to the gel phase (26, 27). 

Cholesterol has several functions including involvement in membrane structure, by modulation of membrane fluidity and permeability, serving as a precursor for steroid hormone and bile acid synthesis, in the covalent modification of proteins, and formation of the central nervous system in embryonic development. The latter role of cholesterol was discovered through mutations and pharmacological agents that block cholesterol biosynthesis that occurs in six steps ... 

Studies of the physical properties of UC, reviewed in Chapter 6 of this volume, have contributed much to our understanding of the role of this Upid in membranes and lipoprotein surfaces. The shape and polarity of UC promote its association with the phosphoUpids of membranes and Upoproteins, and this association has important effects on membrane fluidity and permeability. The physical properties of long-chain fatty acid esters of cholesterol, on the other hand, differ strikingly from those of UC, and cause these esters to be largely excluded from phospholipid bilayers and monolayers and to aggregate instead in oil droplets. 

References (21-23) describe time-resolved fluorescence anisotropy studies (using TMA-DPH and DPH as fluorescent probes), of the effect of immime complexes on macrophage membrane fluidity, the effect of succinate and phenyl succinate on the fluidity of the inner mitochondrial membrane, and the role of cholesterol in modulating the fluidity of renal cortical brush border and basolatered membranes, respectively. 

Cholesterol Tetracyclic ring with double bond in one of the rings and one free hydroxyl group Vital role in maintaining membrane fluidity principal sterol of high animals... 

F. T. Presti, "The role of cholesterol in regulating membrane fluidity",... 

The occurrence of cholesterol and related sterols in the membranes of eukaryotic cells has prompted many investigations of the effect of cholesterol on the thermotropic phase behavior of phospholipids (see References 23-25). Studies using calorimetric and other physical techniques have established that cholesterol can have profound effects on the physical properties of phospholipid bilayers and plays an important role in controlling the fluidity of biological membranes. Cholesterol induces an intermediate state in phospholipid molecules with which it interacts and, thus, increases the fluidity of the hydrocarbon chains below and decreases the fluidity above the gel-to-liquid-crystalline phase transition temperature. The reader should consult some recent reviews for a more detailed treatment of cholesterol incorporation on the structure and organization of lipid bilayers (23-25). 

This reaction is responsible for formation of most of the cholesteryl ester in plasma. The preferred substrate is phosphatidylcholine, which contains an unsaturated fatty acid residue on the 2-carbon of the glycerol moiety. HDL and LDL are the major sources of the phosphatidylcholine and cholesterol. Apo A-I, which is a part of HDL, is a powerful activator of LCAT. Apo C-I has also been implicated as an activator of this enzyme however, activation may depend on the nature of the phospholipid substrate. LCAT is synthesized in the liver. The plasma level of LCAT is higher in males than in females. The enzyme converts excess free cholesterol to cholesteryl ester with the simultaneous conversion of lecithin to lysolecithin. The products are subsequently removed from circulation. Thus, LCAT plays a significant role in the removal of cholesterol and lecithin from the circulation, similar to the role of lipoprotein lipase in the removal of triacylglycerol contained in chylomicrons and VLDL. Since LCAT regulates the levels of free cholesterol, cholesteryl esters, and phosphatidylcholine in plasma, it may play an important role in maintaining normal membrane structure and fluidity in peripheral tissue cells. 

Increased amounts of membrane cholesterol have been associated with abnormalities of cell shapes for example, the erythrocytes of patients with liver disease develop a characteristic spur cell appearance which is associated with an increase in membrane cholesterol. These cells regain their normal shape on removal of the excess cholesterol [94]. Increased osmotic fragility has been observed with cholesterol depletion in both mycoplasma [104] and in erythrocytes [94]. There are few rheological studies on cells and the role of cholesterol in determining normal cell shape is not known. However, it is almost certainly linked to the fluidity and permeabihty of the cell membrane. 

The role of cholesterol in the fluidity of biological membranes is characterized as essential. Cholesterol is a silent molecule and in the case of lipid bilayers and liposomes it is included into bilayers to control the rate of the release of encapsulated molecules or to influence the stability of liposomes. The addition of cholesterol in lipid bilayers composed of DPPC, at concentrations more than 20%, results in the decrease of the Tm and elimination of the pretransition temperature. 

Explain the roles of the fatty acid chains of membrane lipids and cholesterol in controlling the fluidity of membranes. 

Sterols are a class of lipids that consist of a steroid and an alcohol. The most physiologically abundant sterol in humans is cholesterol, which is an integral part of the plasma membranes, confaring the fluidity of the lipid bilayer. Due to its amphipathic nature, cholesterol is an important structural component of cell membranes and the outer layer of plasma lipoproteins. Cholesterol plays an essential role both in the structure of cells and as a precursor to corticosteroids, mineral corticoids, bUe acids, vitamin D, and sex hormones such as testosterone, estrogen, and progesterone. As excess free cholesterol has cytotoxicity in cells, it is estrailied to a fatty acid to become a cholesteryl ester, a neutral form of cholesterol. Cholesteryl esters can be stored in the hpid droplets of cells without cytotoxicity, and therefore cholesterol esterification is increased whrai free cholesterol content in cells becomes excessive. 

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