Cholesterol in biological membranes

The organisation and function of cholesterol in biological membranes and the possible interactions with other Upids and proteins need to be clarified in order to achieve an understanding of many ceUular functions at the molecular level. Various disease conditions have been linked with abnormal cholesterol concentrations in cell membranes. Recently the evolutionary development of cholesterol and its role in membrane speciaUsation have become of some interest. 

Cholesterol is ubiquitous for nearly all mammalian membranes and is generally present in a 1 1 stoichiometry with phospholipids/ The structural and functional roles of cholesterol in biological membranes are not known. Several of the properties of this lipid are anomalous. For instance, it has an extinction coefficient of 20 x 10 with a maximum in the uv absorption at 235 nm. ... 

There are other ways in which the lateral organization (and asymmetry) of lipids in biological membranes can be altered. Eor example, cholesterol can intercalate between the phospholipid fatty acid chains, its polar hydroxyl group associated with the polar head groups. In this manner, patches of cholesterol and phospholipids can form in an otherwise homogeneous sea of pure phospholipid. This lateral asymmetry can in turn affect the function of membrane proteins and enzymes. The lateral distribution of lipids in a membrane can also be affected by proteins in the membrane. Certain integral membrane proteins prefer associations with specific lipids. Proteins may select unsaturated lipid chains over saturated chains or may prefer a specific head group over others. 

Figure19.1 A schematic diagram of a plasma membrane. Integral proteins are embedded in a bilayer composed of phospholipids (shown, for clarity, in much greater proportion than they have in biological membranes) and cholesterol. The carbohydrate components of glycoproteins and glycolipids occur only on the external face of the membrane. (Reproduced from D. Voet and J. G. Voet, Biochemistry, 3rd edn, 2004. 2004, Donald and Judith G Voet. Reprinted with permission of John Wiley and Sons, Inc.)...

Schroeder F, Woodford JK, Kavecansky J, Wood WG, Joiner, C. Cholesterol domains in biological membranes. Mol Membr Biol 1995 12 113-119. 

These unique molecules have many important biological roles. They can serve as a source of energy, signal molecules, and components of various cell membranes. The primary lipids in biological membranes are phospholipids, cholesterol, and glycolipids (24),... 

Sterols in biological membranes possess an alcohoUc hydroxyl group at C-3 and a branched chain of 8 or more carbon atoms at C-17. In mammaUan cells, cholesterol is the major sterol present. Cellular membranes such as Uver plasma membranes [6], erythrocyte [7,8] and myelin [7,9] membranes contain high levels of cholesterol in the molar ratios cholesterol phosphoUpid of 0.83, 0.90 and 1.32 respectively. Taking into account the high level of cerebrosides in the myelin membrane, the sterol Upid ratio is about 0.83. 

Fatty acids and derivatives are abundant in biological membranes as components of phospholipids and cholesterol esters. In fact, their presence, in free or bound form, modulates the lipid membrane behaviour. It was demonstrated, with X-ray diffraction, that oleic acid produced important concentration-dependent alterations of the lipid membrane structure. Oleic acid is capable of altering markedly the phospholipid mesomorphism [79],... 

Biological membranes contain, in addition to phosphoglycerides, glycolipids as part of the lipid component. Steroids are present in eukaryotes—cholesterol in animal membranes and similar compounds, called phytosterols, in plants. In the lipid bilayer part of the membrane (Figure 8.10), the polar head groups are in contact with water, and the nonpolar tails lie in the interior of the membrane. The whole bilayer arrangement is held together by noncovalent interactions, such as van der Waals and hydrophobic interactions (Section 2.1). The surface... 

H. Brockerhoff, Model of Interaction of Polar Lipids, Cholesterol, and Proteins in Biological Membranes, Lipids 9, 645-650 (1974). 

Filipin affects sterol-containing membranes at concentrations of 10-30 /Ltg/ml (<50 fiM). The use of higher concentrations for the study of sterols in biological membranes gives results which should be interpretated cautiously because filipin has detergent properties. Results obtained by Bishop (1973, 1974) on the effects of filipin on electron transfer in chloroplasts required 0.1-2 mM concentrations, and detergent effects can therefore not be discounted. Hendrix and Higinbotham (1973) applied filipin (up to 30 fiM) to a stem section ofP. sativum L. (pea). K" " and NOj uptake were inhibited, but respiration was unaffected. The effects of filipin on ion transport could be prevented by prior treatment with cholesterol. 

Cholesterol SAM Cholesterolis another type of rigid molecule, which is present widely in biological membranes. The studies using cholesterol-based SAMs were reported by Yang et al. [5, 413, 414]. 

These are complex lipids containing phosphate and a nitrogenous base. They are found in plasma lipoproteins, in biological membranes and in bile where they help to maintain cholesterol in solution. Phospholipids can be estimated by digestion of a lipid extract followed by measurement of the inorganic phosphate liberated. 

Sphingomyelin (SM) A Hpid with a phosphocholine group linked to a ceramide shares the same head group as phosphatidylcholine (PC) but displays different physicochemical properties. SM and PC do not normally mix in biological membranes, because SM is associated with cholesterol in plasma membrane microdomains such as lipid rafts. 

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