Membrane lipids cholesterol

We have not yet said much about the second major constituent of eukaryotic membrane lipids, cholesterol. Cholesterol broadens the melting transition of the phospholipid bilayer (see fig. 17.20). Below the Tm, cholesterol disorders the membrane because it is too bulky to fit well into the neatly packed arrangement of the fatty acid chains that is favored at low temperatures. Above the Tm, cholesterol restricts further disordering because it is too large and inflexible to join in the rapid fluctuations of the chains. If the amount of cholesterol in a phospholipid bilayer is increased to about 30%, roughly the amount in the plasma membranes of typical animal cells, the melting transition becomes so broad as to be almost undetectable. 

Cholesterol (Fig. ID), which is the metabolic precursor of steroid hormones, is a major component of plasma membranes. Its fused ring system brings a greater rigidity than other membrane lipids. Cholesterol can be esterified on the C3 OH-group to long-chain fatty acids to form cholesteryl esters which are major components of lipoproteins. 

Ans. The hydrophobic portion (steroid ring system) of cholesterol is more rigid than that of other membrane lipids. Cholesterol is a regulator of membrane fluidity, keeping membranes from being too fluid. However, excess cholesterol would make the membrane too rigid. 

GORDESKY MARINETTI, 1973 HAEST 6e DEUTICKE, 1976). It should be noted that the major phospholipids of the endoplasmic reticulum are distributed in the opposite way (DePIERRE 6e DALLNER, 1975). This finding might lend support to the theory of plasma membrane biogenesis from the endoplasmic reticulum. There is some question about the distribution of one major membrane lipid, cholesterol. 

Sterol lipids (ST), such as cholesterol and its derivatives, are an important component of membrane lipids. Cholesterol has a tetracyclic ring system, with a double bond and a free hydroxyl group (see Figure 9.5) it is the most abimdant sterol in animal tissues, where it plays a vital role in... 

Figure 3 Comparison of the densities (in g/cm ) of model compounds for membrane lipids computed from constant-pressure MD simulations with the coiTespondmg experimental values. The model compounds include solid octane and tricosane, liquid butane, octane, tetradecane, and eico-sane, and the glycerylphosphorylcholme, cyclopentylphosphorylcholme monohydrate, dilauroly-glycerol, anhydrous cholesterol, cholesterol monohydrate, and cholesterol acetate crystals. (Models from Refs. 18, 42, and 43).

Jessup W, Gelissen IC, Gaus K, Kritharides L (2006) Roles of ATP binding cassette transporters Al and Gl, scavenger receptor BI and membrane lipid domains in cholesterol export from macrophages. Curr Opin Lipidol 17(3) 247-57... 

Kansy et al. [550] reported the permeability-lipophilicity relationship for about 120 molecules based on the 10% wt/vol egg lecithin plus 0.5% wt/vol cholesterol in dodecane membrane lipid (model 15.0 in Table 7.3), shown in Fig. 7.23. The vertical axis is proportional to apparent permeability [see Eq. (7.9)]. For log Kd > 1.5, Pa decreases with increasing log Kd. In terms of characteristic permeability-lipophilicity plots of Fig. 7.19, the Kansy result in Fig. 7.23 resembles the bilinear case in Fig. (7.19d). Some of the Pa values may be underestimated for the most lipophilic molecules because membrane retention was not considered in the analysis. 

Exploration of the use of liposomes in wool processing stems from the similarity that exists between the bilayer structure of the cell membrane complex of wool and that of the liposomes. Merino wool contains about 1% by weight of lipids, these forming the hydrophobic barrier of the cell membrane complex. Cholesterol is one of the main lipid... 

The structure and roles of membrane microdomains (rafts) in cell membranes are under intensive study but many aspects are still unresolved. Unlike in synthetic bilayers (Fig. 2-2), no way has been found to directly visualize rafts in biomembranes [22]. Many investigators operationally define raft components as those membrane lipids and proteins (a) that remain insoluble after extraction with cold 1% Triton X-100 detergent, (b) that are recovered as a low density band that can be isolated by flotation centrifugation and (c) whose presence in this fraction should be reduced by cholesterol depletion. 

Lipids are transported between membranes. As indicated above, lipids are often biosynthesized in one intracellular membrane and must be transported to other intracellular compartments for membrane biogenesis. Because lipids are insoluble in water, special mechanisms must exist for the inter- and intracellular transport of membrane lipids. Vesicular trafficking, cytoplasmic transfer-exchange proteins and direct transfer across membrane contacts can transport lipids from one membrane to another. The best understood of such mechanisms is vesicular transport, wherein the lipid molecules are sorted into membrane vesicles that bud out from the donor membrane and travel to and then fuse with the recipient membrane. The well characterized transport of plasma cholesterol into cells via receptor-mediated endocytosis is a useful model of this type of lipid transport. [9, 20]. A brain specific transporter for cholesterol has been identified (see Chapter 5). It is believed that transport of cholesterol from the endoplasmic reticulum to other membranes and of glycolipids from the Golgi bodies to the plasma membrane is mediated by similar mechanisms. The transport of phosphoglycerides is less clearly understood. Recent evidence suggests that net phospholipid movement between subcellular membranes may occur via specialized zones of apposition, as characterized for transfer of PtdSer between mitochondria and the endoplasmic reticulum [21]. 

Cardiolipin or diphosphatidyl glycerol is one of the most ancient membrane phospholipids from phylogenic aspects. It is surprising for such a complex molecule as cardiolipin to have evolved as one of the major membrane lipids in prokaryotics, when steroids such as cholesterol and phytosterols did not. In eukaryotic cells, cardiolipin is exclusively localized within the mitochondria where it is particularly emiched in the outer leaflet of the inner membrane. Even though a molecular structure of cardiolipin has been conserved in entire organisms, its biological significance has escaped attention except in the case of anti-cardiolipin auto-antibodies which are clinically associated with the Wasserman reaction. 

Natural biological membranes consist of lipid bilayers, which typically comprise a complex mixture of phospholipids and sterol, along with embedded or surface associated proteins. The sterol cholesterol is an important component of animal cell membranes, which may consist of up to 50 mol% cholesterol. As cholesterol can significantly modify the bilayer physical properties, such as acyl-chain orientational order, model membranes containing cholesterol have been studied extensively. Spectroscopic and diffraction experiments reveal that cholesterol in a lipid-crystalline bilayer increases the orientational order of the lipid acyl-chains without substantially restricting the mobility of the lipid molecules. Cholesterol thickens a liquid-crystalline bilayer and increases the packing density of lipid acyl-chains in the plane of the bilayer in a way that has been referred to as a condensing effect. 

Nutrients. Amphipathic lipids are used by cells to build membranes (see p. 214). Typical membrane lipids include phospholipids, glycolipids, and cholesterol. Fats are only weakly amphiphilic and are therefore not suitable as membrane components. 

The naturally occurring fatty acids are carboxylic acids with unbranched hydrocarbon chains of 4-24 carbon atoms. They are present in all organisms as components of fats and membrane lipids, in these compounds, they are esterified with alcohols (glycerol, sphingosine, or cholesterol). However, fatty acids are also found in small amounts in unesterified form. In this case, they are known as free fatty adds (FFAs). As free fatty acids have strongly amphipathic properties (see p. 28), they are usually present in protein-bound forms. 

The fluidity of membranes primarily depends on their lipid composition and on temperature. At a specific transition temperature, membranes pass from a semicrystalline state to a more fluid state. The double bonds in the alkyl chains of unsaturated acyl residues in the membrane lipids disturb the semicrystalline state. The higher the proportion of unsaturated lipids present, therefore, the lower the transition temperature. The cholesterol content also influences membrane fluidity. While cholesterol increases the fluidity of semicrystalline, closely-packed membranes, it stabilizes fluid membranes that contain a high proportion of unsaturated lipids. 

The illustration shows a model of a small section of a membrane. The phospholipids are the most important group of membrane lipids. They include phosphatidylcholine (lecithin), phosphatidylethanolamine, phos-phatidylserine, phosphatidylinositol, and sphingomyelin (for their structures, see p. 50). in addition, membranes in animal cells also contain cholesterol (with the exception of inner mitochondrial membranes). Clycoli-pids (a ganglioside is shown here) are mainly found on the outside of the plasma membrane. Together with the glycoproteins, they form the exterior coating of the cell (the gly-cocalyx). 

When the individual proportions of lipids in membranes are examined more closely (right part of the illustration), typical patterns for particular cells and tissues are also found. The illustration shows the diversity of the membrane lipids and their approximate quantitative composition. Phospholipids are predominant in membrane lipids in comparison with glycolipids and cholesterol. Triacyl-glycerols (neutral fats) are not found in membranes. 

The spread mixed lipid monolayer studies provide information about the packing and orientation of such molecules at the water interface. These interfacial characteristics affect many other systems. For instance, mixed surfactants are used in froth flotation. The monolayer surface pressure of a pure surfactant is measured after the injection of the second surfactant. From the change in n, the interaction mechanism can be measured. The monolayer method has also been used as a model biological membrane system. In the latter BLM, lipids are found to be mixed with other lipidlike molecules (such as cholesterol). Hence, mixed monolayers of lipids + cholesterol have been found to provide much useful information on BLM. The most important BLM and temperature melting phenomena is the human body temperature regulation. Normal body temperature is 37°C (98°F), at which all BLM function efficiently. 

The interactions obviously differed between the lipid bilayers and the natural membranes. Furthermore, cholesterol slightly hinders the drug partitioning into the liquid-crystalline bilayers, in agreement with several previous reports, and the drug molecules interact electrostatically with membrane proteins at the hydrophilic interface adjacent to the polar headgroups of the phospholipid molecules (7). 

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... 

Ester synthesis of cholesterol linoleate. Cholesterol fatty acid ester is an important cell membrane lipids and has many applications in cosmetics, pharmaceutical and other industries. Akehoshi et aL(7) reported the ester synthesis of the cholesterol fatty acid ester with native lipase. Synthesis of the cholesterol fatty acid ester was also carried out in water-saturated n-hexane by palmitic acid-modified lipase. As shown in Table III, this system made it possible for the synthesis of the cholesterol fatty acid ester in organic solvents using the modified lipase. 

Hydrophobic and Hydrophilic Components of Membrane Lipids A common structural feature of membrane lipids is their amphipathic nature. For example, in phosphatidylcholine, the two fatty acid chains are hydrophobic and the phosphocholine head group is hydrophilic. For each of the following membrane lipids, name the components that serve as the hydrophobic and hydrophilic units (a) phos-phatidylethanolamine (b) sphingomyelin (c) galactosyl-cerebroside (d) ganglioside (e) cholesterol. 

Chemical analyses of membranes isolated from various sources reveal certain common properties. Each kingdom, each species, each tissue or cell type, and the organelles of each cell type have a characteristic set of membrane lipids. Plasma membranes, for example, are enriched in cholesterol and contain no detectable cardiolipin (Fig. 11-2) in the inner mitochondrial membrane of the hepatocyte, this distribution is reversed very low cholesterol and high cardiolipin. Cardiolipin is essential to the function of certain proteins of the inner mitochondrial membrane. Cells clearly have mechanisms to control the kinds and amounts of membrane lipids they synthesize and to target specific lipids to particular organelles. In many cases, we can surmise the adaptive advantages of distinct combinations of membrane lipids in other cases, the functional significance of these combinations is as yet unknown. 

When the membrane is washed with ether to remove all of the cholesterol, the resultant PMR spectrum shows little change in the intensity of the polymethylene chain signal compared with that of the original membrane spectrum. This appears to rule out lipid-cholesterol interaction in this membrane as having a dominant effect upon the polymethylene chain freedom. In the membrane fragments either lipid chain-chain interactions have increased as a result of the protein interaction... 

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