Cholesterol and cholesteryl esters

Cholesterol and its interaction with phospholipids have been studied intensively in order to understand the role of cholesterol in biomembranes. 

Crystals of cholesterol monohydrate occur in various pathological conditions (Bogren and Larsson, 1961). The crystal structure of cholesterol monohydrate has been determined by Craven (1976). Cholesterol sulphate has been found in marine organisms and can form aqueous bilayer phases of the gel-type (Abrahamsson et al., 1977). 

Cholesterol exhibits interesting monolayer properties which certainly are related to its function in membranes. A characteristic II-A isotherm is shown in Fig. 8.61. The molecular cross-section area of the condensed monolayer is about 36 A, close to that in crystals. The monolayer is in a disordered state which can be observed if a powder is spread on the surface. The mobility is about the same as that of monolayers of long-chain amphiphiles 

The L -phase of lipid-water systems is able to solubilize cholesterol. Usually one molecule of cholesterol requires at least two hydrocarbon chains independent of the lipid type. Small (1970) has described the physical state of cholesteryl esters with saturated and unsaturated chains, as well as phase diagrams of cholesterol, triglycerides and cholesteryl esters at different temperatures. 

Abrahamsson, J., Abrahamsson, S., Hellqvist, B., Larsson, K., Pascher, I. and Sundell, S. (1977) Chem. Phys. Lipids, 19, 213. 

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Because they are uncharged, acylglycerols (glycerides), cholesterol, and cholesteryl esters are termed neutral lipids. 

Reaction with lipoprotein lipase results in the loss of approximately 90% of the triacylglycerol of chylomicrons and in the loss of apo C (which remrns to HDL) but not apo E, which is retained. The resulting chy-lotnicron remnant is about half the diameter of the parent chylomicron and is relatively enriched in cholesterol and cholesteryl esters because of the loss of triacylglycerol (Figure 25-3). Similar changes occur to VLDL, with the formation of VLDL remnants or IDL (intermediate-density lipoprotein) (Figure 25-4). 

Figure 25-3. Metabolic fate of chylomicrons. (A, apolipoprotein A B-48, apolipoprotein B-48 , apolipoprotein C E, apolipoprotein E HDL, high-density lipoprotein TG, triacylgiycerol C, cholesterol and cholesteryl ester P, phospholipid HL, hepatic lipase LRP, LDL receptor-reiated protein.) Only the predominant lipids are shown.

Cholesterol and cholesteryl esters appear as red-violet spots cholesterol spot appears before the ester spot... 

Chylomicrons are formed in the intestine and carry triglycerides of dietary origin, unesterified cholesterol, and cholesteryl esters. They transit the thoracic duct to the bloodstream. 

Cholesterol and cholesteryl esters, like triacylglycerols and phospholipids, are essentially insoluble in water, yet must be moved from the tissue of origin to the tissues in which they will be stored or consumed. They are carried in the blood plasma as plasma lipoproteins,... 

When the diet contains more fatty acids than are needed immediately as fuel, they are converted to triacylglycerols in the liver and packaged with specific apolipoproteins into very-low-density lipoprotein (VLDL). Excess carbohydrate in the diet can also be converted to triacylglycerols in the liver and exported as VLDLs (Fig. 21-40a). In addition to triacylglycerols, VLDLs contain some cholesterol and cholesteryl esters, as well as apoB-100, apoC-I, apoC-II, apoC-III, and apo-E (Table 21-3). These lipoproteins are transported in the blood from the liver to muscle and adipose tissue, where activation of lipoprotein lipase by apoC-II causes the release of free fatty acids from the VLDL triacylglycerols. Adipocytes take up these fatty acids, reconvert them to triacylglycerols, and store the products in intracellular lipid droplets myocytes, in contrast, primarily oxidize the fatty acids to supply energy. Most VLDL remnants are removed from the circulation by hepatocytes. The uptake, like that for chylomicrons, is... 

The loss of triacylglycerol converts some VLDL to VLDL remnants (also called intermediate density lipoprotein, IDL) further removal of triacylglycerol from VLDL produces low-density lipoprotein (LDL) (Table 21-2). Very rich in cholesterol and cholesteryl esters and containing apoB-100 as their major apoli-poprotein, LDLs carry cholesterol to extrahepatic tissues that have specific plasma membrane receptors that recognize apoB-100. These receptors mediate the uptake of cholesterol and cholesteryl esters in a process described below. 

Cholesterol and cholesteryl esters are carried in the blood as plasma lipoproteins. VLDL carries cholesterol, cholesteryl esters, and triacylglycerols from the liver to other tissues, where the triacylglycerols are degraded by lipoprotein lipase, converting VLDL to LDL. 

Cholesterol and cholesteryl ester synthesis acetyl-CoA----> cholesterol----> cholesteryl esters... 

LDL particles contain much less triacylglycerol than their VLDL predecessors, and have a high concentration of cholesterol and cholesteryl esters (Figure 18.19). 

Postulated scheme for the synthesis, assembly, and secretion of VLDL by a hepatocyte (liver cell). (1) Synthesis The apoproteins, phospholipid, triacylglycerol, cholesterol, and cholesteryl esters are synthesized in the endoplasmic reticulum. (2) Assembly These components are assembled into a prelipoprotein particle in the lumen of the endoplasmic reticulum. (3) Processing The particle moves to the Golgi apparatus, where modification of the apoproteins occurs. 

Bitman, J. and Wood, D.L. 1980. Cholesterol and cholesteryl esters of eggs from various avian species. Poult. Sci. 59, 2014—2023. 

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... 

Chylomicrons consists of triacylglycerols, cholesterol and cholesteryl esters, surrounded by phospholipids and proteins, identified as apolipoproteins. 

HDLs are synthesised de novo in the liver and small intestine, as primarily protein-rich particles. Newly formed HDLs are essentially devoid of cholesterol and cholesteryl esters. The primary apoproteins of HDLs are apo-A-I, apo-C-I, apo-C-II and apo-E. One major function of HDLs is to act as circulating stores of apo-C-I, apo-C-II and apo-E. 

The level of intracellular cholesterol is regulated through cholesterol-induced suppression of LDL-receptor synthesis and cholesterol-induced inhibition of cholesterol synthesis. The increased level of intracellular cholesterol that results from LDL uptake has the additional effect of activating acyl-CoA cholesteryl acyl transferase (ACAT) (see below), thereby allowing the storage of excess cholesterol within cells. However, the effect of cholesterol-induced suppression of LDL-receptor synthesis is a decrease in the rate at which LDLs and IDLs are removed from the serum. This can lead to excess circulating levels of cholesterol and cholesteryl esters when the dietary intake of fat and cholesterol is excessive. Excess cholesterol tends to be deposited in the skin and tendons and within the arteries, which can lead to atherosclerosis. 

Liebisch G, Binder M, Schifferer R, Langmann T, Schulz B, Schmitz G. High throughput quantification of cholesterol and cholesteryl ester by electrospray ionization tandem mass spectrometry (ESI-MS/MS). Biochim. Biophys. Acta 2006 1761 121-128. 

High levels of circulating LDL, which are rich in cholesterol and cholesteryl esters, cause cholesterol deposition into the endothelium of the so-called lesion-prone sites of the arterial wall. These areas are characterized by increased permeability to albumin, fibrinogen and LDL cholesterol and by a high monocyte recruitment activity. Monocytes migrate from the endothelium to the intima, and differentiate into macrophages. Recruitment and migration are part of an inflammatory... 

Cholesterol and cholesteryl esters Steroid hormones Bile acids Vitamin D... 

Modified LDL taken up by the cell are delivered to the endolysosome pathway, where enzymes hydrolyze cholesteryl esters to free cholesterol and fatty acids. The levels of free cholesterol and cholesteryl esters are regulated with the help of neutral cholesteryl ester hydrolase, which converts cholesteryl ester to free cholesterol. After cholesterol leaves the lysosome, it is transported to the ER and to the plasma membrane by means of an intermediate step through the Golgi apparatus. Recycling compartments, especially multivesicular endosomes, harbor most of the cholesterol in the endocytic pathway. The intra-endosomal membranes of multivesicular late endosomes that are enriched in the phospholipids lyso-bisphosphatidic acid/bismonoacylglycerophosphate serve as important regulators of cholesterol transport (Kobayashi et al. 1999 Ikonen 2008). Lysobisphosphatidic acid is structurally... 

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