Cholesterol esters, fatty acids

Cholesterol Esters Fatty acid esters of cholesterol which constitute about two-thirds of the cholesterol in the plasma. The accumulation of cholesterol esters in the arterial intima is a characteristic feature of atherosclerosis, [nih]... 

Fig. 3. Plasma cholesterol ester fatty acid increases in rats fed an eicosapentaenoic acid (EPAVy-linolenic acid (GLA) diet. Results are means SEM, n = 7, and are expressed as a percentage of control.

Ohrvall M, Berglrmd L, Sahninen I, et al. The serum cholesterol ester fatty acid composition but not the serum concentration of alpha tocopherol predicts the... 

Relation of Age and Race to Serum Cholesterol Ester Fatty Acid Composition... 

Several areas in which ca g on has been sounded on t 0,human use of CPIB involve muscj-g metabolism, certain enzyme changes, antifibrlno-lytic properties, cholesterol ester-fatty acid composition... 

Free cholesterol is determined after precipitation by digitonin. The difference between total and free cholesterol corresponds to the esterified fraction. For estimation of cholesterol esters the value for ester cholesterol is multiplied by the factor 1.67 which is derived from the mean molecular weight of cholesterol ester fatty acids (Bragdon et al. 1956). 

Study of lipid fractions from liver, kidney and brain showed liver cholesterol ester fatty acids to contain the highest proportion of phytanic acid with over 60% significant amounts of the acid were also found in liver and kidney triglycerides. Phytanic acid in brain was present only in the aceton soluble fraction, and, in small concentration, in fatty acids of glycerophosphatides (see table 5). 

The serum of humans and a variety of experimental animals contains a spectrum of lipoproteins, i. e., a series of substances containing various lipids in combination with protein of a very wide range of molecular weights and hydrated densities (4,5,9,10). The major factor responsible for the variation in density is the difference in the lipid-protein ratio from one species to another. This series of lipoproteins represents the transport system for at least 95% of the major serum lipid constituents, such as glyceryl esters, cholesterol, cholesterol esters, fatty acids, and phospholipids (1-3,6). 

Atherosclerotic plaque is a complex lesion which is a result of an inflammatory and reparative process. The atheroma plaque contains extracellular deposits of calcium salts, blood components, cholesterol crystals, and acid mucopolysaccharides. The initial changes, however, seem to occur at the cellular level, often accompanied by an abnormal intracellular storage of lipids, particularly cholesterol esters, fatty acids, and lipoprotein complexes. The rupture of the plaque can generate thrombosis, reductions in the vessel lumen and consequently in the cardiac perfusion, and acute or chronic consequences. 

Typical thin-layer chromatogram of lipids. The solvent system, hexane-diethyl ether-acetic acid (90 10 1). (1) cholesterol, (2) fatty acid, (3) triacylglycerol, (4) fatty acid methyl ester, (5) cholesterol ester, (6) glycerophosphatide, (7) sphingolipid, (8) 1,3- or 1,2-diacylglycerol, (9) 1 - or 2-monoacylglycerol. The Rf for (5), cholesterol ester, is calculated as follows ... 

Lipid standards (2°/o solutions in chloroform) a triacylglycerol (triolein), cholesterol ester (cholesterol linoleate), fatty acid (palmitoleic, oleic, etc.), fatty acid methyl ester (linolenic acid, methyl ester), a glycerophosphatide (phosphatidylcholine, phosphatidylethano-lamine, etc.), a diacylglycerol (diolein), and a monoacylglycerol (monoolein). 

Phospholipid Cholesterol Free fatty acids Itiacyl- glycerols Cholesterol esters Total lipids... 

Both IDL and LDL can be removed from the circulation by the liver, which contains receptors for ApoE (IDL) and ApoB-100 (IDL and LDL). After IDL or LDL interacts with these receptors, they are internalized by the process of receptor-mediated endocytosis. Receptors for ApoB-100 are also present in peripheral tissues, so that clearance of LDL occurs one-half by the liver and one-half by other tissues. In the liver or other cells, LDL is degraded to cholesterol esters and its other component parts. Cholesterol esters are hydrolyzed by an acid lipase and may be used for cellular needs, such as the building of plasma membranes or bile salt synthesis, or they may be stored as such. Esterification of intracellular cholesterol by fatty acids is carried out by acyl-CoA-cholesterol acyltransferase (ACAT). Free cholesterol derived from LDL inhibits the biosynthesis of endogenous cholesterol. B-100 receptors are regulated by endogenous cholesterol levels. The higher the latter, the fewer ApoB-100 receptors are on the cell surface, and the less LDL uptake by cells takes place. 

LDL binds specifically to lipoprotein receptors on the cell surface. The resulting complexes become clustered in regions of the plasma membrane called coated pits. Endocytosis follows (see Fig. 13-3). The clathrin coat dissociates from the endocytic vesicles, which may recycle the receptors to the plasma membrane or fuse with lysosomes. The lysosomal proteases and lipases then catalyze the hydrolysis of the LDL-receptor complexes the protein is degraded completely to amino acids, and cholesteryl esters are hydrolyzed to free cholesterol and fatty acid. New LDL receptors are synthesized on the endoplasmic reticulum (ER) membrane and are subsequently reintroduced into the plasma membrane. The cholesterol is incorporated in small amounts into the endoplasmic reticulum membrane or may be stored after esterification as cholesteryl ester in the cytosol this occurs if the supply of cholesterol exceeds its utilization in membranes. Normally, only very small amounts of cholesteryl ester reside inside cells, and the majority of the free cholesterol is in the plasma membrane. 

Analytical methods for plant sterol analysis are commonly based on procedures used for cholesterol analysis. However, a significant shortcoming of these methods is the fact that cholesterol occurs only as free cholesterol and fatty acid esters. Therefore, the analytical methods optimized for cholesterol analysis are not suitable, or only suitable with some restrictions, for the analysis of conjugates found only in plants (SFs, SGs, and ASGs). Further, the methods described below only give the total amount of plant sterols and no information of the different sterol species found in the samples. However, if detailed information about the sterol composition is not required, and the amount of sterols to be analyzed is sufficiently high for these less sensitive but simpler methods, they provide a less laborious alternative for the analysis. 

The best-known cholesterol esterase (Table I) is also a pancreatic enzyme. Cholesterol esterases not only hydrolyze cholesterol esters but also synthesize them from cholesterol and fatty acid in a reversible reaction. This is important in the digestion of cholesterol itself because... 

Pancreatic and Intestinal wall esterases break down cholesterol esters to free cholesterol and fatty acids. 

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... 

The basis for all enzymatic cholesterol assays is the hydrolysis of cholesterol esters by cholesterol esterase (CEH, EC 3.1.1.13) to free cholesterol and fatty acids and the oxidation of free cholesterol to cholestenone by cholesterol oxidase (COD, EC 1.1.3.6) with concomitant oxygen consumption and hydrogen peroxide formation ... 

LDL have bound to LDL receptors. The coated region surrounding the bound receptor, referred to as a coated pit, pinches off and becomes a coated vesicle. Subsequently, uncoated vesicles are formed as clathrin depolymerizes. Before uncoated vesicles fuse with lysosomes, LDL are uncoupled from LDL receptors as the pH changes from 7 to 5. (This change is created by ATP-driven proton pumps in the vesicle membrane.) LDL receptors are recycled to the plasma membrane, and LDL-containing vesicles fuse with lysosomes. Subsequently, LDL proteins are degraded to amino acids, and cholesteryl esters are hydrolyzed to cholesterol and fatty acids. 

Total serum cholesterol and fatty acids became elevated, but cholesterol esters decreased, in dogs administered 400 ppm carbon disulfide and simultaneously fed high-fat diets (Lewey et al. 1941). These data suggest that carbon disulfide, in conjunction with a high-fat diet, may lead to increases in cholesterol levels above those expected from high-fat diets alone. Rabbits (n=l 1) exposed to higher concentrations of carbon disulfide (750 ppm) for 6 hours a day for 5 months exhibited a transient elevation in total serum cholesterol which was associated with weight loss (Cohen et al. 1959). 

In terms of the nature of processes leading to lipid accumulation during the development of atherosclerosis the mechanisms of normal uptake of lipoproteins by cells as mentioned above must be considered. Normally LDL cholesterol is taken up by cells, following its association with high-affinity cell-surface receptors, by endocytosis. It is then delivered to lysosomes within which the protein part is hydrolysed and the cholesteryl ester is hydrolysed to cholesterol and fatty acids. When sufficient cholesterol... 

Table 3.2. Reactivity of cholesterol and fatty acid methyl esters towards singlet oxygen ( O,) =...

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