Cholesterol esters, fatty acid change

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... 

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. 

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. 

Free fatty acids, derived primarily from adipocyte triglycerides, are transported as a physical complex with plasma albumin. Triglycerides and cholesteryl esters are transported in the core of plasma lipoproteins [134], Deliconstantinos observed the physical state of the Na+/K+-ATPase lipid microenvironment as it changed from a liquid-crystalline form to a gel phase [135], The studies concerning the albumin-cholesterol complex, its behavior, and its role in the structure of biomembranes provided important new clues as to the role of this fascinating molecule in normal and pathological states [135]. 

The structure of the blue phase is of some importance. Among the lipoproteins carrying lipids in the blood, low-density lipoproteins (LDL) have attracted much attention. They are the factors mainly responsible for plaque formation, which ultimately leads to atheriosclerotic changes and heart disease. The major components of the LDL-particles are cholesterol fatty acid esters. A remarlmble property is the constant size of LDL particles [28], which indicates that the interior must possess some degree of order. It seems probable that the structure proposed above for cholesterol esters in the cholesteric liquid-crystalline structure should occur also in the LDL-particle. In that case the LDL particle can be viewed as a dispersed blue phase, whose size is related to the periodicity of the liquid-crystalline phase, and the protein coat at the surface is oriented parallel to adjacent specific crystallographic planes of the blue phase. These amphiphilic proteins will expose lipophilic segments inwards emd expose hydrophilic groups towards tiie enviroiunent. 

Chronic parenchymal liver disease is associated with relatively predictable changes in plasma lipids and lipoproteins. Some of these changes are related to a reduction in the activity of lethicin cholesterol acyltransferase (LCAT). This plasma enzyme is synthesized and glycosylated in the liver then enters the blood, where it catalyzes the transfer of a fatty acid from the 2-position of lecithin to the Sp-OH group of free cholesterol to produce cholesterol ester and lysolecithin. As expected, in severe parenchymal liver disease, in which LCAT activity is decreased, plasma levels of cholesterol ester are reduced and free cholesterol levels normal or increased. 

Froyland, L., Vaagenes, H., Asiedu, D., Garras, A., Lie, 0. Beige, R.K. (1996). Lipidk 31 169-178. Chronic administration of eicosapentaenoic acid and docosahexaenoic acid as ethyl esters reduced plasma cholesterol and changed fatty acid composition in rat blood and organs. 

Recent studies in humans and animal models have revealed that modulation of stearoyl-CoA desaturase-1 (SCDl) activity by dietary intervention or genetic manipulation strongly influences several facets of energy metabolism to affect the susceptibility to obesity, insulin resistance, diabetes and hyperlipidaemia (Flowers and Ntambi, 2008, 2009 Paton and Ntambi, 2008). SCDl catalyzes the DO-di desaturation of a range of fatty acyl-CoA substrates. The preferred substrate is stearoyl-CoA, which produces OA from stearic acid (18 0). The major product of SCDl, OA (18 ln-9), is the key substrate for the formation of complex lipids such as phospholipids, TAG, cholesterol esters, wax esters and alkyl-2,3-diacylglycerols. Reduced OA synthesis is associated with several metabolic changes that elicit protection from obesity, cellular Upid accumulation and insulin resistance (Miyazaki et al., 2000 Ntambi et al., 2002 Sampath et al., 2007). 

Cholesterol accumulated in atheromatous lesions is largely ester-ifled with fatty acids, especially oleic acid. The change in fatty acid composition of cholesterol esters between circulating lipoproteins and atheromas indicates an esterification process operative in the developing lesion. Kotharl et al have demonstrated enzymes in normal artery which catalyze both synthesis and hydrolysis of cholesterol esters. Reaction rates of esterification and hydrolysis were found to be strongly dependent on the physical state of the reactants an emulsified state promoted esterification, whereas a micellar state promoted hydrolysis. 

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