Does Cholesterol Act Alone?
In plasma 30% of cholesterol is free and 70% is in ester form. Due to the insolubility of cholesterol and other fatty compounds in the blood, their redistribution in the body requires specialized carriers capable of solubilizing, ferrying, and unloading them at specific target sites. Free cholesterol and most lipids are packaged and transported in the blood as part of soluble complexes called lipoproteins. The movie on the right demonstrates the process of formation of a lipoprotein particle.
Dietary cholesterol is absorbed within the lumen of the small intestine. Bile salts produced from cholesterol in the liver interact with phosphor to produce a biliary micelles that are transported via bile into the lumen of the intestine. Dietary cholesterol in the lumen is easily incorporated into biliary micelles and absorbed into the enterocytes that make up the walls of the lumen. Once in the cells the cholesterol is esterified for transport with chylomicrons. Thus, chylomicrons are the lipoproteins that transport dietary cholesterol from the small intestine to the blood and other tissues. Cholesterol is transported throughout the body in the form of cholesterol esters. Excess cholesterol is also stored intracellularly as cholesterol esters.
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As cholesterol is a water-insoluble molecule it must be packaged for transport by the blood. The particles that package cholesterol, cholesteryl esters, and triglycerides for transport, are called lipoproteins. Lipoproteins are spherical particles composed of a hydrophobic lipid core surrounded by a hydrophilic layer, which renders the particles soluble. Lipoproteins are composed of:
- cholesteryl esters
- triglycerides
- phospholipids
- cholesterol
- apoproteins
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The lipid core contains primarily triglycerides and cholesteryl esters, as well as small amounts of other fatty compounds and fat-soluble vitamins (e.g. vitamins A, D, E, and K). Cholesteryl esters, which do not contain a free hydroxyl group (-OH) are more hydrophobic than cholesterol, and better accommodated in the core of lipoproteins.
The external hydrophilic layer is made of phospholipids, unesterified cholesterol, and specialized proteins, called apolipoproteins or apoproteins. These proteins facilitate lipid solubilization and help to maintain the structural integrity of LPs. They also serve as ligands for LP receptors and regulate the activity of LP metabolic enzymes. The amphipathic molecules that compose the outer layer of lipoproteins are arranged so that their hydrophobic parts face the central core, and their hydrophilic regions face the surrounding aqueous environment.
During ordinary metabolism, plasma lipoproteins lose, acquire, and exchange their lipid and protein constituents. Normally, fat-rich lipoproteins lose most of their fat within a few hours of food ingestion, and become smaller and denser particles with higher relative cholesterol content. The depletion of fat from lipoproteins is catalyzed by lipoprotein lipase. This lipolytic enzyme is located on the surface of endothelial capillaries, and degrades triglycerides to free fatty acids and glycerol.
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