Ho

Figure 6 Cholesterol.

hence protects the cell from accumulating excess intracellular cholesterol. Free cholesterol inhibits the synthesis of receptors that mediate the uptake of lipoproteins from the bloodstream, thereby limiting the amount of additional cholesterol taken up by the cell. Free cholesterol increases the activity of acyl CoA cholesterol acyltransferase (ACAT), the intracellular enzyme that converts free cholesterol to cholesteryl ester. A high level of intracel-lular free cholesterol is cytotoxic, whereas cholesteryl ester is a highly nonpolar molecule and coalesces into a lipid droplet within the cell, preventing interaction with intracellular components. Increased ACAT activity is an important mechanism in preventing the accumulation of intracellular free cholesterol.

Cholesterol can be esterified intracellularly, as previously indicated, by ACAT. ACAT uses primarily oleoyl CoA as substrate and the resulting product is primarily cholesteryl oleate. Cholesterol can also be esterified in plasma by lecithin cholesterol acyl-transferase (LCAT). LCAT uses phosphotidylcholine as substrate; the resulting products are primarily cholesteryl linoleate and lysolecithin. Cholesteryl ester is less polar than free cholesterol and this difference dictates how the two forms of cholesterol are handled—intracellularly and within lipoprotein particles.

Approximately one-third of cholesterol in plasma circulates as free cholesterol and approximately two-thirds as cholesteryl ester. Cholesterol in circulation is carried on all the lipoprotein particles (both intest-inally derived chylomicrons and hepatically derived very low-density lipoprotein) or those generated during the metabolic cascade (intermediate-density lipoprotein, low-density lipoprotein (LDL), and high-density lipoprotein (HDL)). Free cholesterol is sequestered on the surface of lipoprotein particles within the phospholipid monolayer, whereas choles-teryl ester resides in the core of the lipoprotein particle. The majority of the cholesterol in circulation is carried on LDL particles. Cholesteryl ester is the major component of atherosclerotic plaque. In the arterial wall, cholesteryl ester is derived from the infiltration of lipoprotein-associated cholesteryl ester resulting from LCAT activity or is synthesized in situ as a result of ACAT activity. The fatty acid profile of the cholesteryl ester in arterial plaque can provide some indication of its source.

Food Allergies

Food Allergies

Peanuts can leave you breathless. Cat dander can lead to itchy eyes, a stuffy nose, coughing and sneezing. And most of us have suffered through those seasonal allergies with horrible pollen counts. Learn more...

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