Serious Diseases Result from Cholesterol Deposits

Serious Diseases Result from Cholesterol Deposits 

Familial hypercholesterolemia results from a defective LDL receptor. As a result, the cholesteryl ester in the LDL of the bloodstream cannot be cleared by the normal process, hence, high cholesterol levels occur in the plasma of these patients. Somehow, the high levels of cholesterol lead to the formation of the atherosclerotic lesions, the underlying cause of premature heart disease in these patients. 

The importance of the work done on the LDL receptor and familial hypercholesterolemia was recognized in 1985 when Joseph Goldstein and Michael Brown were awarded the Nobel Prize in Physiology or Medicine. 

High-Density Lipoproteins (HDLs) May Reduce Cholesterol Deposits 

Unlike fatty acids, cholesterol is not degraded to yield energy. Instead excess cholesterol is removed from tissues by HDL for delivery to the liver from which it is excreted in the form of bile salts into the intestine. The transfer of cholesterol from extrahepatic tissues to the liver is called reverse cholesterol transport. When HDL is secreted into the plasma from the liver, it has a discoidal shape and is almost devoid of cholesteryl ester. These newly formed HDL particles are good acceptors for cholesterol in the plasma membranes of cells and are converted into spherical particles by the accumulation of cholesteryl ester. The cholesteryl ester is derived from a reaction between cholesterol and phosphatidylcholine on the surface of the HDL particle catalyzed by lecithimcholesterol acyltransferase (LCAT) (fig. 20.17). LCAT is associated with FIDL in plasma and is activated by apoprotein A-I, a component of HDL (see table 20.3). Associated with the LCAT-HDL complex is cholesteryl ester transfer protein, which catalyzes the transfer of cholesteryl esters from HDL to VLDL or LDL. In the steady state, cholesteryl esters that are synthesized by LCAT are transferred to LDL and VLDL and are catabolized as noted earlier. The HDL particles themselves turn over, but how they are degraded is not firmly established. 

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Serious Diseases Result from Cholesterol Deposits High-Density Lipoproteins (HDLs) May Reduce Cholesterol Deposits... 

Serious Diseases Result from Cholesterol Deposits... 

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