Cholesterol Absorption, Synthesis, Metabolism, and Fate

• Cholesterol regulates membrane fluidity and is a precursor of bile salts, steroid hormones (such as estrogen and testosterone), and vitamin D.
• Cholesterol, because of its hydrophobic nature, is transported in the blood as a component of lipoproteins.
• Within the lipoproteins, cholesterol can appear in its unesterified form in the outer shell of the particle or as cholesterol esters in the core of the particle.
• De novo cholesterol synthesis requires acetyl coenzyme A as a precursor, which is initially converted to β-hydroxy-β-methylglutaryl-coenzyme A (HMG-CoA). The cholesterol synthesized in this way is packaged, along with triglyceride, into very low density lipoprotein in the liver and released into circulation.
• The conversion of HMG-CoA to mevalonic acid, catalyzed by HMG-CoA reductase, is the regulated and rate-limiting step of cholesterol biosynthesis.
• In the circulation, the triglycerides in very low density lipoproteins are digested by lipoprotein lipase, which converts the particle to intermediate-density lipoprotein and then to low-density lipoprotein.
• Intermediate- and low-density lipoprotein bind specifically to receptors on the liver cell, are internalized, and the particle components recycled.
• A third lipoprotein particle, high-density lipoprotein, functions to transfer apolipoprotein E and apolipoprotein C-II to nascent chylomicrons and nascent very low density lipoprotein.
• High-density lipoprotein also participates in reverse cholesterol transport, the movement of cholesterol from cell membranes to the high-density lipoprotein particle, which returns the cholesterol to the liver.
• Atherosclerotic plaques are associated with elevated levels of blood cholesterol levels. High levels of low-density lipoprotein are more strongly associated with the generation of atherosclerotic plaques, whereas high levels of high-density lipoprotein are protective because of their participation in reverse cholesterol transport.