Reverse Cholesterol Transport

HDL is synthesized by both the liver and the intestine. Its precursor form is discoidal in shape and matures in circulation as it picks up unesterified cholesterol from cell membranes and other lipids (phospholipid and triacylglycerol) and proteins (AI, E, and C apolipoproteins) from triacylglycerol-rich lipoproteins (chylomicron and VLDL) as these particles undergo lipolysis. The cholesterol is ester-ified by the action of the lecithin-cholesterol acyl-transferase (LCAT) and the small HDL3 particle becomes a larger HDL2 particle. The esterified cholesterol is either delivered to the liver or transferred by the action of cholesteryl ester transfer protein (CETP) to other lipoproteins (such as chylomicron, VLDL remnants, or LDL) in exchange for triacylgly-cerols. This cholesterol may then be taken up by the liver via receptors specific for these lipoproteins, or it can be delivered again to the peripheral tissues. The triacylglycerol received by HDL2 is hydrolyzed by hepatic lipase and the particle is converted back to HDL3, completing the HDL cycle in plasma. In the liver, cholesterol can be excreted directly into bile, converted to bile acids, or reutilized in lipopro-tein production.

Several genetic disorders have been identified associated with low levels or total deficiency of HDL.

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