Cholesterol is transported in plasma in lipoproteins (see Table 1), with the greater part in the form of cholesteryl ester (Figure 1), and in humans the highest proportion is found in LDL. Dietary cholesterol equilibrates with plasma cholesterol in days and with tissue cholesterol in weeks. Cholesteryl ester in the diet is hydrolyzed to cholesterol, which is then absorbed by the intestine together with dietary unesterified cholesterol and other lipids. With cholesterol synthesized in the intestines, it is then incorporated into chylomicrons. Of the cholesterol absorbed, 80 to 90% is esterified with long-chain fatty acids in the intestinal mucosa. Ninety-five percent of the chylomicron cholesterol is delivered to the liver in chylomicron remnants, and most of the cholesterol secreted by the liver in very-low-density lipoprotein (VLDL) is retained during the formation of intermediate-density lipoprotein (IDL) and ultimately LDL, which is taken up by the LDL receptor in liver and extrahepatic tissues.
Table1. Composition of the Lipoproteins in Plasma of Humans
Fig1. Transport of cholesterol between the tissues in humans. ACAT, acyl-CoA:cholesterol acyltransferase; A-I, apolipoprotein A-I; C, unesterified cholesterol; CE, cholesteryl ester; CETP, cholesteryl ester transfer protein; HDL, high-density lipoprotein; HL, hepatic lipase; IDL, intermediate-density lipoprotein; LCAT, lecithin: cholesterol acyltransferase; LDL, low-density lipoprotein; LPL, lipoprotein lipase; LRP, LDL receptor–related protein-1; TG, triacylglycerol; VLDL, very-low-density lipoprotein.
Plasma LCAT Is Responsible for Virtually All Plasma Cholesteryl Ester in Humans
Lecithin: cholesterol acyltransferase (LCAT) activity is associated with HDL containing apo A-I. As cholesterol in HDL becomes esterified, it creates a concentration gradient and draws in cholesterol from tissues and from other lipoproteins (see Figures 2 and 1), thus enabling HDL to function in reverse cholesterol transport (see Figure 2).
Cholesteryl Ester Transfer Protein Facilitates Transfer of Cholesteryl Ester From HDL to Other Lipoproteins
Cholesteryl ester transfer protein, associated with HDL, is found in plasma of humans and many other species. It facilitates transfer of cholesteryl ester from HDL to VLDL, IDL, and LDL in exchange for triacylglycerol, relieving product inhibition of the LCAT activity in HDL. Thus, in humans, much of the cholesteryl ester formed by LCAT finds its way to the liver via VLDL remnants (IDL) or LDL (see Figure 1). The triacylglycerol-enriched HDL2 delivers its cholesterol to the liver in the HDL cycle (see Figure 2).
Fig2. Factors affecting cholesterol balance at the cellular level. Reverse cholesterol transport may be mediated via the ABCA1 transporter protein (with preβ-HDL as the exogenous acceptor) or the SR-B1 or ABCG1 (with HDL3 as the exogenous acceptor). Stimulatory ( ⊕) or inhibitory (⊖) effects are shown as dotted green or red arrows, respectively. (ACAT, acyl-CoA:cholesterol acyltransferase; A-I, apolipoprotein A-I; C, cholesterol; CE, cholesteryl ester; LCAT, lecithin:cholesterol acyltransferase; LDL, low-density lipoprotein; PL, phospholipid; VLDL, very-low-density lipoprotein.) LDL and HDL are not shown to scale.
