Digestion, absorption and transport in the blood

The digestion and absorption of cholesterol occurs in the small intestine (for review, see Grundy, 1983). The secretion of bile acids into the gut disperses the fat into small droplets, while pancreatic secretions into the gut contain the enzymes for fat digestion. Cholesterol ester is broken down by a pancreatic cholesterol esterase to free cholesterol, which is the form of cholesterol absorbed into the cells lining the intestine. Endogenous cholesterol (as bile acids) and dietary cholesterol are both digested in the gut and absorbed. The absorption of endogenous choles- 

including cholesterol, absorbed from the diet is insoluble in the water-based medium of the blood. To enable transport through the blood system, the various fat components are incorporated into particles called lipoproteins (for reviews on lipoprotein metabolism, see Grundy, 1983 Mahley and Innerarity, 1983). Lipoproteins consist of a lipid core of triglyceride and cholesterol ester with a surface of mainly phospholipid and protein (referred to as apolipoprotein), plus some free cholesterol. The different apolipoproteins present function to regulate lipoprotein metabolism (for review on apolipoproteins, see Mahley et al., 1984). The cholesterol in lipoproteins is mainly transported as cholesterol ester. There are four main lipoprotein fractions found in the blood chylomicrons, very-low density lipoprotein (VLDL), low density Upopro-tein (LDL), and high density lipoprotein (HDL). 

VLDL is assembled in liver cells from lipid obtained via degradation of lipoproteins, synthesis from dietary carbohydrate and protein, and from fat mobilized from adipose tissue. VLDL is also rich in triglyceride (about 50%) and contains a substantial portion of cholesterol mainly as cholesterol ester. VLDL transports about 15% of the total cholesterol found in the blood. The apohpoproteins present on the surface of VLDL are apo BlOO, Cn and E. VLDL circulates in the blood and is acted upon by lipoprotein lipase in the same manner as for chylomicrons. The resulting VLDL remnants are LDL. 

LDL is mainly obtained by the degradation of triglyceride-rich VLDL, but can also be produced by the liver. LDL is enriched in cholesterol (mainly cholesterol ester) and accounts for about 65% of the total blood 

HDL is produced in liver and other tissues. This lipoprotein fraction is especially enriched in protein and phospholipid, with very little tri-gylceride. The major protein components are apo Aj and An, with small amounts of apo Cn and E. HDL also carries a substantial portion of cholesterol, as much as 20% of the total blood cholesterol level. HDL functions to transport cholesterol from peripheral tissues to the liver. Cholesterol on the surface of cells or other lipoproteins is picked up by HDL and esterified via lecithin-cholesterol acyltransferase (LCAT) to cholesterol ester for transport in the lipid core of HDL. The acquisition of cholesterol appears to be mediated via apo Ai (Barbaras et aL, 1987). LCAT also appears to be activated by apo Aj present within HDL. Cholesterol delivered to the liver by HDL is thought to be excreted as bile acids. 

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