Familial hypercholesterolemia is by far the best characterized abnormality of li_ .... Most patients with primary hypercholesterolemia, i.e., hyperlipoproteinemia.
Bile Acids and Atherosclerosis, Vol. 15, edired by Scott M. Grundy, Raven Press, New York @ 1986
Bile Acids and Lipoprotein Metabolism Bo Angelin and Kurt Einarsson Metabolism Unit, Department of Medicine, Karolinska Institute, Huddinge University Hospital, S-l4l 86 Huddinge, Sweden
Bile acids interact with the metabolism of cholesterol and lipoproteins in several ways. The biliary excretion of bile acids is the major driving force for the hepatic secretion of cholesterol and phospholipid into bile. Bile acids must be present in sufficient amounts in the small intestine to ensure appropriate absorption of fat. conversion of cholesterol to bile acids in the liver represents a major pathway for net excretion of this steroid from the body. It is thus not surprising that a number of studies in humans have indicated the presence of metabolic linkages between bile acid turnover and enterohepatic circulation on the one hand and lipoprotein and cholesterol metabolism on the other. The aim of this presentation is to review the various aspects of bile acid and lipoprotein metabolism in humans and their interrelations in health and disease, and to discuss the possible physiological and clinical implications of these relations in humans.
LIPOPROTEIN METABOLISM As lipids are insoluble in plasma, specific lipid-apoprotein complexes called lipoproteins are formed in order to permit normal lipid transport (88,105,127). The normally occurring lipoproteins of human plasma are listed in Table I together with their major apolipoproteins. chylomicrons, which are synthesized in the intestinal wall from dietary fat and cholesterol (45), contain a specific structural protein, apolipoprotein (apo) B-48 (90). These large particles are secreted into the lymphatics and then enter the plasma compartment. Through the action of lipoprotein lipase in the capillary endothelium of muscular and adipose tissue, chylomicrons are converted into remnants, which are relatively enriched in cholesterol and apoE (105,120,127). The chylomicron remnants are rapidly cleared from the circulation by receptor-mediated uptake in the liver. This uptake is mediated by a specific, high-affinity cell surface receptor recognizing the E apolipoprotein; this
receptor has been designated the apoE receptor
or the remnant receptor
(11,49,50,55,103,104). Consequently, the clearance of chylomicrons from the circulation occurs very rapidly, with a half-life of only a few minutes, and this class of lipoproteins is not present in fasting plasma of healthy subjects.
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BILE ACIDS AND LIPOPROTEIN METABOLISM
42
TABLE 1. Normally occurring human plasma lipoproteins
Density
Origin and Lipoprotein lntestine Chylomicrons
Chylomicron remnants
Major apolipoproteins
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