Receptor-mediated low-density lipoprotein catabolism.

Low-density lipoprotein (LDL) receptors are demonstrable in cultured fibroblasts from normal subjects but are decreased or absent in cells from patients with heterozygous or homozygous familial hypercholesterolaemia. In vivo receptor-mediated LDL catabolism, determined as the difference between the turnover rates of 125I-LDL and 131I-LDL coupled with cyclohexanedione, is responsible for approximately one-third of the total catabolism of LDL in normal subjects, but less than one-fifth in heterozygotes and is totally absent in homozygotes. Receptor-mediated catabolism can be stimulated in normal subjects and in heterozygotes by measures that promote bile acid synthesis, namely, administration of anion-exchange resins or creating a partial ileal bypass. Studies in dogs have shown that such measures stimulate the high-affinity binding of LDL by liver cell membranes. Taken together, these observations suggest the existence of LDL receptors in human liver, the function of which is to maintain cholesterol homeostasis within the hepatocyte during periods of increased demand. Partial or complete absence of such hepatic receptors may play a major role in the pathogenesis of familial hypercholesterolaemia.