The lipoprotein receptor concept.

The interaction of plasma lipoproteins with mammalian cells is facilitated by specific receptors on the cell surface. The chylomicron remnant receptor recognises apolipoprotein E (apo E) and mediates the uptake of chylomicron remnants by the liver. The low density lipoprotein (LDL) receptor recognises lipoproteins containing apolipoprotein B100 or an activated form of apo E. The LDL receptor therefore mediates the uptake of intermediate density lipoprotein (IDL) and LDL by the liver, and it also facilitates uptake of LDL by other tissues. A receptor for high density lipoprotein (HDL) has been postulated to permit the interaction of HDL with the cell surface to remove intracellular cholesterol for transport ultimately to the liver. Knowledge of the structure and function of the chylomicron remnant receptor and the HDL receptor is still incomplete, but extensive information about the physiological importance of the LDL receptor is now available. Cells utilise the LDL receptor to take up and degrade LDL to obtain cholesterol for cellular use. In vivo these receptors affect the plasma LDL-cholesterol level by regulating both the synthesis and catabolism of LDL. Genetic mutations that impair LDL receptor function cause familial hypercholesterolaemia (FH). Patients with FH have elevated LDL-cholesterol levels and are at increased risk for the development of atherosclerosis. Patients with heterozygous FH have 1 abnormal and 1 normal allele at the LDL receptor locus; the normal allele enables them to respond to certain cholesterol-lowering medications by producing more LDL receptors. Patients with homozygous FH have 2 mutant alleles at the LDL receptor locus and lack the genetic capacity to produce any normal LDL receptors.(ABSTRACT TRUNCATED AT 250 WORDS)