Studies of the cell surface binding, internalization, and metabolism of low-density lipoprotein (LDL) in cultured cells have provided useful information regarding the general aspects of receptor-mediated endocytosis. The study of the LDL receptor has been facilitated by analysis of mutant fibroblasts obtained from human subjects with disorders of cholesterol metabolism. The most informative cells, obtained from patients with familial hypercholesterolemia (FH), have defects in the gene encoding the LDL receptor. The existence of three classes of mutant alleles at the LDL receptor locus has been deduced on the basis of genetic and kinetic data. One of these alleles specifies a receptor that is unable to bind LDL. The second type of allele specifies a receptor that can bind small amounts of LDL; and the third type of allele specifies a receptor that can bind LDL but cannot be incorporated into coated pits and hence cannot carry the LDL into the cell. The first two alleles are common among FH patients, whereas the third allele is extremely rare.
ASJC Scopus subject areas
- Molecular Biology