Defective receptor binding of low density lipoprotein from pigs possessing mutant apolipoprotein B alleles

• Published in: The Journal of biological chemistry Vol. 263; no. 30; pp. 15467 - 15473
• Main Authors: Lowe, S W, Checovich, W J, Rapacz, J, Attie, A D
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Elsevier Inc 25.10.1988; American Society for Biochemistry and Molecular Biology
• Subjects: Algorithms; Alleles; Animals; apolipoproteins; Apolipoproteins B - genetics; Biological and medical sciences; Cell receptors; Cell structures and functions; cerdo; Fundamental and applied biological sciences. Psychology; gene; genes; lipoprotein (low density); lipoproteinas; lipoproteine; lipoproteins; Lipoproteins, LDL - genetics; Lipoproteins, LDL - metabolism; Molecular and cellular biology; mutant; mutantes; mutants; Mutation; porcin; Receptors, LDL - metabolism; Swine; Cell culture; Deficiency; Metabolism; Cholesterol; Pig; Lipoprotein LDL; Vertebrata; Membrane receptor; Mammalia; Hypercholesterolemia; Turnover; Artiodactyla; Mutation; Fibroblast; Ungulata
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/S0021-9258(19)37612-4

We previously identified a defect in the in vivo catabolism of low density lipoprotein (LDL) from hypercholesterolemic pigs carrying a mutant apolipoprotein B allele. In the present studies, we examined the in vitro metabolism of mutant LDL in cultured pig fibroblasts. A 3-fold higher concentration of mutant LDL (compared to control) was needed to displace 50% of control 125I-LDL binding. Mutant LDL had a 6-fold higher dissociation constant than control LDL. Scatchard plots of the binding data were concave upward, suggesting multiple classes of binding sites or negative cooperativity. The mutant LDL degradation rate was reduced by 40%; this decrease could be attributed to a dense LDL subspecies. Mutant and control buoyant LDL subspecies were degraded more slowly than the corresponding dense LDL subspecies. Together, these studies show that diminished LDL receptor binding can result from mutations in apolipoprotein B and from changes in the lipid composition of LDL particles.