The Role of Receptors in Apolipoprotein B Metabolism

  • C. J. Packard
  • J. Shepherd
  • H. R. Slater
Conference paper


A new perspective on lipoprotein metabolism has been gained from the identification and characterisation of Specific high affinity lipoprotein receptors. These are located on cell membranes and serve to facilitate and control the ingress of lipoprotein cholesterol into the cell. They exhibit two important properties. First, they are subject to autoregulation so that when cellular cholesterol requirements rise, the receptors are stimulated to promote lipoprotein assimilation. Conversely, when the cell is replete with the sterol, receptor activity is suppressed. Second, they demonstrate a high degree of ligand specificity which derives from selective interaction between the receptor and apoproteins on the surface of lipoproteins. Two polypeptides, apolipoproteins B and E, have been implicated in this recognition process and two distinct membrane receptor activities have also been identified (1,2,3,4). One seems to be confined to hepatocytes and apparently operates as an efficient mechanism for the cellular assimilation of chylomicron remnants. The other which appears to be identical to the fibroblast receptor of Goldstein and Brown (1) is widely distributed throughout the tissues of the body and plays an important role in the metabolism of low density lipoproteins (LDL).


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Goldstein JL, Brown MS (1977) The low density lipoprotein pathway and its relation to atherosclerosis. Ann Rev Biochem 46: 897–930PubMedCrossRefGoogle Scholar
  2. 2.
    Brown MS, Goldstein JL (1978) General scheme for regulation of cholesterol metabolism in mammalian cells. In: Distrubances in Lipid and Lipoprotein Metabolism; editors Dietschy J M, Gotto A M and Ontko J A. American Physiological Society, Bethesda, Md, pp 173–180Google Scholar
  3. 3.
    Mahley RW and Innerarity TL (1978) Properties of lipoproteins responsible for high affinity bind to cell surface receptors of fibroblasts and smooth muscle cells. Adv Exp Med Biol 109: 99–127PubMedGoogle Scholar
  4. 4.
    Mahley R W, Hui D Y, Innerarity T L, Weisgraber K H (1981) Two independent lipoprotein receptors on hepatic membranes of dog, swine and man. J Clin Invest 68: 1197–1206PubMedCrossRefGoogle Scholar
  5. 5.
    Kovanen P T, Basu S K, Goldstein J L and Brown M S (1979) Low density lipoprotein receptors in bovine adrenal cortex II. Low density lipoprotein binding to membranes prepared from fresh tissue. Endocrinology 104: 610–616PubMedCrossRefGoogle Scholar
  6. 6.
    Mahley R W, Innerarity T L, Pitas R E, Weisgraber K H, Brown J H, Gross E (1977) Inhibition of lipoprotein binding to cell surface receptors of fibroblasts following selective modification of arginyl residues in arginine rich and B apoproteins. J Biol Chem 252: 7279–7287PubMedGoogle Scholar
  7. 7.
    Shepherd J, Bicker S, Lorimer A R, Packard C J (1979) Receptor mediated low density lipoprotein catabolism in man. J Lipid Res 20: 999–1006PubMedGoogle Scholar
  8. 8.
    Slater H R, Packard C J, Bicker S, Shepherd J (1980) Effects of cholestyramine on receptor mediated plasma clearance and tissue uptake of human low density lipoprotein in the rabbit. J Biol Chem 255: 10210–10213PubMedGoogle Scholar
  9. 9.
    Slater H R, Packard C J, Shepherd J (1982) Measurement of receptor independent lipoprotein catabolism using 1, 2 cyclohexanedione-modified low density lipoprotein. J Lipid Res 23: 92–96PubMedGoogle Scholar
  10. 10.
    Shepherd J, Packard C J, Bicker S, Lawrie T D V, Morgan H G (1980) Cholestyramine promotes receptor mediated low density lipoproteins catabolism. N Engl J Med 302: 1219–1222PubMedCrossRefGoogle Scholar
  11. 11.
    Stewart J M, Packard C J, Lorimer A R, Boag D E, Shepherd J (1982) Effects of bezafibrate on receptor mediated and receptor independent low density lipoprotein catabolism in type II hyperlipoproteinemic subjects. Atherosclerosis (in press).Google Scholar
  12. 12.
    Spengel F A, Jadhav A, Duffield R G M, Wood C B, Thompson G R (1981) Superiority of partialileal bypass over cholestyramine in reducing cholesterol in familial hypercholesterolemia. Lancet 768–770Google Scholar
  13. 13.
    Thompson G R,, Soutar A K, Spengel F A, Jadhav A, Gavigan S P, Myant N B (1981) Defects of receptor mediated low density lipoprotein catabolism in homozygous familial hypercholesterolemia and hypothyroidism in vivo. Proc Natl Acad Sci, USA 78: 2591–2595PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1983

Authors and Affiliations

  • C. J. Packard
  • J. Shepherd
  • H. R. Slater

There are no affiliations available

Personalised recommendations