Advertisement

The Role of Apolipoprotein E in Modulating the Metabolism of Apolipoprotein B-48 and Apolipoprotein B-100 Containing Lipoproteins in Humans

  • Richard E. Gregg
  • H. Bryan BrewerJr.
Part of the Advances in Experimetal Medicine and Biology book series (AEMB, volume 201)

Abstract

ApoE* is a glycoprotein of 299 amino acids which is associated primarily with VLDL and HDL in human plasma (1,2). It is a polymorphic protein with three common alleles inherited in a co-dominant fashion (3,4), the most common allele coding for apoE3. Homozygosity for this allele is present in approximately 60% of normal subjects, and this is considered to be the normal phenotype (5). Two other common alleles, which code for apoE2 and apoE4, differ from apoE3 by only one amino acid each (6). The allelic frequency of each of these two alleles is approximately 10–15%. Homozygosity for the apoE2 allele is associated with type III hyperlipoproteinemia (3,4) while apoE4 is associated with type V hyperlipoproteinemia (7). Previous investigations have demonstrated that apoE2 is catabolized abnormally slowly in vivo (8) and has a reduced binding affinity for cellular receptors (9). ApoE4 has a normal cellular receptor binding activity when compared to apoE3 (9). The results of these and other studies have led to the proposal that apoE has a major role in modulating the catabolism of remnants of triglyceride-rich lipoprotein particles from the intestine.

Keywords

Homozygous Familial Hypercholesterolemia Fractional Catabolic Rate Remnant Particle Iodine Monochloride VLDL Remnant 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    C.B. Blum, L. Aron, and R. Sciacca. Radioimmunoassay studies on human apolipoprotein E. J Clin Invest 66:1240 (1980).CrossRefGoogle Scholar
  2. 2.
    R.J. Havel, L. Kotite, J.L. Vigne, J.P. Kane, P. Tun, N. Phillips, and G.C. Chen. Radioimmunoassay of human arginine-rich apolipoprotein, apolipoprotein E. J Clin Invest 66:1351 (1980).CrossRefGoogle Scholar
  3. 3.
    G. Utermann, M. Jaeschke, and J. Menzel. Familial hyperlipoproteinemia type III: deficiency of a specific apolipoprotein (apoE-III) in the very low density lipoproteins. FEBS Lett 56:352 (1975).PubMedCrossRefGoogle Scholar
  4. 4.
    V.I. Zannis, and J.L. Breslow. Human very low density lipoprotein apolipoprotein E isoprotein polymorphism is explained by genetic variation and post-translational modification. Biochemistry 20:1033 (1981).PubMedCrossRefGoogle Scholar
  5. 5.
    G. Ghiselli, R.E. Gregg, L.A. Zech, E.J. Schaefer, and H.B. Brewer, Jr. Phenotype study of apolipoprotein E isoforms in hyperlipoproteinemia patients. Lancet ii:405 (1982).CrossRefGoogle Scholar
  6. 6.
    S.C. Rall, Jr., K.H. Weisgraber, and R.W. Mahley. Human apolipoprotein E. The complete amino acid sequence. J Biol Chem 257:4171 (1982).PubMedGoogle Scholar
  7. 7.
    G. Ghiselli, E.J. Schaefer, L.A. Zech, R.E. Gregg, and H.B. Brewer, Jr. Increased prevalence of apolipoprotein E4 in type V hyperlipoproteinemia. J Clin Invest 70:474 (1982).PubMedCrossRefGoogle Scholar
  8. 8.
    R.E. Gregg, L.A. Zech, E.J. Schaefer, and H.B. Brewer, Jr. Type III hyperlipoproteinemia: defective metabolism of an abnormal apolipoprotein E. Science 211:584 (1981).PubMedCrossRefGoogle Scholar
  9. 9.
    K. H. Weisgraber, T.L. Innerarity, and R.W. Mahley. Abnormal lipoprotein receptor-binding activity of the human E apoprotein due to cysteine-arginine interchange at a single site. J Biol Chem 257:2518 (1982).PubMedGoogle Scholar
  10. 10.
    J.L. Goldstein, M.S. Brown, in The Metabolic Basis of InheritedDisease, J.B. Stanbury, J.B. Wyngaarden, D.S. Frederickson, J.L. Goldstein, and M.S. Brown, Eds., McGraw-Hill, New York, N.Y. pp. 672–712 (1983).Google Scholar
  11. 11.
    G. Utermann, K.H. Vogelberg, A. Steinmetz, W. Schoenborn, N. Pruin, M. Jaeschke, M. Hees. Polymorphism of apolipoprotein E. II. Genetics of hyperlipoproteinemia type III. Clin Genet 15:37 (1979).PubMedCrossRefGoogle Scholar
  12. 12.
    H.-J. Menzel, R.-G. Kladetzky, G. Assmann. Apolipoprotein E polymorphism and coronary artery disease. Arteriosclerosis 3:310 (1983).PubMedCrossRefGoogle Scholar
  13. 13.
    D. Bouthillier, C.F. Sing, and J. Davignon. Apolipoprotein E phenotyping with a single gel method: Application to the study of informative matings. J Lipid Res 24:1060 (1983).PubMedGoogle Scholar
  14. 14.
    G. Utermann, I. Kindermann, H. Kaffarnik, and A. Steinmetz. Apolipoprotein E phenotypes and hyperlipidemia. Hum Genet 65:232 (1984).PubMedCrossRefGoogle Scholar
  15. 15.
    G. Assmann, G. Schmitz, H.-J. Menzel, and H. Schulte. Apolipoprotein E polymorphism and hyperlipidemia. Clin Chem 30:641 (1984).PubMedGoogle Scholar
  16. 16.
    C. F. Sing, and J. Davignon. Role of the apolipoprotein E polymorphism in determining normal plasma lipid and lipoprotein variation. Am J Hum Genet 37:268 (1985).PubMedGoogle Scholar
  17. 17.
    H.B. Brewer, Jr., L.A. Zech, R.E. Gregg, D.S. Schwartz, and E.J. Schaefer. Type III hyperlipoproteinemia: diagnosis, molecular defects, pathology, and treatment. Ann Intern Med 98:623 (1983).Google Scholar
  18. 18.
    R.E. Gregg, R. Ronan, L.A. Zech, G. Ghiselli, E.J. Schaefer, and H.B. Brewer, Jr. Abnormal metabolism of apolipoprotein E4. Arteriosclerosis 2:420a (1982).Google Scholar
  19. 19.
    R.E. Gregg, L.A. Zech, E.J. Schaefer, and H.B. Brewer, Jr. Apolipoprotein E metabolism in normolipoproteinemic human subjects. J Lipid Res 25:1167 (1984).PubMedGoogle Scholar
  20. 20.
    R.E. Gregg, E.J. Schaefer, L.A. Zech, H.B. Brewer, Jr. Lipoprotein distribution of radioiodinated type III and type V apolipoprotein E (apoE). Arteriosclerosis 1:85 (1981).Google Scholar
  21. 21.
    R.E. Gregg, L.A. Zech, C. Gabelli, D. Stark, D. Wilson, H.B. Brewer, Jr. LDL catabolism in normolipidemic apoE2 homozygotes. Circulation 70, Supp 11:312 (1984).Google Scholar
  22. 22.
    J.P. Kane. Apolipoprotein B.: structure and metabolic heterogeneity. Ann Rev Physiol 45:632 (1983).CrossRefGoogle Scholar
  23. 23.
    G. Ghiselli, E.J. Schaefer, P. Gascon, and H.B. Brewer, Jr. Type III hyperlipoproteinemia associated with plasma apolipoprotein E deficiency. Science 214:1239 (1981).PubMedCrossRefGoogle Scholar
  24. 24.
    C. Gabelli, D.G. Stark, R.E. Gregg, H.B. Brewer, Jr. Separation of apolipoprotein B species by agarose-acrylamide gel electrophoresis. J Lipid Res (in press).Google Scholar
  25. 25.
    E.J. Schaefer, L.A. Zech, G. Ghiselli, H.B. Brewer, Jr. ApoB-48 metabolism: retarded catabolism due to apoE deficiency. Arteriosclerosis 2:424a (1982).Google Scholar
  26. 26.
    C. Gabelli, R.E. Gregg, L.A. Zech, J.M. Hoeg, H.B. Brewer, Jr. ApoB-48 catabolism in normal and homozygous familial hypercholesterolemic individuals. Clin Res 32:116a (1984).Google Scholar

Copyright information

© Springer Science+Business Media New York 1986

Authors and Affiliations

  • Richard E. Gregg
    • 1
  • H. Bryan BrewerJr.
    • 1
  1. 1.Molecular Disease BranchNational Heart, Lung, and Blood Institute, National Institutes of HealthBethesdaUSA

Personalised recommendations