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The Role of Apolipoprotein E and the Low-Density Lipoprotein Receptor in Modulating the in Vivo Metabolism of Apolipoprotein-B-Containing Lipoproteins

  • Richard E. Gregg
  • Loren A. Zech
  • Carlo Gabelli
  • Jeffrey M. Hoeg
  • H. Bryan BrewerJr.
Part of the GWUMC Department of Biochemistry Annual Spring Symposia book series (GWUN)

Abstract

Apolipoprotein (apo) E and receptors that bind apo E are important in modulating the catabolism of apo-B-containing lipoproteins. In order to investigate the role of apo E and the low-density lipoprotein (LDL) receptor in modulating the catabolism of lipoproteins containing apo B-48 and apo B-100, the following in vivo metabolic studies were performed. The residence times of apo E2, apo E3, and apo E4 were determined in normal subjects with a homozygous E3 phenotype. Assuming apo E3 to be normal, apo E2 was catabolized more slowly and apo E4 more rapidly than normal. Therefore, both apo E2 and apo E4 were metabolically abnormal, but the catabolic abnormality was in opposite directions compared to apo E3.

Individuals with an E2 phenotype have decreased plasma LDL concentrations whereas the E4 phenotype is associated with elevated levels. The metabolism of LDL was studied in subjects with a homozygous E2 or E3 phenotype. The decreased LDL concentration in the E2 subjects was secondary to both a decreased synthesis rate and an increased fractional catabolic rate (FCR) of LDL. When the FCR of the LDL from both types of subjects were compared in the same subject, the LDL from the E2 subject was catabolized more slowly than the LDL from the E3 subject. In addition, the E2 subject catabolized the same type of LDL faster than the E3 subject. Thus, the apo E phenotype is important in regulating the rate of formation of LDL, modulates the receptor-mediated endocytosis of LDL, and is important in forming metabolically normal LDL.

The catabolism of remnants of triglyceride-rich lipoproteins containing apo B-48 and apo B-100 was investigated in subjects with homozygous familial hypercholesterolemia (FH) and in a subject with apo E deficiency. The subjects with homozygous FH had normal catabolism of the apo B-48-containing remnants, whereas the apo-E-deficient subject had markedly delayed catabolism, indicating that apo E, but not the LDL receptor, is important in modulating the catabolism of apo-B-48-containing remnants. In the homozygous FH subjects, the apo-B-100-containing remnants were catabolized more slowly than in normal subjects, and a greater percentage of the remnants were converted to IDL and LDL; however, 50% of the apo B-100 remnants were still rapidly catabolized directly from VLDL. In the apo-E-deficient subject, the apo B-100 remnants were very slowly catabolized with little conversion to IDL or LDL. Thus, there is direct catabolism of apo-B-100-containing remnants by both LDL receptor and apo-E-mediated non-LDL receptor processes. In addition, apo E is important in modulating the conversion of apo B-100 remnants to IDL and LDL.

In conclusion, apo E is important in regulating the direct catabolism of both apo-B-48-and apo-B-100-containing remnants and the conversion of apo B-100 remnants to IDL and LDL. In addition, both apo E2 and apo E4 are metabolically abnormal, with the apo E phenotype modulating plasma LDL levels by regulating the catabolic rate of LDL and the rate of formation of metabolically normal LDL.

Keywords

Familial Hypercholesterolemia Lipoprotein Particle Homozygous Familial Hypercholesterolemia Fractional Catabolic Rate Remnant Particle 
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.

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Copyright information

© Plenum Press, New York 1987

Authors and Affiliations

  • Richard E. Gregg
    • 1
  • Loren A. Zech
    • 1
  • Carlo Gabelli
    • 2
  • Jeffrey M. Hoeg
    • 3
  • H. Bryan BrewerJr.
    • 3
  1. 1.National Heart, Lung, and Blood InstituteNational Institutes of HealthBethesdaUSA
  2. 2.Department of Internal MedicineUniversity of PaduaPadovaItaly
  3. 3.The Molecular Disease Branch, National Heart, Lung, and Blood InstituteNational Institutes of HealthBethesdaUSA

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