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The composition, structural properties and binding of very-low-density and low-density lipoproteins to the LDL receptor in normo- and hypertriglyceridemia: relation to the apolipoprotein E phenotype

  • Alexander D. Dergunov , Alexey V. Novoselov , Sophie Visvikis , Gerard Siest , Vladimir V. Yakushkin and Vladimir Tsibulsky
Published/Copyright: July 5, 2005
Biological Chemistry
From the journal Volume 386 Issue 5

Abstract

The composition, apolipoprotein structure and lipoprotein binding to the LDL receptor were studied for very-low-density (VLDL) and low-density lipoprotein (LDL) particles isolated from subjects with apoE phenotype E3/3 (E3), E2/2 or E2/3 (E2+) and E3/4 or E4/4 (E4+) and a wide range of plasma triglyceride (TG) contents. The data combined for all three phenotype groups can be summarized as follows. (i) A decrease in accessibility of VLDL tryptophan residues to I- anions with a decrease in tryptophan surface density, concomitant with an increase in VLDL dimensions, reflects the increased efficiency of protein-protein interactions. (ii) A gradual increase in the quenching constant for LDL apoB fluorescence with an increase in TG/cholesterol (Chol) ratio reflects the ‘freezing’ effect of Chol molecules on apoB dynamics. (iii) Different mechanisms specific for a particular lipoprotein from E3/3 or E2/3 subjects are responsible for apoE-mediated VLDL binding and apoB-mediated LDL binding to the LDL receptor in a solid-phase binding assay. (iv) The ‘spacing’ effect of apoC-III molecules on apoE-mediated VLDL binding results in a decrease in the number of binding sites. (v) The maximum of the dependence of the LDL binding affinity constant on relative tryptophan density corresponds to LDL intermediate size. VLDL particles from hypertriglyceridemic E2/3 heterozygotic individuals had remnant-like properties (increased cholesterol, apoE and decreased apoC-III content) while their binding efficiency was unchanged. Based on the affinity constant value and LDL-Chol content, increased competition between VLDL and LDL for the binding to the LDL receptor upon increase in plasma TG is suggested, and LDL from hypertriglyceridemic E3/3 homozygotic individuals is the most efficient competitor.

Keywords: apolipoprotein C-III; apolipoprotein E; low-density lipoprotein (LDL); low-density lipoprotein receptor; very-low-density lipoprotein (VLDL)
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Published Online: 2005-07-05
Published in Print: 2005-05-01

© Walter de Gruyter Berlin New York

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https://doi.org/10.1515/BC.2005.053
Keywords for this article
apolipoprotein C-III; apolipoprotein E; low-density lipoprotein (LDL); low-density lipoprotein receptor; very-low-density lipoprotein (VLDL)

Articles in the same Issue

  1. Saccharomyces cerevisiae translational activator Cbs1p is associated with translationally active mitochondrial ribosomes
  2. Evolution of vitamin B2 biosynthesis: riboflavin synthase of Arabidopsis thaliana and its inhibition by riboflavin
  3. Molecular basis of the complex formation between the two calcium-binding proteins S100A8 (MRP8) and S100A9 (MRP14)
  4. An extracellular carboxylesterase from the basidiomycete Pleurotus sapidus hydrolyses xanthophyll esters
  5. The composition, structural properties and binding of very-low-density and low-density lipoproteins to the LDL receptor in normo- and hypertriglyceridemia: relation to the apolipoprotein E phenotype
  6. Adrenodoxin (Adx) and CYP11A1 (P450scc) induce apoptosis by the generation of reactive oxygen species in mitochondria
  7. Ultraspiracle promotes the nuclear localization of ecdysteroid receptor in mammalian cells
  8. Polyadenylate polymerase modulations in human epithelioid cervix and breast cancer cell lines, treated with etoposide or cordycepin, follow cell cycle rather than apoptosis induction
  9. The anti-inflammatory compound curcumin inhibits Neisseria gonorrhoeae-induced NF-κB signaling, release of pro-inflammatory cytokines/chemokines and attenuates adhesion in late infection
  10. Susceptibility of the interchain peptide of a bromelain inhibitor precursor to the target proteases bromelain, chymotrypsin, and trypsin
  11. Blocking effect of a biotinylated protease inhibitor on the egress of Plasmodium falciparum merozoites from infected red blood cells
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