Apolipoprotein B-100 conformation and particle surface charge in human LDL subspecies: implication for LDL receptor interaction.
Level 5 - mechanism / opinion, no new human data
In vitro biophysical and biochemical characterization of isolated human lipoprotein subspecies.
PubMed 9737865 · doi:10.1021/bi980828m
What was done
The authors examined lysine microenvironments (pKa) in apolipoprotein B-100 across human small dense, intermediate, and light LDL subspecies using carbon-13 nuclear magnetic resonance (13C NMR). They also measured the net surface charge of each subfraction at pH 8.6 using electrophoretic mobility to evaluate structural determinants of cellular LDL receptor binding.
What was found
Relative to the total LDL fraction, small dense and light LDL subspecies had a decreased number of pKa 8.9 Lys residues, whereas intermediate-density LDL showed a consistently higher number of pKa 8.9 Lys. Electrophoretic mobility measurements showed that light LDL was -26e to -34e more negative than intermediate-density LDL, while small dense LDL was -7e to -17e more negative than intermediate-density LDL.
Why it matters
This study provides a biophysical mechanism explaining why small dense LDL particles bind poorly to the LDL receptor, suggesting conformational alterations in apo B-100 prolong plasma clearance and elevate atherogenicity.
Limits
The abstract does not report the number of human plasma donors, sample demographics, or direct cellular binding assays in this dataset. Findings reflect in vitro physical measurements rather than clinical cardiovascular outcomes.
Cited by
- supports As LDL particles shrink in size, the apoB receptor recognition site becomes obscured, giving smaller LDL particles lower binding affinity for the LDL receptor.
- supports Small LDL particles are cleared less efficiently by LDL receptors than larger LDL particles.