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Journal of Lipid Research, Vol 37, 1924-1935, Copyright © 1996 by Lipid Research, Inc.
JR McNamara, DM Small, Z Li and EJ Schaefer
In order to investigate causes of variability in low density lipoprotein
(LDL) particle size, we have assessed LDL composition in plasma from 66
subjects, each with a single LDL band, by 2-16% gradient gel
electrophoresis, with a total of eight discrete sizes (LDL-1 to LDL- 8).
Lipoprotein concentrations were analyzed by standard methods; specific
proteins were assessed by immunoassay and electrophoresis. Results showed
decreased anhydrous molecular weight with size (2.67 +/- 0.07 x 10(6) to
1.78 +/- 0.19 x 10(6)), along with decreased relative content for
cholesteryl ester (41.5% to 24.3%), free cholesterol (10.1% to 4.6%), and
phospholipid (23.7% to 18.9%), and increased triglyceride (4.1% to 21.0%)
and protein (20.5% to 31.2%) content. As LDL size decreased, the ratio of
surface cholesterol to phospholipid decreased from 0.53 to 0.29, and the
fraction of surface area covered by lipid decreased from 0.74 to 0.47.
Moreover, core volume decreased with size from 24.2 A3 x 10(5) to 15.9 A3 x
10(5), and the ratio of surface-to- core lipids fell from 0.59 to 0.46.
Based on surface pressures of 30 mN/m, the area covered by surface lipid
was calculated to range from 6.45 A2 x 10(4) in the largest LDL, to 3.10 A2
x 10(4) in the smallest. Computer modeling indicates that alterations in
the tertiary structure of apoB-100 are required to account for surface
changes. The estimated core surface area requiring coverage by apoB
increased with decreasing particle size from 2.26 A2 x 10(4) to 3.46 A2 x
10(4). To accommodate coverage of increasing relative surface area
associated with decreasing size, apoB thickness at the interface was
calculated to decrease from approximately 25 A to 16 A. Such conformational
changes in apoB may alter exposed epitopes, possibly causing changes in LDL
receptor binding affinity and resistance to oxidation.
ARTICLES
Differences in LDL subspecies involve alterations in lipid composition and conformational changes in apolipoprotein B
Lipid Metabolism Laboratory, USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA 02111, USA.
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