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Journal of Lipid Research, Vol 28, 719-732, Copyright © 1987 by Lipid Research, Inc.
AV Nichols, EL Gong, PJ Blanche, TM Forte and VG Shore
The lecithin:cholesterol acyltransferase (LCAT)-induced transformation of
two discrete species of model complexes that differ in number of
apolipoprotein A-I (apoA-I) molecules per particle was investigated. One
complex species (designated 3A-I(UC)-complexes) contained 3 apoA-I per
particle, was discoidal (13.5 X 4.4 nm), and had a molar composition of
22:78:1 (unesterified cholesterol (UC):egg yolk phosphatidylcholine (egg
yolk PC):apoA-I). The other complex species (designated 2A-I(UC)complexes)
containing 2 apoA-I per particle was also discoidal (8.4 X 4.1 nm) and had
a molar composition of 6:40:1. Transformation of 3A-I(UC)complexes by
partially purified LCAT yielded a product (24 hr, 37 degrees C) with a
cholesteryl ester (CE) core, 3 apoA-I, and a mean diameter of 9.2 nm. The
2A-I(UC)complexes were only partially transformed to a core-containing
product (24 hr, 37 degrees C) which also had 3 apoA-I; this product,
however, was smaller (diameter of 8.5 nm) than the product from
3A-I(UC)complexes. Transformation of 3A-I(UC)complexes appeared to result
from build-up of core CE directly within the precursor complex.
Transformation of 2A- I(UC)complexes, however, followed a stepwise pathway
to the product with 3 apoA-I, apparently involving fusion of transforming
precursors and release of one apoA-I from the fusion product. In the
presence of low density lipoprotein (LDL), used as a source of additional
cholesterol, conversion of 2A-I(UC)complexes to the product with 3 apoA- I
was more extensive. The transformation product of 3A-I(UC)complexes in the
presence of LDL also had 3 apoA-I but was considerably smaller in size (8.6
vs. 9.2 nm, diameter) and had a twofold lower molar content of PC compared
with the product formed without LDL. LDL appeared to act both as a donor of
UC and an acceptor of PC. Transformation products with 3 apoA-I obtained
under the various experimental conditions in the present studies appear to
be constrained in core CE content (between 13 to 22 CE per apoA-I; range of
9 CE molecules) but relatively flexible in content of surface PC molecules
they can accommodate (between 24 to 49 PC per apoA-I; range of 25 PC
molecules). The properties of the core-containing products with 3 apoA- I
compare closely with those of the major subpopulation of human plasma HDL
in the size range of 8.2-8.8 nm that contains the molecular weight
equivalent of 3 apoA-I molecules.
ARTICLES
Pathways in the formation of human plasma high density lipoprotein subpopulations containing apolipoprotein A-I without apolipoprotein A- II
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