Volume 270,
Number 9,
Issue of March 3, 1995 pp. 4280-4287
©1995 by The American Society for Biochemistry and Molecular Biology, Inc.
Effect of LpA-I
Composition and Structure on Cholesterol Transfer between Lipoproteins
(Received for publication, May 20, 1994; and in revised form, December 12, 1994)
Qiang-Hua
Meng,
Daniel
L.
Sparks,
Yves L.
Marcel
The effect of high density lipoprotein composition on the rates
of unesterified cholesterol exchange between low density lipoproteins
(LDL) and well-defined homogeneous discoidal lipoproteins (LpA-I)
reconstituted with phosphatidylcholine, cholesterol, and apolipoprotein
A-I (apoA-I) has been investigated. LpA-I containing cholesterol and 2,
3, and 4 apoA-I molecules per particle differed in their ability to
accept or donate cholesterol. A significant cholesterol exchange occurs
between LDL and Lp2A-I (7.8 and 9.6 nm), while there is little or no
cholesterol exchange detectable between LDL and Lp3A-I (10.8 and 13.4
nm) and Lp4A-I (17.0 nm) complexes. The cholesterol transfer from LDL
to the cholesterol-free Lp2A-I (9.6 nm), Lp3A-I (13.4 nm), and Lp4A-I
(17.0 nm) particles also shows significant cholesterol transfer to
Lp2A-I, while there is no detectable transfer to Lp3- and 4A-I
particles. The rates of cholesterol transfer to cholesterol-free and
cholesterol-containing Lp2A-I appear to differ significantly.
Cholesterol transfer from LDL to cholesterol-free Lp2A-I is zero order
with respect to acceptor concentrations when the Lp2A-I/LDL ratio is
above 10. Transfer rates from LDL to cholesterol-free Lp2A-I are faster
for the smaller Lp2A-I (8.5 nm) than to the larger Lp2A-I (9.7 nm) and
exhibit half-times (t
) at 25 °C of 4.0 and
5.3 h, respectively. In contrast, cholesterol transfer from LDL to
cholesterol-containing Lp2A-I remains dependent upon acceptor
concentrations to an acceptor/donor particle ratio of 80. In addition,
transfer from LDL to cholesterol-containing Lp2A-I is faster to the 9.6
nm than to 7.8 nm particles, with t of 1.4 and
2.3 h, respectively. The rates of cholesterol transfer from Lp2A-I to
LDL are higher than in the opposite direction, in particular for the
small Lp2A-I (7.8 nm), which has a t of
approximately 50 min. The results show that changes in the composition
and structure of apoA-I-containing particles have a significant effect
on inter-lipoprotein exchange of cholesterol. This suggests that the
kinetics of cholesterol transfer to and from reconstituted discoidal
LpA-I particles cannot be fully explained by passive aqueous diffusion.
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