Spontaneous lipid transfers between low density lipoproteins and reconstituted high density lipoproteins
Bottum, Kathleen Mary
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Permalink
https://hdl.handle.net/2142/23318
Description
Title
Spontaneous lipid transfers between low density lipoproteins and reconstituted high density lipoproteins
Author(s)
Bottum, Kathleen Mary
Issue Date
1995
Doctoral Committee Chair(s)
Jonas, Ana
Department of Study
Biochemistry
Discipline
Biochemistry
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Keyword(s)
Chemistry, Biochemistry
Language
eng
Abstract
Spontaneous lipid transfers are important components in the metabolism of low density lipoprotein (LDL) and high density lipoprotein (HDL). Cholesterol spontaneously transfers from LDL to HDL; phospholipid transfer proceeds in the reverse direction. Reconstituted HDL (rHDL) particles were employed in this study. Cholesterol transfer from LDL to rHDL depended on the ratio of the two particles and their concentrations. When rHDL exceeded LDL, transfer became independent of rHDL concentration. These experiments are consistent with the aqueous diffusion mechanism of cholesterol transfer.
The chemical and physical properties of both LDL and rHDL influence cholesterol transfer. Density gradient ultracentrifugation separated LDL into five subfractions which were progressively more dense, contained less lipid, and were smaller. The smaller subfractions donated less cholesterol to rHDL, and the transfer rate was diminished from these subfractions. Several rHDL properties did not influence cholesterol transfer, namely the shape of the particle (sphere or disk) and the apolipoprotein component (apolipoprotein Al or apolipoprotein All). The rHDL phospholipid packing and initial cholesterol content affected some kinetic parameters of cholesterol transfer, but not others. The most dramatic differences in cholesterol transfer properties were observed with rHDL size. Smaller rHDL accepted cholesterol with the shortest half life, although they ultimately held less cholesterol. These experiments emphasize the importance of a complete kinetic analysis. Determinations of a single kinetic parameter yield insufficient information for an accurate comparison of the ability of different particles to accept cholesterol.
Rearrangements of rHDL accompany spontaneous phospholipid transfers. When rHDL lost phospholipid to LDL, the number of lipid binding alpha helices in apolipoprotein Al decreased and the particle shrunk. This process explains one type of rearrangement. In a second type, rHDL gained phospholipid and an apolipoprotein Al molecule. The particle may have acquired an apolipoprotein with a small amount of attached lipid, or there may have been a collision between rHDL particles. In general, particles with the least amount of alpha helices per apolipoprotein Al were the most stable. Only slight rearrangements were seen in rHDL prepared with apolipoprotein All, although these particles lost phospholipid to the same extent as rHDL prepared with apolipoprotein Al.
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