Lecithin-Cholesterol Acyltransferase and Plasma Lipid Transfer Protein

  • John J. Albers
Part of the GWUMC Department of Biochemistry Annual Spring Symposia book series (GWUN)


High-density lipoproteins (HDL), LCAT, and lipid transfer proteins play key roles in lipid transport. They assist in the removal of unesterified cholesterol from extrahepatic tissues and in transporting cholesterol to the liver. The HDL represent a heterogeneous population of particles that differ in composition and function based on apoprotein composition. They contain two major subclasses: particles that contain A-I and A-II, Lp(A — I + A — II), and particles that contain A-I without A-II, Lp(A-I). Each of these subpopulations is heterogeneous in size and apoprotein composition. The majority of LCAT (approximately 70%) and the neutral lipid transfer protein, or LTP-1 (approximately 80%), in plasma is associated with Lp(A-I) particles. In both plasma and Lp(A-I) particles isolated by populations (mean Stokes diameter 102 Å by gPAGE, 129 Å by gel filtration), whereas LTP-I activity is in the smaller-sized subpopulations (mean Stokes diameter 86 Å by gPAGE, 113 Å by gel filtration).

The LCAT is synthesized and secreted by the human liver cell line HepG2 (approximately 2 μg of LCAT/g cell protein per hr) and catalyzes the hydrolysis of fatty acid from phosphatidylcholine and transfers the fatty acid to unesterified cholesterol to form cholesteryl ester. This lecithin-cholesterol acyltransferase-mediated reaction requires an apoprotein cofactor, primarily apoprotein A-I. Some data suggest that apoproteins other than A-I may also serve as physiological cofactors for the LCAT reaction. In the presence of low-density lipoproteins (LDL), LCAT can also catalyze the transfer of fatty acid to lysolecithin to form lecithin. Preferential formation of disaturated phospholipid species occurs with this lysolecithin acyltransferase reaction.

The cholesteryl ester formed by the LCAT reaction is transferred from HDL to very-low-density lipoproteins (VLDL) and chylomicron remnants by LTP-1, which also facilitates the net mass transfer of cholesteryl ester from HDL to remnants of VLDL and chylomicrons, the net transfer of triglyceride from remnant lipoproteins to LDL or HDL, and the net mass transfer of phosphatidylcholine from VLDL to HDL. Thus, LTP-1 can cause extensive remodeling of plasma lipoproteins. The LTP-1 has an apparent molecular weight of 64,000, an isoelectric point of 5.0, and is heat stable. At 58°C for 1 hr, only 5% of the activity is lost. A neutral lipid transfer protein with properties similar to the plasma-derived LTP-1 is synthesized and secreted by both human monocyte derived macrophages and HepG2 cells.

Human plasma also contains a phospholipid transfer protein (LTP-2), which can facilitate the net mass transfer of phosphatidylcholine from VLDL to HDL. The LTP-2 has an apparent molecular weight of approximately 69,000, an isoelectric point of 5.0, and is heat labile. At 58°C for 1 hr, 90% of the activity is lost.

Some animal species, such as pig and rat, do not have measurable neutral lipid transfer activity in their plasma. However, significant amounts of LTP activity can be isolated from their plasma after passage of lipoprotein-deficient plasma over a hydrophobic matrix. The apparent lack of neutral lipid transfer activity in these species appears to result from plasma protein inhibitor(s). Passage of human lipoprotein-deficient plasma over a hydrophobic matrix leads to a significant enhancement of transfer activity, suggesting that human plasma also contains protein inhibitor(s) of LTP-1. These inhibitors have been purified from plasma and characterized. Plasma protein inhibitors of LTP-1 may be major determinants of the differences in lipid transfer activity between and among animal species.


Cholesteryl Ester Transfer Activity Lipid Transfer Protein Acyl Donor LCAT Activity 
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Copyright information

© Plenum Press, New York 1987

Authors and Affiliations

  • John J. Albers
    • 1
  1. 1.Departments of Medicine and PathologyUniversity of Washington School of MedicineSeattleUSA

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