HDL biology
A minor pre-beta lipoprotein containing apoD, LCAT, and CETP channels newly esterified cell cholesterol into HDL (J Biol Chem 1989)
Original title: Distribution and functions of lecithin:cholesterol acyltransferase and cholesteryl ester transfer protein in plasma lipoproteins. Evidence for a functional unit containing these activities together with apolipoproteins A-I and D that catalyzes the esterification and transfer of cell-derived cholesterol
Two-dimensional electrophoresis and immunoblotting mapped the distribution of apolipoprotein A-I, apolipoprotein D, LCAT, and CETP in fasting human plasma, while pulse-labeling plasma briefly incubated with cholesterol-labeled fibroblasts tracked which lipoprotein species carried newly synthesized cholesteryl esters. After early appearance of labeled free cholesterol in two pre-beta-migrating apoA-I species, labeled cholesteryl esters appeared, following a 2-minute delay, in a third pre-beta-migrating species that also contained apolipoprotein D, LCAT, and CETP. Pulse-chase experiments showed label in this fraction was the precursor of most labeled cholesteryl esters subsequently found in bulk alpha-migrating HDL, while less than 10% of labeled cholesteryl esters appeared in LDL or VLDL over the 15-minute time course, indicating that cell-derived cholesterol and its esters are channeled through a preferred pathway involving minor pre-beta lipoproteins carrying apoD, LCAT, and CETP together en route to HDL.
Original abstract
The distribution of apolipoprotein A-I, apolipoprotein D, lecithin:cholesterol acyltransferase, and cholesteryl ester transfer protein in fasting normal human plasma was determined by two-dimensional electrophoresis followed by immunoblotting. The synthesis and transfer of labeled cholesteryl esters generated in plasma briefly incubated with [3H]cholesterol-labeled fibroblasts was followed in terms of the lipoprotein species containing these antigens. Following the early appearance of labeled free cholesterol in two pre beta-migrating apolipoprotein A-I species (Castro, G. R., and Fielding, C. J. (1988) Biochemistry 27, 25-29), labeled esters were first detected, after a 2-min delay, in a third pre beta-migrating species which also contained apolipoprotein D, lecithin:cholesterol acyltransferase, and cholesteryl ester transfer protein. Pulse-chase experiments determined that label generated in this fraction was the precursor of at least a major part of labeled cholesteryl esters in the bulk of alpha-migrating high density lipoprotein. Over the maximum time course of these experiments (15 min, 37 degrees C), less than 10% of labeled cholesteryl esters were recovered in low or very low density lipoproteins separated by electrophoresis, immunoaffinity, or heparin-agarose chromatography. These data suggest channeling of cell-derived cholesterol and cholesteryl esters derived from it through a preferred pathway involving several minor pre beta-migrating lipoproteins to alpha-migrating high density lipoprotein.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.