Characterization of subspecies of lipoprotein containing apolipoprotein A-I in heterozygotes for familial lecithin:cholesterol acyltransferase deficiency.

We characterized two species of lipoproteins containing apo A-I, one containing only apo A-I (LpA-I) and the other containing both apo A-I and apo A-II (LpA-I/A-II), in three heterozygotes for familial lecithin:cholesterol acyltransferase deficiency (LCAT). In these patients, particle size and the chemical composition of LpA-I differed from those in normal controls. Small particles < 8.8 nm in diameter were predominant, and protein content was higher in patients' LpA-I than that in normal LpA-I. Changes in LpA-I/A-II were mostly quantitative. Percent lipid and protein composition in LpA-I/A-II were similar to those in normal controls. Despite low LCAT mass and activity in the heterozygotes, the molar and fractional rate of cholesterol esterification in their LpA-I and LpA-I/A-II particles were similar to, or higher than, that of normal controls. We conclude that: (i) low LCAT mass and activity is the likely cause of the quantitative and qualitative differences in LpA-I in heterozygotes; and (ii) a deficiency of normal LpA-I particles 11.1 nm in diameter and the existence of small particles < 8.8 nm in diameter may be responsible for the normal, or higher than normal, cholesterol esterification rate of LpA-I and LpA-I/A-II in heterozygotes.