INTERACTION BETWEEN APO A-I-CONTAINING LIPOPROTEINS AND LECITHIN-CHOLESTEROL ACYLTRANSFERASE

HDL(2) and HDL(3) subfractions of two species of apo A-I-containing lipoprotein, one containing only apo A-I (LpA-I) and the other containing both apo A-I and apo A-II (LpA-I/A-II), were tested for reactivity to lecithin:cholesterol acyltransferase (LCAT). These subfractions and their mixtures were incubated with lipoprotein-deficient plasma (LCAT source), and the rate of cholesterol esterification and kinetic parameters were determined. Apparent V-max (appV(max)) and apparent K-m (appK(m)) for HDL(2) subfractions of LpA-I and LpA-I/A-II were significantly lower than those of their HDL(3) counterparts. Differences between subfractions were much more prominent in LpA-I than in LpA-I/A-II. appV(max) the HDL(2) subfraction of LpA-I (LpA-I-HDL2) was one-fifth, and appK(m) was one-third of those for the HDL(3) subfraction (LPA-I-HDL3). appV(max) and appK(m) of LpA-I-HDL2 were both lowest among the apo A-I-containing lipoprotein subfractions. When LpA-I-HDL2 was added to other subfractions, the molar rate of cholesterol esterification was suppressed. Since LpA-I-HDL2 consists of a particle 11.1 nm in diameter, our observations suggest that LpA-I-HDL2 suppresses cholesterol esterification in apo A-I-containing lipoprotein, possibly by displacing LCAT from other subfractions with higher appK(m) and higher appV(max) to 11.1 nm LpA-I particles with lower appK(m) and lower appV(max). All of these data suggest that the relative amount of 11.1 nm LpA-I particles in plasma regulates the reactivity of apo A-I-containing lipoprotein to LCAT and may play a key role on the production of cholesteryl esters in plasma.