We studied the effects of the
lecithin:cholesterol acyltransferase reaction on the size and composition of the small spherical
high density lipoproteins of patients afflicted with familial
lecithin:cholesterol acyltransferase deficiency. We isolated these
lipoproteins by preparative ultracentrifugation and rate
zonal ultracentrifugation, determined their diameter by gradient gel electrophoresis, and then calculated their composition by relating measurements of their
lipid and
apolipoprotein content to particle volume. Our results revealed
lipoprotein particles 6.0-6.2 nm in diameter that contained approximately 2 molecules of
apolipoprotein A-I, 37-38 molecules of
phospholipid, 3-9 molecules of unesterified
cholesterol, 1-2 molecules of
cholesteryl ester, and 1-2 molecules of
triacylglycerol. Upon being incubated with
lecithin:cholesterol acyltransferase and a source of additional unesterified
cholesterol, these
lipoproteins increased in content of total
cholesterol and in particle size to form discrete
lipoprotein products 6.6-8.6 nm in diameter. The increase in size occurred despite a net decrease in product unesterified
cholesterol and
phospholipid and though the net change in total
lipid volume was small. Moreover, specific product
lipoproteins, isolated by rate
zonal ultracentrifugation, contained an increased amount of
apolipoprotein A-I. These results seem best explained by a process involving
lecithin:cholesterol acyltransferase-induced particle rearrangement reactions. The possibility that a similar process normally occurs in vivo deserves to be explored.