Effect of the surface lipid composition of reconstituted LPA-I on apolipoprotein A-I structure and lecithincholesterol acyltransferase activity》.pdf

Biochimica et Biophysica Acta 1390 1998 160–172 Effect of the surface lipid composition of reconstituted LPA-I on apolipoprotein A-I structure and lecithin:cholesterol acyltransferase activity Daniel L. Sparks , Philippe G. Frank, Tracey A.-M. Neville Lipoproteins and Atherosclerosis Group, Ottawa Ciic Hospital, Uniersity of Ottawa Heart Institute H-452, 1053 Carling Aenue, Ottawa, Ont., Canada K1Y 4E9 Received 18 July 1997; accepted 10 September 1997 Abstract Characterization of the factors that regulate plasma cholesterol esterification shows that the increased activity of lecithin:cholesterol acyltransferase LCAT in the plasma of hyperlipidemic subjects is due to enhanced interactions with a preferred substrate. The details of how the physical properties of high density lipoproteins HDL may affect their ability to stimulate cholesterol esterification by LCAT have been investigated in homogeneous reconstituted HDL particles containing two molecules of apolipoprotein apo A-I Lp2A-I and palmitoyl-oleoyl phosphatidylcholine POPC . Increasing the POPC or sphingomyelin SPH content in an Lp2A-I complex increases particle size and stability but decreases the negative surface charge of apoA-I. Increasing Lp2A-I POPC or SPH content also significantly inhibits cholesterol esterification by LCAT. Increase in the maximum rate of CE production V by LCAT is directly related to an increased negative charge max on the different Lp2A-I particles and to a reduced amount and stability of amphipath