Evidence for a lipoprotein carrier in human plasma catalyzing sterol efflux from cultured fibroblasts and its relationship to lecithin:cholesterol acyltransferase.
Immunoaffinity chromatography has been used to study the determinants of sterol efflux and net transport from cultured fibroblasts to human plasma medium. Sterol efflux was highly (approximately 80%) dependent upon a minor lipoprotein fraction containing apolipoprotein A-I unassociated with other apolipoproteins. The remaining activity was associated with the lipoprotein-free fraction of plasma and could be replaced by apoprotein-free albumin. Efflux was independent of lecithin:cholesterol acyltransferase (EC 2.3.1.43) activity. Net transport (i.e., the excess of efflux over influx) was completely inhibited by inhibition of lecithin:cholesterol acyltransferase or its removal by affinity chromatography on immobilized antibodies to apolipoprotein A-I or D (components of the transfer complex in human plasma). In uninhibited plasma, efflux and net transport rates had similar kinetics, suggesting that these were linked functions and that net transport was initiated by a carrier-dependent efflux step that, in the absence of lecithin:cholesterol acyltransferase activity, was associated with an equivalent influx of free sterol to the cells and that, in the presence of lecithin:cholesterol acyltransferase, was associated with esterification and transfer protein activity. The cholesterol carrier lipoprotein function (approximately 5% of plasma apolipoprotein A-I) appears to be the first step of lecithin:cholesterol acyltransferase-linked sterol transport from cells.
D001053:Apolipoproteins / Q000378:metabolism; D001692:Biological Transport; D002478:Cells, Cultured; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D008074:Lipoproteins / Q000378:metabolism*; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000378:metabolism*; D013261:Sterols / Q000378:metabolism*
D001053:Apolipoproteins; D008074:Lipoproteins; D013261:Sterols; D007862:Phosphatidylcholine-Sterol O-Acyltransferase