Activation of plasma lysolecithin acyltransferase reaction by apolipoproteins A-I, C-I and E.
The lysolecithin acyltransferase (LAT) activity of lecithin-cholesterol acyltransferase (LCAT) converts lysophosphatidylcholine (lyso PC) to PC, and requires low-density lipoproteins (LDL). To determine whether LDL can be replaced by defined substrates, we tested proteoliposomes containing egg PC, labeled lyso PC and apoprotein (apo) A-I at molar ratios of 250:12.5:0.8, as substrate for purified enzyme. A significant percent of lyso PC in this substrate was acylated to PC, indicating that apo A-I can substitute for apo B in LAT reaction, and that PC is the acyl donor in the reaction. Apo C-I and apo E were, respectively, 70% and 40% as effective as apo A-I. When both lyso PC and free cholesterol (FC) were incorporated into the same proteoliposome, they competed with each other for the acyl groups, with 72% of the total acylation being directed to FC and 28% to lyso PC, at equimolar concentrations. With the native lipoproteins, the esterification of lyso PC was dominant in LDL, whereas FC esterification was dominant in high-density lipoproteins (HDL). Albumin inhibited LAT and activated LCAT in both lipoproteins, but its effects were more pronounced in HDL. These results indicate that the esterification of lyso PC and FC involve the same mechanism, and that the relative predominance of LAT on LDL is due to higher affinity of lyso PC to LDL, compared to HDL.
Liu
M
M
Department of Medicine, Rush Medical College, Chicago, IL 60612.
Subbaiah
P V
PV
D008243:1-Acylglycerophosphocholine O-Acyltransferase / Q000037:antagonists & inhibitors / Q000097:blood / Q000378:metabolism*; D016632:Apolipoprotein A-I / Q000494:pharmacology*; D053302:Apolipoprotein C-I; D001056:Apolipoproteins C / Q000494:pharmacology*; D001057:Apolipoproteins E / Q000494:pharmacology*; D002784:Cholesterol; D004789:Enzyme Activation; D004951:Esterification; D006801:Humans; D007700:Kinetics; D008075:Lipoproteins, HDL / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000378:metabolism*; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000378:metabolism*; D010713:Phosphatidylcholines / Q000494:pharmacology; D011510:Proteolipids
D016632:Apolipoprotein A-I; D053302:Apolipoprotein C-I; D001056:Apolipoproteins C; D001057:Apolipoproteins E; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D010713:Phosphatidylcholines; D011510:Proteolipids; C020485:proteoliposomes; D002784:Cholesterol; D008243:1-Acylglycerophosphocholine O-Acyltransferase; D007862:Phosphatidylcholine-Sterol O-Acyltransferase