Isolation and specificity of rat lecithin: cholesterol acyltransferase: comparison with the human enzyme using reassembled high-density lipoproteins containing ether analogs of phosphatidylcholine.
Rat plasma lecithin: cholesterol acyltransferase, a 68 kDa glycoprotein, has been purified 14 000-fold by a modification of a procedure used for the human enzyme. The activity of lecithin: cholesteryl acyltransferase in human and rat plasma are the same, although activation of both enzymes by human apolipoprotein A-I is greater than that produced by rat apolipoprotein A-I. Using reassembled high-density lipoproteins composed of human apolipoprotein A-I, phosphatidylcholine ethers and a series of different phosphatidylcholines, the separate effects of molecular species specificity and microenvironment on the rate of cholesteryl ester formation was determined. Substitution of a fluid lipid, 1-palmityl-2-oleyl-sn-glycero-3-phosphorylcholine, for a solid lipid, 1,2-dipalmityl-sn-glycero-3-phosphorylcholine, produced an 8-fold increase in the activity of all molecular species of phosphatidylcholine. With either solid or fluid lipid environments, the activity decreased as a function of increasing chain length of saturated acyl groups. Addition of one or more double bonds greatly increased the activity of a given saturated homologue. One major difference between the molecular specificity of rat and human lecithin: cholesteryl acyltransferase was that the latter had a two-fold preference for phosphatidylcholines containing arachidonate at the sn-2-position.
D000596:Amino Acids / Q000032:analysis; D000818:Animals; D016632:Apolipoprotein A-I; D001054:Apolipoproteins A / Q000378:metabolism; D002788:Cholesterol Esters / Q000378:metabolism; D006801:Humans; D008075:Lipoproteins, HDL / Q000378:metabolism*; D008433:Mathematics; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000302:isolation & purification* / Q000378:metabolism; D010713:Phosphatidylcholines / Q000378:metabolism*; D051381:Rats; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
D000596:Amino Acids; D016632:Apolipoprotein A-I; D001054:Apolipoproteins A; D002788:Cholesterol Esters; D008075:Lipoproteins, HDL; D010713:Phosphatidylcholines; C037978:high density lipoprotein phosphatidylcholine; D007862:Phosphatidylcholine-Sterol O-Acyltransferase