Isolation and specificity of rat lecithin: cholesterol acyltransferase: comparison with the human enzyme using reassembled high-density lipoproteins containing ether analogs of phosphatidylcholine

• Published in: Biochimica et biophysica acta Vol. 833; no. 3; p. 456
• Main Authors: Pownall, H J, Pao, Q, Massey, J B
• Format: Journal Article
• Language: English
• Published: Netherlands 06-03-1985
• Subjects: Amino Acids - analysis; Animals; Apolipoprotein A-I; Apolipoproteins A - metabolism; Cholesterol Esters - metabolism; Humans; Lipoproteins, HDL - metabolism; Mathematics; Phosphatidylcholine-Sterol O-Acyltransferase - isolation & purification; Phosphatidylcholine-Sterol O-Acyltransferase - metabolism; Phosphatidylcholines - metabolism; Rats; Structure-Activity Relationship; Substrate Specificity
• ISSN: 0006-3002
• DOI: 10.1016/0005-2760(85)90103-1

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.