Stereochemical substrate requirements of lecithin:cholesterol acyltransferase and its inhibition by enantiomeric lysolecithins.
The suitability of 1-sn-phosphorylcholine- and 2-sn-phosphorylcholine-diacylglycerols as substrates for lecithin:cholesterol acyltransferase (LCAT) was assayed under standardized conditions using sonicated liposomes of radioactive phospholipids. The results were compared with those obtained for the corresponding molecular species of the natural 3-sn-phosphorylcholinediacylglycerol. It was found that with the 2-sn-phosphorylcholinediacylglycerol, LCAT had only 16% of the activity that it showed for 3-sn-phosphorylcholinediacylglycerol, while its activity with 1-sn-phosphorylcholinediacyglycerol as the substrate was not significant. It is concluded that LCAT possesses highly specific steric and positional requirements for its phosphatidylcholine substrates and that, like phospholipase A2, it has a significant activity with the 2-sn-phosphorylcholinedicacylglycerol. It wa also shown that the activity of LCAT is inhibited by both enantiomers of lysophosphatidylcholine as well as Triton X-100. In all instances the inhibition was reversed by the addition of lipid-free albumin. It is concluded, therefore, that the inhibition of LCAT by lysophosphatidylcholine is a detergent rather than an end-product inhibition phenomenon.
D005997:Glycerylphosphorylcholine; D008244:Lysophosphatidylcholines / Q000494:pharmacology*; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013237:Stereoisomerism; D013379:Substrate Specificity
D008244:Lysophosphatidylcholines; D005997:Glycerylphosphorylcholine; D007862:Phosphatidylcholine-Sterol O-Acyltransferase