Inhibition of lecithin cholesterol acyltransferase by phosphatidylcholine hydroperoxides

To gain insight into the nature of the lecithin-cholesterol acyltransferase inhibitory factor(s), we separated and collected the oxidation products from oxidized lipoproteins after lipoxygenase treatment. Isolated fractions identified by chemiluminescence, as hydroperoxides of phosphatidylcholine, w...

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Bibliographic Details
Published in:FEBS letters 1999-03, Vol.447 (1), p.106-110
Main Authors: Davit-Spraul, Anne, Thérond, Patrice, Leroy, Arnaud, Palmade-Rieunier, Françoise, Rousset, Céline, Moatti, Nicole, Legrand, Alain
Format: Article
Language:English
Subjects:
Apolipoprotein A-I
Cholesterol
Chromatography, High Pressure Liquid
Dose-Response Relationship, Drug
Enzyme inhibition
Hydroperoxide
Lecithin-cholesterol acyltransferase
Lipid Peroxidation
Lipoproteins, HDL
Phosphatidylcholine
Phosphatidylcholine-Sterol O-Acyltransferase - antagonists & inhibitors
Phosphatidylcholines - pharmacology
Phospholipids
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Summary:To gain insight into the nature of the lecithin-cholesterol acyltransferase inhibitory factor(s), we separated and collected the oxidation products from oxidized lipoproteins after lipoxygenase treatment. Isolated fractions identified by chemiluminescence, as hydroperoxides of phosphatidylcholine, were found to produce a significant reduction of lecithin-cholesterol acyltransferase activity. The reaction kinetics of lecithin-cholesterol acyltransferase with reconstitued high density lipoproteins were studied in the presence of 0.6 and 1.2 μM hydroperoxides of phosphatidylcholine. No significant changes in the apparent V max were observed but a concentration-dependent increase in slope of the reciprocal plots and in the apparent K m values was observed with increasing hydroperoxide concentrations. These results show that the active site of lecithin-cholesterol acyltransferase is not affected by the presence of phosphatidylcholine hydroperoxides. Nevertheless, hydroperoxides of phosphatidylcholine altered the reactivity of lecithin-cholesterol acyltransferase for reconstitued high density lipoproteins suggesting either an alteration of the binding of lecithin-cholesterol acyltransferase to the reconstitued high density lipoproteins or a competitive inhibition mechanism.
ISSN:0014-5793
1873-3468
DOI:10.1016/S0014-5793(99)00278-1