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Inhibition of lecithin cholesterol acyltransferase by phosphatidylcholine hydroperoxides
Author(s) -
Davit-Spraul Anne,
Thérond Patrice,
Leroy Arnaud,
Palmade-Rieunier Françoise,
Rousset Céline,
Moatti Nicole,
Legrand Alain
Publication year - 1999
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(99)00278-1
Subject(s) - phosphatidylcholine , acyltransferase , chemistry , lecithin , sterol o acyltransferase , cholesterol , biochemistry , chemiluminescence , enzyme , phospholipid , chromatography , lipoprotein , membrane
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.