Inhibition of lecithin cholesterol acyltransferase by phosphatidylcholine hydroperoxides

FEBS Letters

Thérond, Patrice¹  Moatti, Nicole³  Rousset, Céline³  Legrand, Alain²  Palmade-Rieunier, Françoise³  Davit-Spraul, Anne²  Leroy, Arnaud³ 

[1] Inserm U347, Le Kremlin Bicêtre, France;Biochimie, Hôpital Bicêtre, Laboratoire de Biochimie, 78, rue du Général Leclerc, 94275 Le Kremlin Bicêtre, France;Biochimie, Faculté de Pharmacie, Châtenay Malabry, France

关键词: Lecithin-cholesterol acyltransferase;    Hydroperoxide;    Phosphatidylcholine;    Enzyme inhibition;   

DOI  :  10.1016/S0014-5793(99)00278-1

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown