ラット大動脈壁の1-acylglycerophosphorylcholine or ethanolamine Acyltransferaseの研究

Abstract

Phospholipids in the aorta play an important role in the progression or regression of atherosclerosis. The properties of phospholipids are in part affected by the fatty acid composition of phospholipids, especially by polyunsaturated fatty acids (PUFA) at the second position.1-Acylglycerophosphate acyltransferase was reported to be a key enzyme to incorporate PUFA into the second position of phospholipids. In the aorta, there are few reports on this enzyme in spite of its significance. In this study, characterization of this enzyme was carried out in the rat aorta and the role of this enzyme in the phospholipid metabolism in the aorta was discussed.Whole homogenate enzyme activity was onefifth of that in the liver. Enzyme activities increased as a function of enzyme protein, incubation time, substrates (PUFA) and acceptor concentrations. When lyso PC was used as the acceptor, the enzyme kinetics showed a sigmoid curve with increased concentration of either the acceptor (lyso PC) or substrate fatty acids. However when lyso PE was used as the acceptor, the kinetics showed a Michaelis-Menten type curve with increased concentration of either the acceptor (lyso PE) or substrate fatty acids.When lyso PC was used as the acceptor, linoleic acid had a higher affinity to the enzyme than arachidonic acid because the S50 value of linoleic acid was lower and the Vmax value of linoleic acid was higher than those of arachidonic acid. When lyso PE was used as the acceptor, the Km and Vmax values of arachidonic acid were higher than those of linoleic acid.When linoleic acid was used as the substrate, the synthesis of phosphatidylcholine (PC) was higher than phosphatidylethanolamine (PE) at any concentration of linoleic acid. However, when arachidonic acid was used as the substrate, the synthesis of PE was higher than PC at low concentration of arachidonic acid, but that of PC was higher than PE at high concentration of arachidonic acid.Fatty acid specificity was as follows:When lyso PC was used as the acceptor, Vmax was in the order of linoleic acid>linolenic acid>eicosapentaenoic acid. When lyso PE was used as the acceptor, Vmax was in the order of arachidonic acid>eicosapentaenoic acid>linoleic acid. Saturated fatty acid (palmitic acid) and docosahexaenoic acid were poor substrates.These results indicate that acyltransferase was regulated not only by the concentration of enzyme protein, acceptors and substrates, but also by the specificity of the acceptors and substrates. PUFA such as arachidonic acid are decreased in the phospholipids of atheromatous lesions. The impaired regulation of this enzyme might be responsible for the abnormal phospholipids in the athermatous lesions.