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Journal of Lipid Research, Vol. 42, 1979-1986, December 2001
Copyright © 2001 by Lipid Research, Inc.

A novel pathway for lipid biosynthesis: the direct acylation of glycerol

Douglas P. Leea, Andrew S. Deonarinea, Martin Kienetza, Quansheng Zhua, Monika Skrzypczaka, Monroe Chana, and Patrick C. Choya
a Department of Biochemistry and Medical Genetics, Faculty of Medicine, University of Manitoba, 770 Bannatyne Ave., Winnipeg, Manitoba, Canada R3E 0W3

Correspondence to: Patrick C. Choy, To whom correspondence should be addressed., pchoy{at}ms.umanitoba.ca (E-mail)

The acylation of glycerol-3-phosphate by acyl-CoA is regarded as the first committed step for the synthesis of the lipoidal moiety in glycerolipids. The direct acylation of glycerol in mammalian tissues has not been demonstrated. In this study, lipid biosynthesis in myoblasts and hepatocytes was reassessed by conducting pulse-chase experiments with [1,3-3H]glycerol. The results demonstrated that a portion of labeled glycerol was directly acylated to form monoacylglycerol and, subsequently, diacylglycerol and triacylglycerol. The direct acylation of glycerol became more prominent when the glycerol-3-phosphate pathway was attenuated or when exogenous glycerol levels became elevated. Glycerol:acyl-CoA acyltransferase activity, which is responsible for the direct acylation of glycerol, was detected in the microsomal fraction of heart, liver, kidney, skeletal muscle, and brain tissues. The enzyme from pig heart microsomes displayed optimal activity at pH 6.0 and the preference for arachidonyl-CoA as the acyl donor. The apparent Km values for glycerol and arachidonyl-CoA were 1.1 mM and 0.17 mM, respectively.

The present study demonstrates the existence of a novel lipid biosynthetic pathway that may be important during hyperglycerolemia produced in diabetes or other pathological conditions. Lee, D. P., A. S. Deonarine, M. Kienetz, Q. Zhu, M. Skrzypczak, M. Chan, and P. C. Choy. A novel pathway for lipid biosynthesis: the direct acylation of glycerol. J. Lipid Res. 2001. 42: 1979–1986.

Supplementary key words: monoacylglycerol, arachidonyl-CoA, acyltransferase, lipid biosynthesis, cardiac myoblast, hepatocyte


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