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Journal of Lipid Research, Vol. 46, 1502-1511, July 2005
Copyright © 2005 by American Society for Biochemistry and Molecular Biology
The triacylglycerol synthesis enzyme DGAT1 also catalyzes the synthesis of diacylglycerols, waxes, and retinyl esters
,**
* Gladstone Institute of Cardiovascular Disease, University of California, San Francisco, CA 94158
Cardiovascular Research Institute, University of California, San Francisco, CA 94158
** Department of Medicine, University of California, San Francisco, CA 94158
Western Human Nutrition Research Center, United States Department of Agriculture, Davis, CA 95616
Published, JLR Papers in Press, April 16, 2005. DOI 10.1194/jlr.M500036-JLR200
1 To whom correspondence should be addressed. e-mail: eyen{at}gladstone.ucsf.edu
The final step of triacylglycerol biosynthesis is catalyzed by acyl CoA:diacylglycerol acyltransferase (DGAT) enzymes. The two known DGATs, DGAT1 and DGAT2, are encoded by unrelated genes. Although both DGAT1 and DGAT2 knockout mice have reduced tissue triacylglycerol contents, they have disparate phenotypes, prompting us to investigate whether the two enzymes have unrecognized functional differences. We now report that DGAT1 exhibits additional acyltransferase activities in vitro, including those of acyl CoA:monoacylglycerol acyltransferase (MGAT), wax monoester and wax diester synthases, and acyl CoA:retinol acyltransferase (ARAT), which catalyze the synthesis of diacylglycerols, wax esters, and retinyl esters, respectively. These activities were demonstrated in in vitro assays with membranes from insect cells or homogenates from COS7 cells overexpressing DGAT1. Wax synthase and ARAT activities were also demonstrated in intact COS7 cells expressing DGAT1. Additionally, cells and tissues from DGAT1-deficient mice exhibited reduced ARAT activity, and the mice had increased levels of unesterified retinol in their livers on a high-retinol diet.
Our findings indicate that DGAT1 can utilize a variety of acyl acceptors as substrates in vitro and suggest that these activities may be relevant to the in vivo functions of DGAT1.
Abbreviations: ACAT, acyl CoA:cholesterol acyltransferase; ARAT, acyl CoA:retinol acyltransferase; CoA, coenzyme A; DGAT, acyl CoA:diacylglycerol acyltransferase; LRAT, lecithin:retinol acyltransferase; MEF, mouse embryonic fibroblast; MGAT, acyl CoA:monoacylglycerol acyltransferase; TLC, thin-layer chromatography
Supplementary key words acyl CoA:diacylglycerol acyltransferase • retinol (vitamin A) • wax ester • monoacylglycerol
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