出版社：American Society for Biochemistry and Molecular Biology
摘要：The final step of triacylglycerol biosynthesis is catalyzedby acyl CoA:diacylglycerol acyltransferase (DGAT) enzymes. Thetwo known DGATs, DGAT1 and DGAT2, are encoded by unrelated genes.Although both DGAT1 and DGAT2 knockout mice have reduced tissuetriacylglycerol contents, they have disparate phenotypes, promptingus to investigate whether the two enzymes have unrecognizedfunctional differences. We now report that DGAT1 exhibits additionalacyltransferase activities in vitro, including those of acylCoA:monoacylglycerol acyltransferase (MGAT), wax monoester andwax diester synthases, and acyl CoA:retinol acyltransferase(ARAT), which catalyze the synthesis of diacylglycerols, waxesters, and retinyl esters, respectively. These activities weredemonstrated in in vitro assays with membranes from insect cellsor homogenates from COS7 cells overexpressing DGAT1. Wax synthaseand ARAT activities were also demonstrated in intact COS7 cellsexpressing DGAT1. Additionally, cells and tissues from DGAT1-deficientmice exhibited reduced ARAT activity, and the mice had increasedlevels of unesterified retinol in their livers on a high-retinoldiet.
Our findings indicate that DGAT1 can utilize a variety of acylacceptors as substrates in vitro and suggest that these activitiesmay 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
