Abstract
Acyl-CoA-dependent O-acyltransferases catalyze reactions in which fatty acyl-CoAs are joined to acyl acceptors containing free hydroxyl groups to produce neutral lipids. In this report, we characterize a human multifunctional O-acyltransferase (designated MFAT) that belongs to the acyl-CoA:diacylglycerol acyltransferase 2/acyl-CoA:monoacylglycerol acyltransferase (MGAT) gene family and is highly expressed in the skin. Membranes of insect cells and homogenates of mammalian cells overexpressing MFAT exhibited significantly increased MGAT, acyl-CoA:fatty acyl alcohol acyltransferase (wax synthase), and acyl-CoA:retinol acyltransferase (ARAT) activities, which catalyze the synthesis of diacylglycerols, wax monoesters, and retinyl esters, respectively. Furthermore, when provided with the appropriate substrates, intact mammalian cells overexpressing MFAT accumulated more waxes and retinyl esters than control cells. We conclude that MFAT is a multifunctional acyltransferase that likely plays an important role in lipid metabolism in human skin.
Highlights
Acyl-CoA-dependent O-acyltransferases catalyze reactions in which fatty acyl-CoAs are joined to acyl acceptors containing free hydroxyl groups to produce neutral lipids
multifunctional acyltransferase (MFAT) is a member of the DGAT2 gene family [National Center for Biotechnology Information (NCBI) Conserved Domain Database: pfam 03982 DAGAT; Fig. 1A], which includes MGAT1, MGAT2, MGAT3, and two additional members, DC3 and DC7
We examined whether the monoacylglycerol acyltransferase (MGAT), wax synthase, and acyl-CoA:retinol acyltransferase (ARAT) activities of MFAT could be demonstrated with labeled acyl acceptors that were specific for the respective activities, and we determined whether these acyltransferase activities were dependent on the presence of acyl-CoA
Summary
Acyl-CoA-dependent O-acyltransferases catalyze reactions in which fatty acyl-CoAs are joined to acyl acceptors containing free hydroxyl groups to produce neutral lipids. Mice lacking acyl-CoA:diacylglycerol acyltransferase 1 (DGAT1), another enzyme expressed highly in sebaceous glands, have atrophic sebaceous glands and reduced levels of type II wax diesters in their fur lipids, resulting in impaired water repulsion [15]. We studied the in vitro biochemical activities of the expressed enzyme and show that the DC4-encoded enzyme uses a variety of acyl acceptors in in vitro assays, catalyzing the synthesis of diacylglycerols, wax monoesters, and retinyl esters.
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
