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A more recent version of this article appeared on April 15, 2005
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M500025200v1
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Papers In Press, published online ahead of print January 25, 2005
J. Biol. Chem, 10.1074/jbc.M500025200
Submitted on January 3, 2005
Revised on January 25, 2005
Accepted on January 25, 2005

Identification of two novel human Acyl-CoA wax alcohol acyltransferases: Members of the diacylglycerol acyltransferase 2 (DGAT2) gene superfamily

Aaron R. Turkish, Annette L. Henneberry, Debra Cromley, Mahajabeen Padamsee, Peter Oelkers, Hisham Bazzi, Angela M. Christiano, Jeffrey T. Billheimer, and Stephen L. Sturley

Institute of Human Nutrition, Columbia University, New York, NY 10032

Corresponding Author: sls37{at}columbia.edu

The esterification of alcohols such as sterols, diacylglycerols and monoacylglycerols with fatty acids represents the formation of both storage and cytoprotective molecules. Conversely, the overproduction of these molecules is associated with several disease pathologies, including atherosclerosis and obesity. The human acyl-CoA:diacylglycerol acyltransferase (DGAT) 2 gene superfamily comprises 7 members, four of which have been previously implicated in the synthesis of di- or tri-acylglycerol. The remaining 3 members comprise an X-linked locus and have not been characterized. We describe here the expression of DGAT2 and the 3 X-linked genes in Saccharomyces cerevisiae strains virtually devoid of neutral lipids. All 4 gene products mediate the synthesis of triacylglycerol; however, two of the X-linked genes act as acyl-CoA wax alcohol acyltransferases (AWAT 1 and 2) that predominantly esterify long chain (wax) alcohols with acyl-CoA derived fatty acids to produce wax esters. AWAT1 and AWAT2 have very distinct substrate preferences in terms of alcohol chain length and fatty acyl saturation. The enzymes are expressed in many human tissues but predominate in skin. In situ hybridizations demonstrate a differentiation specific expression pattern within the human sebaceous gland for the two AWAT genes, consistent with a significant role in the composition of sebum.


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