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

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 a...

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Bibliographic Details
Published in:The Journal of biological chemistry 2005-04, Vol.280 (15), p.14755-14764
Main Authors: Turkish, Aaron R, Henneberry, Annette L, Cromley, Debra, Padamsee, Mahajabeen, Oelkers, Peter, Bazzi, Hisham, Christiano, Angela M, Billheimer, Jeffrey T, Sturley, Stephen L
Format: Article
Language:English
Subjects:
Acyltransferases - biosynthesis
Acyltransferases - chemistry
Acyltransferases - genetics
Acyltransferases - metabolism
Amino Acid Sequence
Blotting, Northern
Chromosomes, Human, X
Databases as Topic
Diacylglycerol O-Acyltransferase
Evolution, Molecular
Humans
In Situ Hybridization
Lipid Metabolism
Lipids - chemistry
Models, Genetic
Molecular Sequence Data
Phylogeny
Plasmids - metabolism
Saccharomyces cerevisiae
Saccharomyces cerevisiae - metabolism
Sequence Homology, Amino Acid
Substrate Specificity
Tissue Distribution
Triglycerides - chemistry
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Summary: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 seven members, four of which have been previously implicated in the synthesis of di- or triacylglycerol. The remaining 3 members comprise an X-linked locus and have not been characterized. We describe here the expression of DGAT2 and the three X-linked genes in Saccharomyces cerevisiae strains virtually devoid of neutral lipids. All four 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.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M500025200