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 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.
Turkish
Aaron R
AR
Department of Pediatrics, Columbia University Medical Center, New York, New York 10032, USA.
Henneberry
Annette L
AL
Cromley
Debra
D
Padamsee
Mahajabeen
M
Oelkers
Peter
P
Bazzi
Hisham
H
Christiano
Angela M
AM
Billheimer
Jeffrey T
JT
Sturley
Stephen L
SL
D000217:Acyltransferases / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D000595:Amino Acid Sequence; D015152:Blotting, Northern; D041321:Chromosomes, Human, X; D019992:Databases as Topic; D051048:Diacylglycerol O-Acyltransferase; D019143:Evolution, Molecular; D006801:Humans; D017403:In Situ Hybridization; D050356:Lipid Metabolism; D008055:Lipids / Q000737:chemistry; D008957:Models, Genetic; D008969:Molecular Sequence Data; D010802:Phylogeny; D010957:Plasmids / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity; D014018:Tissue Distribution; D014280:Triglycerides / Q000737:chemistry
D008055:Lipids; D014280:Triglycerides; D000217:Acyltransferases; C500796:AWAT2 protein, human; C494881:DGAT1 protein, human; C494885:DGAT2 protein, human; D051048:Diacylglycerol O-Acyltransferase; C500795:AWAT1 protein, human; C079165:long-chain-alcohol O-fatty-acyltransferase