| diacylglycerol O-acyltransferase | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Identifiers | |||||||||
| EC no. | 2.3.1.20 | ||||||||
| CAS no. | 9029-98-5 | ||||||||
| Databases | |||||||||
| IntEnz | IntEnz view | ||||||||
| BRENDA | BRENDA entry | ||||||||
| ExPASy | NiceZyme view | ||||||||
| KEGG | KEGG entry | ||||||||
| MetaCyc | metabolic pathway | ||||||||
| PRIAM | profile | ||||||||
| PDB structures | RCSB PDBPDBePDBsum | ||||||||
| Gene Ontology | AmiGO /QuickGO | ||||||||
| |||||||||
| diacylglycerol O-acyltransferase 1 | |||||||
|---|---|---|---|---|---|---|---|
| Identifiers | |||||||
| Symbol | DGAT1 | ||||||
| NCBI gene | 8694 | ||||||
| HGNC | 2843 | ||||||
| OMIM | 604900 | ||||||
| RefSeq | NM_012079 | ||||||
| UniProt | O75907 | ||||||
| Other data | |||||||
| Locus | Chr. 8q24.3 | ||||||
| |||||||
Diglyceride acyltransferase (orO-acyltransferase),DGAT, catalyzes the formation oftriglycerides (triacylglycerols) fromdiacylglycerol andacyl-CoA.[1] The reaction catalyzed by DGAT is considered the terminal and onlycommitted step in the acyl-CoA-dependent triglyceride synthesis, universally important in animal, plants, and microorganisms. The conversion is essential for intestinal absorption (i.e. DGAT1) and adipose tissue formation (i.e. DGAT2) in mammalian.[2] DGAT1 are homologous to othermembrane-boundO-acyltransferases, but not all other DGATs.[1]
Two important DGATisozymes are encoded by the genesDGAT1[3] and DGAT2.[4] Although both isozymes catalyze similar reactions, they share no sequence homology, which is similar to other DGATs reported in various organisms.[1] The location of DGAT1 and DGAT2 in other organisms, as well as other DGATs have been reported in various literatures.[1]
DGAT1 is mainly located in absorptiveenterocyte cells that line the intestine and duodenum where it reassemblestriglycerides that were decomposed through lipolysis in the process of intestinal absorption. DGAT1 reconstitutes triglycerides in a committed step after which they are packaged together with cholesterol and proteins to formchylomicrons.
DGAT2 is mainly located in fat, liver and skin cells.
Mice with genetic disruption of theDGAT1 orDGAT2 genes have been made by the Farese laboratory atUCSF. Surprisingly, DGAT1−/− mice[5] are healthy and fertile and have no changes in triglyceride levels. These mice are also lean and resistant to diet-induced obesity, consequently generating interest in DGAT1 inhibitors for the treatment of obesity. However, these mice also fail tolactate, showing a complete lack of milk production due to their inability to produce milk lipid droplets.[5] In contrast, DGAT2−/− mice[6] have reduced triglyceride levels but are lipopenic, suffer from skin barrier abnormalities (including the inability to retain moisture), and die shortly after birth.
DGAT1 inhibitors have potential for the treatment ofobesity[7][8] and a number of DGAT-1 inhibitors are inclinical trials for this indication.[9]
DGAT is also important in lipid biotechnology in plants, microorganisms, and animals.[1]
