- 同
- DGAT
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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/02/12 17:14:55」(JST)
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| diacylglycerol O-acyltransferase |
| Identifiers |
| EC number |
2.3.1.20 |
| CAS number |
9029-98-5 |
| Databases |
| IntEnz |
IntEnz view |
| BRENDA |
BRENDA entry |
| ExPASy |
NiceZyme view |
| KEGG |
KEGG entry |
| MetaCyc |
metabolic pathway |
| PRIAM |
profile |
| PDB structures |
RCSB PDB PDBe PDBsum |
| Gene Ontology |
AmiGO / EGO |
| Search |
| PMC |
articles |
| PubMed |
articles |
| NCBI |
proteins |
|
| diacylglycerol O-acyltransferase homolog 1 (mouse) |
| Identifiers |
| Symbol |
DGAT1 |
| Entrez |
8694 |
| HUGO |
2843 |
| OMIM |
604900 |
| RefSeq |
NM_012079 |
| UniProt |
O75907 |
| Other data |
| Locus |
Chr. 8 q24.3 |
| diacylglycerol O-acyltransferase homolog 2 (mouse) |
| Identifiers |
| Symbol |
DGAT2 |
| Entrez |
84649 |
| HUGO |
16940 |
| OMIM |
606983 |
| RefSeq |
NM_032564 |
| UniProt |
Q96PD7 |
| Other data |
| Locus |
Chr. 11 q13.3 |
Diglyceride acyltransferase (or O-acyltransferase), DGAT, catalyzes the formation of triglycerides from diacylglycerol and Acyl-CoA. The reaction catalyzed by DGAT is considered the terminal and only committed step in triglyceride synthesis and to be essential for the formation of adipose tissue.[1] The protein is homologous to other membrane-bound O-acyltransferases.
Contents
- 1 Isoforms
- 2 Knockout studies
- 3 Therapeutic application
- 4 References
Isoforms
There are two isozymes of DGAT encoded by the genes DGAT1[2] and DGAT2.[3] Although both isozymes catalyze similar reactions, they have no sequence homology to each other.
Knockout studies
Mice with genetic disruption of the dgat1 or dgat2 genes have been made by the Farese laboratory at UCSF. Surprisingly, DGAT1−/− mice[4] 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. In contrast, DGAT2−/− mice[5] have reduced triglyceride levels but are lipopenic, suffer from skin barrier abnormalities (including the inability to retain moisture), and die shortly after birth.
Therapeutic application
DGAT-1 inhibitors have potential for the treatment of obesity[6][7] and a number of DGAT-1 inhibitors are in clinical trials for this indication.[8]
References
- ^ Cases S, Smith SJ, Zheng YW, Myers HM, Lear SR, Sande E, Novak S, Collins C, Welch CB, Lusis AJ, Erickson SK, Farese RV (1998). "Identification of a gene encoding an acyl CoA:diacylglycerol acyltransferase, a key enzyme in triacylglycerol synthesis". Proc. Natl. Acad. Sci. U.S.A. 95 (22): 13018–23. doi:10.1073/pnas.95.22.13018. PMC 23692. PMID 9789033.
- ^ Oelkers P, Behari A, Cromley D, Billheimer JT, Sturley SL (October 1998). "Characterization of two human genes encoding acyl coenzyme A:cholesterol acyltransferase-related enzymes". J. Biol. Chem. 273 (41): 26765–71. doi:10.1074/jbc.273.41.26765. PMID 9756920.
- ^ Cases S, Stone SJ, Zhou P, Yen E, Tow B, Lardizabal KD, Voelker T, Farese RV (October 2001). "Cloning of DGAT2, a second mammalian diacylglycerol acyltransferase, and related family members". J. Biol. Chem. 276 (42): 38870–6. doi:10.1074/jbc.M106219200. PMID 11481335.
- ^ Smith SJ, Cases S, Jensen DR, Chen HC, Sande E, Tow B, Sanan DA, Raber J, Eckel RH, Farese RV (May 2000). "Obesity resistance and multiple mechanisms of triglyceride synthesis in mice lacking Dgat". Nat. Genet. 25 (1): 87–90. doi:10.1038/75651. PMID 10802663.
- ^ Stone SJ, Myers HM, Watkins SM, Brown BE, Feingold KR, Elias PM, Farese RV (March 2004). "Lipopenia and skin barrier abnormalities in DGAT2-deficient mice". J. Biol. Chem. 279 (12): 11767–76. doi:10.1074/jbc.M311000200. PMID 14668353.
- ^ Chen HC, Farese RV (March 2005). "Inhibition of triglyceride synthesis as a treatment strategy for obesity: lessons from DGAT1-deficient mice". Arterioscler. Thromb. Vasc. Biol. 25 (3): 482–6. doi:10.1161/01.ATV.0000151874.81059.ad. PMID 15569818.
- ^ Cheng D, Iqbal J, Devenny J, Chu CH, Chen L, Dong J, Seethala R, Keim WJ, Azzara AV, Lawrence RM, Pelleymounter MA, Hussain MM (October 2008). "Acylation of acylglycerols by acyl coenzyme A:diacylglycerol acyltransferase 1 (DGAT1). Functional importance of DGAT1 in the intestinal fat absorption". J. Biol. Chem. 283 (44): 29802–11. doi:10.1074/jbc.M800494200. PMC 2662058. PMID 18768481.
- ^ "Pfizer, Bristol finalize deal on metabolic drugs". Reuters. 2007-08-27. Retrieved 2007-08-27.
|
Transferases: acyltransferases (EC 2.3)
|
|
| 2.3.1: other than amino-acyl groups |
- acetyltransferases: Acetyl-Coenzyme A acetyltransferase
- N-Acetylglutamate synthase
- Choline acetyltransferase
- Dihydrolipoyl transacetylase
- Acetyl-CoA C-acyltransferase
- Beta-galactoside transacetylase
- Chloramphenicol acetyltransferase
- N-acetyltransferase
- Serotonin N-acetyl transferase
- HGSNAT
- ARD1A
- Histone acetyltransferase
- palmitoyltransferases: Carnitine O-palmitoyltransferase
- Serine C-palmitoyltransferase
- other: Acyltransferase like 2
- Aminolevulinic acid synthase
- Beta-ketoacyl-ACP synthase
- Glyceronephosphate O-acyltransferase
- Lecithin—cholesterol acyltransferase
- Glycerol-3-phosphate O-acyltransferase
- 1-acylglycerol-3-phosphate O-acyltransferase
- 2-acylglycerol-3-phosphate O-acyltransferase
- ABHD5
|
|
| 2.3.2: Aminoacyltransferases |
- Gamma-glutamyl transpeptidase
- Peptidyl transferase
- Transglutaminase
- Tissue transglutaminase
- Keratinocyte transglutaminase
- Factor XIII
|
|
| 2.3.3: converted into alkyl on transfer |
- Citrate synthase
- ATP citrate lyase
- HMG-CoA synthase
- Malate synthase
|
|
|
Proteins: enzymes
|
|
| Activity |
- Active site
- Binding site
- Catalytic triad
- Oxyanion hole
- Enzyme promiscuity
- Catalytically perfect enzyme
- Coenzyme
- Cofactor
- Enzyme catalysis
- Enzyme kinetics
- Lineweaver–Burk plot
- Michaelis–Menten kinetics
|
|
| Regulation |
- Allosteric regulation
- Cooperativity
- Enzyme inhibitor
|
|
| Classification |
- EC number
- Enzyme superfamily
- Enzyme family
- List of enzymes
|
|
| Types |
- EC1 Oxidoreductases(list)
- EC2 Transferases(list)
- EC3 Hydrolases(list)
- EC4 Lyases(list)
- EC5 Isomerases(list)
- EC6 Ligases(list)
|
|
UpToDate Contents
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English Journal
- Lipid body biogenesis and the role of microtubules in lipid synthesis in Ornithogalum umbellatum lipotubuloids.
- Kwiatkowska M, Popłońska K, Wojtczak A, Stępiński D, Polit JT.SourceDepartment of Cytophysiology, University of d, Pomorska 141143, 90236 d, Poland.
- Cell biology international.Cell Biol Int.2012 May 1;36(5):455-62.
- Lipid bodies present in lipotubuloids of Ornithogalum umbellatum ovary epidermis take the form of a lens between leaflets of ER (endoplasmic reticulum) membrane filled with a highly osmiophilic substance. The two enzymes, DGAT1 [DAG (diacylglycerol) acyltransferase 1] and DGAT2 (DAG acyltransferase
- PMID 22295975
- Protective effects of arachidonic acid against palmitic acid-mediated lipotoxicity in HIT-T15 cells.
- Cho YS, Kim CH, Kim KY, Cheon HG.SourceDivision of Drug Discovery, Korea Research Institute of Chemical Technology, P.O. Box 107, Yuseong-gu, Daejeon, 305-600, Korea.
- Molecular and cellular biochemistry.Mol Cell Biochem.2012 May;364(1-2):19-28. Epub 2011 Dec 28.
- Saturated fatty acids have been considered major contributing factors in type 2 diabetes, whereas unsaturated fatty acids have beneficial effects for preventing the development of diabetes. However, the effects of polyunsaturated fatty acids in pancreatic β cells have not been reported. Here, we ex
- PMID 22203421
Japanese Journal
- Inhibition of Ubiquitin Ligase F-box and WD Repeat Domain-containing 7α (Fbw7α) Causes Hepatosteatosis through Krüppel-like Factor 5 (KLF5)/Peroxisome Proliferator-activated Receptor γ2 (PPARγ2) Pathway but Not SREBP-1c Protein in Mice
- Kumadaki Shin,Karasawa Tadayoshi,Matsuzaka Takashi,Ema Masatsugu,Nakagawa Yoshimi,Nakakuki Masanori,Saito Ryo,Yahagi Naoya,Iwasaki Hitoshi,Sone Hirohito,Takekoshi Kazuhiro,Yatoh Shigeru,Kobayashi Kazuto,Takahashi Akimitsu,Suzuki Hiroaki,Takahashi Satoru,Yamada Nobuhiro,Shimano Hitoshi,松坂 賢,依馬 正次,中川 嘉,矢作 直也,岩﨑 仁,曽根 博仁,竹越 一博,矢藤 繁,小林 和人,高橋 昭光,鈴木 浩明,高橋 智,山田 信博,島野 仁
- The journal of biological chemistry 286(47), 40835-40846, 2011-11
- … These genes included fatty acid transporter Cd36, diacylglycerol acyltransferase 1 (Dgat1), and fat-specific protein 27 (Cidec). …
- NAID 120003674222
- 3Ea12 脂質蓄積性を高めた出芽酵母によるステアリドン酸の生産 : 活性型ジアシルグリセロールアシルトランスフェラーゼの導入(タンパク質工学/脂質工学,一般講演)
Related Links
- forum Join the Word of the Day Mailing List For webmasters TheFreeDictionary Google Bing? Word / Article Starts with Ends with Text ... di·ac·yl·glyc·er·ol ac·yl·trans·fer·ase an enzyme, in fat biosynthesis, that catalyzes the ...
- 1. Lipids. 2006 Dec;41(12):1073-88. Diacylglycerol acyltransferase: a key mediator of plant triacylglycerol synthesis. Lung SC, Weselake RJ. Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton ...
★リンクテーブル★
[★]
- 英
- diacylglycerol acyltransferase
- 関
- ジアシルグリセロール-O-アシルトランスフェラーゼ、ジアシルグリセロールアシル転移酵素、ジアシルグリセロールアシル基転移酵素
[★]
- 英
- diacylglycerol acyltransferase
- 関
- ジアシルグリセロールアシルトランスフェラーゼ、ジアシルグリセロールアシル基転移酵素
[★]
- 英
- diacylglycerol acyltransferase
- 関
- ジアシルグリセロールアシルトランスフェラーゼ、ジアシルグリセロールアシル転移酵素
[★]
アシルトランスフェラーゼ、アシル転移酵素、アシル基転移酵素
- 関
- transacylase
[★]
ジアシルグリセロール。DG DAG