モノアシルグリセロールリパーゼ
WordNet
- an enzyme secreted in the digestive tract that catalyzes the breakdown of fats into individual fatty acids that can be absorbed into the bloodstream
PrepTutorEJDIC
- リパーゼ(脂肪分解酵素)
Wikipedia preview
出典(authority):フリー百科事典『ウィキペディア(Wikipedia)』「2014/09/02 17:49:01」(JST)
[Wiki en表示]
monoglyceride lipase |
Identifiers |
Symbol |
MGLL |
Entrez |
11343 |
HUGO |
17038 |
OMIM |
609699 |
RefSeq |
NM_007283 |
UniProt |
Q99685 |
Other data |
Locus |
Chr. 3 p13-q13.33 |
Monoacylglycerol lipase, also known as MAG lipase, MAGL, MGL or MGLL is a protein that, in humans, is encoded by the MGLL gene.[1][2][3] MAGL is a 33-kDa, membrane-associated member of the serine hydrolase superfamily and contains the classical GXSXG consensus sequence common to most serine hydrolases. The catalytic triad has been identified as Ser122, His269, and Asp239.[2][4]
Contents
- 1 Function
- 2 Inhibitors and assay
- 3 Reaction
- 4 References
- 5 External links
Function
Monoacylglycerol lipase functions together with hormone-sensitive lipase (LIPE) to hydrolyze intracellular triglyceride stores in adipocytes and other cells to fatty acids and glycerol. MGLL may also complement lipoprotein lipase (LPL) in completing hydrolysis of monoglycerides resulting from degradation of lipoprotein triglycerides.[5]
Monoacylglycerol lipase is a key enzyme in the hydrolysis of the endocannabinoid 2-arachidonoylglycerol.[6][7] It converts monoacylglycerols to the free fatty acid and glycerol. The contribution of MAGL to total brain 2-AG hydrolysis activity has been estimated to be ~85%,[8] and this in vitro estimate has been confirmed in vivo by the selective MAGL inhibitor JZL184.[9]
Inhibitors and assay
The enzyme was reported to be inhibited by URB754; however this inhibitor has subsequently been shown to be inactive and its reported activity due to contamination.[10] While the compound N-arachidonoyl maleimide (NAM) inhibits MAGL,[11] NAM is not selective due to its chemically reactive maleimide functional group, which can also react with other thiol-containing small molecules and proteins (e.g., glutathione).
JZL184 is the first efficacious and selective inhibitor of MAGL that can elevate brain 2-AG levels in vivo.[9] JZL184 has >300-fold selectivity for MAGL over other brain serine hydrolases, including FAAH.
MAGL activity is commonly detected by measuring free fatty acid release from a monoacylglycerol substrate using a liquid chromatography mass spectrometry system or the radiolabelled substrate 2-oleoyl-[3H]-glycerol.
Reaction
Reaction catalyzed by MGLL, in which a free fatty acid (FFA) is released from a monoacylglycerol (MAG).
References
- ^ Wall EM, Cao J, Chen N, Buller RM, Upton C (December 1997). "A novel poxvirus gene and its human homolog are similar to an E. coli lysophospholipase". Virus Res. 52 (2): 157–67. doi:10.1016/S0168-1702(97)00122-6. PMID 9495531.
- ^ a b Karlsson M, Contreras JA, Hellman U, Tornqvist H, Holm C (October 1997). "cDNA cloning, tissue distribution, and identification of the catalytic triad of monoglyceride lipase. Evolutionary relationship to esterases, lysophospholipases, and haloperoxidases". J. Biol. Chem. 272 (43): 27218–23. doi:10.1074/jbc.272.43.27218. PMID 9341166.
- ^ "Entrez Gene: monoglyceride lipase".
- ^ Tornqvist H, Belfrage P (February 1976). "Purification and some properties of a monoacylglycerol-hydrolyzing enzyme of rat adipose tissue". J. Biol. Chem. 251 (3): 813–9. PMID 1249056.
- ^ Karlsson M, Reue K, Xia YR, Lusis AJ, Langin D, Tornqvist H, Holm C (July 2001). "Exon-intron organization and chromosomal localization of the mouse monoglyceride lipase gene". Gene 272 (1–2): 11–8. doi:10.1016/S0378-1119(01)00559-5. PMID 11470505.
- ^ Dinh TP, Carpenter D, Leslie FM, Freund TF, Katona I, Sensi SL, Kathuria S, Piomelli D (August 2002). "Brain monoglyceride lipase participating in endocannabinoid inactivation". Proc. Natl. Acad. Sci. U.S.A. 99 (16): 10819–24. doi:10.1073/pnas.152334899. PMC 125056. PMID 12136125.
- ^ Makara JK, Mor M, Fegley D, Szabó SI, Kathuria S, Astarita G, Duranti A, Tontini A, Tarzia G, Rivara S, Freund TF, Piomelli D (September 2005). "Selective inhibition of 2-AG hydrolysis enhances endocannabinoid signaling in hippocampus". Nat. Neurosci. 8 (9): 1139–41. doi:10.1038/nn1521. PMID 16116451.
- ^ Blankman JL, Simon GM, Cravatt BF (December 2007). "A Comprehensive Profile of Brain Enzymes that Hydrolyze the Endocannabinoid 2-Arachidonoylglycerol". Chem. Biol. 14 (12): 1347–56. doi:10.1016/j.chembiol.2007.11.006. PMC 2692834. PMID 18096503.
- ^ a b Long JZ, Li W, Booker L, Burston JJ, Kinsey SG, Schlosburg JE, Pavón FJ, Serrano AM, Selley DE, Parsons LH, Lichtman AH, Cravatt BF (November 2008). "Selective blockade of 2-arachidonoylglycerol hydrolysis produces cannabinoid behavioral effects". Nat. Chem. Biol. 5 (1): 37–44. doi:10.1038/nchembio.129. PMC 2605181. PMID 19029917.
- ^ Saario SM, Palomäki V, Lehtonen M, Nevalainen T, Järvinen T, Laitinen JT (August 2006). "URB754 has no effect on the hydrolysis or signaling capacity of 2-AG in the rat brain". Chem. Biol. 13 (8): 811–4. doi:10.1016/j.chembiol.2006.07.008. PMID 16931330.
- ^ Burston JJ, Sim-Selley LJ, Harloe JP, Mahadevan A, Razdan RK, Selley DE, Wiley JL (November 2008). "N-Arachidonyl Maleimide Potentiates the Pharmacological and Biochemical Effects of the Endocannabinoid 2-Arachidonylglycerol through Inhibition of Monoacylglycerol Lipase". J. Pharmacol. Exp. Ther. 327 (2): 546–53. doi:10.1124/jpet.108.141382. PMC 2605346. PMID 18682568.
External links
- Monoacylglycerol lipases at the US National Library of Medicine Medical Subject Headings (MeSH)
- EC 3.1.1.23
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
Hydrolase: esterases (EC 3.1)
|
|
3.1.1: Carboxylic ester hydrolases |
- Cholinesterase
- Acetylcholinesterase
- Butyrylcholinesterase
- Pectinesterase
- 6-phosphogluconolactonase
- PAF acetylhydrolase
- Lipase
- Bile salt-dependent
- Gastric/Lingual
- Pancreatic
- Lysosomal
- Hormone-sensitive
- Endothelial
- Hepatic
- Lipoprotein
- Monoacylglycerol
- Diacylglycerol
|
|
3.1.2: Thioesterase |
- Palmitoyl protein thioesterase
- Ubiquitin carboxy-terminal hydrolase L1
|
|
3.1.3: Phosphatase |
- Alkaline phosphatase
- Acid phosphatase (Prostatic)/Tartrate-resistant acid phosphatase/Purple acid phosphatases
- Nucleotidase
- Glucose 6-phosphatase
- Fructose 1,6-bisphosphatase
- Phosphoprotein phosphatase
- OCRL
- Pyruvate dehydrogenase phosphatase
- Fructose 6-P,2-kinase:fructose 2,6-bisphosphatase
- PTEN
- Phytase
- Inositol-phosphate phosphatase
- Phosphoprotein phosphatase: Protein tyrosine phosphatase
- Protein serine/threonine phosphatase
- Dual-specificity phosphatase
|
|
3.1.4: Phosphodiesterase |
- Autotaxin
- Phospholipase
- Sphingomyelin phosphodiesterase
- PDE1
- PDE2
- PDE3
- PDE4A/PDE4B
- PDE5
- Lecithinase (Clostridium perfringens alpha toxin)
- Cyclic nucleotide phosphodiesterase
|
|
3.1.6: Sulfatase |
- arylsulfatase
- Arylsulfatase A
- Arylsulfatase B
- Arylsulfatase E
- Steroid sulfatase
- Galactosamine-6 sulfatase
- Iduronate-2-sulfatase
- N-acetylglucosamine-6-sulfatase
|
|
Nuclease (includes
deoxyribonuclease and
ribonuclease) |
3.1.11-16: Exonuclease |
Exodeoxyribonuclease |
|
|
Exoribonuclease |
|
|
|
3.1.21-31: Endonuclease |
Endodeoxyribonuclease |
- Deoxyribonuclease I
- Deoxyribonuclease II
- Deoxyribonuclease IV
- Restriction enzyme
- UvrABC endonuclease
|
|
Endoribonuclease |
- RNase III
- RNase H
- RNase P
- RNase A
- RNase T1
- RNA-induced silencing complex
|
|
either deoxy- or ribo- |
- Aspergillus nuclease S1
- Micrococcal nuclease
|
|
|
|
- B
- enzm
- 1.1
- 2
- 3
- 4
- 5
- 6
- 7
- 8
- 10
- 11
- 13
- 14
- 15-18
- 2.1
- 3.1
- 4.1
- 5.1
- 6.1-3
|
|
|
|
Cannabinoidergics
|
|
Receptor |
CB1
|
- Agonists: 2-AG
- 2-AGE (noladin ether)
- 11-Hydroxy-THC
- AB-CHMINACA
- AM-1220
- AM-1235
- AM-2201
- AM-2232
- Arvanil
- AZ-11713908
- Cannabinol
- CP 47,497
- CP 55,940
- Dimethylheptylpyran
- Epicatechin gallate
- Epigallocatechin gallate
- Gallocatechol (gallocatechin)
- HU-210
- JWH-007
- JWH-018
- JWH-073
- Kavain
- L-759,633
- Levonantradol
- Menabitan
- Nabilone
- Nabitan
- NADA
- O-1812
- Oleamide
- Serinolamide A
- THC (dronabinol)
- WIN 55,212-2
- Yangonin
- Note: The above list contains only some known CB1R agonists, as too many exist to list here completely. Refer here instead for more.
- Antagonists: AM-251
- AM-6545
- Cannabidiol
- Cannabigerol
- Drinabant
- Hemopressin
- Ibipinabant
- LY-320,135
- MK-9470
- NADA
- NESS-0327
- O-2050
- Otenabant
- PF-514273
- PipISB
- Rimonabant
- Rosonabant
- Surinabant
- Taranabant
- THCV
- TM-38837
- VCHSR
- Virodhamine
|
|
CB2
|
- Agonists: 2-AG
- 2-AGE (noladin ether)
- A-796,260
- A-834,735
- A-836,339
- AM-1221
- AM-1235
- AM-1241
- AM-2232
- Anandamide
- AZ-11713908
- Cannabinol
- Caryophyllene
- CBS-0550
- CP-55,940
- GW-405,833 (L-768,242)
- GW-842,166X
- HU-308
- JTE 7-31
- JWH-007
- JWH-015
- JWH-018
- JWH-73
- JWH-133
- L-759,633
- L-759,656
- MDA-19
- Nabitan
- PF-03550096
- S-444,823
- SER-601
- Serinolamide A
- UR-144
- Tedalinab
- THC (dronabinol)
- THCV
- Virodhamine
- Antagonists: AM-630
- BML-190
- Cannabidiol
- JTE-907
- SR-144,528
- WIN 54,461
- WIN 56,098
|
|
GPR55
|
- Agonists: 2-AGE (noladin ether)
- Abnormal cannabidiol
- AM-251
- CP 55,940
- GSK-494581A
- Lysophosphatidylinositol
- ML-184
- ML-185
- ML-186
- O-1602
- Oleoylethanolamide
- Palmitoylethanolamide
- THC (dronabinol)
- Antagonists: Cannabidiol
- CID-16020046
- ML-191
- ML-192
- ML-193
- O-1918
- PSB-SB-487
- PSB-SB-1202
- PSB-SB-1203
|
|
GPR18
|
- Agonists: Abnormal cannabidiol
- ACPA
- AM251
- Anandamide
- Cannabidiol
- NADGly
- THC (dronabinol)
- O-1602
|
|
GPR119
|
- Agonists: 2-Oleoylglycerol
- Anandamide
- APD668
- AR-231,453
- AS-1269574
- MBX-2982
- N-Oleoyldopamine
- Oleoylethanolamide
- Olvanil
- PSN-375,963
- PSN-632,408
|
|
|
Transporter
(inhibitors) |
- 5'-DMH-CBD
- AM-404
- AM-1172
- Arachidonoyl serotonin
- Arvanil
- Cannabidiol
- LY-2183240
- O-2093
- OMDM-2
- Paracetamol (acetaminophen)
- SB-FI-26
- UCM-707
- URB-597
- VDM-11
|
|
Enzyme
(inhibitors) |
FAAH
|
- 4-Nonylphenylboronic acid
- AACOCF3
- AM-1172
- AM-404
- Arachidonyl serotonin
- Biochanin A
- Genistein
- IDFP
- JNJ-1661010
- JZL-195
- Kaempferol
- LY-2183240
- MAFP
- Palmitoylisopropylamide
- Paracetamol (acetaminophen)
- PF-3845
- PF-04457845
- PF-750
- SA-47
- SA-57
- TC-F 2
- URB-597
|
|
MAGL
|
- IDFP
- JZL-184
- JZL-195
- URB-602
|
|
ABHD6
|
|
|
|
UpToDate Contents
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English Journal
- Alterations in the endocannabinoid system in the rat valproic acid model of autism.
- Kerr DM, Downey L, Conboy M, Finn DP, Roche M.SourcePhysiology, School of Medicine, National University of Ireland Galway, Ireland; Pharmacology and Therapeutics, School of Medicine, National University of Ireland Galway, Ireland; NCBES Neuroscience Centre and Centre for Pain Research, National University of Ireland Galway, Ireland.
- Behavioural brain research.Behav Brain Res.2013 Jul 15;249:124-32. doi: 10.1016/j.bbr.2013.04.043. Epub 2013 May 1.
- The endocannabinoid system plays a crucial role in regulating emotionality and social behaviour, however it is unknown whether this system plays a role in symptoms associated with autism spectrum disorders. The current study evaluated if alterations in the endocannabinoid system accompany behavioura
- PMID 23643692
- Peripheral endocannabinoid system dysregulation in first-episode psychosis.
- Bioque M, García-Bueno B, Mac-Dowell KS, Meseguer A, Saiz PA, Parellada M, Gonzalez-Pinto A, Rodriguez-Jimenez R, Lobo A, Leza JC, Bernardo M.SourceSchizophrenia Clinic Unit. Neuroscience Institute, Hospital Clínic de Barcelona, Barcelona, Spain.
- Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology.Neuropsychopharmacology.2013 Jul 4. doi: 10.1038/npp.2013.165. [Epub ahead of print]
- Several hypotheses involving alterations of the immune system have been proposed among etiological explanations for psychotic disorders. The endocannabinoid system (ECS) plays a homeostatic role as an endogenous neuroprotective and anti-inflammatory system. Alterations of this system have been assoc
- PMID 23822951
Japanese Journal
- Molecular and Morphological Configuration for 2-Arachidonoylglycerol-Mediated Retrograde Signaling at Mossy Cell-Granule Cell Synapses in the Dentate Gyrus
- Uchigashima Motokazu,Yamazaki Maya,Yamasaki Miwako,Tanimura Asami,Sakimura Kenji,Kano Masanobu,Watanabe Masahiko
- The Journal of Neuroscience 31(21), 7700-7714, 2011
- … First, we showed by electrophysiology that 2-AG produced by diacylglycerol lipase α(DGLα) mediated both depolarization-induced suppression of excitation and its enhancement by group I metabotropic glutamate receptor activation at MC-GC synapses, as they were abolished in DGLα-knock-out mice. … On the other hand, the major 2-AG-degrading enzyme, monoacylglycerol lipase (MGL), was absent at MC-GC synapses but was expressed in astrocytes and some inhibitory terminals. …
- NAID 120003521155
- High extracellular Ca2+ stimulates Ca2+-activated Cl- currents in frog parathyroid cells through the mediation of arachidonic acid cascade.
- Okada Yukio,Imendra Kotapola G,Miyazaki Toshihiro,Hotokezaka Hitoshi,Fujiyama Rie,Toda Kazuo
- PLoS One 6(4), 19158, 2011
- … All blockers for phospholipase C, diacylglycerol (DAG) lipase, monoacylglycerol (MAG) lipase and lipoxygenase inhibited extracellular Ca(2+)-induced current. … These results indicate that high extracellular Ca(2+) raises intracellular Ca(2+) concentration through the DAG lipase/lipoxygenase pathway, resulting in the activation of Cl(-) conductance. …
- NAID 120003238497
- 2Aa03 組換えモノグリセリドリパーゼの精製及び生化学的特性解析(プロセス工学,一般講演)
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モノアシルグリセロール
- 関
- monoglyceride