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monoglyceride lipase
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| Identifiers | |
| Symbol | MGLL |
| Entrez | 11343 |
| HUGO | 17038 |
| OMIM | 609699 |
| RefSeq | NM_007283 |
| UniProt | Q99685 |
| Other data | |
| EC number | 3.1.1.23 |
| Locus | Chr. 3 p13-q13.33 |
Monoacylglycerol lipase, also known as MAG lipase, MAGL, MGL or MGLL is a protein which in humans is encoded by the MGLL gene.123
Contents |
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.4
Monoacylglycerol lipase is a key enzyme in the hydrolysis of the endocannabinoid 2-arachidonoylglycerol.56 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%,7 and this in vitro estimate has been confirmed in vivo by the selective MAGL inhibitor JZL184.8
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.9 While the compound N-arachidonoyl maleimide (NAM) inhibits MAGL,10 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.8 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
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:. PMID 9495531.
- ^ 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:. PMID 9341166.
- ^ "Entrez Gene: monoglyceride lipase".
- ^ 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:. 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:. 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:. 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:. 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.. doi:. 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:. 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:. PMID 18682568.
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- This page was last modified on 28 November 2008, at 07:54.
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