Monoacylglycerol lipase
| monoglyceride lipase | |
|---|---|
| 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 that, in humans, is encoded by the MGLL gene. 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.
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.
Monoacylglycerol lipase is a key enzyme in the hydrolysis of the endocannabinoid 2-arachidonoylglycerol (2-AG). 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% (ABHD6 and ABHD12 are responsible for ~4% and ~9%, respectively, of the remainder), and this in vitro estimate has been confirmed in vivo by the selective MAGL inhibitor JZL184. Chronic inactivation of MAGL results in massive (>10-fold) elevations of brain 2-AG in mice, along with marked compensatory downregulation of CB1 receptors in selective brain areas.
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. While the compound N-arachidonoyl maleimide (NAM) inhibits MAGL, 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).
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