• Source: Monoacylglycerol lipase

Monoacylglycerol lipase (EC 3.1.1.23; systematic name glycerol-ester acylhydrolase, also known as MAG lipase, acylglycerol lipase, MAGL, MGL or MGLL) is an enzyme 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.




Function


Monoacylglycerol lipase catalyzes a reaction that uses water molecules to break the glycerol monoesters of long-chain fatty acids:

hydrolyses glycerol monoesters of long-chain fatty acids
It 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.




Inhibitors


MAGL enzyme inhibitors, for instance URB-602, URB-754, and JZL-184, produce cannabinoid-like behavioral effects in mice.
Further examples include:

KML-29
JZL-195 – dual MAGL and FAAH inhibitor
JW-642
As well as the following compounds which are under pharmaceutical development:

CC-97489 – dual MAGL and FAAH inhibitor
Elcubragistat (ABX-1431; Lu AG06466)
PF-06818883
RG-6182
Small molecule MGLLi




See also


Endocannabinoid enhancer
Endocannabinoid reuptake inhibitor
Triacylglycerol lipase
Fatty acid amide hydrolase




References



Mentlein R, Heiland S, Heymann E (1980). "Simultaneous purification and comparative characterization of six serine hydrolases from rat liver microsomes". Arch. Biochem. Biophys. 200 (2): 547–59. doi:10.1016/0003-9861(80)90386-0. PMID 6776896.
Pope JL, McPherson JC, Tidwell HC (1966). "A study of a monoglyceride-hydrolyzing enzyme of intestinal mucosa". J. Biol. Chem. 241 (10): 2306–10. doi:10.1016/S0021-9258(18)96621-4. PMID 5916497.




External links


Monoacylglycerol+lipases at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
EC 3.1.1.23
Monoglyceride lipase (MGLL) Human Protein Atlas
This article incorporates text from the United States National Library of Medicine, which is in the public domain.

Kata Kunci Pencarian:

• Endotelial lipase
• Monoacylglycerol lipase
• Lipoprotein lipase
• Lipolysis
• Hormone-sensitive lipase
• Serine hydrolase
• Endocannabinoid system
• Monoglyceride
• Triacylglycerol lipase
• Fatty-acid amide hydrolase 1
• 2-Oleoylglycerol