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 MGLLgene.[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]
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.[5]
Monoacylglycerol lipase is a key enzyme in the hydrolysis of the endocannabinoid2-arachidonoylglycerol (2-AG).[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% (ABHD6 and ABHD12 are responsible for ~4% and ~9%, respectively, of the remainder),[8][9] and this in vitro estimate has been confirmed in vivo by the selective MAGL inhibitor JZL184.[10] 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.[11]
^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 Research. 52 (2): 157–67. doi:10.1016/S0168-1702(97)00122-6. PMID9495531.
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. PMID6776896.
