Monoacylglycerol lipase (EC 3.1.1.23; systematic nameglycerol-ester acylhydrolase, also known asMAG lipase,acylglycerol lipase,MAGL, MGL orMGLL) is anenzyme that, in humans, is encoded by theMGLLgene.[1][2][3] MAGL is a 33-kDa, membrane-associated member of theserine hydrolase superfamily and contains the classical GXSXG consensus sequence common to most serine hydrolases. Thecatalytic triad has been identified as Ser122, His269, and Asp239.[2][4]
hydrolyses glycerol monoesters of long-chain fatty acids
It functions together withhormone-sensitive lipase (LIPE) to hydrolyze intracellular triglyceride stores in adipocytes and other cells to fatty acids and glycerol. MGLL may also complementlipoprotein lipase (LPL) in completing hydrolysis of monoglycerides resulting from degradation of lipoprotein triglycerides.[5]
Monoacylglycerol lipase is a key enzyme in the hydrolysis of theendocannabinoid2-arachidonoylglycerol (2-AG).[6][7] It convertsmonoacylglycerols to the freefatty acid andglycerol. The contribution of MAGL to total brain 2-AG hydrolysis activity has been estimated to be ~85% (ABHD6 andABHD12 are responsible for ~4% and ~9%, respectively, of the remainder),[8][9] and thisin vitro estimate has been confirmedin vivo by the selective MAGL inhibitorJZL184.[10] Chronic inactivation of MAGL results in massive (>10-fold) elevations of brain 2-AG in mice, along with marked compensatorydownregulation 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 anE. 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.
