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 ==