fig1

Figure 1. Pathways of 2-AG synthesis and metabolism. 2-AG is largely synthesized from DAG, which is formed from membrane phospholipids through PLC, by DAGLα/β. 2-AG in the brain is primarily hydrolyzed by MAGL to glycerol and AA. It is also hydrolyzed by ABHD6/12 to AA and metabolized oxidatively by COX-2 to form a new type of prostaglandin glycerol esters when expression and activity of COX-2 are excessively elevated during inflammation. AA is a precursor of prostaglandins through the enzymes COX-1/2 and HPETE through the enzyme arachidonate 5-LOX to form leukotrienes (LTA4 to E4). 2-AG: 2-arachidonoylglycerol; PLC: phospholipase C; DAG: diacylglycerol; DAGLα/β: diacylglycerol lipase α and β; PLA2: phospholipase A2; AA: arachidonic acid; COX-2: cyclooxygenase-2; MAGL: monoacylglycerol lipase; ABHD6/12: α/β hydrolase domaincontaining protein 6 and 12; HPETE: hydroperoxyeicosatetraenoic acid; LOX: lipoxygenase.