Overview of AEA and 2-AG production and metabolism. The endocannabinoids 2-AG and AEA are formed from arachidonic acid-containing phospholipids. 2-AG is formed from DAG by DGLα
and is metabolized either via COX-2 to form prostaglandin glyceryl esters or by ABHD6 or MAG-L to form arachidonic acid. The production of AEA occurs through conversion of NAPE by either a NAPE-PLD dependent or independent pathway. Once formed, AEA is broken down by either NAAA or FAAH to form arachidonic acid or occasionally by COX-2 to form prostamides. Arachidonic acid can be synthesized via phospholipase A2
) from phospholipids and is also broken down by COX-2, forming prostaglandins and other eicosanoids. Additionally, arachidonic acid can be converted back to a phospholipid [30
]. Dashed lines indicate multistep pathway; gray lines indicate weak pathway.