Figure 1.

Endocannabinoid anandamide (AEA) and 2-arachidonoylglycerol (2-AG) are formed from arachidonic acid-containing phospholipids. AEA is formed from a two-step catalysis of phospholipids to form N-arachidonoylphosphatidylethanolamine (NAPE). NAPE is cleaved by phospholipase D (PLD) to form AEA. AEA is metabolized by the enzyme fatty acid amide hydrolase (FAAH) and by N-acylethanolamine-hydrolyzing acid amidase (NAAA) to form arachidonic acid or by COX to form prostaglandin ethanolamide (prostamides). 2-AG is synthesized from diacylglycerol (formed from phosphoinositides by the action of phospholipase C) by the action of diacylglycerol lipase (DAGL). 2-AG is metabolized either via COX to form prostaglandin glycerol esters or by both monoacylglycerol lipase (MAG-L) and α,β-hydrolase domain-containing 6 (ABHD6) to form arachidonic acid. Additionally, arachidonic acid can be synthesized directly from phospholipids by phospholipase A2 (PLA₂) which is further metabolized by lipoxygenase (LOX) to produce leukotrienes (LTs), cyclooxygenase (COX) to form prostaglandin glycerol esters, and cytochrome P450 (CYP) enzymes to form eicosanoids. EETs: epoxyeicosatrienoic acids; HETEs: hydroxyeicosatetraenoic acids.