Figure 1.

Anandamide and 2-arachidonoylglycerol (2-AG) are formed via phospholipid precursors by the enzymes N-acylphosphatidylethanolamine phospholipase D (NAPE-PLD) and diacylglycerol lipase (DAGL). These active lipids interact with membrane and intracellular receptors, including the G protein–coupled receptors 119 and 55 (GPR119 and GPR55), the cannabinoid 1 and 2 receptors (CB1 and CB2), the transient receptor potential vanilloid subtype 1 receptor (TRPV1), and the peroxisome proliferator-activated receptors (PPARs), among others. Anandamide is hydrolyzed intracellularly by N-acylethanolamine-hydrolyzing acid amidase (NAAA) and fatty acid amide hydrolase (FAAH), and 2-AG is hydrolyzed intracellularly by monoacylglycerol lipase (MAGL) and alpha/beta-hydrolase domain 6 (ABHD6).⁸