Biosynthesis and metabolism of endocannabinoids and their congeners from the monoacylglycerol and N-acyl-ethanolamine families

Abstract

The endocannabinoids 2-arachidonoyl-glycerol (2-AG) and N-arachidonoyl-ethanolamine (AEA) are eicosanoids implicated in numerous physiological processes like appetite, adipogenesis, inflammatory pain and inflammation. They mediate most of their physiological effects by activating the cannabinoid (CB) receptors 1 and 2. Other than directly binding to the CB receptors, 2-AG and AEA are also metabolized by most eicosanoid biosynthetic enzymes, yielding many metabolites that are part of the oxyendocannabinoidome. Some of these metabolites have been found in vivo, have the ability to modulate specific receptors and thus potentially influence physiological processes. In this review, we discuss the biosynthesis and metabolism of 2-AG and AEA, as well as their congeners from the monoacyl-glycerol and N-acyl-ethanolamine families, with a special focus on the metabolism by oxygenases involved in arachidonic acid metabolism. We highlight the knowledge gaps in our understanding of the regulation and roles the oxyendocannabinoidome mediators.

Keywords: Cyclooxygenase; Cytrochrome P450; Endocannabinoid; Hydrolase; Lipoxygenase.