Critical enzymes involved in endocannabinoid metabolism.
Investigations of the pathways involved in the metabolism of endocannabinoids have grown exponentially in recent years following the discovery of cannabinoid receptors (CB) and their endogenous ligands, such as anandamide (AEA) and 2-arachidonoylglycerol (2-AG). The in vivo biosynthesis of AEA has been shown to occur through several pathways mediated by N-acylphosphatidylethanolamide-phospholipase D (NAPE-PLD), a secretory PLA(2) and PLC. 2-AG, a second endocannabinoid is generated through the action of selective enzymes such as phosphatidic acid phsophohydrolase, diacylglycerol lipase (DAGL), phosphoinositide-specific PLC (PI-PLC) and lyso-PLC. A putative membrane transporter or facilitated diffusion is involved in the cellular uptake or release of endocannabinoids. AEA is metabolized by fatty acid amidohydrolase (FAAH) and 2-AG is metabolized by both FAAH and monoacylglycerol lipase (MAGL). The author presents an integrative overview of current research on the enzymes involved in the metabolism of endocannabinoids and discusses possible therapeutic interventions for various diseases, including addiction.
Basavarajappa
Balapal S
BS
Division of Analytical Psychopharmacology, New York State Psychiatric Institute, College of Physicians & Surgeons, Columbia University, New York, NY 10032, USA. Basavaraj@nki.rfmh.org
D000581:Amidohydrolases / Q000378:metabolism / Q000502:physiology; D000818:Animals; D001095:Arachidonic Acids / Q000096:biosynthesis / Q000378:metabolism; D001921:Brain / Q000201:enzymology / Q000378:metabolism; D063385:Cannabinoid Receptor Modulators / Q000378:metabolism*; D063388:Endocannabinoids; D004798:Enzymes / Q000502:physiology*; D005989:Glycerides / Q000378:metabolism; D006801:Humans; D053858:Metabolic Networks and Pathways / Q000235:genetics / Q000502:physiology; D008954:Models, Biological; D008994:Monoacylglycerol Lipases / Q000502:physiology; D010739:Phospholipase D / Q000235:genetics / Q000502:physiology; D053284:Polyunsaturated Alkamides / Q000378:metabolism; D014018:Tissue Distribution; D000099252:Fatty Acid Amide Hydrolases
D000581:Amidohydrolases; D001095:Arachidonic Acids; D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D004798:Enzymes; D005989:Glycerides; D008994:Monoacylglycerol Lipases; D010739:Phospholipase D; D053284:Polyunsaturated Alkamides; D000099252:Fatty Acid Amide Hydrolases; C094503:glyceryl 2-arachidonate; C506062:Napepld protein, mouse; C078814:anandamide