title: Biosynthesis and degradation of the endocannabinoid 2-arachidonoylglycerol.
abstract: 2-Arachidonoylglycerol (2-AG) is a monoacylglycerol (MAG) molecule containing an esterified arachidonic acid chain at sn-2 position of the glycerol backbone. Together with structurally similar N-arachidonoylethanolamine (anandamide), 2-AG has been extensively studied as an endogenous ligand of cannabinoid receptors (an endocannabinoid) in brain and other mammalian tissues. Accumulating evidence demonstrates that the endocannabinoid system, including the central-type cannabinoid receptor CB1 and 2-AG, is responsible for synaptic retrograde signaling in the central nervous system. As 2-AG is rapidly formed from membrane phospholipids on cellular stimuli and degraded to arachidonic acid and glycerol, the enzymes catalyzing its biosynthesis and degradation are believed to play crucial roles in the regulation of its tissue levels. The major biosynthetic pathway appears to consist of sequential hydrolyses of inositol phospholipids via diacylglycerol (DAG) by β-type phospholipase C and DAG lipase, while MAG lipase is a principal enzyme in the degradation. In this short review, we will briefly outline rapid advances in enzymological research on the biosynthetic and degradative pathways of 2-AG.
authors.affiliation: Department of Biochemistry, Kagawa University School of Medicine, 1750-1 Ikenobe, Miki, Kagawa, Japan. nueda@med.kagawa-u.ac.jp
authors.forename: Natsuo
authors.initials: N
authors.lastname: Ueda
authors.forename: Kazuhito
authors.initials: K
authors.lastname: Tsuboi
authors.forename: Toru
authors.initials: T
authors.lastname: Uyama
authors.forename: Taira
authors.initials: T
authors.lastname: Ohnishi
mesh_terms: D000818:Animals; D001095:Arachidonic Acids / Q000096:biosynthesis* / Q000378:metabolism; D063385:Cannabinoid Receptor Modulators / Q000096:biosynthesis* / Q000378:metabolism; D063388:Endocannabinoids; D005989:Glycerides / Q000096:biosynthesis* / Q000378:metabolism; D006801:Humans; D008071:Lipoprotein Lipase / Q000378:metabolism; D008994:Monoacylglycerol Lipases / Q000378:metabolism; D011487:Protein Conformation
chemical_list: D001095:Arachidonic Acids; D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D005989:Glycerides; C094503:glyceryl 2-arachidonate; D008994:Monoacylglycerol Lipases; D008071:Lipoprotein Lipase