Biology of endocannabinoid synthesis system.
Endocannabinoids (endogenous ligands of cannabinoid receptors) exert diverse physiological and pathophysiological functions in animal tissues. N-Arachidonoylethanolamine (anandamide) and 2-arachidonoylglycerol (2-AG) are two representative endocannabinoids. Both the compounds are arachidonic acid-containing lipid molecules generated from membrane glycerophospholipids, but their biosynthetic pathways are totally different. Anandamide is principally formed together with other N-acylethanolamines (NAEs) in a two-step pathway, which is composed of Ca(2+)-dependent N-acyltransferase and N-acylphosphatidylethanolamine-hydrolyzing phospholipase D (NAPE-PLD). cDNA cloning of NAPE-PLD and subsequent analysis of its gene-disrupted mice led to the discovery of alternative pathways comprising multiple enzymes. As for the 2-AG biosynthesis, recent results, including cDNA cloning of diacylglycerol lipase and analyses of phospholipase Cbeta-deficient mice, demonstrated that these two enzymes are responsible for the in vivo formation of 2-AG functioning as a retrograde messenger in synapses. In this review article, we will focus on recent progress in the studies on the enzymes responsible for the endocannabinoid biosyntheses.
Wang
Jun
J
Department of Biochemistry, Kagawa University School of Medicine, Miki, Kagawa, Japan.
Ueda
Natsuo
N
D000217:Acyltransferases / Q000378:metabolism; D000581:Amidohydrolases / Q000378:metabolism; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D001095:Arachidonic Acids / Q000096:biosynthesis*; D063385:Cannabinoid Receptor Modulators / Q000096:biosynthesis*; D063388:Endocannabinoids; D005260:Female; D005989:Glycerides / Q000096:biosynthesis*; D006801:Humans; D007527:Isoenzymes; D008071:Lipoprotein Lipase / Q000378:metabolism; D008297:Male; D010739:Phospholipase D / Q000378:metabolism; D053284:Polyunsaturated Alkamides; D011247:Pregnancy; D015398:Signal Transduction; D010738:Type C Phospholipases / Q000378:metabolism
D001095:Arachidonic Acids; D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D005989:Glycerides; D007527:Isoenzymes; D053284:Polyunsaturated Alkamides; D016718:Arachidonic Acid; C094503:glyceryl 2-arachidonate; D000217:Acyltransferases; D008071:Lipoprotein Lipase; D010738:Type C Phospholipases; D010739:Phospholipase D; D000581:Amidohydrolases; C523108:NAAA protein, human; C078814:anandamide