Enzymatic formation of anandamide.
In animal tissues anandamide and other bioactive N-acylethanolamines are principally produced from glycerophospholipids through the transacylation-phosphodiesterase pathway consisting of two enzymatic reactions. The first reaction is the generation of N-acylphosphatidylethanolamine (NAPE) by transferring an acyl group esterified at sn-1 position of glycerophospholipid to the amino group of phosphatidylethanolamine. This reaction is catalyzed by Ca(2+)-dependent N-acyltransferase. The discovery of Ca(2+)-independent N-acyltransferase revealed the existence of plural enzymes which are capable of catalyzing this reaction. The second reaction is the release of N-acylethanolamine from NAPE catalyzed by NAPE-hydrolyzing phospholipase D (NAPE-PLD). The enzyme belongs to the metallo-beta-lactamase family and specifically hydrolyzes NAPEs. Recent studies, including analysis of NAPE-PLD-deficient mice, led to the discovery of NAPE-PLD-independent pathways for the anandamide biosynthesis.
Okamoto
Yasuo
Y
The Department of Biochemistry, Kagawa University School of Medicine, Kagawa, Japan.
Tsuboi
Kazuhito
K
Ueda
Natsuo
N
D000217:Acyltransferases / Q000737:chemistry / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001095:Arachidonic Acids / Q000096:biosynthesis*; D002118:Calcium / Q000494:pharmacology; D063385:Cannabinoid Receptor Modulators / Q000096:biosynthesis*; D063388:Endocannabinoids; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009928:Organ Specificity; D010714:Phosphatidylethanolamines / Q000378:metabolism; D010739:Phospholipase D / Q000737:chemistry / Q000172:deficiency / Q000378:metabolism; D010740:Phospholipases / Q000378:metabolism*; D053284:Polyunsaturated Alkamides; D016415:Sequence Alignment
D000217:Acyltransferases; D001095:Arachidonic Acids; D002118:Calcium; D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D010714:Phosphatidylethanolamines; D010739:Phospholipase D; D010740:Phospholipases; D053284:Polyunsaturated Alkamides; C483858:phosphatidylethanolamine; C506062:Napepld protein, mouse; C078814:anandamide