The enzymatic inactivation of the fatty acid amide class of signaling lipids.
The fatty acid amide (FAA) class of signaling lipids modulates a number of neurobehavioral processes in mammals, including pain, sleep, feeding, and locomotor activity. Representative FAAs include the endogenous cannabinoid anandamide and the sleep-inducing lipid oleamide. Despite activating several neuroreceptor systems in vitro, most FAAs produce only weak and transient behavioral effects in vivo, presumably due to their expeditious catabolism. This review focuses on one enzyme, fatty acid amide hydrolase (FAAH) that appears to play a major role in regulating the amplitude and duration of FAA signals in vivo. In particular, we will highlight a series of recent papers that have investigated the physiological functions of the mouse and human FAAH enzymes. Collectively, these studies promote FAAH as a central component of FAA signaling pathways, especially those mediated by the endocannabinoid anandamide, and suggest that this enzyme may represent an attractive pharmaceutical target for the treatment of pain and related neurophysiological disorders.
Cravatt
Benjamin F
BF
Departments of Cell Biology and Chemistry, The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 N Torrey Pines Road, La Jolla, CA 92037, USA. cravatt@scripps.edu
Lichtman
Aron H
AH
D000577:Amides / Q000737:chemistry / Q000378:metabolism*; D000581:Amidohydrolases / Q000494:pharmacology / Q000502:physiology*; D000595:Amino Acid Sequence; D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism; D063385:Cannabinoid Receptor Modulators; D002186:Cannabinoids / Q000378:metabolism; D063388:Endocannabinoids; D005227:Fatty Acids / Q000378:metabolism*; D006801:Humans; D053284:Polyunsaturated Alkamides; D015398:Signal Transduction; D013569:Synapses / Q000378:metabolism; D000099252:Fatty Acid Amide Hydrolases
D000577:Amides; D000581:Amidohydrolases; D001095:Arachidonic Acids; D063385:Cannabinoid Receptor Modulators; D002186:Cannabinoids; D063388:Endocannabinoids; D005227:Fatty Acids; D053284:Polyunsaturated Alkamides; D000099252:Fatty Acid Amide Hydrolases; C078814:anandamide