The fatty acid amide hydrolase (FAAH)

The topic of this review is fatty acid amide hydrolase (FAAH), one of the b est-characterized enzymes involved in the hydrolysis of bioactive lipids su ch as anandamide, 2-arachidonoylglycerol (2-AG), and oleamide. Herein, we d iscuss the nomenclature, the various assays that have been developed, the r elative activity of the various substrates and the reversibility of the enz yme reactions catalyzed by FAAH. We also describe the cloning of the enzyme from rat and subsequent cDNA isolation from mouse, human, and pig. The pro teins and the mRNAs from different species are compared. Cloning the enzyme permitted the purification and characterization of recombinant FAAH. The c onserved regions of FAAH are described in terms of sequence and function, i ncluding the amidase domain which contains the serine catalytic nucleophile , the hydrophobic domain important for self association, and the proline ri ch domain region, which may be important for subcellular localization. The distribution of FAAH in the major organs of the body is described as well a s regional distribution in the brain and its correlation with cannabinoid r eceptors. Since FAAH is recognized as a drug target, a large number of inhi bitors have been synthesized and tested since 1994 and these are reviewed i n terms of reversibility, potency, and specificity for FAAH and cannabinoid receptors. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.