- FAAH
protein
Name = Fatty acid amide hydrolase
caption = Fatty acid amide hydrolase (FAAH) dimer shown with covalent inhibitor (MAFP , yellow) bound in the active site.
width = 300
HGNCid = 3553
Symbol = FAAH
AltSymbols =
EntrezGene = 2166
OMIM = 602935
RefSeq = NM_001441
UniProt = O00519
PDB = 1MT5
ECnumber = 3.5.1.-
Chromosome = 1
Arm = p
Band = 35
LocusSupplementaryData = -p34Fatty acid amide hydrolase or FAAH is anintegral membrane protein (IMP) that hydrolyzes bioactive amides including theendocannabinoid anandamide (an agonist ofcannabinoid receptor s andTRPV1 vanilloid receptors) and agonists of theperoxisome proliferator-activated receptor s such asN-oleoylethanolamine andN-palmitoylethanolamine to freefatty acid andethanolamine . [ McKinney M.K., Cravatt B.F., "Structure and Function of Fatty Acid Amide Hydrolase." Ann. Rev. Biochem. 74:411(2005). PMID 15952893 ] It is also the primary terminator of the hypnotic lipidoleamide as well as the less well-characterized N-acyl taurines.Due to its ability to regulate
anandamide levels, it is currently viewed as an attractive drug target. A human mutation (proline 129 tothreonine ) has been associated with problem drug use. [Sipe J.C., Chiang K., Gerber A.L., Beutler E., Cravatt B.F., "A missense mutation in human fatty acid amide hydrolase associated with problem drug use." Proc. Natl. Acad. Sci. U.S.A. 99:8394-8399(2002). PMID 12060782 ] Additionally, genetic ablation or pharmacological inhibition of FAAH results inanalgesia (lack of sensitivity to pain) in mice due, perhaps, to the effects ofanandamide oncannabinoid receptor s.FAAH was cloned in
1996 byBen Cravatt atThe Scripps Research Institute where it continues to be intensively studied and characterized. [Cravatt B.F., Giang D.K., Mayfield S.P., Boger D.L., Lerner, R.A.; "Molecular characterization of an enzyme that degrades neuromodulatory fatty-acid amides"; Nature 384:83 (1996). PMID 8900284 ] cite journal |author=Bracey MH, Hanson MA, Masuda KR, Stevens RC, Cravatt BF |title=Structural adaptations in a membrane enzyme that terminates endocannabinoid signaling |journal=Science |volume=298 |issue=5599 |pages=1793–6 |year=2002 |pmid=12459591 |doi=10.1126/science.1076535]Inhibitors and assays
Both non-selective and selective inhibitors of the
enzyme have been described. Examples of non-selective inhibitors includePMSF (phenylmethylsulfonylfluoride),MAFP , and ATMK (arachidonoyltrifluoromethylketone), whileURB597 is widely regarded as the current 'gold standard' FAAH inhibitor.Fact|date=February 2007The enzyme is typically assayed making use of a radiolabelled anandamidesubstrate , which generates free labelledethanolamine , although alternativespectrophotometric methods have also been described.References
External links
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