Oleamide hydrolase

The actual enzymes involved in fatty acid amides (FAAs) metabolism remained unknown until the late 1990s, when a rat liver oleamide hydrolase activity was affinity-purified and its cDNA was cloned (Cravatt et al., 1996). Oleamide amidase was connected to AEA hydrolysis, because AEA and oleamide were catalyzed by the same enzyme, called fatty acid amide hydrolase (FAAH A-arachidonoylethanolamine amidohydrolase, EC 3.5.1.4) (Maurelli et al.,... 

Oleamide (cw-9-octadecenamide Scheme 2.2.1) is a brain constituent that accumulates under conditions of sleep deprivation and disappears upon sleep recovery. Nanomolar quantities induce physiological sleep when oleamide is injected intravascularly. An integral membrane oleamide hydrolase then catalyzes its degradation (Cravatt et al, 1996 Patterson et al, 1996). 

Boger DL, Sato H, Lerner AE, Hedrick MP, Fesik RA, Miyauchi H, Wilkie GD, Austin BJ, Patricelli MP, Cravatt BF. Exceptionally potent inhibitors of fatty acid amide hydrolase the enzyme responsible for degradation of endogenous oleamide and anandamide. Proc Natl Acad Sci USA 2000 97 5044-5049. 

LodolaA, MMor, JC Hermann, GTarzia, DPiomelli, AJ Mulholland (2005) QM/MM modelling of oleamide hydrolysis in fatty acid amide hydrolase (FAAH) reveals a new mechanism of nucleophile activation. Chem. Comm. (35) 43994 401... 

Oleamide, a lipid originally named cerebrodiene, was first iso lated from partially sleep-deprived cats (Lerner et al 1994). The molecule, with the chemical formula C18H35NO, is a long-chain base structurally related to sphingosine and sphinganine (Lerner et al 1994). Oleamide, or cerebrodiene, is chemically characterized as cis-9,10-octadecenoamide (Cravatt et al 1995). Oleamide is degraded by the brain enzyme fatty acid amide hydrolase (FAAH), which also degrades anandamide (Cravatt et al. Nature 1996). 

See Boring 1996 Lerner 1994 for oleamide cannabinoid activity. Anti-cancer Activity See Di Marzo et al Palmitoylethanolamide Inhibits the Expression of Fatty Acid Amide Hydrolase and Enhances the anti-proliferative Effect of Anandamide in Human Breast Cancer Cells. Biochem J. (2001) 358 (Pt 1) 249-55. 

Studies of the degradation and regulation of oleamide revealed that it was hydrolyzed to oleic acid and ammonia by the action of a. membrane-bound enzyme, which based on the inhibition of its activity, seemed to be a serine or cysteine protease. Isolation and sequencing of the protein led to the cloning of its cDNA and expression in COS-7 cells. The expressed enzyme was found to not only hydrolyze oleamide but a number of other fatty acid amides and was thus designated as fatty acid amide hydrolase or FAAH (206). 

Fowler CJ, Jonsson KO, Tiger G (2001) Fatty acid amide hydrolase biochemistry, pharmacology, and therapeutic possibilities for an enzyme hydrolyzing anandamide, 2-arachidonoylglycerol, palmitoylethanolamide, and oleamide. Biochem Pharmacol 2001 62 517-526... 

Thomas EA, Cravatt BF, Danielson PE, Gilula NB, Sutcliffe JG (1997) Fatty acid amide hydrolase, the degradative enzyme for anandamide and oleamide, has selective distribution in neurons within the rat central nervous system. J Neurosci Res 50 1047-1052... 

Egertova, M., Cravatt, B.E, Elphick, M.R. (2000) Fatty acid amide hydrolase expression in rat choroids plexus possible role in regulation of the sleep-inducing action of oleamide. Neurosci. Lett. 282, 13-16. 

Romero FA, Du W, Hwang I, Rayl TJ, Kimball FS, Leung D, Hoover HS, Apodaca RL, Breitenbucher JG, Cravatt BF, Boger DL (2007) Potent and selective a-ketoheterocycle-based inhibitors of the anandamide and oleamide cataboUzing enzyme, fatty add amide hydrolase. J Med Chem 50 1058-1068... 

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