Fatty acid amide hydrolase (FAAH) catalyzes the hydrolysis of biologically significant fatty acid amides.¹ Characterization of FAAH, its substrates, and inhibitors have helped to partially elucidate the molecular regulation of sleep,² nociception,^3,4 and cancer. FAAH is an intracellular enzyme linked to the plasma-membrane via its N-terminal domain.^5,6 The purified enzyme from rat has an estimated molecular mass of 63,000.⁵ Cloning and characterization of pig, murine, and human FAAH indicate highly conserved homology with the rat sequence.⁶ Northern and immunoblot analyses reveals that FAAH exists in a wide variety of tissues and is particularly abundant in liver, pancreas, brain, testes, uterus, small intestine, and ocular tissue.^7,1,6,8

1 Fowler, C.J., Jonsson, K., and Tiger, G. Fatty acid amide hydrolase: Biochemistry, pharmacology, and therapeutic possibilities for an enzyme hydrolyzing anandamide, 2-arachidonoylglycerol, palmitoylethanolamide, and oleamide. Biochem Pharmacol 62 517-526 (2001).

2 Boger, D.L., Henriksen, S.J., and Cravatt, B.F. Oleamide: An endogenous sleep-inducing lipid and prototypical member of a new class of biological signaling molecules. Curr Pharm Des 4 303-314 (1998).

3 Cravatt, B.F., Demarest, K., Patricelli, M.P., et al. Supersensitivity to anandamide and enhanced endogenous cannabinoid signaling in mice lacking fatty acid amide hydrolase. Proc Natl Acad Sci USA 98(16) 9371-9376 (2001).

4 Di Marzo, V., Bisogno, T., Melck, D., et al. Interactions between synthetic vanilloids and the endogenous cannabinoid system. FEBS Lett 436 449-454 (1998).

5 Cravatt, B.F., Giang, D.K., Mayfield, S.P., et al. Molecular characterization of an enzyme that degrades neuromodulatory fatty-acid amides. Nature 384 83-87 (1996).

6 Giang, D.K., and Cravatt, B.F. Molecular characterization of human and mouse fatty acid amide hydrolases. Proc Natl Acad Sci USA 94 2238-2242 (1997).

7 Van Sickle, M.D., Oland, L.D., Ho, W., et al. Cannabinoids inhibit emesis through CB₁ receptors in the brainstem of the ferret. Gastroenterology 121 767-774 (2001).

8 Katayama, K., Ueda, N., Kurahashi, Y., et al. Distribution of anandamide amidohydrolase in rat tissues with special reference to small intestine. Biochim Biophys Acta 1347 212-218 (1997).

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

Katayama, K., Ueda, N., Kurahashi, Y., et al. Distribution of anandamide amidohydrolase in rat tissues with special reference to small intestine. Biochim Biophys Acta 1347 212-218 (1997).

Di Marzo, V., Bisogno, T., Melck, D., et al. Interactions between synthetic vanilloids and the endogenous cannabinoid system. FEBS Lett 436 449-454 (1998).

Bisogno, T., Katayama, K., Melck, D., et al. Biosynthesis and degradation of bioactive fatty acid amides in human breast cancer and rat pheochromocytoma cells. Implications for cell proliferation and differentiation. Eur J Biochem 254 634-642 (1998).

Cravatt, B.F., Giang, D.K., Mayfield, S.P., et al. Molecular characterization of an enzyme that degrades neuromodulatory fatty-acid amides. Nature 384 83-87 (1996).

Van Sickle, M.D., Oland, L.D., Ho, W., et al. Cannabinoids inhibit emesis through CB₁ receptors in the brainstem of the ferret. Gastroenterology 121 767-774 (2001).

Giang, D.K., and Cravatt, B.F. Molecular characterization of human and mouse fatty acid amide hydrolases. Proc Natl Acad Sci USA 94 2238-2242 (1997).

Cravatt, B.F., Demarest, K., Patricelli, M.P., et al. Supersensitivity to anandamide and enhanced endogenous cannabinoid signaling in mice lacking fatty acid amide hydrolase. Proc Natl Acad Sci USA 98(16) 9371-9376 (2001).

Boger, D.L., Henriksen, S.J., and Cravatt, B.F. Oleamide: An endogenous sleep-inducing lipid and prototypical member of a new class of biological signaling molecules. Curr Pharm Des 4 303-314 (1998).

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