Abstract
ENDOGENOUS neuromodulatory molecules are commonly coupled to specific metabolic enzymes to ensure rapid signal inactivation. Thus, acetylcholine is hydrolysed by acetylcholine esterase1 and tryptamine neurotransmitters like serotonin are degraded by monoamine oxidases2. Previously, we reported the structure and sleep-inducing properties of cis-9-octadecenamide, a lipid isolated from the cerebrospinal fluid of sleep-deprived cats3, cis-9-Octadecenamide, or oleamide, has since been shown to affect serotonergic systems4 and block gap-junction communication in glial cells (our unpublished results). We also identified a membrane-bound enzyme activity that hydrolyses oleamide to its inactive acid, oleic acid3. We now report the mechanism-based isolation, cloning and expression of this enzyme activity, originally named oleamide hydrolase5, from rat liver plasma mem-branes. We also show that oleamide hydrolase converts anandamide, a fatty-acid amide identified as the endogenous ligand for the cannabinoid receptor6, to arachidonic acid, indi-cating that oleamide hydrolase may serve as the general inactivating enzyme for a growing family of bioactive signalling molecules, the fatty-acid amides6â8. Therefore we will hereafter refer to oleamide hydrolase as fatty-acid amide hydrolase, in recognition of the plurality of fatty-acid amides that the enzyme can accept as substrates.
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Cravatt, B., Giang, D., Mayfield, S. et al. Molecular characterization of an enzyme that degrades neuromodulatory fatty-acid amides. Nature 384, 83â87 (1996). https://doi.org/10.1038/384083a0
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DOI: https://doi.org/10.1038/384083a0
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