Molecular characterization of an enzyme that degrades neuromodulatory fatty-acid amides
- 1 November 1996
- journal article
- letter
- Published by Springer Science and Business Media LLC in Nature
- Vol. 384 (6604), 83-87
- https://doi.org/10.1038/384083a0
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oleamide, has since been shown to affect serotonergic systems4 and block gap-junction communication in glial cells (our unpublished results).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 amides6–8. 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.Keywords
This publication has 26 references indexed in Scilit:
- Brain lipids that induce sleep are novel modulators of 5-hydroxytrypamine receptors.Proceedings of the National Academy of Sciences of the United States of America, 1996
- Inhibition of Oleamide Hydrolase Catalyzed Hydrolysis of the Endogenous Sleep-Inducing Lipid cis-9-OctadecenamideJournal of the American Chemical Society, 1996
- Chemical Characterization of a Family of Brain Lipids That Induce SleepScience, 1995
- Monoamine oxidases: old friends hold many surprisesThe FASEB Journal, 1995
- Mast cells express a peripheral cannabinoid receptor with differential sensitivity to anandamide and palmitoylethanolamide.Proceedings of the National Academy of Sciences of the United States of America, 1995
- Isolation and Structure of a Brain Constituent That Binds to the Cannabinoid ReceptorScience, 1992
- Isolation of fatty acid amide as an angiogenic principle from bovine mesenteryBiochemical and Biophysical Research Communications, 1990
- The nucleotide sequence of the amdS gene of Aspergillus nidulans and the molecular characterization of 5′ mutationsGene, 1987
- Nucleotide sequences of the Pseudomonas savastanoi indoleacetic acid genes show homology with Agrobacterium tumefaciens T-DNAProceedings of the National Academy of Sciences of the United States of America, 1985
- Nucleotide sequence of the tms genes of the pTiA6NC octopine Ti plasmid: two gene products involved in plant tumorigenesis.Proceedings of the National Academy of Sciences of the United States of America, 1984