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Fatty Acid Amide Hydrolase, an Enzyme with Many Bioactive Substrates. Possible Therapeutic Implications
Abstract
During the last eight years a number of bioactive lipid mediators, the amides or esters of long chain fatty acids, have been discovered or re-discovered. These are: anandamide (N-arachidonoyl-ethanolamine, AEA) and 2-arachidonoylglycerol (2-AG), two endogenous agonists of cannabinoid receptors; oleamide (cis-9- octadecenoamide), a putative endogenous sleep-inducing factor; N-palmitoylethanol amine (PEA), a compound with promising anti-inflammatory and immune-modulatory activity. These compounds are all substrates for the same hydrolytic enzyme, fatty acid amide hydrolase (FAAH), whose molecular characterization was obtained in 1996. The molecular and enzymatic properties, tissue distribution, substrate recognition properties, physiological regulation and biological role of FAAH are discussed in this article, with special emphasis on the possible pharmacological manipulation of the activity of this enzyme with therapeutic purpose. Keywords: fatty acid amide hydrolase, enzyme, n-palmitoylethanol amine(pea), anandamide, n-palmitoylethanolamine(pea), 2-arachidonoyl-glycerol(2-ag), cis-9-octadecenoamide, faah inhibitors, lipoaminoacids
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“PEA may indirectly alter levels of endocannabinoids by competing with anandamide and other fatty-acid amides for degradation by FAAH or by suppressing FAAH expression at the transcriptional level.27, 28”
From Cannabinoids as Pharmacotherapies for Neuropathic Pain: From the Bench to the Bedside (2009) · cites this paper as [28]
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N-Oleoyldopamine, a Novel Endogenous Capsaicin-like Lipid That Produces Hyperalgesia
Chu, C. J., Huang, S. M., PETROCELLIS, L. D., Bisogno, T., Ewing, S. A., Miller, J. D., Zipkin, R. E., Daddario, N., Appendino, G., Marzo, V. D., et al. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m211231200 · Cited by 345
Self-citationTsuboi, K., Sun, Y.-X., Okamoto, Y., Araki, N., Tonai, T., & Ueda, N. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m413473200 · Cited by 330
Endocannabinoids: synthesis and degradation
Marzo, V. D. (2006) · Reviews of physiology, biochemistry and pharmacology · doi:10.1007/112_0505 · Cited by 320
Self-citationCannabinoids as Pharmacotherapies for Neuropathic Pain: From the Bench to the Bedside
Rahn, E. J., & Hohmann, A. G. (2009) · Neurotherapeutics · doi:10.1016/j.nurt.2009.08.002 · Cited by 305
“PEA may indirectly alter levels of endocannabinoids by competing with anandamide and other fatty-acid amides for degradation by FAAH or by suppressing FAAH expression at the transcriptional level.(27,28) FAAH / mice are hypoalge-”
BackgroundMor, M., Rivara, S., Lodola, A., Plazzi, P. V., Tarzia, G., Duranti, A., Tontini, A., Piersanti, G., Kathuria, S., & Piomelli, D. (2004) · Journal of Medicinal Chemistry · doi:10.1021/jm031140x · Cited by 277
Metadata
- Authors
- Bisogno, T., Petrocellis, L., & Marzo, V.
- Affiliations
- Istituto di Chimica Biomolecolare (IT)
- Corresponding author
- Marzo, Vincenzo
- Venue
- Current Pharmaceutical Design
- Publisher
- Bentham Science Publishers Ltd.
- Published
- 2002-03-01
- Volume
- 8
- Issue
- 7
- Pages
- 533-547
- ISSN
- 1381-6128 (ISSN-L)
- OpenAlex
- W2012917330
- Cited by
- 112
- References
- 0
- Citations by year
- 2025: 1 · 2024: 2 · 2023: 1 · 2022: 3 · 2021: 1 · 2020: 2 · 2019: 4 · 2018: 3 · 2017: 3 · 2016: 5 · 2015: 3 · 2014: 2 · 2013: 5 · 2012: 3
- FWCI
- 7.87
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Current Pharmaceutical Design (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Cannabis and Cannabinoid Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Eicosanoids and Hypertension Pharmacology
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Keywords
- fatty acid amide hydrolase, FAAH inhibitors, anandamide, 2-arachidonoylglycerol, oleamide, N-palmitoylethanolamine, endocannabinoid system, endocannabinoid receptors, bioactive lipid mediators, enzyme substrate specificity, anti-inflammatory activity
- MeSH terms
- Fatty Acid Amide Hydrolases, Amides, Amidohydrolases, Animals, Arachidonic Acids, Enzyme Inhibitors, Ethanolamines, Glycerides, Humans, Molecular Sequence Data, Oleic Acids, Palmitic Acids, Structure-Activity Relationship, Substrate Specificity, Swine, Sequence Homology, Amino Acid, Mice, Rats, Polyunsaturated Alkamides, Endocannabinoids
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