ArticleScientific reports2020
The endocannabinoid hydrolase FAAH is an allosteric enzyme.
Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 24 papers, 2 of them syntheses that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
24 citing papers in PubMed, 2 syntheses or guidelines pooled it, 48 citations in OpenAlex.
- Association between the FAAH C385A variant (rs324420) and obesity-related traits: a systematic review.International journal of obesity (2005) · 2024Pooled it
- Contribution of Fatty Acid Amide Hydrolase to Alcohol Use Disorder: A Systematic Review.Cannabis and cannabinoid research · 2021Pooled it
- Untargeted Metabolomics Reveal New Endogenous Plasma Biomarkers Associated with CYP3A Inhibition in Humans.Clinical pharmacology and therapeutics · 2026Article
- Lipid Composition Drives Mutant Huntingtin Dimerization and Membrane Association: Insights from Computational Simulations.Molecules (Basel, Switzerland) · 2026Article
- FRAIL: fragment-based reinforcement learning for molecular design and benchmarking on fatty acid amide hydrolase 1 (FAAH-1).Molecular diversity · 2026Article
- Postpartum lipid dysregulation in African American women who experienced cardiometabolic complications of pregnancy.iScience · 2025Article
- Serum metabolomics-driven network pharmacology elucidate the anti-rheumatoid arthritis potential of garden cress.Scientific reports · 2025Article
- Stress-induced changes in the molecular processes underlying fear memories: implications for PTSD and relevant animal models.Molecular psychiatry · 2025Review
- Review
- Anticonvulsant Effects of SyntheticMolecules (Basel, Switzerland) · 2025Article
- Predicting the bioactive compounds ofHeliyon · 2024Article
- Lipid metabolism-derived FAAH is a sensitive marker for the prognosis and immunotherapy of osteosarcoma patients.Heliyon · 2024Article
- Impact of various high fat diets on gene expression and the microbiome across the mouse intestines.Scientific reports · 2023Article
- Goods and Bads of the Endocannabinoid System as a Therapeutic Target: Lessons Learned after 30 Years.Pharmacological reviews · 2023Review
- The CB1 cannabinoid receptor regulates autophagy in the tibialis anterior skeletal muscle in mice.Biological research · 2023Article
- Regulation of Human Endogenous Metabolites by Drug Transporters and Drug Metabolizing Enzymes: An Analysis of Targeted SNP-Metabolite Associations.Metabolites · 2023Article
- FAAH served a key membrane-anchoring and stabilizing role for NLRP3 protein independently of the endocannabinoid system.Cell death and differentiation · 2023Article
- Article
- Hippocampal differential expression underlying the neuroprotective effect of delta-9-tetrahydrocannabinol microdose on old mice.Frontiers in neuroscience · 2023Article
- Assessment of NSAIDs as potential inhibitors of the fatty acid amide hydrolase I (FAAH-1) using three different primary fatty acid amide substrates in vitro.BMC pharmacology & toxicology · 2022Article
Corrections and comments
- Erratum issued
Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Fatty acid amide hydrolase (FAAH) is a membrane-bound homodimeric enzyme that in vivo controls content and biological activity of N-arachidonoylethanolamine (AEA) and other relevant bioactive lipids termed endocannabinoids. Parallel orientation of FAAH monomers likely allows both subunits to simultaneously recruit and cleave substrates. Here, we show full inhibition of human and rat FAAH by means of enzyme inhibitors used at a homodimer:inhibitor stoichiometric ratio of 1:1, implying that occupation of only one of the two active sites of FAAH is enough to fully block catalysis. Single W445Y substitution in rat FAAH displayed the same activity as the wild-type, but failed to show full inhibition at the homodimer:inhibitor 1:1 ratio. Instead, F432A mutant exhibited reduced specific activity but was fully inhibited at the homodimer:inhibitor 1:1 ratio. Kinetic analysis of AEA hydrolysis by rat FAAH and its F432A mutant demonstrated a Hill coefficient of ~1.6, that instead was ~1.0 in the W445Y mutant. Of note, also human FAAH catalysed an allosteric hydrolysis of AEA, showing a Hill coefficient of ~1.9. Taken together, this study demonstrates an unprecedented allosterism of FAAH, and represents a case of communication between two enzyme subunits seemingly controlled by a single amino acid (W445) at the dimer interface. In the light of extensive attempts and subsequent failures over the last decade to develop effective drugs for human therapy, these findings pave the way to the rationale design of new molecules that, by acting as positive or negative heterotropic effectors of FAAH, may control more efficiently its activity.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.