ArticleThe Journal of biological chemistry2010
Lipid droplets are novel sites of N-acylethanolamine inactivation by fatty acid amide hydrolase-2.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 99 citations in OpenAlex.
- Acute Pain After Total Knee Arthroplasty: 2-Arachidonoylglycerol Tone and Endocannabinoid/Eicosanoid Crosstalk.Anesthesia and analgesia · 2026Article
- Enhancing anandamide signalling through fatty acid amide hydrolase inhibition: An update on the pharmacological strategy for treating psychiatric disorders.Translational psychiatry · 2026Review
- Characterization of a Fatty Acid Amide Hydrolase (FAAH) in Hirudo Verbana.Neurochemical research · 2024Article
- Characterization of a Fatty Acid Amide Hydrolase (FAAH) in Hirudo verbana.Research square · 2024Article
- Goods and Bads of the Endocannabinoid System as a Therapeutic Target: Lessons Learned after 30 Years.Pharmacological reviews · 2023Review
- The Role of Cannabinoids in CNS Development: Focus on Proliferation and Cell Death.Cellular and molecular neurobiology · 2023Review
- Role of integrating cannabinoids and the endocannabinoid system in neonatal hypoxic-ischaemic encephalopathy.Frontiers in molecular neuroscience · 2023Review
- Mechanisms of endocannabinoid transport in the brain.British journal of pharmacology · 2022Review
- Classical and Unexpected Effects of Ultra-Micronized PEA in Neuromuscular Function.Biomolecules · 2022Review
- Abnormal accumulation of lipid droplets in neurons induces the conversion of alpha-Synuclein to proteolytic resistant forms in a Drosophila model of Parkinson's disease.PLoS genetics · 2021Article
- The Role of PPAR Alpha in the Modulation of Innate Immunity.International journal of molecular sciences · 2021Review
- The rise and fall of anandamide: processes that control synthesis, degradation, and storage.Molecular and cellular biochemistry · 2021Review
- The Basal Pharmacology of Palmitoylethanolamide.International journal of molecular sciences · 2020Review
- Inhibition of fatty acid amide hydrolase in the CNS prevents and reverses morphine tolerance in male and female mice.British journal of pharmacology · 2020Article
- Modulation of Mast Cell Reactivity by Lipids: The Neglected Side of Allergic Diseases.Frontiers in immunology · 2019Review
- Proteomic analysis of monolayer-integrated proteins on lipid droplets identifies amphipathic interfacial α-helical membrane anchors.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Neuroprotection in Oxidative Stress-Related Neurodegenerative Diseases: Role of Endocannabinoid System Modulation.Antioxidants & redox signaling · 2018Review
- Fatty acid-binding protein 5 controls microsomal prostaglandin E synthase 1 (mPGES-1) induction during inflammation.The Journal of biological chemistry · 2018Article
- Effect of maternal high-fat diet on key components of the placental and hepatic endocannabinoid system.American journal of physiology. Endocrinology and metabolism · 2018Article
- Involvement of TRPV1 Channels in Energy Homeostasis.Frontiers in endocrinology · 2018Review
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Anandamide (AEA) and other bioactive N-acylethanolamines (NAEs) are primarily inactivated by the enzyme fatty acid amide hydrolase (FAAH). Recently, FAAH-2 was discovered in humans, suggesting an additional enzyme can mediate NAE inactivation in higher mammals. Here, we performed a biochemical characterization of FAAH-2 and explored its capacity to hydrolyze NAEs in cells. In homogenate activity assays, FAAH-2 hydrolyzed AEA and palmitoylethanolamide (PEA) with activities approximately 6 and approximately 20% those of FAAH, respectively. In contrast, FAAH-2 hydrolyzed AEA and PEA in intact cells with rates approximately 30-40% those of FAAH, highlighting a potentially greater contribution toward NAE catabolism in vivo than previously appreciated. In contrast to endoplasmic reticulum-localized FAAH, immunofluorescence revealed FAAH-2 was localized on lipid droplets. Supporting this distribution pattern, the putative N-terminal hydrophobic region of FAAH-2 was identified as a functional lipid droplet localization sequence. Lipid droplet localization was essential for FAAH-2 activity as chimeras excluded from lipid droplets lacked activity and/or were poorly expressed. Lipid droplets represent novel sites of NAE inactivation. Therefore, we examined substrate delivery to these organelles. AEA was readily trafficked to lipid droplets, confirming that lipid droplets constitute functional sites of NAE inactivation. Collectively, these results establish FAAH-2 as a bone fide NAE-catabolizing enzyme and suggest that NAE inactivation is spatially separated in cells of higher mammals.
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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.