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Information on EC 3.5.1.99 - fatty acid amide hydrolase and Organism(s) Mus musculus and UniProt Accession O08914
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3.5.1.99 fatty acid amide hydrolaseIUBMB Comments
Integral membrane protein, the enzyme is responsible for the catabolism of neuromodulatory fatty acid amides, including anandamide and oleamide, occurs in mammalia.
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Word Map
- 3.5.1.99
-
endocannabinoids
- cannabinoids
- pain
- lipase
- agonist
- monoacylglycerol
- 2-arachidonoylglycerol
-
anxiety
-
analgesic
- cannabis
- n-acylethanolamines
-
vanilloid
-
2-arachidonoyl
- ethanolamide
- palmitoylethanolamide
- carbamate
-
rimonabant
- hyperalgesia
-
reward
-
tone
-
nociceptive
-
cannabimimetic
- n-arachidonoylethanolamine
- marijuana
-
anxiolytic
- nape-pld
-
antinociceptive
- oleoylethanolamide
-
emotional
-
neuropathic
- delta9-tetrahydrocannabinol
- amidase
-
amygdalar
- medicine
- catalepsy
- pharmacology
-
anti-allodynic
-
anxiolytic-like
- monoglyceride
- cannabidiol
-
psychoactive
-
sleep-inducing
-
phytocannabinoids
-
anxiety-like
-
arachidonyl
-
monoacyl
-
capsazepine
-
aversive
- tetrahydrocannabinol
- drug development
-
anti-hyperalgesic
-
neuromodulatory
- fluorophosphonate
The taxonomic range for the selected organisms is: Mus musculus
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
Reaction Schemes
+
=
+
Synonyms
fatty acid amide hydrolase, fatty-acid amide hydrolase, anandamide amidohydrolase, endocannabinoid-degrading enzyme, hfaah, oleamide hydrolase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
PATHWAY SOURCE
PATHWAYS
-
-
SYSTEMATIC NAME
IUBMB Comments
fatty acylamide amidohydrolase
Integral membrane protein, the enzyme is responsible for the catabolism of neuromodulatory fatty acid amides, including anandamide and oleamide, occurs in mammalia.
CAS REGISTRY NUMBER
COMMENTARY
153301-19-0
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
2-arachidonoylglycerol + H2O
?
-
FAAH is responsible for approximately one-half of the 2-arachidonoylglycerol hydrolysis occurring in BV-2 cell homogenate
-
-
?
anandamide + H2O
arachidonic acid + ethanolamine
-
i.e. N-arachidonoylethanolamine
-
-
?
anandamide + H2O
arachidonic acid + ethanolamine
-
i.e. arachidonoyl ethanolamide
-
-
?
anandamide + H2O
ethanolamine + arachidonic acid
-
anandamide hydrolysis in BV-2 cells is entirely attributable to FAAH
-
-
?
anandamide + H2O
ethanolamine + arachidonic acid
-
fatty acid amide hydrolase is a modulator of endogenous signaling compounds affecting sleep (oleamide) and analgesia (anandamide)
-
-
?
oleamide + H2O
oleic acid + NH3
-
fatty acid amide hydrolase is a modulator of endogenous signaling compounds affecting sleep (oleamide) and analgesia (anandamide)
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
2-arachidonoylglycerol + H2O
?
-
FAAH is responsible for approximately one-half of the 2-arachidonoylglycerol hydrolysis occurring in BV-2 cell homogenate
-
-
?
oleamide + H2O
oleic acid + NH3
-
fatty acid amide hydrolase is a modulator of endogenous signaling compounds affecting sleep (oleamide) and analgesia (anandamide)
-
-
?
anandamide + H2O
arachidonic acid + ethanolamine
-
i.e. N-arachidonoylethanolamine
-
-
?
anandamide + H2O
arachidonic acid + ethanolamine
-
i.e. arachidonoyl ethanolamide
-
-
?
anandamide + H2O
ethanolamine + arachidonic acid
-
anandamide hydrolysis in BV-2 cells is entirely attributable to FAAH
-
-
?
anandamide + H2O
ethanolamine + arachidonic acid
-
fatty acid amide hydrolase is a modulator of endogenous signaling compounds affecting sleep (oleamide) and analgesia (anandamide)
-
-
?
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
URB597
less effective inhibitor in the brain after oral administration while it reaches similar effects by intranasal (i.n.) and intraperitoneal routes. Intranasal URB597 delivery always increased N-acyl-ethanolamine levels in brain areas, whereas a parallel increase is not observed in the liver. By showing the efficacy of intranasal FAAH inhibition, evidence is provided that nose-to-brain delivery is a suitable alternative to enhance brain endocannabinoid tone for the treatment of neurodegenerative disorders and improve compliance of the patients
(5Z,8Z,11Z,14Z)-N-(2-hydroxyethyl)icosa-5,8,11,14-tetraenamide
-
i.e. (5Z,8Z,11Z,14Z)-N-(2-hydroxyethyl)icosa-5,8,11,14-tetraenamide or N-arachidonoylethanolamine, competitive
cyclohexylcarbamic acid 3'-carbamoylbiphenyl-3-yl ester
-
i.e. URB597, attenuates the development of lipopolysaccharide-induced paw edema and reverses lipopolysaccharide-induced hyperalgesia through the respective CB2 and CB1 mechanisms of action. The inhibition is not affected by capsazepine, a transient receptor potential vanilloid type 1 antagonist
methyl arachidonyl fluorophosphonate
-
MAFP, a potent irreversible FAAH inhibitor
additional information
-
the microglial-specific isozyme is not inhibited by URB597, i.e. 3'-carbamoyl-biphenyl-3-ylcyclohexylcarbamate, and inhibitors of cyclooxygenases, lipooxygenases, and diacylglycerol lipases, overview
-
additional information
-
organophosphorus compound-induced FAAH inhibition and the associated anandamide accumulation may lead to reduced limb mobility as a secondary neurotoxic effect
-
additional information
-
synthesis of 18 aryl analogues of anandamide. In vitro evaluation of inhibitory potency, binding to CB1 and CB2 cannabinoid receptors, and potential as metabolic trapping tracers of 4-methoxyphenethyllinoleoylamide and 4-methoxyphenethylarachidonoylamide, overview
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
Mus musculus
-
pIC50, i.e. -log IC50. values of anadamide analogue inhibitors, overview
-
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
full-wall bladder and mucosa, urothelium, no FAAH immunoreactivity in other structures of the bladder
-
temporal changes in mouse brain fatty acid amide hydrolase activity, determination by ex vivo autoradiography, overview
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
metabolism
-
fatty acid amide hydrolase is a key regulator of endocannabinoid-induced myocardial tissue injury
physiological function
additional information
-
anandamide induces enhanced cell death in human cardiomyocytes pretreated by FAAH inhibitor, and enhances sensitivity to reactive oxygen species generation in inflammatory cells of FAAH knockouts, it triggers concentration-dependent respiratory burst (ROS generation) in neutrophil granulocytes isolated from FAAH+/+ mice
malfunction
-
genetic deletion of FAAH is associated with enhanced acute doxorubicin-induced myocardial cell death and decreased survival, mechanism of the doxorubicin-induced myocardial cell death in FAAH+/+ and FAAH-/- mice, overview
malfunction
-
tissue-specific changes in N-acyl ethanolamine congeners and N-acyl taurines metabolism caused by FAAH disruption in central and peripheral tissues, overview
physiological function
-
FAAH is the chief catabolic enzyme regulating the endogenous cannabinoid N-arachidonoylethanolamine, i.e. anandamide
physiological function
-
genetic or pharmacological ablation of FAAH promotes analgesia and anxiolytic effects without disrupting motor coordination
physiological function
-
importance of FAAH in controlling endogenous anandamide levels in the brain and consequently the importance of FAAH as a regulatory enzyme for key physiological functions. FAAH is one of the main enzymes responsible for terminating the signaling of endocannabinoids in the brain, it has a role in neuropsychiatric disorders
physiological function
-
endocannabinoid-degrading enzyme fatty acid amide hydrolase. FAAH substrates in the urinary bladder act via local CB2-mediated signals
physiological function
-
fatty acid amide hydrolase is a key regulator of endocannabinoid-induced myocardial tissue injury
physiological function
-
fatty acid amide hydrolase is the principal enzyme responsible for anandamide hydrolysis in mammalian tissues and regulates amidated lipid transmitters, including the endocannabinoid anandamide and its N-acyl ethanolamine congeners and transient receptor potential channel agonists N-acyl taurines, in a tissue-specific manner, overview
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). FAAH1_MOUSE
579
1
63221
Swiss-Prot
Secretory Pathway (Reliability: 2)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
there is evidence indicating that enhancing the endocannabinoid (eCB) tone has therapeutic potential in several brain disorders. The inhibition of endocannabinoid degradation by fatty acid amide hydrolase blockade, is the best-known option to increase N-acyl-ethanolamines-mediated signaling. By showing the efficacy of intranasal FAAH inhibition, evidence is provided that nose-to-brain delivery is a suitable alternative to enhance brain endocannabinoid tone for the treatment of neurodegenerative disorders and improve patients' compliance
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Quistad, G.B.; Klintenberg, R.; Caboni, P.; Liang, S.N.; Casida, J.E.
Monoacylglycerol lipase inhibition by organophosphorus compounds leads to elevation of brain 2-arachidonoylglycerol and the associated hypomotility in mice
Toxicol. Appl. Pharmacol.
211
78-83
2006
Mus musculus
Muccioli, G.G.; Xu, C.; Odah, E.; Cudaback, E.; Cisneros, J.A.; Lambert, D.M.; Lopez Rodriguez, M.L.; Bajjalieh, S.; Stella, N.
Identification of a novel endocannabinoid-hydrolyzing enzyme expressed by microglial cells
J. Neurosci.
27
2883-2889
2007
Mus musculus
Wei, B.Q.; Mikkelsen, T.S.; McKinney, M.K.; Lander, E.S.; Cravatt, B.F.
A second fatty acid amide hydrolase with variable distribution among placental mammals
J. Biol. Chem.
281
36569-36578
2006
Homo sapiens (O00519), Homo sapiens (Q6GMR7), Homo sapiens, Mus musculus (O08914), Mus musculus, Rattus norvegicus (P97612)
Fowler, C.J.; Jonsson, K.O.; Tiger, G.
Fatty acid amide hydrolase: biochemistry, pharmacology, and therapeutic possibilities for an enzyme hydrolyzing anandamide, 2-arachidonoylglycerol, palmitoylethanolamide, and oleamide
Biochem. Pharmacol.
62
517-26
2001
Homo sapiens, Mus musculus, Rattus norvegicus, Sus scrofa
Giang, D.K.; Cravatt, B.F.
Molecular characterization of human and mouse fatty acid amide hydrolases
Proc. Natl. Acad. Sci. USA
94
2238-2242
1997
Rattus norvegicus, Homo sapiens (O00519), Homo sapiens, Mus musculus (O08914), Mus musculus
Quistad, G.B.; Sparks, S.E.; Casida, J.E.
Fatty acid amide hydrolase inhibition by neurotoxic organophosphorus pesticides
Toxicol. Appl. Pharmacol.
173
48-55
2001
Mus musculus
Wyffels, L.; Muccioli, G.G.; De Bruyne, S.; Moerman, L.; Sambre, J.; Lambert, D.M.; De Vos, F.
Synthesis, in vitro and in vivo evaluation, and radiolabeling of aryl anandamide analogues as candidate radioligands for in vivo imaging of fatty acid amide hydrolase in the brain
J. Med. Chem.
52
4613-4622
2009
Mus musculus
Naidu, P.S.; Kinsey, S.G.; Guo, T.L.; Cravatt, B.F.; Lichtman, A.H.
Regulation of inflammatory pain by inhibition of fatty acid amide hydrolase
J. Pharmacol. Exp. Ther.
334
182-190
2010
Mus musculus
Glaser, S.T.; Kaczocha, M.
Temporal changes in mouse brain fatty acid amide hydrolase activity
Neuroscience
163
594-600
2009
Mus musculus
Strittmatter, F.; Gandaglia, G.; Benigni, F.; Bettiga, A.; Rigatti, P.; Montorsi, F.; Gratzke, C.; Stief, C.; Colciago, G.; Hedlund, P.
Expression of fatty acid amide hydrolase (FAAH) in human, mouse, and rat urinary bladder and effects of FAAH inhibition on bladder function in awake rats
Eur. Urol.
61
98-106
2012
Homo sapiens, Mus musculus, Rattus norvegicus, Rattus norvegicus Sprague-Dawley
Mukhopadhyay, P.; Horvath, B.; Rajesh, M.; Matsumoto, S.; Saito, K.; Batkai, S.; Patel, V.; Tanchian, G.; Gao, R.Y.; Cravatt, B.F.; Hasko, G.; Pacher, P.
Fatty acid amide hydrolase is a key regulator of endocannabinoid-induced myocardial tissue injury
Free Radic. Biol. Med.
50
179-195
2011
Homo sapiens, Mus musculus, Mus musculus C57/BL6J
Long, J.Z.; LaCava, M.; Jin, X.; Cravatt, B.F.
An anatomical and temporal portrait of physiological substrates for fatty acid amide hydrolase
J. Lipid Res.
52
337-344
2011
Mus musculus
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