<i>N</i>-Acylethanolamine turnover | Enzymes | IUPHAR/BPS Guide to PHARMACOLOGY

N-Acylethanolamine turnover C

Unless otherwise stated all data on this page refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).

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Enzymes

NAPE-PLD (N-Acylphosphatidylethanolamine-phospholipase D) C Show summary »« Hide summary

Target Id	1398
Nomenclature	N-Acylphosphatidylethanolamine-phospholipase D
Common abbreviation	NAPE-PLD
Previous and unofficial names	chromosome 7 open reading frame 18, N-acyl-phosphatidylethanolamine-hydrolyzing phospholipase D \| FMP30
Genes	NAPEPLD (Hs), Napepld (Mm), Napepld (Rn)
Ensembl ID	ENSG00000161048 (Hs), ENSMUSG00000044968 (Mm), ENSRNOG00000011363 (Rn)
UniProtKB AC	Q6IQ20 (Hs), Q8BH82 (Mm), Q769K2 (Rn)
Comment	NAPE-PLD activity appears to be enhanced by polyamines in the physiological range [5], but fails to transphosphatidylate with alcohols [6] unlike phosphatidylcholine-specific phospholipase D.

FAAH (Fatty acid amide hydrolase) C Show summary »« Hide summary More detailed page

Target Id

1400

Nomenclature

Fatty acid amide hydrolase

Common abbreviation

FAAH

Previous and unofficial names

FAAH1 | Oleamide hydrolase, anandamide hydrolase | anandamide amidohydrolase 1

Genes

FAAH (Hs), Faah (Mm), Faah (Rn)

Ensembl ID

ENSG00000117480 (Hs), ENSMUSG00000034171 (Mm), ENSRNOG00000011019 (Rn)

UniProtKB AC

O00519 (Hs), O08914 (Mm), P97612 (Rn)

EC number

3.5.1.99	anandamide + H₂O <=> arachidonic acid + ethanolamine oleamide + H₂O <=> oleic acid + NH₃
The enzyme is responsible for the catabolism of neuromodulatory fatty acid amides, including anandamide and oleamide anandamide + H₂O <=> arachidonic acid + ethanolamine oleamide + H₂O <=> oleic acid + NH₃

Rank order of affinity

anandamide > oleamide > N-oleoylethanolamide > N-palmitoylethanolamine [12]

Selective inhibitors

JNJ1661010 pIC₅₀ 7.8 [4]

OL135 pIC₅₀ 7.4 [12]

PF750 pIC₅₀ 6.3 – 7.8 [1]

URB597 pIC₅₀ 6.3 – 7.0 [12]

PF3845 pIC₅₀ 6.6 [2]

FAAH2 (Fatty acid amide hydrolase-2) C Show summary »« Hide summary More detailed page

Target Id

1401

Nomenclature

Fatty acid amide hydrolase-2

Common abbreviation

FAAH2

Previous and unofficial names

AMDD | FAAH-2

Genes

FAAH2 (Hs)

Ensembl ID

ENSG00000165591 (Hs)

UniProtKB AC

Q6GMR7 (Hs)

EC number

3.5.1.99	anandamide + H₂O <=> arachidonic acid + ethanolamine oleamide + H₂O <=> oleic acid + NH₃
The enzyme is responsible for the catabolism of neuromodulatory fatty acid amides, including anandamide and oleamide anandamide + H₂O <=> arachidonic acid + ethanolamine oleamide + H₂O <=> oleic acid + NH₃

Rank order of affinity

oleamide > N-oleoylethanolamide > anandamide > N-palmitoylethanolamine [12]

Inhibitors

LY2077855 pIC₅₀ 8.5 [3]

JNJ1661010 pIC₅₀ 5.2 [3]

Selective inhibitors

OL135 pIC₅₀ 7.9 – 8.4 [3,12]

URB597 pIC₅₀ 7.5 – 8.3 [3,12]

Comment

The FAAH2 gene is found in many primate genomes, marsupials, and other distantly related vertebrates, but not a variety of lower placental mammals, including mouse and rat [12].

NAAA (N-Acylethanolamine acid amidase) C Show summary »« Hide summary More detailed page

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References

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1. Ahn K, Johnson DS, Fitzgerald LR, Liimatta M, Arendse A, Stevenson T, Lund ET, Nugent RA, Nomanbhoy TK, Alexander JP et al.. (2007) Novel mechanistic class of fatty acid amide hydrolase inhibitors with remarkable selectivity. Biochemistry, 46 (45): 13019-30. [PMID:17949010]

2. Ahn K, Johnson DS, Mileni M, Beidler D, Long JZ, McKinney MK, Weerapana E, Sadagopan N, Liimatta M, Smith SE et al.. (2009) Discovery and characterization of a highly selective FAAH inhibitor that reduces inflammatory pain. Chem. Biol., 16 (4): 411-20. [PMID:19389627]

3. Karbarz MJ, Luo L, Chang L, Tham CS, Palmer JA, Wilson SJ, Wennerholm ML, Brown SM, Scott BP, Apodaca RL et al.. (2009) Biochemical and biological properties of 4-(3-phenyl-[1,2,4] thiadiazol-5-yl)-piperazine-1-carboxylic acid phenylamide, a mechanism-based inhibitor of fatty acid amide hydrolase. Anesth. Analg., 108 (1): 316-29. [PMID:19095868]

4. Keith JM, Apodaca R, Xiao W, Seierstad M, Pattabiraman K, Wu J, Webb M, Karbarz MJ, Brown S, Wilson S et al.. (2008) Thiadiazolopiperazinyl ureas as inhibitors of fatty acid amide hydrolase. Bioorg. Med. Chem. Lett., 18 (17): 4838-43. [PMID:18693015]

5. Liu Q, Tonai T, Ueda N. (2002) Activation of N-acylethanolamine-releasing phospholipase D by polyamines. Chem. Phys. Lipids, 115 (1-2): 77-84. [PMID:12047899]

6. Petersen G, Hansen HS. (1999) N-acylphosphatidylethanolamine-hydrolysing phospholipase D lacks the ability to transphosphatidylate. FEBS Lett., 455 (1-2): 41-4. [PMID:10428468]

7. Ribeiro A, Pontis S, Mengatto L, Armirotti A, Chiurchiù V, Capurro V, Fiasella A, Nuzzi A, Romeo E, Moreno-Sanz G et al.. (2015) A Potent Systemically Active N-Acylethanolamine Acid Amidase Inhibitor that Suppresses Inflammation and Human Macrophage Activation. ACS Chem. Biol., 10 (8): 1838-46. [PMID:25874594]

8. Solorzano C, Zhu C, Battista N, Astarita G, Lodola A, Rivara S, Mor M, Russo R, Maccarrone M, Antonietti F et al.. (2009) Selective N-acylethanolamine-hydrolyzing acid amidase inhibition reveals a key role for endogenous palmitoylethanolamide in inflammation. Proc. Natl. Acad. Sci. U.S.A., 106 (49): 20966-71. [PMID:19926854]

9. Tsuboi K, Hilligsmann C, Vandevoorde S, Lambert DM, Ueda N. (2004) N-cyclohexanecarbonylpentadecylamine: a selective inhibitor of the acid amidase hydrolysing N-acylethanolamines, as a tool to distinguish acid amidase from fatty acid amide hydrolase. Biochem. J., 379 (Pt 1): 99-106. [PMID:14686878]

10. Tsuboi K, Ikematsu N, Uyama T, Deutsch DG, Tokumura A, Ueda N. (2013) Biosynthetic pathways of bioactive N-acylethanolamines in brain. CNS Neurol Disord Drug Targets, 12 (1): 7-16. [PMID:23394527]

11. Ueda N, Yamanaka K, Yamamoto S. (2001) Purification and characterization of an acid amidase selective for N-palmitoylethanolamine, a putative endogenous anti-inflammatory substance. J. Biol. Chem., 276 (38): 35552-7. [PMID:11463796]

12. Wei BQ, Mikkelsen TS, McKinney MK, Lander ES, Cravatt BF. (2006) A second fatty acid amide hydrolase with variable distribution among placental mammals. J. Biol. Chem., 281 (48): 36569-78. [PMID:17015445]

NC-IUPHAR subcommittee and family contributors

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How to cite this family page

Database page citation:

Stephen Alexander, Patrick Doherty, Christopher Fowler. N-Acylethanolamine turnover. Accessed on 12/07/2017. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=273.

Concise Guide to PHARMACOLOGY citation:

Alexander SPH, Fabbro D, Kelly E, Marrion N, Peters JA, Benson HE, Faccenda E, Pawson AJ, Sharman JL, Southan C, Davies JA and CGTP Collaborators (2015) The Concise Guide to PHARMACOLOGY 2015/16: Enzymes. Br J Pharmacol. 172: 6024-6109.