2-Acylglycerol ester turnover | Enzymes | IUPHAR/BPS Guide to PHARMACOLOGY

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Endocannabinoid turnover
2-Acylglycerol ester turnover

2-Acylglycerol ester 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).

Enzymes

DAGLα (Diacylglycerol lipase α) C Show summary »« Hide summary More detailed page

Target Id

1396

Nomenclature

Diacylglycerol lipase α

Common abbreviation

DAGLα

Previous and unofficial names

Genes

DAGLA (Hs), Dagla (Mm), Dagla (Rn)

Ensembl ID

ENSG00000134780 (Hs), ENSMUSG00000035735 (Mm), ENSRNOG00000027264 (Rn)

UniProtKB AC

Q9Y4D2 (Hs), Q6WQJ1 (Mm), Q5YLM1 (Rn)

EC number

3.1.1.-

Endogenous substrates

diacylglycerol

Selective inhibitors

orlistat pIC₅₀ 7.2 [3]

RHC80267 pIC₅₀ 4.2 [6]

DAGLβ (Diacylglycerol lipase β) C Show summary »« Hide summary More detailed page

Target Id

1397

Nomenclature

Diacylglycerol lipase β

Common abbreviation

DAGLβ

Previous and unofficial names

Genes

DAGLB (Hs), Daglb (Mm), Daglb (Rn)

Ensembl ID

ENSG00000164535 (Hs), ENSMUSG00000039206 (Mm), ENSRNOG00000001079 (Rn)

UniProtKB AC

Q8NCG7 (Hs), Q91WC9 (Mm), P0C1S9 (Rn)

EC number

3.1.1.-

Endogenous substrates

diacylglycerol

Selective inhibitors

orlistat pIC₅₀ 7.0 [3]

RHC80267

MAGL (Monoacylglycerol lipase) C Show summary »« Hide summary More detailed page

ABHD6 (αβ-Hydrolase 6) C Show summary »« Hide summary More detailed page

Target Id

2919

Nomenclature

αβ-Hydrolase 6

Common abbreviation

ABHD6

Previous and unofficial names

2-arachidonoylglycerol hydrolase | abhydrolase domain-containing protein 6 | alpha/beta-Hydrolase domain containing 6

Genes

ABHD6 (Hs), Abhd6 (Mm), Abhd6 (Rn)

Ensembl ID

ENSG00000163686 (Hs), ENSMUSG00000025277 (Mm), ENSRNOG00000008167 (Rn)

UniProtKB AC

Q9BV23 (Hs), Q8R2Y0 (Mm), Q5XI64 (Rn)

EC number

3.1.1.23

Endogenous substrates

1-arachidonoylglycerol > 2-arachidonoylglycerol > 1-oleoylglycerol > 2-oleoyl glycerol [9]

Selective inhibitors

WWL70 pIC₅₀ 7.2 [7]

WWL123 pIC₅₀ 6.4 [2]

Comment

WWL70 has also been suggested to have activity at oxidative metabolic pathways independent of ABHD6 [11].

References

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1. Aaltonen N, Savinainen JR, Ribas CR, Rönkkö J, Kuusisto A, Korhonen J, Navia-Paldanius D, Häyrinen J, Takabe P, Käsnänen H et al.. (2013) Piperazine and piperidine triazole ureas as ultrapotent and highly selective inhibitors of monoacylglycerol lipase. Chem. Biol., 20 (3): 379-90. [PMID:23521796]

2. Bachovchin DA, Ji T, Li W, Simon GM, Blankman JL, Adibekian A, Hoover H, Niessen S, Cravatt BF. (2010) Superfamily-wide portrait of serine hydrolase inhibition achieved by library-versus-library screening. Proc. Natl. Acad. Sci. U.S.A., 107 (49): 20941-6. [PMID:21084632]

3. Bisogno T, Howell F, Williams G, Minassi A, Cascio MG, Ligresti A, Matias I, Schiano-Moriello A, Paul P, Williams EJ et al.. (2003) Cloning of the first sn1-DAG lipases points to the spatial and temporal regulation of endocannabinoid signaling in the brain. J. Cell Biol., 163 (3): 463-8. [PMID:14610053]

4. Chang JW, Niphakis MJ, Lum KM, Cognetta 3rd AB, Wang C, Matthews ML, Niessen S, Buczynski MW, Parsons LH, Cravatt BF. (2012) Highly selective inhibitors of monoacylglycerol lipase bearing a reactive group that is bioisosteric with endocannabinoid substrates. Chem. Biol., 19 (5): 579-88. [PMID:22542104]

5. Ghafouri N, Tiger G, Razdan RK, Mahadevan A, Pertwee RG, Martin BR, Fowler CJ. (2004) Inhibition of monoacylglycerol lipase and fatty acid amide hydrolase by analogues of 2-arachidonoylglycerol. Br. J. Pharmacol., 143 (6): 774-84. [PMID:15492019]

6. Johnston M, Bhatt SR, Sikka S, Mercier RW, West JM, Makriyannis A, Gatley SJ, Duclos Jr RI. (2012) Assay and inhibition of diacylglycerol lipase activity. Bioorg. Med. Chem. Lett., 22 (14): 4585-92. [PMID:22738638]

7. Li W, Blankman JL, Cravatt BF. (2007) A functional proteomic strategy to discover inhibitors for uncharacterized hydrolases. J. Am. Chem. Soc., 129 (31): 9594-5. [PMID:17629278]

8. Long JZ, Li W, Booker L, Burston JJ, Kinsey SG, Schlosburg JE, Pavón FJ, Serrano AM, Selley DE, Parsons LH et al.. (2009) Selective blockade of 2-arachidonoylglycerol hydrolysis produces cannabinoid behavioral effects. Nat. Chem. Biol., 5 (1): 37-44. [PMID:19029917]

9. Navia-Paldanius D, Savinainen JR, Laitinen JT. (2012) Biochemical and pharmacological characterization of human α/β-hydrolase domain containing 6 (ABHD6) and 12 (ABHD12). J. Lipid Res., 53 (11): 2413-24. [PMID:22969151]

10. Niphakis MJ, Cognetta 3rd AB, Chang JW, Buczynski MW, Parsons LH, Byrne F, Burston JJ, Chapman V, Cravatt BF. (2013) Evaluation of NHS carbamates as a potent and selective class of endocannabinoid hydrolase inhibitors. ACS Chem Neurosci, 4 (9): 1322-32. [PMID:23731016]

11. Tanaka M, Moran S, Wen J, Affram K, Chen T, Symes AJ, Zhang Y. (2017) WWL70 attenuates PGE2 production derived from 2-arachidonoylglycerol in microglia by ABHD6-independent mechanism. J Neuroinflammation, 14 (1): 7. [PMID:28086912]

NC-IUPHAR subcommittee and family contributors

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How to cite this family page

Database page citation:

Stephen P.H. Alexander, Patrick Doherty, Christopher J. Fowler. 2-Acylglycerol ester turnover. Accessed on 23/02/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=944.

Concise Guide to PHARMACOLOGY citation:

Alexander SPH, Fabbro D, Kelly E, Marrion NV, Peters JA, Faccenda E, Harding SD, Pawson AJ, Sharman JL, Southan C, Davies JA; CGTP Collaborators. (2017) The Concise Guide to PHARMACOLOGY 2017/18: Enzymes. Br J Pharmacol. 174 Suppl 1: S272-S359.