Hydrolases 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).
Overview
Listed in this section are hydrolases not accumulated in other parts of the Concise Guide, such as monoacylglycerol lipase and acetylcholinesterase. Pancreatic lipase is the predominant mechanism of fat digestion in the alimentary system; its inhibition is associated with decreased fat absorption. CES1 is present at lower levels in the gut than CES2 (P23141), but predominates in the liver, where it is responsible for the hydrolysis of many aliphatic, aromatic and steroid esters. Hormone-sensitive lipase is also a relatively non-selective esterase associated with steroid ester hydrolysis and triglyceride metabolism, particularly in adipose tissue. Endothelial lipase is secreted from endothelial cells and regulates circulating cholesterol in high density lipoproteins.
Enzymes
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DAGLα (Diacylglycerol lipase α)
C
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DAGLβ (Diacylglycerol lipase β)
C
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FAAH (Fatty acid amide hydrolase)
C
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MAGL (Monoacylglycerol lipase)
C
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sPLA2-2A
C
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PLA2-G7
C
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PLD2
C
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AChE (acetylcholinesterase (Cartwright blood group))
C
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Leukotriene A4 hydrolase
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BChE (butyrylcholinesterase)
C
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PNLIP (pancreatic lipase)
C
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LIPG (lipase G, endothelial type)
C
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CES1 (carboxylesterase 1)
C
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LIPE (lipase E, hormone sensitive type)
C
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NTPDase-1 (ectonucleoside triphosphate diphosphohydrolase 1 / CD39)
C
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NTPDase-2 (ectonucleoside triphosphate diphosphohydrolase 2 / CD39L1)
C
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Further reading
References
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. 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]
3. 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]
4. 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]
5. Blackie JA, Bloomer JC, Brown MJ, Cheng HY, Hammond B, Hickey DM, Ife RJ, Leach CA, Lewis VA, Macphee CH et al.. (2003) The identification of clinical candidate SB-480848: a potent inhibitor of lipoprotein-associated phospholipase A2. Bioorg. Med. Chem. Lett., 13 (6): 1067-70. [PMID:12643913]
6. Brunschweiger A, Iqbal J, Umbach F, Scheiff AB, Munkonda MN, Sévigny J, Knowles AF, Müller CE. (2008) Selective nucleoside triphosphate diphosphohydrolase-2 (NTPDase2) inhibitors: nucleotide mimetics derived from uridine-5'-carboxamide. J. Med. Chem., 51 (15): 4518-28. [PMID:18630897]
7. Bustanji Y, Issa A, Mohammed M, Hudaib M, Tawah, K, Alkhatib H, Almarsi I, Al-Khalidi B. (2010) Inhibition of hormone sensitive lipase and pancreatic lipase by Rosmarinus officinalis extract and selected phenolic constituents. Journal of Medicinal Plants Research, 4 (21): 2235-2242.
8. Butini S, Campiani G, Borriello M, Gemma S, Panico A, Persico M, Catalanotti B, Ros S, Brindisi M, Agnusdei M et al.. (2008) Exploiting protein fluctuations at the active-site gorge of human cholinesterases: further optimization of the design strategy to develop extremely potent inhibitors. J. Med. Chem., 51 (11): 3154-70. [PMID:18479118]
9. Cardozo MG, Iimura Y, Sugimoto H, Yamanishi Y, Hopfinger AJ. (1992) QSAR analyses of the substituted indanone and benzylpiperidine rings of a series of indanone-benzylpiperidine inhibitors of acetylcholinesterase. J. Med. Chem., 35 (3): 584-9. [PMID:1738151]
10. 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]
11. Clark JK, Cowley P, Muir AW, Palin R, Pow E, Prosser AB, Taylor R, Zhang MQ. (2002) Quaternary salts of E2020 analogues as acetylcholinesterase inhibitors for the reversal of neuromuscular block. Bioorg. Med. Chem. Lett., 12 (18): 2565-8. [PMID:12182861]
12. Galli A, Mori F, Benini L, Cacciarelli N. (1994) Acetylcholinesterase protection and the anti-diisopropylfluorophosphate efficacy of E2020. Eur. J. Pharmacol., 270 (2-3): 189-93. [PMID:8039548]
13. 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]
14. Giacobini E. (2003) Cholinesterases: new roles in brain function and in Alzheimer's disease. Neurochem. Res., 28 (3-4): 515-22. [PMID:12675140]
15. 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]
16. 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]
17. Lavieri RR, Scott SA, Selvy PE, Kim K, Jadhav S, Morrison RD, Daniels JS, Brown HA, Lindsley CW. (2010) Design, synthesis, and biological evaluation of halogenated N-(2-(4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-8-yl)ethyl)benzamides: discovery of an isoform-selective small molecule phospholipase D2 inhibitor. J. Med. Chem., 53 (18): 6706-19. [PMID:20735042]
18. 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]
19. Lopez I, Arnold RS, Lambeth JD. (1998) Cloning and initial characterization of a human phospholipase D2 (hPLD2). ADP-ribosylation factor regulates hPLD2. J. Biol. Chem., 273 (21): 12846-52. [PMID:9582313]
20. Luo W, Yu QS, Kulkarni SS, Parrish DA, Holloway HW, Tweedie D, Shafferman A, Lahiri DK, Brossi A, Greig NH. (2006) Inhibition of human acetyl- and butyrylcholinesterase by novel carbamates of (-)- and (+)-tetrahydrofurobenzofuran and methanobenzodioxepine. J. Med. Chem., 49 (7): 2174-85. [PMID:16570913]
21. Orning L, Krivi G, Fitzpatrick FA. (1991) Leukotriene A4 hydrolase. Inhibition by bestatin and intrinsic aminopeptidase activity establish its functional resemblance to metallohydrolase enzymes. J. Biol. Chem., 266 (3): 1375-8. [PMID:1846352]
22. Preininger AM, Henage LG, Oldham WM, Yoon EJ, Hamm HE, Brown HA. (2006) Direct modulation of phospholipase D activity by Gbetagamma. Mol. Pharmacol., 70 (1): 311-8. [PMID:16638972]
23. Sarri E, Pardo R, Fensome-Green A, Cockcroft S. (2003) Endogenous phospholipase D2 localizes to the plasma membrane of RBL-2H3 mast cells and can be distinguished from ADP ribosylation factor-stimulated phospholipase D1 activity by its specific sensitivity to oleic acid. Biochem. J., 369 (Pt 2): 319-29. [PMID:12374567]
24. 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]
25. Wilensky RL, Macphee CH. (2009) Lipoprotein-associated phospholipase A(2) and atherosclerosis. Curr. Opin. Lipidol., 20 (5): 415-20. [PMID:19667981]
NC-IUPHAR subcommittee and family contributors
Subcommittee members:
Anthony J Turner
David Fairlie
Christopher M Overall
Neil Rawlings
Christopher Southan |
How to cite this family page
Database page citation:
Hydrolases. Accessed on 12/07/2017. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=799.
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.
