Hydrolases & Lipases 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
|
AChE (acetylcholinesterase (Yt blood group))
C
Show summary »« Hide summary
More detailed page
|
|||||||||||||||||||||||||||||||||
|
BChE (butyrylcholinesterase)
C
Show summary »« Hide summary
More detailed page
|
|||||||||||||||||||||||||||||||||
|
DAGLα (diacylglycerol lipase α)
C
Show summary »« Hide summary
More detailed page
|
|||||||||||||||||||||||||||||||||
|
DAGLβ (diacylglycerol lipase β)
C
Show summary »« Hide summary
More detailed page
|
|||||||||||||||||||||||||||||||||
|
CES1 (carboxylesterase 1)
C
Show summary »« Hide summary
More detailed page
|
|||||||||||||||||||||||||||||||||
|
NTPDase-1 (ectonucleoside triphosphate diphosphohydrolase 1 / CD39)
C
Show summary »« Hide summary
More detailed page
|
|||||||||||||||||||||||||||||||||
|
NTPDase-2 (ectonucleoside triphosphate diphosphohydrolase 2 / CD39L1)
C
Show summary »« Hide summary
More detailed page
|
|||||||||||||||||||||||||||||||||
|
epoxide hydrolase 2
Show summary »« Hide summary
More detailed page
|
|||||||||||||||||||||||||||||||||
|
FAAH (Fatty acid amide hydrolase)
C
Show summary »« Hide summary
More detailed page
|
|||||||||||||||||||||||||||||||||
|
Leukotriene A4 hydrolase
C
Show summary »« Hide summary
More detailed page
|
|||||||||||||||||||||||||||||||||
|
LIPE (lipase E, hormone sensitive type)
C
Show summary »« Hide summary
More detailed page
|
|||||||||||||||||||||||||||||||||
|
LIPG (lipase G, endothelial type)
C
Show summary »« Hide summary
More detailed page
|
|||||||||||||||||||||||||||||||||
|
lysophospholipase 1 Show summary »« Hide summary
|
|||||||||||||||||||||||||||||||||
|
lysophospholipase 2 Show summary »« Hide summary
|
|||||||||||||||||||||||||||||||||
|
MAGL (monoacylglycerol lipase)
C
Show summary »« Hide summary
More detailed page
|
|||||||||||||||||||||||||||||||||
|
nudix hydrolase 7
Show summary »« Hide summary
More detailed page
|
|||||||||||||||||||||||||||||||||
|
neuraminidase 1 Show summary »« Hide summary
|
|||||||||||||||||||||||||||||||||
|
neuraminidase 2 Show summary »« Hide summary
|
|||||||||||||||||||||||||||||||||
|
O-GlcNAcase
Show summary »« Hide summary
More detailed page
|
|||||||||||||||||||||||||||||||||
|
PNLIP (pancreatic lipase)
C
Show summary »« Hide summary
More detailed page
|
|||||||||||||||||||||||||||||||||
|
patatin like phospholipase domain containing 2 Show summary »« Hide summary
|
|||||||||||||||||||||||||||||||||
|
PLA2-G7
Show summary »« Hide summary
More detailed page
|
|||||||||||||||||||||||||||||||||
|
sPLA2-2A
Show summary »« Hide summary
More detailed page
|
|||||||||||||||||||||||||||||||||
|
PLD2
C
Show summary »« Hide summary
More detailed page
|
|||||||||||||||||||||||||||||||||
|
vanin 1
Show summary »« Hide summary
More detailed page
|
|||||||||||||||||||||||||||||||||
Further reading
* Key recommended reading is highlighted with an asterisk
Allard B, Longhi MS, Robson SC, Stagg J. (2017) The ectonucleotidases CD39 and CD73: Novel checkpoint inhibitor targets. Immunol Rev, 276 (1): 121-144. [PMID:28258700]
* Coleman RA. (2020) The "discovery" of lipid droplets: A brief history of organelles hidden in plain sight. Biochim Biophys Acta Mol Cell Biol Lipids, 1865 (9): 158762. DOI: 10.1016/j.bbalip.2020.158762 [PMID:32622088]
* Haas CB, Lovászi M, Braganhol E, Pacher P, Haskó G. (2021) Ectonucleotidases in Inflammation, Immunity, and Cancer. J Immunol, 206 (9): 1983-1990. [PMID:33879578]
* Kishore BK, Robson SC, Dwyer KM. (2018) CD39-adenosinergic axis in renal pathophysiology and therapeutics. Purinergic Signal, 14 (2): 109-120. [PMID:29332180]
* Lan L, Ren X, Yang J, Liu D, Zhang C. (2020) Detection techniques of carboxylesterase activity: An update review. Bioorg Chem, 94: 103388. [PMID:31676115]
Markey GM. (2011) Carboxylesterase 1 (Ces1): from monocyte marker to major player. J Clin Pathol, 64 (2): 107-9. [PMID:21177752]
Rasmussen HB, Madsen MB, INDICES Consortium. (2018) Carboxylesterase 1 genes: systematic review and evaluation of existing genotyping procedures. Drug Metab Pers Ther, 33 (1): 3-14. [PMID:29427553]
Takenaka MC, Robson S, Quintana FJ. (2016) Regulation of the T Cell Response by CD39. Trends Immunol, 37 (7): 427-439. [PMID:27236363]
* Zimmermann H. (2021) Ectonucleoside triphosphate diphosphohydrolases and ecto-5'-nucleotidase in purinergic signaling: how the field developed and where we are now. Purinergic Signal, 17 (1): 117-125. [PMID:33336318]
* Zou LW, Jin Q, Wang DD, Qian QK, Hao DC, Ge GB, Yang L. (2018) Carboxylesterase Inhibitors: An Update. Curr Med Chem, 25 (14): 1627-1649. [PMID:29210644]
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. Baek YB, Kwon HJ, Sharif M, Lim J, Lee IC, Ryu YB, Lee JI, Kim JS, Lee YS, Kim DH et al.. (2022) Therapeutic strategy targeting host lipolysis limits infection by SARS-CoV-2 and influenza A virus. Signal Transduct Target Ther, 7 (1): 367. [PMID:36253361]
5. Baggelaar MP, Chameau PJ, Kantae V, Hummel J, Hsu KL, Janssen F, van der Wel T, Soethoudt M, Deng H, den Dulk H et al.. (2015) Highly Selective, Reversible Inhibitor Identified by Comparative Chemoproteomics Modulates Diacylglycerol Lipase Activity in Neurons. J Am Chem Soc, 137 (27): 8851-7. [PMID:26083464]
6. 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]
7. Blocher R, Lamers C, Wittmann SK, Diehl O, Hanke T, Merk D, Steinhilber D, Schubert-Zsilavecz M, Kahnt AS, Proschak E. (2016) Design and synthesis of fused soluble epoxide hydrolase/peroxisome proliferator-activated receptor modulators. Medchemcomm, 7: 1209-1216. DOI: 10.1039/C6MD00042H
8. Boersma YL, Newman J, Adams TE, Cowieson N, Krippner G, Bozaoglu K, Peat TS. (2014) The structure of vanin 1: a key enzyme linking metabolic disease and inflammation. Acta Crystallogr D Biol Crystallogr, 70 (Pt 12): 3320-9. [PMID:25478849]
9. 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]
10. 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.
11. 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]
12. 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]
13. 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]
14. 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]
15. Dasgupta A, Gangai S, Narayan R, Kapoor S. (2023) Mapping the Lipid Signatures in COVID-19 Infection: Diagnostic and Therapeutic Solutions. J Med Chem, 66 (21): 14411-14433. [PMID:37899546]
16. Davda D, Martin BR. (2014) Acyl protein thioesterase inhibitors as probes of dynamic S-palmitoylation. Medchemcomm, 5 (3): 268-276. [PMID:25558349]
17. de Jong JC, Sørensen LG, Tornqvist H, Jacobsen P. (2004) Carbazates as potent inhibitors of hormone-sensitive lipase. Bioorg Med Chem Lett, 14 (7): 1741-4. [PMID:15026062]
18. 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]
19. 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]
20. Giacobini E. (2003) Cholinesterases: new roles in brain function and in Alzheimer's disease. Neurochem Res, 28 (3-4): 515-22. [PMID:12675140]
21. Goodman KB, Bury MJ, Cheung M, Cichy-Knight MA, Dowdell SE, Dunn AK, Lee D, Lieby JA, Moore ML, Scherzer DA et al.. (2009) Discovery of potent, selective sulfonylfuran urea endothelial lipase inhibitors. Bioorg Med Chem Lett, 19 (1): 27-30. [PMID:19058966]
22. Granchi C, Rizzolio F, Bordoni V, Caligiuri I, Manera C, Macchia M, Minutolo F, Martinelli A, Giordano A, Tuccinardi T. (2016) 4-Aryliden-2-methyloxazol-5(4H)-one as a new scaffold for selective reversible MAGL inhibitors. J Enzyme Inhib Med Chem, 31 (1): 137-46. [PMID:25669350]
23. Guo T, Héon-Roberts R, Zou C, Zheng R, Pshezhetsky AV, Cairo CW. (2018) Selective Inhibitors of Human Neuraminidase 1 (NEU1). J Med Chem, 61 (24): 11261-11279. [PMID:30457869]
24. Habib AM, Okorokov AL, Hill MN, Bras JT, Lee MC, Li S, Gossage SJ, van Drimmelen M, Morena M, Houlden H et al.. (2019) Microdeletion in a FAAH pseudogene identified in a patient with high anandamide concentrations and pain insensitivity. Br J Anaesth, 123 (2): e249-e253. DOI: 10.1016/j.bja.2019.02.019 [PMID:30929760]
25. Hsu KL, Tsuboi K, Adibekian A, Pugh H, Masuda K, Cravatt BF. (2012) DAGLβ inhibition perturbs a lipid network involved in macrophage inflammatory responses. Nat Chem Biol, 8 (12): 999-1007. [PMID:23103940]
26. Jin W, Millar JS, Broedl U, Glick JM, Rader DJ. (2003) Inhibition of endothelial lipase causes increased HDL cholesterol levels in vivo. J Clin Invest, 111 (3): 357-62. [PMID:12569161]
27. 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]
28. 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]
29. 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]
30. 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]
31. 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]
32. Mayer N, Schweiger M, Romauch M, Grabner GF, Eichmann TO, Fuchs E, Ivkovic J, Heier C, Mrak I, Lass A et al.. (2013) Development of small-molecule inhibitors targeting adipose triglyceride lipase. Nat Chem Biol, 9 (12): 785-7. [PMID:24096302]
33. 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]
34. Ogasawara D, Deng H, Viader A, Baggelaar MP, Breman A, den Dulk H, van den Nieuwendijk AM, van den Nieuwendijk AM, Soethoudt M, van der Wel T et al.. (2016) Rapid and profound rewiring of brain lipid signaling networks by acute diacylglycerol lipase inhibition. Proc Natl Acad Sci USA, 113 (1): 26-33. [PMID:26668358]
35. 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]
36. 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]
37. 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]
38. Sun S, Dean R, Jia Q, Zenova A, Zhong J, Grayson C, Xie C, Lindgren A, Samra P, Sojo L et al.. (2013) Discovery of XEN445: a potent and selective endothelial lipase inhibitor raises plasma HDL-cholesterol concentration in mice. Bioorg Med Chem, 21 (24): 7724-34. [PMID:24211162]
39. Watabiki T, Tsuji N, Kiso T, Ozawa T, Narazaki F, Kakimoto S. (2017) In vitro and in vivo pharmacological characterization of ASP8477: A novel highly selective fatty acid amide hydrolase inhibitor. Eur J Pharmacol, 815: 42-48. [PMID:29017758]
40. 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]
41. Wilensky RL, Macphee CH. (2009) Lipoprotein-associated phospholipase A(2) and atherosclerosis. Curr Opin Lipidol, 20 (5): 415-20. [PMID:19667981]
42. Won SJ, Eschweiler JD, Majmudar JD, Chong FS, Hwang SY, Ruotolo BT, Martin BR. (2017) Affinity-Based Selectivity Profiling of an In-Class Selective Competitive Inhibitor of Acyl Protein Thioesterase 2. ACS Med Chem Lett, 8 (2): 215-220. [PMID:28197315]
43. Wyatt RM, Fraser I, Welty N, Lord B, Wennerholm M, Sutton S, Ameriks MK, Dugovic C, Yun S, White A et al.. (2020) Pharmacologic Characterization of JNJ-42226314, [1-(4-Fluorophenyl)indol-5-yl]-[3-[4-(thiazole-2-carbonyl)piperazin-1-yl]azetidin-1-yl]methanone, a Reversible, Selective, and Potent Monoacylglycerol Lipase Inhibitor. J Pharmacol Exp Ther, 372 (3): 339-353. [PMID:31818916]
44. Yamada Y, Kato T, Ogino H, Ashina S, Kato K. (2008) Cetilistat (ATL-962), a Novel Pancreatic Lipase Inhibitor, Ameliorates Body Weight Gain and Improves Lipid Profiles in Rats. Horm Metab Res, 40 (8): 539-543. DOI: 10.1055/s-2008-1076699
NC-IUPHAR subcommittee and family contributors
Subcommittee members:
Anthony J. Turner
David Fairlie
Christopher M. Overall
Neil Rawlings
Christopher Southan |
Other contributors:
Stephen P.H. Alexander
Patrick Doherty
Christopher J. Fowler |
How to cite this family page
Database page citation (select format):
Concise Guide to PHARMACOLOGY citation:
Alexander SPH, Fabbro D, Kelly E, Mathie AA, Peters JA, Veale EL, Armstrong JF, Faccenda E, Harding SD, Davies JA et al. (2023) The Concise Guide to PHARMACOLOGY 2023/24: Enzymes. Br J Pharmacol. 180 Suppl 2:S289-373.
