Acetylcholinesterase

File:AChe mechanism of action.jpg

AChE is a hydrolase that hydrolyzes choline esters. It has a very high catalytic activity—each molecule of AChE degrades about 5,000 molecules of acetylcholine (ACh) per second,{{Cite book | vauthors = Purves D, Augustine GJ, Fitzpatrick D, Katz LC, LaMantia AS, McNamara JO, Williams SM |url=https://www.ncbi.nlm.nih.gov/books/NBK10799/ |title=Neuroscience |publisher=Sinauer Associates |year=2001 |isbn=978-0-87893-697-7 |edition=2nd |location=Sunderland (MA) | chapter = Chapter 6. Neurotransmitters: Acetylcholine |language=en }} approaching the limit allowed by diffusion of the substrate.{{cite journal | vauthors = Quinn DM | title = Acetylcholinesterase: enzyme structure, reaction dynamics, and virtual transition states | journal = Chemical Reviews | volume = 87 | issue = 5| pages = 955–79 | year = 1987 | doi = 10.1021/cr00081a005 }}{{cite journal | vauthors = Taylor P, Radić Z | title = The cholinesterases: from genes to proteins | journal = Annual Review of Pharmacology and Toxicology | volume = 34 | pages = 281–320 | year = 1994 | pmid = 8042853 | doi = 10.1146/annurev.pa.34.040194.001433 }} The active site of AChE comprises two subsites—the anionic site and the esteratic subsite. The structure and mechanism of action of AChE have been elucidated from the crystal structure of the enzyme.{{cite journal | vauthors = Sussman JL, Harel M, Frolow F, Oefner C, Goldman A, Toker L, Silman I | title = Atomic structure of acetylcholinesterase from Torpedo californica: a prototypic acetylcholine-binding protein | journal = Science | volume = 253 | issue = 5022 | pages = 872–9 | date = August 1991 | pmid = 1678899 | doi = 10.1126/science.1678899 | bibcode = 1991Sci...253..872S | s2cid = 28833513 }}{{cite journal | vauthors = Sussman JL, Harel M, Silman I | title = Three-dimensional structure of acetylcholinesterase and of its complexes with anticholinesterase drugs | journal = Chem. Biol. Interact. | volume = 87 | issue = 1–3 | pages = 187–97 | date = June 1993 | pmid = 8343975 | doi = 10.1016/0009-2797(93)90042-W | bibcode = 1993CBI....87..187S }}

The anionic subsite accommodates the positive quaternary amine of acetylcholine as well as other cationic substrates and inhibitors. The cationic substrates are not bound by a negatively charged amino acid in the anionic site, but by interaction of 14 aromatic residues that line a gorge leading to the active site.{{cite journal | vauthors = Radić Z, Gibney G, Kawamoto S, MacPhee-Quigley K, Bongiorno C, Taylor P | title = Expression of recombinant acetylcholinesterase in a baculovirus system: kinetic properties of glutamate 199 mutants | journal = Biochemistry | volume = 31 | issue = 40 | pages = 9760–7 | date = October 1992 | pmid = 1356436 | doi = 10.1021/bi00155a032 }}{{cite journal | vauthors = Ordentlich A, Barak D, Kronman C, Ariel N, Segall Y, Velan B, Shafferman A | title = Contribution of aromatic moieties of tyrosine 133 and of the anionic subsite tryptophan 86 to catalytic efficiency and allosteric modulation of acetylcholinesterase | journal = J. Biol. Chem. | volume = 270 | issue = 5 | pages = 2082–91 | date = February 1995 | pmid = 7836436 | doi = 10.1074/jbc.270.5.2082 | doi-access = free }}{{cite journal | vauthors = Ariel N, Ordentlich A, Barak D, Bino T, Velan B, Shafferman A | title = The 'aromatic patch' of three proximal residues in the human acetylcholinesterase active centre allows for versatile interaction modes with inhibitors | journal = Biochem. J. | volume = 335 | issue = 1 | pages = 95–102 | date = October 1998 | pmid = 9742217 | pmc = 1219756 | doi = 10.1042/bj3350095 }} {{open access}} All 14 amino acids in the aromatic gorge are highly conserved across different species.{{cite journal | vauthors = Ordentlich A, Barak D, Kronman C, Flashner Y, Leitner M, Segall Y, Ariel N, Cohen S, Velan B, Shafferman A | title = Dissection of the human acetylcholinesterase active center determinants of substrate specificity. Identification of residues constituting the anionic site, the hydrophobic site, and the acyl pocket | journal = J. Biol. Chem. | volume = 268 | issue = 23 | pages = 17083–95 | date = August 1993 | doi = 10.1016/S0021-9258(19)85305-X | pmid = 8349597 | doi-access = free }} {{open access}} Among the aromatic amino acids, tryptophan 84 is critical and its substitution with alanine results in a 3000-fold decrease in reactivity.{{cite journal | vauthors = Tougu V | title = Acetylcholinesterase: Mechanism of Catalysis and Inhibition | journal = Current Medicinal Chemistry - Central Nervous System Agents| volume = 1 | issue = 2| pages = 155–170 | year = 2001 | doi = 10.2174/1568015013358536 |url = https://www.researchgate.net/publication/233701777}} {{closed access}} The gorge is approximately 20 angstroms deep and five angstroms wide.{{cite journal | vauthors=Cheng S, Song W, Yuan X, Xu Y | title=Gorge Motions of Acetylcholinesterase Revealed by Microsecond Molecular Dynamics Simulations | journal=Scientific Reports | volume=7 | issue=1 | pages=3219 | year=2017 | pmid=28607438 | pmc=5468367 | doi= 10.1038/s41598-017-03088-y | doi-access=free | bibcode=2017NatSR...7.3219C }}

The esteratic subsite, where acetylcholine is hydrolyzed to acetate and choline, contains the catalytic triad of three amino acids: serine 203, histidine 447 and glutamate 334. These three amino acids are similar to the triad in other serine proteases except that the glutamate is the third member rather than aspartate. Moreover, the triad is of opposite chirality to that of other proteases.{{cite journal | vauthors = Tripathi A | title = Acetylcholinsterase: A Versatile Enzyme of Nervous System | journal = Annals of Neurosciences | volume = 15 | issue = 4 | pages = 106–111|date=October 2008 | doi = 10.5214/ans.0972.7531.2008.150403}} The hydrolysis reaction of the carboxyl ester leads to the formation of an acyl-enzyme and free choline. Then, the acyl-enzyme undergoes nucleophilic attack by a water molecule, assisted by the histidine 440 group, liberating acetic acid and regenerating the free enzyme.{{cite journal | vauthors = Pauling L | title = Molecular Architecture and Biological Reactions | journal = Chemical & Engineering News | volume = 24 | issue = 10| pages = 1375–1377 | year = 1946 | doi = 10.1021/cen-v024n010.p1375| url = http://sgreports.nlm.nih.gov/ps/access/MMBBRM.pdf }}{{cite book | vauthors = Fersht A | title = Enzyme structure and mechanism|year=1985|publisher=W.H. Freeman|location=San Francisco|isbn= 0-7167-1614-3|pages=14}}

AChE is found in many biological species, including humans and other mammals, non-vertebrates, and plants.{{cite journal | url=https://link.springer.com/article/10.1007/s00344-023-11152-3 | doi=10.1007/s00344-023-11152-3 | title=Identification of Acetylcholinesterase Like Gene Family and Its Expression Under Salinity Stress in Solanum lycopersicum | date=2023 | journal=Journal of Plant Growth Regulation | s2cid=265016505 | vauthors = Sarangle Y, Bamel K, Purty RS | volume=43 | issue=3 | pages=940–960 | url-access=subscription }}{{cite journal | url=http://annalsofneurosciences.org/journal/index.php/annal/article/viewarticle/95/200 | title=Acetylcholinesterase :A Versatile Enzyme of Nervous System | journal=Annals of Neurosciences | date=January 2, 2010 | volume=15 | issue=4 | pages=106–111 | doi=10.5214/ans.0972.7531.2008.150403 | vauthors = Tripathi A, Srivastava UC | url-access=subscription }}{{cite journal | url=https://link.springer.com/article/10.1007/s10646-006-0075-3 | doi=10.1007/s10646-006-0075-3 | title=Acetylcholinesterase activities in marine snail (Cronia contracta) as a biomarker of neurotoxic contaminants along the Goa coast, West coast of India | date=2006 | journal=Ecotoxicology | volume=15 | issue=4 | pages=353–358 | pmid=16676216 | s2cid=25702252 | vauthors = Gaitonde D, Sarkar A, Kaisary S, Silva CD, Dias C, Rao DP, Ray D, Nagarajan R, De Sousa SN, Sarker S, Patill D | bibcode=2006Ecotx..15..353G | url-access=subscription }}{{cite journal | doi=10.1007/s42995-020-00065-9 | title=Acetylcholinesterase inhibitors and antioxidants mining from marine fungi: Bioassays, bioactivity coupled LC–MS/MS analyses and molecular networking | date=2020 | journal=Marine Life Science & Technology | volume=2 | issue=4 | pages=386–397 | vauthors = Nie Y, Yang W, Liu Y, Yang J, Lei X, Gerwick WH, Zhang Y | doi-access=free | bibcode=2020MLST....2..386N }}

In humans, AChE is a cholinergic enzyme involved in the hydrolysis of the neurotransmitter acetylcholine (ACh) into its constituents, choline, and acetate.

Overall, in mammals, AChE is primarily involved in the termination of impulse transmission at cholinergic synapses by rapid hydrolysis of the neurotransmitter acetylcholine. In non-vertebrates, AChE plays a similar role in nerve conduction processes at the neuromuscular junction. It is usually located in the membranes of these animals and controls ionic currents in excitable membranes.

In plants, the biological functions of AChE are less clear, and its existence has been recognized by indirect evidence of its activity. For instance, a study on Solanum lycopersicum (tomato) identified 87 SlAChE genes containing GDSL lipase/acylhydrolase domain. The study also showed up-and down-regulation of SlAChE genes under salinity stress condition.

Some marine fungi have been found to produce compounds that inhibit AChE. However, the specific role and mechanisms of AChE in fungi are not as well-studied as in mammals. The presence and role of AChE in bacteria is not well-documented.

During neurotransmission, ACh is released from the presynaptic neuron into the synaptic cleft and binds to ACh receptors on the post-synaptic membrane, relaying the signal from the nerve. AChE is concentrated in the synaptic cleft, where it terminates the signal transmission by hydrolyzing ACh. The liberated choline is taken up again by the pre-synaptic neuron and ACh is synthesized by combining with acetyl-CoA through the action of choline acetyltransferase.{{cite journal | vauthors = Whittaker VP | title = The Contribution of Drugs and Toxins to Understanding of Cholinergic Function | journal = Trends in Pharmacological Sciences | volume = 11 | issue = 1 | pages = 8–13 | year = 1990 | pmid = 2408211 | doi = 10.1016/0165-6147(90)90034-6 | url = http://pubman.mpdl.mpg.de/pubman/item/escidoc:603084/component/escidoc:2355598/603084.pdf | hdl = 11858/00-001M-0000-0013-0E8C-5 | hdl-access = free }}{{cite book | vauthors = Purves D, Augustine GJ, Fitzpatrick D, Hall WC, LaMantia AS, McNamara JO, White LE | title = Neuroscience | edition = 4th | year = 2008 | publisher = Sinauer Associates | isbn = 978-0-87893-697-7 | pages = 121–122 }}

A cholinomimetic drug disrupts this process by acting as a cholinergic neurotransmitter that is impervious to acetylcholinesterase's lysing action.{{citation needed|date=May 2024}}

{{main|Acetylcholinesterase inhibitor}}

Drugs or toxins that inhibit AChE lead to persistence of high concentrations of ACh within synapses, leading to increased cholinergic signaling within the central nervous system, autonomic ganglia and neuromuscular junctions.{{cite book | vauthors = English BA, Webster AA | title=Primer on the Autonomic Nervous System | chapter=Acetylcholinesterase and its Inhibitors | publisher=Elsevier | year=2012 | isbn=978-0-12-386525-0 | doi=10.1016/b978-0-12-386525-0.00132-3 | pages=631–633}}

File:AChe inhibitors pic.jpg

Irreversible inhibitors of AChE may lead to muscular paralysis, convulsions, bronchial constriction, and death by asphyxiation. Organophosphates (OP), esters of phosphoric acid, are a class of irreversible AChE inhibitors.{{cite web|title=National Pesticide Information Center-Diazinon Technical Fact Sheet|url=http://npic.orst.edu/factsheets/archive/diazinontech.pdf|access-date=February 24, 2012}} Cleavage of OP by AChE leaves a phosphoryl group in the esteratic site, which is slow to be hydrolyzed (on the order of days) and can become covalently bound. Irreversible AChE inhibitors have been used in insecticides (e.g., malathion) and nerve gases for chemical warfare (e.g., Sarin and VX). Carbamates, esters of N-methyl carbamic acid, are AChE inhibitors that hydrolyze in hours and have been used for medical purposes (e.g., physostigmine for the treatment of glaucoma). Reversible inhibitors occupy the esteratic site for short periods of time (seconds to minutes) and are used to treat of a range of central nervous system diseases. Tetrahydroaminoacridine (THA) and donepezil are FDA-approved to improve cognitive function in Alzheimer's disease. Rivastigmine is also used to treat Alzheimer's and Lewy body dementia, and pyridostigmine bromide is used to treat myasthenia gravis.{{cite web|title=Clinical Application: Acetylcholine and Alzheimer's Disease|url=http://web.williams.edu/imput/synapse/pages/IA5.html|access-date=February 24, 2012}}{{cite book|vauthors=Stoelting RK|title=Anticholinesterase Drugs and Cholinergic Agonists", in Pharmacology and Physiology in Anesthetic Practice|year=1999|publisher=Lippincott-Raven|isbn=978-0-7817-5469-9|url=http://www.anesthesia2000.com/Autonomics/Cholinergics/Cholin2.htm|access-date=February 26, 2012|archive-url=https://web.archive.org/web/20160303232519/http://www.anesthesia2000.com/Autonomics/Cholinergics/Cholin2.htm|archive-date=March 3, 2016|url-status=usurped}}{{cite book|vauthors=Taylor P, Hardman JG, Limbird LE, Molinoff PB, Ruddon RW, Gilman AG|title=The Pharmacologial Basis of Therapeutics|year=1996|publisher=THe McGraw-Hill Companies|isbn=978-0-07-146804-6|pages=161–174|chapter-url=http://nursingpharmacology.info/Autonomics/Cholinergics/Cholin1.htm|chapter=5: Autonomic Pharmacology: Cholinergic Drugs|access-date=February 26, 2012|archive-date=March 4, 2016|archive-url=https://web.archive.org/web/20160304043428/http://nursingpharmacology.info/Autonomics/Cholinergics/Cholin1.htm|url-status=dead}}{{cite book | vauthors = Blumenthal D, Brunton L, Goodman LS, Parker K, Gilman A, Lazo JS, Buxton I | title = Goodman & Gilman's The pharmacological basis of therapeutics | publisher = McGraw-Hill | location = New York | year = 1996 | pages = 1634 | isbn = 978-0-07-146804-6 | chapter=5: Autonomic Pharmacology: Cholinergic Drugs }}{{cite book|vauthors=Drachman DB, Isselbacher KJ, Braunwald E, Wilson JD, Martin JB, Fauci AS, Kasper DL|title=Harrison's Principles of Internal Medicine|year=1998|publisher=The McCraw-Hill Companies|isbn=978-0-07-020291-7|pages=[https://archive.org/details/harrisonsprincie14harr/page/2469 2469]–2472|edition=14|url-access=registration|url=https://archive.org/details/harrisonsprincie14harr}}{{cite book | vauthors = Raffe RB | title = Autonomic and Somatic Nervous Systems in Netter's Illustrated Pharmacology|publisher=Elsevier Health Science|isbn=978-1-929007-60-8|pages=43| year = 2004}}

An endogenous inhibitor of AChE in neurons is Mir-132 microRNA, which may limit inflammation in the brain by silencing the expression of this protein and allowing ACh to act in an anti-inflammatory capacity.{{cite journal | vauthors = Shaked I, Meerson A, Wolf Y, Avni R, Greenberg D, Gilboa-Geffen A, Soreq H | title = MicroRNA-132 potentiates cholinergic anti-inflammatory signaling by targeting acetylcholinesterase | journal = Immunity | volume = 31 | issue = 6 | pages = 965–73 | year = 2009 | pmid = 20005135 | doi = 10.1016/j.immuni.2009.09.019 | doi-access = free }}

It has also been shown that the main active ingredient in cannabis, tetrahydrocannabinol, is a competitive inhibitor of acetylcholinesterase.{{cite journal | vauthors = Eubanks LM, Rogers CJ, Beuscher AE, Koob GF, Olson AJ, Dickerson TJ, Janda KD | title = A molecular link between the active component of marijuana and Alzheimer's disease pathology | journal = Mol. Pharm. | volume = 3 | issue = 6 | pages = 773–7 | year = 2006 | pmid = 17140265 | pmc = 2562334 | doi = 10.1021/mp060066m }}

AChE is found in many types of conducting tissue: nerve and muscle, central and peripheral tissues, motor and sensory fibers, and cholinergic and noncholinergic fibers. The activity of AChE is higher in motor neurons than in sensory neurons.{{cite journal | vauthors = Massoulié J, Pezzementi L, Bon S, Krejci E, Vallette FM | title = Molecular and cellular biology of cholinesterases | journal = Progress in Neurobiology | volume = 41 | issue = 1 | pages = 31–91 | date = July 1993 | pmid = 8321908 | doi = 10.1016/0301-0082(93)90040-Y | s2cid = 21601586 }}{{cite journal | vauthors = Chacko LW, Cerf JA | title = Histochemical localization of cholinesterase in the amphibian spinal cord and alterations following ventral root section | journal = Journal of Anatomy | volume = 94 | issue = Pt 1 | pages = 74–81 | year = 1960 | pmid = 13808985 | pmc = 1244416 }}{{cite journal | vauthors = Koelle GB | title = The histochemical localization of cholinesterases in the central nervous system of the rat | journal = Journal of Comparative Neurology | volume = 100 | issue = 1 | pages = 211–35 | year = 1954 | pmid = 13130712 | doi = 10.1002/cne.901000108 | s2cid = 23021010 }}

Acetylcholinesterase is also found on the red blood cell membranes, where different forms constitute the Yt blood group antigens.{{cite journal | vauthors = Bartels CF, Zelinski T, Lockridge O | title = Mutation at codon 322 in the human acetylcholinesterase (ACHE) gene accounts for YT blood group polymorphism | journal = Am. J. Hum. Genet. | volume = 52 | issue = 5 | pages = 928–36 | date = May 1993 | pmid = 8488842 | pmc = 1682033 }} Acetylcholinesterase exists in multiple molecular forms, which possess similar catalytic properties, but differ in their oligomeric assembly and mode of attachment to the cell surface.{{citation needed|date=May 2024}}

In mammals, acetylcholinesterase is encoded by a single AChE gene while some invertebrates have multiple acetylcholinesterase genes. Note higher vertebrates also encode a closely related paralog BCHE (butyrylcholinesterase) with 50% amino acid identity to ACHE.{{cite journal | vauthors = Johnson G, Moore SW | year = 2012| title = Why has butyrylcholinesterase been retained? Structural and functional diversification in a duplicated gene. 2012 | journal = Neurochem. Int. | volume = 16 | issue = 5| pages = 783–797 | doi = 10.1016/j.neuint.2012.06.016 | pmid = 22750491| s2cid = 39348660}} Diversity in the transcribed products from the sole mammalian gene arises from alternative mRNA splicing and post-translational associations of catalytic and structural subunits. There are three known forms: T (tail), R (read through), and H (hydrophobic).{{cite journal | vauthors = Massoulié J, Perrier N, Noureddine H, Liang D, Bon S | title = Old and new questions about cholinesterases | journal = Chem. Biol. Interact. | volume = 175 | issue = 1–3 | pages = 30–44 | year = 2008 | pmid = 18541228 | doi = 10.1016/j.cbi.2008.04.039 | bibcode = 2008CBI...175...30M }}

The major form of acetylcholinesterase found in brain, muscle, and other tissues, known as is the hydrophilic species, which forms disulfide-linked oligomers with collagenous, or lipid-containing structural subunits. In the neuromuscular junctions AChE expresses in asymmetric form which associates with ColQ or subunit. In the central nervous system it is associated with PRiMA which stands for Proline Rich Membrane anchor to form symmetric form. In either case, the ColQ or PRiMA anchor serves to maintain the enzyme in the intercellular junction, ColQ for the neuromuscular junction and PRiMA for synapses.

The other, alternatively spliced form expressed primarily in the erythroid tissues, differs at the C-terminus, and contains a cleavable hydrophobic peptide with a PI-anchor site. It associates with membranes through the phosphoinositide (PI) moieties added post-translationally.{{cite web | title = Entrez Gene: ACHE acetylcholinesterase (Yt blood group)| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=43}}

The third type has, so far, only been found in Torpedo sp. and mice although it is hypothesized in other species. It is thought to be involved in the stress response and, possibly, inflammation.{{cite journal | vauthors = Dori A, Ifergane G, Saar-Levy T, Bersudsky M, Mor I, Soreq H, Wirguin I | title = Readthrough acetylcholinesterase in inflammation-associated neuropathies | journal = Life Sci. | volume = 80 | issue = 24–25 | pages = 2369–74 | year = 2007 | pmid = 17379257 | doi = 10.1016/j.lfs.2007.02.011 }}

The nomenclatural variations of ACHE and of cholinesterases generally are discussed at Cholinesterase § Types and nomenclature.

{{main|Acetylcholinesterase inhibitor}}

For acetylcholine esterase (AChE), reversible inhibitors are those that do not irreversibly bond to and deactivate AChE.{{cite journal | vauthors = Millard CB, Kryger G, Ordentlich A, Greenblatt HM, Harel M, Raves ML, Segall Y, Barak D, Shafferman A, Silman I, Sussman JL | title = Crystal structures of aged phosphonylated acetylcholinesterase: nerve agent reaction products at the atomic level | journal = Biochemistry | volume = 38 | issue = 22 | pages = 7032–9 | date = June 1999 | pmid = 10353814 | doi = 10.1021/bi982678l | s2cid = 11744952 }} Drugs that reversibly inhibit acetylcholine esterase are being explored as treatments for Alzheimer's disease and myasthenia gravis, among others. Examples include tacrine and donepezil.{{cite book | title = A Primer of Drug Action | vauthors = Julien RM, Advokat CD, Comaty JE | publisher = Worth Publishers | isbn = 978-1-4292-0679-2 | edition = Eleventh | pages = [https://archive.org/details/primerofdrugacti0000juli/page/50 50] | date = October 12, 2007 | url = https://archive.org/details/primerofdrugacti0000juli/page/50 }}

Exposure to acetylcholinesterase inhibitors is one of several studied explanations for the chronic cognitive symptoms veterans displayed after returning from the Gulf War. Soldiers were dosed with AChEI pyridostigmine bromide (PB) as protection from nerve agent weapons. Studying acetylcholine levels using microdialysis and HPLC-ECD, researchers at the University of South Carolina School of Medicine determined PB, when combined with a stress element can lead to cognitive responses.{{cite journal | vauthors = Macht VA, Woodruff JL, Maissy ES, Grillo CA, Wilson MA, Fadel JR, Reagan LP | title = Pyridostigmine bromide and stress interact to impact immune function, cholinergic neurochemistry and behavior in a rat model of Gulf War Illness | journal = Brain, Behavior, and Immunity | volume = 80 | pages = 384–393 | date = August 2019 | pmid = 30953774 | pmc = 6790976 | doi = 10.1016/j.bbi.2019.04.015 }}

• Phytocannabinoids{{cite journal | vauthors = Puopolo T, Liu C, Ma H, Seeram NP | title = Inhibitory Effects of Cannabinoids on Acetylcholinesterase and Butyrylcholinesterase Enzyme Activities | journal = Medical Cannabis and Cannabinoids | volume = 5 | issue = 1 | pages = 85–94 | date = April 19, 2022 | pmid = 35702400 | doi = 10.1159/000524086 | pmc = 9149358 | doi-access = free }}
• Cannabidiol
• Δ⁸-Tetrahydrocannabinol
• Cannabigerol
• Cannabigerolic acid
• Cannabicitran
• Cannabidivarin
• Cannabichromene
• Cannabinol

• Cholinesterases

{{reflist|32em}}

{{refbegin|32em}}

• {{cite journal | vauthors = Silman I, Futerman AH | title = Modes of attachment of acetylcholinesterase to the surface membrane | journal = Eur. J. Biochem. | volume = 170 | issue = 1–2 | pages = 11–22 | year = 1988 | pmid = 3319614 | doi = 10.1111/j.1432-1033.1987.tb13662.x | doi-access = free }}
• {{cite journal | vauthors = Sussman JL, Harel M, Frolow F, Oefner C, Goldman A, Toker L, Silman I | title = Atomic structure of acetylcholinesterase from Torpedo californica: a prototypic acetylcholine-binding protein | journal = Science | volume = 253 | issue = 5022 | pages = 872–9 | year = 1991 | pmid = 1678899 | doi = 10.1126/science.1678899 | bibcode = 1991Sci...253..872S | s2cid = 28833513 }}
• {{cite journal | vauthors = Soreq H, Seidman S | title = Acetylcholinesterase--new roles for an old actor | journal = Nature Reviews Neuroscience | volume = 2 | issue = 4 | pages = 294–302 | year = 2001 | pmid = 11283752 | doi = 10.1038/35067589 | s2cid = 5947744 }}
• {{cite journal | vauthors = Shen T, Tai K, Henchman RH, McCammon JA | title = Molecular dynamics of acetylcholinesterase | journal = Acc. Chem. Res. | volume = 35 | issue = 6 | pages = 332–40 | year = 2003 | pmid = 12069617 | doi = 10.1021/ar010025i }}
• {{cite journal | vauthors = Pakaski M, Kasa P | title = Role of acetylcholinesterase inhibitors in the metabolism of amyloid precursor protein | journal = Current Drug Targets. CNS and Neurological Disorders | volume = 2 | issue = 3 | pages = 163–71 | year = 2003 | pmid = 12769797 | doi = 10.2174/1568007033482869 }}
• {{cite journal | vauthors = Meshorer E, Soreq H | title = Virtues and woes of AChE alternative splicing in stress-related neuropathologies | journal = Trends Neurosci. | volume = 29 | issue = 4 | pages = 216–24 | year = 2006 | pmid = 16516310 | doi = 10.1016/j.tins.2006.02.005 | s2cid = 18983474 }}
• {{cite journal | vauthors = Ehrlich G, Viegas-Pequignot E, Ginzberg D, Sindel L, Soreq H, Zakut H | title = Mapping the human acetylcholinesterase gene to chromosome 7q22 by fluorescent in situ hybridization coupled with selective PCR amplification from a somatic hybrid cell panel and chromosome-sorted DNA libraries | journal = Genomics | volume = 13 | issue = 4 | pages = 1192–7 | year = 1992 | pmid = 1380483 | doi = 10.1016/0888-7543(92)90037-S }}
• {{cite journal | vauthors = Spring FA, Gardner B, Anstee DJ | title = Evidence that the antigens of the Yt blood group system are located on human erythrocyte acetylcholinesterase | journal = Blood | volume = 80 | issue = 8 | pages = 2136–41 | year = 1992 | pmid = 1391965 | doi = 10.1182/blood.V80.8.2136.2136| doi-access = free }}
• {{cite journal | vauthors = Shafferman A, Kronman C, Flashner Y, Leitner M, Grosfeld H, Ordentlich A, Gozes Y, Cohen S, Ariel N, Barak D | title = Mutagenesis of human acetylcholinesterase. Identification of residues involved in catalytic activity and in polypeptide folding | journal = J. Biol. Chem. | volume = 267 | issue = 25 | pages = 17640–8 | year = 1992 | doi = 10.1016/S0021-9258(19)37091-7 | pmid = 1517212 | doi-access = free }}
• {{cite journal | vauthors = Getman DK, Eubanks JH, Camp S, Evans GA, Taylor P | title = The human gene encoding acetylcholinesterase is located on the long arm of chromosome 7 | journal = Am. J. Hum. Genet. | volume = 51 | issue = 1 | pages = 170–7 | year = 1992 | pmid = 1609795 | pmc = 1682883 }}
• {{cite journal | vauthors = Li Y, Camp S, Rachinsky TL, Getman D, Taylor P | title = Gene structure of mammalian acetylcholinesterase. Alternative exons dictate tissue-specific expression | journal = J. Biol. Chem. | volume = 266 | issue = 34 | pages = 23083–90 | year = 1992 | doi = 10.1016/S0021-9258(18)54466-5 | pmid = 1744105 | doi-access = free }}
• {{cite journal | vauthors = Velan B, Grosfeld H, Kronman C, Leitner M, Gozes Y, Lazar A, Flashner Y, Marcus D, Cohen S, Shafferman A | title = The effect of elimination of intersubunit disulfide bonds on the activity, assembly, and secretion of recombinant human acetylcholinesterase. Expression of acetylcholinesterase Cys-580----Ala mutant | journal = J. Biol. Chem. | volume = 266 | issue = 35 | pages = 23977–84 | year = 1992 | doi = 10.1016/S0021-9258(18)54380-5 | pmid = 1748670 | doi-access = free }}
• {{cite journal | vauthors = Soreq H, Ben-Aziz R, Prody CA, Seidman S, Gnatt A, Neville L, Lieman-Hurwitz J, Lev-Lehman E, Ginzberg D, Lipidot-Lifson Y | title = Molecular cloning and construction of the coding region for human acetylcholinesterase reveals a G + C-rich attenuating structure | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 87 | issue = 24 | pages = 9688–92 | year = 1991 | pmid = 2263619 | pmc = 55238 | doi = 10.1073/pnas.87.24.9688 | bibcode = 1990PNAS...87.9688S | doi-access = free }}
• {{cite journal | vauthors = Chhajlani V, Derr D, Earles B, Schmell E, August T | title = Purification and partial amino acid sequence analysis of human erythrocyte acetylcholinesterase | journal = FEBS Lett. | volume = 247 | issue = 2 | pages = 279–82 | year = 1989 | pmid = 2714437 | doi = 10.1016/0014-5793(89)81352-3 | s2cid = 41843002 | doi-access = | bibcode = 1989FEBSL.247..279C }}
• {{cite journal | vauthors = Lapidot-Lifson Y, Prody CA, Ginzberg D, Meytes D, Zakut H, Soreq H | title = Coamplification of human acetylcholinesterase and butyrylcholinesterase genes in blood cells: correlation with various leukemias and abnormal megakaryocytopoiesis | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 86 | issue = 12 | pages = 4715–9 | year = 1989 | pmid = 2734315 | pmc = 287342 | doi = 10.1073/pnas.86.12.4715 | bibcode = 1989PNAS...86.4715L | doi-access = free }}
• {{cite journal | vauthors = Bazelyansky M, Robey E, Kirsch JF | title = Fractional diffusion-limited component of reactions catalyzed by acetylcholinesterase | journal = Biochemistry | volume = 25 | issue = 1 | pages = 125–30 | year = 1986 | pmid = 3954986 | doi = 10.1021/bi00349a019 }}
• {{cite journal | vauthors = Gaston SM, Marchase RB, Jakoi ER | title = Brain ligatin: a membrane lectin that binds acetylcholinesterase | journal = J. Cell. Biochem. | volume = 18 | issue = 4 | pages = 447–59 | year = 1982 | pmid = 7085778 | doi = 10.1002/jcb.1982.240180406 | s2cid = 22975039 }}
• {{cite journal | vauthors = Ordentlich A, Barak D, Kronman C, Ariel N, Segall Y, Velan B, Shafferman A | title = Contribution of aromatic moieties of tyrosine 133 and of the anionic subsite tryptophan 86 to catalytic efficiency and allosteric modulation of acetylcholinesterase | journal = J. Biol. Chem. | volume = 270 | issue = 5 | pages = 2082–91 | year = 1995 | pmid = 7836436 | doi = 10.1074/jbc.270.5.2082 | doi-access = free }}
• {{cite journal | vauthors = Maruyama K, Sugano S | title = Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides | journal = Gene | volume = 138 | issue = 1–2 | pages = 171–4 | year = 1994 | pmid = 8125298 | doi = 10.1016/0378-1119(94)90802-8 }}
• {{cite journal | vauthors = Ben Aziz-Aloya R, Sternfeld M, Soreq H | title = Promoter elements and alternative splicing in the human ACHE gene | journal = Prog. Brain Res. | volume = 98 | pages = 147–53 | year = 1994 | pmid = 8248502 | doi = 10.1016/s0079-6123(08)62392-4 }}
• {{cite journal | vauthors = Massoulié J, Pezzementi L, Bon S, Krejci E, Vallette FM | title = Molecular and Cellular Biology of Cholinesterases | journal = Prog. Brain Res. | volume = 41 | issue = 1 | pages = 31–91 | year = 1993 | pmid = 8321908 | doi = 10.1016/0301-0082(93)90040-Y | s2cid = 21601586 }}

{{refend}}

• [https://www.atsdr.cdc.gov/csem/cholinesterase-inhibitors/inhibitors.html ATSDR Case Studies in Environmental Medicine: Cholinesterase Inhibitors, Including Insecticides and Chemical Warfare Nerve Agents] U.S. Department of Health and Human Services
• {{Proteopedia|Acetylcholinesterase}}
• {{Proteopedia|AChE_inhibitors_and_substrates}}
• {{Proteopedia|AChE_inhibitors_and_substrates_(Part_II)}}
• {{Proteopedia|AChE_bivalent_inhibitors AChE bivalent inhibitors}}
• [https://web.archive.org/web/20190301095524/http://www.ebi.ac.uk/pdbe/quips?story=AChE Acetylcholinesterase: A gorge-ous enzyme]—PDBe
• [https://pdb101.rcsb.org/motm/54 Acetylcholinesterase]—RCSB PDB
• {{UCSC gene info|ACHE}}
• {{PDBe-KB2|P22303|Human Acetylcholinesterase}}

{{PDB Gallery|geneid=43}}

{{Neurotransmitter metabolism enzymes}}

{{Esterases}}

{{Enzymes}}

{{Acetylcholine metabolism and transport modulators}}

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Category:Acetylcholine

Category:EC 3.1.1