View source for Acetylcholinesterase

{{Redirect|ACHE||Ache (disambiguation){{!}}Ache}}
{{enzyme
| Name = acetylcholinesterase
| EC_number = 3.1.1.7
| CAS_number = 9000-81-1 
| IUBMB_EC_number = 3/1/1/7
| GO_code = 0003990
| image = The reaction catalyzed by acetylcholinesterase.tif
| width = 
| caption = Acetylcholinesterase catalyzes the hydrolysis of acetylcholine to acetate ion and choline
}}
{{Infobox_gene}}
'''Acetylcholinesterase''' ([[HUGO Gene Nomenclature Committee|HGNC]] symbol '''ACHE'''), also known as '''AChE''' or '''acetylhydrolase''', is the primary [[cholinesterase]] in the body. It is an [[enzyme]] that [[catalysis|catalyzes]] the breakdown of [[acetylcholine]] and of some other [[choline]] esters that function as [[neurotransmitter]]s. AChE is found at mainly [[neuromuscular junction]]s and in [[chemical synapse]]s of the [[cholinergic]] type, where its activity serves to terminate [[neurotransmission|synaptic transmission]]. It belongs to [[carboxylesterase family]] of enzymes. It is the primary target of inhibition by [[organophosphorus]] compounds such as [[nerve agents]] and [[pesticides]].

==Enzyme structure and mechanism==
[[File:AChe mechanism of action.jpg|thumb|left|AChe mechanism of action<ref>{{cite book | vauthors = Katzung BG | title = Basic and clinical pharmacology:Introduction to autonomic pharmacology | year = 2001 | publisher = The McGraw Hill Companies | isbn = 978-0-07-160405-5 | pages = 75–91 | edition = 8 }}</ref>]]

AChE is a [[hydrolase]] that [[hydrolyzes]] choline esters. It has a very high [[catalytic]] activity - each molecule of AChE degrades about 25000 molecules of [[acetylcholine]] (ACh) per second, approaching the limit allowed by [[diffusion]] of the [[Enzyme substrate (biology)|substrate]].<ref name = "Quinn_1987">{{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 | pmid =  | doi = 10.1021/cr00081a005 }}</ref><ref>{{cite journal | vauthors = Taylor P, Radić Z | title = The cholinesterases: from genes to proteins | journal = Annual Review of Pharmacology and Toxicology | volume = 34 | issue =  | pages = 281–320 | year = 1994 | pmid = 8042853 | doi = 10.1146/annurev.pa.34.040194.001433 }}</ref> The [[active site]] of AChE comprises 2 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.<ref name="pmid1678899">{{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 }}</ref><ref name="pmid8343975">{{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 }}</ref>

The anionic subsite accommodates the positive quaternary [[amine]] of acetylcholine as well as other cationic substrates and [[Enzyme inhibitor|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 the gorge leading to the active site.<ref name="pmid1356436">{{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 }}</ref><ref name="pmid7836436">{{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 }}</ref><ref name="pmid9742217">{{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 }} {{open access}}</ref> All 14 amino acids in the aromatic gorge are highly conserved across different species.<ref name="pmid8349597">{{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 | pmid = 8349597 }} {{open access}}</ref> Among the aromatic amino acids, [[tryptophan]] 84 is critical and its substitution with [[alanine]] results in a 3000-fold decrease in reactivity.<ref>{{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_Acetylcholinesterase_Mechanism_of_Catalysis_and_Inhibition/file/72e7e5163e39a2e539.pdf}} {{closed access}}</ref> The gorge penetrates halfway through the enzyme and is approximately 20 [[angstroms]] long.  The active site is located 4 angstroms from the bottom of the molecule.<ref>{{cite journal | vauthors = Harel M, Schalk I, Ehret-Sabatier L, Bouet F, Goeldner M, Hirth C, Axelsen PH, Silman I, Sussman JL | title = Quaternary ligand binding to aromatic residues in the active-site gorge of acetylcholinesterase | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 90 | issue = 19 | pages = 9031–5 | year = 1993 | pmid = 8415649 | pmc = 47495 | doi = 10.1073/pnas.90.19.9031 | bibcode = 1993PNAS...90.9031H }}</ref>

The esteratic subsite, where acetylcholine is hydrolyzed to acetate and choline, contains the [[catalytic triad]] of three amino acids: [[serine]] 200, [[histidine]] 440 and [[glutamate]] 327.  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.<ref>{{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 | pmid =  | doi =  10.5214/ans.0972.7531.2008.150403}}</ref> 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.<ref>{{cite journal | vauthors = Pauling L | title = Molecular Architecture and Biological Reactions | journal = Chemical & Engineering News | volume = 24 | issue =  10| pages = 1375–1377 | year = 1946 | pmid =  | doi =  10.1021/cen-v024n010.p1375| url = http://sgreports.nlm.nih.gov/ps/access/MMBBRM.pdf }}</ref><ref>{{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}}</ref>

==Biological function==

During [[neurotransmission]], ACh is released from the presynaptic neuron into the [[Synapse|synaptic]] cleft and binds to ACh receptors on the post-synaptic membrane, relaying the signal from the nerve. AChE, also located on the post-synaptic membrane, 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]].<ref>{{cite journal | vauthors = Whittaker VP | title = The Contribution of Drugs and Toxins to Understanding of Cholinergic Function | journal = Trends in Physiological Sciences | volume = 11 | issue = 1 | pages = 8–13 | year = 1990 | pmid = 2408211 | doi = 10.1016/0165-6147(90)90034-6 }}</ref><ref>{{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 = 121–2 }}</ref>

A [[cholinomimetic]] drug disrupts this process by acting as a cholinergic neurotransmitter that is impervious to acetylcholinesterase's lysing action.

==Disease relevance==
{{main|Acetylcholinesterase inhibitor}}
For a cholinergic neuron to receive another impulse, ACh must be released from the ACh receptor. This occurs only when the concentration of ACh in the synaptic cleft is very low. [[Enzyme inhibitor|Inhibition]] of AChE leads to accumulation of ACh in the synaptic cleft and results in impeded neurotransmission.<ref>[citation needed]</ref>

[[File:AChe inhibitors pic.jpg|thumb|left|Mechanism of Inhibitors of AChE]]

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.<ref>{{cite web|title=National Pesticide Information Center-Diazinon Technical Fact Sheet|url=http://npic.orst.edu/factsheets/diazinontech.pdf|accessdate=24 February 2012}}</ref> 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 [[Soman]]). [[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]].<ref>{{cite web|title=Clinical Application: Acetylcholine and Alzheimer's Disease|url=http://web.williams.edu/imput/synapse/pages/IA5.html|accessdate=24 February 2012}}</ref><ref>{{cite book | last = Stoelting | first = R.K. | name-list-format = vanc | 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}}</ref><ref>{{cite book | last = Taylor | first = P | name-list-format = vanc | title = The Pharmacologial Basis of Therapeutics|year=1996|publisher=THe McGraw-Hill Companies|isbn=978-0-07-146804-6|pages=161–174|url=http://nursingpharmacology.info/Autonomics/Cholinergics/Cholin1.htm|author2=Hardman, J.G |author3=Limbird, L.E |author4=Molinoff, P.B. |author5=Ruddon, R.W |author6=Gilman, A.G. |chapter=5: Autonomic Pharmacology: Cholinergic Drugs}}</ref><ref name="isbn0-07-146804-8">{{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 }}</ref><ref>{{cite book | last = Drachman | first = D.B. | name-list-format = vanc | title=Harrison's Principles of Internal Medicine|year=1998|publisher=The McCraw-Hill Companies|isbn=978-0-07-020291-7|pages=2469–2472|edition=14|author2=Isselbacher, K.J. |author3=Braunwald, E. |author4=Wilson, J.D. |author5=Martin, J.B. |author6=Fauci, A.S. |author7=Kasper, D.L. }}</ref><ref>{{cite book | last = Raffe | first = RB | name-list-format =vanc | title = Autonomic and Somatic Nervous Systems in Netter's Illustrated Pharmacology|publisher=Elsevier Health Science|isbn=978-1-929007-60-8|pages=43}}</ref>
 
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.<ref name="pmid20005135">{{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 }}</ref>

It has also been shown that the main active ingredient in cannabis, [[tetrahydrocannabinol]], is a competitive inhibitor of acetylcholinesterase.<ref name="pmid17140265">{{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 }}</ref>

== Distribution ==

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.<ref>{{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 }}</ref><ref>{{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 | doi =  }}</ref><ref>{{cite journal | vauthors = Koelle GB | title = The histochemical localization of cholinesterases in the central nervous system of the rat | journal = Journal of Comparative Anatomy | volume = 100 | issue = 1 | pages = 211–35 | year = 1954 | pmid = 13130712 | doi = 10.1002/cne.901000108 }}</ref>

Acetylcholinesterase is also found on the [[red blood cell]] membranes, where different forms constitute the [[Yt blood group]] [[antigen]]s.<ref name="pmid8488842">{{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 | doi =  }}</ref> 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.

== AChE gene ==

In mammals, acetylcholinesterase is encoded by a single AChE gene while some invertebrates have multiple acetylcholinesterase genes. Diversity in the transcribed products from the sole mammalian gene arises from alternative [[alternative splicing|mRNA splicing]] and [[post-translational]] associations of catalytic and structural subunits. There are three known forms: T (tail), R (read through), and H(hydrophobic).<ref name="pmid18541228">{{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 }}</ref>

===AChE<sub>T</sub>===
The major form of acetylcholinesterase found in brain, muscle, and other tissues, known as is the hydrophilic species, which forms disulfide-linked oligomers with [[collagen]]ous, or [[lipid]]-containing structural subunits. In the neuromuscular junctions AChE expresses in asymmetric form which associates with [[COLQ|ColQ]] or subunit. In the central nervous system it is associated with [[PRIMA1|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.

===AChE<sub>H</sub>===
The other, alternatively spliced form expressed primarily in the [[red blood cell|erythroid]] tissues, differs at the [[C-terminus]], and contains a cleavable [[hydrophobic]] [[peptide]] with a [[Glycophosphatidylinositol|PI-anchor]] site. It associates with [[Cell membrane|membranes]] through the [[phosphoinositide]] (PI) moieties added post-translationally.<ref>{{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| accessdate = }}</ref>

===AChE<sub>R</sub>===
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.<ref name="pmid17379257">{{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 }}</ref>

==Nomenclature==
The nomenclatural variations of ACHE and of cholinesterases generally are discussed at ''[[Cholinesterase#Types and nomenclature|Cholinesterase § Types and nomenclature]]''.

== Inhibitors ==
For [[acetylcholine esterase]] (AChE), '''reversible inhibitors''' are those that do not irreversibly bond to and decactivate AChE.<ref>{{cite journal|last1=Millary|first1=CB|last2=Kryger|first2=G|year=199|title=Crystal structures of aged phosphorylated acetylcholinesterase: nerve agent reaction products at the atomic level|journal=Biochemistry|publisher=Weizmann Institute of Science|volume=38|issue=22|pages=7032–7039|doi=10.1021/bi982678l|pmid=10353814}}</ref> 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]].<ref>{{Cite book|url=|title=A Primer of Drug Action|last=Julien|first=Robert|date=|publisher=Worth Publishers|isbn=978-1-4292-0679-2|edition=Eleventh|series=|volume=|location=|pages=50|doi=|jfm=|mr=|zbl=|authorlink=|coauthors=}}</ref>

== See also ==
*[[Acetylcholinesterase inhibitor]]
*[[Cholinesterase]]s

== References ==
{{reflist | 35em}}

== Further reading ==
{{refbegin | 35em}}
* {{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 }}
* {{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 }}
* {{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 }}
* {{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 }}
* {{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 =  }}
* {{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 | pmid = 1517212 | doi =  }}
* {{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 | doi =  }}
* {{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 | pmid = 1744105 | doi =  }}
* {{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 | pmid = 1748670 | doi =  }}
* {{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 }}
* {{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 }}
* {{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 }}
* {{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 }}
* {{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 }}
* {{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 | issue =  | 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 }}
{{refend}}

== External links ==
* [http://www.atsdr.cdc.gov/csem/cholinesterase/ 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}}
*[http://www.ebi.ac.uk/pdbe/quips?story=AChE Acetylcholinesterase: A gorge-ous enzyme] – PDBe
*[http://pdb101.rcsb.org/motm/54 Acetylcholinesterase] – RCSB PDB
* {{UCSC gene info|ACHE}}

{{PDB Gallery|geneid=43}}
{{Neurotransmitter metabolism enzymes}}
{{Esterases}}
{{Enzymes}}
{{Acetylcholine metabolism and transport modulators}}
{{Authority control}}
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[[Category:Acetylcholine]]
[[Category:EC 3.1.1]]