Просмотр кода страницы Английская Википедия:Cholinesterase

{{Английская Википедия/Панель перехода}}
{{Short description|Esterase that lyses choline-based esters}}
{{distinguish|Acetylcholinesterase}}
{{infobox protein
| Name = [[acetylcholinesterase|acetylcholinesterase (Yt blood group)]]
| caption = Diagram of [[Pacific electric ray]] acetylcholinesterase. From {{PDB|1EA5}}.
| image = Acethylcholinesterase_TC_1EA5.png
| width = 200
| HGNCid = 108
| Symbol = [https://www.genenames.org/cgi-bin/gene_symbol_report?hgnc_id=HGNC:108 ACHE]
| AltSymbols = YT
| EntrezGene = 43
| OMIM = 100740
| RefSeq = NM_015831
| UniProt = P22303
| PDB = 
| ECnumber = 3.1.1.7
| Chromosome = 7
| Arm = q
| Band = 22
| LocusSupplementaryData = 
}}
{{infobox protein
| Name = [[butyrylcholinesterase]]
| caption = Cartoon diagram of human butyrylcholinesterase. From {{PDB|1P0I}}.
| image = Butyrylcholinesterase 1P0I.png
| width = 
| HGNCid = 983
| Symbol = [https://www.genenames.org/cgi-bin/gene_symbol_report?hgnc_id=HGNC:983 BCHE]
| AltSymbols = CHE1, CHE2, E1
| EntrezGene = 590
| OMIM = 177400
| RefSeq = NM_000055
| UniProt = P06276
| PDB = 
| ECnumber = 3.1.1.8
| Chromosome = 3
| Arm = q
| Band = 26.1
| LocusSupplementaryData = -26.2
}}

The enzyme '''cholinesterase''' (EC 3.1.1.8, '''choline esterase'''; systematic name '''acylcholine acylhydrolase''') catalyses the hydrolysis of [[choline]]-based [[ester]]s:

: an acylcholine + H<sub>2</sub>O = choline + a carboxylate

Several of these serve as [[neurotransmitter]]s.<ref name="Colovic Krstic Lazarevic-Pasti Bondzic pp. 315–335"/> Thus, it is either of two [[enzyme]]s that [[catalyst|catalyze]] the [[hydrolysis]] of these [[cholinergic]] neurotransmitters, such as breaking [[acetylcholine]] into [[choline]] and [[acetic acid]].<ref name="Colovic Krstic Lazarevic-Pasti Bondzic pp. 315–335">{{cite journal | vauthors = Colović MB, Krstić DZ, Lazarević-Pašti TD, Bondžić AM, Vasić VM | title = Acetylcholinesterase inhibitors: pharmacology and toxicology | journal = Current Neuropharmacology | volume = 11 | issue = 3 | pages = 315–35 | date = May 2013 | pmid = 24179466 | pmc = 3648782 | doi = 10.2174/1570159x11311030006 | publisher = Bentham Science Publishers Ltd. }}</ref> These reactions are necessary to allow a cholinergic [[neuron]] to return to its resting state after activation. For example, in [[muscle contraction]], acetylcholine at a [[neuromuscular junction]] triggers a contraction; but for the muscle to relax afterward, rather than remaining locked in a tense state, the acetylcholine must be broken down by a choline esterase. The main type for that purpose is [[acetylcholinesterase]] (also called choline esterase I<ref name="Dorlands">{{Citation |author=Elsevier |author-link=Elsevier |title=Dorland's Illustrated Medical Dictionary |publisher=Elsevier |url=http://dorlands.com/ |postscript=. |access-date=2015-09-24 |archive-date=2014-01-11 |archive-url=https://web.archive.org/web/20140111192614/http://dorlands.com/ |url-status=dead }}</ref> or erythrocyte cholinesterase); it is found mainly in [[chemical synapse]]s and [[red blood cell]] membranes. The other type is [[butyrylcholinesterase]] (also called choline esterase II<ref name="Dorlands"/> or plasma cholinesterase); it is found mainly in the [[blood plasma]].

== Types and nomenclature ==

The two types of cholinesterase are [[acetylcholinesterase]] (ACHE) and [[butyrylcholinesterase]] (BCHE). The difference between the two types has to do with their respective preferences for [[substrate (biochemistry)|substrate]]s: the former hydrolyses [[acetylcholine]] more quickly; the latter hydrolyses [[butyrylcholine]] more quickly.

The term ''cholinesterase'' is sometimes used to refer specifically to butyrylcholinesterase,<ref name="Dorlands"/> but this [[usage]] produces the oddity that ''cholinesterase'' and ''false cholinesterase'' (''pseudocholinesterase'') under that scheme mean the same thing<ref name="Dorlands"/> (confusingly), and acetylcholinesterase is then called ''true cholinesterase'' in contrast,<ref name="Dorlands"/> producing the second oddity that ''cholinesterase'' and ''true cholinesterase'' then do not mean the same thing. But such usage is now outdated; the current, unambiguous [[HUGO Gene Nomenclature Committee|HGNC]] names and symbols are acetylcholinesterase (ACHE) and butyrylcholinesterase (BCHE).

Acetylcholinesterase ({{EC number|3.1.1.7}}) (ACHE), also known as AChE, choline esterase I, RBC cholinesterase, or erythrocyte cholinesterase, true cholinesterase, choline esterase I, or (most formally) acetylcholine acetylhydrolase, is found primarily in the [[blood]] on [[red blood cell]] membranes, in [[neuromuscular junction]]s, and in other neural [[synapse]]s. Acetylcholinesterase exists in multiple molecular forms.  In the mammalian brain the majority of AChE occurs as a tetrameric, G4 form (10) with much smaller amounts of a monomeric G1 (4S) form.<ref name="pmid15956816">{{cite journal | vauthors = Wang R, Tang XC | title = Neuroprotective effects of huperzine A. A natural cholinesterase inhibitor for the treatment of Alzheimer's disease | journal = Neuro-Signals | volume = 14 | issue = 1–2 | pages = 71–82 | year = 2005 | pmid = 15956816 | doi = 10.1159/000085387 | doi-access = free }}</ref>

Butyrylcholinesterase ({{EC number|3.1.1.8}}) (BCHE), also known as cholinesterase, choline esterase II, BChE, BuChE, pseudocholinesterase (PCE), plasma cholinesterase (PChE), serum cholinesterase (SChE), butylcholinesterase, or (most formally) acylcholine acylhydrolase, is produced in the [[liver]] and found primarily in [[blood plasma]]. The [[butyl]] and [[butyric acid|butyryl]] syllables both refer to [[butane]] with one of its terminal [[methyl group]]s substituted.

The half-life of BCHE is approximately 10 to 14 days.<ref name="pmid6992635">{{cite journal | vauthors = Whittaker M | title = Plasma cholinesterase variants and the anaesthetist | journal = Anaesthesia | volume = 35 | issue = 2 | pages = 174–197 | year = 1980 | pmid = 6992635 | doi = 10.1111/j.1365-2044.1980.tb03800.x | s2cid = 32806785 | doi-access =  }}</ref> BCHE levels may be reduced in patients with advanced [[liver disease]].  The decrease must be greater than 75% before significant prolongation of neuromuscular blockade occurs with [[succinylcholine]].<ref>{{cite book | last1 = Barash | first1 = Paul G. | last2 = Cullen | first2 = Bruce F. | last3 = Stoelting | first3 = Robert K. | name-list-style = vanc  | title = Handbook of Clinical Anesthesia | date = 2006 | publisher = Lippincott Williams & Wilkins | location = Philadelphia | isbn = 978-0-7817-5745-4 | pages = 546–9 | edition = 5th }}</ref><ref>{{cite book | last1 = Miller | first1 = Ronald D. | name-list-style = vanc | title = Miller's Anesthesia | date = 2005 | publisher = Elsevier/Churchill Livingstone | location = Philadelphia, Penns. | isbn = 978-0-443-06618-4 | pages = [https://archive.org/details/millersanesthesi0006unse/page/487 487–8] | edition = 6th | url = https://archive.org/details/millersanesthesi0006unse/page/487 }}</ref>

== Discovery ==

In 1968, Walo Leuzinger ''et al.'' successfully purified and crystallized acetylcholinesterase from [[electric eel]]s at Columbia University, New York.<ref name="pmid16591490">{{cite journal | vauthors = Leuzinger W, Baker AL | title = Acetylcholinesterase, I. Large-scale purification, homogeneity, and amino Acid analysis | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 57 | issue = 2 | pages = 446–51 | date = Feb 1967 | pmid = 16591490 | pmc = 335526 | doi = 10.1073/pnas.57.2.446 | bibcode = 1967PNAS...57..446L | doi-access = free }}</ref><ref name="pmid5238989">{{cite journal | vauthors = Leuzinger W, Baker AL, Cauvin E | title = Acetylcholinesterase. II. Crystallization, absorption spectra, isoionic point | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 59 | issue = 2 | pages = 620–3 | date = Feb 1968 | pmid = 5238989 | pmc = 224717 | doi = 10.1073/pnas.59.2.620 | bibcode = 1968PNAS...59..620L | doi-access = free }}</ref>

The 3D structure of acetylcholinesterase was first determined in 1991 by [[Joel Sussman]] ''et al.'' using protein from the [[Pacific electric ray]].<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 = Aug 1991 | pmid = 1678899 | doi = 10.1126/science.1678899 | bibcode = 1991Sci...253..872S | s2cid = 28833513 }}</ref>

Clinically useful quantities of butyrylcholinesterase were synthesized in 2007 by [[PharmAthene]], through the use of genetically modified goats.<ref name="pmid17660298">{{cite journal | vauthors = Huang YJ, Huang Y, Baldassarre H, Wang B, Lazaris A, Leduc M, Bilodeau AS, Bellemare A, Côté M, Herskovits P, Touati M, Turcotte C, Valeanu L, Lemée N, Wilgus H, Bégin I, Bhatia B, Rao K, Neveu N, Brochu E, Pierson J, Hockley DK, Cerasoli DM, Lenz DE, Karatzas CN, Langermann S | title = Recombinant human butyrylcholinesterase from milk of transgenic animals to protect against organophosphate poisoning | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 104 | issue = 34 | pages = 13603–8 | date = Aug 2007 | pmid = 17660298 | pmc = 1934339 | doi = 10.1073/pnas.0702756104 | bibcode = 2007PNAS..10413603H | doi-access = free }}
*{{cite news |date=24 July 2007 |title=Nerve gas antidote made by goats |work=BBC News |url=http://news.bbc.co.uk/1/hi/sci/tech/6912807.stm}}</ref>

== Clinical significance ==

An absence or mutation of the BCHE enzyme leads to a medical condition known as [[pseudocholinesterase deficiency]]. This is a silent condition that manifests itself only when people that have the deficiency receive the muscle relaxants [[succinylcholine]] or [[mivacurium]] during a surgery.

Pseudocholinesterase deficiency may also affect local anaesthetic selection in dental procedures. The enzyme plays an important role in the metabolism of ester-based local anaesthetics, a deficiency lowers the margin of safety and increases the risk of systemic effects with this type of anaesthetic. The selection of an amide-based solution is recommended in such patients.

Elevation of plasma BCHE levels was observed in 90.5% of cases of acute [[myocardial infarction]].<ref>{{cite book | last1 = Shinde | first1 = Rana | last2 = Chatterjea | first2 = MN | name-list-style = vanc | title = Textbook of Medical Biochemistry | date = 2005 | publisher = Jaypee Brothers Medical Publications (P) Ltd. | location = New Delhi | isbn = 978-9350254844 | page = 565 | edition = 6th }}</ref>

The presence of ACHE in the amniotic fluid may be tested in early pregnancy. A sample of amniotic fluid is removed by [[amniocentesis]], and presence of ACHE can confirm several common types of birth defect, including [[abdominal wall defects]] and [[neural tube defects]].<ref>[http://www.fbr.org/publications/resguide/rg-t_acheinh.html FBR Resource Guide: Acetylcholinesterase-Amniotic Fluid] {{webarchive|url=https://web.archive.org/web/20070625081717/http://www.fbr.org/publications/resguide/rg-t_acheinh.html |date=2007-06-25 }}. Foundation for Blood Research (September 7, 2007). Retrieved on 2007-11-21.</ref>

BCHE can be used as a [[prophylactic]] agent against [[nerve gas]] and other organophosphate poisoning.<ref name="pmid17660298"/>

Some early research points to genetic butylcholinesterase deficiency as a possible candidate component in [[sudden infant death syndrome]].<ref>{{cite journal|title=Butyrylcholinesterase is a potential biomarker for Sudden Infant Death Syndrome|date=2022-05-06|doi=10.1016/j.ebiom.2022.104041|pmid=35533499 |pmc=9092508 |last1=Harrington |first1=C. T. |last2=Hafid |first2=N. A. |last3=Waters |first3=K. A. |journal=eBioMedicine |volume=80 }}</ref>

The enzyme  Acetylcholin esterase, and its inhibition, plays a role in the development of myofascial trigger points and the associated myofascial pain syndrome. By injecting a mouse with acetylcholin esterase inhibitors and electrical stimulation, the muscle develops [[Myofascial trigger point|trigger points]].<ref>{{cite journal |last1=Mense |first1=S. |last2=Simons |first2=D.G. |last3=Hoheisel |first3=U. |last4=Quenzer |first4=B. |title=Lesions of rat skeletal muscle after local block of acetylcholinesterase and neuromuscular stimulation |journal=J Appl Physiol |date=2003 |volume=94 |issue=6 |pages=2494–2901 |doi=10.1152/japplphysiol.00727.2002 |pmid=12576409 |s2cid=1829156 |url=https://pubmed.ncbi.nlm.nih.gov/12576409/ |access-date=2023-09-24}}</ref><ref>{{cite journal |last1=Simons |first1=David G. |title=Review of enigmatic MTrPs as a common cause of enigmatic musculoskeletal pain and dysfunction |journal=Journal of Electromyography and Kinesiology|date=February 2004 |volume=14 |issue=1 |pages=95–107 |doi=10.1016/j.jelekin.2003.09.018 |pmid=14759755 |url=https://pubmed.ncbi.nlm.nih.gov/14759755/ |issn=1050-6411}}</ref>

== Inhibitors ==

A [[cholinesterase inhibitor]] (or "anticholinesterase") suppresses the action of the enzyme. Because of its essential function, chemicals that interfere with the action of cholinesterase are potent [[neurotoxin]]s, causing excessive salivation and eye-watering in low doses, followed by muscle spasms and ultimately death (examples are some [[snake venoms]], and the nerve gases [[sarin]] and [[VX (nerve agent)|VX]]). One counteracting medication is [[pralidoxime]]. The so-called nerve gases and many substances used in insecticides have been shown to act by combining with a residue of serine in the active site of acetylcholine esterase, inhibiting the enzyme completely. The enzyme acetylcholine esterase breaks down the neurotransmitter acetylcholine, which is released at nerve and muscle junctions, in order to allow the muscle or organ to relax. The result of acetylcholine esterase inhibition is that acetylcholine builds up and continues to act so that any nerve impulses are continually transmitted and muscle contractions do not stop.

Among the most common acetylcholinesterase inhibitors are phosphorus-based compounds, which are designed to bind to the active site of the [[enzyme]]. The structural requirements are a [[phosphorus]] atom bearing two [[lipophilic]] groups, a leaving group (such as a [[halide]] or [[thiocyanate]]), and a [[Polymer|terminal]] [[oxygen]]. The entry on [[Lawesson's reagent]] has some details on one sub-class of the phosphorus-based compounds.

Some [[benzodiazepines]], e.g., [[temazepam]] have an inhibitory effect on cholinesterase.<ref>{{cite journal | vauthors = Holmes JH, Kanfer I, Zwarenstein H | title = Effect of benzodiazepine derivatives on human blood cholinesterase in vitro | journal = Research Communications in Chemical Pathology and Pharmacology | volume = 21 | issue = 2 | pages = 367–70 | date = Aug 1978 | pmid = 29327 }}</ref>

Cholinesterase levels can be used as an indirect marker of arsenic exposure.<ref>{{cite journal | vauthors = Ali N, Hoque MA, Haque A, Salam KA, Karim MR, Rahman A, Islam K, Saud ZA, Khalek MA, Akhand AA, Hossain M, Mandal A, Karim MR, Miyataka H, Himeno S, Hossain K | title = Association between arsenic exposure and plasma cholinesterase activity: a population based study in Bangladesh | journal = Environmental Health | year = 2010 | volume = 9 | pages = 36 | pmid = 20618979 | doi = 10.1186/1476-069X-9-36 | pmc=2911418 | doi-access = free }}</ref>

Outside of [[biochemical warfare]], anticholinesterases are also used for reversing medication induced paralysis during [[anesthesia]]; as well as in the treatment of [[myasthenia gravis]], [[glaucoma]], and [[Alzheimer's disease]].  Such compounds are used for killing [[insects]] in a range of products including [[sheep dip]], [[organophosphate]] pesticides, and [[carbamate]] pesticides.  In addition to acute poisoning as described above, a semi-acute poisoning characterized by strong mental disturbances can occur. Also, prolonged exposure can cause [[birth defects]].{{Citation needed|date=September 2020}}

==Additional images==
<gallery>
 Image:Acetylcholine.svg|[[Acetylcholine]]
 Image:Choline-skeletal.svg|[[Choline]]
 Image:Acetic-acid-2D-skeletal.svg|[[Acetic acid]]
 Image:Butyrylcholine.png|[[Butyrylcholine]]
</gallery>

== References ==
{{reflist|33em}}

== External links ==
* [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]]
*[http://www.weizmann.ac.il/sb/faculty_pages/Sussman/movies.html Movies at weizmann.ac.il] showing the structure of acetylcholinesterase and interactions with various inhibitors.
* {{Proteopedia|Acetylcholinesterase}}
* {{PDB Molecule of the Month|54|Cholinesterase}}
* {{MeshName|Acetylcholinesterase}}
* {{MeshName|Pseudocholinesterase}}

{{Neurotransmitter metabolism enzymes}}
{{Cholinergics}}
{{Esterases}}
{{Enzymes}}
{{Portal bar|Biology|border=no}}
{{Authority control}}

[[Category:Acetylcholine]]
[[Category:Peripheral membrane proteins]]
[[Category:EC 3.1.1]]
{{Навигационная таблица/Портал/Английская Википедия}}
[[Категория:Английская Википедия]]
[[Категория:Википедия]]
[[Категория:Статья из Википедии]]
[[Категория:Статья из Английской Википедии]]