View source for Cholinesterase enzyme

{{protein
| Name = acetylcholinesterase (Yt blood group)
| caption = 
| image = Acetylcholinesterase-1EA5.png
| width = 200
| HGNCid = 108
| Symbol = 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 = 
}}
{{protein
| Name = butyrylcholinesterase
| caption = 
| image = 
| width = 
| HGNCid = 983
| Symbol = BCHE
| AltSymbols = CHE1
| 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
}}
{{SI}}

{{CMG}}

{{EH}}

==Overview==
In [[biochemistry]], '''cholinesterase''' is an enzyme which [[catalyst|catalyzes]] the [[hydrolysis]] of the [[neurotransmitter]] [[acetylcholine]] into [[choline]] and [[acetic acid]], a reaction necessary to allow a [[cholinergic]] neuron to return to its resting state after activation. 

==Types==
There are two types:
*'''Acetylcholinesterase''' ({{EC number|3.1.1.7}}) (AChE), also known as ''[[red blood cell|RBC]] cholinesterase'', ''erythrocyte cholinesterase'', or (most formally) ''acetylcholine acetylhydrolase'', found primarily in the [[blood]] and [[neural]] [[synapse]]s
*'''Pseudocholinesterase''' ({{EC number|3.1.1.8}}) (BChE or BuChE), also known as ''plasma cholinesterase'', ''butyrylcholinesterase'', or (most formally) ''acylcholine acylhydrolase'', found primarily in the [[liver]]

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

==History==
In 1968, Walo Leuzinger ''et al'' successfully purified and crystallized the enzyme from [[electric eel]]s at Columbia University, NY. <ref>* Leuzinger W, Baker AL. ''Acetylcholinesterase, i. Large-scale purification, homogeneity, and amino acid analysis''. Proc Natl Acad Sci U S A. 1967 Feb; 57(2): 446-451. PMCID: 335526</ref><ref>Leuzinger W, Baker A L, Cauvin E. Acetylcholinesterase, II. ''Crystallization, Absorption Spectra, Isoionic Point.'' Proc Natl Acad Sci U S A, Vol. 59, No. 2 (Feb. 15, 1968), pp. 620-623. PMCID: 224717 </ref>

The 3D structure of acetylcholinesterase was first determined in 1991 by [[Joel Sussman]] ''et al'' using protein from the [[Pacific electric ray]].<ref>Sussman JL, Harel M, Frolow F, Oefner C, Goldman A, Toker L, Silman I. ''Atomic structure of acetylcholinesterase from Torpedo californica: a prototypic acetylcholine-binding protein.'' Science 1991;253:872-9. PMID 1678899.</ref>

Clinically-useful quantities of butyrylcholinesterase were synthesized in 2007 by PharmAthene, through the use of genetically-modified goats.<ref>[http://news.bbc.co.uk/1/hi/sci/tech/6912807.stm Nerve gas antidote made by goats]</ref>

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

Elevation of plasma pseudocholinesterase was observed in 90.5% cases of acute [[myocardial infarction]].<ref>Textbook of Medical Biochemistry, MN Chatterjea & Rana Shinde, 6th Ed, 2005 (Pg 565)</ref>

Acetylcholinesterase is tested in early pregnancy. A sample of amniotic fluid is removed by [[amniocentesis]]. The presence of AChE in the amniotic fluid can confirm a [[neural tube defect]], a common type of birth defect.[http://www.fbr.org/psl/psl-tests.html]

Butyrylcholinesterase can be used as a [[prophylactic]] agent against [[nerve gas]] and other organophosphate poisoning.<ref>[http://news.bbc.co.uk/1/hi/sci/tech/6912807.stm Nerve gas antidote made by goats]</ref>

==Cholinesterase 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]].

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.

Outside of biochemical warfare, anticholinesterases are also used in [[anesthesia]] or in the treatment of [[myasthenia gravis]], [[glaucoma]] and [[Alzheimer's disease]]. Also, 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]].

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

==Reference==
<references/>

==External links==
*[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.
* {{PDB Molecule of the Month|pdb54_1}}
* {{MeshName|Acetylcholinesterase}}
* {{MeshName|Pseudocholinesterase}}

{{Esterases}}
{{Antidotes}}
[[Category:Neurotransmitters]]
[[Category:Peripheral membrane proteins]]

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