- Cholinesterase enzyme
Name = acetylcholinesterase (Yt blood group)
caption = Diagram of
Pacific electric rayacetylcholinesterase. From PDB|1EA5.
width = 200
HGNCid = 108
AltSymbols = YT
EntrezGene = 43
OMIM = 100740
RefSeq = NM_015831
UniProt = P22303
ECnumber = 22.214.171.124
Chromosome = 7
Arm = q
Band = 22
LocusSupplementaryData = protein
caption = Cartoon diagram of human butyrylcholinesterase. From PDB|1P0I.
HGNCid = 983
Symbol = BCHE
AltSymbols = CHE1
EntrezGene = 590
OMIM = 177400
RefSeq = NM_000055
UniProt = P06276
ECnumber = 126.96.36.199
Chromosome = 3
Arm = q
Band = 26.1
LocusSupplementaryData = -26.2
biochemistry, cholinesterase is an enzyme that catalyzes the hydrolysisof the neurotransmitter acetylcholineinto cholineand acetic acid, a reaction necessary to allow a cholinergicneuron to return to its resting state after activation.
There are two types:
*Acetylcholinesterase (EC number|188.8.131.52) (AChE), also known as "RBC cholinesterase", "erythrocyte cholinesterase", or (most formally) "acetylcholine acetylhydrolase", found primarily in the
bloodand neural synapses
*Pseudocholinesterase (EC number|184.108.40.206) (BChE or BuChE), also known as "plasma cholinesterase", "butyrylcholinesterase", or (most formally) "acylcholine acylhydrolase", found primarily in the
The difference between the two types of cholinesterase has to do with their respective preferences for substrates: the former hydrolyses acetylcholine more quickly; the latter hydrolyses
In 1968, Walo Leuzinger "et al." successfully purified and crystallized the enzyme from
electric eels at Columbia University, NY. [Leuzinger W, Baker AL (1967). "Acetylcholinesterase, I. Large-scale purification, homogeneity, and amino acid analysis". "Proc Natl Acad Sci USA" 57 (2): 446–451. PMID 16591490. PMC|335526] [Leuzinger W, Baker AL, Cauvin E (1968). "Acetylcholinesterase. II. Crystallization, absorption spectra, isoionic point". "Proc Natl Acad Sci USA" 59 (2): 620–3. PMID 5238989. PMC|224717]
The 3D structure of acetylcholinesterase was first determined in 1991 by
Joel Sussman"et al." using protein from the Pacific electric ray. [Sussman JL, Harel M, Frolow F, "et al." (1991). "Atomic structure of acetylcholinesterase from "Torpedo californica": a prototypic acetylcholine-binding protein". "Science" 253 (5022): 872–9. PMID 1678899.]
Clinically-useful quantities of butyrylcholinesterase were synthesized in 2007 by
PharmAthene, through the use of genetically-modified goats. [http://news.bbc.co.uk/1/hi/sci/tech/6912807.stm Nerve gas antidote made by goats] . BBC( 24 July 2007). Retrieved on 2007-11-21.] Huang YJ, Huang Y, Baldassarre H, et al (2007). "Recombinant human butyrylcholinesterase from milk of transgenic animals to protect against organophosphate poisoning". Proc Natl Acad Sci USA 104 (34): 13603–8. doi|10.1073/pnas.0702756104. PMID 17660298. PMC|1934339]
An absence or mutation of the pseudocholinesterase 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 succinylcholineor mivacuriumduring a surgery. A deficiency of serum pseeudocholinesterase has been reported in premenstrual syndrome [ AJ Giannini, WA Price, MC Giannini, RH Loiselle. Pseudocholinestrase in premenstrual syndrome. Journal of Clinical Psychiatry. 45:139-141,1985 ] and chronic pain [ Decreased pseudocholinesterase activity in patients with chronic pain. Psychiatric Forum:(13)2:98-99,1984] .
Elevation of plasma pseudocholinesterase was observed in 90.5% cases of acute
myocardial infarction. [Textbook of Medical Biochemistry, MN Chatterjea & Rana Shinde, 6th Ed, 2005 (Pg 565)]
The presence of acetylcholinesterase 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 defectsand neural tube defects. [ [http://www.fbr.org/publications/resguide/rg-t_acheinh.html FBR Resource Guide: Acetylcholinesterase-Amniotic Fluid] . Foundation for Blood Research ( September 7 2007. Retrieved on 2007-11-21.]
Butyrylcholinesterase can be used as a
prophylacticagent against nerve gasand other organophosphate poisoning.
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 neurotoxins, 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 sarinand 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 phosphorusatom bearing two lipophilicgroups, a leaving group (such as a halideor thiocyanate), and a terminal oxygen. The entry on Lawesson's reagenthas some details on one sub-class of the phosphorus-based compounds. Benzodiazepines, eg temazepamhave an inhibitory effect on cholinesterase. [cite journal | author = Holmes JH | coauthors = Kanfer I, Zwarenstein H. | year = 1978 | month = Aug | title = Effect of benzodiazepine derivatives on human blood cholinesterase in vitro. | journal = Res Commun Chem Pathol Pharmacol | volume = 21 | issue = 2 | pages = 367-70 | pmid = 29327 ]
biochemical warfare, anticholinesterases are also used in anesthesiaor in the treatment of myasthenia gravis, glaucoma, and Alzheimer's disease. Also, such compounds are used for killing insectsin a range of products including sheep dip, organophosphatepesticides, and carbamatepesticides. 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.
* On of "",
Olivia Bensonis taken to the hospitalafter being exposed to organophosphates, where she is told her cholinesterase level is low.
* [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
* [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.
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