In biochemistry, cholinesterase is an enzyme that 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:
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 butyrylcholine more quickly.
History
In 1968, Walo Leuzinger et al. successfully purified and crystallized the enzyme from electric eels at Columbia University, NY. [1][2]
The 3D structure of acetylcholinesterase was first determined in 1991 by Joel Sussman et al. using protein from the Pacific electric ray.[3]
Clinically-useful quantities of butyrylcholinesterase were synthesized in 2007 by PharmAthene, through the use of genetically-modified goats.[4][5]
Clinical significance
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 succinylcholine or mivacurium during a surgery. A deficiency of serum pseeudocholinesterase has been reported in premenstrual syndrome [6] and chronic pain [7].
Elevation of plasma pseudocholinesterase was observed in 90.5% cases of acute myocardial infarction.[8]
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 defects and neural tube defects.[9]
Butyrylcholinesterase can be used as a prophylactic agent against nerve gas and other organophosphate poisoning.[4][5]
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 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 sarin and 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 terminal oxygen. The entry on Lawesson's reagent has some details on one sub-class of the phosphorus-based compounds.
Benzodiazepines, eg temazepam have an inhibitory effect on cholinesterase.[10]
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.
Pop culture
Additional images
References
- ^ 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. Full text at 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. Full text at PMC: 224717
- ^ 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.
- ^ a b Nerve gas antidote made by goats. BBC (24 July 2007). Retrieved on 2007-11-21.
- ^ a b 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. Full text at PMC: 1934339
- ^ AJ Giannini, WA Price, MC Giannini, RH Loiselle. Pseudocholinestrase in premenstrual syndrome. Journal of Clinical Psychiatry. 45:139-141,1985
- ^ Decreased pseudocholinesterase activity in patients with chronic pain. Psychiatric Forum:(13)2:98-99,1984
- ^ Textbook of Medical Biochemistry, MN Chatterjea & Rana Shinde, 6th Ed, 2005 (Pg 565)
- ^ FBR Resource Guide: Acetylcholinesterase-Amniotic Fluid. Foundation for Blood Research (September 7, 2007. Retrieved on 2007-11-21.
- ^ Holmes JH; Kanfer I, Zwarenstein H. (Aug 1978). "Effect of benzodiazepine derivatives on human blood cholinesterase in vitro.". Res Commun Chem Pathol Pharmacol 21 (2): 367-70. PMID 29327.
External links
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Hydrolase: esterases (EC 3.1) |
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| 3.1.1: Carboxylic ester hydrolases |
Cholinesterase ( Acetylcholinesterase, Butyrylcholinesterase) - Pectinesterase - 6-phosphogluconolactonase - PAF acetylhydrolase
Lipase (Gastric/Lingual, Pancreatic, Lysosomal, Hormone-sensitive, Endothelial, Hepatic, Lipoprotein, Monoacylglycerol, Diacylglycerol)
Phospholipase ( A1, A2, B)
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| 3.1.2: Thioesterase |
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| 3.1.3: Phosphatase |
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| 3.1.4: Phosphodiesterase |
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| 3.1.6: Sulfatase |
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| other |
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