|acetylcholinesterase (Yt blood group)|
|Locus||Chr. 7 q22|
|Locus||Chr. 3 q26.1-26.2|
In biochemistry, cholinesterase is a family of enzymes that catalyze 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.
There are two types:
- Acetylcholinesterase (EC 220.127.116.11) (AChE), also known as RBC cholinesterase, erythrocyte cholinesterase, or (most formally) acetylcholine acetylhydrolase, found primarily in the blood on red blood cell membranes, in neuromuscular junctions, and in neural synapses. 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.
- Pseudocholinesterase (EC 18.104.22.168) (BChE or BuChE), also known as plasma cholinesterase, butyrylcholinesterase, or (most formally) acylcholine acylhydrolase, is produced in the liver and found primarily in plasma.
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.
The half-life of pseudocholinesterase is approximately 8–16 hours. Pseudocholinesterase 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.
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.
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.
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.
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. 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 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 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.
- On season eight of Law and Order: SVU, Olivia Benson is taken to the hospital after being exposed to organophosphates, where she is told her cholinesterase level is low.
- In the film The I Inside, Simon Cable is poisoned with cholinesterase inhibitors and he is given atropine and pralidoxime to help reverse the poison. The doctor is also shown dispensing a diazepam at the beginning of the movie.
- In the film The Rock, Dr. Goodspeed (Nicolas Cage) describes the effects of the chemical weapon VX gas as a cholinesterase inhibitor to John Mason (Sean Connery) as they remove guidance chips from the rocket designed to deliver the gas into San Francisco from Alcatraz.
- Indie band Ruet Caelum have a song entitled 'Showing Signs of Cholinesterase Inhibition"
- Wang R, Tang XC (2005). "Neuroprotective Effects of Huperzine A.". Neurosignals 14 (1–2): 71–82. doi:10.1159/000085387. PMID 15956816.
- Brash: Clinical Anesthesia, 5th ed, pp 546-549
- Miller: Anesthesia, 6th ed, pp 487-488
- Leuzinger W, Baker AL (February 1967). "Acetylcholinesterase, I. Large-scale purification, homogeneity, and amino acid analysis". Proc. Natl. Acad. Sci. U.S.A. 57 (2): 446–451. doi:10.1073/pnas.57.2.446. PMC 335526. PMID 16591490.
- Leuzinger W, Baker AL, Cauvin E (February 1968). "Acetylcholinesterase. II. Crystallization, absorption spectra, isoionic point". Proc. Natl. Acad. Sci. U.S.A. 59 (2): 620–3. doi:10.1073/pnas.59.2.620. PMC 224717. PMID 5238989.
- Sussman JL, Harel M, Frolow F, Oefner C, Goldman A, Toker L, Silman I (August 1991). "Atomic structure of acetylcholinesterase from Torpedo californica: a prototypic acetylcholine-binding protein". Science 253 (5022): 872–9. doi:10.1126/science.1678899. PMID 1678899.
- 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 (August 2007). "Recombinant human butyrylcholinesterase from milk of transgenic animals to protect against organophosphate poisoning". Proc. Natl. Acad. Sci. U.S.A. 104 (34): 13603–8. doi:10.1073/pnas.0702756104. PMC 1934339. PMID 17660298. Lay summary – BBC News.
- 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. (August 1978). "Effect of benzodiazepine derivatives on human blood cholinesterase in vitro". Res Commun Chem Pathol Pharmacol 21 (2): 367–70. PMID 29327.
- Patlolla AK, Tchounwou PB. Serum acetyl cholinesterase as a biomarker of arsenic induced neurotoxicity in sprague-dawley rats. Int J Environ Res Public Health. 2005;2(1):80-3.
- 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. Association between arsenic exposure and plasma cholinesterase activity: a population based study in Bangladesh. Environ Health. 2010;9:36.
- ATSDR Case Studies in Environmental Medicine: Cholinesterase Inhibitors, Including Insecticides and Chemical Warfare Nerve Agents U.S. Department of Health and Human Services
- Movies at weizmann.ac.il showing the structure of acetylcholinesterase and interactions with various inhibitors.
- Proteopedia Acetylcholinesterase
- PDB Molecule of the Month pdb54_1
- Acetylcholinesterase at the US National Library of Medicine Medical Subject Headings (MeSH)
- Pseudocholinesterase at the US National Library of Medicine Medical Subject Headings (MeSH)