The Full Wiki

Cholinesterase enzyme: Wikis

Advertisements

Note: Many of our articles have direct quotes from sources you can cite, within the Wikipedia article! This article doesn't yet, but we're working on it! See more info or our list of citable articles.

Encyclopedia

(Redirected to Cholinesterase article)

From Wikipedia, the free encyclopedia

acetylcholinesterase (Yt blood group)
Acethylcholinesterase TC 1EA5.png
Diagram of Pacific electric ray acetylcholinesterase. From PDB 1EA5.
Identifiers
Symbol ACHE
Alt. symbols YT
Entrez 43
HUGO 108
OMIM 100740
RefSeq NM_015831
UniProt P22303
Other data
EC number 3.1.1.7
Locus Chr. 7 q22
butyrylcholinesterase
Butyrylcholinesterase 1P0I.png
Cartoon diagram of human butyrylcholinesterase. From PDB 1P0I.
Identifiers
Symbol BCHE
Alt. symbols CHE1
Entrez 590
HUGO 983
OMIM 177400
RefSeq NM_000055
UniProt P06276
Other data
EC number 3.1.1.8
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.

Contents

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]

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.

Elevation of plasma pseudocholinesterase was observed in 90.5% cases of acute myocardial infarction.[5]

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.[6]

Butyrylcholinesterase can be used as a prophylactic agent against nerve gas and other organophosphate poisoning.[4]

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.[7]

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.

Pop culture

  • 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, which is contraindicated in cholinesterase inhibition.

Additional images

References

  1. ^ 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. PMID 16591490.  
  2. ^ 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. PMID 5238989.  
  3. ^ 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. PMID 1678899.  
  4. ^ a b 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. PMID 17660298. Lay summary – BBC News.  
  5. ^ Textbook of Medical Biochemistry, MN Chatterjea & Rana Shinde, 6th Ed, 2005 (Pg 565)
  6. ^ FBR Resource Guide: Acetylcholinesterase-Amniotic Fluid. Foundation for Blood Research (September 7, 2007. Retrieved on 2007-11-21.
  7. ^ 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.  

External links

Advertisements

Advertisements






Got something to say? Make a comment.
Your name
Your email address
Message