Cholinesterase enzyme

Types

There are two types:

• Acetylcholinesterase (synapses
• Pseudocholinesterase (EC 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 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 succinylcholine or mivacurium during a surgery.

Elevation of plasma pseudocholinesterase was observed in 90.5% cases of acute myocardial infarction.^[6]

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.^[7]

Butyrylcholinesterase can be used as a prophylactic agent against nerve gas and other organophosphate poisoning.^[4][5]

Cholinesterase inhibitors

A pralidoxime.

Among the most common acetylcholinesterase inhibitors are phosphorus-based compounds, which are designed to bind to the active site of the Lawesson's reagent has some details on one sub-class of the phosphorus-based compounds.

Outside of 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.

Additional images

References

1. ^ 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
2. ^ 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
3. ^ 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.
4. ^ ^{a b} Nerve gas antidote made by goats. BBC (24 July 2007). Retrieved on 2007-11-21.
5. ^ ^{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
6. ^ Textbook of Medical Biochemistry, MN Chatterjea & Rana Shinde, 6th Ed, 2005 (Pg 565)
7. ^ FBR Resource Guide: Acetylcholinesterase-Amniotic Fluid. Foundation for Blood Research (September 7 2007. Retrieved on 2007-11-21.