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Information about Acetylcholinesterase

acetylcholinesterase (Yt blood group)
Identifiers
SymbolACHE
Alt. SymbolsYT
Entrez43
HUGO108
OMIM100740
RefSeqNM_015831
UniProtP22303
Other data
EC number3.1.1.7
LocusChr. 7 q22
butyrylcholinesterase
Identifiers
SymbolBCHE
Alt. SymbolsCHE1
Entrez590
HUGO983
OMIM177400
RefSeqNM_000055
UniProtP06276
Other data
EC number3.1.1.8
LocusChr. 3 q26.1-26.2
In biochemistry, cholinesterase is an enzyme which 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:
  • Acetylcholinesterase (EC 3.1.1.7) (AChE), also known as RBC cholinesterase, erythrocyte cholinesterase, or (most formally) acetylcholine acetylhydrolase, found primarily in the blood and neural 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]

Clinical significance

An absence or mutation of the pseudocholinesterase enzyme leads to a medical condition known simply as pseudocholinesterase deficiency. This is a silent condition that only manifests itself when people who 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]

Acetylcholinesterase is tested in early pregnancy. A sample of amniotic fluid is removed by amniocentesis. The presence of AChE in the amniotic fluid can confirm a neural tube defect, a common type of birth defect.[1]

Butyrylcholinesterase can be used as a prophylactic agent against nerve gas and other organophosphate poisoning.[6]

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.

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


Acetylcholine

Choline

Acetic acid

Butyrylcholine


References

1. ^ * Leuzinger W, Baker AL. Acetylcholinesterase, i. Large-scale purification, homogeneity, and amino acid analysis. Proc Natl Acad Sci U S A. 1967 Feb; 57(2): 446-451. PMCID: 335526
2. ^ Leuzinger W, Baker A L, Cauvin E. Acetylcholinesterase, II. Crystallization, Absorption Spectra, Isoionic Point. Proc Natl Acad Sci U S A, Vol. 59, No. 2 (Feb. 15, 1968), pp. 620-623. PMCID: 224717
3. ^ Sussman JL, Harel M, Frolow F, Oefner C, Goldman A, Toker L, Silman I. Atomic structure of acetylcholinesterase from Torpedo californica: a prototypic acetylcholine-binding protein. Science 1991;253:872-9. PMID 1678899.
4. ^ Nerve gas antidote made by goats
5. ^ Textbook of Medical Biochemistry, MN Chatterjea & Rana Shinde, 6th Ed, 2005 (Pg 565)
6. ^ Nerve gas antidote made by goats

External links

 •  • [ e]
Hydrolase: esterases (EC 3.1)
3.1.1: Carboxylic ester hydrolasesCholinesterase - Pectinesterase - Lipase (Lipoprotein, Lysosomal, Pancreatic, Hormone-sensitive, Lingual, Diacylglycerol, Monoacylglycerol) - Phospholipase (A1, A2, B) - 6-phosphogluconolactonase - PAF acetylhydrolase
3.1.2: ThioesterasePalmitoyl thioesterase - Ubiquitin carboxy-terminal hydrolase L1
3.1.3: PhosphataseAlkaline phosphatase - Acid phosphatase (Prostatic)/Tartrate resistant acid phosphatase/Purple acid phosphatases - Nucleotidase - Glucose 6-phosphatase - Fructose 1,6-bisphosphatase - Calcineurin - Phosphoprotein phosphatase (PP2A) - OCRL - Pyruvate dehydrogenase phosphatase - Fructose 2,6-bisphosphatase - Protein tyrosine phosphatase - PTEN
3.1.4: PhosphodiesteraseAutotaxin - Phospholipase C - Phospholipase D - Sphingomyelin phosphodiesterase - PDE1 - PDE2 - PDE3 - PDE5
3.1.6: SulfataseArylsulfatase B - Steroid sulfatase - Galactosamine-6 sulfatase - Arylsulfatase A - Iduronate-2-sulfatase - N-acetylglucosamine-6-sulfatase
otherNuclease
 •  • [ e]
Antidotes (V03AB)
Ipecacuanha - Nalorphine - Edetates - Oximes (Pralidoxime, Obidoxime) - Prednisolone/promethazine - Thiosulfate - Sodium nitrite - Dimercaprol - Protamine - Naloxone - Ethanol - Methylthioninium chloride - Potassium permanganate - Physostigmine - Copper sulfate - Potassium iodide - Amyl nitrite - Acetylcysteine - Digitalis antitoxin - Flumazenil - Methionine - 4-Dimethylaminophenol - Cholinesterase - Prussian blue - Glutathione - Hydroxocobalamin - Fomepizole
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Swiss-Prot is a manually curated biological database of protein sequences. Swiss-Prot was created in 1986 by Amos Bairoch during his PhD and developed by the Swiss Institute of Bioinformatics and the European Bioinformatics Institute.
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Enzyme Commission number (EC number) is a numerical classification scheme for enzymes, based on the chemical reactions they catalyze. As a system of enzyme nomenclature, every EC number is associated with a recommended name for the respective enzyme.
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locus (plural loci) is a fixed position on a chromosome, such as the position of a gene or a biomarker (genetic marker). A variant of the DNA sequence at a given locus is called an allele. The ordered list of loci known for a particular genome is called a genetic map.
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The Entrez Global Query Cross-Database Search System is a powerful federated search engine, or web portal that allows users to search many discrete health sciences databases at the National Center for Biotechnology Information (NCBI) website.
..... Click the link for more information.
Hugo is a male given name, a latinized form of the name Hugh, a German/Teutonic name meaning "Bright in Mind and Spirit".

Hugo is one of the most popular names in Europe ranking as high as #2 in France, #6 in Spain, and #7 in Belgium in 2006.
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The National Center for Biotechnology Information (NCBI) is part of the United States National Library of Medicine (NLM), a branch of the National Institutes of Health. The NCBI is located in Bethesda, Maryland and was founded in 1988.
..... Click the link for more information.
Swiss-Prot is a manually curated biological database of protein sequences. Swiss-Prot was created in 1986 by Amos Bairoch during his PhD and developed by the Swiss Institute of Bioinformatics and the European Bioinformatics Institute.
..... Click the link for more information.
Enzyme Commission number (EC number) is a numerical classification scheme for enzymes, based on the chemical reactions they catalyze. As a system of enzyme nomenclature, every EC number is associated with a recommended name for the respective enzyme.
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locus (plural loci) is a fixed position on a chromosome, such as the position of a gene or a biomarker (genetic marker). A variant of the DNA sequence at a given locus is called an allele. The ordered list of loci known for a particular genome is called a genetic map.
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Biochemistry is the study of the chemical processes in living organisms.[1] The word "biochemistry" comes from the Greek word βιοχημεία biochēmeia, which means "the chemistry of life.
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catalysis is the acceleration (increase in rate) of a chemical reaction by means of a substance called a catalyst, which is itself not consumed by the overall reaction.
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:Not to be confused with electrolysis


Hydrolysis is a chemical reaction or process in which a chemical compound is broken down by reaction with water.[1][2] This is the type of reaction that is used to break down polymers.
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Neurotransmitters are chemicals that are used to relay, amplify and modulate signals between a neuron and another cell. According to the prevailing beliefs of the 1960s, a chemical can be classified as a neurotransmitter if it meets the following conditions:

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The chemical compound acetylcholine, often abbreviated as ACh, was the first neurotransmitter to be identified. It is a chemical transmitter in both the peripheral nervous system (PNS) and central nervous system (CNS) in many organisms including humans.
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Choline is an organic compound, classified as an essential nutrient[1][2][3] and usually grouped within the Vitamin B complex. This natural amine is found in the lipids that make up cell membranes and in the neurotransmitter acetylcholine.
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Acetic acid, also known as ethanoic acid, is an organic chemical compound best recognized for giving vinegar its sour taste and pungent smell. Its structural formula is represented as CH3COOH.
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A synapse is cholinergic if it uses acetylcholine as its neurotransmitter.

Cholinergic means "related to the neurotransmitter acetylcholine", and is typically used in a neurological perspective. The parasympathetic nervous system is entirely cholinergic.
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Enzyme Commission number (EC number) is a numerical classification scheme for enzymes, based on the chemical reactions they catalyze. As a system of enzyme nomenclature, every EC number is associated with a recommended name for the respective enzyme.
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Red blood cells are the most common type of blood cell and the vertebrate body's principal means of delivering oxygen from the lungs or gills to body tissues via the blood.
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Blood is a specialized biological fluid consisting of red blood cells (also called RBCs or erythrocytes), white blood cells (also called leukocytes) and platelets (also called thrombocytes) suspended in a complex fluid medium known as blood plasma.
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nervous system of an animal coordinates the activity of the muscles, monitors the organs, constructs and also stops input from the senses, and initiates actions. Prominent parts of a nervous system include neurons and nerves, which are used in coordination.
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synapse. Synapses allow nerve cells to communicate with one another through axons and dendrites, converting electrical impulses into chemical signals.]]

Chemical synapses
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Enzyme Commission number (EC number) is a numerical classification scheme for enzymes, based on the chemical reactions they catalyze. As a system of enzyme nomenclature, every EC number is associated with a recommended name for the respective enzyme.
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liver is an organ present in vertebrates and some other animals. It plays a major role in metabolism and has a number of functions in the body, including glycogen storage, decomposition of red blood cells, plasma protein synthesis, and detoxification.
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In biochemistry, a substrate is a molecule upon which an enzyme acts. Enzymes catalyze chemical reactions involving the substrate(s). The substrate binds with the enzyme's active site, and an enzyme-substrate complex is formed.
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Butyrylcholine is an acetylcholine-like molecule, with activation of some of the same receptors as acetylcholine. It is hydrolysed by acetylcholinesterase and butyrylcholinesterase (also known as pseudocholinesterase), with butyrylcholinesterase being more efficient than
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Electrophorus

Species: E. electricus

Binomial name
Electrophorus electricus
(Linnaeus, 1766)

The electric eel,
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