Acetylcholinesterase

Acetylcholinesterase, also known as AChE, is an enzyme that degrades (through its hydrolytic activity) the neurotransmitter acetylcholine, producing choline and an acetate group. It is mainly found at neuromuscular junctions and cholinergic synapses in the central nervous system, where its activity serves to terminate synaptic transmission. AChE has a very high catalytic activity - each molecule of AChE degrades about 5000 molecules of acetylcholine per second. The choline produced by the action of AChE is recycled - it is transported, through reuptake, back into nerve terminals where it is used to synthesize new acetylcholine molecules.cite book | author = Purves, Dale, George J. Augustine, David Fitzpatrick, William C. Hall, Anthony-Samuel LaMantia, James O. McNamara, and Leonard E. White | title = Neuroscience. 4th ed. | publisher = Sinauer Associates | pages = 121-2 | year = 2008 | id = ISBN 978-0-87893-697-7]

Acetylcholinesterase is also found on the red blood cell membranes, where it constitutes the Yt blood group antigen. Acetylcholinesterase exists in multiple molecular forms, which possess similar catalytic properties, but differ in their oligomeric assembly and mode of attachment to the cell surface.

AChE gene

Acetylcholinesterase is encoded by the single AChE gene; and the structural diversity in the gene products arises from alternative mRNA splicing and post-translational associations of catalytic and structural subunits. The major form of acetylcholinesterase found in brain, muscle, and other tissues is the hydrophilic species, which forms disulfide-linked oligomers with collagenous, or lipid-containing structural subunits. The other, alternatively-spliced form, expressed primarily in the erythroid tissues, differs at the C-terminus, and contains a cleavable hydrophobic peptide with a GPI-anchor site. It associates with membranes through the phosphoinositide (PI) moieties added post-translationally. [cite web | title = Entrez Gene: ACHE acetylcholinesterase (Yt blood group)| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=43| accessdate = ]

AChE inhibitors

Acetylcholinesterase is the target of many nerve gases, particularly the organophosphates (e.g. Sarin). These agents - known as cholinesterase inhibitors - block the function of acetylcholinesterase and thus cause excessive acetylcholine to accumulate in the synaptic cleft. The excess acetylcholine causes neuromuscular paralysis (i.e. interminable muscle contractions) throughout the entire body, leading to death by asphyxiation.

ee also

*Acetylcholinesterase inhibitor
*Cholinesterase enzyme

References

Further reading

PBB_Further_reading
citations =
*cite journal | author=Silman I, Futerman AH |title=Modes of attachment of acetylcholinesterase to the surface membrane. |journal=Eur. J. Biochem. |volume=170 |issue= 1-2 |pages= 11–22 |year= 1988 |pmid= 3319614 |doi=
*cite journal | author=Soreq H, Seidman S |title=Acetylcholinesterase--new roles for an old actor. |journal=Nat. Rev. Neurosci. |volume=2 |issue= 4 |pages= 294–302 |year= 2001 |pmid= 11283752 |doi= 10.1038/35067589
*cite journal | author=Shen T, Tai K, Henchman RH, McCammon JA |title=Molecular dynamics of acetylcholinesterase. |journal=Acc. Chem. Res. |volume=35 |issue= 6 |pages= 332–40 |year= 2003 |pmid= 12069617 |doi=
*cite journal | author=Pakaski M, Kasa P |title=Role of acetylcholinesterase inhibitors in the metabolism of amyloid precursor protein. |journal=Current drug targets. CNS and neurological disorders |volume=2 |issue= 3 |pages= 163–71 |year= 2003 |pmid= 12769797 |doi=
*cite journal | author=Meshorer E, Soreq H |title=Virtues and woes of AChE alternative splicing in stress-related neuropathologies. |journal=Trends Neurosci. |volume=29 |issue= 4 |pages= 216–24 |year= 2006 |pmid= 16516310 |doi= 10.1016/j.tins.2006.02.005
*cite journal | author=Ehrlich G, Viegas-Pequignot E, Ginzberg D, "et al." |title=Mapping the human acetylcholinesterase gene to chromosome 7q22 by fluorescent in situ hybridization coupled with selective PCR amplification from a somatic hybrid cell panel and chromosome-sorted DNA libraries. |journal=Genomics |volume=13 |issue= 4 |pages= 1192–7 |year= 1992 |pmid= 1380483 |doi=
*cite journal | author=Spring FA, Gardner B, Anstee DJ |title=Evidence that the antigens of the Yt blood group system are located on human erythrocyte acetylcholinesterase. |journal=Blood |volume=80 |issue= 8 |pages= 2136–41 |year= 1992 |pmid= 1391965 |doi=
*cite journal | author=Shafferman A, Kronman C, Flashner Y, "et al." |title=Mutagenesis of human acetylcholinesterase. Identification of residues involved in catalytic activity and in polypeptide folding. |journal=J. Biol. Chem. |volume=267 |issue= 25 |pages= 17640–8 |year= 1992 |pmid= 1517212 |doi=
*cite journal | author=Getman DK, Eubanks JH, Camp S, "et al." |title=The human gene encoding acetylcholinesterase is located on the long arm of chromosome 7. |journal=Am. J. Hum. Genet. |volume=51 |issue= 1 |pages= 170–7 |year= 1992 |pmid= 1609795 |doi=
*cite journal | author=Li Y, Camp S, Rachinsky TL, "et al." |title=Gene structure of mammalian acetylcholinesterase. Alternative exons dictate tissue-specific expression. |journal=J. Biol. Chem. |volume=266 |issue= 34 |pages= 23083–90 |year= 1992 |pmid= 1744105 |doi=
*cite journal | author=Velan B, Grosfeld H, Kronman C, "et al." |title=The effect of elimination of intersubunit disulfide bonds on the activity, assembly, and secretion of recombinant human acetylcholinesterase. Expression of acetylcholinesterase Cys-580----Ala mutant. |journal=J. Biol. Chem. |volume=266 |issue= 35 |pages= 23977–84 |year= 1992 |pmid= 1748670 |doi=
*cite journal | author=Soreq H, Ben-Aziz R, Prody CA, "et al." |title=Molecular cloning and construction of the coding region for human acetylcholinesterase reveals a G + C-rich attenuating structure. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=87 |issue= 24 |pages= 9688–92 |year= 1991 |pmid= 2263619 |doi=
*cite journal | author=Chhajlani V, Derr D, Earles B, "et al." |title=Purification and partial amino acid sequence analysis of human erythrocyte acetylcholinesterase. |journal=FEBS Lett. |volume=247 |issue= 2 |pages= 279–82 |year= 1989 |pmid= 2714437 |doi=
*cite journal | author=Lapidot-Lifson Y, Prody CA, Ginzberg D, "et al." |title=Coamplification of human acetylcholinesterase and butyrylcholinesterase genes in blood cells: correlation with various leukemias and abnormal megakaryocytopoiesis. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=86 |issue= 12 |pages= 4715–9 |year= 1989 |pmid= 2734315 |doi=
*cite journal | author=Bazelyansky M, Robey E, Kirsch JF |title=Fractional diffusion-limited component of reactions catalyzed by acetylcholinesterase. |journal=Biochemistry |volume=25 |issue= 1 |pages= 125–30 |year= 1986 |pmid= 3954986 |doi=
*cite journal | author=Gaston SM, Marchase RB, Jakoi ER |title=Brain ligatin: a membrane lectin that binds acetylcholinesterase. |journal=J. Cell. Biochem. |volume=18 |issue= 4 |pages= 447–59 |year= 1982 |pmid= 7085778 |doi= 10.1002/jcb.1982.240180406
*cite journal | author=Ordentlich A, Barak D, Kronman C, "et al." |title=Contribution of aromatic moieties of tyrosine 133 and of the anionic subsite tryptophan 86 to catalytic efficiency and allosteric modulation of acetylcholinesterase. |journal=J. Biol. Chem. |volume=270 |issue= 5 |pages= 2082–91 |year= 1995 |pmid= 7836436 |doi=
*cite journal | author=Maruyama K, Sugano S |title=Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides. |journal=Gene |volume=138 |issue= 1-2 |pages= 171–4 |year= 1994 |pmid= 8125298 |doi=
*cite journal | author=Ben Aziz-Aloya R, Sternfeld M, Soreq H |title=Promoter elements and alternative splicing in the human ACHE gene. |journal=Prog. Brain Res. |volume=98 |issue= |pages= 147–53 |year= 1994 |pmid= 8248502 |doi=

External links

*
* [http://www.atsdr.cdc.gov/csem/cholinesterase ATSDR Case Studies in Environmental Medicine: Cholinesterase Inhibitors, Including Pesticides and Chemical Warfare Nerve Agents] U.S. Department of Health and Human Services

PBB_Controls
update_page = yes
require_manual_inspection = no
update_protein_box = yes
update_summary = yes
update_citations = yes