From Wikipedia, the free encyclopedia
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.[1]
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.
[edit] 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.[2]
[edit] 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.[1]
[edit] See also
[edit] References
[edit] Further reading
- Silman I, Futerman AH (1988). "Modes of attachment of acetylcholinesterase to the surface membrane.". Eur. J. Biochem. 170 (1-2): 11–22. PMID 3319614.
- Soreq H, Seidman S (2001). "Acetylcholinesterase--new roles for an old actor.". Nat. Rev. Neurosci. 2 (4): 294–302. doi:10.1038/35067589. PMID 11283752.
- Shen T, Tai K, Henchman RH, McCammon JA (2003). "Molecular dynamics of acetylcholinesterase.". Acc. Chem. Res. 35 (6): 332–40. PMID 12069617.
- Pakaski M, Kasa P (2003). "Role of acetylcholinesterase inhibitors in the metabolism of amyloid precursor protein.". Current drug targets. CNS and neurological disorders 2 (3): 163–71. PMID 12769797.
- Meshorer E, Soreq H (2006). "Virtues and woes of AChE alternative splicing in stress-related neuropathologies.". Trends Neurosci. 29 (4): 216–24. doi:10.1016/j.tins.2006.02.005. PMID 16516310.
- Ehrlich G, Viegas-Pequignot E, Ginzberg D, et al. (1992). "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.". Genomics 13 (4): 1192–7. PMID 1380483.
- Spring FA, Gardner B, Anstee DJ (1992). "Evidence that the antigens of the Yt blood group system are located on human erythrocyte acetylcholinesterase.". Blood 80 (8): 2136–41. PMID 1391965.
- Shafferman A, Kronman C, Flashner Y, et al. (1992). "Mutagenesis of human acetylcholinesterase. Identification of residues involved in catalytic activity and in polypeptide folding.". J. Biol. Chem. 267 (25): 17640–8. PMID 1517212.
- Getman DK, Eubanks JH, Camp S, et al. (1992). "The human gene encoding acetylcholinesterase is located on the long arm of chromosome 7.". Am. J. Hum. Genet. 51 (1): 170–7. PMID 1609795.
- Li Y, Camp S, Rachinsky TL, et al. (1992). "Gene structure of mammalian acetylcholinesterase. Alternative exons dictate tissue-specific expression.". J. Biol. Chem. 266 (34): 23083–90. PMID 1744105.
- Velan B, Grosfeld H, Kronman C, et al. (1992). "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.". J. Biol. Chem. 266 (35): 23977–84. PMID 1748670.
- Soreq H, Ben-Aziz R, Prody CA, et al. (1991). "Molecular cloning and construction of the coding region for human acetylcholinesterase reveals a G + C-rich attenuating structure.". Proc. Natl. Acad. Sci. U.S.A. 87 (24): 9688–92. PMID 2263619.
- Chhajlani V, Derr D, Earles B, et al. (1989). "Purification and partial amino acid sequence analysis of human erythrocyte acetylcholinesterase.". FEBS Lett. 247 (2): 279–82. PMID 2714437.
- Lapidot-Lifson Y, Prody CA, Ginzberg D, et al. (1989). "Coamplification of human acetylcholinesterase and butyrylcholinesterase genes in blood cells: correlation with various leukemias and abnormal megakaryocytopoiesis.". Proc. Natl. Acad. Sci. U.S.A. 86 (12): 4715–9. PMID 2734315.
- Bazelyansky M, Robey E, Kirsch JF (1986). "Fractional diffusion-limited component of reactions catalyzed by acetylcholinesterase.". Biochemistry 25 (1): 125–30. PMID 3954986.
- Gaston SM, Marchase RB, Jakoi ER (1982). "Brain ligatin: a membrane lectin that binds acetylcholinesterase.". J. Cell. Biochem. 18 (4): 447–59. doi:10.1002/jcb.1982.240180406. PMID 7085778.
- Ordentlich A, Barak D, Kronman C, et al. (1995). "Contribution of aromatic moieties of tyrosine 133 and of the anionic subsite tryptophan 86 to catalytic efficiency and allosteric modulation of acetylcholinesterase.". J. Biol. Chem. 270 (5): 2082–91. PMID 7836436.
- Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides.". Gene 138 (1-2): 171–4. PMID 8125298.
- Ben Aziz-Aloya R, Sternfeld M, Soreq H (1994). "Promoter elements and alternative splicing in the human ACHE gene.". Prog. Brain Res. 98: 147–53. PMID 8248502.
- Massoulie J, Pezzementi L, Bon S, Krejci E, Valette F (1993). "Molecular and Cellular Biology of Cholinesterases.". Prog. Brain Res. 93: 31-91. PMID 8321908.
[edit] External links
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Hydrolase: esterases (EC 3.1) |
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| 3.1.1: Carboxylic ester hydrolases |
Cholinesterase ( Acetylcholinesterase, Butyrylcholinesterase) - Pectinesterase - 6-phosphogluconolactonase - PAF acetylhydrolase
Lipase (Gastric/Lingual, Pancreatic, Lysosomal, Hormone-sensitive, Endothelial, Hepatic, Lipoprotein, Monoacylglycerol, Diacylglycerol)
Phospholipase ( A1, A2, B)
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| 3.1.2: Thioesterase |
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| 3.1.3: Phosphatase |
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| 3.1.4: Phosphodiesterase |
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| 3.1.6: Sulfatase |
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