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Gene Review

ACHE  -  acetylcholinesterase (Yt blood group)

Homo sapiens

Synonyms: ACEE, AChE, ARACHE, Acetylcholinesterase, N-ACHE, ...
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Disease relevance of ACHE

  • Our findings suggest that inherited interactive weakness of AChE and PON1 expression increases the insecticide-induced occurrence of Parkinson's disease [1].
  • Congenital myasthenic syndrome (CMS) with end-plate acetylcholinesterase (AChE) deficiency is a rare autosomal recessive disease, recently classified as CMS type Ic (CMS-Ic) [2].
  • Surgical pieces of non-small lung carcinomas (NSLC) and their adjacent non-cancerous tissues (ANCT) were analysed for AChE and BChE activities [3].
  • The probable involvement of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) in cancer and the relevance of cholinergic responses for lung cancer growth prompted us to study whether cholinesterase activity of human lung is altered by malignancy [3].
  • To minimize toxicity, however, a cholinesterase inhibitor selective for only AChE would be an ideal treatment [4].

Psychiatry related information on ACHE


High impact information on ACHE

  • Under all experimental conditions, any change in the rate of AChE secretion was accompanied by an identical change in the rate of ACh receptor incorporation into the plasma membrane [10].
  • Moreover, atypical BuChE demonstrated 1/200th the affinity for tacrine of normal BuChE or the related enzyme acetylcholinesterase (AChE) [11].
  • Synapses form when cultures are grown in the presence of acetylcholine receptor antagonists, but AChE does not accumulate at these synapses [12].
  • The appearance of acetylcholinesterase (AChE) at newly formed nerve-muscle synapses depends on synaptic transmission [12].
  • Treatment with dibutyryl cyclic GMP mimics muscle activity, directly inducing synaptic AChE appearance [12].

Chemical compound and disease context of ACHE

  • A significant fraction of the amphiphilic AChE species was converted into hydrophilic components by incubation of the soluble enzyme with phosphatidylinositol-specific phospholipase C (PIPLC) from Bacillus thuringiensis, this fraction being increased by a double treatment with PIPLC and alkaline hydroxylamine [13].
  • Donepezil HCI is a piperidine-based reversible acetylcholinesterase (AChE) inhibitor, chemically distinct from other cholinesterase (ChE) inhibitors and rationally designed to treat the symptoms of Alzheimer's disease (AD) [14].
  • OBJECTIVE: This preliminary open-label study aims to investigate the effects of rivastigmine, an inhibitor of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), in 20 patients diagnosed with frontotemporal dementia (FTD) [15].
  • Inhibition of RBC AChE activity is consistently exhibited at lower dosages of chlorpyrifos than those required to result in clinical symptoms of OP toxicity, or alterations in cognitive functional responses [16].
  • Exposure to organophosphate (OP) chemical warfare agents (CWAs), pesticides, anesthetics, and a variety of drugs such as cocaine, as well as some neurodegenerative and liver disease states, selectively reduces AChE or BChE activity [17].

Biological context of ACHE

  • To delineate the protein domains that are responsible for this phenomenon, we mutated residues within the rim of the active site gorge, the region parallel to the peripheral site in the homologous enzyme acetylcholinesterase [AChE (acetylcholine acetyl hydrolase); EC], the oxyanion hole, and the choline-binding site [18].
  • Transcripts encoding ColQ increased during myogenic differentiation of C2C12 cells; the increase was in parallel with AChE catalytic subunit [19].
  • These phenotypes showed a relative risk (RR) of 8.8 of erythrocyte AChE inhibition when compared to the usual phenotype [20].
  • These results indicate that the molecular determinants which distinguish BuChE from AChE are inherent to its primary amino acid sequence and that additional, tissue-specific protein(s) are involved in the modulation of subunit assembly within particular biological milieues [21].
  • Injected BuChE-mRNA induced the biosynthesis of a protein exhibiting the catalytic activity, substrate specificity, and sensitivity to selective inhibitors characteristic of native human serum BuChE, and clearly distinct from the related enzyme acetylcholinesterase (AChE) [21].

Anatomical context of ACHE


Associations of ACHE with chemical compounds


Physical interactions of ACHE

  • Rabbit polyclonal antibodies prepared against the purified clone-produced BuChE polypeptides interacted in immunoblots with denatured serum BuChE as well as with purified and denatured erythrocyte AChE [29].
  • An analysis of the structure/anticholinesterase activity relationship of the described compounds, together with molecular modeling, confirmed the catalytic triad mechanism of the binding of this class of carabamate analogues within AChE and BChE and defined structural requirements for their differential inhibition [30].
  • We have shown that AChE interacts with the amyloid beta-peptide (Abeta) and promotes amyloid fibril formation by a hydrophobic environment close to the peripheral anionic binding site (PAS) of the enzyme [31].
  • Interestingly, treatment with Abeta-AChE complexes decreases the cytoplasmic beta-catenin level, a key component of Wnt signaling [32].

Regulatory relationships of ACHE

  • 4. Both hydrolysis steps by erythrocyte AChE were totally blocked by the selective AChE inhibitor BW284c51 but were not blocked by the BuChE-specific inhibitor, iso-OMPA (tetraisopropylpyrophosphoramide) [33].
  • We examine the effects of the mutations on the assembly of asymmetric AChE by coexpressing each genetically engineered COLQ mutant with ACHE(T) in COS cells [34].
  • In order to identify the structural domains of the amyloid-beta-peptide (Abeta) involved in the aggregation induced by AChE, we have studied the effect of this cholinergic enzyme on Abeta peptide fragments of different sizes [35].
  • AChE was able to promote the aggregation of these fragments in a very specific way and both mutant peptides were able to form amyloid fibrils, as revealed by negative staining under the electron microscope [35].
  • A remarkable inhibition of MSA was obtained with propidium iodide, suggesting that AChE triggers PrP 106-126 and Abeta aggregation through a similar mechanism [36].

Other interactions of ACHE

  • Serum AChE and PON enzyme activities were both found to be affected by demographic parameters, and showed inverse, reciprocal associations with anxiety measures [37].
  • AChE was predominantly expressed in neurons of the anterodorsal, midline, ventral, intralaminar, and reticular nuclei [23].
  • The collagen-tailed form of AChE, which is normally concentrated at NMJs, is composed of catalytic tetramers associated with a specific collagen, COLQ [2].
  • When all biomarkers of individual susceptibility to pesticides were considered at the same time, the GSTT1 null allele determined higher ALA-D and AChE activities at the period of high exposure to pesticides [38].

Analytical, diagnostic and therapeutic context of ACHE


  1. Acetylcholinesterase/paraoxonase interactions increase the risk of insecticide-induced Parkinson's disease. Benmoyal-Segal, L., Vander, T., Shifman, S., Bryk, B., Ebstein, R.P., Marcus, E.L., Stessman, J., Darvasi, A., Herishanu, Y., Friedman, A., Soreq, H. FASEB J. (2005) [Pubmed]
  2. Mutation in the human acetylcholinesterase-associated collagen gene, COLQ, is responsible for congenital myasthenic syndrome with end-plate acetylcholinesterase deficiency (Type Ic). Donger, C., Krejci, E., Serradell, A.P., Eymard, B., Bon, S., Nicole, S., Chateau, D., Gary, F., Fardeau, M., Massoulié, J., Guicheney, P. Am. J. Hum. Genet. (1998) [Pubmed]
  3. Cholinesterase activity of human lung tumours varies according to their histological classification. Martínez-Moreno, P., Nieto-Cerón, S., Torres-Lanzas, J., Ruiz-Espejo, F., Tovar-Zapata, I., Martínez-Hernández, P., Rodríguez-López, J.N., Vidal, C.J., Cabezas-Herrera, J. Carcinogenesis (2006) [Pubmed]
  4. Cholinesterase inhibitors proposed for treating dementia in Alzheimer's disease: selectivity toward human brain acetylcholinesterase compared with butyrylcholinesterase. Pacheco, G., Palacios-Esquivel, R., Moss, D.E. J. Pharmacol. Exp. Ther. (1995) [Pubmed]
  5. Butyrylcholinesterase: an important new target in Alzheimer's disease therapy. Greig, N.H., Lahiri, D.K., Sambamurti, K. International psychogeriatrics / IPA. (2002) [Pubmed]
  6. Cerebrospinal fluid cholinesterases in aging and in dementia of the Alzheimer type. Atack, J.R., May, C., Kaye, J.A., Kay, A.D., Rapoport, S.I. Ann. Neurol. (1988) [Pubmed]
  7. Acetylcholinesterase and butyrylcholinesterase activity in the cerebrospinal fluid of patients with neurodegenerative diseases involving cholinergic systems. Ruberg, M., Villageois, A., Bonnet, A.M., Pillon, B., Rieger, F., Agid, Y. J. Neurol. Neurosurg. Psychiatr. (1987) [Pubmed]
  8. Blood cells cholinesterase activity in early stage Alzheimer's disease and vascular dementia. von Bernhardi, R., Alarcón, R., Mezzano, D., Fuentes, P., Inestrosa, N.C. Dementia and geriatric cognitive disorders. (2005) [Pubmed]
  9. Inhibition of acetyl- and butyryl-cholinesterase in the cerebrospinal fluid of patients with Alzheimer's disease by rivastigmine: correlation with cognitive benefit. Giacobini, E., Spiegel, R., Enz, A., Veroff, A.E., Cutler, N.R. Journal of neural transmission (Vienna, Austria : 1996) (2002) [Pubmed]
  10. Secretion of acetylcholinesterase: relation to acetylcholine receptor metabolism. Rotundo, R.L., Fambrough, D.M. Cell (1980) [Pubmed]
  11. Genetic predisposition to adverse consequences of anti-cholinesterases in 'atypical' BCHE carriers. Loewenstein-Lichtenstein, Y., Schwarz, M., Glick, D., Nørgaard-Pedersen, B., Zakut, H., Soreq, H. Nat. Med. (1995) [Pubmed]
  12. Regulation of acetylcholinesterase appearance at neuromuscular junctions in vitro. Rubin, L.L., Schuetze, S.M., Weill, C.L., Fischbach, G.D. Nature (1980) [Pubmed]
  13. Monomers and dimers of acetylcholinesterase in human meningioma are anchored to the membrane by glycosylphosphatidylinositol. Sáez-Valero, J., Vidal, C.J. Neurosci. Lett. (1995) [Pubmed]
  14. Perspectives in the management of Alzheimer's disease: clinical profile of donepezil. Rogers, S.L. Dementia and geriatric cognitive disorders. (1998) [Pubmed]
  15. Rivastigmine in frontotemporal dementia: an open-label study. Moretti, R., Torre, P., Antonello, R.M., Cattaruzza, T., Cazzato, G., Bava, A. Drugs & aging. (2004) [Pubmed]
  16. Human red blood cell acetylcholinesterase inhibition as the appropriate and conservative surrogate endpoint for establishing chlorpyrifos reference dose. Chen, W.L., Sheets, J.J., Nolan, R.J., Mattsson, J.L. Regulatory toxicology and pharmacology : RTP. (1999) [Pubmed]
  17. Oral administration of pyridostigmine bromide and huperzine A protects human whole blood cholinesterases from ex vivo exposure to soman. Gordon, R.K., Haigh, J.R., Garcia, G.E., Feaster, S.R., Riel, M.A., Lenz, D.E., Aisen, P.S., Doctor, B.P. Chem. Biol. Interact. (2005) [Pubmed]
  18. Overlapping drug interaction sites of human butyrylcholinesterase dissected by site-directed mutagenesis. Loewenstein-Lichtenstein, Y., Glick, D., Gluzman, N., Sternfeld, M., Zakut, H., Soreq, H. Mol. Pharmacol. (1996) [Pubmed]
  19. Transcriptional regulation of acetylcholinesterase-associated collagen ColQ in fast- and slow-twitch muscle fibers. Ting, A.K., Siow, N.L., Kong, L.W., Tsim, K.W. Chem. Biol. Interact. (2005) [Pubmed]
  20. Butyrylcholinesterase variants (BCHE and CHE2 Loci) associated with erythrocyte acetylcholinesterase inhibition in farmers exposed to pesticides. Fontoura-da-Silva, S.E., Chautard-Freire-Maia, E.A. Hum. Hered. (1996) [Pubmed]
  21. Expression and tissue-specific assembly of human butyrylcholine esterase in microinjected Xenopus laevis oocytes. Soreq, H., Seidman, S., Dreyfus, P.A., Zevin-Sonkin, D., Zakut, H. J. Biol. Chem. (1989) [Pubmed]
  22. Butyrylcholinesterase in human brain and acetylcholinesterase in human plasma: trace enzymes measured by two-site immunoassay. Brimijoin, S., Hammond, P. J. Neurochem. (1988) [Pubmed]
  23. Differential distribution of butyrylcholinesterase and acetylcholinesterase in the human thalamus. Darvesh, S., Hopkins, D.A. J. Comp. Neurol. (2003) [Pubmed]
  24. Cerebrospinal fluid levels of biomarkers and activity of acetylcholinesterase (AChE) and butyrylcholinesterase in AD patients before and after treatment with different AChE inhibitors. Parnetti, L., Amici, S., Lanari, A., Romani, C., Antognelli, C., Andreasen, N., Minthon, L., Davidsson, P., Pottel, H., Blennow, K., Gallai, V. Neurol. Sci. (2002) [Pubmed]
  25. Antidepressants inhibit human acetylcholinesterase and butyrylcholinesterase activity. Müller, T.C., Rocha, J.B., Morsch, V.M., Neis, R.T., Schetinger, M.R. Biochim. Biophys. Acta (2002) [Pubmed]
  26. In vivo butyrylcholinesterase activity is not increased in Alzheimer's disease synapses. Kuhl, D.E., Koeppe, R.A., Snyder, S.E., Minoshima, S., Frey, K.A., Kilbourn, M.R. Ann. Neurol. (2006) [Pubmed]
  27. Mutagenesis of human acetylcholinesterase. Identification of residues involved in catalytic activity and in polypeptide folding. Shafferman, A., Kronman, C., Flashner, Y., Leitner, M., Grosfeld, H., Ordentlich, A., Gozes, Y., Cohen, S., Ariel, N., Barak, D. J. Biol. Chem. (1992) [Pubmed]
  28. Sustained cholinesterase inhibition in AD patients receiving rivastigmine for 12 months. Darreh-Shori, T., Almkvist, O., Guan, Z.Z., Garlind, A., Strandberg, B., Svensson, A.L., Soreq, H., Hellström-Lindahl, E., Nordberg, A. Neurology (2002) [Pubmed]
  29. Cross-homologies and structural differences between human cholinesterases revealed by antibodies against cDNA-produced human butyrylcholinesterase peptides. Dreyfus, P., Zevin-Sonkin, D., Seidman, S., Prody, C., Zisling, R., Zakut, H., Soreq, H. J. Neurochem. (1988) [Pubmed]
  30. Methyl analogues of the experimental Alzheimer drug phenserine: synthesis and structure/activity relationships for acetyl- and butyrylcholinesterase inhibitory action. Yu, Q., Holloway, H.W., Flippen-Anderson, J.L., Hoffman, B., Brossi, A., Greig, N.H. J. Med. Chem. (2001) [Pubmed]
  31. A structural motif of acetylcholinesterase that promotes amyloid beta-peptide fibril formation. De Ferrari, G.V., Canales, M.A., Shin, I., Weiner, L.M., Silman, I., Inestrosa, N.C. Biochemistry (2001) [Pubmed]
  32. Acetylcholinesterase (AChE)--amyloid-beta-peptide complexes in Alzheimer's disease. the Wnt signaling pathway. Inestrosa, N.C., Urra, S., Colombres, M. Current Alzheimer research. (2004) [Pubmed]
  33. Human erythrocyte but not brain acetylcholinesterase hydrolyses heroin to morphine. Salmon, A.Y., Goren, Z., Avissar, Y., Soreq, H. Clin. Exp. Pharmacol. Physiol. (1999) [Pubmed]
  34. The spectrum of mutations causing end-plate acetylcholinesterase deficiency. Ohno, K., Engel, A.G., Brengman, J.M., Shen, X.M., Heidenreich, F., Vincent, A., Milone, M., Tan, E., Demirci, M., Walsh, P., Nakano, S., Akiguchi, I. Ann. Neurol. (2000) [Pubmed]
  35. Acetylcholinesterase promotes the aggregation of amyloid-beta-peptide fragments by forming a complex with the growing fibrils. Alvarez, A., Opazo, C., Alarcón, R., Garrido, J., Inestrosa, N.C. J. Mol. Biol. (1997) [Pubmed]
  36. Acetylcholinesterase triggers the aggregation of PrP 106-126. Pera, M., Román, S., Ratia, M., Camps, P., Muñoz-Torrero, D., Colombo, L., Manzoni, C., Salmona, M., Badia, A., Clos, M.V. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
  37. Acetylcholinesterase/paraoxonase genotype and expression predict anxiety scores in Health, Risk Factors, Exercise Training, and Genetics study. Sklan, E.H., Lowenthal, A., Korner, M., Ritov, Y., Landers, D.M., Rankinen, T., Bouchard, C., Leon, A.S., Rice, T., Rao, D.C., Wilmore, J.H., Skinner, J.S., Soreq, H. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  38. Changes in erythrocyte enzymes in humans long-term exposed to pesticides: influence of several markers of individual susceptibility. Hernández, A.F., López, O., Rodrigo, L., Gil, F., Pena, G., Serrano, J.L., Parrón, T., Alvarez, J.C., Lorente, J.A., Pla, A. Toxicol. Lett. (2005) [Pubmed]
  39. Molecular forms of acetylcholinesterase and butyrylcholinesterase in the aged human central nervous system. Atack, J.R., Perry, E.K., Bonham, J.R., Candy, J.M., Perry, R.H. J. Neurochem. (1986) [Pubmed]
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