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Gene Review

BCHE  -  butyrylcholinesterase

Homo sapiens

Synonyms: Acylcholine acylhydrolase, Butyrylcholine esterase, CHE1, CHE2, Choline esterase II, ...
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Disease relevance of BCHE

  • Of the 15 squamous cell lung carcinomas, 6 showed amplification for at least 1 of the genes, with BCHE and SLC2A2 as the genes most frequently amplified [1].
  • Amplification of the genes BCHE and SLC2A2 in 40% of squamous cell carcinoma of the lung [1].
  • CONCLUSION: A five-mutation screen for investigation of post-SC apnea identified BCHE gene abnormalities for 80% of a referral population [2].
  • PvuII restriction analysis and DNA blot hybridization of the amplified ACHE and BCHE sequences demonstrated apparent aberrations in both genes, suggesting that malfunctioning of modified, partially amplified cholinesterase genes may be involved in the etiology of thrombocytopenia associated with SLE [3].
  • At the clinical level, abnormal expression of both ACHE and BCHE and the in vivo amplification of the ACHE and BCHE genes has been variously associated with abnormal megakaryocytopoiesis, leukemias and brain and ovarian tumors [4].

Psychiatry related information on BCHE

  • In Alzheimer's disease, BChE may have thus acquired an inverse role to that of AChE by adopting imperfect amphipathic characteristics of its C terminus [5].
  • Our results point to a possible association between an abnormal lipid metabolism and the BChE activity and might have implications as regards the pathomechanism of both Alzheimer's and vascular dementias and the cholinesterase inhibitor therapy of dementing disorders [6].
  • Protein concentration and acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activities were assayed in the cerebrospinal fluid (CSF) of 26 healthy normal subjects (20-86 years old), 27 patients with dementia of the Alzheimer type (DAT), and 10 patients with dementia of the Alzheimer type with extrapyramidal signs (EDAT) [7].
  • Scores of some of the neuropsychological tests associated with memory and attention were correlated with both plasma and CSF AChE and BuChE inhibition for up to 6 months [8].
  • Pretreatment with wild-type BChE or A328W tetramers at a dose of 2.8 units/g i.p. reduced cocaine-induced locomotor activity by 50 and 80% [9].

High impact information on BCHE


Chemical compound and disease context of BCHE


Biological context of BCHE


Anatomical context of BCHE

  • Transient expression of BCHE-reporter gene constructs showed that a 194-bp fragment of the 5'-flanking region of human BCHE and a 570-bp fragment of rabbit BCHE were sufficient for promoting chloramphenicol acetyltransferase activity in HeLa cells [19].
  • The objectives of our study were to examine whether the BCHE K variant is associated with Type 2 diabetes or estimates of pancreatic beta cell function in large-scale populations of glucose-tolerant Caucasians [22].
  • Butyrylcholinesterase variants (BCHE and CHE2 Loci) associated with erythrocyte acetylcholinesterase inhibition in farmers exposed to pesticides [23].
  • The findings do not support the premise that inhibitor therapy should target BuChE so as to prevent increased levels of BuChE from hydrolyzing acetylcholine in AD cerebral cortex [24].
  • Thus, low BuChE in a patient's CSF may predict extensive incorporation in neuritic plaques, increased neurotoxicity and greater central neurodegeneration [25].

Associations of BCHE with chemical compounds

  • The frequencies of the BCHE K and TF C2 did not differ between the AD patients and controls (P > 0.1) [15].
  • INTERPRETATION: Failure to observe increased [(11)C]BMP hydrolysis in vivo makes it less likely that incremental BuChE contributes importantly to acetylcholine hydrolysis in AD [24].
  • METHODS: To examine this issue in vivo, we quantified human cerebral cortical BuChE activity using tracer kinetic estimates (k(3)) of 1-[(11)C]methyl-4-piperidinyl n-butyrate ([(11)C]BMP) hydrolysis determined by positron emission tomography [24].
  • Positron emission tomography scans in AD patients (n = 15) and control subjects (n = 12) measured both BuChE (using [(11)C]BMP) and AChE activity (using N-[(11)C] methylpiperidin-4-yl propionate, an established method) [24].
  • The "atypical" BuChE variant, in which Asp70 at the rim of the active site gorge is substituted by glycine, displayed a more drastically weakened interaction with tacrine than with cocaine, dibucaine, succinylcholine, BW284c51 [1,5-bis(4-allyldimethylammoniumphenyl)pentan-3-one dibromide], or alpha-solanine [26].
  • Cognitive decline in male BuChE-K and functional decline and incident AD in female BuChE wt/wt were significantly attenuated by rivastigmine [27].

Physical interactions of BCHE

  • The 3D structure of the CPT-11/AChE complex also permits modeling of CPT-11 complexed with mammalian butyrylcholinesterase and carboxylesterase, both of which are known to hydrolyze the drug to the active metabolite [28].

Co-localisations of BCHE


Regulatory relationships of BCHE


Other interactions of BCHE


Analytical, diagnostic and therapeutic context of BCHE


  1. Amplification of the genes BCHE and SLC2A2 in 40% of squamous cell carcinoma of the lung. Brass, N., Rácz, A., Heckel, D., Remberger, K., Sybrecht, G.W., Meese, E.U. Cancer Res. (1997) [Pubmed]
  2. Butyrylcholinesterase (BCHE) genotyping for post-succinylcholine apnea in an Australian population. Yen, T., Nightingale, B.N., Burns, J.C., Sullivan, D.R., Stewart, P.M. Clin. Chem. (2003) [Pubmed]
  3. In vivo gene amplification in non-cancerous cells: cholinesterase genes and oncogenes amplify in thrombocytopenia associated with lupus erythematosus. Zakut, H., Lapidot-Lifson, Y., Beeri, R., Ballin, A., Soreq, H. Mutat. Res. (1992) [Pubmed]
  4. Mutations and impaired expression in the ACHE and BCHE genes: neurological implications. Soreq, H., Ehrlich, G., Schwarz, M., Loewenstein, Y., Glick, D., Zakut, H. Biomed. Pharmacother. (1994) [Pubmed]
  5. Butyrylcholinesterase attenuates amyloid fibril formation in vitro. Diamant, S., Podoly, E., Friedler, A., Ligumsky, H., Livnah, O., Soreq, H. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  6. Increased serum butyrylcholinesterase activity in type IIb hyperlipidaemic patients. Kálmán, J., Juhász, A., Rakonczay, Z., Abrahám, G., Zana, M., Boda, K., Farkas, T., Penke, B., Janka, Z. Life Sci. (2004) [Pubmed]
  7. 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]
  8. 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]
  9. Wild-type and A328W mutant human butyrylcholinesterase tetramers expressed in Chinese hamster ovary cells have a 16-hour half-life in the circulation and protect mice from cocaine toxicity. Duysen, E.G., Bartels, C.F., Lockridge, O. J. Pharmacol. Exp. Ther. (2002) [Pubmed]
  10. Adenovirus 2 Ip+ locus codes for a 19 kd tumor antigen that plays an essential role in cell transformation. Chinnadurai, G. Cell (1983) [Pubmed]
  11. Insights into the ubiquitin transfer cascade from the structure of the activating enzyme for NEDD8. Walden, H., Podgorski, M.S., Schulman, B.A. Nature (2003) [Pubmed]
  12. Interaction of E1 and hSNF5 proteins stimulates replication of human papillomavirus DNA. Lee, D., Sohn, H., Kalpana, G.V., Choe, J. Nature (1999) [Pubmed]
  13. 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]
  14. Relation between butyrylcholinesterase K variant, paraoxonase 1 (PON1) Q and R and apolipoprotein E epsilon 4 genes in early-onset coronary artery disease. Nassar, B.A., Darvesh, S., Bevin, L.D., Rockwood, K., Kirkland, S.A., O'Neill, B.J., Bata, I.R., Johnstone, D.E., Title, L.M. Clin. Biochem. (2002) [Pubmed]
  15. Neither the butyrylcholinesterase K variant nor transferrin C2 variant confers a risk for Alzheimer's disease in Koreans. Kim, K.W., Jhoo, J.H., Lee, J.H., Lee, K.U., Lee, D.Y., Youn, J.C., Youn, J.Y., Woo, J.I. Journal of neural transmission (Vienna, Austria : 1996) (2001) [Pubmed]
  16. The cloned butyrylcholinesterase (BCHE) gene maps to a single chromosome site, 3q26. Allderdice, P.W., Gardner, H.A., Galutira, D., Lockridge, O., LaDu, B.N., McAlpine, P.J. Genomics (1991) [Pubmed]
  17. Butyrylcholinesterase and obesity in individuals with the CHE2 C5+ and CHE2 C5- phenotypes. Alcântara, V.M., Oliveira, L.C., Réa, R.R., Suplicy, H.L., Chautard-Freire-Maia, E.A. Int. J. Obes. Relat. Metab. Disord. (2003) [Pubmed]
  18. Effect of butyrylcholinesterase genotype on the response to rivastigmine or donepezil in younger patients with Alzheimer's disease. Blesa, R., Bullock, R., He, Y., Bergman, H., Gambina, G., Meyer, J., Rapatz, G., Nagel, J., Lane, R. Pharmacogenet. Genomics (2006) [Pubmed]
  19. Promoter and transcription start site of human and rabbit butyrylcholinesterase genes. Jbilo, O., Toutant, J.P., Vatsis, K.P., Chatonnet, A., Lockridge, O. J. Biol. Chem. (1994) [Pubmed]
  20. Butyrylcholinesterase K variant is genetically associated with late onset Alzheimer's disease in Northern Ireland. McIlroy, S.P., Crawford, V.L., Dynan, K.B., McGleenon, B.M., Vahidassr, M.D., Lawson, J.T., Passmore, A.P. J. Med. Genet. (2000) [Pubmed]
  21. 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. Ehrlich, G., Viegas-Pequignot, E., Ginzberg, D., Sindel, L., Soreq, H., Zakut, H. Genomics (1992) [Pubmed]
  22. Large-scale studies of the functional K variant of the butyrylcholinesterase gene in relation to Type 2 diabetes and insulin secretion. Johansen, A., Nielsen, E.M., Andersen, G., Hamid, Y.H., Jensen, D.P., Glümer, C., Drivsholm, T., Borch-Johnsen, K., Jørgensen, T., Hansen, T., Pedersen, O. Diabetologia (2004) [Pubmed]
  23. 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]
  24. 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]
  25. Differential CSF butyrylcholinesterase levels in Alzheimer's disease patients with the ApoE epsilon4 allele, in relation to cognitive function and cerebral glucose metabolism. Darreh-Shori, T., Brimijoin, S., Kadir, A., Almkvist, O., Nordberg, A. Neurobiol. Dis. (2006) [Pubmed]
  26. 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]
  27. Progression from mild cognitive impairment to Alzheimer's disease: effects of sex, butyrylcholinesterase genotype, and rivastigmine treatment. Ferris, S., Nordberg, A., Soininen, H., Darreh-Shori, T., Lane, R. Pharmacogenet. Genomics (2009) [Pubmed]
  28. The crystal structure of the complex of the anticancer prodrug 7-ethyl-10-[4-(1-piperidino)-1-piperidino]-carbonyloxycamptothecin (CPT-11) with Torpedo californica acetylcholinesterase provides a molecular explanation for its cholinergic action. Harel, M., Hyatt, J.L., Brumshtein, B., Morton, C.L., Yoon, K.J., Wadkins, R.M., Silman, I., Sussman, J.L., Potter, P.M. Mol. Pharmacol. (2005) [Pubmed]
  29. Ultrastructural localization of butyrylcholinesterase in senile plaques in the brains of aged and Alzheimer disease patients. Gómez-Ramos, P., Morán, M.A. Mol. Chem. Neuropathol. (1997) [Pubmed]
  30. 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]
  31. Protease inhibitors and indoleamines selectively inhibit cholinesterases in the histopathologic structures of Alzheimer disease. Wright, C.I., Guela, C., Mesulam, M.M. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  32. Analysis of the butyrylcholinesterase gene and nearby chromosome 3 markers in Alzheimer disease. Brindle, N., Song, Y., Rogaeva, E., Premkumar, S., Levesque, G., Yu, G., Ikeda, M., Nishimura, M., Paterson, A., Sorbi, S., Duara, R., Farrer, L., St George-Hyslop, P. Hum. Mol. Genet. (1998) [Pubmed]
  33. Evaluation of polymorphisms in the presenilin-1 gene and the butyrylcholinesterase gene as risk factors in sporadic Alzheimer's disease. Tilley, L., Morgan, K., Grainger, J., Marsters, P., Morgan, L., Lowe, J., Xuereb, J., Wischik, C., Harrington, C., Kalsheker, N. Eur. J. Hum. Genet. (1999) [Pubmed]
  34. Analysis of mutations in the plasma cholinesterase gene of patients with a history of prolonged neuromuscular block during anesthesia. Barta, C., Sasvari-Szekely, M., Devai, A., Kovacs, E., Staub, M., Enyedi, P. Mol. Genet. Metab. (2001) [Pubmed]
  35. Acetylcholinesterase and butyrylcholinesterase expression in adult rabbit tissues and during development. Jbilo, O., L'Hermite, Y., Talesa, V., Toutant, J.P., Chatonnet, A. Eur. J. Biochem. (1994) [Pubmed]
  36. Butyrylcholinesterase in human brain and acetylcholinesterase in human plasma: trace enzymes measured by two-site immunoassay. Brimijoin, S., Hammond, P. J. Neurochem. (1988) [Pubmed]
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