The Full Wiki

Butyrylcholinesterase: Wikis

  

Note: Many of our articles have direct quotes from sources you can cite, within the Wikipedia article! This article doesn't yet, but we're working on it! See more info or our list of citable articles.

Encyclopedia

From Wikipedia, the free encyclopedia

edit
Butyrylcholinesterase

PDB rendering based on 1p0i.
Available structures
1p0i, 1p0m, 1p0p, 1p0q, 1xlu, 1xlv, 1xlw, 2j4c
Identifiers
Symbols BCHE; CHE1; E1
External IDs OMIM177400 MGI894278 HomoloGene20065 GeneCards: BCHE Gene
EC number 3.1.1.8
RNA expression pattern
PBB GE BCHE 205433 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 590 12038
Ensembl ENSG00000114200 ENSMUSG00000027792
UniProt P06276 Q499C7
RefSeq (mRNA) NM_000055 NM_009738
RefSeq (protein) NP_000046 NP_033868
Location (UCSC) Chr 3:
166.97 - 167.04 Mb
Chr 3:
73.72 - 73.79 Mb
PubMed search [1] [2]

Butyrylcholinesterase, also known as pseudocholinesterase, BCHE or BuChE, is an enzyme that, in humans, is encoded by the BCHE gene.[1] Butyrylcholinesterase is also called serum cholinesterase. It is very similar to the neuronal acetylcholinesterase, and is a non-specific cholinesterase found in the blood plasma, which hydrolyses many different choline esters. Butyrylcholine is a synthetic compound and does not occur in the body naturally. It is used as a tool to distinguish between acetyl- and butyrylcholinesterase.

Contents

Clinical significance

Pseudocholinesterase deficiency results in delayed metabolism of only a few compounds of clinical significance, including the following: succinylcholine, mivacurium, procaine, and cocaine. Of these, its most clinically important substrate is the depolarizing neuromuscular blocking agent, succinylcholine, which the pseudocholinesterase enzyme hydrolyzes to succinylmonocholine and then to succinic acid.

In individuals with normal plasma levels of normally functioning pseudocholinesterase enzyme, hydrolysis and inactivation of approximately 90-95% of an intravenous dose of succinylcholine occurs before it reaches the neuromuscular junction. The remaining 5-10% of the succinylcholine dose acts as an acetylcholine receptor agonist at the neuromuscular junction, causing prolonged depolarization of the postsynaptic junction of the motor-end plate. This depolarization initially triggers fasciculation of skeletal muscle. As a result of prolonged depolarization, endogenous acetylcholine released from the presynaptic membrane of the motor neuron does not produce any additional change in membrane potential after binding to its receptor on the myocyte. Flaccid paralysis of skeletal muscles develops within 1 minute. In normal subjects, skeletal muscle function returns to normal approximately 5 minutes after a single bolus injection of succinylcholine as it passively diffuses away from the neuromuscular junction. Pseudocholinesterase deficiency can result in higher levels of intact succinylcholine molecules reaching receptors in the neuromuscular junction, causing the duration of paralytic effect to continue for as long as 8 hours. This condition is recognized clinically when paralysis of the respiratory and other skeletal muscles fails to spontaneously resolve after succinylcholine is administered as an adjunctive paralytic agent during anesthesia procedures. In such cases respiratory assistance is required.[2]

In 2008, an experimental new drug was discovered for the potential treatment of cocaine abuse and overdose based on the pseudocholiesterase structure. It was shown to remove cocaine from the body 2000 times as fast as the natural form of BChE. Studies in rats have shown that the drug prevented convulsions and death when administered cocaine overdoses.[3] This enzyme also metabolizes succinylcholine which accounts for its rapid degradation in the liver and plasma. There may be genetic variability in the kinetics of this enzyme that can lead to prolonged muscle blockade and potentially dangerous respiratory depression that needs to be treated with assisted ventilation.

Mutant alleles at the BCHE locus are responsible for suxamethonium sensitivity. Homozygous persons sustain prolonged apnea after administration of the muscle relaxant suxamethonium in connection with surgical anesthesia. The activity of pseudocholinesterase in the serum is low and its substrate behavior is atypical. In the absence of the relaxant, the homozygote is at no known disadvantage.[4]

Finally, pseudocholinesterase metabolism of procaine results in formation of paraaminobenzoic acid (PABA). If the patient receiving procaine is on sulfonamide antibiotics such as bactrim the antibiotic effect will be antagonized by providing a new source of PABA to the microbe for subsequent synthesis of folic acid.

See also

Cholinesterase enzyme

References

  1. ^ Allderdice PW, Gardner HA, Galutira D, Lockridge O, LaDu BN, McAlpine PJ (October 1991). "The cloned butyrylcholinesterase (BCHE) gene maps to a single chromosome site, 3q26". Genomics 11 (2): 452–4. PMID 1769657. 
  2. ^ emedicine.medscape.com, Pseudocholinesterase deficiency;
  3. ^ Zheng F, Yang W, Ko MC, Liu J, Cho H, Gao D, Tong M, Tai HH, Woods JH, Zhan CG (September 2008). "Most efficient cocaine hydrolase designed by virtual screening of transition states". J. Am. Chem. Soc. 130 (36): 12148–55. doi:10.1021/ja803646t. PMID 18710224. Lay summary – ScienceDaily. 
  4. ^ "Entrez Gene: BCHE butyrylcholinesterase". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=590. 

Further reading

  • Lockridge O (1989). "Structure of human serum cholinesterase.". Bioessays 9 (4): 125–8. doi:10.1002/bies.950090406. PMID 3067729. 
  • Allderdice PW, Gardner HA, Galutira D, et al. (1992). "The cloned butyrylcholinesterase (BCHE) gene maps to a single chromosome site, 3q26.". Genomics 11 (2): 452–4. PMID 1769657. 
  • Gaughan G, Park H, Priddle J, et al. (1992). "Refinement of the localization of human butyrylcholinesterase to chromosome 3q26.1-q26.2 using a PCR-derived probe.". Genomics 11 (2): 455–8. PMID 1769658. 
  • Arpagaus M, Kott M, Vatsis KP, et al. (1990). "Structure of the gene for human butyrylcholinesterase. Evidence for a single copy.". Biochemistry 29 (1): 124–31. doi:10.1021/bi00453a015. PMID 2322535. 
  • Nogueira CP, McGuire MC, Graeser C, et al. (1990). "Identification of a frameshift mutation responsible for the silent phenotype of human serum cholinesterase, Gly 117 (GGT----GGAG).". Am. J. Hum. Genet. 46 (5): 934–42. PMID 2339692. 
  • McGuire MC, Nogueira CP, Bartels CF, et al. (1989). "Identification of the structural mutation responsible for the dibucaine-resistant (atypical) variant form of human serum cholinesterase.". Proc. Natl. Acad. Sci. U.S.A. 86 (3): 953–7. doi:10.1073/pnas.86.3.953. PMID 2915989. 
  • Prody CA, Zevin-Sonkin D, Gnatt A, et al. (1987). "Isolation and characterization of full-length cDNA clones coding for cholinesterase from fetal human tissues.". Proc. Natl. Acad. Sci. U.S.A. 84 (11): 3555–9. doi:10.1073/pnas.84.11.3555. PMID 3035536. 
  • Lockridge O, Adkins S, La Du BN (1987). "Location of disulfide bonds within the sequence of human serum cholinesterase.". J. Biol. Chem. 262 (27): 12945–52. PMID 3115973. 
  • McTiernan C, Adkins S, Chatonnet A, et al. (1987). "Brain cDNA clone for human cholinesterase.". Proc. Natl. Acad. Sci. U.S.A. 84 (19): 6682–6. doi:10.1073/pnas.84.19.6682. PMID 3477799. 
  • Lockridge O, Bartels CF, Vaughan TA, et al. (1987). "Complete amino acid sequence of human serum cholinesterase.". J. Biol. Chem. 262 (2): 549–57. PMID 3542989. 
  • Jbilo O, Toutant JP, Vatsis KP, et al. (1994). "Promoter and transcription start site of human and rabbit butyrylcholinesterase genes.". J. Biol. Chem. 269 (33): 20829–37. PMID 8063698. 
  • Mattes C, Bradley R, Slaughter E, Browne S (1996). "Cocaine and butyrylcholinesterase (BChE): determination of enzymatic parameters.". Life Sci. 58 (13): PL257–61. doi:10.1016/0024-3205(96)00065-3. PMID 8622553. 
  • Iida S, Kinoshita M, Fujii H, et al. (1996). "Mutations of human butyrylcholinesterase gene in a family with hypocholinesterasemia.". Hum. Mutat. 6 (4): 349–51. doi:10.1002/humu.1380060411. PMID 8680411. 
  • Kamendulis LM, Brzezinski MR, Pindel EV, et al. (1996). "Metabolism of cocaine and heroin is catalyzed by the same human liver carboxylesterases.". J. Pharmacol. Exp. Ther. 279 (2): 713–7. PMID 8930175. 
  • Hidaka K, Iuchi I, Tomita M, et al. (1998). "Genetic analysis of a Japanese patient with butyrylcholinesterase deficiency.". Ann. Hum. Genet. 61 (Pt 6): 491–6. doi:10.1046/j.1469-1809.1997.6160491.x. PMID 9543549. 
  • Browne SP, Slaughter EA, Couch RA, et al. (1998). "The influence of plasma butyrylcholinesterase concentration on the in vitro hydrolysis of cocaine in human plasma.". Biopharmaceutics & drug disposition 19 (5): 309–14. doi:10.1002/(SICI)1099-081X(199807)19:5<309::AID-BDD108>3.0.CO;2-9. PMID 9673783. 
  • Altamirano CV, Lockridge O (1999). "Conserved aromatic residues of the C-terminus of human butyrylcholinesterase mediate the association of tetramers.". Biochemistry 38 (40): 13414–22. doi:10.1021/bi991475+. PMID 10529218. 
  • Darvesh S, Kumar R, Roberts S, et al. (2002). "Butyrylcholinesterase-Mediated enhancement of the enzymatic activity of trypsin.". Cell. Mol. Neurobiol. 21 (3): 285–96. doi:10.1023/A:1010947205224. PMID 11569538. 
  • Barta C, Sasvari-Szekely M, Devai A, et al. (2002). "Analysis of mutations in the plasma cholinesterase gene of patients with a history of prolonged neuromuscular block during anesthesia.". Mol. Genet. Metab. 74 (4): 484–8. doi:10.1006/mgme.2001.3251. PMID 11749053. 

External links








Got something to say? Make a comment.
Your name
Your email address
Message