J Appl Biomed 3:91-99, 2005 | DOI: 10.32725/jab.2005.011

Oxime reactivation of acetylcholinesterase inhibited by toxic phosphorus esters: in vitro kinetics and thermodynamics

Jiří Patočka1,2, Jiří Cabal1, Kamil Kuča1,*, Daniel Jun1
1 Department of Toxicology, Faculty of Military Health Sciences, University of Defence, Hradec Králové, Czech Republic
2 Department of Radiology and Toxicology, Faculty of Health and Social Studies, University of South Bohemia, České Budějovice, Czech Republic

Owing to the threat of organophosphate exposures, not only to pesticides but also to nerve agents, it is very important to know the whole process of organophosphates-inhibited acetylcholinesterase (AChE, EC 3.1.1.7) reactivation. Although current antidotes against organophosphorus intoxications consist also of prophylactics, AChE reactivators are still needed especially in the case of intoxications with high doses of organophosphates, for which prophylactic treatment is not effective. For this reason, new AChE reactivators are still being developed. Our work summarizes accurately the whole reactivation process, and offers some help for scientists who are interested in the area of AChE reactivation.

Keywords: acetylcholinesterase; reactivation; nerve agents; in vitro; kinetics; thermodynamics; oximes

Received: February 3, 2005; Revised: March 8, 2005; Published: July 31, 2005  Show citation

ACS AIP APA ASA Harvard Chicago Chicago Notes IEEE ISO690 MLA NLM Turabian Vancouver
Patočka J, Cabal J, Kuča K, Jun D. Oxime reactivation of acetylcholinesterase inhibited by toxic phosphorus esters: in vitro kinetics and thermodynamics. J Appl Biomed. 2005;3(2):91-99. doi: 10.32725/jab.2005.011.
Share...
Download citation
  • BibTeX (.bib)
  • Bookends (.ris)
  • EasyBib (.ris)
  • EndNote (.enw)
  • EndNote 8 (.xml)
  • ISI WoS (.isi)
  • Medlars (.medlars)
  • Mendeley (.ris)
  • MODS (.xml)
  • Papers (.ris)
  • RefWorks (.txt)
  • RefManager (.ris)
  • RIS (.ris)
  • MS Word (.xml)
  • Zotero (.ris)
    • Open full article

    References

    1. Aldridge W.N., Reiner E.: Acetylcholinesterase. Two types of inhibition by an organophosphorus compound: one the formation of phosphorylated enzyme and the other analogous to inhibition by substrate. Biochem. J. 115:147-162, 1969. Go to original source... Go to PubMed...
    2. Bajgar J.: Organophosphates/nerve agents poisoning: mechanism of action, diagnosis, prophylaxis and treatment. Adv. Clin. Chem. 38:151-216, 2004. Go to original source... Go to PubMed...
    3. Bajgar J.: Prophylaxis against organophosphorus poisoning. J. Med. Chem. Def. 1:1-16, 2004.
    4. Berman H.A., Leonard K.: Ligand exclusion on acetylcholinesterase. Biochemistry 29:10640-10649, 1990. Go to original source... Go to PubMed...
    5. Bourne Y., Taylor P., Radic Z., Marchot P.: Structural insight into ligand interactions at the acetylcholinesterase peripheral anionic site. EMBO J 22:1-12, 2003. Go to original source... Go to PubMed...
    6. Cabal J.: Comparison of dialkylamidofluorphosphate acid esters features with other fluoroorganophosphates. Voj. Zdrav. Listy 61:215-221, 1992. (In Czech)
    7. Cabal J., Hampl F., Liska F. et al.: Hydrates of quaternary ammonium aldehydes as potential reactivators of sarin-inhibited acetylcholinesterase. 63:1021-1030, 1998. Go to original source...
    8. Cabal J., Kuča K., Kassa J.: Specification of the structure of oximes able to reactivate tabun inhibited acetylcholinesterase. Pharmacol. Toxicol. 95:81-86, 2004. Go to original source... Go to PubMed...
    9. Childs A.F., Davies D.R., Green A.L., Rutland J.P.: The reactivation by oximes and hydroxamic acids of cholinesterase inhibited by organo-phosphorus compounds. Br. J. Pharmacol. 10:462-465, 1955. Go to original source... Go to PubMed...
    10. Davies D.R., Green A.L.: The kinetics of reactivation, by oximes, of cholinesterase inhibited by organophosphorus compounds. Biochem. J. 63:529-535, 1956. Go to original source... Go to PubMed...
    11. Dohnal V., Kuča K., Havel J., Cabal J.: Prediction of new efficient cyclosarin-inhibited acetylcholinesterase reactivators structures using method of arteficial neural networks. Chem. Listy 97:1201-1202, 2003.
    12. Harel M., Schalk I., Ehret-Sabatier L. et al.: Quaternary ligand binding to aromatic residues in the active-site gorge of acetylcholinesterase. Proc. Natl. Acad. Sci. USA 90: 9031-9035, 1993. Go to original source... Go to PubMed...
    13. Heath D.F.: Organophosphorus Poisons: Anticholinesterases and Related Compounds. Pergamon Press, Oxford 1961, pp.403.
    14. Hobbiger F., O'Sullivan D.G., Sadler P.W.: New potent reactivators of acetylcholinesterase inhibited by tetraethyl pyrophosphate. Nature 182:1498-1499, 1958. Go to original source... Go to PubMed...
    15. Kassa J., Cabal J.: A comparison of the efficacy of acetylcholine reactivators against cyclohexyl methylphosphonofluoridate (GF agent) by in vitro and in vivo methods. Pharmacol. Toxicol. 84:41-45, 1999. Go to original source... Go to PubMed...
    16. Kuča K., Bielavský J., Cabal J., Bielavská M.: Synthesis of a potential reactivator of acetylcholinesterase 1-(4-hydroxyiminomethylpyridinium)-3-(carbamoylpyridinium)-propane dibromide. Tetrahedron Lett. 44:3123-3125, 2003a. Go to original source...
    17. Kuča K., Bielavský J., Cabal J., Kassa J.: Synthesis of a new reactivator of tabun inhibited acetylcholinesterase. Bioorg. Med. Chem. Lett. 13:3545-3547, 2003b. Go to original source...
    18. Kuča K., Patocka J., Cabal J.: Reactivation of organophosphate inhibited acetylcholinesterase activity by α,ω-bis-(4-hydroxyiminomethylpyridinium)alkanes in vitro. J. Appl. Biomed. 1:207-211, 2003c. Go to original source...
    19. Kuča K., Pícha J., Cabal J., Liška F.: Synthesis of the three monopyridinium oximes and evaluation of their potency to reactivate acetylcholinesterase inhibited by nerve agents. J. Appl. Biomed. 2:51-56, 2004. Go to original source...
    20. Kuča K., Kassa J.: A Comparison of the ability of a new bispyridinium oxime - 1-(4-hydroxyiminomethylpyridinium)-4-(4-carbamoylpyridinium)butane dibromide and currently used oximes to reactivate nerve agent-inhibited rat brain acetylcholinesterase by in vitro methods. J. Enzyme Inhib. Med. Chem. 18:529-535, 2003. Go to original source... Go to PubMed...
    21. Kuča K., Patočka J.: Reactivation of cyclosarin-inhibited rat brain acetylcholinesterase by pyridinium-oximes. J. Enzyme Inhib. Med. Chem. 19:39-43, 2004. Go to original source... Go to PubMed...
    22. Leader H., Vincze A., Manisterski B. et al.: Characterization of O,O-diethylphosphoryl oximes as inhibitors of cholinesterases and substrates of phosphotriesterases. Biochem. Pharmacol. 58:503-15, 1999. Go to original source... Go to PubMed...
    23. Mager P.P.: Quantitative structure-reactivity and structure-toxicity relationships of reactivators ofager P.P.: QSAR applied to aging of phosphylated acetylcholinesterase. Pharmazie 36:450-451, 1981. Go to PubMed...
    24. Mager P.P.: QSAR applied to aging of phosphylated acetylcholinesterase. Pharmazie 38: 271-272, 1983. Go to PubMed...
    25. Mager P.P., Weber A.: Structural Bioinformatics and QSAR Analysis Applied to the Acetylcholinesterase and Bispyridinium Aldoximes. Drug Des. Dis. 18:127-150, 1983. Go to original source...
    26. Millard C.B., Kryger G., Ordentlich A. et al.: Crystal structures of aged phosphonylated acetylcholinesterase: nerve agent reaction products at the atomic level. Biochemistry 38:7032-7039, 1999. Go to original source... Go to PubMed...
    27. O'Brien R.D.: Toxic Phosphorus Esters. Academic Press, New York, London 1960, pp. 74.
    28. Pang Y.P., Kollmeyer T.M., Hong F. et al.: Rational design of alkylene-linked bis-pyridiniumaldoximes as improved acetylcholinesterase reactivators. Chem. Biol. 10:491-502, 2003. Go to original source... Go to PubMed...
    29. Patočka J.: Reactivation of isopropylmethylphosphonylated rat brain acetylcholinesterase by oximes. Coll. Czech. Chem. Commun. 37:899-906, 1972a. Go to original source...
    30. Patočka J.: Reactivation of isopropylmethylphosphonylated acetylcholinesterase by α,ω-bis-(4-hydroxyiminomethylpyridinium)-2-trans-butene dibromide. The effect of temperature. Biochem. Pharmacol. 21:3192-3196, 1972b. Go to original source... Go to PubMed...
    31. Patočka J., Bielavský J.: Afinity of bis-quaternary pyridiniumaldoximes for the active centre of intact and isopropylmethylphosphonylated acetylcholinesterase. Coll. Czech. Chem. Commun. 37:2110-2116, 1972a. Go to original source...
    32. Patočka J., Bielavský J.: Reactivation of isopropylmethylphosphonylated acetylcholinesterase by α,ω-bis-(4-hydroxyiminomethylpyridinium)-2-trans-butene dibromide - The effect of pH. Biochem. Pharmacol. 21:742-745, 1972b. Go to original source... Go to PubMed...
    33. Patočka J., Kuča K., Jun D.: Acetylcholinesterase: crucial enzyme of human body. Acta Medica (Hradec Kralove) 47:215-230, 2004. Go to original source...
    34. Schumacher M., Camp S., Maulet Y. et al.: Primary structure of Torpedo californica acetylcholinesterase deduced from its cDNA sequence. Nature 319:407-409, 1986. Go to original source... Go to PubMed...
    35. Sussman J.L., Harel M., Frolow F. et al.: Atomic structure of acetylcholinesterase from Torpedo californica: a prototypic acetylcholine-binding protein. Science 253:872-879, 1991. Go to original source... Go to PubMed...
    36. Wilson I.B., Ginsburg S.: A powerful reactivator of alkylphosphate-inhibited acetylcholinesterase. Biochim. Biophys. Acta 18:168-170, 1955. Go to original source... Go to PubMed...

    Return to the content