Bulletin of the Korean Chemical Society

  • 제24권1호
  • /
  • Pages.65-69
  • /
  • 2003
  • /
  • 0253-2964(pISSN)
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  • 1229-5949(eISSN)
대한화학회 (Korean Chemical Society)
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Acetylcholinesterase(AChE)-Catalyzed Hydrolysis of Long-Chain Thiocholine Esters: Shift to a New Chemical Mechanism

  • Jung, Dai-Il (Department of Chemistry, Dong-A University) ;
  • Shin, Young-Ju (Department of Chemistry, Dong-A University) ;
  • Lee, Eun-Seok (Department of Chemical Technology, Hanbat National University) ;
  • Moon, Tae-sung (Bioanalysis and Biotransformation Research Center, Korea Institute of Science and Technology) ;
  • Yoon, Chang-No (Bioanalysis and Biotransformation Research Center, Korea Institute of Science and Technology) ;
  • Lee, Bong-Ho (Department of Chemical Technology, Hanbat National University)
  • 발행 : 2003.01.20
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초록

The kinetic and chemical mechanisms of AChE-catalyzed hydrolysis of short-chain thiocholine esters are relatively well documented. Up to propanoylthiocholine (PrTCh) the chemical mechanism is general acid-base catalysis by the active site catalytic triad. The chemical mechanism for the enzyme-catalyzed butyrylthiocholine(BuTCh) hydrolysis shifts to a parallel mechanism in which general base catalysis by E199 of direct water attack to the carbonyl carbon of the substrate. [Selwood, T., et al. J. Am. Chem. Soc. 1993, 115, 10477- 10482] The long chain thiocholine esters such as hexanoylthiocholine (HexTCh), heptanoylthiocholine (HepTCh), and octanoylthiocholine (OcTCh) are hydrolyzed by electric eel acetylcholinesterase (AChE). The kinetic parameters are determined to show that these compounds have a lower Michaelis constant than BuTCh and the pH-rate profile showed that the mechanism is similar to that of BuTCh hydrolysis. The solvent isotope effect and proton inventory of AChE-catalyzed hydrolysis of HexTCh showed that one proton transfer is involved in the transition state of the acylation stage. The relationship between the dipole moment and the Michaelis constant of the long chain thiocholine esters showed that the dipole moment is the most important factor for the binding of a substrate to the enzyme active site.

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참고문헌

  1. Rosenberry, T. L. Adv. Enzymol. Relat. Areas Mol. Biol. 1975, 43,103-218. https://doi.org/10.1002/9780470122884.ch3
  2. Quinn, D. M. Chem. Rev. 1987, 87, 955-979. https://doi.org/10.1021/cr00081a005
  3. Finkelstein, B. L.; Benner, E. A.; Hendrixson, M. C.; Kranis, K.T.; Rauh, J. J.; Sethuraman, M. R.; McCann, S. F. Bioorg. Med.Chem. 2002, 10, 599-613. https://doi.org/10.1016/S0968-0896(01)00326-1
  4. Rocca, P.; Cocuzza, E.; Marchiaro, L.; Bogetto, F. Prog.Neuropsychopharmacol. Biol. Psychiatry 2002, 26, 369-373. https://doi.org/10.1016/S0278-5846(01)00283-4
  5. Potkin, S. G.; Anand, R.; Fleming, K.; Alva, G.; Keator, D.;Carreon, D.; Messina, J.; Wu, J. C.; Hartman, R.; Fallon, J. H. Int.J. Neuropsychopharmacol. 2001, 4, 223-230.
  6. Sussman, J. L.; Harel, M.; Frolow, F.; Oefner, C.; Goldman, A.;Toker, L.; Silman, I. Science 1991, 253, 872-879. https://doi.org/10.1126/science.1678899
  7. Bourne, Y.; Taylor, P.; Bougis, P. E.; Marchot, P. J. Biol. Chem.1999, 274(5), 2963-2970. https://doi.org/10.1074/jbc.274.5.2963
  8. Selwood, T.; Feaster, S. R.; States, M. J.; Pryor, A. N.; Quinn, D.M. J. Am. Chem. Soc. 1993, 115, 10477-10482. https://doi.org/10.1021/ja00076a002
  9. Saxena, A.; Redman, A. M. G.; Jiang, X.; Lockridge, O.; Doctor,B. P. Biochem. 1997, 36, 14642-14651. https://doi.org/10.1021/bi971425+
  10. Quinn, D. M.; Selwood, T.; Pryor, A. N.; Lee, B. H.; Leu, L. S.; Acheson, S. A.; Silman, I.; Doctor, B. P.; Rosenberry, T. L. In Multidisciplinary Approaches to Cholinesterase Functions; Shafferman, A., Velan, B., Eds.; Plenum: New York, 1992; pp 141-148.
  11. Ellman, G. L.; Coutney, K. D.; Andres, V., Jr.; Featherstone, R. M.Biochem. Pharmacol. 1961, 7, 88-95. https://doi.org/10.1016/0006-2952(61)90145-9
  12. Pryor, A. N.; Selwood, T.; Leu, L. S.; Andracki, M. A.; Lee, B. H.;Rao, M.; Rosenberry, T.; Doctor, B. P.; Silman, I.; Quinn, D. M. J.Am. Chem. Soc. 1992, 114, 3896-3900. https://doi.org/10.1021/ja00036a043
  13. Salomma, P.; Schaleger, L. L.; Long, F. A. J. Am. Chem. Soc.1964, 86, 1-7. https://doi.org/10.1021/ja01055a001
  14. Schowen, K. B. J. In Transition States of Biochemical Processes; Gandour, R. D., Schowen, R. L., Eds.; Plenum: New York, 1978;pp 225-283.
  15. Schowen, K. B.; Schowen, R. L. Methods Enzymol. 1982, 87,551-606. https://doi.org/10.1016/S0076-6879(82)87031-6
  16. Venkatasubban, K. S.; Schowen, R. L. CRC Crit. Rev. Biochem.1985, 17, 1-44. https://doi.org/10.3109/10409238409110268
  17. Quinn, D. M.; Sutton, L. D. In Enzyme Mechanism from Isotope Effects; Cook, P. F., Ed.; CRC Press: Boca Raton, FL, 1991; pp 73-126.
  18. Ripoll, D. R.; Faerman, C. H.; Axelsen, P. H.; Silman, I.;Sussman, J. L. Proc. Natl. Acad. Sci. U.S.A. 1993, 90, 5128-5139. https://doi.org/10.1073/pnas.90.11.5128
  19. Wentworth, W. E. J. Chem. Edu. 1965, 42, 96-103. https://doi.org/10.1021/ed042p96
  20. Boyle, N. A. J.; Talesa, V.; Giovannini, E.; Rosi, G.; Norton, S. J.J. Med. Chem. 1997, 40, 3009-3013. https://doi.org/10.1021/jm970141k
  21. Cho, Y.; Cha, S. H.; Sok, D. E. Neurochem. Res. 1994, 19, 799-803. https://doi.org/10.1007/BF00967447
  22. Cardozo, M. G.; Iimura, Y.; Sugimoto, H.; Yamanishi, Y.;Hopfinger, A. J. J. Med. Chem. 1992, 35, 584-593. https://doi.org/10.1021/jm00081a022
  23. Inoue, A.; Kawai, T.; Wakita, M.; Iimura, Y.; Sugimoto, H.;Kawakami, Y. J. Med. Chem. 1996, 39, 4460-4470. https://doi.org/10.1021/jm950596e
  24. Camps, P.; Achab, R. E.; Görbig, D. M.; Morral, J.; Muñoz-Torreo, D.; Badia, A.; Baños, J. E.; Vivas, N. M.; Barril, X.;Orozco, M.; Luque, F. J. J. Med. Chem. 1999, 42, 3227-3242. https://doi.org/10.1021/jm980620z

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