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Acetylcholinesterase kinetics

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Abstract

Three mechanisms have been suggested to describe the inhibition of acetylcholinesterase (EC. 3.1.1.7) by an excess of acetylcholine.

  1. (i)

    Substrate inhibition occurs through the reaction of acetylcholine with acetylated enzyme. The deacetylation of this ternary complex is supposed to be completely inhibited.

  2. (ii)

    A ternary complex is formed as in (i). However, the deacetylation is not completely inhibited.

  3. (iii)

    A two-site-mechanism is discussed. Acetylcholine binds either to the active site or to the modifier site. Binding to the latter changes the activity of the active site.

Steady state treatment was applied to (i)–(iii). A least squares fit led to catalytic parameters. It is demonstrated that mechanism (ii) is the most simple one which can describe satisfactorily the experimental data. Limits for a set of rate constants are derived from the catalytic parameters. A numerical integration shows that the steady state approximation may be used even when the mechanisms are rather complex.

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References

  • Anglister L, Silman I (1978) Molecular structure of elongated forms of electric eel acetylcholinesterase. J Mol Biol 125: 293–311

    Google Scholar 

  • Beauregard G, Roufogalis BD (1979) Involvement of calcium ions in the properties of cardiolipin-associated erythrocyte acetylcholinesterase. Biochim Biophys Acta 557: 102–111

    Google Scholar 

  • Bender ML, Kézdy FJ, Gunter CR (1964) The anatomy of an enzymatic catalysis. α-Chymotrypsin. J Am Chem Soc 86: 3714–3721

    Google Scholar 

  • Bolger MB, Taylor P (1979) Kinetics of association between bisquaternary ammonium ligands and acetylcholinesterase. Evidence for two conformational states of the enzyme from stopped-flow measurements of fluorescence. Biochemistry 18: 3622–3629

    Google Scholar 

  • Bon S, Huet M, Lemonnier M, Rieger F, Massoulié J (1976) Molecular forms of Electrophorus acetylcholinesterase; molecular weight and composition. Eur J Biochem 68: 523–530

    Google Scholar 

  • Bon S, Massoulié J (1976) An active monomeric form of Electrophorus electricus acetylcholinesterase. FEBS Lett 67: 99–103

    Google Scholar 

  • Bon S, Massoulié J (1976) Molecular forms of Electrophorus acetylcholinesterase; the catalytic subnits: Fragmentation, intra-and inter-subunit disulfide bonds. FEBS Lett 71: 273–278

    Google Scholar 

  • Chen YT, Rosenberry TL, Chang HW (1974) Subunit heterogeneity of acetylcholinesterase. Arch Biochem Biophys 161: 479–487

    Google Scholar 

  • Dudai Y, Herzberg M, Silman I (1973) Molecular structures of acetylcholinesterase from electric organ tissue of the electric eel. Proc Natl Acad Sci USA 70: 2473–2476

    Google Scholar 

  • Froede HC, Wilson IB (1980) Acetylcholinesterase — the acylenzyme intermediate. Neurochem Int 2: 193–197

    Google Scholar 

  • Gear CW (1971) Numerical initial value problems in ordinary differential equations. Prentice Hall, Englewood Cliffs, NJ

    Google Scholar 

  • Gentinetta R, Brodbeck U (1976) Differences in subunit activities in acetylcholinesterase as possible cause for apparent deviation from normal Michaelis-Menten kinetics. Biochim Biophys Acta 438: 437–448

    Google Scholar 

  • Haldane JBS (1965) Enzymes. London: Longmans, Green and Company (1930) reprinted by the MIT Press, Cambridge, MA

    Google Scholar 

  • Heilbronn E (1958) The pS-activity curve of a serum fraction IV-6-3 studied with butyrylcholine at pS above 3. Acta Chem Scand 12: 1879–1880

    Google Scholar 

  • Hopff WH (1976) Isolierung von Acetylcholinesterase und Charakterisierung der katalytisch aktiven Stelle. Vierteljahrsschr Naturforsch Ges Zürich 121: 223–260

    Google Scholar 

  • Krupka RM, Laidler KJ (1961) Molecular mechanisms for hydrolytic enzyme action. J Am Chem Soc 83: 1445–1460

    Google Scholar 

  • Krupka RM (1964) Acetylcholinesterase: Trimethylammonium-ion inhibition of deacetylation. Biochemistry 3: 1749–1754

    Google Scholar 

  • Meunier JC, Changeux JP (1969) On the irreversible binding of p-(trimethylammonium) benzenediazonium fluoroborate (TDF) to acetylcholinesterase from electrogenic tissue. FEBS Lett 2: 224–226

    Google Scholar 

  • Mooser G, Schulman H, Sigman DS (1972) Fluorescent probes of acetylcholinesterase. Biochemistry 11: 1595–1602

    Google Scholar 

  • Mooser G, Sigman DS (1974) Ligand binding properties of acetylcholinesterase determined with fluorescent probes. Biochemistry 13: 2299–2307

    Google Scholar 

  • Murray DRP (1930) The inhibition of esterases by excess substrate. Biochem J 24: 1890–1896

    Google Scholar 

  • Nachmansohn D, Rothenberg MA (1945) Studies on cholinesterase. I. On the specificity of the enzyme in nerve tissue. J Biol Chem 158: 653–666

    Google Scholar 

  • Nachmansohn D, Wilson IB (1951) The enzymic hydrolysis and synthesis of acetylcholine. Adv Enzymol 12: 259–339

    Google Scholar 

  • Neumann E, Rosenberry TL, Chang HW (1978) Elementary chemical reactions of acetylcholine with receptor and esterase: Relationship to neuronal information transfer. In: Karlin A, Tennyson VM, Vogel HJ (eds) Neuronal information transfer. Academic Press, New York, pp 183–210

    Google Scholar 

  • Rosenberry TL, Bernhard SA (1971) Studies of catalysis by acetylcholinesterase. Fluorescent titration with a carbamoylating agent. Biochemistry 10: 4114–4120

    Google Scholar 

  • Rosenberry TL, Bernhard SA (1972) Studies of catalysis by acetylcholinesterase. Synergistic effects of inhibitors during the hydrolysis of acetic acid esters. Biochemistry 11: 4308–4321

    Google Scholar 

  • Rosenberry TL, Chang HW, Chen YT (1972) Purification of acetylcholinesterase by affinity chromatography and determination of active site stoichiometry. J Biol Chem 247: 1555–1565

    Google Scholar 

  • Webb G, Clark DG (1978) Acetylcholinesterase: Differential affinity chromatographic purification of 11S and 18S plus 14S forms; the importance of multiple-site interactions and salt concentration. Arch Biochem Biophys 191: 278–288

    Google Scholar 

  • Wermuth B, Brodbeck U (1973) Interaction of proflavine and acriflavine with acetylcholinesterase. Eur J Biochem 37: 377–388

    Google Scholar 

  • Wilson IB, Cabib E (1956) Acetylcholinesterase: Enthalpies and entropies of activation. J Am Chem Soc 78: 202–207

    Google Scholar 

  • Wilson IB, Alexander J (1962) Acetylcholinesterase: Reversible inhibitors, substrate inhibition. J Biol Chem 237: 1323–1326

    Google Scholar 

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Hofer, P., Fringeli, U.P. Acetylcholinesterase kinetics. Biophys. Struct. Mechanism 8, 45–59 (1981). https://doi.org/10.1007/BF01047105

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  • DOI: https://doi.org/10.1007/BF01047105

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