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2000 | 47 | 1 | 233-257
Article title

Inhibition and activation of enzymes. The effect of a modifier on the reaction rate and on kinetic parameters.

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Abstracts
EN
A combined analysis of enzyme inhibition and activation is presented, based on a rapid equilibrium model assumption in which one molecule of enzyme binds one molecule of substrate (S) and/or one molecule of a modifier X. The modifier acts as activator (essential or non-essential), as inhibitor (total or partial), or has no effect on the reaction rate (v), depending on the values of the equilibrium constants, the rate constants of the limiting velocity steps, and the concentration of substrate ([S]). Different possibilities have been analyzed from an equation written to emphasize that v = Ł([X]) is, in general and at a fixed [S], a hyperbolic function. Formulas for Su (the value of [S], different from zero, at which v is unaffected by the modifier) and vsu (v at that particular [S]) were deduced. In Lineweaver-Burk plots, the straight lines related to different [X] generally cross in a point (P) with coordinates (Su, vsu). In certain cases, point P is located in the first quadrant which implies that X acts as activator, as inhibitor, or has no effect, depending on [S]. Furthermore, we discuss: (1) the apparent Vmax and Km displayed by the enzyme in different situations; (2) the degree of effect (inhibition or activation) observed at different concentrations of substrate and modifier; (3) the concept of Ke, a parameter that depends on the concentration of substrate and helps to evaluate the effect of the modifier: it equals the value of [X] at which the increase or decrease in the reaction rate is half of that achieved at saturating [X]. Equations were deduced for the general case and for particular situations, and used to obtain computer-drawn graphs that are presented and discussed. Formulas for apparent Vmax, Km and Ke have been written in a way making it evident that these parameters can be expressed as pondered means.
Publisher

Year
Volume
47
Issue
1
Pages
233-257
Physical description
Dates
published
2000
received
1999-11-3
Contributors
author
  • Instituto de Investigaciones Biomédicas Alberto Sols, UAM-CSIC, Departamento de Bioquímica, Facultad de Medicina, Arzobispo Morcillo 4, E-28029 Madrid, Spain
  • Instituto de Investigaciones Biomédicas Alberto Sols, UAM-CSIC, Departamento de Bioquímica, Facultad de Medicina, Arzobispo Morcillo 4, E-28029 Madrid, Spain
  • Instituto de Investigaciones Biomédicas Alberto Sols, UAM-CSIC, Departamento de Bioquímica, Facultad de Medicina, Arzobispo Morcillo 4, E-28029 Madrid, Spain
References
  • 1. Segel, I.H. (1975; reprinted 1993) Enzyme Kinetics. John Wiley & Sons, New York.
  • 2. Dixon, M. & Weeb, E.C. (1979) Enzymes, 3rd Edn., Longman, London.
  • 3. Fersht, A. (1985) Enzyme Structure and Mechanism, 2nd Edn., Fremann, New York.
  • 4. Palmer, T. (1991) Understanding Enzymes, 3rd Edn., Ellis Horwood, New York.
  • 5. Cornish-Bowden, A. (1995) Fundamentals of Enzyme Kinetics, Portland Press, London.
  • 6. Cleland, W.W. (1970) Steady state kinetics; in The Enzymes, 3rd Edn. (Boyer, P.D., ed.) vol. 2, pp. 1-65, Academic Press, New York.
  • 7. Sandler, M. & Smith, H.J. (1989) Introduction to the use of enzyme inhibitors as drugs; in Design of Enzyme Inhibitors as Drugs (Sandler, M. & Smith, H.J., eds.) pp. 1-18, Oxford University Press, Oxford.
  • 8. Botts, J. & Morales, M. (1953) Analytical description of the effects of modifiers and of enzyme multivalency upon the steady state catalyzed reaction rate. Trans. Faraday Soc. 49, 696-707.
  • 9. Mahler, H.R. & Cordes, E.H. (1966) Biological Chemistry, Harper & Row, New York.
  • 10. Ricard, J. (1973) Cinetique et mecanismes d'action des enzymes, Doin, Paris.
  • 11. Metzler, D.E. (1977) Biochemistry, Academic Press, New York.
  • 12. Mathews, C.K. & van Holde, K.E. (1996) Biochemistry, 2nd Edn., Benjamin/Cummings, Redwood City (California).
  • 13. Ribeiro, J.M., Juzgado, D., Crespo, E. & Sillero, A. (1990) Computer program for the reservoir model of metabolic crossroads. Comput. Biol. Med. 20, 35-46.
  • 14. Ribeiro, J.M., Fontes, R. & Sillero, A. (1994) Enzyme inhibition as visualized with the reservoir model: relationships between I50 and inhibition constant(s) of an enzyme inhibitor. Comput. Biol. Med. 24, 129-144.
  • 15. Fontes, R., Ribeiro, J.M. & Sillero, A. (1994) A tridimensional representation of enzyme inhibition useful for diagnostic purposes. J. Enzyme Inhib. 8, 73-85.
  • 16. Frieden, C. (1964) Treatment of enzyme kinetic data. I. The effect of modifiers on the kinetic parameters of single substrate enzymes. J. Biol. Chem. 239, 3522-3531.
  • 17. Fontes, R., Ribeiro, J.M. & Sillero, A. (1999) An easy procedure to transform the ratio of two polynomials of first degree into Michaelis-Menten-type equations. Application to the ordered Uni Bi enzyme mechanism. Acta Biochim. Polon. 47, 259-268.
Document Type
Publication order reference
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YADDA identifier
bwmeta1.element.bwnjournal-article-abpv47i1p233kz
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