Skip to main content
Log in

Susceptibilities of an Irreversible Michaelis – Menten Enzyme

  • Original Article
  • Published:
Bulletin of Mathematical Biology Aims and scope Submit manuscript

Abstract

The nonlinear response of the simplest irreversible Michaelis – Menten enzyme is considered. In the context of metabolic networks, i.e. in vivo, the enzyme is subject to sustained, frequently time-dependent, input fluxes that keep the system out of equilibrium. The connection between the fluxes and the response is investigated by means of a new sensitivity analysis. The kinetics of the enzyme is simple enough to allow for the computations to be carried out analytically. In particular, a set of sensitivities of the response with respect to the substrate influx, the susceptibilities, is derived. The susceptibilities are multivariate functions and thus are suitable for predicting complete progress curves of several variables of biochemical interest, namely, rates and concentrations. This is shown by means of an example. The relationship between the susceptibilities and the stoichiometry of the reaction is also taken into account. Moreover, all the required information comes from decay experiments of initial concentrations, which are common in enzymological setups.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Carlitz, L., 1965. The coefficients in an asymptotic expansion. P. Am. Math. Soc. 16, 248–252.

    Article  MATH  Google Scholar 

  • Carpenter, R.H.S., 2004. Homeostasis: a plea for a unified approach. Adv. Physiol. Educ. 28, S180–S187.

    Article  Google Scholar 

  • Corless, R.M., Gonnet, G.H., Hare, D.E.G., Jeffrey, D.J., Knuth, D.E., 1996. On the Lambert Ω function. Adv. Comput. Math. 5, 329–359.

    Article  MathSciNet  MATH  Google Scholar 

  • Duggleby, R.G., 1983. Determination of the kinetic properties of enzymes catalysing coupled reaction sequences. Biochim. Biophys. Acta 744, 249–259.

    Google Scholar 

  • Duggleby, R.G., 1995. Analysis of enzyme progress curves by non-linear regression. Methods Enzymol. 249, 61–90.

    Article  Google Scholar 

  • Duggleby, R.G., Clarke, R.B., 1991. Experimental designs for estimating the parameters of the Michaelis–Menten equation from progress curves of enzyme-catalysed reactions. Biochim. Biophys. Acta 1080, 231–236.

    Google Scholar 

  • Duggleby, R.G., Morrison, J.F., 1977. The analysis of progress curves for enzyme-catalysed reactions by non-linear regression. Biochim. Biophys. Acta 481, 297–312.

    Google Scholar 

  • Duggleby, R.G., Nash, J.C., 1989. A single parameter family of adjustments for fitting enzyme kinetic models to progress curve data. Biochem. J. 257, 57–64.

    Google Scholar 

  • Gessel, I., Stanley, R.P., 1978. Stirling polynomials. J. Comb. Theory A 24, 24–33.

    Article  MathSciNet  MATH  Google Scholar 

  • Goudar, C.T., Sonnad, J.R., Duggleby, R.G., 1999. Parameter estimation using a direct solution of the integrated Michaelis–Menten equation. Biochim. Biophys. Acta 1429, 377–383.

    Google Scholar 

  • Graham, L., Knuth, D.E., Patashnik, O., 1994. Concrete Mathematics. A Foundation for Computer Science. Addison-Wesley, Reading, MA.

    MATH  Google Scholar 

  • Heinrich, R., Rapoport, T.A., 1974. A linear steady-state treatment of enzymatic chains. General properties, control and effector strength. Eur. J. Biochem. 42, 89–95.

    Article  Google Scholar 

  • Kacser, H., Burns, J.A., 1973. The control of flux. Symp. Soc. Exp. Biol. 32, 65–104.

    Google Scholar 

  • Kremling, A., Jahreis, K., Lengeler, J., Gilles, E., 2000. The organization of metabolic reaction networks: a signal-oriented approach to cellular models. Metab. Eng. 2, 190–200.

    Article  Google Scholar 

  • Rodríguez, Y., Torralba, A.S., Montero, F., 2002. Periodic signal transmission through metabolic pathways with Michaelian kinetics. J. Phys. Chem. B 106, 5536–5542.

    Article  Google Scholar 

  • Schnell, S., Maini, P., 2000. Enzyme kinetics at high enzyme concentration. Bull. Math. Biol. 62, 483–499.

    Article  Google Scholar 

  • Schnell, S., Mendoza, C., 1997. Closed form solution for time-dependent enzyme kinetics. J. Theor. Biol. 187, 207–212.

    Article  Google Scholar 

  • Schnell, S., Mendoza, C., 2000. Time-dependent closed form solutions for fully competitive enzyme reactions. Bull. Math. Biol. 62, 321–336.

    Article  Google Scholar 

  • Schnell, S., Mendoza, C., 2001. A fast method to estimate kinetic constants for enzyme inhibitors. Acta Biotheor. 49, 109–113.

    Article  Google Scholar 

  • Torralba, A.S., 2003. Susceptibility of non-linear systems as an approach to metabolic responses. Bioinformatics 19, 2428–2435.

    Article  Google Scholar 

  • Torralba, A.S., Yu, K., Shen, P., Oefner, P.J., Ross, J., 2003. Experimental test of a method for determining causal connectivities of species in reactions. Proc. Natl. Acad. Sci. U.S.A. 100, 1494–1498.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Antonio S. Torralba.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Torralba, A.S., Rodríguez, Y. Susceptibilities of an Irreversible Michaelis – Menten Enzyme. Bull. Math. Biol. 68, 1335–1353 (2006). https://doi.org/10.1007/s11538-006-9111-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11538-006-9111-y

Keywords

Navigation