Metabolic Control Analysis


These pages are dedicated to the memory of Henrik Kacser (full list of his publications and an annotated bibliography).

What is MCA?

Metabolic control analysis (MCA) is a phenomenological quantitative sensitivity analysis of fluxes and metabolite concentrations. In MCA one studies the relative control exerted by each step (enzyme) on the system's variables (fluxes and metabolite concentrations). This control is measured by applying a perturbation to the step being studied and measuring the effect on the variable of interest after the system has settled to a new steady state.

A more detailed introduction can be found in the Metabolic Control Analysis FAQ maintained by Athel Cornish Bowden.

Our WWW tutorial on MCA:


Theoretical and modelling:

Westerhoff, H.V. & Kell, D.B. (1987) Matrix method for determining the steps most rate- limiting to metabolic fluxes in biotechnological processes. Biotechnol. Bioeng. 30, 101-107.

Westerhoff, H.V. & Kell, D.B. (1988) A control theoretical analysis of inhibitor titrations of metabolic channelling. Comments Mol. Cell. Biophys. 5, 57-107.

Kell, D.B., van Dam, K. & Westerhoff, H.V. (1989) Control analysis of microbial growth and productivity. Symp. Soc. Gen. Microbiol. 44, 61-93.

Mendes, P. & Kell, D.B. (1993) Control analysis of metabolic channelling. In Modern Trends in Biothermokinetics, eds S. Schuster, M. Rigoulet, R. Ouhabi & J.-P. Mazat, Plenum Press, New York and London, 211-216.

Mendes, P. (1993) GEPASI: a software package for modelling the dynamics, steady states and control of biochemical and other systems. Comput. Appl. Biosci. 9, 563-571.

Mendes, P, Kell, D.B. & Westerhoff, H.V. (1994) How to vary the proportion of dynamic channelling flux at constant total flux (and decrease the intermediate pool size…). in What is controlling life? 50 years after Schrödinger's What is Life? (E. Gnaiger, F.N. Gellerich & M. Wyss, eds) Modern Trends in Biothermokinetics Vol 3, 202-204. Innsbruck University Press, Innsbruck.


Kell, D.B. & Westerhoff, H.V. (1986) Metabolic control theory: its role in microbiology and biotechnology. FEMS Microbiol. Rev. 39, 305-320.

Kell, D.B. & Westerhoff, H.V. (1986) Towards a rational approach to the optimization of flux in microbial biotransformations. Trends in Biotechnol. 4, 137-142.

Kell, D.B. (1987) Forces, fluxes and the control of microbial growth and metabolism. The twelfth Fleming lecture. J. Gen. Microbiol. 133, 1651-1665.

Kell, D.B. & Westerhoff, H.V. (1990) Control analysis of organised multienzyme systems. In Structural and organizational aspects of metabolic regulation (P. Srere, M.E. Jones & C. Mathews, eds), UCLA Symposia on Molecular and Cellular Biology, New Series 134, pp. 273-289. Alan R. Liss, New York.

Kell, D.B. & Westerhoff, H.V. (1990) Metabolic control analysis: theory and practice. In: Mixed and multiple substrates and feedstocks, ed. G. Hamer, T. Egli & M. Snozzi, pp.107- 119, Hartung-Gorre, Konstanz.

Westerhoff, H.V., van Heeswijk,W., Kahn, D. & Kell, D.B. (1991) Quantitative approaches to the analysis of the control and regulation of microbial metabolism. Antonie. van Leeuwenhoek 60, 193-207.

Kell, D.B., Westerhoff, H.V., Fell, D., Thomas, S. & Mendes, P. (1993) Demonstration programs illustrating the modelling of metabolic systems [meeting report], Binary 5, 47-49.


More MCA educational material on the net:

Other MCA related web pages: