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:
- Control coefficients and rate-limiting steps
- Enzyme kinetics and MCA: the elasticity coefficients
- A metabolic web: the connectivity relations
- Control by external effectors: the response coefficients
- The real world: branches, cycles, enzyme-enzyme interactions and enzyme cascades
- Putting it all together: the matrix methods
- Getting your hands dirty: experimental approaches
- Software for metabolic control analysis
- Selected references
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:
- The Metabolic control analysis FAQ by Athel Cornish-Bowden
- Hypertext version of the Chapter 10 (MCA) of Athel Cornish-Bowden's book Fundamentals of Enzyme Kinetics.
- A 'canon' of reviews on metabolic organisation, channelling and control
- Teaching Metabolic Control Analysis and kinetic modelling. Towards a portable teaching module. a paper by Jacky Snoep, Pedro Mendes and Hans Westerhoff that appeared in the February 1999 issue of the The Biochemist [full text PDF (244 kb)] Mounted on the Internet with kind permission from the Biochemical Society (1999)
Other MCA related web pages:
- MCA 99 10-16 April 1999, Visegrád, Hungary. NATO Advanced Research Workshop on Technological and Medical Implications of Metabolic Control Analysis, organised by Athel Cornish-Bowden
- The BTK study group had another meeting in Fiskebäckskil, July 1998
- Doug Kell's group (we!) have a Home page and a list of our publications on MCA.
- The FTP archive of David Fell's group where you can find various software packages and documents
- Martin Brand's lab (Univ. Cambridge)
- Reinhart Heinrich's Group (Humboldt-University Berlin)
- The Marseilles Group (CNRS).
- Hans Westerhoff (Free Univ. Amsterdam)
- Marta Cascante (Univ. Barcelona)
- Guy Brown's lab (Univ. Cambridge)
- Paul Schlosser
- Luis Acerenza
- The bionet.metabolic-reg newsgroup, where MCA is discussed in USENET. And now it can be accessed through the web.
Last updated: May 31, 2016 at 10:10 am