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Co-response analysis: a new paper

Jannie Hofmeyr jhsh at maties.sun.ac.za
Thu May 5 09:49:45 EST 1994


Dear Netters

A paper by Athel Cornish-Bowden and myself has just appeared in Biochemical
Journal (1994) 298, 367-375. In it we examine the robustness of co-response
analysis, a method we proposed last year [Eur. J. Biochem 212, 833-837
(1993)] for the complete control and elasticity analysis of metabolic systems
without the need for measuring enzyme activities. This method was a spin-off
from our ideas on metabolic regulation analysis. We believe co-response
analysis holds great promise for experimental control and regulation
analysis and hope that many of you will try it on your own problems. We were
surprised at how robust co-response analysis turned out to be, albeit in
numerical experiments. Here follows the abstract:

ABSTRACT

The control structure of a metabolic system can in principle
be determined without the need for purification of the
component enzymes and study of their kinetic properties,
provided that their activities can be perturbed by amounts
sufficient to produce measurable changes in the steady-state
variables, i.e. the fluxes through the system and the
concentrations of the intermediates. Each perturbation is
characterized in terms of the co-response coefficients of all
pairs of variables, i.e. the slopes of the lines produced when
the logarithm of one variable is plotted against the logarithm
of another, both varying in response to the same perturbation.
If all the co-response coefficients are assembled into a
matrix, the inverse of this matrix can be transformed into a
matrix containing all the component elasticities, which can be
inverted to provide the complete matrix of control
coefficients. In a simple three-enzyme pathway studied, the
analysis proves not to require unrealistically high accuracy
in the original co-response measurements: even with errors
with standard deviation plus minus 5.77 degrees in the angles
to the horizontal of the lines in the co-response plots
(equivalent at best to errors of +- 20% in the corresponding
co-response coefficients), the final control coefficient
matrix may be adequate for assessing the control structure of
the system. Examination of literature data from studies of
mitochondrial respiration and of gluconeogenesis indicates
that considerably higher precision than this is achievable.

Comments and discussion?

Best regards
Jannie Hofmeyr

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Jannie Hofmeyr                    InterNet e-mail: jhsh at maties.sun.ac.za
Dept. of Biochemistry                   Telephone: +27 21 8083039
University of Stellenbosch                    Fax: +27 21 8083022
Stellenbosch 7600
South Africa
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