Dear Petr
Pedro Mendes wrote
>> (2) follows Henrik Kacser's spirit of a description that does
>> not require knowledge of mechanism, while (1) does not. It is
>> interesting that so far (2) has not been much used for such
>> systems.
with regard to which you asked
> Excuse the outsider again for interrupting the experts, but why
> -wouldn't- we "require the knowledge of mechanism" for any biochemical
> system? A -molecular- system should never be too complex to be
> described successfully in elementary physico-chemical terms (mass action
> law, diffusion, ...).
Kacser's point (we called it `Kacser's dream' in our 1993 EJB paper
[Hofmeyr, Cornish-Bowden, Rohwer (1993) Eur.J.Biochem. 212,
833-837.]) was that detailed knowledge of individual reaction
mechanisms should not be needed to understand the control of
steady-state concentration and flux. He did not mean that knowledge
of mechanism per se is not required in general or not important. In
the above paper we stumbled on to a solution to Kacser's dream that
was subsequently developed into what we now call `co-response
analysis' (a full treatment is given in Hofmeyr and Cornish-Bowden
(1996) J. Theor. Biol. 182, 371-380). I say "stumbled onto" because
we did not originally set out to fulfil Henrik's dream, but rather
sought to find the relationship between co-response coefficients and
internal response coefficients.
All that is required to conduct a co-response analysis is (1) the
ability to alter independently the activity of the steps in the
system (2) the ability to measure changes in the steady-state fluxes
and concentrations. Co-response analysis differs from conventional
control analysis in that it does not require knowledge of the
magnitude of the activity changes (conventionally, one would have to
measure the fractional change in the activity and the fractional
change in the steady-state variable in order to calculate a response
coefficient). In other words, no local enzyme measurements need to be
made in principle and therefore no mechanistic information is
required. The slopes of log-log plots of steady-state variables
against each other give the co-response coefficients, and provided
one has enough of them, one can calculate all the control and
elasticity coefficients.
Best regards
Jannie
Prof. Jannie Hofmeyr Tel: +27 21 808 3039
Dept. of Biochemistry Fax: +27 21 808 3022
University of Stellenbosch e-mail: jhsh at maties.sun.ac.za
Stellenbosch 7600
South Africa
