On 18 Aug 2000, at 15:46, David Fell wrote:
> snipped some discussion on MCA vs MCT
> ...
> ...
> What could be possible contenders for the statements of MCT? I
> suggest:
>> 1. The total amount of control of flux exertable by the enzymes
> of a metabolic pathway is limited. (No need to tie it to the
> particular value of 1)
> 2. The control of metabolite concentrations is not so limited.
> 3. The control is potentially distributed over the components
> of the system in a way that depends on all the components of the
> system and varies with the operating conditions of the pathway.
>> Corollary of 1: large changes of flux are not achieved by
> control at a single enzyme site.
> Corollary of 2 : specific control mechanisms are needed to limit
> concentration changes when fluxes change.
While I agree with these statements, they appear to me to be too
restrictive about what MCA/MCT can do. The reason is that the
focus is too much on flux and concentration control (most of the
time only on flux control). This, I suppose is necessary to counter
the "rate limiting step" dogma and emphasise that in general
control is shared.
However, this misses what is in my opinion the most important
contribution of MCA: the relation of systemic properties (control
coefficients) to local properties (elasticities), as generalised in
the C.E=I matrix equation. This enables us to _understand_
systemic behaviour in terms of the properties of the components,
for example how the value of a certain control coefficient
depends (or not) on certain elasticities, which elasticities are
important and which are not, etc.
Used in this way, MCA is more of an "analysis" than a "theory", it
is a language for discussing behaviour of metabolic systems.
Flux and concentration control are just one part of it. A much
stronger tenet of MCA is that the properties of all the
components of a (metabolic, or hierarchical if we extend the
analysis) system are sufficient to explain the _systemic_
behaviour. We don't need to invoke any magic...
What do you think?
Johann
--
Johann M. Rohwer
Dept. of Biochemistry, Univ. of Stellenbosch
Private Bag X1, 7602 Matieland
SOUTH AFRICA
Tel.: +27-21-8085843
Fax: +27-21-8085863
E-mail: jr at maties.sun.ac.za
WWW: http://www.sun.ac.za/biochem/
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