MCA starts from a number of postulates
(such as that there is a steady state, the system is homogenous, and N*V=0),
and (analytically) derives a number of theorems (e.g. the summation theorem).
The theorems themselves are not empirically (experimentally) falsifiable
(testable) given the postulates, because they are analytically (logically)
derived from the postulates. (Although of course there might have been
a logical (or mathmatical) mistake in their derivation).
But when we apply MCA to a real biological system we make an additional
assumption (or hypothesis) i.e. that the postulates are actually true
of the system under study. This hypothesis (together with the postulates
and theorems derived from them) then become empirically testable (or
falsifiable). So that for example if we find that the experimenatly
measured flux control coefficients do not add up to 1 we can conclude
that one or more of the postulates is false (ignoring the possibility
of experimental error).
Thus I think that the body of theorems that make up MCA is not itself
a theory. It only becomes so when we add the additional hypothesis
that the postulates of MCA actually are generally true of real metabolism.
We might call this MCT, and this is of course falsifiable.
Virtually all theories I can think of have a similar structure (consisting
of a mixture of logical and empirical statements). For example
Enzyme kinetics or Euclidian Geometry.
At 16:05 20/07/00 +0200, you wrote:
>Lately I have been wondering whether metabolic control analysis as developed
>originally by Kascer & Burns and Heinrich & Rapoport is a genuine theory or
>not. Personally I think a theory should be falsifiable in the Popper sense.
>I'm quite convinced that metabolic control analysis is not falsifiable since
>it holds for any (nonlinear) dynamical system under steady state conditions
>(all theorems can be obtained from implicit differentiation of N*V=0).
>>An example:
>Let's say that according to MCA the flux control coefficient of succinate
>dehydrogenase on TCA flux =0.21 (obtained with a mathematical model
>consisting of detailed enzyme kinetics (obtained from in vitro rate kinetic
>measurements)). But when measured it turmed out to be 0.8. Does this flasify
>MCA? No. It falsifies only the mathematical model!
>>Therefore I'm inclined to think that MCA is not a theory but a tool and
>therefore its MCA and not MCT.
>>Can anybody think of a way to falsify MCA?
>Can anybody make an argument why MCA is a theory even though not
>falsifiable?
>Are there examples of similar theories?
>>>>>>Dr Guy C. Brown
Department of Biochemistry,
University of Cambridge,
Tennis Court Road,
Cambridge CB2 1QW, UK.
Tel: (44) (0)1223 333342
Fax: (44) (0)1223 333345
e-mail: gcb at mole.bio.cam.ac.ukhttp://www.bio.cam.ac.uk/dept/biochem/brown
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