IUBio

Is it Metabolic Control THEORY or Metabolic Control ANALYSIS

Petr Kuzmic pkuzmic at biokin.com
Mon Aug 28 09:49:25 EST 2000



Athel Cornish-Bowden wrote:

> [...] If I say "I'd like
> to understand what's going on inside the White House" 

If you mean the U.S. President's residence, let's not "go there", as
they say ...

> it's likely that I
> want understanding at a coarser level than in terms of chemical reactions.

... because we might find that, indeed, important historical events in
the recent administration are understandable largely in terms of
pheromones:

   http://www.time.com/time/daily/scandal/monica/aug61.html

Anyway, back to the topic on hand.

> Metabolic control analysis wants to know what the various enzymes are
> doing, but not how they are doing it (which is a perfectly legitimate, but
> separate, area of enquiry). Returning to David Garfinkel, therefore, I
> think that in some of his investigations he made it unnecessarily difficult
> and complicated by concentrating on the mechanisms of the individual
> enzyme-catalysed reactions when it would have given the same information in
> a more understandable form if he had used rate equations for the complete
> reactions. I think that somewhere he showed that this was legitimate but
> then continued with detailed mechanisms regardless.

I understand many people's strong need to emphasize molecular mechanisms
in their biochemical research.  It is my impression that the history of
life sciences is largely a "recursive descent" path, from organisms to
cells to molecules and even to elementary particles.  (I forgot the name
of a German scientist who proposed in the early 1980's that the observed
chirality of DNA is a result of a quantum-mechanical effect.)  In any
case, this is the usual deductive or analytical approach.

I also understand the need to move away from mechanisms in those cases
where we do not know what they are.  For example, we've all see enzyme
reactions with a complex substrate-velocity dependence similar to this
(sigmoidal increase to a maximum, followed by a decrease to an
asymptote):

V

|                  o
|               o     o
|             o           o  
|            o                  o      o       o
|           o
|          o
|        o
|     o
| o
+------------------------------------------------- [S]

This behavior could have many different mechanistic interpretations, so
why not just describe it by some rational polynomial,

	V = (a + b[S] + c[S]^2 + ...) / (d + e[S] + f[S]^2 + ...),

determine the coefficients a, b, c, ... from the available data, and use
the polynomial model  without ever even trying to ascribe physical
meaning to a, b, c, etc.  But what are the limitations of this empirical
(as opposed to mechanistic) model building?  Isn't it true that the
empirical model so built is only applicable to the exact conditions that
were used to construct it?

I apologize if my questions seem naive.  As you can see, I know
practically nothing about the formal aspects of MCA / MCT, because thus
far I've been sufficiently embroiled in biochemical mechanisms.  Thanks
for any kind words of wisdom you might have.

	- Petr

_____________________________________________________________________
P e t r   K u z m i c,  Ph.D.               mailto:pkuzmic at biokin.com
BioKin Ltd. * Software and Consulting           http://www.biokin.com






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