Is it Metabolic Control THEORY or Metabolic Control ANALYSIS

[Bignone]

> Herbert M Sauro wrote:
> > 
> > MCA Analysis or Theory?
> >
> > [...] I remember as an
> > undergrad, our metabolic pathway lecturer ridiculing the so-called 'armchair
> > biochemists' (i.e the theorists) and that experiment alone was the only true
> > way forward for our science (perhaps unknown to him he was of course
> > theorizing all the time if he'd only stop to think!). I grew up, so to
> > speak, and I'm sure many others did too, thinking that theory was something
> > that one didn't speak too loudly about, and computers, well one didn't go
> > near computers! 
>

This is an aspect important and interesting at the same time. In my opinion
it is a pseudo-problem. It depends from which point of view you are looking
the system from. As an aside, this fact is in the literature from the '60.
Jacob and Monod had already noticed that there is no correlation between
the ragulation of one enzyme - its induction at the genetic level - and
the metabolite that this enzyme act upon, they where defining the interaction
"gratuitous" (Monod, "Chance and necessity"). THis imply, obviously, that
proteins (enzymes) are able to do a sort of combinatorics, which is huge.
Creating chemical correlations between molecules that would not interact
on a strict chemical basis.

So there is no way, or depending on cases it is extremely difficult, to predict 
the components of a pathway theoretically. And this has given experimentalists
the possibility to forget about theory for decades. Being the pathways so
complex you can push the intervention of theory very far. At present several
experimentalists do not know theory that much.

This was not the case at the beginning of this story, most of the initial work
done on DNA and proteins, was done by people who knew the theory well.

But then the snake hit you back. Once the stamp collection is finished you
are left with the problem of using it. Then you find yourself with a huge
phase space where you do not understand any more what will happen if you
try to change one of the pieces. And this is the revenge of theory.

Are now some years that I was waiting for this to happen, and here it is.
In this discussion somebody was citing the paper of Kurt Kohn - former
director of the Pharmacology Dept. at NCI -. Take a look at the interactions
described for P53, you can imagine the effect when people where knocking
off the gene and mices still developed basically normally, or when 
trying to make onco-mice introducing into mice the Ras oncogene people
got animals with arthritis.

;-)

Regrads

F. Bignone

-- 
---------------------------------------------------------
 Franco A. Bignone, 

 National Cancer Institute, I.S.T., Dept. Experimental Oncology,
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         abignone at unige.it
         fbignone at gatto.chem.utoronto.ca

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