In article <5dcdvq$pk3 at mserv1.dl.ac.uk>, Guy C Brown
<g.c.brown at bioc.cam.ac.uk> writes
>Dear All,
>>I thought of a problem in the bath last night:
How to find the soap? Just joking!
>>The problem relates to a general theory of the effects of gene deletion or total
>inhibition of an enzyme, and also relates to the problem of how we are to work
>out what all the genes in the genome do.
I'm not sure if you can produce a general theory on the effects of gene
deletion etc. You know yourself that the moment you consider large
changes you're into the relm of nonlinear dynamics and not even the
physicists have a general answer to that problem. Your only option is
numerical simulation of specific examples and see whether you can work
out any generalisations. You might you never know.
snip
>>We can quantify the effect on a particular flux (J) as -deltaJ/J when the
>activity
>of a particular enzyme (E) goes to zero, and call this the "total control"
>(T) by E over J.
The deltaJ must be a finite change, it can't be infinitessimal. The
deltaE/E will equal one. Since E equals deltaE. Of course deltaJ/J will
be a number that can be measured and simualated and there may well be
patterns in their values. But relating any discovered patterns to some
mathematical theory might be more difficult, and you're more than likely
going to have to make some gross assumptions on the degree of
nonlinearity to the extent that the system is linear. What you mention
sounds like Rankin and Henirk's work on finite changes? And there they
did have to make some major assumptions.
>>In the case of a linear pathway obviously (but importantly) the total
>control of each
>and every enzyme is 1.
>>In the case of a branched pathway the total control of an enzyme is 1 over
>the flux
>through its own branch, but between 1 and minus infinity for the fluxes in
>the other
>branches. The problem is can we say anything interesting or useful about
So you have found some patterns.
>the level
>of this total control? E.g. Is there a relation to the fluxes, the total
>or integral
>elasticities, the other total control levels? Is the total control
>constrained by the
>eleasticities or control coefficients of MCA? What happens with 2 knockouts?
>What about other pathway structures? Or is there nothing useful to be said?
Until you try, you'll never know.
>>>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
>>
--
Herbert M Sauro
Future Skill Software (Specialists in Science Software for Education)
email: HSauro at fssc.demon.co.uk
Telephone: 01974 282428
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