IUBio

MCA

Guy C Brown g.c.brown at bioc.cam.ac.uk
Thu Feb 6 06:06:34 EST 1997


Dear All,

I thought of a problem in the bath last night:

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.

What effects will totally inhibiting the activity of a particular enzyme
have on the
steady-state fluxes of a system?  Can we say anything interesting or
useful about this?

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.

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
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?


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





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