On 6 Feb 1997 11:06:34 -0000, g.c.brown at bioc.cam.ac.uk (Guy C Brown)
wrote:
>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?
Interesting question. Allow me to ramble on a bit about this. The
effect of removing or completely inhibiting a step in the system
effectively changes the structure of the system. The bit of the
pathway between the preceeding branchpoint (or fixed concentration in
the case of a linear pathway) will be a dangling piece of pathway in
equilibrium. So, if one has two branches, the effective deletion of
one branch will change the rest of the system into a linear pathway
with one flux (with an equilibrium limb dangling from the original
branchpoint metabolite).
Stefan and Ronny Schuster published a few interesting papers on
pathways that contain such equilibrium bits (what they called detailed
balanced subnetworks). Two of these are (Stefan, please add if I
missed important papers).
@ARTICLE{S161,
author = {Schuster, S. and Schuster, R.},
year = 1991,
title = {Detecting strictly detailed balanced subnetworks in open
chemical reaction networks},
journal = {J. Math. Chem.},
volume = 6,
pages = {17--40},
}
@ARTICLE{S169,
author = {Schuster, S. and Schuster, R.},
year = 1992,
title = {Decomposition of biochemical reaction systems according to
flux control insusceptibility},
journal = {J. Chem. Phys.},
volume = 89,
pages = {1887--1910},
}
Jannie
