Using the Yeast Glycolysis Example with COPASI...

[Kevin Knight]

Using the Yeast Glycolysis Example with COPASI, which enzyme would I change the concentration of to get an ATP:ADP output of great than 3:1?

If anyone could help me with this, that would be amazing!

[Pedro Mendes]

Hello Kevin,

this seems to be an interesting problem for optimization. However, if
you want to achieve this by changing only one enzyme, then you have to
decide which one ahead of time. Of course you can do this for every one
of them and then find out which one required the smallest change.

In optimization define an objective function that is the ratio of [ATP]
over [ADP] minus 3 squared. It should look like this:
({[ATP])/{[ADP]}-3)^2
(note that the {[ATP]} and {[ADP]} must be selected from the little
copasi icon to the right). This objective function will look for
conditions that produce exactly a ratio of 3 (if you want more, just
type 3.001 or 3.1 etc). Then select the Vmax parameter of one reaction
and carry out a minimization. Then remove that parameter and instead add
the Vmax from another reaction, etc. until you do all reactions.

You will find out that not all enzymes are capable of changing the
ATP/ADP ratio that much... the hexose transporter or the ATPase are
likely to be the best ones...

Another way of looking at this is to define a global quantity of type
"assignment", defined as the ratio of ATP/ADP:
{[ATP])/{[ADP]}
then carry out sensitivity analysis of this (using single object and
then chosing this global quantity you've defined). That will tell you
which of the Vmax values has the strongest influence on the ratio, and
that is your best bet.

Pedro

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--
Pedro Mendes
Professor of Computational Systems Biology
http://www.comp-sys-bio.org
School of Computer Science
Manchester Centre for Integrative Systems Biology
University of Manchester

Manchester Institute of Biotechnology
131 Princess Street
Manchester, M1 7DN, U.K.

[Matthias König]

Hi Kevin,
Mainly you have to vary all the Vmax like Pedro said.

There are two options (see analysis ipython notebook HTML attached), which are separated from the reference model state via a valley of instability (not sure if model gets unstable or solver problem)
- make HK_Vmax small
- make HXT_Vmax small

SBML exported from Copasi & than all Vmax varied.
M

[Pedro Mendes]

Matthias,
the model is unstable, mostly because the branches have constant flux;
so below certain rates of glucose input some concentrations go negative.
This is a well-known problem of this model...

Pedro

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[König, Matthias]

So the model sits with its Vmax of HXT and HK on the border of instabilty. So no physiological way to change the Vmax to get ATP/ADP >3.
M
________________________________________
Von: copasi-u...@googlegroups.com [copasi-u...@googlegroups.com]&quot; im Auftrag von &quot;Pedro Mendes [pedro....@manchester.ac.uk]
Gesendet: Freitag, 19. Februar 2016 10:51
An: copasi-u...@googlegroups.com
Betreff: Re: [copasi-user-forum] Re: Using the Yeast Glycolysis Example with COPASI...

Pedro

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[Kevin Knight]

Thank you everyone! This was a huge help, I was the only person in my class who got the problem right thanks!