Couple reactions with logic function

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Akhila George

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May 30, 2023, 1:07:06 AM5/30/23
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Hi,

There are two analogous reversible reactions in the model which form futile cycle in FBA. In the real case scenario, either one of these reactions is functional in a particular condition. In COBRA Toolbox, does it include an option to couple two reactions with a logical function like OR function, a constraint that allows flux through either one of the given two reactions at a time?

Thanks!


John Irudayaraj

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Jun 2, 2023, 1:01:57 AM6/2/23
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Hi Akhila,
    if the reactants/products are same and gpr is different then you can basically keep one reaction and update the gpr with OR association. can you share the reactions?

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Ronan M.T. Fleming

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Jun 2, 2023, 8:10:53 AM6/2/23
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Hi All,
what exactly is a 'futile cycle' in this case?

It sounds like a pair of reactions
A + B -> C + D
C + D -> A+ B
Is that really a 'futile cycle'? It seems more like a thermodynamically infeasible cycle.

To remove thermodynamically infeasible cyclic flux you can try
solution = optimizeCbModel(model, osenseStr, minNorm)
with minNorm = 1.
Alternatively, try

I think we need a minimal example of a 'futile cycle' to clarify if it is any different from a thermodynamically infeasible cycle.

Regards,

Ronan



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Akhila George

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Jul 12, 2023, 9:20:07 PM7/12/23
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Thank you, John and Ronan. 
What if those reactions are not analogous. For example, one reaction is involved in biosynthesis, and another is involved in degradation pathway of the same metabolite, like the reactions given below. 
A + ATP -> B + ADP + H+  
B + water -> A + Pi
In experiments, either one of them carries flux depending on the substrate provided. However, while simulating growth, the excess ATP synthesized in the network, gets involved in the loop mentioned above, instead of being consumed by other reactions. 
I was wondering if there is a way to resolve it other than applying condition-based constraints to these reactions.

Kind regards,
Akhila

Ronan M.T. Fleming

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Jul 13, 2023, 7:56:15 AM7/13/23
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Hi Akhila,
I am curious if such a futile cycle would be eliminated using this function...
You could also try
with
minNorm = 'one'
or 
minNorm = 'two'
Regards,
Ronan

John Irudayaraj

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Jul 13, 2023, 12:05:46 PM7/13/23
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Hi akhila,
    For this set of reactions to form a loop you need ATP. I would check if my model is  generating ATP out of nothing through some unbalanced reactions. 
Such ATP wasting futile cycles can happen in reality and in your model they can happen if  you have excess ATP being generated over and above what is needed for your optimality condition. You might need to consider adding some ATP maintenance requirements to your model. 

Regards,
John

Ronan M.T. Fleming

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Jul 13, 2023, 12:09:27 PM7/13/23
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Hi Akhila,
just to add to John's valuable advice, you can find the largest subset of supposed internal reactions that are balanced using:
Regards,
Ronan

Akhila George

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Jul 13, 2023, 8:20:52 PM7/13/23
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Thanks Ronan and John! Let me try your suggestions. 

Kind regards,
Akhila
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