Identify if ATP is lower than the thermodynamically feasible limit.

[ChristianLieven]

Problem description

A related one is the need for ATP production to be lower than the thermodynamically feasible limit. Typically 60-80% of the limit

• Radhakrishnan Mahadevan

Hi Krishna, how do I determine the thermodynamically feasible limit? I suppose that is different for each organism? Do you have a publication you can point me to perhaps?

• My response

It does not depend on the organism but on the substrate donor and acceptor pair. You can find details on this in the Rittmann and McCarty book. For additional details, please contact Kevin Correia in my group who can help out

• Radhakrishnan Mahadevan

So here I go: @kcorreia, I summon thee!

[Midnighter]

@kcorreia can you help us with this issue, please?

[kcorreia]

Sorry I missed this!

This is a tough one to implement, especially at scale. I'll offer my quick views, but look into it a bit more to see if I can offer anything else.

Previously I used metabolic reconstruction and metabolic models interchangeably. But since working with the memote project I have learned that some people define a metabolic model as a reconstruction with initial conditions / other boundary conditions. Studying ATP production is more relevant to the model than reconstruction since you can have many conditions that an organism can grow on (for example glucose, fructose, galactose, citrate, ethanol, acetate, etc in yeast). Some boundary conditions are also more important to an organism's physiology than others - for example, glucose is more relevant to yeast than citrate. To continue with Prof. Mahadevan's mention of electron donors and acceptors, the low-hanging fruit option for memote is to have a user select an electron donor/acceptor for respiration, say glucose and oxygen, and compare how much ATP it yields to some table, or let the end user decide if the yield indicates problems with the metabolic network. We could also see what the default inputs are for the model, which for most fungi, and likely most organisms, would be glucose and oxygen. For complete respiration with glucose+oxygen that max would be 36 mol ATP / mol glucose.

You could also have a similar exercise for fermentation, but I don't think you would have as many issues since there is no proton motive force involved.

On a related note, ATP hydrolysis (atp + h2o -> adp + pi + h) should always be present in the reconstruction since you need a sink for ATP production that isn't coupled to biomass in this test. And the lower bound limit when running these checks should be zero. Some models have a value greater than zero for the lb or do not have ATP hydrolysis (sometimes called NGAM / non-growth associated maintenance).

On a somewhat related note, I recall someone mentioned a test that may partially contribute to a higher ATP yield. You should not be able to generate a "free" proton motive force without a substrate being fed to the model.

I'll look into Rittmann and McCarty and other biochemistry texts.

[ChristianLieven]

I'll put this in the icebox for now. Seems to be a tricky problem the implementation of which may differ from condition to condtion/ organism to organism.