Reversibility of MAR04644

[manas-kohli]

I have created some models under nutrient low conditions (constrained the uptake of various metabolites) in enzyme constraint models and came across a reaction that would seem ordinarily infeasible in physiological conditions:

[5,10-methylene-THF][c] + [dUMP][c] ⇔ [dTMP][c] + [dihydrofolate] [c]

The forward reaction is fine and catalysed by TYMS but the literature seems to suggest that the reverse reaction is irreversible:
https://pmc.ncbi.nlm.nih.gov/articles/PMC4658596/. I get as a result a shortcut in some of my models of DHF going directly to 5-10-methylene-THF to support folate metabolism without the necessary NADPH oxidation that would be required from DHF going to THF.

Suggestion: Make the reaction irreversible in the forward direction.