While all of these reactions are irreversible they form a perfectly closed loop.
ALATA_L, AGT, GLYTA, SGAT, SPTc
This reactions form a perfectly closed loop. The TIC is specially resilient, since some redundancy allows to maintain the loop even after makingAGT and SPTc irreversible. The remaining reversible reactions are known to be reversible with thermodynamics close to equilibrium.
RNF, FRNDPR2r, BIF, HYDA, H2ASE_syn
These redox reactions loop around electron transfer cofactors. It is known that the directionality of these reactions is highly dependent on metabolite concentrations. For example, setting BIF irreversible and H2ASE_syn as irreversible in the opposite direction (upper bound=0), removes the loop.
Solved
They are detected in the file:
PPAKr, PACPT, PTA2
These reactions formed a loop before PPAKr was consolidated into one.
NDPK1 related
All abc transporters were made irreversible. Which solved several.
CYTDK1 , CYTDK2
CYTDK2 was made irreversible
PGBI, PGIA, G6PI_1
This loop disappeared when isomers where consolidated.
MDH, ME, PC
This loop converts nadh into nadph. Which enables (in part) the H2ASE_syn, FRNDPR2r loop.
By setting MDH.lower_bound = 0 , the intereference of this part is removed.
This loop was eliminated during the curation process, it is not clear what solved it. Likely the fact that now nadh and nadph are synthesized from basic substrates, instead of providing
akg_c: GLUDy GLUS, OXSCL
If GLUDy operates only in the reverse direction ( upper bound = 0). These reactions are no longer unbounded.(see equilibrator and other references). This loop occurs due to pyroglutamate synthesis, if this pathway is blocked, the loop disappears. In regards to the pathway it self:
First the transport reaction PYRGt did not translocate protons. By making this reaction a symporter, the rate of GLUDy goes down form 500 to 100. This is still an unrealistic flux, and pyroglutamate yield. The issue was that citrate import was allowed at 1000. So the loop, which occured under citrate uptake was corrected by setting the PYRGt transporter to use protons.
Solve TICs when possible.
Unsolved
ACADCOAT, ACADT, ACS
While all of these reactions are irreversible they form a perfectly closed loop.
ALATA_L, AGT, GLYTA, SGAT, SPTc
This reactions form a perfectly closed loop. The TIC is specially resilient, since some redundancy allows to maintain the loop even after makingAGT and SPTc irreversible. The remaining reversible reactions are known to be reversible with thermodynamics close to equilibrium.
RNF, FRNDPR2r, BIF, HYDA, H2ASE_syn
These redox reactions loop around electron transfer cofactors. It is known that the directionality of these reactions is highly dependent on metabolite concentrations. For example, setting BIF irreversible and H2ASE_syn as irreversible in the opposite direction (upper bound=0), removes the loop.
Solved
They are detected in the file:
PPAKr, PACPT, PTA2
These reactions formed a loop before PPAKr was consolidated into one.
NDPK1 related
All abc transporters were made irreversible. Which solved several.
CYTDK1 , CYTDK2
CYTDK2 was made irreversible
PGBI, PGIA, G6PI_1
This loop disappeared when isomers where consolidated.
MDH, ME, PC
This loop converts nadh into nadph. Which enables (in part) the H2ASE_syn, FRNDPR2r loop.
By setting MDH.lower_bound = 0 , the intereference of this part is removed.This loop was eliminated during the curation process, it is not clear what solved it. Likely the fact that now nadh and nadph are synthesized from basic substrates, instead of providingakg_c: GLUDy GLUS, OXSCL
If GLUDy operates only in the reverse direction ( upper bound = 0). These reactions are no longer unbounded.(see equilibrator and other references). This loop occurs due to pyroglutamate synthesis, if this pathway is blocked, the loop disappears. In regards to the pathway it self: First the transport reaction PYRGt did not translocate protons. By making this reaction a symporter, the rate of GLUDy goes down form 500 to 100. This is still an unrealistic flux, and pyroglutamate yield. The issue was that citrate import was allowed at 1000. So the loop, which occured under citrate uptake was corrected by setting the PYRGt transporter to use protons.