While speculative, the significant increase in net α-KG efflux with zero palmitate might be explained by net flux toward succinate, since under these conditions there is minimal fuel-derived acetyl-CoA to combine with oxaloacetate.
The delay has been observed consistently for eukaryotic systems and can mostly be explained by exchange fluxes with storage polymers (trehalose and glycogen) [ 55].
Therefore, the pathway position correlated with functional constraint levels can be explained by the information flux theory that the elements located at branch point of pathway exert a greater flux control and subjected to stronger selective constraints [ 14, 23].
This observation can be explained by a higher flux through the PP pathway, which results in a direct and significant loss of 13C labelled carbon dioxide and formation of 2 moles NADPH.
The (low) operation of the ethylmalonyl-CoA pathway in succinate-grown cells may best be explained by some (low) flux of carbon from PHB to the central carbon metabolism, which might actually be driven by the requirement of propionyl-CoA for the synthesis of odd-numbered fatty acids.
The increase in mitochondrial membrane potential could be explained by a higher flux of malate into the mitochondria because the concentration of malate outside the mitochondria was much higher due to the repression of ME1.
However, the predicted change of flux (−1.7 %) is lower than that, which can be explained by the distribution of flux control over several reactions of the network.
Failed water reabsorption in genetic corneal dystrophies can be explained by loss of water-flux across the basolateral endothelial surface.
On the other hand, the left section of the profile (Fig. 5) can be explained by realizing that pyruvate flux-sum attenuation is also accompanied by decreased ATP regeneration due to lower ACK and pyruvate kinase (PYK) fluxes.
The behavior of the DPGA concentration predicted by both flux-based R-DFBA variants at the beginning of the simulation is very close to the kinetic modeling results, which can be explained by the coupling between fluxes and concentrations giving rise to particular temporal profiles.
