A single mechanism or a distinct pathway cannot explain the effectiveness of a cancer drug.
We reviewed the paper of Glossmann et al. regarding our articles about statins and vitamin D. The authors were right indicating that the magnitude of the rise in 25-hydroxy vitamin D observed with rosuvastatin treatment is surprising and our hypothesis that a common catabolic pathway, cannot explain this magnitude of increase alone.
The past several decades have witnessed great progress in the identification of mechanisms necessary for axon pathfinding, yet known pathways still cannot explain all of the complexity required to build nervous systems (O'Donnell et al. 2009; Schmitz et al. 2007).
Our current understanding of the cytosolic signaling pathways of these fusion proteins alone cannot explain the basis for these differences, and we reasoned that examination of gene expression changes regulated by the three fusions might provide insights in this regard.
This overflow metabolism rationale suggests that cells would only use fermentation once the high-yield pathway runs at maximum rate, but it cannot explain why cells would decrease the flux through the high-yield pathway.
This pathway can be now excluded as it cannot explain the presence of the hydroxy-dodecadienoyl-CoA intermediate and the completely reduced intermediates dodecanoyl-CoA, decanoyl-CoA and octanoyl-CoA that were newly detected in the presented experiments.
Horizontal acquisition from more distantly related strains also cannot explain the sporadic occurrence of these pathways, since in that case they would not be identical, nor would they be likely to always lie in precisely the same positions.
In the uncontrolled case, our model cannot explain the checkpoint behavior, independently of which pathway is chosen (Figure 2A B).
Currently, we cannot explain every single finding, and at this stage, we can only speculate about the biochemical pathways involved.
However Yu et al.20 showed convincingly that the FAS-II pathway is not important for the propagation of P. falciparum in erythrocytes and so inhibition of PfENR cannot explain the effect of triclosan on blood-stage parasites.
