Figure 1.
Examples for problems in elementary mode analysis. (A) Condensed network of glycolysis (dark reactions) and Entner–Doudoroff pathway (gray reactions). The pentose phosphate pathway has been omitted for clarity. In most analyses of glycolysis, the Entner–Doudoroff pathway is not considered. Hence, not all pathways from glucose into the TCA cycle are found, and the wrong conclusion might be drawn that only the pentose–phosphate pathway (not shown) can be used to bypass the knockout of one of the enzymes converting G6P to FDP. In vivo the knockout of the corresponding reactions is partially bypassed by a flux through the Entner–Doudoroff pathway (Fischer and Sauer 2003). (B) Modeling the Entner–Doudoroff pathway by adding an outflow of G6P and an inflow of G3P and Pyr only partially resolves the problem (thick arrows). Such an approach is often used in elementary mode analysis to avoid the consideration of some pathways in detail (e.g., the outflow of succinyl-CoA from the TCA cycle in Schuster et al. 1999, analyzed in Results). However, this can lead to fluxes like in C, which are not part of any feasible pathway when the entire network in A is considered. This is because the coupling of the influx of Pyr with the outflow reactions of G6P and the inflow reaction of G3P are neglected in B. (D) Elementary mode analysis does not allow one to analyze the dependencies between the subsystems S1 and S2 unless the reactions connecting them are taken into account. Thus, it is not possible to deduce that a zero flux from G6P to FDP in S1 would imply that there cannot be a positive flux from DHAP to G3P in S2. A list of abbreviations can be found in Supplemental material S2.