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Biology Articles » Biomathematics » The intricate side of systems biology » Figures

Figures
- The intricate side of systems biology

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Fig. 1. Simplified representation of glycolysis and lactate production in L. lactis. Black arrows show flow of material. Gray arrows indicate signals, minus sign indicates inhibition, and plus signs indicate activation.

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Fig. 2. Dynamics of metabolite pools in L. lactis strain MG1363 derived from 20 mM [6-13C]glucose metabolized under aerobic conditions at pH 6.5 (5). Experimental data (dark blue diamonds) were obtained with in vivo 13C-NMR techniques. Under the experimental conditions used, the detection limit for intracellular phosphorylated metabolites was 3 mM. Green lines, a priori inferred dynamics of 3-PGA and PEP below the detection level. Orange lines, dynamics of unlabeled 3-PGA and PEP, inferred from a model analysis of the observation that 3-PGA and PEP are still high in concentration after 40 min of starvation, a situation that should be similar to the beginning of the experiment. Support of this inference came from the fact that the NMR technique measures only labeled compounds but not the unlabeled 3-PGA and PEP pools at the beginning of the experiment. Light blue lines, simulation results with a mathematical model constructed under the guidelines of Biochemical Systems Theory (3, 6–9) (see Methods and supporting information for details).

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Fig. 3. Simulation of a tandem experiment (1), in which a second glucose bolus is given after 23 min (arrow in A). The dynamics is captured rather well, even though no parameters were readjusted. Differences seem to be caused, at least in part, by the rate of disappearance of the first bolus of glucose, which is faster than in the experimental data we used originally. (A) Observed dynamics of glucose (circles) and lactate (squares), superimposed with model simulation (lines). (B) Observed dynamics of FBP (squares), 3-PGA (circles), and PEP (triangles), superimposed with model simulation (lines). Data redrawn from ref. 1.


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Fig. 4. Generic linear feedforward activated pathway in which a downstream metabolite (X4) is needed as a second substrate for the first step.

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Fig. 5. Responses of the pathway in Fig. 4, as implemented in Eq. 1, where the main substrate influx is stopped between t = 10 and t = 60. (A) X2 activates the degradation of X4. (B) The activation of the degradation of X4 by X2 is eliminated.

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Fig. 6. Dynamics of inorganic phosphate during lactate production in L. lactis. Measurements were obtained with in vivo NMR techniques (5).

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