Network Level Regulation. A. The linear conversion model of the metabolic network. B. The corresponding non-linear, enzymecentric model. The grey arrow starting from Pyr depicts metabolic flow shifting to valine while pyruvate (Pyr) increasing. Black vertical arrows depict up- or down- regulated metabolites. C and D are the spectra of threonine (upstream of Pyr) and isoleucine (downstream of Pyr) responses over the Pyr perturbation using Model A and Model B, respectively. X-axis: Pyr from 50 to 10,000 uM. Y-axis: the simulated steady state levels of threoine and isoleucine at given Pyr concentrations. The dish images are growth assays given low (left) and high (right) Pyr. E. The spectrum of valine production using the Model B. F. The black arrow on the top right-hand corner depicts while Pyr passing the threshold, turning on the reverse TC enzyme reaction to switch the direction of metabolic flux.