Research Paper Volume 15, Issue 19 pp 9896—9912

Figure 3. Identification of optimal nodes using flux balance analysis in the neuron-astrocyte metabolic network suggests division of labor between the neuron and astrocyte in response to neurotransmission workload. (A–C) Reactions considered in the metabolic objective; here, metabolite names correspond to the same as in the model reported by Lewis et al. (2010). (A) Fluxes associated with the Astrocyte-Neuron Lactate Shuttle (ANLS); left side: Lactate efflux from astrocyte to the interstitial space (Lact-Ast); right side: Lactate from the interstitial space entering neurons (Lact-Neu). (B) Fluxes related to the Glutamate-Glutamine Cycle (GGC); left side: vesicle-exported glutamate from neuron (GluVe-Neu); right side: glutamine excretion from astrocyte (GlnEx-As). (C) Neuronal sodium efflux associated with its removal via sodium ATPase pump. (D–G) Phenotypìc phase planes are shown as two-dimensional color maps. Here, the Flux Balance Analysis (FBA) solution is represented by the red-filled circle, while all fluxes shown correspond to micromolar per second (uM/s). A white piece-wise line depicts the specific contour level of the solution. (H) The neuron-astrocyte metabolic network is represented as a bipartite network; here, node shape (circle or square) denotes the partition where it belongs, i.e., reaction or metabolite. (I) left side, flux values distribution in each cell; right side: the bipartite network presented in (H) showing node size proportional to absolute flux. (J) left side, sensitivity values distribution in each cell; right side: the bipartite network presented in (H) showing node size proportional to absolute sensitivity. (K) Distribution of the Absolute Optimality values in neuron and astrocyte, the 90 percentile is highlighted by a red dashed line. This line depicts the cutoff over which a reaction was classified as an optimal metabolic reaction. (L) Optimal metabolic reactions (descending order) sorted by their Absolute Optimality and presented alongside their flux and sensitivity.