Example illustrating the calculation of a ShReD based on flux weights. Circles and boxes show reactions and metabolites, respectively. The top and bottom numbers in the circles refer to the reaction number and corresponding flux, respectively. The ShReDs are highlighted with grey circles and boxes. (A) Day 4 model flux distribution around reaction nodes comprising the ShReD for the reaction pair [R42, R50]. The reactions comprising the ShReD are as follows. R50: palmitate synthesis, R48: oxidative phosphorylation, R34: pyruvate dehydrogenase and citrate synthase, R54: mitochondrial transport of 2-oxoglutarate and malate, R42: citrate lyase. (B) Reaction-to-reaction distances calculated using the fluxes shown in panel (A) and equation 3. Note that the path from R50 to R42 in ShReD42,50 proceeds through R48, R34, and R54 due to the long weighted distance from R50 to R42, which in turn is due to the relatively small contribution of R50 to the CoA flux. (C) Day 12 model flux distribution around reaction nodes comprising ShReD42,50. (D) Reaction-to-reaction distances calculated using the fluxes shown in panel (A) and equation 3. Note that ShReD42,50 for the Day 12 model involves only R42 and R50, as the contribution of R50 to the CoA flux is significantly larger compared to the Day 4 mode.