Shortest paths between glucose and all other metabolites were calculated using either: general reaction-based maps without COBRA constraints, general reaction-based maps with COBRA constraints, or CTMs with COBRA constraints. The COBRA constraints were for aerobic glucose minimal media conditions. General reaction-based maps connected all reactants to all products; however, some highly connected metabolites were eliminated (see methods for details). (A) The percent of metabolites with or without paths from glucose. (B) Histogram of shortest paths lengths for metabolites with paths from glucose. (C) Shortest paths between extracellular glucose and different central metabolic intermediates found using CTMs with COBRA constraints. The numbers reported next to each metabolite indicate the shortest path lengths found using CTMs with COBRA constraints (left) and reaction-based maps with COBRA constraints (right, in parentheses). Boxes highlight where the two calculated path lengths differ. The different colored path length numbers match the colored arrows used in the path. For example, the shortest path to pyruvate using CTMs (with path length of 6, shown in blue) uses reactions shown in blue.