Characterizing the capabilities, criticalities and response to perturbations of genome-scale metabolic networks is a basic problem with important applications. A key question concerns the identification of the potentially most harmful knockouts. The integration of combinatorial methods with sampling techniques to explore the space of viable flux states may provide crucial insights on this issue. We assess the replaceability of every metabolic conversion in the human red blood cell by enumerating the alternative paths from substrate to product, obtaining a complete map of the potential damage of single enzymopathies. Sampling the space of optimal flux states in the healthy and in the mutated cell reveals both correlations and complementarity between topologic and dynamical aspects.
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