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Metabolism is a universal property of living organisms. While the metabolic network itself has been well characterized, the logic of its regulation remains largely mysterious. We analyze several representative metabolic modules - starting from a linear pathway to a bidirectional pathway and metabolic cycle, and finally to integration of two different nutrient inputs. In each case,we find that product-feedback inhibition can minimize futile cycling and optimize fluxes, however, at the cost of high levels of metabolite pools. These large metabolite pool sizes can be restricted if feedback inhibition is ultrasensitive. To experimentally test our predictions from our analysis, we examine the case of nitrogen assimilation in E. coli, which involves both nutrient integration and a metabolic cycle. We find that the feedback regulation scheme suggested by our analysis closely aligns with the actual regulation of the network and is sufficient to explain much of the dynamical behavior of relevant metabolite pool sizes in nutrient-switching experiments. Host: Anton Zilman, zilmana@lanl.gov, 7-3216 |