A structural approach to understanding enzymatic regulation of chemical reaction networks

In living cells, chemical reactions are connected by sharing their products and substrates, and form complex systems, i.e. chemical reaction network. One of the largest missions in modern biology is to understand behaviors of such systems logically based on information of network structures. However, there are series of obstacles to study dynamical behaviors of complex network systems in biology. For example, network structure does not provide sufficient information to determine details of the dynamical behaviors. In this review, I will introduce a novel mathematical theory, structural sensitivity analysis, by which the responses of reaction systems upon the changes in enzyme activities/amounts are determined from network structure alone. The patterns of responses exhibit characteristic features, localization and hierarchy, depending on the topology of the network. The theory also shows that ranges of enzymatic regulations are governed by a mathematical law characterized by local topology of substructures. These findings imply that the network topology is one of the origins of biological robustness.