The organization of metabolic reaction networks: a signal-oriented approach to cellular models.

Complex metabolic networks are characterized by a great number of elements and many regulatory loops. The description of these networks with mathematical models requires the definition of functional units that group together several cellular processes. The approach presented here is based on the idea that cellular functional units may be assigned directly to mathematical modeling objects. Because the proposed modeling objects have defined inputs and outputs, they can be connected with other modeling objects until eventually the whole metabolism is covered. This modular approach guarantees a high transparency for biologists as well as for engineers. Three criteria are introduced to demarcate functional units. The criteria consider the physiological pathways, the organization of the corresponding genes, and the observation that cellular systems can be structured into units showing a hierarchy of signal transduction and processing. As an example, the carbon catabolic reactions in Escherichia coli are discussed as members of a functional unit catabolism. Copyright 2000 Academic Press.