Steady-State Measurements and Identifiability of Regulatory Patterns in Metabolic Studies

A main objective in investigating a metabolic pathway is to obtain a definite idea of both its structure, in terms of material and information relationships, and its behavior. Traditionally, the schematic representation of a given pathway is based on previous information mainly obtained by experiments in vitro. Measurements on the intact system are then used for testing the resulting structure. This is justified by the idea that knowing the elements of a given pathway will lead us to a deep understanding of both its properties and its behavior under specified conditions. However, there is now increasing evidence that complete characterization of each element in vitro does not necessarily lead to a correct description of the whole system1–4. In practice, and especially if we consider the relevant regulatory signals within the system, it is often difficult to agree on a single scheme, and different possibilities arise. On one hand, the in situ conditions can make it some of the effects shown in vitro irrelevant. On the other hand, it is possible that some interactions not shown in vitro could be of interest in situ. Hence, we are dealing with a situation close to a black box, in the sense that the relationships within the system are not clearly established.