HOW TO RECOGNIZE MONOFUNCTIONAL UNITS IN A METABOLIC SYSTEM

In intracellular metabolic networks, it is often useful to discern sub systems (modules) of which the metabolites are only produced or consum ed by reactions within that subsystem or by a limited number of fluxes crossing the borders of the subsystem. In many cases such subsystems function as units with respect to their effect on the remainder of the system. In this paper we show that the co-response of two metabolic v ariables outside that subsystem to a perturbation of a subsystem react ion does not depend on which subsystem reaction is perturbed if three conditions are fulfilled: (1) the reactions outside the subsystem are not affected directly by metabolites belonging to the subsystem; (2) t here are no conservation relations linking the subsystem to the rest; and(3) the subsystem is linked to the remainder of the system only via one degree of freedom in fluxes. We propose the name ''monofunctional units'' for subsystems fulfilling these three criteria. Identificatio n of such units greatly simplifies metabolic control analysis. Only on e reaction per unit needs to be perturbed to analyse control in the sy stem. Difficulties, such as the inaccessibility of some reactions to e xperimental perturbation, may be circumvented by perturbing another re action within the unit that leads to the same co-response coefficients . The analysis can also serve to identify unsuspected regulatory inter actions in the metabolic network. The differences in the behaviour bet ween metabolic units and other types of subsystems are illustrated by numerical examples. (C) 1996 Academic Press Limited.