Optimal design of feedback control by inhibition: dynamic considerations.

The local stability of unbranched biosynthetic pathways is examined by mathematical analysis and computer simulation using a novel nonlinear formalism that appears to accurately describe biochemical systems. Four factors affecting the stability are examined: strength of feedback inhibition, equalization of the values among the corresponding kinetic parameters for the reactions of the pathway, pathway length, and alternative patterns of feedback interactions. The strength of inhibition and the pattern of feedback interactions are important determinants of steady-state behavior. The simple pattern of end-product inhibition in unbranched pathways may have evolved because it optimizes the steady-state behavior and is temporally most responsive to change. Stability in these simple systems is achieved by shortening pathway length either physically or, in the case of necessarily long pathways, kinetically by a wide devergence in the values of the corresponding kinetic parameters for the reactions of the pathway. These conclusions are discussed in the light of available experimental evidence.