A comparison of variant theories of intact biochemical systems. II. flux-oriented and metabolic control theories

Abstract

In the past two decades, several theories, all ultimately based upon the same power-law formalism, have been proposed to relate the behavior of intact biochemical system to the properties of their underlying determinants. Confusion concerning the relatedness of these alternatives has become acute because the implications of these theories have never been compared. In the preceding paper we characterized a specific system involving enzyme- enzyme interactions for reference in comparing alternative theories. We also analyzed the reference system by using an explicit variant that involves the S-system representation within biochemical systems theory (BST). We now analyze the same reference system according to two other variants within BST. First, we carry out the analysis by using an explicit variant that involves the generalized mass action representation, which includes the flux-oriented theory of Crabtee and Newsholme as a special case. Second, we carry out the analysis by using an implicit variant that involves the generalized mass action representation, which includes the metabolic control theory of Kacser and his colleagues as a special case. The explicit variants are found to provide a more complete characterization of the reference system that the implicit variants. Within each of these variant classes, the S-system representation is shown to be more mathematically tractable and accurate than the generalized mass action representation. The results allow one to make clear distinctions among the variant theories.