CONTROL BY ENZYMES, COENZYMES AND CONSERVED MOIETIES - A GENERALIZATION OF THE CONNECTIVITY THEOREM OF METABOLIC CONTROL ANALYSIS

The control and regulation of metabolic systems are determined by thei r responses to changes in the internal metabolites (the internal state ) and parameters of the system. In many cases, the concentrations of t he intermediates are constrained by moiety conservations, for example those requiring that all intermediate forms of any enzyme sum to the c onserved total concentration of that enzyme. In this study, we show ho w responses to changes in the internal state are related to responses to changes in the total amounts of conserved moieties. The relationshi p between these two different measures of control leads to a generalis ation of the connectivity theorems. The results have important implica tions for the study of a variety of phenomena such as metabolite (coen zyme) sequestration, group-transfer and channelling. The relationships we derive make it possible to determine the control features of these pathways. As an illustration, two examples are chosen. The first show s the effect of sequestration of substrate moiety while the second dea ls with the sequestration of the enzyme moieties and enzyme/enzyme int eractions.