Moiety-conserved cycles and metabolic control analysis: problems in sequestration and metabolic channelling

This paper considers certain aspects of the analysis of moiety-conserved cycles in terms of metabolic control analysis. Two response coefficients are discussed: the response coefficient with respect to the total number of moles in a cycle (RVT), and the response coefficient with respect to perturbations to the internal state of a pathway (RVS). The relationship between these two different measures is derived and two examples are given to illustrate how the results may be used to simplify the analysis of particular complex pathways. One example considers how metabolite sequestration affects the flux summation theorem for which the analysis confirms the known result that sequestration can depress the value of the summation to below unity. The second example investigates the effect of metabolic channelling on the summation theorems. The analysis indicates that in contrast to metabolite sequestration, metabolic channelling can cause the flux summation theorem to exceed the value of unity. In addition, the maximum value that the summation theorem can reach under these conditions is shown to be equal to 2. Finally, this analysis indicates how one might use control analysis through the use of enzyme titration to determine whether metabolic channelling occurs in real systems or not.