The Analysis of Flux in Substrate Cycles

Abstract

Within the network that makes up the metabolism of a cell, there are to be found cyclic routes. These cycles can be of different types, but amongst them are the ‘futile’ or substrate cycles that are often defined as cyclic fluxes that lead to no net changes other than the dissipation of energy in the coupled reactions through which they are driven. It is presumed that in vivo, regulation of the enzyme(s) in opposite limbs of such cycles might limit the energy dissipation by unnecessary cycling, but this is an issue that must be determined by experiment. Often such experiments are carried out using isotopic labeling techniques in order to estimate the fluxes through individual reactions. Earlier work has looked at how these results might be analyzed in order to derive the cyclic flux^1,2. My purpose in this paper is to show that once a network has a certain degree of complexity, knowing the individual reaction fluxes does not always allow an unambiguous estimate of the amount of cycling, and this problem appears to have been overlooked.