DETERMINATION OF CONTROL COEFFICIENTS IN INTACT METABOLIC SYSTEMS

The control structure of a metabolic system can in principle be determ ined without the need for purification of the component enzymes and st udy of their kinetic properties, provided that their activities can be perturbed by amounts sufficient to produce measurable changes in the steady-state variables, i.e. the fluxes through the system and the con centrations of the intermediates. Each perturbation is characterized i n terms of the co-response coefficients of all pairs of variables, i.e . the slopes of the lines produced when the logarithm of one variable is plotted against the logarithm of another, both varying in response to the same perturbation. If all the co-response coefficients are asse mbled into a matrix, the inverse of this matrix can be transformed int o a matrix containing all the component elasticities, which can be inv erted to provide the complete matrix of control coefficients. In a sim ple three-enzyme pathway studied, the analysis proves not to require u nrealistically high accuracy in the original co-response measurements: even with errors with standard deviation +/- 5.77 degrees in the angl es to the horizontal of the lines in the co-response plots (equivalent at best to errors of +/- 20% in the corresponding coresponse coeffici ents), the final control coefficient matrix may be adequate for assess ing the control structure of the system. Examination of literature dat a from studies of mitochondrial respiration and of gluconeogenesis ind icates that considerably higher precision than this is achievable.