CONTROL-THEORY OF GROUP-TRANSFER PATHWAYS

Relay or group-transfer pathways are important for metabolism and signal transduction. Yet, they are not addressed by standard metabolic control analysis. In this paper the control theory for this type of pathways is developed. Control coefficients are defined both with respect to modulation of enzyme concentration (enzyme control coefficient) and with respect to modulation of 'elemental' process activity (process control coefficient). Whereas the latter obeys the theorems of standard metabolic control theory, the more operational, former type of control coefficient obeys new control theorems: (i) the sum of enzyme control coefficients on the flux of group transfer equals 2 minus the control by pathway boundary substrates and products, divided by the extent to which the pathway enzymes are complexed, (ii) the sum of the controls on the concentration of any of the non-complexed pathway components is 1 (iii) the sum of the controls on the concentration of any of enzyme-enzyme complexes is 2, with the same corrections as above, (iv) the control exerted by enzyme concentrations can be calculated from the kinetic properties (elasticity coefficients). The implications for metabolism and signal transduction of the special control properties of relay pathways are discussed.