Control, regulation and thermodynamics of free-energy transduction.

The quantitative formalism called Metabolic Control Theory makes it possible to be precise in discussions of metabolic control. To illustrate this, I will mention 2 experimental systems where free energy is converted from one form to another, i.e., bacteriorhodopsin liposomes and mitochondrial oxidative phosphorylation. More specifically I shall discuss how the distribution of the control of fluxes, concentrations and potentials, among the various enzymes (catalysts) in these systems has been measured and how this distribution can be understood in terms of the enzyme properties. From the outset, Metabolic Control Theory was valid for branched metabolic pathways with non-linear kinetics. Yet, it seemed to be limited to metabolic pathways without enzyme-enzyme interactions and to steady states. It is now clear that these limitations were apparent only and recent extensions to Metabolic Control Theory deal explicitly with enzyme-enzyme interaction and with transient-time analysis. Other limitations are inherent. For instance, Metabolic Control Theory pays for its clarity and exactness by being limited to small modulations. Mosaic Non Equilibrium Thermodynamics and Biochemical System Analysis are formalisms that deal with larger changes, at the cost of accuracy and exactness.