The Thermodynamic-Buffer Enzymes

Abstract

Oxidative phosphorylation operates at optimal efficiency only if the condition of conductance matching L33/L11 = .**GRAPHIC**. is fulfilled. In this relation L11 is the phenomenological conductance of phosphorylation, L33 the phenomenological conductance of the load, i.e., the irreversible ATP-utilizing processes in the cell, and q the degree of coupling of oxidative phosphorylation driven by respiration. Since during short time intervals L11 and q are constant whereas L33 fluctuates in the cell, oxidative phosphorylation would rarely operate at optimal efficiency due to violation of conductance matching. The reversible ATP-utilizing reaction catalyzed by adenylate kinase (EC 2.7.4.3) can effectively compensate deviations from conductance matching in the presence of a fluctuating L33 and allows oxidative phosphorylation to operate at optimal efficiency in the cell. Since the adenylate kinase reaction buffered a thermodynamic potential, i.e., the phosphate potential, this finding was generalized to the concept of thermodynamic buffering. The thermodynamic buffering ability of the adenylate kinase reaction was demonstrated by experiments with incubated rat-liver mitochondria. Considerations of changes introduced in the entropy production by the adenylate kinase reaction allowed to establish the theoretical framework for thermodynamic buffering. The ability of thermodynamic buffering to compensate deviations from conductance matching in the presence of fluctuating loads was demonstrated by computer simulations. The possibility of other reversible ATP-utilizing reactions, like the ones catalyzed by creatinine kinase (EC 2.7.3.2) and arginine kinase (EC 2.7.3.3), to contribute to thermodynamic buffering is discussed. The comparison of the theoretically calculated steady-state cytosolic adenine nucleotide concentrations with experimental data from perfused livers demonstrated that in livers from fed rats conductance matching is fulfilled on a time average and that the degree of coupling corresponded to .**GRAPHIC**. = 0.97 permitting the most economic maintenance of a maximal output power of oxidative phosphorylation. For the case of livers from starved rats this analysis indicated that the degree of coupling corresponded to .**GRAPHIC**. = 0.95, permitting the most economic maintenance of a maximal net rate of ATP synthesis at optimal efficiency of oxidative phosphorylation.