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Y Termonia

Publications and source records attributed to Y Termonia.

5 recordsLinked to original sources
PubMed1982

Entrainment and resonance in glycolysis.

We have proposed a comprehensive model for the glycolytic reaction mechanism and have shown the possibility of self-tuning to resonance, with consequent increase in efficiency of energy transduction by separating the model into two subsystems: one for the phosphofructokinase (PFKase; ATP:D-fructose-6-phosphate 1-phosphotransferase, EC 2.7.1.11) reaction and the other for the pyruvate kinase (PKase; ATP:pyruvate 2-O-phosphotransferase, EC 2.7.1.40) reaction. The purpose of this article is to present an alternative theoretical approach-one more directly applicable to experimental situations-for the detection of these effects without the need for any decomposition. The approach consists in studying the response of such systems to externally applied periodic perturbations inside the fundamental entrainment band by computation. We show, in agreement with previous results obtained for simpler reaction schemes, that large increases and decreases in dissipation may occur in a narrow range of the period of entrainment of the entire mechanism. If the period of the autonomous glycolytic oscillation past marginal stability approaches a value, T(0) (lim), that is close to the period of relaxation oscillation of the PKase subsystem, T(PKase), then tuning of the primary oscillophor, the PFKase system, has been effected by the PKase system; in such cases we predict, for larger values of the amplitude of perturbation, two peaks in the response spectrum: one near the period of the autonomous oscillation and the other at the period of the PKase system. For small amplitudes of perturbation, there is only one resonance peak near the period of the autonomous oscillation. If T(0) (lim) is not close to T(PKase), then there is only one resonance peak for small and large amplitudes of external perturbations. Our computer results lead to a classification of the chemical species in the reaction mechanism into two categories. The first category has the following two properties. (i) When fundamental entrainment occurs, the amplitude of the response in all species in the reaction mechanism is largest when the oscillation in the perturbation of a chemical species is in phase with the oscillation of that variable in the mechanism. (ii) If the amplitude of the external periodic perturbation is monitored in time so as to keep that variable in the mechanism always constant, then there is no oscillatory response in the whole reaction pathway. The variables having these two properties have been found to be essential for the generation of self-sustained oscillations in our model. For the second category neither of these two properties holds.

Glucose↗
PubMed1981

Oscillations and control features in glycolysis: numerical analysis of a comprehensive model.

We present an analysis of glycolysis based on experimental findings and an interpretation based on concepts of efficiency, resonance response, and control features available in highly nonlinear reaction kinetics. We begin with a model for the glycolytic mechanism that is comprehensive, includes a large number of known activations and inhibitions of enzymes by metabolites, and couples the phosphofructokinase (PFKase) and the pyruvate kinase (PKase) reactions. The PFKase and PKase reactions and the coupling between them are modeled according to experimental information, but we do not attempt to model the glyceraldehyde-3-phosphate dehydrogenase-3-phosphoglycerate kinase reaction. We use experimental data to obtain the best estimates for the kinetic parameters and test the model by calculating the concentration variations of the intermediate metabolites. We confirm oscillatory behavior and calculate the ATP/ADP ratio and the free-energy dissipation for an extended range of the kinetic parameters as a function of the driving force for the glycolytic pathway, a measure of which is the total adenine nucleotide concentration. We find agreement of the calculated results with experimental findings except for the insufficiently represented reactions. Our model shows that the average ATP/ADP ratio is increased and the average free-energy dissipation is decreased in an oscillatory compared with a steady state mode of operation. The average values of the ATP/ADP ratio and of the free energy dissipation change abruptly past the onset of sustained oscillations.

Adenosine Diphosphate↗
PubMed1981

Oscillations and control features in glycolysis: analysis of resonance effects.

We have presented [Termonia, Y. & Ross, J. (1981) Proc. Natl. Acad. Sci. USA 78, 2952-2956] an analysis of glycolysis based on experimental findings. Here, we give an interpretation based on the concepts of efficiency, resonance response, and control features available to highly nonlinear reaction kinetics. The comprehensive model of glycolysis, for which we presented numerical evaluation of concentration oscillations, entropy production, and average ATP/ADP ratios is separated into two subsystems: one for the phosphofructokinase (PFKase) reaction, the other for the pyruvate kinase (PKase) reaction. We analyze each subsystem separately and find that, for a range of parameter values around the best estimates obtained from experimental data, the PFKase reaction exhibits sustained oscillations. The PKase reaction, on the other hand, is in a stable stationary state and shows an oscillatory relaxation. The period of the PFKase reaction is within 25% of that obtained by computer simulation of the full model. Moreover, if, for a given set of kinetic parameters, the period of the oscillations in the PFKase reaction is of the same order of magnitude as the period of the oscillatory relaxation of the PKase reaction, then the onset of oscillatory behavior past marginal stability forces a tuning of the PFKase reaction period to that of the PKase reaction. Thus, the PKase reaction tunes the frequency of the primary oscillophor, the PFKase reaction, so that a resonance response results in the PKase reaction. We find this result for a substantial range of parameters. The sharp increase in the ATP/ADP ratio and the decrease in the dissipation (entropy production) are seen to be a result of the forced tuning to resonance. The origin of the remarkable control feature of the tuning of one part of the pathway by another that follows in the reaction mechanism is the coupling of the two parts and, in the case of glycolysis, this is realized by the intermediate fructose 1,6-diphosphate, which participates crucially in the PFKase and PKase reactions.

Adenine Nucleotides↗