Stability of yeast glycolysis is not controlled by a single oscillophore

Karin Reijenga, Yvonne M.G.A. van Megen, Barbara M. Bakker, Bob W. Kooi, Jacky L. Snoep, Henk W. van Verseveld and Hans V. Westerhoff.


Spontaneous biochemical oscillations are often thought to be caused by a so-called oscillophore, a key enzyme that is the primary source of the oscillations. In yeast glycolytic oscillations phosphofructokinase seemed to be such an oscillophore, since removing the positive feedback regulation on this enzyme in a core model of glycolysis, removed the oscillations completely at any combination of kinetic parameter values.

In real glycolysis, however, more than one possible source of oscillations has been identified. In order to quantify to which extent each enzyme contributes to the occurrence of oscillations, we applied the principles of Metabolic Control Analysis. We calculated the control exerted by each enzyme on the real part and the trace of the eigenvalues of stable as well as of instable steady states. We concluded that even in the above mentioned core model, the control on the eigenvalues was distributed among several enzymes. In a detailed and realistic model of yeast glycolysis most, but not all control of the eigenvalues was shared by glucose transport, pyruvate decarboxylase and the utilization of ATP. From these results we conclude that the concept of an oscillophore cannot be applied to complex biochemical networks. Instead, Metabolic Control Analysis provides an unambiguous method to determine the importance of each enzyme for the emergence of oscillations.