Control of glycolytic dynamics by hexose transport in Saccharomyces cerevisiae

It is becoming accepted that steady-state fluxes are not necessarily contro lled by single rate-limiting steps. This leaves open the issue whether cell ular dynamics are controlled by single pacemaker enzymes, as has often been proposed. This paper shows that yeast sugar transport has substantial but not complete control of the frequency of glycolytic oscillations. Addition of maltose, a competitive inhibitor of glucose transport, reduced both aver age glucose consumption flux and frequency of glycolytic oscillations. Assu ming a single kinetic component and a symmetrical carrier, a frequency cont rol coefficient of between 0.4 and 0.6 and an average-flux control coeffici ent of between 0.6 and 0.9 were calculated for hexose transport activity. I n a second approach, mannose was used as the carbon and free-energy source, and the dependencies on the extracellular mannose concentration of the tra nsport activity, of the frequency of oscillations, and of the average flux were compared. In this case the frequency control coefficient and the avera ge-flux control coefficient of hexose transport activity amounted to 0.7 an d 0.9, respectively. From these results, we conclude that 1) transport is h ighly important for the dynamics of glycolysis, 2) most but not all control resides in glucose transport, and 3) there should at least be one step oth er than transport with substantial control.