Glycolytic Oscillations and Limits on Robust Efficiency

Both engineering and evolution are constrained by trade-offs between efficiency and robustness, but theory that formalizes this fact is limited. For a simple two-state model of glycolysis, we explicitly derive analytic equations for hard trade-offs between robustness and efficiency with oscillations as an inevitable side effect. The model describes how the trade-offs arise from individual parameters, including the interplay of feedback control with autocatalysis of network products necessary to power and catalyze intermediate reactions. We then use control theory to prove that the essential features of these hard trade-off laws are universal and fundamental, in that they depend minimally on the details of this system and generalize to the robust efficiency of any autocatalytic network. The theory also suggests worst-case conditions that are consistent with initial experiments.