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Glycolytic Oscillations and Limits on Robust Efficiency Fiona A Chandra 1 , Genti Buzi 2 , John C Doyle 2 Departments of 1 BioEngineering and 2 Control and Dynamical Systems, California Institute of Technology, Pasadena, CA Corresponding Author: Fiona Chandra 1200 E California Blvd MC 107-81 Pasadena, CA 91125 [email protected]
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Summary We illustrate fundamental tradeoffs between robustness, efficiency, and complexity using the glycolysis pathway and show that glycolytic oscillations are the consequence of such tradeoffs stemming from the pathway’s autocatalytic structure. Abstract Both engineering and evolution are constrained by tradeoffs between efficiency and robustness, but theory that formalizes this fact is limited. Using a simple two-state model of glycolysis, we explicitly derive hard tradeoffs between metabolic overhead, network fragility, and oscillations. These theoretical results are confirmed with single cell experiments. Glycolytic oscillations are among the most studied dynamics in biology, yet whether the oscillations are beneficial or simply an evolutionary accident is unresolved. We prove a third alternative: Oscillations are the inevitable consequence of tradeoffs between metabolic overhead and robustness to disturbances, and the interplay of feedback control with the autocatalysis of network products necessary to power and catalyze intermediate reactions. Furthermore, the essential features of the hard tradeoff “law” do not depend on the details of this system, and generalize to the robust efficiency of any autocatalytic network, no matter how complex.
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Introduction Hard limits on computation, prediction, energy conversion, communication, control, and even measurement are at the heart of modern theories of systems in engineering and science [1]. Unfortunately, these subjects remain largely fragmented and incompatible, even as the tradeoffs between these limits grow in importance. Minimizing waste and resource use as well as robustness to perturbations in system components, operation, and environment [2] are crucial to sustainability, from cells to engineering infrastructure. This paper explores such robust efficiency via integration of elementary concepts from biochemistry and control theory [3][4] using the familiar example of glycolytic oscillations. Since glycolytic oscillation in yeast extract was observed in the 1960s, glycolysis has become a classic case study in control and dynamical systems [5], with a rich and sophisticated literature both experimentally (see [6] for a review), and theoretically [7],[8]. Numerous mathematical models have been developed, some with extensive mechanistic detail [9], while others aim for minimal models that capture a few essentials [10]-[11]. Glycolysis is arguably both the most studied control system and the most common, found in most of the planet’s roughly 10 30 cells from bacteria to human, and presumably has been under intense evolutionary pressure for robust efficiency. Thus new insights are less likely to be confounded by either gaps in understanding or evolutionary accidents, compared with more obscure biological circuitry.
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FinalBodyCaptions - Glycolytic Oscillations and Limits on...

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