Glycolysis_Main

Glycolysis_Main - Glycolytic Oscillations and Limits on...

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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 derive a precise description of the features of an optimized network based on fundamental tradeoffs among robustness, efficiency, and network complexity, and illustrate the tradeoff ‘law’ using the well-known model of glycolytic oscillations. Abstract Both engineering and evolution are shaped by tradeoffs between efficiency and robustness, but theory that formalizes fundamentals of the interaction between them is limited. Using the example of glycolytic oscillations, we explicitly derive hard tradeoffs between metabolic overhead, network fragility, and oscillations. A central issue is the interplay of feedback control with the autocatalytic feedback of network products necessary to power and catalyze intermediate reactions. Glycolysis is a classic example of autocatalysis, as ATP is both produced and consumed. Glycolytic oscillations are among the most studied dynamics in biology, with a rich and sophisticated literature both experimental and theoretical. Despite intensive study, whether the oscillations are beneficial or simply an evolutionary accident is unresolved. Using a simple two-state model, we propose and prove a third alternative: that oscillations are the inevitable consequence of tradeoffs regarding autocatalysis, metabolic overhead, and robustness to disturbances, and are consistent with the fluctuating transient response which we observe experimentally in single yeast cells. These results clarify the highly evolved nature of the yeast wild type control network as an optimal balance of robustness, efficiency, and complexity. Furthermore, the essential features of the hard tradeoff, or “law,” do not depend on the details of this model or system, and generalize to the robust efficiency of any autocatalytic network, no matter how complex. Such tradeoffs have potentially wide-ranging
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implications, from cryptic physiological variability in medicine to the failures of complex technological and financial networks and the challenges of sustainable infrastructure.
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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 are of growing importance. Crucial to sustainable infrastructure is not only efficiency in minimizing waste and resource use, but also robustness to perturbations in system components, operation, and environment [22]. This paper explores such robust efficiency via integration of elementary concepts from biochemistry and control theory [2][3] using the familiar
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This note was uploaded on 01/04/2012 for the course CDS 212 taught by Professor Tarraf,d during the Fall '08 term at Caltech.

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Glycolysis_Main - Glycolytic Oscillations and Limits on...

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