Open AccessBook
The Regulation of Cellular Systems
TLDR
The basic equations of metabolic control analysis are rewritten in terms of co-response coefficients and internal response coefficients to describe the interaction of optimization methods and the interrelation with evolution.Abstract:
Introduction Fundamentals of biochemical modeling Balance equations Rate laws Generalized mass-action kinetics Various enzyme kinetic rate laws Thermodynamic flow-force relationships Power-law approximation Steady states of biochemical networks General considerations Stable and unstable steady states Multiple steady states Metabolic oscillations Background Mathematical conditions for oscillations Glycolytic oscillations Models of intracellular calcium oscillations A simple three-variable model with only monomolecular and bimolecular reactions Possible physiological significance of oscillations Stoichiometric analysis Conservation relations Linear dependencies between the rows of the stoichiometry matrix Non-negative flux vectors Elementary flux modes Thermodynamic aspects A generalized Wegscheider condition Strictly detailed balanced subnetworks Onsager's reciprocity reactions for coupled enyme reactions Time hierarchy in metabolism Time constants The quasi-steady-state approximation The Rapid equilibrium approximation Modal analysis Metabolic control analysis Basic definitions A systematic approach Theorems of metabolic control analysis Summation theorems Connectivity theorems Calculation of control coefficients using the theorems Geometrical interpretation Control analysis of various systems General remarks Elasticity coefficients for specific rate laws Control coefficients for simple hypothetical pathways Unbranched chains A branched system Control of erythrocyte energy metabolism The reaction system Basic model Interplay of ATP production and ATP consumption Glycolytic energy metabolism and osmotic states A simple model of oxidative phosphorylation A three-step model of serine biosynthesis Time-dependent control coefficients Are control coefficients always parameter independent? Posing the problem A system without conserved moieties A system with a conserved moiety A system including dynamic channeling Normalized versus non-normalized coefficients Analysis in terms of variables other than steady-state concentrations and fluxes General analysis Concentration ratios and free-energy-differences as state variables Entropy production as response variable Control of transient times Control of oscillations A second-order approach A quantitative approach to metabolic regulations Co-response coefficients Fluctuations of internal variables versus parameter perturbations Internal response coefficients Rephrasing the basic equations of metabolic control analysis in terms of co-response coefficients and internal response coefficients Control within and between subsystems Modular approach Overall elasticities Overall control coefficients Flux control insusceptibility Control exerted by elementary steps in enzyme catalysis Control analysis of metabolic channeling Comparison of metabolic control analysis and power-law formalism Computational aspects Application of optimization methods and the interrelation with evolution Optimization of the catalytic properties of single enzymes Basic assumptions Optimal values of elementary rate constants Optimal Michaelis constants Optimization of multienzyme systems Maximization of steady-state flux Influence of osmotic constraints and minimization of intermediate concentrations Minimization of transient times Optimal stoichiometries.read more
Citations
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Proceedings ArticleDOI
Design tradeoffs in a synthetic gene control circuit for metabolic networks
Diego A. Oyarzún,Guy-Bart Stan +1 more
TL;DR: It is shown that enzyme half-lives are an upper bound on the speed at which the pathway can adapt to a changing metabolic demand and a compromise between operon and non-operon topologies in terms of robustness and design flexibility is highlighted.
Proceedings Article
Fast Stochastic Simulation of Metabolic Networks.
TL;DR: A new software tool is presented that is platform independent, user friendly and offers several unique features of simulation and modeling methods and numerical considerations and support for the switching between simulation methods are discussed.
Abstractions, Analysis Techniques, and Synthesis of Scalable Control Strategies for Robot Swarms
TL;DR: A comprehensive approach to modeling a robot swarm, analyzing its behavior, and synthesizing scalable, decentralized stochastic control policies with theoretical guarantees on performance is presented.
Journal ArticleDOI
Dynamic sensitivity and control analyses of metabolic insulin signalling pathways
TL;DR: The authors have calculated the time-dependent sensitivities of the concentration of the membrane GLUT4 with respect to all reaction parameters (reaction rate constants and initial concentrations of the effectors) to provide dynamic information about pathways, in particular, the separate roles of the negative and positive feedbacks in the network.
Posted Content
Sensitivity Analysis of Stoichiometric Networks: An Extension of Metabolic Control Analysis to Non-equilibrium Trajectories
Brian Ingalls,Herbert M. Sauro +1 more
TL;DR: A sensitivity analysis of general stoichiometric networks is considered and an expression for time-varying sensitivity coefficients is given, and the Summation and Connectivity Theorems are generalized.
References
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Book
Linear Multivariable Control: A Geometric Approach
TL;DR: In this article, the authors present an approach to controlability, feedback assignment, and pole shifting in a single linear functional model, where the observer is assumed to be a dynamic observer.