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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Journal ArticleDOI
Global self-regulation of the cellular metabolic structure.
Ildefonso M. De la Fuente,Luis Martínez,Alberto Pérez-Samartín,Leire Ormaetxea,Cristian Amezaga,Antonio Vera-López +5 more
TL;DR: This work has found that the existence of a high number of enzymatic subsystems belonging to the DMNs is the fundamental element for the spontaneous emergence of a functional reactive structure characterized by a metabolic core formed by several sets of enzymes always in an active state.
Journal ArticleDOI
From molecular networks to qualitative cell behavior.
Julien Gagneur,Georg Casari +1 more
TL;DR: Constrained‐based techniques and qualitative modeling have proven themselves to be valid approaches in cell biology and offer formal support to check the consistency of molecular networks against phenotypic observations in the light of dynamic systems.
Journal ArticleDOI
Metabolic control analysis: biological applications and insights.
TL;DR: This work focuses on metabolic control analysis, which has already shed light on some of the principles underlying the regulation of metabolic pathways, and is well suited to the analysis of the types of data emerging from genomic studies.
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On the identifiability of metabolic network models.
TL;DR: This work addresses the detection and resolution of identifiability problems for a class of pseudo-linear models of metabolism, so-called linlog models, and develops precise definitions of structural and practical identifiable, and clarifies the fundamental relations between these concepts.
Journal ArticleDOI
Circadian oscillators in eukaryotes
TL;DR: The issue of temperature compensation (TC) is discussed, and the present understanding of the underlying genetic and biochemical mechanisms in circadian oscillators are described with special emphasis on Neurospora crassa, mammals, and plants.
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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.