The Regulation of Cellular Systems

About this book

This book deals with problems and approaches to cellular systems and will cover a wide range of cell types and cell systems, including nerve cells. It will be of interest to cell biologists interested in modeling, and to any students interested in the field. It will also appeal to the theoretical and mathematical biology community, and would have relevance to individuals interested in evolutionary issues as they bear on cellular metabolic models. It will be a solid theoretical book, with an empirical base and an evolution connection, that fits exactly to the initial theme of the theoretical biology series.

Contents

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.

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