The Regulation of Cellular Systems

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.