Now in its fourth edition, this textbook is one of the few titles worldwide to cover enzyme kinetics in its entire scope and the only one to include its implications for bioinformatics and systems biology. Multi-enzyme complexes and cooperativity are therefore treated in more detail than in any other textbook on the market. The respected and well known author is one of the most experienced researchers into the topic and writes with outstanding style and didacticclarity. As with the previous editions, he presents here steady-state kinetics and fast reactions, supplementing each chapter with problems and solutions. For the first time, this edition features color illustrations and a companion website. INDICE: 1 Basic Principles of Chemical Kinetics1.1 Abbreviations and symbols1.2 Order of a reaction1.3 Dimensions of rate constants1.4 Reversible reactions1.5 Determination of first-order rate constants1.6 Catalysis1.7 The influence of temperature and pressure on rate constantsProblems2 Introduction to Enzyme Kinetics2.1 The idea of an enzyme?substrate complex2.2 The Michaelis?Mentenequation2.3 The steady state of an enzyme-catalysed reaction2.5 Validity of the steady-state assumption2.6 Graphs of the Michaelis?Menten equation2.7 The reversible Michaelis?Menten mechanism2.8 Product inhibition2.9 Integration of enzyme rate equations2.10 Artificial enzymes, RNA enzymes and catalytic antibodiesProblems3 Practical Aspects of Kinetic Studies3.1 Enzyme assays3.2 Estimating the initial rate3.3 Detecting enzyme inactivation3.4 Experimental design3.5Treatment of ionic equilibriaProblems4 Deriving Steady-State Rate Equations4.1 Introduction4.2 The principle of the King?Altman method4.3 The method of King and Altman4.4 The method of Wong and Hanes4.5 Modifications to the King?Altman method4.6 Reactions containing steps at equilibrium4.7 Analysing mechanismsby inspection4.3 The method of King and Altman4.4 The method of Wong and Hanes4.5 Modifications to the King?Altman method4.6 Reactions containing steps at equilibrium4.7 Analysing mechanisms by inspection4.8 A simpler method for irreversible reactions4.9 Derivation of rate equations by computerProblems5 Reversible Inhibition and Activation5.1 Introduction5.2 Linear inhibition5.3 Plotting inhibition results5.4 Multiple inhibitors5.5 Relationship between inhibitionconstants and the concentration for 50% inhibition5.6 Inhibition by a competing substrate5.7 Enzyme activation5.8 Design of inhibition experiments5.9 Inhibitory effects of substratesProblems6 Tight-binding and Irreversible Inhibitors6.1 Tight-binding inhibitors6.2 Irreversible inhibitors6.3 Substrate protection experiments6.4 Mechanism-based inactivation6.5 Chemical modification as a means of identifying essential groups6.6 Inhibition as the basis of drug designProblems7 Reactions of More than One Substrate7.1 Introduction7.2 Classification of mechanisms7.3 Rate equations7.3.4 Haldane relationships7.4 Initial-rate measurements in the absence of products7.5 Substrate inhibition7.6 Product inhibition7.7 Design of experiments7.8 Reactions with three or more substratesProblems8 Use of Isotopes for Studying Enzyme Mechanisms8.1 Isotope exchange and isotope effects8.2 Principles of isotope exchange8.3 Isotope exchange at equilibrium8.4 Isotope exchange in substituted-enzyme mechanisms8.5 Non-equilibrium isotope exchange8.6 Theory of kinetic isotope effects8.7 Primary isotope effects in enzyme kinetics8.8 Solvent isotope effectsProblems9 Effect of pH on Enzyme Activity9.1 Enzymes and pH9.2 Acid?base properties of proteins9.3 Ionization of a dibasic acid9.4 Effect of pH on enzyme kinetic constants9.5 Ionization of the substrate9.6 More complicated pH effectsProblems10 Temperature Effects on Enzyme Activity10.1 Temperature denaturation10.2 Temperature optimum10.3 Application of the Arrhenius equation to enzymes10.4 Entropy?enthalpy compensationProblems11 Regulation of Enzyme Activity11.1 Function of cooperative and allosteric interactions11.2 The development of models to explain cooperativity11.3 Analysis of binding experiments11.4 Induced fit11.5 The symmetry model of Monod, Wyman and Changeux11.6 Comparison between the principal models of cooperativity11.7 The sequential model of Koshland, Nemethy and Filmer11.8 Kinetic cooperativityProblems12 Kinetics of Multi-Enzyme Systems12.1 Enzymes in their physiological context12.2 Metabolic control analysis12.3 Elasticities12.4 Control coefficients12.5 Properties of control coefficients12.5.2 Implications for large changes12.5.3 Constrained enzyme concentrations12.6 Relationships betweenelasticities and control coefficients12.7 Response coefficients: the partitioned response12.8 Control and regulation12.9 Mechanisms of regulation12.10 Computer modelling of metabolic systems12.11 Implications for biotechnology and drug discoveryProblems13 Fast Reactions13.1 Limitations of steady-state measurements13.2 Product release before completion of the catalytic cycle13.3 Experimental techniques13.4 Transient-state kineticsProblems14 Estimation of Kinetic Constants14.1 The effect of experimental error on kinetic analysis14.2 Least-squares fit to the Michaelis?Menten equation14.2.4 Estimating weights from replicate observations14.3 Statistical aspects of the direct linear plot14.4 Precision of estimated kinetic parameters14.4.4 Km as the least precise Michaelis?Menten parameter14.5 Generalizing the results to more than two parameters14.6 Residual plots and their usesProblemsAPPENDIX: Standards for Reporting Enzymology DataSolutions and Notes to Problems
- ISBN: 978-3-527-33074-4
- Editorial: John Wiley & Sons
- Encuadernacion: Rústica
- Páginas: 510
- Fecha Publicación: 25/01/2012
- Nº Volúmenes: 1
- Idioma: Inglés