Site map > Home page > CV > Books > Fundamentals > Fundamentals of Enzyme Kinetics

Fundamentals of Enzyme Kinetics
(2nd Edition, 1995)

This page describes the book Fundamentals of Enzyme Kinetics (2nd edition) by Athel Cornish-Bowden, published by Portland Press (1995). This page and the pages linked from it are now obsolete as the 3rd edition is now published. There is no intention to update them in the future.

 Cover design

Publication details

The 2nd edition was published by Portland Press, London, 1995

Reprinted 1999 (with corrections), 2001 and 2002. Corrections made in 1999 to the 1995 printing are listed on another page. They are mostly minor.

Paperback, 344 pages, ISBN 1 85578 072 0

What the reviewers have thought...

High competence...

This is a rewritten edition of a respected 1979 contribution to enzyme kinetics. Neither the basic outline nor the high competence has been changed, but there have been additions throughout. (Analytical Biochemistry)

A readable reference text...

This is a readable reference text both for teachers and researchers, and one which confident undergraduates might also dip into. (Clive Bullock in Education in Chemistry)

A renowned expert...

Cornish-Bowden, a renowned expert in the field of enzyme kinetics, focuses on the purely kinetic behavior of enzymes. (K. Cornely in Choice)

Fondamenti per la comprensione...

Il testo fornisce i fondamenti per la comprensione della cinetica enzimatica, qualunque sia il livello di preparazione del lettore. (N.C. in Scienza e Governo)

A truly excellent book...

Cornish-Bowden’s recently revised Fundamentals of Enzyme Kinetics allows me to offer praise while retaining my self respect, for this is a truly excellent book... I have not compared this book with the previous edition, mainly because my copy of that book was borrowed (permanently) by a person unknown. This is probably an indication of the value of the previous edition. I shall be guarding my copy of the present book more carefully. (Ronald Duggleby in Protein Science)

The best presentation available...

A revised edition of a very good text published in 1979... It gives the best presentation available and is an essential complement to modern texts of biochemistry, which tend to minimize their treatment of enzyme kinetics. (Herbert Gutfreund in Molecular Membrane Biology)

A valuable resource...

The book is a valuable resource for those approaching enzyme kinetics for the first time as well as for those wishing to renew their acquaintance with the subject. (Ariane Marolewski in Journal of Medicinal Chemistry)

Outstanding and up to date...

There are several good books on enzyme kinetics but this one is outstanding and up to date... Every biochemical library should have at least two copies, one for reference and one for borrowing, and I advise anyone teaching enzyme kinetics to get their own copy, it will be £18/US$29 well invested. (Michael Selwyn in Biochemical Education)

An almost literary book...

My fear is that ... those who need to know them would be too intimidated to pick up a whole book on enzyme kinetics. This would be a pity, since Cornish-Bowden has written an almost literary book on what is probably considered by most biochemists to be the dullest and driest of subjects, albeit one with a history as long as classical physical chemistry. (Michael Silverberg in the Quarterly Review of Biology)

I welcome this volume...

The time that has elapsed before the appearance of this new edition has been, in my view, far too long. I welcome this volume not only because of some of the new material that it contains but also because my copies of the earlier versions have long since vanished on permanent loan to unidentifiable students. (Keith Tipton in The Biochemist)

Strongly recommended...

Strongly recommended as an accompaniment to more detailed research literature. (Richard Virden in Experimental Physiology)`

Clear and intelligent intro to enzyme kinetics

 5 stars from an Amazon reviewer This is a superb introduction to enzyme kinetics for advanced undergraduate and graduate students, as well as anyone who has ever taken an introductory biochemistry course. If everyone who is doing enzyme kinetics these days read this book, their experimental design would be far less sloppy, and results much more reliable. It is not nearly as comprehensive as Segel’s book, but its pedagogical value is great. (The only objection I had is that author’s style of exposition sometimes gets a bit too acerbic. But, after all, the author is English :) (A reader from Stockholm, Sweden)

COMPLETE REVIEWS

Course adoptions

The following is a selection of university courses that have adopted Fundamentals of Enzyme Kinetics as either a required or a recommended text. Every link was valid at the time it was added to this page, but it may have lapsed since (e.g. because the course in question is not offered every year). Links that failed when last tested (on 31 August 2001) are marked *.

Contents

1. Basic Principles of Chemical Kinetics

1.1 Order of a reaction: order and molecularity; determination of the order of a reaction

1.2 Dimensions of rate constants

1.3 Reversible reactions

1.4 Determination of first-order rate constants

1.5 The influence of temperature on rate constants: the Arrhenius equation; elementary collision theory; transition-state theory

Problems

2. Introduction to Enzyme Kinetics

Warning: Two typographical errors in the original (1995) printing of this chapter are noted elsewhere.

2.1 Early studies: the idea of an enzyme-substrate complex

2.2 The Michaelis-Menten equation

2.3 The steady state of an enzyme-catalysed reaction: the Briggs-Haldane treatment; the Michaelis-Menten equation; units of enzyme activity; the curve defined by the Michaelis-Menten equation; ways of writing the Michaelis-Menten equation

2.4 Validity of the steady-state assumption

2.5 Graphs of the Michaelis-Menten equation: plotting v against a; the double-reciprocal plot; the plot of a/v against a; the plot of v against v/a; the direct linear plot

2.6 The reversible Michaelis-Menten mechanism: the reversible rate equation; the Haldane relationship; one-way enzymes

2.7 Product inhibition

2.8 Integration of the Michaelis-Menten equation

2.9 Artificial enzymes, RNA enzymes and catalytic antibodies: alternative enzymes; artificial enzymes; catalytic RNA; catalytic antibodies

Problems

3. Practical Aspects of Kinetic Studies

3.1 Enzyme assays: discontinuous and continuous assays; estimating the initial rate; increasing the straightness of the progress curve; coupled assays

3.2 Detecting enzyme inactivation

3.3 Experimental design: choice of substrate concentrations; choice of pH, temperature and other conditions; use of replicate observations

3.4 Treatment of ionic equilibria

Problems

4. How to Derive Steady-State Rate Equations

4.1 Introduction

4.2 The principle of the King-Altman method

4.3 The method of King and Altman

4.4 The method of Wong and Hanes

4.5 Modifications to the King-Altman method

4.6 Reactions containing steps at equilibrium

4.7 Analysing mechanisms by inspection: topological reasoning; mechanisms with alternative routes; dead-end steps

4.8 Derivation of rate equations by computer

Problems

5. Inhibition and Activation of Enzymes

5.1 Reversible and irreversible inhibition: catalytic poisons; analysis of the rate of inactivation; types of reversible inhibition

5.2 Linear inhibition: competitive inhibition (specific inhibition); mixed inhibition; uncompetitive inhibition (catalytic inhibition); summary of linear inhibition types

5.3 Plotting inhibition results

5.4 Inhibition by a competing substrate: enzyme specificity; testing if two reactions occur at the same site; substrate protection experiments

5.5 Enzyme activation: miscellaneous uses of the term activation; specific activation; hyperbolic activation and inhibition

5.6 Design of inhibition experiments

5.7 Inhibitory effects of substrates: non-productive binding; substrate inhibition

5.8 Chemical modification as a means of identifying essential groups

Problems

6. Reactions of More than One Substrate

6.1 Introduction

6.2 Classification of mechanisms: ternary-complex mechanisms; substituted-enzyme mechanisms; comparison between chemical and kinetic classifications

6.3 Rate equations: compulsory-order ternary-complex mechanism; random-order ternary-complex mechanism; substituted-enzyme mechanism; calculation of rate constants from kinetic parameters

6.4 Initial-rate measurements in the absence of products: meanings of the parameters; apparent Michaelis-Menten parameters; primary plots for ternary-complex mechanisms; secondary plots for ternary-complex mechanisms; plots for the substituted-enzyme mechanism

6.5 Substrate inhibition: why substrate inhibition occurs; compulsory-order ternary-complex mechanism; random-order ternary-complex mechanism; substituted-enzyme mechanism; diagnostic value of substrate inhibition

6.6 Product inhibition

6.7 Design of experiments

6.8 Reactions with three or more substrates

Problems

7. Use of Isotopes for Studying Enzyme Mechanisms

New chapter: not in the original edition

7.1 Isotope exchange and isotope effects

7.2 Principles of isotope exchange

7.3 Isotope exchange at equilibrium

7.4 Isotope exchange in substituted-enzyme mechanisms

7.5 Non-equilibrium isotope exchange: chemiflux ratios; isomerase kinetics; tracer perturbation

7.6 Theory of kinetic isotope effects: primary isotope effects; secondary isotope effects; equilibrium isotope effects

7.7 Primary isotope effects in enzyme kinetics

8. Environmental Effects on Enzymes

8.1 pH and enzyme kinetics

8.2 Acid-base properties of proteins

8.3 Ionization of a dibasic acid: expression in terms of group dissociation constants; molecular dissociation constants; bell-shaped curves

8.4 Effect of pH on enzyme kinetic constants: underlying assumptions; pH dependence of V and V/Km; pH-independent parameters and their relationship to apparent parameters; pH dependence of Km; experimental design

8.5 Ionization of the substrate

8.6 More complex pH effects

8.7 Temperature dependence of enzyme-catalysed reactions: temperature denaturation; temperature optimum; application of the Arrhenius equation to enzymes

8.8 Solvent isotope effects

Problems

9. Control of Enzyme Activity

9.1 Function of cooperative and allosteric interactions: futile cycles; inadequacy of Michaelis-Menten kinetics for regulation; cooperativity; allosteric interactions

9.2 The development of models to explain cooperativity: the Hill equation; an alternative index of cooperativity; assumption of equilibrium binding in cooperative kinetics; the Adair equation; mechanistic and operational definitions of cooperativity

9.3 Analysis of binding experiments: the Scatchard plot

9.4 Induced fit

9.5 Modern models of cooperativity: the symmetry model of Monod, Wyman and Changeux; the sequential model of Koshland, Némethy and Filmer; association-dissociation models

9.6 Kinetic cooperativity

Problems

10. Kinetics of Multi-Enzyme Systems

New chapter: not in the original edition

A hypertext version of this chapter can be consulted on the web.

Warning: Three typographical errors in the original (1995) printing of this chapter are noted elsewhere.

10.1 Enzymes in their physiological context

10.2 Metabolic control analysis

10.3 Elasticities: definition of elasticity; common properties of elasticities; enzyme kinetics viewed from control analysis

10.4 Control coefficients

10.5 Summation relationships

10.6 Relationships between elasticities and control coefficients: connectivity properties; control coefficients in a three-step pathway; expression of summation and connectivity relationships in matrix form; connectivity relationship for a metabolite not involved in feedback; relationship of flux control coefficients to elasticities and concentration control coefficients

10.7 Response coefficients: the partitioned response

10.8 Control and regulation

10.9 Mechanisms of regulation: metabolite channelling; interconvertible enzyme cascades; the metabolic role of adenylate kinase

Problems

11. Fast Reactions

11.1 Limitations of steady-state measurements

11.2 Product release before completion of the catalytic cycle: burst kinetics; active site titration

11.3 Experimental techniques: classes of method; continuous flow; stopped flow; quenched flow; relaxation methods

11.4 Transient-state kinetics: systems far from equilibrium; simplification of complex mechanisms; systems close to equilibrium

Problems

12. Estimation of Kinetic Constants

The topic of this chapter is covered in more detail in a separate book, which includes a PC program Leonora designed for statistical analysis of enzyme kinetic data...

Analysis of Enzyme Kinetic Data

12.1 The effect of experimental error on kinetic analysis

12.2 Least-squares fit to the Michaelis-Menten equation: introduction of error in the Michaelis-Menten equation; estimation of V and Km; corresponding results for a uniform standard deviation in the rates

12.3 Statistical aspects of the direct linear plot: comparison between classical and distribution-free statistics; application to the direct linear plot; lack of need for weighting; insensitivity to outliers; handling of negative parameter estimates

12.4 Precision of estimated kinetic parameters

12.5 Residual plots and their uses

Problems

References

Solutions to Problems

Index

Corrections

Errors in the first (1995) printing are listed elsewhere. Nearly all of these were corrected in later printings, but a small number survived even to the 3rd edition.