Table Of ContentCONTRIBUTORS TO THIS VOLUME
Bernard Axelrod
J. J. Burns
David E. Green
W. Z. Hassid
Lloyd L. Ingraham
John M. Lowenstein
David H. MacLennan
Arthur B. Pardee
Metabolic Pathways
THIRD EDITION
EDITED BY
David M. Greenberg
University of California
San Francisco Medical Center
San Francisco, California
VOLUME I
Energetics, Tricarboxylic Acid Cycle, and Carbohydrates
ACADEMIC PRESS New York and London 1967
COPYRIGHT © 1967, BY ACADEMIC PRESS, INC.
ALL RIGHTS RESERVED
NO PART OF THIS BOOK MAY BE REPRODUCED IN ANY FORM,
BY PHOTOSTAT, MICROFILM, RETRIEVAL SYSTEM, OR ANY
OTHER MEANS, WITHOUT WRITTEN PERMISSION FROM
THE PUBLISHERS.
ACADEMIC PRESS, INC.
Ill Fifth Avenue, New York, New York 10003
United Kingdom Edition published by
ACADEMIC PRESS, INC. (LONDON) LTD.
Berkeley Square House, London W1X 6BA
LIBRARY OF CONGRESS CATALOG CARD NUMBER: 67-23160
Third Printing, 1971
PRINTED IN THE UNITED STATES OF AMERICA
List of Contributors
Numbers in parentheses indicate the pages on which the authors' contributions begin.
BERNARD AXELROD, Department of Biochemistry, Purdue University,
Lafayette, Indiana (112, 271)
J. J. BURNS, Research Division, Hoffmann-La Roche Inc., Nutley, New
Jersey (394)
DAVID E. GREEN, University of Wisconsin, Institute for Enzyme Research,
Madison, Wisconsin (47)
W. Z. HASSID, Department of Biochemistry, University of California, Berkeley
California (307)
LLOYD L. INGRAHAM, Department of Biochemistry and Biophysics, University
of California, Davis, California (1)
JOHN M. LOWENSTEIN, Graduate Department of Biochemistry, Brandeis
University, Waltham, Massachusetts (146)
DAVID H. MACLENNAN, Institute for Enzyme Research, University of Wiscon
sin, Madison, Wisconsin (47)
ARTHUR B. PARDEE, Biology Department, Princeton University, Princeton,
New Jersey (1)
V
Preface
Increase in biochemical knowledge has been foremost in developing a basic
understanding of the fundamental nature of life processes. The discoveries
of the past twenty-five or thirty years have yielded a penetrating insight into
the dynamic events of cellular metabolism. New discoveries have led to chang
ing emphasis in thought and research. Previously, the major research effort
was devoted to the determination of the sequential steps of the different meta
bolic pathways and the isolation and characterization of the enzymes cata
lyzing the several steps. The great, recent discoveries in the knowledge of
molecular genetics have now directed investigation more and more into the
nature of the genetic determinants of metabolism and of the various mechan
isms for its regulation to meet the physiological needs of individual cells and
of multicellular organisms as a whole.
The purpose of this work remains, as in previous editions, to survey the
existing knowledge of the chemical steps in the metabolism of the constituents
of major importance in living organisms. With the vast increase in the rate
of publication of the biochemical literature, interpretive works, such as this,
assume progressively greater value, since no single individual can keep abreast
of the advances in all facets of biochemistry. Reviews by competent authorities
are now one of the major means of being cognizant of the state of develop
ment of any particular field of biochemistry. Noted authorities have been
sought to write about their particular areas of specialization in the new edi
tion of " Metabolic Pathways." Most of the contributors are the same as those
of the previous edition, but there have been, of necessity, a number of changes
in authorship.
The great mass of biochemical literature also gives rise to the problem that
greater space is required to give an adequate coverage of the different bio
chemical areas reviewed in this work. This has made it necessary to increase
the number of volumes in order to keep each volume of reasonable size.
DAVID M. GREENBERG
San Francisco, California
October, 1967
vii
Contents of Other Volumes
Volume II
Chapter 8. FATTY ACID OXIDATION
D. E. GREEN AND D. W. ALLMANN
Chapter 9. BIOSYNTHESIS OF FATTY ACIDS
D. E. GREEN AND D. W. ALLMANN
Chapter 10. METABOLISM OF PHOSPHATIDES
R. J. ROSSITER
Chapter 11. STEROID METABOLISM
HENRY DANIELSSON AND T. T. TCHEN
Chapter 12. METABOLISM OF STEROID HORMONES
LEO T. SAMUELS AND KRISTEN B. EIK-NES
Chapter 13. CAROTENOIDS AND VITAMIN A
G. MACKINNEY
AUTHOR INDEX SUBJECT INDEX
Volume III
Chapter 14. NITROGEN METABOLISM OF AMINO ACIDS
H. J. SALLACH AND L. A. FAHIEN
Chapter 15 (Part I). CARBON CATABOLISM OF AMINO ACIDS
DAVID M. GREENBERG
Chapter 15 (Part II). CARBON CATABOLISM OF AMINO ACIDS
VICTOR W. RODWELL
Chapter 16 (Part I). BIOSYNTHESIS OF AMINO ACIDS AND
RELATED COMPOUNDS
DAVID M. GREENBERG
Chapter 16 (Part II). BIOSYNTHESIS OF AMINO ACIDS AND
RELATED COMPOUNDS
VICTOR W. RODWELL
xii
CONTENTS OF OTHER VOLUMES Xlll
Chapter 17. SELECTED ASPECTS OF SULFUR METABOLISM
ERNEST KUN
Chapter 18. METABOLISM OF PORPHYRINS AND
CORRINOIDS
BRUCE F. BURNHAM
AUTHOR INDEX SUBJECT INDEX
Volume IV
Chapter 19. PURINES AND PYRIMIDINES
STANDISH C. HARTMAN
Chapter 20. NUCLEOTIDES AND NUCLEIC ACIDS
SAUL KIT
Chapter 21. PROTEIN SYNTHESIS
C. BAGLIONI AND B. COLOMBO
Chapter 22. BIOSYNTHESIS OF RIBOFLAVIN AND RELATED
COMPOUNDS
T. W. GOODWIN
Chapter 23. BIOGENESIS AND METABOLISM OF THIAMINE
GENE M. BROWN
Chapter 24. BIOGENESIS AND METABOLISM OF FOLIC ACID
GENE M. BROWN
Chapter 25. METABOLISM OF VITAMIN B
6
VICTOR W. RODWELL
AUTHOR INDEX SUBJECT INDEX
Volume V (In preparation): Metabolic Regulation
Volume Editor: Henry J. Vogel
Chapter 26. ADENINE NUCLEOTIDES AS STOICHIOMETRIC
COUPLING AGENTS IN METABOLISM AND AS
REGULATORY MODIFIERS: THE ADENYLATE
ENERGY CHARGE
DANIEL E. ATKINSON
Chapter 27. REGULATION OF FATTY ACID SYNTHESIS
M. DANIEL LANE AND JOEL MOSS
Chapter 28. REGULATION OF CYTOCHROME BIOSYNTHESIS
IN SOME EUKARYOTES
MARY E. KING
XIV CONTENTS OF OTHER VOLUMES
Chapter 29. δ-AMINOLEVULINIC ACID SYNTHETASE AND
THE CONTROL OF HEME AND CHLOROPHYLL
SYNTHESIS
S. GRANICK AND SHIGERU SASSA
Chapter 30. TRANSFER RNA AND REGULATION AT THE
TRANSLATIONAL LEVEL
MICHAEL WILCOX
Chapter 31. REGULATION OF GENE EXPRESSION IN
MAMMALIAN CELLS
DAVID W. MARTIN, JR.
Chapter 32. GENE CLUSTERS AND THE REGULATION OF
BIOSYNTHETIC PATHWAYS IN FUNGI
GERALD R. FINK
Chapter 33. REGULATION OF PURINE AND PYRIMIDINE
METABOLISM
JOSEPH S. GOTS
Chapter 34. REGULATION IN THE L-ARABINOSE SYSTEM
ELLIS ENGLESBERG
Chapter 35. REGULATING THE LAC OPERON
GEOFFREY ZUBAY AND DONALD A. CHAMBERS
Chapter 36. THE HISTIDINE OPERON AND ITS REGULATION
MICHAEL BRENNER AND BRUCE N. AMES
Chapter 37. REGULATION OF TRYPTOPHAN SYNTHESIS
PAUL MARGOLIN
Chapter 38. THE REGULATION OF ENZYME LEVELS IN
THE PATHWAYS TO THE BRANCHED CHAIN
AMINO ACIDS
H. E. UMBARGER
Chapter 39. THE ARGININE BIOSYNTHETIC SYSTEM AND
ITS REGULATION
RUTH H. VOGEL, WILLIAM L. MCLELLAN,
ALICE P. HIRVONEN, AND HENRY J. VOGEL
Chapter 40. REGULATION OF ENZYME FORMATION IN
SOME ANABOLIC AND CATABOLIC SEQUENCES
IN PSEUDOMONADS
I. C. GUNSALUS AND S. F. QUEENER
AUTHOR INDEX SUBJECT INDEX
Volume VI (In preparation): Transport
Volume Editor: Lowell Hokin
CHAPTER 1
Free Energy and Entropy in Metabolism
Lloyd L. Ingraham
and
Arthur B. Pardee
I. Introduction 2
II. Free Energy and Its Determination 3
A. The Nature of Free Energy 3
B. Free Energy of Activation 6
C. Free Energy of Formation 7
D. Dependence of AF° on Concentration 7
E. Relation between AF° and the Equilibrium Constant 9
F. Relation between AF° and Electromotive Force 10
G. Determination of AF° from Thermodynamic Data 12
H. Combination of Equations 13
I. Dependence of Free Energy on pH 13
J. Dependence of Free Energy on Temperature 15
III. Heat of Reaction 16
A. Nature of Heat Content and Bond Energy 16
B. Measurements of Heats of Reaction 18
IV. Entropy 18
A. Introduction 18
B. Physical State and Entropy 21
C. Structure and Entropy 21
D. Sources of Entropy Values 22
E. Change in Entropy during Reaction 25
F. Entropy of Activation during Reaction 27
G. Entropy Changes during Protein Denaturations 29
H. Entropy Changes during Enzyme Reactions 30
V. Sources of Energy 31
A. Photosynthesis 32
B. Energy from Inorganic Compounds 34
C. Assimilation 35
1
2 LLOYD L. INGRAHAM AND ARTHUR B. PARDEE
VI. Release of Energy 36
A. Controlled Energy Release 36
B. Coupling of Reactions 37
C. High-Energy Phosphate 38
D. Production of High-Energy Phosphate 41
E. Storage of High-Energy Phosphate 42
F. Utilization of Energy 42
References 43
I. INTRODUCTION
The most useful concept that biochemists have acquired from thermo
dynamics is that of free energy. By considering the free energy change
of a reaction, one can tell whether it may proceed spontaneously or
whether it must be "driven" by other reactions. Further, one can
calculate the amount of energy given off by a reaction or required by it,
and this is a most important feature of many reactions. From free energy
data one can easily calculate equilibrium constants and electromotive
forces.
With a knowledge of the closely related but difficultly available values
for free energy of activation for a given reaction, it is also possible to
calculate the rate of the reaction and to judge whether the mechanism
is plausible or not.
In this chapter, an attempt will first be made to introduce the concept
of free energy in a simple, descriptive way. The various methods of
obtaining free energy data will be shown. This section will also provide
relations between free energy and other quantities of direct interest, such
as equilibrium constants, heats of reactions, and electromotive forces.
Unfortunately for biochemists, thermodynamics developed during the
nineteenth century in a study of heat engines. Because students of bio
chemistry are usually much more interested in the hydrolysis of ATP
than in engines undergoing Carnot cycles, the stress in this chapter will
be on the relation between chemical structure and thermodynamics.
Free energy of activation will also be introduced, and the usefulness
of this concept in determining rates and mechanisms will be discussed.
The next two sections will be devoted to heat content and entropy
because these terms that comprise free energy are often more easily
estimated separately from molecular structural data than free energy
itself. Entropy values for a reaction are particularly important, because
they may give an insight into structural changes of the products relative
to the reactants. The remainder of the chapter will be devoted to applica
tions of thermodynamics that will serve to indicate areas of biochemistry
