Biochemistry. The Chemical Reactions Of Living Cells

1139 Pages·1977·108.16 MB·English

by  David Metzler (Auth.)

BIOCHEMISTRY
The Chemical Reactions of Living Cells
DAVID E. METZLER
Iowa State University
Copyright © 1977, by Academic Press, Inc.
All rights reserved. No part of this publication may be
reproduced or transmitted in any form or by any means,
electronic or mechanical, including photocopy, recording,
or any information storage and retrieval system, without
permission in writing from the publisher.
ACADEMIC PRESS, INC.
I l l Fifth Avenue, New York, New York 10003
United Kingdom Edition published by
ACADEMIC PRESS, INC. (LONDON) LTD.
24/28 Oval Road, London NW1
Library of Congress Cataloging in Publication Data
Metzler, David E
Biochemistry (TX)
Includes bibliographical references and index.
1. Cytochemistry. 2. Chemical reactions.
tie. [DNLM: 1. Cels. 2. Biochemistry.
cytochemistry. QH611 M596c]
QH61.M4 574.876 75-32031
ISBN 0-12-492550 2
PRINTED IN THE UNITED STATES OF AMERICA
Preface
Because the study of the chemical reactions of living cells is a vast and complex field that
touches almost every branch of chemistry and biology, writing an introductory textbook in this
field is a difficult task. I would never have undertaken such a project if my goal had been merely
to try to improve on the textbooks currently available, but I am convinced that a new approach
to biochemistry will be useful to a broad range of students and teachers. Therefore, rather than
dividing biochemistry into segments centered around specific chemical compounds such as
proteins, nucleic acids, lipids, and carbohydrates, I treat chemical reactions of cells as a primary
theme. While stressing biological concerns, I try to trace all physiological phenomena back to
the underlying chemistry.
For the student, the study of biochemistry in all of its complexities and nuances may seem
overwhelming. I have tried in various ways to make this task easier for students with diverse
backgrounds. For instance, the main body of the text focuses on a clear and uncluttered
presentation of biochemical principles. Ancillary information on vitamins, metallic elements,
poisons, research techniques, and metabolic diseases may be fascinating to some students but
of lesser interest to others. Therefore, such information is set off from the main text in special
boxes, where it will not interrupt the flow of the fundamental material. (These boxes are noted
on the detailed table of contents, and are also listed under eight subject headings on p. xxix.) In
addition to trying to provide a clear and highly readable introduction to the basic principles of
biochemistry, I have also attempted to provide the student with a book that can be used in the
future as a reference source. Literature citations of three types have been included: (1) those to
standard reference books such as "The Enzymes" (edited by Paul Boyer; Academic Press, New
York; a treatise in 13 volumes); (2) references to especially important papers, some old and some
recent; and (3) current references that should help the student become acquainted with the
research literature. Study questions and problems accompany each chapter.
In brief, I hope this book will provide a readable, student-oriented introduction to the
chemical structures and reactions of living cells. The end result is not a radical departure from
previous textbooks, but rather a distinctive perspective on the subject combined with some
fresh approaches.
The first section of the book (Chapters 1-3) contains introductory material on cell structure,
molecular architecture, and energetics. Chapter 1 provides, quantitative information on sizes of
cells and organelles and on the genetic complexity of organisms, and also describes characteris-
tics of important species considered in later chapters. It is designed especially for students with
a minimum of biological knowledge and will serve as a review for others. In this chapter, as
well as throughout the book, the coverage includes bacteria, plants, and animals. In the second
chapter a brief review of structural principles for molecules is followed by a systematic consid-
eration of molecular structure and chemical properties of proteins, carbohydrates, nucleic acids,
and lipids. A modern approach is followed whereby conformational properties as well as
structures and reactivities are emphasized. A section on inorganic elements is followed by a
review of methods of structure determination, including nmr techniques.
The third chapter, which starts with a review of thermodynamic equations, presents a
practical approach to biochemical thermodynamics with a series of tabulated data. All of the
free energy and enthalpy values cited later in the text are consistent with those in the tables. I
chose to use the SI unit of kilojoules per mole throughout after I became convinced that this is
the accepted norm in the international biochemical literature. The change from the more
familiar kilocalories per mole is simple. An innovation is the use of free energies of combustion
+
by NAD which simplifies the arithmetic in evaluating free energy changes for metabolic
processes.
Chapters 4 and 5 (the second major section of the book) deal with the ways in which
biomolecules interact. From the quantitative treatment of binding to the structures of
oligomeric enzymes, microtubules, viruses, and muscle, the treatment in Chapter 4 pursues a
rigorous contemporary approach. Allosteric effects are considered quantitatively and systemat-
ically. Chapter 5 covers the structures and chemical properties of membranes and of the
surrounding cell coats. A major aim of this and other chapters is to provide students with
sufficient background so that they can begin to read the current research literature without
immediately having to consult a variety of other background sources.
In the third major section of the book (Chapters 6-8) the general properties of enzymes, the
kinetics of chemical reactions, and the various mechanisms employed in enzymatic catalysis are
discussed. Chapter 6 presents enzyme kinetics in sufficient detail to satisfy the needs of most
students and provides a description of the mechanisms by which enzymatic reactions are
controlled within cells. In Chapter 7 a systematic and rational classification of enzymatic
reactions is given, including information about a variety of enzymes and the techniques used to
study them. Chapter 8 treats the chemistry and special functions of coenzymes, relating these
functions to reaction types considered in preceding chapters. These chapters contain much
reference material, and do not have to be read completely in sequence. However, it will be easy
for the student or instructor to discern the principles emphasized and to apply them. Materials
from these chapters may, if desired, be incorporated with material from Chapter 2 into units
dealing with proteins, carbohydrates, nucleic acids, and lipids without difficulty.
The fourth major section (Chapters 9-14) of the book treats reaction sequences found in
metabolism. Chapter 9 explores the "logic" of metabolic cycles and other pathways. Patterns are
shown to arise as a natural result of the kind of chemistry needed to obtain a desired product
from a given reactant. I hope that this presentation will be a distinct improvement over the
conventional ones. Chapter 10 deals with electron transport and oxidative phosphorylation as
well as with the energy-yielding reactions of chemiautotrophs. Many otherwise confusing
aspects of metabolism are shown to be simple when it is understood (Chapter 11) that certain
steps are needed to couple cleavage of ATP to biosynthesis. In the specialized chapter on
carbohydrate and lipid metabolism (Chapter 12) most of the sequences are easy to understand
in the light of preceding discussions.
A unique chapter, Light in Biology (Chapter 13), covers not only photosynthesis, vision,
and other biological responses to light, but light absorption spectra, circular dichroism, and
fluorescence. Chapter 14 provides details of the biosynthesis and catabolism of an enormous
number of nitrogenous compounds. It can serve as a starting point for individual literature
research projects by biochemistry students and could profitably be used in courses on natural
products chemistry.
The last section (Chapters 15 and 16) deals with topics of genetic and hormonal control of
metabolism, development, and brain function. Chapter 15 not only covers biosynthesis of
nucleic acids and proteins but also includes a succinct summary of methods used in the study of
biochemical genetics. Although this material has been placed near the end of the book, it is
entirely possible to present part or all of it to a class at an earlier stage of the course. The final
chapter (16) provides a brief introduction to the problems of cell communication, neurochemis-
try, differentiation, and ecological problems (metabolism in the environment).
I would like to acknowledge with thanks the many people who have helped me in the
preparation of this text: among them my colleagues at Iowa State University, especially John
Foss and Bernard White, and many scientists in other institutions. Special thanks are due the
John Simon Guggenheim Foundation for a fellowship, Iowa State University for a faculty
improvement leave, and the staff and students of the Department of Biochemistry of the
University of California, Berkeley, for many helpful discussions and criticisms. Special thanks
go to Peggy Johnston, Jeanne Peters, and Wilma Holdren for excellent and dedicated help in the
preparation of the manuscript; to Carol Harris for computations, supervising the proofreading,
and for checking every numerical value; and to the graduate students who checked every
equation and reference. The members of the staff of Academic Press have my gratitude for their
patience and encouragement. It has been a pleasure to work with them.
David E. Metzler
Acknowledgments
I wish to express my appreciation to the following reviewers, each of whom read and
criticized part or all of the manuscript, for their generous assistance: Michael J. Chamberlin,
University of California, Berkeley; Eric E. Conn, University of California, Davis; Charles H.
Doering, Stanford University; Harrison Echols, University of California, Berkeley; Lloyd L.
Ingraham, University of California, Davis; Martin D. Kamen, University of Southern Califor-
nia; Edward A. Khairallah, University of Connecticut; Daniel E. Koshland, Jr., University of
California, Berkeley; Christopher K. Mathews, University of Arizona; Donald B. McCormick,
Cornell University; J. B. Neilands, University of California, Berkeley; Lester Packer, University
of California, Berkeley; Daniel L. Purich, University of California, Santa Barbara; P. K. Stumpf,
University of California, Davis; R. G. Wolfe, University of Oregon; and W. A. Wood, Michigan
State University.
A Note about
the Boxed Information
Boxes containing ancillary information on various subjects are included throughout the text. These
boxes fall under eight subject headings. These groups themselves can be combined in order to develop
various themes. Thus, a nutntional theme is provided by the boxes on Vitamins together with those on
Essential Elements. A complete list of boxes, in eight groups, follows:
1. One series describes the properties of The Vitamins and the history of their discovery. The
corresponding coenzymatic functions are discussed in the main text, as is the biosynthesis of
several of the vitamins.
8-A The Discovery of the Vitamins, 430
8-B Pantothenic Acid, 433
8-C Biotin, 436
8-D Thiamine (Vitamin BJ, 442
8-E The Vitamin B6 Family: Pyridoxine, Pyridoxal, and Pyridoxamine, 445
8-H Nicotinic Acid and Nicotinamide, 468
8-1 Riboflavin, 477
8-J Folic Acid (Pteroylglutamic Acid), 494
8-K Cobalamin (Vitamin B12), 500
10-C The Vitamin E Family: The Tocopherols, 578
10-D The Vitamin K Family, 580
10-G Vitamin C (Ascorbic Acid), 621
12-C Vitamin A, 725
12-D Vitamin D, 735
xxx A Note about the Boxed Information
2. Another series describes functions of most of the Essential Elements. In addition, such topics as
complex formation, ion transport, cobalt in Vitamin Bl2 and others are dealt with in the main text.
2-B Silicon: An Essential Trace Element, 89
5-C The Alkali Metal Ions, 270
5-E Calcium, 278
6-B Urease and the Trace Metal Nickel, 325
7-E Magnesium, 387
7-F Zinc, 397
9-F Selenium, a Deadly Poison and a Nutritional Essential, 536
10-B Vanadium, 567
10-H Copper-Containing Proteins, 622
11-D Chromium, 669
13-A Manganese, 782
14-A Molybdenum, 808
14-C Metabolism of Iron, 842
Some of the other sections dealing with metal ions are:
Chapter 2, Section F
Chapter 3, Section B,5
Chapter 4, Section C,8
Chapter 5, Section B,2
Chapter 7, Section E,7
Chapter 8, Section L
Chapter 10, Sections B; C
3. The importance of mutations is introduced in Chapter 1 and many examples of known Metabolic
Defects in humans are considered, both in the main text and in the following boxes:
1-D Inherited Metabolic Diseases, 25
4-D Sickle Cell Anemia, 235
9-B Refsum's Disease, 523
9-G Methylmalonic Aciduria, 539
10-A Glutathione Peroxidase and Abnormalities of Red Blood Cells, 564
11-B Genetic Defects of Collagen Structure, 664
11-C Diabetes Mellitus, 667
11-E Genetic Diseases of Glycogen Metabolism, 671
14-B The "Maple Syrup Urine" Disease and Jamaican Vomiting Sickness, 835
14-E Gout and Other Defects of Purine Metabolism, 883
Some related sections in the main text are:
Chapter 4, Section E,7
Chapter 12, Sections D,l and 2
Chapter 15, Section H
A Note about the Boxed Information χχχί
4. Structures and properties of many of the best known Antibiotics are given, often in boxes:
5-D Antibiotics, 273
7-D Penicillins and Related Antibiotics, 380
12-A The Biosynthesis of Streptomycin, 689
15-A The Antibiotics Rifamycin and Rifampicin, 913
15-B Actinomycin D, a Toxic Antibiotic, 916
Material on antibiotics in the main text includes:
Chapter 5, Section B,2
Chapter 12, Sections G; 1,4
Chapter 15, Section C,2
5. The actions of a variety oi Poisons including their uses in biochemical investigations are described:
4-A Microtubules and the Action of Colchicine, 206
6-A The Sulfonamides as Antimetabolites, 319
7-A Arsenic, 366
7-B Insecticides, 372
8-G Antagonists of PLP Enzymes, 454
9-D Fluoroacetate and "Lethal Synthesis," 528
15-C A Powerful Poison from Mushrooms, a-Amanitin, 918
15-F Toxic Proteins: The Diphtheria Toxin, 991
See also Chapter 12, Section 1,4
6. Several boxes deal with Methods and Measurements:
1-A About Measurements, 3
1-B Molecular Weights and Daltons, 3
1-C The Electron Microscope, Thin Sections and Replicas, 8
2-C Isotopes in Biochemical Investigations, 124
5-A Relaxation Times in Magnetic Resonance Spectroscopy, 258
5-B Electron Paramagnetic Resonance and "Spin Labels," 260
9-E Use of Isotopie Tracers in Study of the Tricarboxylic Acid Cycle, 529
14
11-A C and the Calvin Cycle, 646
16-A Radioimmunoassay, 1001
7. Topics in Physiological Chemistry characterize one set of boxes. Material on related topics is found
throughout the text:
2-A The Proteins of Blood Plasma, 77
4-C The Viruses, 212
5-F The Antibodies, 284
5-G Complement, 290
7-C Protease Inhibitors of Animals and Plants, 377
9-C Discovery of the Citric Acid Cycle, 526
xxxii A Note about the Boxed Information
10-E Using Metabolism to Generate Heat. Thermogenic Tissues, 593
10-F The Chemistry of Muscular Contraction, 601
11-F Malignant Hyperthermia and Stress-Prone Pigs, 675
14-D Thymidylate Synthetase, A Target Enzyme in Cancer Chemotherapy, 876
15-E Haploid Plants and Cell Fusion, 963
8. Other Topics include the following:
3-A The Adenylate System, 166
4-B Bacterial Flagella, 208
4-E The T-Even Bacteriophage, 245
7-G Glutathione, Intracellular Tripeptide, 421
8-F Ninhydrin, 447
9-A An Early Labeling Experiment, 520
12-B How the Flowers Make Their Pigments, 716
15-D Replication of RNA-Containing Bacteriophage, 943
The following journals are cited with nonstandard abbreviations: ABB, Arch. Biochem. Biophys.; BBA,
Biochim. Biophys. Ada; BJ, Biochem. / . ; BBRC, Biochem. Biophys. Res. Commun.; EJB, Eur. ) . Biochem.; JACS,
/. Amer. Chem. Soc; JBC, /. Biol. Chem.; JMB, /. Mol. Biol; PNAS, Proc. Nat. Acad. Sci. U.S.