Biochemistry

1377 Pages·2012·71.111 MB·English

by  Christopher K. Mathews, Kensal E. van Holde, Dean R. Appling, Spencer J. Anthony-Cahill

FOURTH EDITION
B I O C H E M I S T R Y
CHRISTOPHER K. MATHEWS
Oregon State University
K. E. VAN HOLDE
Oregon State University
DEAN R. APPLING
The University of Texas at Austin
SPENCER J. ANTHONY-CAHILL
Western Washington University
Toronto
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10 9 8 7 6 5 CKV
Library and Archives Canada Cataloguing in Publication
Biochemistry / [edited by] Christopher K.Mathews ...[et al.].— 4th
U.S.ed.
Includes bibliographical references and index.
ISBN 978-0-13-800464-4
1.Biochemistry.I.Mathews,Christopher K.,1937-
QH345.B43 2012 572’.3 C2011-902175-7
ISBN 978-0-13-800464-4
ABOUT THE AUTHORS
Christopher K. Mathewsis Distinguished Professor Emeritus ofBiochemistry
at Oregon State University.He earned his B.A.in chemistry from Reed College
(1958) and Ph.D.in biochemistry from the University ofWashington (1962).He
served on the faculties ofYale University and the University ofArizona from 1963
to 1978,when he moved to Oregon State University as chair ofthe Department of
Biochemistry and Biophysics,a position he held until 2002.His major research
interest is the enzymology and regulation ofDNA precursor metabolism and the
intracellular coordination between deoxyribonucleotide synthesis and DNA repli-
cation.From 1984 to 1985,Dr.Mathews was an Eleanor Roosevelt International
Cancer Fellow at the Karolinska Institute in Stockholm,and in 1994–1995 he held
the Tage Erlander Guest Professorship at Stockholm University.Dr.Mathews has
published over 175 scientific papers dealing with molecular virology,metabolic
regulation,nucleotide enzymology,and biochemical genetics.He is the author of
Bacteriophage Biochemistry(1971) and coeditor of Bacteriophage T4(1983) and
Structural and Organizational Aspects of Metabolic Regulation (1990).He was a
coauthor of the three previous editions of Biochemistry.His teaching experience
includes undergraduate,graduate,and medical school biochemistry courses.
He has backpacked and floated the mountains and rivers,respectively,ofOregon
and the Northwest.As an enthusiastic birder he has served as President of the
Audubon Society of Corvallis and is President of the Great Basin Society,which
operates the Malheur Field Station.
K. E. van Holde is Distinguished Professor Emeritus of Biophysics and Bio-
chemistry at Oregon State University.He earned his B.A.(1949) and Ph.D.(1952)
from the University ofWisconsin.Over many years,Dr.van Holde’s major research
interest has been the structure ofchromatin;his work resulted in the award ofan
American Cancer Society research professorship in 1977.He has been at Oregon
State University since 1967,and was named Distinguished Professor in 1988.He is
a member ofthe National Academy ofSciences and the American Academy ofArts
and Sciences,and has received Guggenheim,NSF,and EMBO fellowships.He is the
author of over 200 scientific papers and four books in addition to this volume:
Physical Biochemistry (1971, 1985), Chromatin (1988), Principles of Physical
Biochemistry(1998),and Oxygen and the Evolution ofLife(2011).He was also coed-
itor of The Origins ofLife and Evolution(1981).His teaching experience includes
undergraduate and graduate chemistry, biochemistry and biophysics, and the
iii
iv ABOUT THE AUTHORS
physiology and molecular biology course at the Marine Biological Laboratory at
Woods Hole.
Dean R. Applingis the Lester J.Reed Professor of Biochemistry and Associate
Dean for Research and Facilities for the College ofNatural Sciences at the University
ofTexas at Austin,where he has taught and done research for the past 26 years.Dean
earned his B.S.in biology from Texas A&M University,and his Ph.D.in biochem-
istry from Vanderbilt University.The Appling laboratory studies the organization
and regulation of metabolic pathways in eukaryotes,focusing on folate-mediated
one-carbon metabolism.The lab is particularly interested in understanding how
one-carbon metabolism is organized in mitochondria,as these organelles are cen-
tral players in many human diseases.In addition to coauthoring this book,Dean
has published over 60 scientific papers and book chapters.
As much fun as writing a textbook might be,Dean would rather be outdoors.He
is an avid fisherman and hiker. Recently, Dean and his wife, Maureen, have
become entranced by the birds on the Texas coast.They were introduced to bird-
watching by coauthor Chris Mathews and his wife,Kate—an unintended conse-
quence ofworking on this book!
Spencer J. Anthony-Cahillis a Professor in the Department of Chemistry at
Western Washington University (WWU),Bellingham,WA.Spencer earned his
B.A.in chemistry from Whitman College,and his Ph.D.in bioorganic chemistry
from the University ofCalifornia,Berkeley.His graduate work,in the lab ofPeter
Schultz,focused on the biosynthetic incorporation ofunnatural amino acids into
proteins. Spencer was an NIH postdoctoral fellow in the laboratory of Bill
DeGrado (then at DuPont Central Research),where he worked on de novopeptide
design and the prediction of the tertiary structure of the HLH DNA-binding
motif.He then worked for five years as a research scientist in the biotechnology
industry,developing recombinant hemoglobin as a treatment for acute blood loss.
In 1997,Spencer decided to pursue his long-standing interest in teaching and
moved to WWU,where he is today.
Research in the Anthony-Cahill laboratory is directed at the protein engineering of
heme proteins.The primary focus is on circular permutation ofhuman (cid:2)-globin as
a means to develop a single-chain hemoglobin with desirable therapeutic proper-
ties.The lab is also pursuing the design ofself-assembling protein nanowires.
Outside the classroom and laboratory,Spencer is a great fan of the outdoors—
especially the North Cascades and southeastern Utah,where he has often back-
packed,camped,climbed,and mountain biked.Spencer also holds the rank of3rd
Dan in Aikido,and instructs children and adults at the Kulshan Aikikai Dojo in
Bellingham,WA.
PREFACE
A NEW EDITION
What factors might explain the re-emergence of a well-received biochemistry
textbook (Biochemistry,Third Edition,2000,by C.K.Mathews,K.E.van Holde,
and K.G.Ahern),some 12 years after publication of the previous edition? In a
rapidly evolving field like biochemistry,textbooks are typically revised every four
or five years to retain their educational value.
Still, biochemistry instructors and students continued to ask when and
whether a fourth edition might appear.While Chris Mathews was interested in
revising and updating the book,his previous coauthors were unable to commit to
a project ofthis magnitude,and so the search began for a new author team.After
a long and careful selection process,two new coauthors joined Chris Mathews:
Dr.Dean R.Appling,Lester J.Reed Professor ofBiochemistry and Associate Dean
for Research and Facilities for the College ofNatural Sciences at the University of
Texas at Austin,and Dr.Spencer J.Anthony-Cahill,Professor of Chemistry at
Western Washington University,Bellingham.
Dean Appling is an enzymologist with interests in regulation and organization
of metabolic pathways,with particular emphasis upon folate cofactors and the
metabolism of single-carbon units.Much of his work uses NMR and molecular
genetics to probe metabolic compartmentation and control.Spencer Anthony-
Cahill’s chief interest is protein folding and design,with current emphasis upon
folding patterns in protein variants that have circularly permuted sequences.
Before assuming his present faculty position,Spencer worked for five years in the
biotechnology industry,an experience that gives him a valuable perspective in
teaching biochemistry.Both Dean and Spencer have used previous editions of
Biochemistryin their own teaching,so they were well aware ofthe strengths ofthis
book and areas where fresh attention was needed.
The research interests of the new author team created a natural division of
writing responsibilities.Spencer’s writing was focused upon biomolecular struc-
ture and mechanisms,Dean dealt with metabolism and its control,and Chris put
his major effort into genetic biochemistry.However,the project was truly a team
effort.Each chapter draft was scrutinized by all three authors,with revisions made
by each principal draft author before submission to our editors and outside
reviewers.We found our fellow authors to be our strongest critics.And,although
Ken van Holde was not actively involved with this edition,he did review some
drafts and much ofhis graceful writing remains in this new edition.We are proud
to include him as a coauthor ofthis new edition.
v
vi PREFACE
EVOLUTION OF THE TEXT
Major Changes
In addition to dealing with the vast amount of new information appearing since
the publication ofthe third edition in 2000,this new edition introduces three sig-
nificant changes.First is more emphasis upon biochemical reaction mechanisms
in the enzymes and metabolism chapters.Second is a significant reorganization in
the chapters dealing with intermediary metabolism.The coverage ofcarbohydrate
metabolism has been unified,so that we now present glycolysis,gluconeogenesis,
glycogen metabolism, and the pentose phosphate pathway in one chapter
(Chapter 13).To accomplish this without excessive expansion of the chapter,we
moved the section on complex carbohydrate metabolism to Chapter 9;instructors
can present this material as part of the metabolism section of the course,if they
prefer. Redox thermodynamics has been moved from Chapter 15 (Biological
Oxidations) to Chapter 3 (Bioenergetics),where it more properly belongs.The
material on interorgan coordination in mammalian metabolism has been split
into two chapters—Chapter 18 (Interorgan and Intracellular Coordination of
Energy Metabolism in Vertebrates) and Chapter 23(Signal Transduction).
The third major change is the reorganization of genetic biochemistry in the
last major section ofthe book.As in previous editions,we introduce processes in
biological information transfer early,in Chapter 4,with details presented later.In
addition,we have integrated prokaryotic and eukaryotic informational metabo-
lism,rather than presenting them in separate chapters,as in previous editions.
The four genetic biochemistry chapters in previous editions are now six—
Chapters 24 (Genome Organization),25 (DNA Replication),26 (Information
Restructuring),27 (Transcription and Its Control),28 (Protein Synthesis and
Processing),and 29 (Control ofGene Expression).
New Topics
A special challenge in writing a new edition after an interval ofso many years was
incorporating the most important ofthe many spectacular new developments in
molecular life sciences.A partial list ofnew or significantly revised topics includes:
• Phosphorothioate bonds in DNA (Chapter 4)
• Gene sequence analysis, phylogenetic analysis, proteomic analysis, and
amino acid sequencing by mass spectroscopy (Chapter 5)
• New approaches to classifying protein secondary structure,protein struc-
ture prediction,and protein folding energy landscapes (Chapter 6)
• Dynamics of myoglobin,roles of heme proteins in nitric oxide physiology,
and antibody–drug conjugates as anticancer agents (Chapter 7)
• Biological imaging ofcomplex glycoproteins (Chapter 9)
• Lipid rafts (Chapter 10)
• Organic chemical mechanisms of the common biochemical reaction types
(Chapter 12)
• Coordination ofenergy homeostasis,including mTOR,AMPK,and sirtuins
and protein acetylation (Chapter 18)
• Evolution of metabolic pathways (several chapters);regulation of choles-
terol metabolism (Chapter 19)
• Ubiquitin and regulated protein turnover (Chapter 20)
• Methyl group metabolism (Chapter 21)
• Pharmacogenetics (Chapter 22)
PREFACE vii
• A kinase anchoring proteins (Chapter 23)
• Restriction fragment length polymorphisms,single-nucleotide polymor-
phisms and genome mapping,chromatin structure,and the centromere
(Chapter 24)
• Double-strand DNA break repair (Chapter 26)
• Structure and function ofRNA polymerases (Chapter 27) and ofribosomes
(Chapter 28)
• Apoptosis (Chapter 28)
• The role of Mediator in transcription complexes,DNA methylation and
epigenetics,functional significance ofhistone modifications,RNA interfer-
ence,and riboswitches (Chapter 29)
Biochemistry Applications
One feature requested by students and instructors alike is practical applications of
biochemical knowledge—particularly,applications to the health sciences.Unlike
some other textbooks,we prefer to integrate applications with the main text,
instead of setting them apart in boxes.We believe that this makes the text flow
more smoothly.
New applications discussed in this edition include:
• Influenza virus neuraminidase and the action ofTamiflu (Chapter 9)
• Biofuels (Chapter 13)
• Mitochondrial diseases (Chapter 15)
• Artificial photosynthesis (Chapter 16)
• Diabetes,obesity (Chapter 18)
• Calorie restriction and lifespan extension (Chapter 18)
• Methylenetetrahydrofolate reductase variants and disease susceptibility
(Chapter 21)
• Chromosomal translocations and targeted cancer drugs (Chapter 23);map-
ping disease genes (Chapter 24)
• Patterns ofoncogene mutations in cancer (Chapter 23)
Keeping What Works Best
Not everything is new in this edition.We have worked hard to retain and improve
the best-loved features of previous editions, such as an emphasis upon the
physico-chemical concepts upon which biochemical processes and mechanisms
are based,and an emphasis upon the experimental nature of biochemistry.This
latter emphasis is realized with our continued use of the popular Tools of
Biochemistry feature.
TOOLS OF BIOCHEMISTRY
As in past editions,we emphasize the importance of incisive experimental tech-
niques as the engine that drives our increasing understanding of the molecular
nature of life processes.This is accomplished through end-of-chapter essays on
the most important techniques in biochemistry and molecular biology research.
Most ofthe Tools sections in this edition have been updated or introduced for the
first time.New or significantly modified Tools sections include:
• Introduction to Proteomics;Tandem Mass Spectrometry (Chapter 5)
• Nuclear Magnetic Resonance Spectroscopy (Chapter 6)
viii PREFACE
• In VitroEvolution ofProtein Function (Chapter 11)
• Metabolomics (Chapter 12)
• Gene Targeting by Homologous Recombination;Single-Molecule Biochem-
istry (Chapter 26)
• Microarrays;Chromatin Immunoprecipitation (Chapter 27)
Several Tools sections on manipulating DNA have been combined and moved
earlier in the book,to Chapter 4.The Tools section on radioisotopes in Chapter 12
has been considerably shortened.The material on kinetic isotope methods in analy-
sis ofenzyme mechanisms has been strengthened in the Tools section in Chapter 11.
END-OF-CHAPTER PROBLEMS
Wherever possible,we have removed problems that emphasize rote learning and
retained or added problems that require analytical or quantitative thought to be
solved.Several new problems have been added to each chapter.Importantly,we
now include complete solutions to each problem,as well as the answers,at the
back ofthe book.
ABOUT THE COVER
The cover illustration depicts the structure of the yeast 80S ribosome at 4.15
Ångstrom resolution,based upon X-ray crystallography.This complex RNA- and
protein-containing particle is an enormous molecular machine,which binds the
components ofprotein synthesis—messenger RNA,transfer RNAs containing acti-
vated amino acids,and soluble protein factors that aid in all phases oftranslation—
initiation,polypeptide chain elongation,and termination.
Tremendous insight into mechanisms of protein synthesis was gained begin-
ning in 2000,when crystal structures for prokaryotic and archaeal ribosomes were
reported.This work was recognized in 2009,with the Nobel Prize in Chemistry to
V.Ramakrishnan,T.A.Steitz,and A.Yonath.Although basic processes in transla-
tion are similar in all cells,protein synthesis in eukaryotic cells is much more
complex than in bacteria,particularly with regard to steps in initiation,where
many more soluble protein factors must participate.The eukaryotic ribosome is
correspondingly larger and more complex—about 40% larger than the bacterial
ribosome,with correspondingly more different proteins and larger RNA compo-
nents.These factors make solving the eukaryotic ribosome structure an even more
formidable problem.This feat was accomplished in several laboratories,begin-
ning in late 2010.
The structure of the yeast ribosome shown here was described by A.Ben-
Shem,L.Jenner,G.Yusupova,and M.Yusupov,inScience330:1203–1209 (2010).
The image on the cover was created by C.Spiegel and S.Anthony-Cahill,working
from atomic coordinates deposited by Ben-Shem and coauthors in the
Brookhaven Protein Database (PBD). Color scheme: 40S particle (PDB ID:
3O30):RNA is in orange;proteins are in slate blue;60S particle (PDB ID:3O5H):
RNA is in raspberry red;proteins are in forest green.
SUPPLEMENTS
For Instructors
Instructor resources are password protected and available for download via the
Pearson online catalog at www.pearsonhighered.com. For your convenience,
many ofthese resources are also available on the Instructor’s Resource CD-ROM
(IRCD)(ISBN 978-0-13-279159-5).
PREFACE ix
• Test Item File. The fourth edition features a brand new testbank created by
Scott Lefler, Senior Lecturer, Arizona State University, with more than 700
thoughtful questions in editable Word format.The Test Item File can be found on
the IRCD or downloaded from the online catalog.
• PowerPoint® Presentations.Two sets of PowerPoint® slides are available for
the text. The first consists of all the figures and photos in the textbook in
PowerPoint® format. The second set, created by Bruce Burnham, Associate
Professor of Chemistry,Rider University,consists of PowerPoint® lecture slides
that provide an outline to use in a lecture setting,presenting definitions,key con-
cepts,and figures from the textbook.Both sets ofPowerPoint® slides can be found
on the IRCD or downloaded from the online catalog.
• Complete Solutions Manual.As in previous editions,we have created a solu-
tions manual to complement chapter problems in the current edition ofour text.
The complete solutions manual,prepared by Sara Codding and Tim Rhoads of
Oregon State University, contains fully worked solutions for those questions that
may benefit from explanations beyond those provided at the back of the book.
Instructors can arrange with the publisher to make this material available to
students (ISBN 978-0-13-292628-7).
• CourseSmart for Instructors.CourseSmart goes beyond traditional expecta-
tions,providing instant,online access to the textbooks and course materials you
need at a lower cost for students.And even as students save money,you can save
time and hassle with a digital eTextbook that allows you to search for the most rel-
evant content at the very moment you need it.Whether it’s evaluating textbooks
or creating lecture notes to help students with difficult concepts,CourseSmart can
make life a little easier.See how when you visit www.coursesmart.com/instructors.
• Technology Specialists. Pearson’s Technology Specialists work with faculty
and campus course designers to ensure that Pearson technology products,
assessment tools,and online course materials are tailored to meet your specific
needs.This highly qualified team is dedicated to helping schools take full advan-
tage ofa wide range ofeducational resources by assisting in the integration ofa
variety of instructional materials and media formats. Your local Pearson
Education sales representative can provide you with more details on this service
program.
For Students
• The Chemistry Place for Biochemistry,Fourth Edition.The Chemistry Place
is an online tool that provides students with tutorial aids to help them succeed in
biochemistry.This Website includes animations of key concepts and processes
and self-quizzing created by Scott Napper, Associate Professor, University of
Saskatchewan,to allow students to check their understanding of subject matter.
TheChemistryPlace also contains our Pearson eText. Please visit the site at
www.chemplace.com.
• Pearson eText gives students access to the text whenever and wherever they
have access to the Internet.eText pages look exactly like the printed text,offering
powerful new functionality for students and instructors.Users can create notes,
highlight text in different colors, create bookmarks, zoom, click hyperlinked
words and phrases to view definitions,and view in single-page or two-page view.
Pearson eText allows for quick navigation to key parts ofthe eText using a table of
contents and provides full-text search.The eText may also offer links to associated
media files,enabling users to access videos,animations,or other activities as they
read the text.