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The Waylaid Heart Holly Newman Year: 2012 Language: english File: EPUB, 443 KB Your tags: 0 / 0

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[神奇寶貝特別篇]第489-495話 日下秀宪 山本智 Language: chinese File: MOBI , 37.48 MB Your tags: 0 / 0

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Lehninger
Principles of Biochemistry

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Lehninger
Principles of Biochemistry
EIGHTH EDITION
David L. Nelson
Professor Emeritus of Biochemistry
University of Wisconsin–Madison
Michael M. Cox
Professor of Biochemistry
University of Wisconsin–Madison
Aaron A. Hoskins
Associate Professor of Biochemistry
University of Wisconsin–Madison

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Senior Vice President, STEM: Daryl Fox
Executive Program Director: Sandra Lindelof
Program Manager, Biochemistry: Elizabeth Simmons
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Director of Design, Content Management: Diana Blume
Design Services Manager: Natasha Wolfe
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Text Designer: Maureen McCutcheon
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Illustrations: Emiko Paul, H. Adam Steinberg
Director of Digital Production: Keri deManigold
Media Project Manager: Brian Nobile

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Permissions Manager: Michael McCarty
Media Permissions Manager: Christine Buese
Photo Researcher: Jennifer Atkins
Composition: Lumina Datamatics, Inc.
Cover Image, Title Page, and Part Openers: Janet Iwasa, University of
Utah
Library of Congress Control Number: 2020942138
ISBN-13: 978-1-319-32234-2 (epub)
© 2021, 2017, 2013, 2008 by W. H. Freeman and Company
All rights reserved.
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Macmillan Learning
One New York Plaza
Suite 4600
New York, NY 10004-1562
www.macmillanlearning.com

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In 1946, William Freem; an founded W. H. Freeman and Company and published
Linus Pauling’s General Chemistry, which revolutionized the chemistry
curriculum and established the prototype for a Freeman text. W. H. Freeman
quickly became a publishing house where leading researchers can make
significant contributions to mathematics and science. In 1996, W. H. Freeman
joined Macmillan and we have since proudly continued the legacy of providing
revolutionary, quality educational tools for teaching and learning in STEM.

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To Our Teachers
Paul R. Burton
Albert Finholt
Jeff Gelles
William P. Jencks
Eugene P. Kennedy
Homer Knoss
Arthur Kornberg
I. Robert Lehman
Andy LiWang
Patti LiWang
Melissa J. Moore
Douglas A. Nelson
Wesley A. Pearson
David E. Sheppard
JoAnne Stubbe
Harold B. White

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About the Authors

David L. Nelson, born in Fairmont, Minnesota, received his BS in
chemistry and biology from St. Olaf College in 1964, and earned
his PhD in biochemistry at Stanford Medical School, under Arthur
Kornberg. He was a postdoctoral fellow at the Harvard Medical
School with Eugene P. Kennedy, who was one of Albert
Lehninger’s first graduate students. Nelson joined the faculty of
the University of Wisconsin–Madison in 1971 and became a full
professor of biochemistry in 1982. For eight years he was Director
of the Center for Biology Education at the University of
Wisconsin–Madison. He became Professor Emeritus in 2013.

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Nelson’s research focused on the signal transductions that
regulate ciliary motion and exocytosis in the protozoan
Paramecium. For 43 years he taught (with Mike Cox) an intensive
survey of biochemistry for advanced biochemistry
undergraduates in the life sciences. He has also taught graduate
courses on membrane structure and function, as well as on
molecular neurobiology. He has received awards for his
outstanding teaching, including the Dreyfus Teacher–Scholar
Award and the Atwood Distinguished Professorship. In 1991–1992
he was a visiting professor of chemistry and biology at Spelman
College. Nelson’s second love is history, and in his dotage he
teaches the history of biochemistry and collects antique scientific
instruments.
Michael M. Cox was born in Wilmington, Delaware. In his first
biochemistry course, the first edition of Lehninger’s Biochemistry
was a major influence in refocusing his fascination with biology
and inspiring him to pursue a career in biochemistry. A er
graduate work at Brandeis University with William P. Jencks and
postdoctoral work at Stanford with I. Robert Lehman, he moved
to the University of Wisconsin–Madison in 1983. He became a full
professor of Biochemistry in 1992.
Mike Cox has coordinated an active research team at Wisconsin
investigating the function and mechanism of enzymes that act at
the interface of DNA replication, repair, and recombination. That
work has resulted in over 200 publications to date.

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For more than three decades, Cox has taught introductory
biochemistry to undergraduates and has lectured in a variety of
graduate courses. He organized a course on professional
responsibility for first-year graduate students and established a
systematic program to draw talented biochemistry
undergraduates into the laboratory at an early stage of their
college career. He has received multiple awards for both his
teaching and his research, including the Eli Lilly Award in
Biological Chemistry, election as a AAAS fellow, and the UW
Regents Teaching Excellence Award. Cox’s hobbies include
turning 18 acres of Wisconsin farmland into an arboretum, wine
collecting, and assisting in the design of laboratory buildings.
Aaron A. Hoskins was born in Lafayette, Indiana, received his BS
in chemistry from Purdue in 2000, and earned his PhD in
biological chemistry at Massachusetts Institute of Technology
with JoAnne Stubbe. In 2006, he went to Brandeis and University
of Massachusetts Medical School as a postdoctoral fellow with
Melissa Moore and Jeff Gelles. Hoskins joined the University of
Wisconsin–Madison biochemistry faculty in 2011.
Hoskins’s PhD research was on de novo purine biosynthesis. At
Brandeis and University of Massachusetts, he began to study
eukaryotic pre-mRNA splicing. During this time, he developed
new single-molecule microscopy tools for studying the
spliceosome.
Hoskins’s laboratory is focused on understanding how
spliceosomes are assembled and regulated and how they
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recognize introns. Hoskins has won awards for his research,
including being named a Beckman Young Investigator and Shaw
Scientist. He has taught introductory biochemistry for
undergraduates since 2012. Hoskins also enjoys playing with his
cat (Louise) and dog (Agatha), yoga/exercise, and tries to read a
new book each week.

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A Note on the Nature of
Science
In this twenty-first century, a typical science education o en
leaves the philosophical underpinnings of science unstated, or
relies on oversimplified definitions. As you contemplate a career
in science, it may be useful to consider once again the terms
science, scientist, and scientific method.
Science is both a way of thinking about the natural world and the
sum of the information and theory that result from such thinking.
The power and success of science flow directly from its reliance
on ideas that can be tested: information on natural phenomena
that can be observed, measured, and reproduced and theories
that have predictive value. The progress of science rests on a
foundational assumption that is o en unstated but crucial to the
enterprise: that the laws governing forces and phenomena
existing in the universe are not subject to change. The Nobel
laureate Jacques Monod referred to this underlying assumption as
the “postulate of objectivity.” The natural world can therefore be
understood by applying a process of inquiry—the scientific
method. Science could not succeed in a universe that played
tricks on us. Other than the postulate of objectivity, science
makes no inviolate assumptions about the natural world. A useful
scientific idea is one that (1) has been or can be reproducibly
substantiated, (2) can be used to accurately predict new
phenomena, and (3) focuses on the natural world or universe.
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Scientific ideas take many forms. The terms that scientists use to
describe these forms have meanings quite different from those
applied by nonscientists. A hypothesis is an idea or assumption
that provides a reasonable and testable explanation for one or
more observations, but it may lack extensive experimental
substantiation. A scientific theory is much more than a hunch. It is
an idea that has been substantiated to some extent and provides
an explanation for a body of experimental observations. A theory
can be tested and built upon and is thus a basis for further
advance and innovation. When a scientific theory has been
repeatedly tested and validated on many fronts, it can be accepted
as a fact.
In one important sense, what constitutes science or a scientific
idea is defined by whether or not it is published in the scientific
literature a er peer review by other working scientists. As of late
2014, about 34,500 peer-reviewed scientific journals worldwide
were publishing some 2.5 million articles each year, a continuing
rich harvest of information that is the birthright of every human
being.
Scientists are individuals who rigorously apply the scientific
method to understand the natural world. Merely having an
advanced degree in a scientific discipline does not make one a
scientist, nor does the lack of such a degree prevent one from
making important scientific contributions. A scientist must be
willing to challenge any idea when new findings demand it. The
ideas that a scientist accepts must be based on measurable,

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reproducible observations, and the scientist must report these
observations with complete honesty.
The scientific method is a collection of paths, all of which may
lead to scientific discovery. In the hypothesis and experiment path,
a scientist poses a hypothesis, then subjects it to experimental
test. Many of the processes that biochemists work with every day
were discovered in this manner. The DNA structure elucidated by
James Watson and Francis Crick led to the hypothesis that base
pairing is the basis for information transfer in polynucleotide
synthesis. This hypothesis helped inspire the discovery of DNA
and RNA polymerases.
Watson and Crick produced their DNA structure through a
process of model building and calculation. No actual experiments
were involved, although the model building and calculations used
data collected by other scientists. Many adventurous scientists
have applied the process of exploration and observation as a path to
discovery. Historical voyages of discovery (Charles Darwin’s 1831
voyage on H.M.S. Beagle among them) helped to map the planet,
catalog its living occupants, and change the way we view the
world. Modern scientists follow a similar path when they explore
the ocean depths or launch probes to other planets. An analog of
hypothesis and experiment is hypothesis and deduction. Crick
reasoned that there must be an adaptor molecule that facilitated
translation of the information in messenger RNA into protein.
This adaptor hypothesis led to the discovery of transfer RNA by
Mahlon Hoagland and Paul Zamecnik.

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Not all paths to discovery involve planning. Serendipity o en plays
a role. The discovery of penicillin by Alexander Fleming in 1928
and of RNA catalysts by Thomas Cech in the early 1980s were both
chance discoveries, albeit by scientists well prepared to exploit
them. Inspiration can also lead to important advances. The
polymerase chain reaction (PCR), now a central part of
biotechnology, was developed by Kary Mullis a er a flash of
inspiration during a road trip in northern California in 1983.
These many paths to scientific discovery can seem quite different,
but they have some important things in common. They are
focused on the natural world. They rely on reproducible observation
and/or experiment. All of the ideas, insights, and experimental
facts that arise from these endeavors can be tested and
reproduced by scientists anywhere in the world. All can be used
by other scientists to build new hypotheses and make new
discoveries. All lead to information that is properly included in
the realm of science. Understanding our universe requires hard
work. At the same time, no human endeavor is more exciting and
potentially rewarding than trying, with occasional success, to
understand some part of the natural world.

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The authoritative reference with a
framework for understanding.
Lehninger Principles of Biochemistry earned acclaim for its presentation and
organization of complex concepts and connections, anchored in the principles
of biochemistry. This legacy continues in the eighth edition with a new
framework that highlights the principles and supports student learning.

Overview of key features
The definitive Lehninger Principles of Biochemistry, Eighth
Edition, continues to help students navigate the complex
discipline of biochemistry with a clear and coherent
presentation. Renowned authors David Nelson, Michael Cox, and
new coauthor Aaron Hoskins have focused this eighth edition
around the fundamental principles to help students understand
and navigate the most important aspects of biochemistry. Text
features and digital resources in the new Achieve platform
emphasize this focus on the principles, while coverage of recent
discoveries and the most up-to-date research provide fascinating
context for learning the dynamic discipline of biochemistry.
ORGANIZED AROUND PRINCIPLES FOR BETTER
UNDERSTANDING
This edition provides a new learning path for students,
through emphasis on the fundamental principles of
biochemistry.

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Streamlined for easier navigation
A new, vibrant design improves navigation through the
content.
Based on extensive user feedback, the authors have carefully
trimmed topics and subtopics to emphasize crucial content,
resulting in shorter chapters and an overall reduction in
book length.
Clear principles are identified at the outset of each chapter
and called out with icons in the narrative of the chapter. The
end-of-section summaries parallel the section content.
Hundreds of new or revised figures make current research
accessible to the biochemistry student.
Captions have been streamlined throughout, maintaining the
philosophy that the captions should support the
understanding of the figure, independent of the text.
Where possible, figures have been simplified, and many
figures have step-by-step annotations, reducing caption
length.
A revised photo program emphasizes context-rich images.
The end-of-chapter problem sets have been revised to
ensure an equivalent experience whether students are using
the text or doing homework online through Achieve.
Achieve supports educators and students throughout the full
range of instruction, including assets suitable for pre-class
preparation, in-class active learning, and post-class study and
assessment. The pairing of a powerful new platform with
outstanding biochemistry content provides an unrivaled learning
experience.

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FEATURES OF ACHIEVE INCLUDE:
A design guided by learning science research through
extensive collaboration and testing by both students and
faculty, including two levels of Institutional Review Board
approval.
A learning path of powerful content, including pre-class, inclass, and post-class activities and assessments.
A detailed gradebook with insights for just-in-time
teaching and reporting on student achievement by learning
objective.
Easy integration and gradebook sync with iClicker
classroom engagement solutions.
Simple integration with your campus LMS and availability
through Inclusive Access programs.
NEW IN ACHIEVE FOR LEHNINGER PRINCIPLES OF
BIOCHEMISTRY, EIGHTH EDITION:
Virtually all end-of-chapter questions are available as
online assessments in Achieve with hints, targeted feedback,
and detailed solutions.
Skills You Need activities support students with review and
practice of prerequisite skills and concepts from chemistry,
biology, and math for each biochemistry chapter.
Instructor Activity Guides provide everything you need to
plan and implement activities, including interactive media,
clicker questions, and pre- and post-class assessments.
Interactive Molecular Figures allow students to view and
interact with textbook illustrations of protein structures

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online in interactive three-dimensional models for a better
understanding of their three-dimensional structures.
Updated and expanded instructor resources and tools.

Achieve is the culmination of years of development work put
toward creating the most powerful online learning tool for
biochemistry students. It houses all of our renowned
assessments, multimedia assets, e-books, and instructor
resources in a powerful new platform.
Achieve supports educators and students throughout the full
range of instruction, including assets suitable for pre-class
preparation, in-class active learning, and post-class study and
assessment. The pairing of a powerful new platform with
outstanding biochemistry content provides an unrivaled learning
experience.

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For more information or to sign up for a demonstration of
Achieve, contact your local Macmillan representative or visit
macmillanlearning.com/achieve
Full Learning Path and Flexible Resources
Achieve supports flexible instruction and engages student
learning. This intuitive platform includes content for pre-class
preparation, in-class active learning, and post-class engagement

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and assessment, providing an unparalleled environment and
resources for teaching and learning biochemistry.

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Achieve MORE
Achieve supports teaching and learning
with exceptional content and resources.

23

Powerful analytics, viewable in an
elegant dashboard, offer instructors a
window into student progress. Achieve
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gives you the insight to address
students’ weaknesses and
misconceptions before they struggle on
a test.

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The authoritative reference, with a
framework for understanding

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Achieve supports retention and
assessment for Lehninger Principles
of Biochemistry.

27

Tools and Resources to
Support Teaching
Course Preparation
Transition Guide for navigating the changes between
editions
Migration Tool to move your assignments from your
previous Sapling Course into your new Achieve course
Specialized Indices for topics covered throughout the text,
including Nutrition and Evolution
Section Management Courses for making copies of your
course when teaching multiple sections or to serve as a
coordinator for other instructors’ sections
Class Preparation
Skills You Need assignments refresh students on content
from courses frequently taken as prerequisites
Standalone slide decks for content, images, and clicker
questions that can be used as is or edited
Interactive e-book, including assignable sections and
chapters
LearningCurve Adaptive Quizzing assignments to ensure
reading comprehension
Instruction

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Editable all-in-one Lecture Slides that include content,
images, clicker questions, multimedia tools, and activities
Cloud-based iClicker in-class response system
Instructor Activity Guides, developed with instructors and
tied to the principles framework, include both instructor
material and assessable student material
Interactive Metabolic Map and Animated Mechanism
Videos, problem-solving videos, and case studies are
integrated into Lecture Slides and available as stand-alone
resources
Practice and Assessment
Two editable, curated homework assignments, including an
assignment that matches the order and questions in the text
and an assignment tied to the principles framework that uses
questions from the text and other sources
Question Bank with thousands of additional questions to
create an assignment from scratch or add to a curated
assignment
Abbreviated Solutions and Extended Solutions for all text
questions
Case Study assignments
Test Banks and accompanying so ware to create tests
outside of the Achieve environment
Reporting and Analytics
Insights on top learning objectives and assignments to
review are surfaced just-in-time (7-day period)

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Detailed reporting by class, individual students, and
learning objectives
Gradebook that syncs with iClicker for an easy, all-in-one
gradebook

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Acknowledgments
Fi y years ago, Al Lehninger published the first edition of
Biochemistry, defining the basic shape of biochemistry courses
worldwide for generations. We are honored to have been able to
carry on the Lehninger tradition since his passing in 1986, now
introducing the eighth (our seventh) edition of Lehninger
Principles of Biochemistry.
This book is a team effort, and producing it would be impossible
without the outstanding people at Macmillan Learning who have
supported us at every step along the way. Elizabeth Simmons,
Program Manager, Biochemistry, led us fearlessly into the brave
new world of textbook publishing in the media age. Catherine
Murphy, Development Editor, helped develop the revision plan
for this edition, cheerfully kept us focused on that plan, skillfully
evaluated reviewer comments, and edited the text with a clear
eye. Vivien Weiss, Senior Content Project Manager, put all the
pieces together seamlessly. Diana Blume, Natasha Wolfe,
Maureen McCutcheon, and John Callahan are responsible for the
vibrant design of the text and cover of the book. Adam Steinberg
and Emiko Paul created the new art for this edition. Photo
Researcher Jennifer Atkins and Media Permissions Manager
Christine Buese located images and obtained permission to use
them. Cate Dapron copy edited and Paula Pyburn proofread the
text. Karen Misler, Editorial Project Manager, and Senior
Workflow Project Manager Paul W. Rohloff worked diligently to
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keep us on schedule, and Nathan Livingston helped orchestrate
reviews and provided administrative assistance. Cassandra
Korsvik and Kelsey Hughes, Media Editors, and Jim Zubricky,
Learning Solutions Specialist, oversaw the enormous task of
creating the many interactive media enhancements of our
content. Our gratitude also goes to Maureen Rachford, Senior
Marketing Manager, for coordinating the sales and marketing
efforts that bring Lehninger Principles of Biochemistry to the
attention of teachers and learners.
In Madison, Brook Soltvedt is, and has been for all the editions we
have worked on, our invaluable first-line editor and critic. She is
the first to see manuscript chapters, aids in manuscript and art
development, ensures internal consistency in content and
nomenclature, and keeps us on task with more-or-less gentle
prodding. Much of the art and molecular graphics was created by
Adam Steinberg of Art for Science, who o en made valuable
suggestions that led to better and clearer illustrations. The de
hand of Linda Strange, who copyedited six editions of this
textbook (including the first), is still evident in the clarity of the
text. We feel very fortunate to have had such gi ed partners as
Brook, Adam, and Linda on our team. We are also indebted to
Brian White of the University of Massachusetts Boston, who wrote
most of the data analysis problems at the end of chapters.
Many others helped us shape this eighth edition with their
comments, suggestions, and criticisms. To all of them, we are
deeply grateful:

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Ravinder Abrol, California State University–Northridge
Paul Adams, University of Arkansas
Balasubrahmanyam Addepalli, University of Cincinnati
Richard Amasino, University of Wisconsin–Madison
Darryl Aucoin, Caldwell College
Gerald F. Audette, York University, North York
Amy Babbes, Scripps College
Kenneth Balazovich, University of Michigan
Sandra Barnes, Alcorn State University
David Bartley, Adrian College
Zeenat Bashir, Canisius College
Dana Baum, St. Louis University–Main Campus
Donald Beitz, Iowa State University
Henrike Besche, Harvard Medical School

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Mrinal Bhattacharjee, Long Island University–Brooklyn
Joshua M. Blose, College at Brockport–State University of New York
Paul Bond, Shorter University
Michael Borenstein, Temple University School of Pharmacy
Kevin Brown, University of Florida–Gainesville
Robert Brown, Memorial University of Newfoundland
D. Andrew Burden, Middle Tennessee State University
Nicholas Burgis, Eastern Washington University
Bobby Burkes, Grambling State University
Samuel Butcher, University of Wisconsin–Madison
Tamar B. Caceres, Union University
Christopher T. Calderone, Carleton College
Brian Callahan, Binghamton University
Michael Cascio, Duquesne University
Jennifer Cecile, Appalachian State University
Yongli Chen, Hawaii Pacific University–Hilo
John Chik, Mount Royal University
Lilian Chooback, University of Central Oklahoma
Anthony Clementz, Concordia University Chicago
Heather Coan, Western Carolina University
Leah Cohen, College of Staten Island, CUNY
Steven Cok, Framingham State College
Robert B. Congdon, Broome Community College, SUNY
John Conrad, University of Nebraska–Omaha
Silvana Constantinescu, Marymount College–Rancho Palos Verdes
Rebecca Corbin, Ashland University
Christopher Cottingham, University of North Alabama
Garland Crawford, Mercer University–Macon
Tanya Dahms, University of Regina
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Tuhin Das, John Jay College of Criminal Justice, CUNY
Susan Colette Daubner, St. Mary’s University
Margaret Daugherty, Colorado College
Paul DeLaLuz, Lee University
Natasha DeVore, Missouri State University Springfield
Justin DiAngelo, Pennsylvania State University–Berks Campus
Tomas T. Ding, North Carolina Central University
Kristin Dittenhafer-Reed, Hope College
Cassidy Dobson, Truman State University
Artem Domashevskiy, John Jay College of Criminal Justice, CUNY
Donald Doyle, Georgia Institute of Technology
David H. Eagerton, Campbell University
Daniel Edwards, California State University–Chico
Steven Ellis, University of Louisville
Chandrakanth Emani, Western Kentucky University–Bowling Green
Nuran Ercal, Missouri University of Science & Technology
Stylianos Fakas, Alabama A & M University
Russ Feirer, St. Norbert College & Medical College of Wisconsin
Kirsten Fertuck, Northeastern University–Boston
Jennifer Fishovitz, Saint Mary’s College
Kathleen Foley Geiger, Michigan State University
Marcello Forconi, College of Charleston
Isaac Forquer, Portland State University
Jason Fowler, Lincoln Memorial University
Kevin Francis, Texas A&M–Kingsville
Jean Gaffney, Baruch College
Katie Garber, St. Norbert College
Ronald Gary, University Nevada–Las Vegas
Yulia Gerasimova, University of Central Florida
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Dipak K. Ghosh, North Carolina A & T State University
Marina Gimpelev, Dominican College
Burt Goldberg, New York University
Daniel Golemboski, Bellarmine College–Louisville
Lawrence Gracz, Massachusetts College of Pharmacy & Health
Sciences
Jennifer E. Grant, University of Wisconsin Stout
Joel Gray, Texas State University
Amy Greene, Albright College
Nicholas Grossoehme, Winthrop University
Neena Grover, Colorado College
Rishab K. Gupta, University of California–Los Angeles
Paul Hager, East Carolina University
Bonnie Hall, Grand View University
Marilena Hall, Stonehill College
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Matthew Hartman, Virginia Commonwealth University
Mary Hatcher-Skeers, Scripps College
Robin Haynes, Harvard University
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Newton Hilliard, Arkansas Technical University
Danny Ho, Columbia University–New York
Jane Hobson, Kwantlen Polytechnic University
Charles Hoogstraten, Michigan State University
Amber Howerton, Nevada State College
Tom Huxford, San Diego State University
Cheryl Ingram-Smith, Clemson University
Lori Isom, University of Central Arkansas
Bruce Jacobson, St. Cloud State University
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Nitin Jain, University of Tennessee
Blythe Janowiak, St. Louis University
Matthew R. Jensen, Concordia University, St. Paul
Joseph Jez, Washington University in St. Louis
Xiangshu Jin, Michigan State University–East Lansing
Gerwald Jogl, Brown University
Todd Johnson, Weber State University–Ogden
Marjorie A. Jones, Illinois State University
P. Matthew Joyner, Pepperdine University
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Kalju Kahn, University of California–Santa Barbara
Peter Kahn, Rutgers University
Reza Karimi, Pacific University
Bhuvana Katkere, Pennsylvania State University–Main Campus
Kevin Kearney, MCPHS University
Chu-Young Kim, University of Texas–El Paso
Bryan Knuckley, University of North Florida
Michael Koelle, Yale University
Andy Koppisch, Northern Arizona University
Joanna Krueger, University of North Carolina–Charlotte
Terry Kubiseski, York University–Keele Campus
Maria Kuhn, Madonna University
Chandrika Kulatilleke, City University of New York–Baruch College
Allison Lamanna, University of Michigan–Ann Arbor
Kimberly Lane, Radford University
Patrick Larkin, Texas A&M University–Corpus Christi
Paul Larsen, University of California–Riverside
Heather Larson, Indiana University Southeast
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Benjamin Lasseter, Christopher Newport University
Katherine Launer-Felty, Connecticut College
James Lee, Old Dominion University
Sarah Lee, Abilene Christian University
Scott Lefler, Arizona State University–Tempe
Pingwei Li, Texas A&M University
Yingchun Li, Texas A&M University–Prairie View
Yun Li, Delaware Valley University
Andy LiWang, University of California–Merced
Kimberly Lyle-Ippolito, Anderson University
Taylor J. Mach, Concordia University, St. Paul
Meagan Mann, Austin Peay State University
Glover Martin, University of Massachusetts–Boston
Michael Massiah, George Washington University
Brannon McCullough, Northern Arizona University
John Means, University of Rio Grande
Michael Mendenhall, University of Kentucky
Sabeeha Merchant, University of California–Berkeley
Elizabeth Middleton, Purchase College, SUNY
Jeremy T. Mitchell-Koch, Bethel College–North Newton
Somdeb Mitra, New York University
Susan Mitroka, Worcester State University
Judy Moore, Lenoir-Rhyne University–Hickory
Graham Moran, Loyola University Chicago
Fares Najar, University of Oklahoma–Norman
Scott Napper, University of Saskatchewan
Allen Nicholson, Temple University–Philadelphia
James Nolan, Georgia Gwinnett College
George Nora, Northern State University
38

Grazyna Nowak, University of Arkansas for Medical Sciences
Abdel Omri, Laurentian University
Allyn Ontko, Arkansas State University
Siva Panda, Augusta State University
Amanda Parker, William Cary University
Jonathan Parrish, University of Alberta
Donna Pattison, University of Houston
Craig Peebles, University of Pittsburgh
Mary Elizabeth Peek, Georgia Institute of Technology Main Campus
Mario Pennella, University of Wisconsin–Madison
Michael Pikaart, Hope College
Deborah Polayes, George Mason University
Alfred Ponticelli, University at Buffalo, Jacobs School of Medicine and
Biomedical Sciences
Tamiko Porter, Indiana University–Purdue University Indianapolis
Michelle Pozzi, Texas A&M University
Ramin Radfar, Wofford College
Kevin Redding, Arizona State University
Tanea Reed, Eastern Kentucky University
Christopher Reid, Bryant University
John Richardson, Austin College
Katarzyna Roberts, Rogers State University
Jim Roesser, Virginia Commonwealth University
Christopher Rohlman, Albion College
Brenda Royals, Park University
Gillian Rudd, Georgia Gwinnett College
Megan E. Rudock, Wake Forest University
Joshua Sakon, University of Arkansas–Fayetteville
Nianli Sang, Drexel University
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Pradip Sarkar, Parker University
Patrick Schacht, California Baptist University
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Kavita Shah, Purdue University–Main Campus
Wallace Sharif, Morehouse College
Ike Shibley, Pennsylvania State University–Berks Campus
Aaron Sholders, Colorado State University Fort Collins
Kevin Siebenlist, Marquette University
Richard Singiser, Clayton State University
Corin Slown, California State University Monterey Bay
Kelli Slunt, University of Mary Washington
Kerry Smith, Clemson University
Sarah J. Smith, Bucknell University
Mark Snider, The College of Wooster
Jennifer Sniegowski, Arizona State University–Downtown
David Snyder, William Paterson University
Joshua Sokoloski, Salisbury University
Joanne Souza, Stony Brook University
Narasimha Sreerama, Colorado State University
Rekha Srinivasan, Case Western Reserve University
Aleksandra Stamenov, University of California–Merced
Ryan Steed, University of North Carolina–Asheville
Angela K. Stoeckman, Bethel University
Koni Stone, California State University Stanislaus
Evelyn Swain, Presbyterian College
Jeremy Thorner, University of California–Berkeley
Candace Timpte, Georgia Gwinnett College
40

Jamie Towle-Weicksel, Rhode Island College
Michael Trakselis, Baylor University
Brian Trewyn, Colorado School of Mines
Vishwa D. Trivedi, Bethune Cookman University
Didem Vardar-Ulu, Boston University
Thomas Vida, University of Houston
Lori Wallrath, University of Iowa–Iowa City
Chris Wang, Ambrose University
Xuemin Wang, University of Missouri–St. Louis
Yu Wang, The University of Alabama
Robert J. Warburton, Shepherd University
Todd M. Weaver, University of Wisconsin La Crosse
James D. West, The College of Wooster
Chuan Xiao, University of Texas–El Paso
Alexander G. Zestos, American University
We lack the space here to acknowledge all the other individuals
whose special efforts went into this book. We offer instead our
sincere thanks—and the finished book that they helped guide to
completion. We, of course, assume full responsibility for errors of
fact or emphasis.
We want especially to thank our students at the University of
Wisconsin–Madison for their numerous comments and
suggestions. If something in the book does not work, they are
never shy about letting us know it. We are grateful to the students
and staff of our past and present research groups, who helped us
balance the competing demands on our time; to our colleagues in
the Department of Biochemistry at the University of Wisconsin–
41

Madison, who helped us with advice and criticism; and to the
many students and teachers who have written to suggest ways of
improving the book. We hope our readers will continue to provide
input for future editions.
Finally, we express our deepest appreciation to our partners
(Brook, Beth, and Tim) and our families, who showed
extraordinary patience with, and support for, our book writing.
David L. Nelson
Michael M. Cox
Aaron A. Hoskins
Madison, Wisconsin
June 2020

42

Contents in Brief
Preface
1 The Foundations of Biochemistry
I STRUCTURE AND CATALYSIS
2 Water, the Solvent of Life
3 Amino Acids, Peptides, and Proteins
4 The Three-Dimensional Structure of Proteins
5 Protein Function
6 Enzymes
7 Carbohydrates and Glycobiology
8 Nucleotides and Nucleic Acids
9 DNA-Based Information Technologies
10 Lipids
11 Biological Membranes and Transport
12 Biochemical Signaling
II BIOENERGETICS AND METABOLISM
13 Introduction to Metabolism
14 Glycolysis, Gluconeogenesis, and the Pentose
Phosphate Pathway
15 The Metabolism of Glycogen in Animals
16 The Citric Acid Cycle
17 Fatty Acid Catabolism
18 Amino Acid Oxidation and the Production of Urea

43

19 Oxidative Phosphorylation
20 Photosynthesis and Carbohydrate Synthesis in
Plants
21 Lipid Biosynthesis
22 Biosynthesis of Amino Acids, Nucleotides, and
Related Molecules
23 Hormonal Regulation and Integration of Mammalian
Metabolism
III INFORMATION PATHWAYS
24 Genes and Chromosomes
25 DNA Metabolism
26 RNA Metabolism
27 Protein Metabolism
28 Regulation of Gene Expression
Abbreviated Solutions to Problems
Glossary
Index
Resources

44

Contents
1 The Foundations of Biochemistry
1.1 Cellular Foundations
Cells Are the Structural and Functional Units of All
Living Organisms
Cellular Dimensions Are Limited by Diffusion
Organisms Belong to Three Distinct Domains of Life
Organisms Differ Widely in Their Sources of Energy
and Biosynthetic Precursors
Bacterial and Archaeal Cells Share Common Features
but Differ in Important Ways
Eukaryotic Cells Have a Variety of Membranous
Organelles, Which Can Be Isolated for Study
The Cytoplasm Is Organized by the Cytoskeleton and
Is Highly Dynamic
Cells Build Supramolecular Structures
In Vitro Studies May Overlook Important
Interactions among Molecules
1.2 Chemical Foundations
Biomolecules Are Compounds of Carbon with a
Variety of Functional Groups
Cells Contain a Universal Set of Small Molecules
Macromolecules Are the Major Constituents of Cells
BOX 1-1 Molecular Weight, Molecular Mass, and
Their Correct Units

45

Three-Dimensional Structure Is Described by
Configuration and Conformation
BOX 1-2 Louis Pasteur and Optical Activity: In Vino,
Veritas
Interactions between Biomolecules Are
Stereospecific
1.3 Physical Foundations
Living Organisms Exist in a Dynamic Steady State,
Never at Equilibrium with Their Surroundings
Organisms Transform Energy and Matter from Their
Surroundings
Creating and Maintaining Order Requires Work and
Energy
BOX 1-3 Entropy: Things Fall Apart
Energy Coupling Links Reactions in Biology
Keq

and ΔG° Are Measures of a Reaction’s Tendency

to Proceed Spontaneously
Enzymes Promote Sequences of Chemical Reactions
Metabolism Is Regulated to Achieve Balance and
Economy
1.4 Genetic Foundations
Genetic Continuity Is Vested in Single DNA Molecules
The Structure of DNA Allows Its Replication and
Repair with Near-Perfect Fidelity
The Linear Sequence in DNA Encodes Proteins with
Three-Dimensional Structures
1.5 Evolutionary Foundations
46

Changes in the Hereditary Instructions Allow
Evolution
Biomolecules First Arose by Chemical Evolution
RNA or Related Precursors May Have Been the First
Genes and Catalysts
Biological Evolution Began More Than Three and a
Half Billion Years Ago
The First Cell Probably Used Inorganic Fuels
Eukaryotic Cells Evolved from Simpler Precursors in
Several Stages
Molecular Anatomy Reveals Evolutionary
Relationships
Functional Genomics Shows the Allocations of Genes
to Specific Cellular Processes
Genomic Comparisons Have Increasing Importance
in Medicine
I STRUCTURE AND CATALYSIS
2 Water, the Solvent of Life
2.1 Weak Interactions in Aqueous Systems
Hydrogen Bonding Gives Water Its Unusual
Properties
Water Forms Hydrogen Bonds with Polar Solutes
Water Interacts Electrostatically with Charged
Solutes
Nonpolar Gases Are Poorly Soluble in Water
Nonpolar Compounds Force Energetically
Unfavorable Changes in the Structure of Water

47

van der Waals Interactions Are Weak Interatomic
Attractions
Weak Interactions Are Crucial to Macromolecular
Structure and Function
Concentrated Solutes Produce Osmotic Pressure
2.2 Ionization of Water, Weak Acids, and Weak Bases
Pure Water Is Slightly Ionized
The Ionization of Water Is Expressed by an
Equilibrium Constant
The pH Scale Designates the H and OH
Concentrations
+

−

BOX 2-1 On Being One’s Own Rabbit (Don’t Try This
at Home!)
Weak Acids and Bases Have Characteristic Acid
Dissociation Constants
Titration Curves Reveal the pK of Weak Acids
a

2.3 Buffering against pH Changes in Biological Systems
Buffers Are Mixtures of Weak Acids and Their
Conjugate Bases
The Henderson-Hasselbalch Equation Relates pH,
pKa

, and Buffer Concentration

Weak Acids or Bases Buffer Cells and Tissues against
pH Changes
Untreated Diabetes Produces Life-Threatening
Acidosis
3 Amino Acids, Peptides, and Proteins
3.1 Amino Acids
48

Amino Acids Share Common Structural Features
The Amino Acid Residues in Proteins Are L
Stereoisomers
Amino Acids Can Be Classified by R Group
BOX 3-1 Absorption of Light by Molecules: The
Lambert-Beer Law
Uncommon Amino Acids Also Have Important
Functions
Amino Acids Can Act as Acids and Bases
Amino Acids Differ in Their Acid-Base Properties
3.2 Peptides and Proteins
Peptides Are Chains of Amino Acids
Peptides Can Be Distinguished by Their Ionization
Behavior
Biologically Active Peptides and Polypeptides Occur
in a Vast Range of Sizes and Compositions
Some Proteins Contain Chemical Groups Other Than
Amino Acids
3.3 Working with Proteins
Proteins Can Be Separated and Purified
Proteins Can Be Separated and Characterized by
Electrophoresis
Unseparated Proteins Are Detected and Quantified
Based on Their Functions
3.4 The Structure of Proteins: Primary Structure
The Function of a Protein Depends on Its Amino Acid
Sequence
49

Protein Structure Is Studied Using Methods That
Exploit Protein Chemistry
Mass Spectrometry Provides Information on
Molecular Mass, Amino Acid Sequence, and Entire
Proteomes
Small Peptides and Proteins Can Be Chemically
Synthesized
Amino Acid Sequences Provide Important
Biochemical Information
Protein Sequences Help Elucidate the History of Life
on Earth
BOX 3-2 Consensus Sequences and Sequence Logos
4 The Three-Dimensional Structure of Proteins
4.1 Overview of Protein Structure
A Protein’s Conformation Is Stabilized Largely by
Weak Interactions
Packing of Hydrophobic Amino Acids Away from
Water Favors Protein Folding
Polar Groups Contribute Hydrogen Bonds and Ion
Pairs to Protein Folding
Individual van der Waals Interactions Are Weak but
Combine to Promote Folding
The Peptide Bond Is Rigid and Planar
4.2 Protein Secondary Structure
The

α Helix Is a Common Protein Secondary

Structure

BOX 4-1 Knowing the Right Hand from the Le

50

Amino Acid Sequence Affects Stability of the

β

α Helix

The Conformation Organizes Polypeptide Chains
into Sheets

β Turns Are Common in Proteins

Common Secondary Structures Have Characteristic
Dihedral Angles
Common Secondary Structures Can Be Assessed by
Circular Dichroism
4.3 Protein Tertiary and Quaternary Structures
Fibrous Proteins Are Adapted for a Structural
Function
BOX 4-2 Why Sailors, Explorers, and College
Students Should Eat Their Fresh Fruits and
Vegetables
Structural Diversity Reflects Functional Diversity in
Globular Proteins
Myoglobin Provided Early Clues about the
Complexity of Globular Protein Structure
BOX 4-3 The Protein Data Bank
Globular Proteins Have a Variety of Tertiary
Structures
Some Proteins or Protein Segments Are Intrinsically
Disordered
Protein Motifs Are the Basis for Protein Structural
Classification
Protein Quaternary Structures Range from Simple
Dimers to Large Complexes

51

4.4 Protein Denaturation and Folding
Loss of Protein Structure Results in Loss of Function
Amino Acid Sequence Determines Tertiary Structure
Polypeptides Fold Rapidly by a Stepwise Process
Some Proteins Undergo Assisted Folding
Defects in Protein Folding Are the Molecular Basis
for Many Human Genetic Disorders
BOX 4-4 Death by Misfolding: The Prion Diseases
4.5 Determination of Protein and Biomolecular
Structures
X-ray Diffraction Produces Electron Density Maps
from Protein Crystals
Distances between Protein Atoms Can Be Measured
by Nuclear Magnetic Resonance
BOX 4-5 Video Games and Designer Proteins
Thousands of Individual Molecules Are Used to
Determine Structures by Cryo-Electron Microscopy
5 Protein Function
5.1 Reversible Binding of a Protein to a Ligand: OxygenBinding Proteins
Oxygen Can Bind to a Heme Prosthetic Group
Globins Are a Family of Oxygen-Binding Proteins
Myoglobin Has a Single Binding Site for Oxygen
Protein-Ligand Interactions Can Be Described
Quantitatively
Protein Structure Affects How Ligands Bind

52

Hemoglobin Transports Oxygen in Blood
Hemoglobin Subunits Are Structurally Similar to
Myoglobin
Hemoglobin Undergoes a Structural Change on
Binding Oxygen
Hemoglobin Binds Oxygen Cooperatively
Cooperative Ligand Binding Can Be Described
Quantitatively
BOX 5-1 Carbon Monoxide: A Stealthy Killer
Two Models Suggest Mechanisms for Cooperative
Binding
Hemoglobin Also Transports H and CO
+

2

Oxygen Binding to Hemoglobin Is Regulated by 2,3Bisphosphoglycerate
Sickle Cell Anemia Is a Molecular Disease of
Hemoglobin
5.2 Complementary Interactions between Proteins and
Ligands: The Immune System and Immunoglobulins
The Immune Response Includes a Specialized Array
of Cells and Proteins
Antibodies Have Two Identical Antigen-Binding Sites
Antibodies Bind Tightly and Specifically to Antigen
The Antibody-Antigen Interaction Is the Basis for a
Variety of Important Analytical Procedures
5.3 Protein Interactions Modulated by Chemical
Energy: Actin, Myosin, and Molecular Motors
The Major Proteins of Muscle Are Myosin and Actin
53

Additional Proteins Organize the Thin and Thick
Filaments into Ordered Structures
Myosin Thick Filaments Slide along Actin Thin
Filaments
6 Enzymes
6.1 An Introduction to Enzymes
Most Enzymes Are Proteins
Enzymes Are Classified by the Reactions They
Catalyze
6.2 How Enzymes Work
Enzymes Affect Reaction Rates, Not Equilibria
Reaction Rates and Equilibria Have Precise
Thermodynamic Definitions
A Few Principles Explain the Catalytic Power and
Specificity of Enzymes
Noncovalent Interactions between Enzyme and
Substrate Are Optimized in the Transition State
Covalent Interactions and Metal Ions Contribute to
Catalysis
6.3 Enzyme Kinetics as an Approach to Understanding
Mechanism
Substrate Concentration Affects the Rate of EnzymeCatalyzed Reactions
The Relationship between Substrate Concentration
and Reaction Rate Can Be Expressed with the
Michaelis-Menten Equation

54

Michaelis-Menten Kinetics Can Be Analyzed
Quantitatively
Kinetic Parameters Are Used to Compare Enzyme
Activities
Many Enzymes Catalyze Reactions with Two or More
Substrates
Enzyme Activity Depends on pH
Pre–Steady State Kinetics Can Provide Evidence for
Specific Reaction Steps
Enzymes Are Subject to Reversible or Irreversible
Inhibition
BOX 6-1 Curing African Sleeping Sickness with a
Biochemical Trojan Horse
6.4 Examples of Enzymatic Reactions
The Chymotrypsin Mechanism Involves Acylation
and Deacylation of a Ser Residue
An Understanding of Protease Mechanisms Leads to
New Treatments for HIV Infection
Hexokinase Undergoes Induced Fit on Substrate
Binding
The Enolase Reaction Mechanism Requires Metal
Ions
An Understanding of Enzyme Mechanism Produces
Useful Antibiotics
6.5 Regulatory Enzymes
Allosteric Enzymes Undergo Conformational
Changes in Response to Modulator Binding

55

The Kinetic Properties of Allosteric Enzymes Diverge
from Michaelis-Menten Behavior
Some Enzymes Are Regulated by Reversible Covalent
Modification
Phosphoryl Groups Affect the Structure and Catalytic
Activity of Enzymes
Multiple Phosphorylations Allow Exquisite
Regulatory Control
Some Enzymes and Other Proteins Are Regulated by
Proteolytic Cleavage of an Enzyme Precursor
A Cascade of Proteolytically Activated Zymogens
Leads to Blood Coagulation
Some Regulatory Enzymes Use Several Regulatory
Mechanisms
7 Carbohydrates and Glycobiology
7.1 Monosaccharides and Disaccharides
The Two Families of Monosaccharides Are Aldoses
and Ketoses
BOX 7-1 What Makes Sugar Sweet?
Monosaccharides Have Asymmetric Centers
The Common Monosaccharides Have Cyclic
Structures
Organisms Contain a Variety of Hexose Derivatives
Sugars That Are, or Can Form, Aldehydes Are
Reducing Sugars
BOX 7-2 Blood Glucose Measurements in the
Diagnosis and Treatment of Diabetes

56

7.2 Polysaccharides
Some Homopolysaccharides Are Storage Forms of
Fuel
Some Homopolysaccharides Serve Structural Roles
Steric Factors and Hydrogen Bonding Influence
Homopolysaccharide Folding
Peptidoglycan Reinforces the Bacterial Cell Wall
Glycosaminoglycans Are Heteropolysaccharides of
the Extracellular Matrix
7.3 Glycoconjugates: Proteoglycans, Glycoproteins, and
Glycolipids
Proteoglycans Are Glycosaminoglycan-Containing
Macromolecules of the Cell Surface and Extracellular
Matrix
BOX 7-3 Defects in the Synthesis or Degradation of
Sulfated Glycosaminoglycans Can Lead to Serious
Human Disease
Glycoproteins Have Covalently Attached
Oligosaccharides
Glycolipids and Lipopolysaccharides Are Membrane
Components
7.4 Carbohydrates as Informational Molecules: The
Sugar Code
Oligosaccharide Structures Are Information-Dense
Lectins Are Proteins That Read the Sugar Code and
Mediate Many Biological Processes

57

Lectin-Carbohydrate Interactions Are Highly Specific
and O en Multivalent
7.5 Working with Carbohydrates
8 Nucleotides and Nucleic Acids
8.1 Some Basic Definitions and Conventions
Nucleotides and Nucleic Acids Have Characteristic
Bases and Pentoses
Phosphodiester Bonds Link Successive Nucleotides
in Nucleic Acids
The Properties of Nucleotide Bases Affect the ThreeDimensional Structure of Nucleic Acids
8.2 Nucleic Acid Structure
DNA Is a Double Helix That Stores Genetic
Information
DNA Can Occur in Different Three-Dimensional
Forms
Certain DNA Sequences Adopt Unusual Structures
Messenger RNAs Code for Polypeptide Chains
Many RNAs Have More Complex Three-Dimensional
Structures
8.3 Nucleic Acid Chemistry
Double-Helical DNA and RNA Can Be Denatured
Nucleotides and Nucleic Acids Undergo
Nonenzymatic Transformations
Some Bases of DNA Are Methylated
The Chemical Synthesis of DNA Has Been Automated

58

Gene Sequences Can Be Amplified with the
Polymerase Chain Reaction
The Sequences of Long DNA Strands Can Be
Determined
BOX 8-1 A Potent Weapon in Forensic Medicine
DNA Sequencing Technologies Are Advancing
Rapidly
8.4 Other Functions of Nucleotides
Nucleotides Carry Chemical Energy in Cells
Adenine Nucleotides Are Components of Many
Enzyme Cofactors
Some Nucleotides Are Regulatory Molecules
Adenine Nucleotides Also Serve as Signals
9 DNA-Based Information Technologies
9.1 Studying Genes and Their Products
Genes Can Be Isolated by DNA Cloning
Restriction Endonucleases and DNA Ligases Yield
Recombinant DNA
Cloning Vectors Allow Amplification of Inserted DNA
Segments
Cloned Genes Can Be Expressed to Amplify Protein
Production
Many Different Systems Are Used to Express
Recombinant Proteins
Alteration of Cloned Genes Produces Altered
Proteins

59

Terminal Tags Provide Handles for Affinity
Purification
The Polymerase Chain Reaction Offers Many Options
for Cloning Experiments
DNA Libraries Are Specialized Catalogs of Genetic
Information
9.2 Exploring Protein Function on the Scale of Cells or
Whole Organisms
Sequence or Structural Relationships Can Suggest
Protein Function
When and Where a Protein Is Present in a Cell Can
Suggest Protein Function
Knowing What a Protein Interacts with Can Suggest
Its Function
The Effect of Deleting or Altering a Protein Can
Suggest Its Function
Many Proteins Are Still Undiscovered
BOX 9-1 Getting Rid of Pests with Gene Drives
9.3 Genomics and the Human Story
The Human Genome Contains Many Types of
Sequences
Genome Sequencing Informs Us about Our
Humanity
Genome Comparisons Help Locate Genes Involved in
Disease
Genome Sequences Inform Us about Our Past and
Provide Opportunities for the Future

60

BOX 9-2 Getting to Know Humanity’s Next of Kin
10 Lipids
10.1 Storage Lipids
Fatty Acids Are Hydrocarbon Derivatives
Triacylglycerols Are Fatty Acid Esters of Glycerol
Triacylglycerols Provide Stored Energy and
Insulation
Partial Hydrogenation of Cooking Oils Improves
Their Stability but Creates Fatty Acids with Harmful
Health Effects
Waxes Serve as Energy Stores and Water Repellents
10.2 Structural Lipids in Membranes
Glycerophospholipids Are Derivatives of
Phosphatidic Acid
Some Glycerophospholipids Have Ether-Linked Fatty
Acids
Galactolipids of Plants and Ether-Linked Lipids of
Archaea Are Environmental Adaptations
Sphingolipids Are Derivatives of Sphingosine
Sphingolipids at Cell Surfaces Are Sites of Biological
Recognition
Phospholipids and Sphingolipids Are Degraded in
Lysosomes
Sterols Have Four Fused Carbon Rings
BOX 10-2 Abnormal Accumulations of Membrane
Lipids: Some Inherited Human Diseases
10.3 Lipids as Signals, Cofactors, and Pigments
61

Phosphatidylinositols and Sphingosine Derivatives
Act as Intracellular Signals
Eicosanoids Carry Messages to Nearby Cells
Steroid Hormones Carry Messages between Tissues
Vascular Plants Produce Thousands of Volatile
Signals
Vitamins A and D Are Hormone Precursors
Vitamins E and K and the Lipid Quinones Are
Oxidation-Reduction Cofactors
Dolichols Activate Sugar Precursors for Biosynthesis
Many Natural Pigments Are Lipidic Conjugated
Dienes
Polyketides Are Natural Products with Potent
Biological Activities
10.4 Working with Lipids
Lipid Extraction Requires Organic Solvents
Adsorption Chromatography Separates Lipids of
Different Polarity
Gas Chromatography Resolves Mixtures of Volatile
Lipid Derivatives
Specific Hydrolysis Aids in Determination of Lipid
Structure
Mass Spectrometry Reveals Complete Lipid Structure
Lipidomics Seeks to Catalog All Lipids and Their
Functions
11 Biological Membranes and Transport
11.1 The Composition and Architecture of Membranes
62

The Lipid Bilayer Is Stable in Water
Bilayer Architecture Underlies the Structure and
Function of Biological Membranes
The Endomembrane System Is Dynamic and
Functionally Differentiated
Membrane Proteins Are Receptors, Transporters,
and Enzymes
Membrane Proteins Differ in the Nature of Their
Association with the Membrane Bilayer
The Topology of an Integral Membrane Protein Can
O en Be Predicted from Its Sequence
Covalently Attached Lipids Anchor or Direct Some
Membrane Proteins
11.2 Membrane Dynamics
Acyl Groups in the Bilayer Interior Are Ordered to
Varying Degrees
Transbilayer Movement of Lipids Requires Catalysis
Lipids and Proteins Diffuse Laterally in the Bilayer
Sphingolipids and Cholesterol Cluster Together in
Membrane Ra s
Membrane Curvature and Fusion Are Central to
Many Biological Processes
Integral Proteins of the Plasma Membrane Are
Involved in Surface Adhesion, Signaling, and Other
Cellular Processes
11.3 Solute Transport across Membranes
Transport May Be Passive or Active

63

Transporters and Ion Channels Share Some
Structural Properties but Have Different Mechanisms
The Glucose Transporter of Erythrocytes Mediates
Passive Transport
The Chloride-Bicarbonate Exchanger Catalyzes
Electroneutral Cotransport of Anions across the
Plasma Membrane
BOX 11-1 Defective Glucose Transport in Diabetes
Active Transport Results in Solute Movement against
a Concentration or Electrochemical Gradient
P-Type ATPases Undergo Phosphorylation during
Their Catalytic Cycles
V-Type and F-Type ATPases Are ATP-Driven Proton
Pumps
ABC Transporters Use ATP to Drive the Active
Transport of a Wide Variety of Substrates
BOX 11-2 A Defective Ion Channel in Cystic Fibrosis
Ion Gradients Provide the Energy for Secondary
Active Transport
Aquaporins Form Hydrophilic Transmembrane
Channels for the Passage of Water
Ion-Selective Channels Allow Rapid Movement of
Ions across Membranes
The Structure of a K Channel Reveals the Basis for
+

Its Specificity
12 Biochemical Signaling
12.1 General Features of Signal Transduction

64

Signal-Transducing Systems Share Common Features
The General Process of Signal Transduction in
Animals Is Universal
12.2 G Protein–Coupled Receptors and Second
Messengers
The

β-Adrenergic Receptor System Acts through the

Second Messenger cAMP

Cyclic AMP Activates Protein Kinase A
BOX 12-1 FRET: Biochemistry in a Living Cell
Several Mechanisms Cause Termination of the
Adrenergic Response
The

β-

β-Adrenergic Receptor Is Desensitized by

Phosphorylation and by Association with Arrestin
Cyclic AMP Acts as a Second Messenger for Many
Regulatory Molecules
G Proteins Act as Self-Limiting Switches in Many
Processes
BOX 12-2 Receptor Guanylyl Cyclases, cGMP, and
Protein Kinase G
Diacylglycerol, Inositol Trisphosphate, and Ca

2+

Have Related Roles as Second Messengers
Calcium Is a Second Messenger That Is Limited in
Space and Time
12.3 GPCRs in Vision, Olfaction, and Gustation
The Vertebrate Eye Uses Classic GPCR Mechanisms
BOX 12-3 Color Blindness: John Dalton’s
Experiment from the Grave

65

Vertebrate Olfaction and Gustation Use Mechanisms
Similar to the Visual System
All GPCR Systems Share Universal Features
12.4 Receptor Tyrosine Kinases
Stimulation of the Insulin Receptor Initiates a
Cascade of Protein Phosphorylation Reactions
The Membrane Phospholipid PIP Functions at a
3

Branch in Insulin Signaling
Cross Talk among Signaling Systems Is Common and
Complex
12.5 Multivalent Adaptor Proteins and Membrane Ra s
Protein Modules Bind Phosphorylated Tyr, Ser, or
Thr Residues in Partner Proteins
Membrane Ra s and Caveolae Segregate Signaling
Proteins
12.6 Gated Ion Channels
Ion Channels Underlie Rapid Electrical Signaling in
Excitable Cells
Voltage-Gated Ion Channels Produce Neuronal
Action Potentials
Neurons Have Receptor Channels That Respond to
Different Neurotransmitters
Toxins Target Ion Channels
12.7 Regulation of Transcription by Nuclear Hormone
Receptors
12.8 Regulation of the Cell Cycle by Protein Kinases
The Cell Cycle Has Four Stages
66

Levels of Cyclin-Dependent Protein Kinases Oscillate
CDKs Are Regulated by Phosphorylation, Cyclin
Degradation, Growth Factors, and Specific Inhibitors
CDKs Regulate Cell Division by Phosphorylating
Critical Proteins
12.9 Oncogenes, Tumor Suppressor Genes, and
Programmed Cell Death
Oncogenes Are Mutant Forms of the Genes for
Proteins That Regulate the Cell Cycle
Defects in Certain Genes Remove Normal Restraints
on Cell Division
BOX 12-4 Development of Protein Kinase Inhibitors
for Cancer Treatment
Apoptosis Is Programmed Cell Suicide
II BIOENERGETICS AND METABOLISM
13 Introduction to Metabolism
13.1 Bioenergetics and Thermodynamics
Biological Energy Transformations Obey the Laws of
Thermodynamics
Standard Free-Energy Change Is Directly Related to
the Equilibrium Constant
Actual Free-Energy Changes Depend on Reactant and
Product Concentrations
Standard Free-Energy Changes Are Additive
13.2 Chemical Logic and Common Biochemical
Reactions
Biochemical Reactions Occur in Repeating Patterns
67

BOX 13-1 A Primer on Enzyme Names
Biochemical and Chemical Equations Are Not
Identical
13.3 Phosphoryl Group Transfers and ATP
The Free-Energy Change for ATP Hydrolysis Is Large
and Negative
Other Phosphorylated Compounds and Thioesters
Also Have Large, Negative Free Energies of
Hydrolysis
ATP Provides Energy by Group Transfers, Not by
Simple Hydrolysis
ATP Donates Phosphoryl, Pyrophosphoryl, and
Adenylyl Groups
Assembly of Informational Macromolecules
Requires Energy
BOX 13-2 Firefly Flashes: Glowing Reports of ATP
Transphosphorylations between Nucleotides Occur
in All Cell Types
13.4 Biological Oxidation-Reduction Reactions
The Flow of Electrons Can Do Biological Work
Oxidation-Reductions Can Be Described as HalfReactions
Biological Oxidations O en Involve Dehydrogenation
Reduction Potentials Measure Affinity for Electrons
Standard Reduction Potentials Can Be Used to
Calculate Free-Energy Change

68

A Few Types of Coenzymes and Proteins Serve as
Universal Electron Carriers
NAD Has Important Functions in Addition to
Electron Transfer
Flavin Nucleotides Are Tightly Bound in
Flavoproteins
13.5 Regulation of Metabolic Pathways
Cells and Organisms Maintain a Dynamic Steady
State
Both the Amount and the Catalytic Activity of an
Enzyme Can Be Regulated
Reactions Far from Equilibrium in Cells Are
Common Points of Regulation
Adenine Nucleotides Play Special Roles in Metabolic
Regulation
14 Glycolysis, Gluconeogenesis, and the Pentose Phosphate
Pathway
14.1 Glycolysis
An Overview: Glycolysis Has Two Phases
The Preparatory Phase of Glycolysis Requires ATP
The Payoff Phase of Glycolysis Yields ATP and NADH
The Overall Balance Sheet Shows a Net Gain of Two
ATP and Two NADH Per Glucose
14.2 Feeder Pathways for Glycolysis
Endogenous Glycogen and Starch Are Degraded by
Phosphorolysis

69

Dietary Polysaccharides and Disaccharides Undergo
Hydrolysis to Monosaccharides
14.3 Fates of Pyruvate
The Pasteur and Warburg Effects Are Due to
Dependence on Glycolysis Alone for ATP Production
Pyruvate Is the Terminal Electron Acceptor in Lactic
Acid Fermentation
BOX 14-1 High Rate of Glycolysis in Tumors
Suggests Targets for Chemotherapy and Facilitates
Diagnosis
BOX 14-2 Glucose Catabolism at Limiting
Concentrations of Oxygen
Ethanol Is the Reduced Product in Ethanol
Fermentation
Fermentations Produce Some Common Foods and
Industrial Chemicals
14.4 Gluconeogenesis
The First Bypass: Conversion of Pyruvate to
Phosphoenolpyruvate Requires Two Exergonic
Reactions
The Second and Third Bypasses Are Simple
Dephosphorylations by Phosphatases
Gluconeogenesis Is Energetically Expensive, But
Essential
Mammals Cannot Convert Fatty Acids to Glucose;
Plants and Microorganisms Can

70

14.5 Coordinated Regulation of Glycolysis and
Gluconeogenesis
Hexokinase Isozymes Are Affected Differently by
Their Product, Glucose 6-Phosphate
BOX 14-3 Isozymes: Different Proteins That
Catalyze the Same Reaction
Phosphofructokinase-1 and Fructose 1,6Bisphosphatase Are Reciprocally Regulated
Fructose 2,6-Bisphosphate Is a Potent Allosteric
Regulator of PFK-1 and FBPase-1
Xylulose 5-Phosphate Is a Key Regulator of
Carbohydrate and Fat Metabolism
The Glycolytic Enzyme Pyruvate Kinase Is
Allosterically Inhibited by ATP
Conversion of Pyruvate to Phosphoenolpyruvate Is
Stimulated When Fatty Acids Are Available
Transcriptional Regulation Changes the Number of
Enzyme Molecules
14.6 Pentose Phosphate Pathway of Glucose Oxidation
The Oxidative Phase Produces NADPH and Pentose
Phosphates
BOX 14-4 Why Pythagoras Wouldn’t Eat Falafel:
Glucose 6-Phosphate Dehydrogenase Deficiency
The Nonoxidative Phase Recycles Pentose
Phosphates to Glucose 6-Phosphate
Glucose 6-Phosphate Is Partitioned between
Glycolysis and the Pentose Phosphate Pathway

71

Thiamine Deficiency Causes Beriberi and WernickeKorsakoff Syndrome
15 The Metabolism of Glycogen in Animals
15.1 The Structure and Function of Glycogen
Vertebrate Animals Require a Ready Fuel Source for
Brain and Muscle
Glycogen Granules Have Many Tiers of Branched
Chains of D-Glucose
15.2 Breakdown and Synthesis of Glycogen
Glycogen Breakdown Is Catalyzed by Glycogen
Phosphorylase
Glucose 1-Phosphate Can Enter Glycolysis or, in
Liver, Replenish Blood Glucose
The Sugar Nucleotide UDP-Glucose Donates Glucose
for Glycogen Synthesis
BOX 15-1 Carl and Gerty Cori: Pioneers in Glycogen
Metabolism and Disease
Glycogenin Primes the Initial Sugar Residues in
Glycogen
15.3 Coordinated Regulation of Glycogen Breakdown
and Synthesis
Glycogen Phosphorylase Is Regulated by HormoneStimulated Phosphorylation and by Allosteric
Effectors
Glycogen Synthase Also Is Subject to Multiple Levels
of Regulation

72

Allosteric and Hormonal Signals Coordinate
Carbohydrate Metabolism Globally
Carbohydrate and Lipid Metabolism Are Integrated
by Hormonal and Allosteric Mechanisms
16 The Citric Acid Cycle
16.1 Production of Acetyl-CoA (Activated Acetate)
Pyruvate Is Oxidized to Acetyl-CoA and CO

2

The PDH Complex Employs Three Enzymes and Five
Coenzymes to Oxidize Pyruvate
The PDH Complex Channels Its Intermediates
through Five Reactions
16.2 Reactions of the Citric Acid Cycle
The Sequence of Reactions in the Citric Acid Cycle
Makes Chemical Sense
The Citric Acid Cycle Has Eight Steps
BOX 16-1 Moonlighting Enzymes: Proteins with
More Than One Job
The Energy of Oxidations in the Cycle Is Efficiently
Conserved
BOX 16-2 Citrate: A Symmetric Molecule That
Reacts Asymmetrically
16.3 The Hub of Intermediary Metabolism
The Citric Acid Cycle Serves in Both Catabolic and
Anabolic Processes
Anaplerotic Reactions Replenish Citric Acid Cycle
Intermediates

73

Biotin in Pyruvate Carboxylase Carries One-Carbon
(CO2 )

Groups

16.4 Regulation of the Citric Acid Cycle
Production of Acetyl-CoA by the PDH Complex Is
Regulated by Allosteric and Covalent Mechanisms
The Citric Acid Cycle Is Also Regulated at Three
Exergonic Steps
Citric Acid Cycle Activity Changes in Tumors
Certain Intermediates Are Channeled through
Metabolons
17 Fatty Acid Catabolism
17.1 Digestion, Mobilization, and Transport of Fats
Dietary Fats Are Absorbed in the Small Intestine
Hormones Trigger Mobilization of Stored
Triacylglycerols
Fatty Acids Are Activated and Transported into
Mitochondria
17.2 Oxidation of Fatty Acids

β

The Oxidation of Saturated Fatty Acids Has Four
Basic Steps
The Four

β-Oxidation Steps Are Repeated to Yield

Acetyl-CoA and ATP

Acetyl-CoA Can Be Further Oxidized in the Citric
Acid Cycle
BOX 17-1 A Long Winter’s Nap: Oxidizing Fats
during Hibernation

74

Oxidation of Unsaturated Fatty Acids Requires Two
Additional Reactions
Complete Oxidation of Odd-Number Fatty Acids
Requires Three Extra Reactions
Fatty Acid Oxidation Is Tightly Regulated
BOX 17-2 Coenzyme B : A Radical Solution to a
12

Perplexing Problem
Transcription Factors Turn on the Synthesis of
Proteins for Lipid Catabolism
Genetic Defects in Fatty Acyl–CoA Dehydrogenases
Cause Serious Disease
Peroxisomes Also Carry Out
Phytanic Acid Undergoes
Peroxisomes

β Oxidation

α Oxidation in

17.3 Ketone Bodies
Ketone Bodies, Formed in the Liver, Are Exported to
Other Organs as Fuel
Ketone Bodies Are Overproduced in Diabetes and
during Starvation
18 Amino Acid Oxidation and the Production of Urea
18.1 Metabolic Fates of Amino Groups
Dietary Protein Is Enzymatically Degraded to Amino
Acids
Pyridoxal Phosphate Participates in the Transfer of

α-Amino Groups to α-Ketoglutarate

Glutamate Releases Its Amino Group as Ammonia in
the Liver
75

Glutamine Transports Ammonia in the Bloodstream
Alanine Transports Ammonia from Skeletal Muscles
to the Liver
Ammonia Is Toxic to Animals
18.2 Nitrogen Excretion and the Urea Cycle
Urea Is Produced from Ammonia in Five Enzymatic
Steps
The Citric Acid and Urea Cycles Can Be Linked
The Activity of the Urea Cycle Is Regulated at Two
Levels
BOX 18-1 Assays for Tissue Damage
Pathway Interconnections Reduce the Energetic Cost
of Urea Synthesis
Genetic Defects in the Urea Cycle Can Be LifeThreatening
18.3 Pathways of Amino Acid Degradation
Some Amino Acids Can Contribute to
Gluconeogenesis, Others to Ketone Body Formation
Several Enzyme Cofactors Play Important Roles in
Amino Acid Catabolism
Six Amino Acids Are Degraded to Pyruvate
Seven Amino Acids Are Degraded to Acetyl-CoA
Phenylalanine Catabolism Is Genetically Defective in
Some People
Five Amino Acids Are Converted to

α-Ketoglutarate

Four Amino Acids Are Converted to Succinyl-CoA

76

Branched-Chain Amino Acids Are Not Degraded in
the Liver
BOX 18-2 MMA: Sometimes More than a Genetic
Disease
Asparagine and Aspartate Are Degraded to
Oxaloacetate
19 Oxidative Phosphorylation
19.1 The Mitochondrial Respiratory Chain
Electrons Are Funneled to Universal Electron
Acceptors
Electrons Pass through a Series of Membrane-Bound
Carriers
Electron Carriers Function in Multienzyme
Complexes
Mitochondrial Complexes Associate in Respirasomes
Other Pathways Donate Electrons to the Respiratory
Chain via Ubiquinone
The Energy of Electron Transfer Is Efficiently
Conserved in a Proton Gradient
Reactive Oxygen Species Are Generated during
Oxidative Phosphorylation
19.2 ATP Synthesis
In the Chemiosmotic Model, Oxidation and
Phosphorylation Are Obligately Coupled
ATP Synthase Has Two Functional Domains, F and
o

F1

ATP Is Stabilized Relative to ADP on the Surface of F
77

1

The Proton Gradient Drives the Release of ATP from
the Enzyme Surface
Each

β Subunit of ATP Synthase Can Assume Three

Different Conformations

Rotational Catalysis Is Key to the Binding-Change
Mechanism for ATP Synthesis
Chemiosmotic Coupling Allows Nonintegral
Stoichiometries of O Consumption and ATP
2

Synthesis
The Proton-Motive Force Energizes Active Transport
Shuttle Systems Indirectly Convey Cytosolic NADH
into Mitochondria for Oxidation
BOX 19-1 Hot, Stinking Plants and Alternative
Respiratory Pathways
19.3 Regulation of Oxidative Phosphorylation
Oxidative Phosphorylation Is Regulated by Cellular
Energy Needs
An Inhibitory Protein Prevents ATP Hydrolysis
during Hypoxia
Hypoxia Leads to ROS Production and Several
Adaptive Responses
ATP-Producing Pathways Are Coordinately Regulated
19.4 Mitochondria in Thermogenesis, Steroid
Synthesis, and Apoptosis
Uncoupled Mitochondria in Brown Adipose Tissue
Produce Heat

78

Mitochondrial P-450 Monooxygenases Catalyze
Steroid Hydroxylations
Mitochondria Are Central to the Initiation of
Apoptosis
19.5 Mitochondrial Genes: Their Origin and the Effects
of Mutations
Mitochondria Evolved from Endosymbiotic Bacteria
Mutations in Mitochondrial DNA Accumulate
throughout the Life of the Organism
Some Mutations in Mitochondrial Genomes Cause
Disease
A Rare Form of Diabetes Results from Defects in the
Mitochondria of Pancreatic

β Cells

20 Photosynthesis and Carbohydrate Synthesis in Plants
20.1 Light Absorption
Chloroplasts Are the Site of Light-Driven Electron
Flow and Photosynthesis in Plants
Chlorophylls Absorb Light Energy for Photosynthesis
Chlorophylls Funnel Absorbed Energy to Reaction
Centers by Exciton Transfer
20.2 Photochemical Reaction Centers
Photosynthetic Bacteria Have Two Types of Reaction
Center
In Vascular Plants, Two Reaction Centers Act in
Tandem
The Cytochrome b

6

f

Complex Links Photosystems II

and I, Conserving the Energy of Electron Transfer
79

Cyclic Electron Transfer Allows Variation in the Ratio
of ATP/NADPH Synthesized
State Transitions Change the Distribution of LHCII
between the Two Photosystems
Water Is Split at the Oxygen-Evolving Center
20.3 Evolution of a Universal Mechanism for ATP
Synthesis
A Proton Gradient Couples Electron Flow and
Phosphorylation
The Approximate Stoichiometry of
Photophosphorylation Has Been Established
The ATP Synthase Structure And Mechanism Are
Nearly Universal
20.4 CO -Assimilation Reactions
2

Carbon Dioxide Assimilation Occurs in Three Stages
Synthesis of Each Triose Phosphate from CO

2

Requires Six NADPH and Nine ATP
A Transport System Exports Triose Phosphates from
the Chloroplast and Imports Phosphate
Four Enzymes of the Calvin Cycle Are Indirectly
Activated by Light
20.5 Photorespiration and the C and CAM Pathways
4

Photorespiration Results from Rubisco’s Oxygenase
Activity
Phosphoglycolate Is Salvaged in a Costly Set of
Reactions in C Plants
3

80

In C Plants, CO Fixation and Rubisco Activity Are
4

2

Spatially Separated
BOX 20-1 Will Genetic Engineering of
Photosynthetic Organisms Increase Their
Efficiency?
In CAM Plants, CO Capture and Rubisco Action Are
2

Temporally Separated
20.6 Biosynthesis of Starch, Sucrose, and Cellulose
ADP-Glucose Is the Substrate for Starch Synthesis in
Plant Plastids and for Glycogen Synthesis in Bacteria
UDP-Glucose Is the Substrate for Sucrose Synthesis in
the Cytosol of Leaf Cells
Conversion of Triose Phosphates to Sucrose and
Starch Is Tightly Regulated
The Glyoxylate Cycle and Gluconeogenesis Produce
Glucose in Germinating Seeds
Cellulose Is Synthesized by Supramolecular
Structures in the Plasma Membrane
Pools of Common Intermediates Link Pathways in
Different Organelles
21 Lipid Biosynthesis
21.1 Biosynthesis of Fatty Acids and Eicosanoids
Malonyl-CoA Is Formed from Acetyl-CoA and
Bicarbonate
Fatty Acid Synthesis Proceeds in a Repeating
Reaction Sequence

81

The Mammalian Fatty Acid Synthase Has Multiple
Active Sites
Fatty Acid Synthase Receives the Acetyl and Malonyl
Groups
The Fatty Acid Synthase Reactions Are Repeated to
Form Palmitate
Fatty Acid Synthesis Is a Cytosolic Process in Most
Eukaryotes but Takes Place in the Chloroplasts in
Plants
Acetate Is Shuttled out of Mitochondria as Citrate
Fatty Acid Biosynthesis Is Tightly Regulated
Long-Chain Saturated Fatty Acids Are Synthesized
from Palmitate
Desaturation of Fatty Acids Requires a MixedFunction Oxidase
Eicosanoids Are Formed from 20- and 22-Carbon
Polyunsaturated Fatty Acids
BOX 21-1 Oxidases, Oxygenases, Cytochrome P-450
Enzymes, and Drug Overdoses
21.2 Biosynthesis of Triacylglycerols
Triacylglycerols and Glycerophospholipids Are
Synthesized from the Same Precursors
Triacylglycerol Biosynthesis in Animals Is Regulated
by Hormones
Adipose Tissue Generates Glycerol 3-Phosphate by
Glyceroneogenesis

82

Thiazolidinediones Treat Type 2 Diabetes by
Increasing Glyceroneogenesis
21.3 Biosynthesis of Membrane Phospholipids
Cells Have Two Strategies for Attaching Phospholipid
Head Groups
Pathways for Phospholipid Biosynthesis Are
Interrelated
Eukaryotic Membrane Phospholipids Are Subject to
Remodeling
Plasmalogen Synthesis Requires Formation of an
Ether-Linked Fatty Alcohol
Sphingolipid and Glycerophospholipid Synthesis
Share Precursors and Some Mechanisms
Polar Lipids Are Targeted to Specific Cellular
Membranes
21.4 Cholesterol, Steroids, and Isoprenoids:
Biosynthesis, Regulation, and Transport
Cholesterol Is Made from Acetyl-CoA in Four Stages
Cholesterol Has Several Fates
Cholesterol and Other Lipids Are Carried on Plasma
Lipoproteins
HDL Carries Out Reverse Cholesterol Transport
Cholesteryl Esters Enter Cells by Receptor-Mediated
Endocytosis
Cholesterol Synthesis and Transport Are Regulated at
Several Levels

83

Dysregulation of Cholesterol Metabolism Can Lead to
Cardiovascular Disease
Reverse Cholesterol Transport by HDL Counters
Plaque Formation and Atherosclerosis
Steroid Hormones Are Formed by Side-Chain
Cleavage and Oxidation of Cholesterol
BOX 21-2 The Lipid Hypothesis and the
Development of Statins
Intermediates in Cholesterol Biosynthesis Have
Many Alternative Fates
22 Biosynthesis of Amino Acids, Nucleotides, and Related
Molecules
22.1 Overview of Nitrogen Metabolism
A Global Nitrogen Cycling Network Maintains a Pool
of Biologically Available Nitrogen
Nitrogen Is Fixed by Enzymes of the Nitrogenase
Complex
BOX 22-1 Unusual Lifestyles of the Obscure but
Abundant
Ammonia Is Incorporated into Biomolecules through
Glutamate and Glutamine
Glutamine Synthetase Is a Primary Regulatory Point
in Nitrogen Metabolism
Several Classes of Reactions Play Special Roles in the
Biosynthesis of Amino Acids and Nucleotides
22.2 Biosynthesis of Amino Acids

84

Organisms Vary Greatly in Their Ability to Synthesize
the 20 Common Amino Acids

α-Ketoglutarate Gives Rise to Glutamate, Glutamine,
Proline, and Arginine

Serine, Glycine, and Cysteine Are Derived from 3Phosphoglycerate
Three Nonessential and Six Essential Amino Acids
Are Synthesized from Oxaloacetate and Pyruvate
Chorismate Is a Key Intermediate in the Synthesis of
Tryptophan, Phenylalanine, and Tyrosine
Histidine Biosynthesis Uses Precursors of Purine
Biosynthesis
Amino Acid Biosynthesis Is under Allosteric
Regulation
22.3 Molecules Derived from Amino Acids
Glycine Is a Precursor of Porphyrins
Heme Degradation Has Multiple Functions
BOX 22-2 On Kings and Vampires
Amino Acids Are Precursors of Creatine and
Glutathione
d-Amino Acids Are Found Primarily in Bacteria
Aromatic Amino Acids Are Precursors of Many Plant
Substances
Biological Amines Are Products of Amino Acid
Decarboxylation
Arginine Is the Precursor for Biological Synthesis of
Nitric Oxide

85

22.4 Biosynthesis and Degradation of Nucleotides
De Novo Purine Nucleotide Synthesis Begins with
PRPP
Purine Nucleotide Biosynthesis Is Regulated by
Feedback Inhibition
Pyrimidine Nucleotides Are Made from Aspartate,
PRPP, and Carbamoyl Phosphate
Pyrimidine Nucleotide Biosynthesis Is Regulated by
Feedback Inhibition
Nucleoside Monophosphates Are Converted to
Nucleoside Triphosphates
Ribonucleotides Are the Precursors of
Deoxyribonucleotides
Thymidylate Is Derived from dCDP and dUMP
Degradation of Purines and Pyrimidines Produces
Uric Acid and Urea, Respectively
Purine and Pyrimidine Bases Are Recycled by
Salvage Pathways
Excess Uric Acid Causes Gout
Many Chemotherapeutic Agents Target Enzymes in
Nucleotide Biosynthetic Pathways
23 Hormonal Regulation and Integration of Mammalian
Metabolism
23.1 Hormone Structure and Action
Hormones Act through Specific High-Affinity
Cellular Receptors
Hormones Are Chemically Diverse

86

Some Hormones Are Released by a “Top-Down”
Hierarchy of Neuronal and Hormonal Signals
“Bottom-Up” Hormonal Systems Send Signals Back to
the Brain and to Other Tissues
23.2 Tissue-Specific Metabolism
The Liver Processes and Distributes Nutrients
Adipose Tissues Store and Supply Fatty Acids
Brown and Beige Adipose Tissues Are Thermogenic
Muscles Use ATP for Mechanical Work
The Brain Uses Energy for Transmission of Electrical
Impulses
BOX 23-1 Creatine and Creatine Kinase: Invaluable
Diagnostic Aids and the Muscle Builder’s Friends
Blood Carries Oxygen, Metabolites, and Hormones
23.3 Hormonal Regulation of Fuel Metabolism
Insulin Counters High Blood Glucose in the Well-Fed
State

β

Pancreatic Cells Secrete Insulin in Response to
Changes in Blood Glucose
Glucagon Counters Low Blood Glucose
During Fasting and Starvation, Metabolism Shi s to
Provide Fuel for the Brain
Epinephrine Signals Impending Activity
Cortisol Signals Stress, Including Low Blood Glucose
23.4 Obesity and the Regulation of Body Mass
Adipose Tissue Has Important Endocrine Functions

87

Leptin Stimulates Production of Anorexigenic
Peptide Hormones
Leptin Triggers a Signaling Cascade That Regulates
Gene Expression
Adiponectin Acts through AMPK to Increase Insulin
Sensitivity
AMPK Coordinates Catabolism and Anabolism in
Response to Metabolic Stress
The mTORC1 Pathway Coordinates Cell Growth with
the Supply of Nutrients and Energy
Diet Regulates the Expression of Genes Central to
Maintaining Body Mass
Short-Term Eating Behavior Is Influenced by Ghrelin,
, and Cannabinoids
Microbial Symbionts in the Gut Influence Energy
Metabolism and Adipogenesis
23.5 Diabetes Mellitus
Diabetes Mellitus Arises from Defects in Insulin
Production or Action
BOX 23-2 The Arduous Path to Purified Insulin
Carboxylic Acids (Ketone Bodies) Accumulate in the
Blood of Those with Untreated Diabetes
In Type 2 Diabetes the Tissues Become Insensitive to
Insulin
Type 2 Diabetes Is Managed with Diet, Exercise,
Medication, and Surgery
III INFORMATION PATHWAYS

88

24 Genes and Chromosomes
24.1 Chromosomal Elements
Genes Are Segments of DNA That Code for
Polypeptide Chains and RNAs
DNA Molecules Are Much Longer than the Cellular or
Viral Packages That Contain Them
Eukaryotic Genes and Chromosomes Are Very
Complex
24.2 DNA Supercoiling
Most Cellular DNA Is Underwound
DNA Underwinding Is Defined by Topological
Linking Number
Topoisomerases Catalyze Changes in the Linking
Number of DNA
DNA Compaction Requires a Special Form of
Supercoiling
24.3 The Structure of Chromosomes
Chromatin Consists of DNA, Proteins, and RNA
Histones Are Small, Basic Proteins
Nucleosomes Are the Fundamental Organizational
Units of Chromatin
Nucleosomes Are Packed into Highly Condensed
Chromosome Structures
BOX 24-1 Epigenetics, Nucleosome Structure, and
Histone Variants
BOX 24-2 Curing Disease by Inhibiting
Topoisomerases
89

BOX 24-3 X Chromosome Inactivation by an
lncRNA: Preventing Too Much of a Good (or Bad)
Thing
Condensed Chromosome Structures Are Maintained
by SMC Proteins
Bacterial DNA Is Also Highly Organized
25 DNA Metabolism
25.1 DNA Replication
DNA Replication Follows a Set of Fundamental Rules
DNA Is Degraded by Nucleases
DNA Is Synthesized by DNA Polymerases
Replication Is Very Accurate
E. coli Has at Least Five DNA Polymerases
DNA Replication Requires Many Enzymes and
Protein Factors
Replication of the E. coli Chromosome Proceeds in
Stages
Replication in Eukaryotic Cells Is Similar but More
Complex
Viral DNA Polymerases Provide Targets for Antiviral
Therapy
25.2 DNA Repair
Mutations Are Linked to Cancer
All Cells Have Multiple DNA Repair Systems
BOX 25-1 DNA Repair and Cancer

90

The Interaction of Replication Forks with DNA
Damage Can Lead to Error-Prone Translesion DNA
Synthesis
25.3 DNA Recombination
Bacterial Homologous Recombination Is a DNA
Repair Function
Eukaryotic Homologous Recombination Is Required
for Proper Chromosome Segregation during Meiosis
BOX 25-2 Why Proper Segregation of Chromosomes
Matters
Some Double-Strand Breaks Are Repaired by
Nonhomologous End Joining
BOX 25-3 How a DNA Strand Break Gets Attention
Site-Specific Recombination Results in Precise DNA
Rearrangements
Transposable Genetic Elements Move from One
Location to Another
Immunoglobulin Genes Assemble by Recombination
26 RNA Metabolism
26.1 DNA-Dependent Synthesis of RNA
RNA Is Synthesized by RNA Polymerases
RNA Synthesis Begins at Promoters
BOX 26-1 RNA Polymerase Leaves Its Footprint on a
Promoter
Transcription Is Regulated at Several Levels
Specific Sequences Signal Termination of RNA
Synthesis
91

Eukaryotic Cells Have Three Kinds of Nuclear RNA
Polymerases
RNA Polymerase II Requires Many Other Protein
Factors for Its Activity
RNA Polymerases Are Drug Targets
26.2 RNA Processing
Eukaryotic mRNAs Are Capped at the 5 End
′

Both Introns and Exons Are Transcribed from DNA
into RNA
RNA Catalyzes the Splicing of Introns
In Eukaryotes the Spliceosome Carries out Nuclear
pre-mRNA Splicing
Proteins Catalyze Splicing of tRNAs
Eukaryotic mRNAs Have a Distinctive 3 End
Structure
′

A Gene Can Give Rise to Multiple Products by
Differential RNA Processing
BOX 26-2 Alternative Splicing and Spinal Muscular
Atrophy
Ribosomal RNAs and tRNAs Also Undergo Processing
Special-Function RNAs Undergo Several Types of
Processing
Cellular mRNAs Are Degraded at Different Rates
26.3 RNA-Dependent Synthesis of RNA and DNA
Reverse Transcriptase Produces DNA from Viral RNA
Some Retroviruses Cause Cancer and AIDS

92

Many Transposons, Retroviruses, and Introns May
Have a Common Evolutionary Origin
BOX 26-3 Fighting AIDS with Inhibitors of HIV
Reverse Transcriptase
Telomerase Is a Specialized Reverse Transcriptase
Some RNAs Are Replicated by RNA-Dependent RNA
Polymerase
RNA-Dependent RNA Polymerases Share a Common
Structural Fold
26.4 Catalytic RNAs and the RNA World Hypothesis
Ribozymes Share Features with Protein Enzymes
Ribozymes Participate in a Variety of Biological
Processes
Ribozymes Provide Clues to the Origin of Life in an
RNA World
BOX 26-4 The SELEX Method for Generating RNA
Polymers with New Functions
27 Protein Metabolism
27.1 The Genetic Code
The Genetic Code Was Cracked Using Artificial
mRNA Templates
BOX 27-1 Exceptions That Prove the Rule: Natural
Variations in the Genetic Code
Wobble Allows Some tRNAs to Recognize More than
One Codon
The Genetic Code Is Mutation-Resistant

93

Translational Frameshi ing Affects How the Code Is
Read
Some mRNAs Are Edited before Translation
27.2 Protein Synthesis
The Ribosome Is a Complex Supramolecular
Machine
Transfer RNAs Have Characteristic Structural
Features
Stage 1: Aminoacyl-tRNA Synthetases Attach the
Correct Amino Acids to Their tRNAs
Stage 2: A Specific Amino Acid Initiates Protein
Synthesis
BOX 27-2 Natural and Unnatural Expansion of the
Genetic Code
Stage 3: Peptide Bonds Are Formed in the Elongation
Stage
BOX 27-3 Ribosome Pausing, Arrest, and Rescue
Stage 4: Termination of Polypeptide Synthesis
Requires a Special Signal
Stage 5: Newly Synthesized Polypeptide Chains
Undergo Folding and Processing
Protein Synthesis Is Inhibited by Many Antibiotics
and Toxins
27.3 Protein Targeting and Degradation
Posttranslational Modification of Many Eukaryotic
Proteins Begins in the Endoplasmic Reticulum
Glycosylation Plays a Key Role in Protein Targeting

94

Signal Sequences for Nuclear Transport Are Not
Cleaved
Bacteria Also Use Signal Sequences for Protein
Targeting
Cells Import Proteins by Receptor-Mediated
Endocytosis
Protein Degradation Is Mediated by Specialized
Systems in All Cells
28 Regulation of Gene Expression
28.1 The Proteins and RNAs of Gene Regulation
RNA Polymerase Binds to DNA at Promoters
Transcription Initiation Is Regulated by Proteins and
RNAs
Many Bacterial Genes Are Clustered and Regulated in
Operons
The lac Operon Is Subject to Negative Regulation
Regulatory Proteins Have Discrete DNA-Binding
Domains
Regulatory Proteins Also Have Protein-Protein
Interaction Domains
28.2 Regulation of Gene Expression in Bacteria
The lac Operon Undergoes Positive Regulation
Many Genes for Amino Acid Biosynthetic Enzymes
Are Regulated by Transcription Attenuation
Induction of the SOS Response Requires Destruction
of Repressor Proteins

95

Synthesis of Ribosomal Proteins Is Coordinated with
rRNA Synthesis
The Function of Some mRNAs Is Regulated by Small
RNAs in Cis or in Trans
Some Genes Are Regulated by Genetic
Recombination
28.3 Regulation of Gene Expression in Eukaryotes
Transcriptionally Active Chromatin Is Structurally
Distinct from Inactive Chromatin
Most Eukaryotic Promoters Are Positively Regulated
DNA-Binding Activators and Coactivators Facilitate
Assembly of the Basal Transcription Factors
The Genes of Galactose Metabolism in Yeast Are
Subject to Both Positive and Negative Regulation
Transcription Activators Have a Modular Structure
Eukaryotic Gene Expression Can Be Regulated by
Intercellular and Intracellular Signals
Regulation Can Result from Phosphorylation of
Nuclear Transcription Factors
Many Eukaryotic mRNAs Are Subject to Translational
Repression
Posttranscriptional Gene Silencing Is Mediated by
RNA Interference
RNA-Mediated Regulation of Gene Expression Takes
Many Forms in Eukaryotes
Development Is Controlled by Cascades of
Regulatory Proteins

96

Stem Cells Have Developmental Potential That Can
Be Controlled
BOX 28-1 Of Fins, Wings, Beaks, and Things
Abbreviated Solutions to Problems
Glossary
Index
Resources

97

CHAPTER 1

THE FOUNDATIONS OF
BIOCHEMISTRY

1.1 Cellular Foundations
1.2 Chemical Foundations
1.3 Physical Foundations
1.4 Genetic Foundations
1.5 Evolutionary Foundations
About 14 billion years ago, the universe arose as a cataclysmic
explosion of hot, energy-rich subatomic particles. Within
seconds, the simplest elements (hydrogen and helium) were
formed. As the universe expanded and cooled, material
condensed under the influence of gravity to form stars. Some
stars became enormous and then exploded as supernovae,
releasing the energy needed to fuse simpler atomic nuclei into
the more complex elements. Atoms and molecules formed
swirling masses of dust particles, and their accumulation led
eventually to the formation of rocks, planetoids, and planets.
Thus were produced, over billions of years, Earth itself and the
chemical elements found on Earth today. About 4 billion years

98

ago, life arose on Earth — simple microorganisms with the ability
to extract energy from chemical compounds and, later, from
sunlight, which they used to make a vast array of more complex
biomolecules from the simple elements and compounds on the
Earth’s surface. We and all other living organisms are made of
stardust.
Biochemistry asks how the remarkable properties of living
organisms arise from thousands of different biomolecules. When
these molecules are isolated and examined individually, they
conform to all the physical and chemical laws that describe the
behavior of inanimate matter — as do all the processes occurring
in living organisms. The study of biochemistry shows how the
collections of inanimate molecules that constitute living
organisms interact to maintain and perpetuate life governed
solely by the same physical and chemical laws that govern the
nonliving universe.
In each chapter of this book, we organize our discussion around
central principles or issues in biochemistry. In this chapter, we
consider the features that define a living organism, and we
develop these principles:
Cells are the fundamental unit of life. Although they vary
in complexity and can be highly specialized for their
environment or function within a multicellular organism, they
share remarkable similarities.

99

Cells use a relatively small set of carbon-based
metabolites to create polymeric machines, supramolecular
structures, and information repositories. The chemical
structure of these components defines their cellular function.
The collection of molecules carries out a program, the end
result of which is reproduction of the program and selfperpetuation of that collection of molecules — in short, life.
Living organisms exist in a dynamic steady state, never
at equilibrium with their surroundings. Following the laws of
thermodynamics, living organisms extract energy from their
surroundings and employ it to maintain homeostasis and do
useful work. Essentially all of the energy obtained by a cell
comes from the flow of electrons, driven by sunlight or by
metabolic redox reactions.
Cells have the capacity for precise self-replication and
self-assembly using chemical information stored in the
genome. A single bacterial cell placed in a sterile nutrient
medium can give rise to a billion identical “daughter” cells in
24 hours. Each cell is a faithful copy of the original, its
construction directed entirely by information contained in the
genetic material of the original cell. On a larger scale, the
progeny of vertebrate animals share a striking resemblance to
their parents, also the result of their inheritance of parental
genes.
Living organisms change over time by gradual evolution.
The result of eons of evolution is an enormous diversity of life

100

forms, fundamentally related through their shared ancestry,
which can be seen at the molecular level in the similarity of
gene sequences and protein structures.
Despite these common properties and the fundamental unity of
life they reveal, it is difficult to make generalizations about living
organisms. Earth has an enormous diversity of organisms living
in a wide range of habitats, from hot springs to Arctic tundra,
from animal intestines to college dormitories. These habitats are
matched by a correspondingly wide range of specific biochemical
adaptations, achieved within a common chemical framework. For
the sake of clarity, in this book we sometimes risk certain
generalizations, which, though not perfect, remain useful; we
also frequently point out the exceptions to these generalizations,
which can prove illuminating.
Biochemistry describes in molecular terms the structures,
mechanisms, and chemical processes shared by all organisms
and provides organizing principles that underlie life in all its
diverse forms. Although biochemistry provides important
insights and practical applications in medicine, agriculture,
nutrition, and industry, its ultimate concern is with the wonder of
life itself.
In this introductory chapter we give an overview of the cellular,
chemical, physical, and genetic backgrounds of biochemistry and
the overarching principle of evolution — how life emerged and
evolved into the diversity of organisms we see today. As you read
through the book, you may find it helpful to refer back to this
101

chapter at intervals to refresh your memory of this background
material.

102

1.1 Cellular Foundations
The unity and diversity of organisms become apparent even at the
cellular level. The smallest organisms consist of single cells and
are microscopic. Larger, multicellular organisms contain many
different types of cells, which vary in size, shape, and specialized
function.

Despite these obvious differences, all cells of the

simplest and most complex organisms share certain fundamental
properties, which can be seen at the biochemical level.

Cells Are the Structural and
Functional Units of All Living
Organisms
Cells of all kinds share certain structural features (Fig. 1-1). The
plasma membrane defines the periphery of the cell, separating
its contents from the surroundings. It is composed of lipid and
protein molecules that form a thin, tough, pliable, hydrophobic
barrier around the cell. The membrane is a barrier to the free
passage of inorganic ions and most other charged or polar
molecules. Transport proteins in the plasma membrane allow the
passage of certain ions and molecules, receptor proteins transmit
signals into the cell, and membrane enzymes participate in some
reaction pathways. Because the individual lipids and proteins of
the plasma membrane are not covalently linked, the entire
structure is remarkably flexible, allowing changes in the shape
and size of the cell. As a cell grows, newly made lipid and protein

103

molecules are inserted into its plasma membrane; cell division
produces two cells, each with its own membrane. This growth
and cell division (fission) occurs without loss of membrane
integrity.

FIGURE 1-1 The universal features of living cells. All cells have a nucleus or
nucleoid containing their DNA, a plasma membrane, and cytoplasm.
Eukaryotic cells contain a variety of membrane-bounded organelles
(including mitochondria and chloroplasts) and large particles (ribosomes,
for example).

The internal volume enclosed by the plasma membrane, the
cytoplasm (Fig. 1-1), is composed of an aqueous solution, the
cytosol, and a variety of suspended particles with specific
functions. These particulate components (membranous
organelles such as mitochondria and chloroplasts;
supramolecular structures such as ribosomes and proteasomes,
the sites of protein synthesis and degradation) sediment when
cytoplasm is centrifuged at 150,000 g (g is the gravitational force
of Earth). What remains as the supernatant fluid is defined as the
cytosol, a highly concentrated solution containing enzymes and
the RNA (ribonucleic acid) molecules that encode them; the
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components (amino acids and nucleotides) from which these
macromolecules are assembled; hundreds of small organic
molecules called metabolites, intermediates in biosynthetic and
degradative pathways; coenzymes, compounds essential to many
enzyme-catalyzed reactions; and inorganic ions (K
and Ca

2+

,

+

+

, Na

, Mg

2+

,

for example).

All cells have, for at least some part of their life, either a nucleoid
or a nucleus, in which the genome — the complete set of genes,
composed of DNA (deoxyribonucleic acid) — is replicated and
stored, with its associated proteins. The nucleoid, in bacteria and
archaea, is not separated from the cytoplasm by a membrane; the
nucleus, in eukaryotes, is enclosed within a double membrane,
the nuclear envelope. Cells with nuclear envelopes make up the
large domain Eukarya (Greek eu, “true,” and karyon, “nucleus”).
Microorganisms without nuclear membranes, formerly grouped
together as prokaryotes (Greek pro, “before”), are now
recognized as comprising two very distinct groups: the domains
Bacteria and Archaea, described below.

Cellular Dimensions Are Limited by
Diffusion
Most cells are microscopic, invisible to the unaided eye. Animal

μm in diameter, and many
unicellular microorganisms are only 1 to 2 μm long (see the
and plant cells are typically 5 to 100

inside of the back cover for information on units and their

105

abbreviations). What limits the dimensions of a cell? The lower
limit is probably set by the minimum number of each type of
biomolecule required by the cell. The smallest cells, certain
bacteria known as mycoplasmas, are 300 nm in diameter and
have a volume of about 10

−14

mL.

A single bacterial ribosome is

about 20 nm in its longest dimension, so a few ribosomes take up
a substantial fraction of the volume in a mycoplasmal cell.
The upper limit of cell size is probably set by the rate of transport
of nutrients into the cell and waste products out. As the size of a
cell increases, its surface-to-volume ratio decreases. For a
spherical cell, the surface area is a function of the square of the
radius (r

2

),

whereas its volume is a function of r . A bacterial cell
3

the size of Eschericia coli is so small, and the ratio of its surface
area to its volume is so large, that every part of its cytoplasm is
easily reached by nutrients moving across the membrane and
into the cell. With increasing cell size, surface-to-volume ratio
decreases, until metabolism consumes nutrients faster than
transmembrane carriers can supply them. Many types of animal
cells have a highly folded or convoluted surface that increases
their surface-to-volume ratio and allows higher rates of uptake of
materials from their surroundings (Fig. 1-2).

106

FIGURE 1-2 Most animal cells have intricately folded surfaces. The human
lymphocytes in this artificially colored scanning electron micrograph are
about 10–12

μm in diameter. Their convoluted surfaces give them a much

larger surface area than a sphere of the same diameter.

107

Organisms Belong to Three Distinct
Domains of Life
The development of techniques for determining DNA sequences
quickly and inexpensively has greatly improved our ability to
deduce evolutionary relationships among organisms. Similarities
between gene sequences in various organisms provide deep
insight into the course of evolution. In one interpretation of
sequence similarities, all living organisms fall into one of three
large groups (domains) that define three branches of the
evolutionary tree of life originating from a common progenitor
(Fig. 1-3). Two large groups of single-celled microorganisms can
be distinguished on genetic and biochemical grounds: Bacteria
and Archaea. Bacteria inhabit soils, surface waters, and the
tissues of other living or decaying organisms. Many of the
Archaea, recognized as a distinct domain by the microbiologist
Carl Woese in the 1980s, inhabit extreme environments — salt
lakes, hot springs, highly acidic bogs, and the ocean depths. The
available evidence suggests that the Archaea and Bacteria
diverged early in evolution. All eukaryotic organisms, which make
up the third domain, Eukarya, evolved from the same branch that
gave rise to the Archaea; eukaryotes are therefore more closely
related to archaea than to bacteria.

108

FIGURE 1-3 Phylogeny of the three domains of life. Phylogenetic relationships are o en
illustrated by a “family tree” of this type. The basis for this tree is the similarity in
nucleotide sequences of the ribosomal RNAs of each group. [Information from C. R.
Woese, Microbiol. Rev. 51:221, 1987, Fig. 4.]

Within the domains of Archaea and Bacteria are subgroups
distinguished by their habitats. In aerobic habitats with a
plentiful supply of oxygen, some resident organisms derive
energy from the transfer of electrons from fuel molecules to
oxygen within the cell. Other environments are anaerobic, devoid
of oxygen, and microorganisms adapted to these environments
obtain energy by transferring electrons to nitrate (forming N ),
2

sulfate (forming H S), or CO (forming CH ). Many organisms
2

2

4

that have evolved in anaerobic environments are obligate
anaerobes: they die when exposed to oxygen. Others are
facultative anaerobes, able to live with or without oxygen.

109

Organisms Differ Widely in Their
Sources of Energy and Biosynthetic
Precursors
We can classify organisms according to how they obtain
the energy and carbon they need for synthesizing cellular
material (as summarized in Fig. 1-4). There are two broad
categories based on energy sources: phototrophs (Greek trophē,
“nourishment”) trap and use sunlight, and chemotrophs derive
their energy from oxidation of a chemical fuel. Some
chemotrophs oxidize inorganic fuels — HS to S (elemental
−

sulfur), S to SO
0

−
4

, NO

−
2

to NO

−
3

,

or Fe

2+

to Fe

0

3+

,

for example.

Phototrophs and chemotrophs may be further divided into those
that can synthesize all of their biomolecules directly from CO

2

(autotrophs) and those that require some preformed organic
nutrients made by other organisms (heterotrophs). We can
describe an organism’s mode of nutrition by combining these
terms. For example, cyanobacteria are photoautotrophs; humans
are chemoheterotrophs. Even finer distinctions can be made, and
many organisms can obtain energy and carbon from more than
one source under different environmental or developmental
conditions.

110

FIGURE 1-4 All organisms can be classified according to their source of energy (sunlight
or oxidizable chemical compounds) and their source of carbon for the synthesis of
cellular material.

Bacterial and Archaeal Cells Share
Common Features but Differ in
Important Ways
The best-studied bacterium, Escherichia coli, is a usually harmless
inhabitant of the human intestinal tract. The E. coli cell (Fig. 1-5a)
is an ovoid about 2

μm long and a little less than 1 μm in

diameter, but other bacteria may be spherical or rod-shaped, and
some are substantially larger. E. coli has a protective outer
111

membrane and an inner plasma membrane that encloses the
cytoplasm and the nucleoid. Between the inner and outer
membranes is a thin but strong layer of a high molecular weight
polymer (peptidoglycan) that gives the cell its shape and rigidity.
The plasma membrane and the layers outside it constitute the cell
envelope. The plasma membranes of bacteria consist of a thin
bilayer of lipid molecules penetrated by proteins. Archaeal
plasma membranes have a similar architecture, but the lipids can
be strikingly different from those of bacteria (see Fig. 10-6).

FIGURE 1-5 Some common structural features of bacterial and archaeal cells. (a) This
correct-scale drawing of E. coli serves to illustrate some common features. (b) The cell
envelope of gram-positive bacteria is a single membrane with a thick, rigid layer of
peptidoglycan on its outside surface. A variety of polysaccharides and other complex
polymers are interwoven with the peptidoglycan, and surrounding the whole is a porous
“solid layer” composed of glycoproteins. (c) E. coli is gram-negative and has a double
membrane. Its outer membrane has a lipopolysaccharide (LPS) on the outer surface and

112

phospholipids on the inner surface. This outer membrane is studded with protein
channels (porins) that allow small molecules, but not proteins, to diffuse through. The
inner (plasma) membrane, made of phospholipids and proteins, is impermeable to both
large and small molecules. Between the inner and outer membranes, in the periplasm, is
a thin layer of peptidoglycan, which gives the cell shape and rigidity, but does not retain
Gram’s stain. (d) Archaeal membranes vary in structure and composition, but all have a
single membrane surrounded by an outer layer that includes either a peptidoglycan-like
structure or a porous protein shell (solid layer), or both. [(a) David S. Goodsell. (b, c, d)
Information from S.-V. Albers and B. H. Meyer, Nature Rev. Microbiol. 9:414, 2011, Fig. 2.]

Bacteria and archaea have group-specific specializations of their
cell envelopes (Fig. 1-5b–d). Some bacteria, called gram-positive
because they are colored by Gram’s stain (introduced by Hans
Christian Gram in 1884), have a thick layer of peptidoglycan
outside their plasma membrane but lack an outer membrane.
Gram-negative bacteria have an outer membrane composed of a
lipid bilayer into which are inserted complex lipopolysaccharides
and proteins called porins that provide transmembrane channels
for the diffusion of low molecular weight compounds and ions
across this outer membrane. The structures outside the plasma
membrane of archaea differ from organism to organism, but they,
too, have a layer of peptidoglycan or protein that confers rigidity
on their cel