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 Preface vii

Teaching and Learning Tools

In addition to providing an engaging contextual framework for the biochemis-
try throughout the book, we have created several opportunities for students to
check their understanding, reinforce connections across the book, and practice
what they have learned. These opportunities present themselves both in features
throughout the text and in the many resources offered in LaunchPad.

ACTIVE LEARNING RESOURCES

In this new edition, we’ve responded to instructor requests to provide
resources that aid in creating an active classroom environment. All of the new
media resources for Biochemistry: A Short Course will be available in our new
system. For more information on LaunchPad see page ix. To
help students adapt to an interactive course, we’ve added the following resources:

NEW Case Studies are a series of online biochemistry case studies that
are assignable and assessable. Authored by Justin Hines, Assistant Professor of
Chemistry at Lafayette College, each case study gives students practice in work-
ing with data, developing critical thinking skills, connecting topics, and applying
knowledge to real scenarios. We also provide instructional guidance with each
case study (with suggestions on how to use the case in the classroom) and aligned
assessment questions for quizzes and exams.

NEW Clicker Questions are aligned with key concepts and misconceptions
in each chapter so instructors can assess student understanding in real time dur-
ing lectures.

END-OF-CHAPTER PROBLEMS
Each chapter includes a robust set of practice problems. We have revised and
added to the total number of questions in the third edition.
• Data Interpretation Problems train students to analyze data and reach
scientific conclusions.
• Chapter Integration Problems draw connections between concepts across
chapters.
• Challenge Problems require calculations, understanding of chemical
structures, and other concepts that are challenging for most students.
Brief solutions to all the end-of-chapter problems are provided in the
“Answers to Problems” section in the back of the textbook. We are also pleased
to offer expanded solutions in the accompanying Student Companion, by Frank
Deis, Nancy Counts Gerber, Richard Gumport, and Roger Koeppe. (For more
details on this supplement see page x.)

MARGIN FEATURES
We use the margin features in the textbook in several ways to help engage stu-
dents, emphasize the relevance of biochemistry to their lives, and make it more
accessible. We have given these features a new look to make them clearer and
more easily identifiable.
 270 15 Metabolism: Basic concepts and Design
Reactive site is reduced to a methylene group in several steps. This sequence of reactions
requires an input6.4ofenzymes Facilitate the Formation of the transition State 103
four electrons:
consequently cannotHalter the H equilibrium of a chemical reaction. Consider an + Enzyme
H2 H2
viii Preface enzyme-catalyzed reaction, the conversion O
12.5 A Major of substrate,
role ofRS,Membrane
into
C product,
R9 P.
Proteins
+ 4H + 4e
C presence + Is to C R9
– Function as Transporters
R C + H2O 215
Figure 6.2 graphs H the rate of product formation with time in the
H2
254 cotransporters.
14 Digestion: Turning a Meal These proteins
into Cellular andcan
Biochemicals be classified
absence N+ as
of enzyme. Noteeither
thatNH anti-
the
2 amount of product A
formed Ois the same A B
O
porters or symporters. Antiporters whether or notOthethe
couple enzyme His present, but, in the present example, the amount
downhill flow CELL

Product
PLearning
•Oof– product Objectives are used in many different
take hours ways in the classroom. To help
LUMEN INTESTINAL The electron donor in most reductive biosyntheses is NADPH, the reduced form
formed in seconds whenNH the enzyme is present might
of one species to the uphillor Oflow of another in the opposite 2 of nicotinamide adenine dinucleotide phosphate (NADP+). NADPH differs from
direction across the membrane; reinforce
centuries
O
HOkeyOH
to
symporters
Why
formconcepts
if
does the rateHuse
the enzyme
N
the flow
of product
while
were
of the
formation
absent student
(Table
NADH in thatisthe
6.1). reading
2′-hydroxyl
level off with time? The reaction
thegroup
chapter we havemoiety
of its adenosine indicated
is esterified with
No enzyme
Triacylglycerols them O P
one species to drive the flow of Oa different
has – with
reached
O
a and ✓ number
speciesN in the same
equilibrium. Substrate S N and
is still integrated
phosphate
SER
being (Figure
converted them
into 15.16).
producton P, a
NADPH chapter level
carries electronsasinwell as in
the same waythe
as NADH.
but P is being convertedO rate suchHowever,
into S Nat aPhospholipids, NADPH
that the amount of isP used almost exclusivelySeconds
remains for reductive biosyntheses, whereas
direction
H 2O
across the membrane section (Figureintroductions.
12.18).
constant. Enzymes accelerate the attainment
They H are also
ofNADH
cholesterol, tied
is used
equilibria but do
to the
primarily end-of-chapter
not shift for
problems
theirthe generation of ATP.Time
to assist
Hours
The extra phosphoryl group
Glucose is moved into students some
positions.animal
The cells
inequilibriumby the
developing sodium-
positionproblem-solving
is and ononly
proteins
a function NADPH skills
of the isfree-energy and
a tag that instructors
enables
differ- enzymes toindistinguish
assessing students’
between high-potential
Lipases HO
reactantsOPO products. by electrons to be used in anabolismFigure 6.2 Enzymes
2–
glucose linked transporter (SGLT), ence between a symporter and3powered and those accelerate
to be used the reaction
in catabolism.
understanding of some of the key concepts
TAG in each chapter.
rate. the
TAGsame equilibrium point is reached but
the simultaneous entry of Figure
Na+. 15.16
This The free-energy
structure of input of 3. An Activated Carrier of Two-Carbon much moreFragments. Coenzyme
quickly in the presence A (also called
of an enzyme.
Na flowing
+
down its concentration gradient
Fatty acids nicotinamide is+sufficient to
adenine dinucleotide
+
CoA-SH), anotherB central molecule in metabolism, is a carrier of acyl groups
Chylomicrons To lymph
phosphate (NADP ). NaDp provides (Figure 15.17). A key constituent of
generate a +66-fold concentration6.4
electrons gradient
FABPEnzymes
for biosynthetic of an uncharged
Facilitate the Formation of theAntiporter
Transition ✓coenzyme
system2 Explain A isrelation
the the vitamin
Symporter betweenpantothenate.
the
FATPpurposes. NoticeTriacylglycerols
Acyl groups are important constituents both in
transition catabolism,
state as insite
and the active theofoxidation
molecule such as glucose (Figure 12.19).
State
that the reactive site isRecall
the samethat the so-
in NaDp +
of fatty12.18
acids, and in anabolism, as an
in enzyme,
the synthesis
and listofthe
membrane lipids. The
characteristics
Monoacylglycerols and NaD+. Figure Antiporters and symporters. Secondary transporters
dium ion gradient was initially generated
The free-energy by thebetween
difference Na+–K +
terminal
reactantscan
and sulfhydryl
products
transport group
accounts
two for inthe
substrates inCoA isof
opposite
active
the sites.site. Acyl groups are linked to
reactive
directions (antiporters) or two
ATPase, demonstrating thatequilibrium
the action of aofreaction,
the secondary
but enzymesac-accelerate howsulfhydryl
the
substratesquickly this
in the equilibrium
group
same of CoAis by
direction thioester bonds. The resulting derivative is
(symporters).
attained. How can we explain the rate enhancement inan terms ofCoA.
thermodynam-
tive transporter depends on the 14.10
Figure primary active
Chylomicron transporter. acids andacyl
formation. Free fattycalled An acyl group
monoacylglycerols often linked to CoA is the acetyl unit; this
are absorbed
ics? To do so, we have to consider not the end points of the reaction but the
called acetyl
derivative
by intestinal epithelial cells. Triacylglycerols are resynthesized andis packaged withCoA.
otherThe ΔG°′
lipids and for the hydrolysis of acetyl CoA has a
chemical pathway between the end points. large negative value:
proteins to form chylomicrons, which are then released into the lymph system.
A chemicalK reaction
+ of substrate+S to form product P goes through a transition
+ + K Na+
state that has+a Na
X‡Na higher free
Na+energy than+ does eitherNa+ SCoA
Acetyl or P. +
The double dagger +
+ H2O m acetate + CoA + H
+ Na Na
Na
3 Na+ denotes the transitionNastate.
+ TheNatransition
+ Namolecular
state is a fleeting structure
Na+ + +
NatheGlucose ΔG°′ = −31.4 kJ mol−1 (−7.5 kcal mol−1)
that is no longer
Na the substrate+but is not+ yet product. The Natransition
+ state is the
Na+ After a meal rich in Nalipids,Nathe blood
least-stable and most-seldom-occurring species appears
along themilky because
reaction pathwayof the high
content
becauseofit chylomicrons.
is the one with theThese
highestparticles
free energy. bind to membrane-bound
Reactive group K+ lipoprotein NH2
N
lipases, primarily at adipose tissue and muscle, where the triacylglycerols –are O –
O
S m X‡ → P OH
once again degraded into free fatty acids and monoacylglycerol H
N
H forHtransport into
N P P N
N
The difference in free energy between the transition state and the substrate is
•called
the Quick
tissue. The Quizzes + emulate
triacylglycerols are thenthatHS momentand
resynthesized in astored.
lectureIn thewhen O a professor
muscle O O asks,
O
N
? QUICk QUIz explain why a person
who has a trypsinogen deficiency will andΔGother
“Do ‡
you
(Figure get
K+ ofNa
the+ free energy
6.3): it?”
K+
activation
K tissues, they can be
These
or simply the activation energy, symbolized
K oxidized to provide energy,
+
questions allow as willObe
students
O
to
by
H 3Cdiscussed
check
CH3
O
in
their
O
understanding of
suffer from more digestion difficulties than
Na+–K+ ATPase Chapter 27.Na Chylomicrons
+
+ also ‡function in SGLT
the transport+ of fat-soluble vitamins 2–O PO
3 OH
will a person lacking most other zymogens. the
and material
Figure 15.17
cholesterol.
A (CoA-SH).
as they coenzyme
The structureKof
+
read
ΔG =itGsoX −they
‡
can immediately
GS-Mercapto-
ethylamine unitNa+
K Pantothenate unitgauge whether they need to
K Glucose
review
Note that athediscussion or can
energy of activation, advance
or ΔG ‡
, does nottoenter
Glucose K+the next topic.
into the final ΔG Answers are given at the
calculation for the reaction,
Na+because the energy that
The had to beof
hydrolysis Ka+thioester
added to reach
is the
thermodynamically more favorable than that of an
ATP + H2O 2 K+
end
ADP +ofPi each
transition state ischapter.
released whenGlucose
the transition state ester,
oxygen becomessuchthe
as product. The acids, because the electrons of the C=O bond
those in fatty
activation energy immediately suggests how enzymes form lessaccelerate the reaction
stable resonance rate
structures with the C−S bond than with the C−O
BIOLOgICAL
without altering ΔG ofInSIgHT
the
Figure 12.19 Secondary transport. The ion gradient set reaction:
up by theenzymes
Na+–K +function to lower the activation
bond.ATPase can be
Consequently, Transition state, X ‡
acetyl CoA has a high acetyl-group-transfer potential be-
energy.
Snake
used to move materials into the cell,
In
O Venoms
through
other words,
the actionDigest enzymes
of aOfrom
facilitate
the Inside
secondary
the •
formation
transporterOutsuch
cause
Margin
of
transfer
the Structures
transition state. provide
of the acetyl group is exergonic.
as the ‡
a quick reminder
Acetyl CoA carries an activated
The combination of substrate and enzyme creates a reaction pathway whose ∆G (uncatalyzed)
Na+–glucose linked transporter, aMost
symporter.
Canimals
transition-state CoAingest
energyfood isClowerand,CoA in response
than
of toagroup,
acetyl
what it would
molecule
this just as ATP
beingestion,
or carries
group
without theproduce
an that
enzyme enzymes
students
activated phosphoryl maygroup. have
∆G‡ (catalyzed)
isseen Additional features ofhaveactivated
thethecarriers are responsible for two key aspects of
R
that digest
(Figure
S
6.3).the food.
Because
H3C
Many
the
S
venomous
activation energysnakes, lower, onearlier
morethe otherin
molecules the
hand, book
do or in another course.
statemetabolism. First, NADH,
will be NADPH, and FADH 2 react slowly with O2 in the absence
Acyl CoA Acetyl CoA Substrate
energy required to reachdigestive
the transition and more product formed

Free energy
opposite. They inject enzymes into
ofThis their
allows
a catalyst. prospective
Likewise, students
ATP meals to
andofacetyltounderstand
begin
CoA are hydrolyzed theslowly
topic at∆G of many
(in times
faster. Decreasing the activation barrier is analogous to lowering the height a
CLInICAL InSIGHT the digestion
O process from O –
the inside out, hours before
orbar. they
even eveninconsume
days) the absence theofmeals.
a catalyst. These moleculesreaction
for the
are kinetically
high-jump bar; more athletes will be able to clear
Snake venom, handsaliva,
the without
The essence needing
of catalysis to look updriving a basic structure
of the a highly + modified form
quiteofstable consists
face of of 50 to 60
C R9 C R9 in the a large thermodynamic force for reaction with O2
+is stabilization
+ O transition O state.Dephosphorylation
Digitalis Inhibits the nadifferent –K
R Pump protein by andBlocking
R
peptideIts components orregard
organic
that differ
to theamongchemistryspeciesFigure principle
of 12.20
snake elsewhere.
Foxglove.
ATP and Foxglove
(in electron carriers) and H2O (for ProductThe kinetic
acetyl CoA).
The interplay between active and transport
possibly
O andamong
even secondary
O– individual activesnakes
The Formation of an Enzyme–Substrate Complex Is the First Step
transport
stability issame
of these
of the molecules (Digitalis
species.inConsider
the absence purpurea) is a catalysts
of specific highly poisonous
is essential for their
especially well illustrated rattlesnakes
by biological function because
a hostit ofenables
plant dueenzymes
to the to control
high the flow ofoffree
concentration
Reaction progress energy and
potent
in theC action of the14.11).
R9(Figure cardiotonic
+ Rattlesnakesteroids. venomHeart contains enzymes
C R9
Enzymatic Catalysis
R S R S reducing power. cardiotonic steroids.
Figure Digitalis,decrease
6.3 Enzymes one of the the most
that
failure can result if the muscles Much digest
in
Oxygenof
the
the
the are tissues
heart
catalytic areof
power the
not victim.
able to Phospholipases
contract
of enzymes comes from with
theirmost digest
binding cell membranes
to and then at
esters stabilized by resonance Second, interchanges of activated
widely used groups
activation
drugs, isin metabolism
energy.
obtained
enzymesfrom are accomplished
foxglove.
accelerate
the
sufficient strength to effectively site
altering of
thethe
pump
structures not snakebite,
blood.
structure
available of the causing
Certain
substrate
to thioesters. atoloss
steroids of
promote cellular
byderived
athe
components.
from
formation
rather small set of the The (Tablereactions
transition
of carriers 15.2). The
by decreasing
existenceΔG‡,of
theafree energy set of
recurring
[roger hall/Shutterstock.]
plants, such as digitalis and phospholipases
ouabain, arealso
state. Thus, the first stepdisrupt
known theismembranes
in catalysis the formationof
as cardiotonic steroids
activated
of red blood
because
carriers cells,
an enzyme–substrate
in all destroying
organisms
(ES)
is onethem
of activation.
of the unifying motifs of biochemistry.
of their ability to strengthen (a process called hemolysis).
heart contractions. Collagenase
Interestingly, digests the protein collagen, a major
cardiotonic
steroids exert their effect by component of
Did YoutheKnow?
• inhibiting connective tissue
Na –K features
+ +
pump. are shorthyaluronidase
(p. 56), whereas asides digests
hyaluronidate, a glycosaminoglycan (p. 178) component of connective DiD You tissue.Know?
Digitalis is a mixture ofto the
cardiotonic
The biochemical
combined
steroids
action of both topic
derived being discussed.
from
collagenase
the dried leaf of
and hyaluronidase is to destroyInterestingly, digitalis was used effectively
292 16 Glycolysis Tymoczko_c06_095-110hr_pv2.0.1.indd
the foxglove plant Digitalis purpurea
103
(Figure 12.20). The compound increases
12/30/14 1:39 PM

They
tissue
derived
atput
the sitea personal
of the bite,face on
enabling science,
the venom or,to spread more readily long before the discovery of the Na+–K+
nuTriTion FACTS the force of contraction heartfrom
ofthroughout muscle the vitamin
Tymoczko_c15_257-280hr1_pv2.0.2.indd niacin, a dietary
and270is consequently requirement
a choice drug for human beings. Con- 1/23/15 1:42 PM

in the treatment of congestive

in the
sequently, heart
vein
NAD the+of
failure.
Biological
victim.
must be regenerated
Inhibition
Insights,
of thefor
Na + provide
glycolysis
–K +
pump
ATPase. In 1785, William Withering, a
to proceed. Thus, the final
Various proteolytic enzymes in the venom degrade basement membranes
British physician, heard tales of an elderly
by digitalis means that Na glimpses
process
+
is not
(a thin
in the of
sheetpumped how
pathway
outiswe
of fibrous
the
of use
the
proteins,
biochemistry
regeneration
cell, of NAD
diminishing
including
+
collagen,
in
thethrough the metabolism
that underlies the
of
epithelial
woman, known as “the old woman of
pyruvate.
Na+ gradient. The reduced everyday
Na +
gradient life. in turn affects the sodium–calcium
cells) and components of the extracellular matrix, leading to severe tissue Shropshire,” who cured people of “dropsy”
Figure 14.11 A rattlesnake poised to
exchanger. This exchanger,
strike. rattlesnakes inject digestive enzymes an
damage. example
Some of secondary
venoms contain active transport,
proteolytic enzymesrelies on
that stimulate (which today would be recognized as
the
Fermentations Are a Means of Oxidizing NADH
into their prospective Na
meals.influx
+
to simultaneously
[Biosphoto/ powerofthe
formation bloodexpulsion of Ca
clots as well from thethat
as+enzymes cell. Theblood clots. congestive
digest The net heart failure) with an extract of
Daniel Heuclin.] diminished Na gradienteffect
+ The sequence
results of in
these of reactions
enzymes
slower from
acting of
extrusion glucose
in Ca
concert
2+ to pyruvate
bymay
the be tois deplete
sodium– similar all
in most organisms
foxglove.
clotting factorsWithering conducted the first
and most types of cells. In contrast, the fate of pyruvate2+is variable. Three reac-
scientific study of the effects of foxglove
calcium exchanger. The subsequent increase in the intracellular level of Ca
tions of pyruvate are of primary importance: conversion into ethanol,onlactate, or heart failure and
congestive
enhances the ability of cardiac muscle and
carbon dioxide to contract.
water (Figure 16.4). The first two reactions aredocumented fermenta- its effectiveness.
tions that take place in the absence of oxygen. Fermentations are ATP-generating
processes in which organic compounds act as both donors and acceptors of elec-
Tymoczko_c14_245-256hr1_pv2.0.2.indd 254
trons. In the presence of oxygen, the most common situation in multicellular 1/23/15 12:27 PM
NiacinAlsocalledvitaminB3,niacinis organisms and for many unicellular ones, pyruvate is metabolized to carbon
acomponentofcoenzymesnAD+ • Nutrition Facts highlight essential vitamins in the margin next to where
dioxide and water through the citric acid cycle and the electron-transport chain
andnADP+(pp.268-270),whichare they are
(Sections discussed
8 and as part of an
9). In these circumstances, enzyme
oxygen acceptsmechanism or metabolic pathway.
electrons and protons
usedinelectron-transferreactions.
Tymoczko_c12_203-224hr1_pv2.0.3.indd 215
Therearemanysourcesofniacin,
toIn these
form water.boxes,
We now students
take a closer will discover
look at these threehow wefates
possible obtain vitamins from our 1/23/15
of pyruvate. 12:25 PM

includingchickenbreast.niacin diets and what happens if we do not have enough of them. These important
deficiencyresultsinthepotentially
fataldiseasepellagra,acondition molecules and their structures
Pyruvate are listed in table form in the appendix of the
characterizedbydermatitis,dementia, book as well, to help students easily
NADH find where each vitamin is discussed in
anddiarrhea.[BrandxPictures]
the book. CO
NAD2+ CO 2

Acetaldehyde Lactate Acetyl CoA

Figure 16.4 Diverse fates of pyruvate.
ethanolandlactatecanbeformedby NADH
reactionsthatincludenADh.Alternatively,a
two-carbonunitfrompyruvatecanbe NAD+
coupledtocoenzymeA(seeChapter18)to Ethanol Further
 Preface ix

Media and Supplements

All of the new media resources for Biochemistry: A Short Course are available in
our new system.
www.macmillanhighered.com/launchpad/tymoczko3e
LaunchPad is a dynamic, fully integrated learning environment that brings
together all of our teaching and learning resources in one place. It includes
easy-to-use, powerful assessment tracking and grading tools, a personalized
calendar, an announcement center, and communication tools to help you man-
age your course. This learning system also contains the fully interactive e-Book
and other newly updated resources for students and instructors, including the
following:

For Students
• Case Studies are a series of online biochemistry case studies that are
assignable and assessable. Authored by Justin Hines, Assistant Professor of
Chemistry at Lafayette College, each case study gives students practice in
working with data, developing critical thinking skills, connecting topics, and
applying knowledge to real scenarios.
• e-Book allows students to read the online version of the textbook, which
combines the contents of the printed book, electronic study tools, and a full
complement of student media specifically created to support the text.
• Hundreds of Self-Graded Practice Problems allow students to test their
understanding of concepts explained in the text, with immediate feedback.
• Metabolic Map helps students understand the principles and applications of
the core metabolic pathways. Students can work through guided tutorials with
embedded assessment questions, or explore the Metabolic Map on their own
using the dragging and zooming functionality of the map.
• Problem-Solving Videos, created by Scott Ensign of Utah State University,
provide 24/7 online problem-solving help to students. Through a two-part
approach, each 10-minute video covers a key textbook problem representing a
topic that students traditionally struggle to master. Dr. Ensign first describes a
proven problem-solving strategy and then applies the strategy to the problem
at hand in clear, concise steps. Students can easily pause, rewind, and review
any steps they wish until they firmly grasp not just the solution but also the
reasoning behind it. Working through the problems in this way is designed to
make students better and more confident at applying key strategies as they solve
other textbook and exam problems.
• Living Figures allow students to view textbook illustrations of protein
structures online in interactive 3-D using Jmol. Students can zoom and rotate 54
“live” structures to get a better understanding of their three-dimensional nature
and can experiment with different display styles (space-filling, ball-and-stick,
ribbon, backbone) by means of a user-friendly interface.
• Self-Assessment Tool allows students to test their understanding by taking
an online multiple-choice quiz provided for each chapter, as well as a general
chemistry review.
• Animated Techniques illustrate laboratory techniques described in the
text.
x Preface

• Learning Curve is a self-assessment tool that helps

students evaluate their progress. Students can test their
understanding by taking an online multiple-choice quiz
provided for each chapter, as well as a general chemistry
review.

For Instructors
All the features listed above for students plus:
• e-Book Instructors teaching from the e-Book can assign
either the entire textbook or a custom version that includes
only the chapters that correspond to their syllabi. They can
choose to add notes to any page of the e-Book and share
these notes with their students. These notes may include
text, animations, or photographs.
• Clicker Questions are aligned with key concepts and misconceptions in
each chapter so instructors can assess student understanding in real time during
lectures.
• Newly Updated Lecture PowerPoint Files have been developed to
minimize preparation time for new users of the book. These files offer suggested
lectures including key illustrations and summaries that instructors can adapt to
their teaching styles.
• Updated Textbook Images and Tables are offered as high-resolution JPEG
files. The JPEGs are also offered in separate PowerPoint files.
• Test Bank, by Harvey Nikkel of Grand Valley State University, Susan Knock
of Texas A&M University at Galveston, and Joseph Provost of Minnesota State
University Moorhead, offers more than 1500 questions in editable Word format.

Student Companion
(1-319-03295-8)
For each chapter of the textbook, the Student Companion includes:
• Chapter Learning Objectives and Summary
• Self-Assessment Problems, including multiple-choice, short-answer,
matching questions, and challenge problems, and their answers
• Expanded Solutions to the end-of-chapter problems in the textbook

CLINICAL INSIGHTS This icon signals the beginning of a Clinical Insight in the text.
Defects in organelle function may lead to disease (p. 14)
Pathological conditions result if protein intake is
inadequate (p. 44)
Defects in collagen structure result in pathological
conditions (p. 57)
Protein misfolding and aggregation are associated with some
neurological diseases (p. 63)
Variations in KM can have physiological consequences (p. 114)
Loss of allosteric control may result in pathological
conditions (p. 123)
Penicillin irreversibly inactivates a key enzyme in bacterial
­cell-wall synthesis (p. 138)
Functional magnetic resonance imaging reveals regions of the
brain processing sensory information (p. 152)
Hemoglobin’s oxygen affinity is adjusted to meet
­environmental needs (p. 154)
Sickle-cell anemia is a disease caused by a mutation in
­hemoglobin (p. 157)
Thalassemia is caused by an imbalanced production of
­hemoglobin chains (p. 159)
Glucose is a reducing sugar (p. 171)
The hormone erythropoietin is a glycoprotein (p. 178)
Proteoglycans are important components of cartilage (p. 179)
Mucins are glycoprotein components of mucus (p. 180)
Lack of glycosylation can result in pathological conditions (p. 182)
Lectins facilitate embryonic development (p. 183)
Influenza virus binds to sialic acid residues (p. 183)
Premature aging can result from the improper attachment of a
hydrophobic group to a protein (p. 199)
Lipid vesicles can be formed from phospholipids (p. 207)
The association of prostaglandin H2 synthase-1 with the
membrane accounts for the action of aspirin (p. 211)
Multidrug resistance highlights a family of membrane pumps
with ATP-binding domains (p. 214)
Harlequin ichthyosis is a dramatic result of a mutation in an
ABC transporter protein (p. 214)
Digitalis inhibits the Na+–K+ pump by blocking its
dephosphorylation (p. 215)
Mutations in protein kinase A can cause Cushing’s
syndrome (p. 230)
Cholera and whooping cough are due to altered G-protein
activity (p. 231)
Some receptors contain tyrosine kinase domains within their
covalent structures (p. 235)
The conversion of proto-oncogenes into oncogenes disrupts
the regulation of cell growth (p. 239)
Protein kinase inhibitors may be effective anticancer
drugs (p. 240)
Protein digestion begins in the stomach (p. 248)
Celiac disease results from the inability to properly digest
­certain proteins (p. 251)
Exercise depends on various means of generating ATP (p. 265)
Lack of activated pantothenate results in neurological
problems (p. 271)
Preface xi
The six-carbon sugar is cleaved into two three-carbon
fragments (p. 287)
Excessive fructose consumption can lead to pathological
conditions (p. 295)
Many adults are intolerant of milk because they are deficient in
lactase (p. 297)
Galactose is highly toxic if the transferase is missing (p. 298)
Aerobic glycolysis is a property of rapidly growing cells (p. 304)
Cancer and exercise training affect glycolysis in a similar
fashion (p. 305)
Insulin fails to inhibit gluconeogenesis in type 2 diabetes (p. 323)
Substrate cycles amplify metabolic signals (p. 323)
Defective regulation of pyruvate dehydrogenase results in lactic
acidosis (p. 338)
Enhanced pyruvate dehydrogenase kinase activity facilitates the
development of cancer (p. 339)
The disruption of pyruvate metabolism is the cause of
beriberi (p. 339)
Defects in the citric acid cycle contribute to the development of
cancer (p. 354)
Loss of iron-sulfur cluster results in Friedreich’s ataxia (p. 371)
ATP synthase can be regulated (p. 395)
Oxidative phosphorylation can be inhibited at many
stages (p. 398)
Mitochondrial diseases are being discovered in increasing
numbers (p. 399)
Hers disease is due to a phosphorylase deficiency (p. 453)
Diabetes mellitus results from insulin insufficiency and
glucagon excess (p. 466)
A biochemical understanding of glycogen-storage diseases is
possible (p. 467)
The pentose phosphate pathway is required for rapid cell
growth (p. 481)
Glucose 6-phosphate dehydrogenase deficiency causes a drug-
induced hemolytic anemia (p. 481)
Triacylglycerols are hydrolyzed by hormone-stimulated
lipases (p. 490)
Pathological conditions result if fatty acids cannot enter the
mitochondria (p. 493)
Ketogenic diets may have therapeutic properties (p. 498)
Diabetes can lead to a life-threatening excess of ketone-body
production (p. 499)
Ketone bodies are a crucial fuel source during
starvation (p. 500)
Some fatty acids may contribute to the development of
pathological conditions (p. 501)
Fatty acid metabolism is altered in tumor cells (p. 513)
A small fatty acid that causes big problems (p. 513)
Aspirin exerts its effects by covalently modifying a key
enzyme (p. 515)
Phosphatidylcholine is an abundant phospholipid (p. 526)
Gangliosides serve as binding sites for pathogens (p. 527)
Disrupted lipid metabolism results in respiratory distress
syndrome and Tay–Sachs disease (p. 528)
xii Preface
The absence of the LDL receptor leads to familial
­hypercholesterolemia and atherosclerosis (p. 536)
Cycling of the LDL receptor is regulated (p. 537)
HDL seems to protect against atherosclerosis (p. 537)
The clinical management of cholesterol levels can be
­understood at a biochemical level (p. 538)
Bile salts facilitate lipid absorption (p. 539)
Vitamin D is necessary for bone development (p. 541)
Androgens can be used to artificially enhance athletic
performance (p. 542)
Blood levels of aminotransferase serve a diagnostic
function (p. 553)
Metabolism in context: inherited defects of the urea cycle cause
hyperammonemia (p. 558)
Inborn errors of metabolism can disrupt amino acid
degradation (p. 565)
Determining the basis of the neurological symptoms of
­phenylketonuria is an active area of research (p. 566)
Tetrahydrofolate carries activated one-carbon units (p. 576)
High homocysteine levels correlate with vascular disease (p. 578)
Salvage pathways recycle pyrimidine bases (p. 589)
Several valuable anticancer drugs block the synthesis of
thymidylate (p. 595)
The synthesis of deoxyribonucleotides is controlled by the
regulation of ribonucleotide reductase (p. 597)
The loss of adenosine deaminase activity results in severe
combined immunodeficiency (p. 598)
Gout is induced by high serum levels of urate (p. 599)
Lesch–Nyhan syndrome is a dramatic consequence of
mutations in a salvage-pathway enzyme (p. 600)
Folic acid deficiency promotes birth defects such as spina
bifida (p. 600)
Damaging DNA can inhibit cancer-cell growth (p. 622)
BIOLOGICAL INSIGHTS This icon signals the beginning of a Biological Insight in the text.
Hemoglobin adaptations allow oxygen transport in extreme
environments (p. 155)
Glucosinolates protect plants and add flavor to our diets (p. 173)
Blood groups are based on protein glycosylation patterns (p. 181)
Membranes of extremophiles are built from ether lipids with
branched chains (p. 197)
Venomous pit vipers use ion channels to generate a thermal
image (p. 216)
Snake venoms digest from the inside out (p. 254)
Fermentations provide usable energy in the absence of
oxygen (p. 294)
Mitochondria are the result of an endosymbiotic event (p. 365)
The dead zone: too much respiration (p. 377)
Regulated uncoupling leads to the generation of heat (p. 396)
Chloroplasts, like mitochondria, arose from an endosymbiotic
event (p. 409)
Chlorophyll in potatoes suggests the presence of a toxin (p. 413)
Many herbicides inhibit the light reactions of
photosynthesis (p. 421)
The separation of DNA strands requires specific helicases and
ATP hydrolysis (p. 630)
Bacterial topoisomerase is a therapeutic target (p. 632)
Telomeres are replicated by telomerase, a specialized
polymerase that carries its own RNA template (p. 639)
Some genetic diseases are caused by the expansion of repeats of
three nucleotides (p. 644)
Many cancers are caused by the defective repair of
DNA (p. 650)
Many potential carcinogens can be detected by their mutagenic
action on bacteria (p. 650)
Some antibiotics inhibit transcription (p. 667)
Many bacterial cells release chemical signals that regulate gene
expression in other cells (p. 670)
Inappropriate enhancer use may cause cancer (p. 680)
Induced pluripotent stem cells can be generated by
­introducing four transcription factors into differentiated
cells (p. 680)
Steroid-hormone receptors are targets for drugs (p. 683)
Mutations that affect pre-mRNA splicing cause disease
(p. 696)
Most human pre-mRNAs can be spliced in alternative ways to
yield different proteins (p. 697)
Mutations in eukaryotic initiation factor 2 cause a curious
pathological condition (p. 730)
Some antibiotics inhibit protein synthesis (p. 730)
Diphtheria toxin blocks protein synthesis in eukaryotes by
inhibiting translocation (p. 731)
Ricin fatally modifies 28S ribosomal RNA (p. 732)
Next-generation sequencing methods enable the rapid
­determination of a complete genome sequence (p. 753)
PCR is a powerful technique in medical diagnostics, forensics,
and studies of molecular evolution (p. 756)
A volcanic eruption can affect photosynthesis worldwide
(p. 432)
Why bread becomes stale: the role of starch (p. 434)
Glycogen depletion coincides with the onset of fatigue
(p. 455)
A deficiency of glucose 6-phosphate dehydrogenase confers an
evolutionary advantage in some circumstances (p. 483)
Hibernation presents nitrogen disposal problems (p. 558)
Urea is not the only means of disposing of excess
nitrogen (p. 559)
Enzymes of the purine-synthesis pathway are associated with
one another in vivo (p. 592)
Many bacterial cells release chemical signals that regulate gene
expression in other cells (p. 670)
RNA editing changes the proteins encoded by mRNA (p. 698)
Next-generation sequencing methods enable the rapid
­determination of a complete genome sequence (p. 753)
PCR is a powerful technique in medical diagnostics, forensics,
and studies of molecular evolution (p. 756)
 Preface xiii

Acknowledgments
Our thanks go to the instructors and professors who have reviewed the ­chapters
of this book. Their sharp eyes and keen insights strongly influenced us as we
wrote and shaped the various drafts of each chapter to create this completed work.

Tabitha Amora, Kris Koudelka,

Ball State University Point Loma Nazarene University
Bynthia Anose, Ramaswamy Krishnamoorthi,
Bethel University Kansas State University
Kimberly Bagley, Isabel Larraza,
SUNY Buffalo State North Park University
David Baker, Linda Luck,
Delta College SUNY Plattsburgh
Michael Barbush, Kumaran Mani,
Baker University University of Wyoming
Ellen Batchelder, Jairam Menon,
Unity College University of Michigan Medical School
Moriah Beck, David Mitchell,
Wichita State University College of Saint Benedict &
Nina Bernstein, Saint John's University
MacEwan University Mautusi Mitra,
Veronic Bezaire, University of West Georgia
Carleton University Ashvin Mohindra,
Mary Bruno, Fleming College
University of Connecticut William Newton,
John Cannon, Virginia Tech
Trinity International University Brian Nichols,
James Cheetham, University of Illinois at Chicago
Carleton University Carleitta Paige-Anderson,
Silvana Constantinescu, Virginia Union University
Marymount California University Janice Pellino,
Peter DiMaria, Carthage College
Delaware State University Ivana Peralta,
Caryn Evilia, Vincennes University
Idaho State University Elizabeth Roberts-Kirchhoff,
Brenda Fredette, University of Detroit Mercy
Medaille College John Rose,
Scott Gabriel, University of Georgia
Viterbo University Martina Rosenberg,
Ratna Gupta, University of New Mexico
Our Lady of the Lake College Tricia Scott,
Sarah Hosch, Dalton State College
Oakland University Richard Sheardy,
Kelly Johanson, Texas Woman's University
Xavier University of Louisiana Kevin Siebenlist,
Marjorie Jones, Marquette University
Illinois State University Matt Thomas,
Susan Knock, State College of Florida
Texas A&M University at Jennifer Tsui,
Galveston Marygrove College
xiv Preface

Timothy Vail, Harvey Wiener,

Northern Arizona University Manchester Community College
Todd Weaver, Marc Wold,
University of Wisconsin–La Crosse University of Iowa
Korin Wheeler, Adele Wolfson,
Santa Clara University Wellesley College

The German scientist, writer, and statesman Johann Wolfgang von Goethe once
remarked, “Thinking is easy, acting is difficult, and to put one’s thoughts into
action is the most difficult thing in the world.” While we may disagree with
Goethe’s assertion that thinking is easy, we emphatically agree with the rest of the
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a book that is clear, welcoming, stimulating, and challenging is, if not the most
difficult thing in the world, still very demanding. This task would be utterly im-
possible without our wonderful colleagues at W. H. Freeman. They are intelligent,
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the pleasure of working with our collaborators at W. H. Freeman on a number of
projects, our appreciation of and gratefulness for their efforts and guidance are as
sincere now as they were when we were inexperienced authors. Our experiences
with this edition have been as delightful and rewarding as our past projects. We
have many people to thank for this experience, some of whom we have worked
with previously and some new to the effort. First, we would like to acknowledge
the encouragement, patience, excellent advice, and good humor of our Publisher,
Kate Ahr Parker. Kate can suggest difficult challenges with such grace and equa-
nimity that we readily accept the challenge. New to our book team is our Senior
Acquisitions Editor, Lauren Schultz. Her unfailing enthusiasm was a source of
support and energy for the author team. New to our book team for this edition is
Heidi Bamatter, our Developmental Editor. Heidi is another in a line of outstand-
ing development editors that we have had the pleasure to work with at Freeman.
Her insight, patience, and guidance made this effort successful and enjoyable.
Elizabeth Geller, Senior Project Editor, managed the flow of the project with ad-
mirable efficiency. Teresa Wilson, our Manuscript Editor, enhanced the literary
consistency and clarity of the text. Vicki Tomaselli, Design Manager, produced a
design and layout that made the book welcoming and accessible. ­Christine Buese
and Jacquelyn Wong, Photo Editor and Photo Researcher, respectively, found the
photographs that helped to achieve one of our main goals—linking biochemistry
to the everyday world of the student while making the text a visual treat. Janice
Donnola, Illustration Coordinator, deftly directed the rendering of new illustra-
tions. Paul Rohloff, Production Manager, made sure the difficulties of schedul-
ing, composition, and manufacturing were readily overcome. We are more ap-
preciative of the sales staff at W. H. Freeman for their enthusiastic support than
we can put into words. Without the efforts of the sales force to persuade profes-
sors to examine our book, all of our own excitement and enthusiasm for this
text would be meaningless. We also thank Susan Winslow. Her vision for science
­textbooks and her skill at gathering exceptional personnel make working with
W. H. Freeman a true pleasure.
Thanks also to our many colleagues at our own institutions as well as through-
out the country who patiently answered our questions and encouraged us on our
quest. Finally, we owe a debt of gratitude to our families. Without their support,
comfort, and understanding, this project could never have been undertaken, let
alone successfully completed.
Brief Contents

PART I SECTION 10 The Light Reactions of

The Molecular Design of Life Photosynthesis and the Calvin Cycle 405
Chapter 22 The Light Reactions 407
SECTION 1 Biochemistry Helps Us Understand
Our World 1 Chapter 23 The Calvin Cycle 427
Chapter 1 Biochemistry and the Unity of Life 3 SECTION 11 Glycogen Metabolism and
Chapter 2 Water, Weak Bonds, and the the Pentose Phosphate Pathway 443
Generation of Order Out of Chaos 17 Chapter 24 Glycogen Degradation 445
SECTION 2 Protein Composition and Structure 35 Chapter 25 Glycogen Synthesis 459
Chapter 3 Amino Acids 37 Chapter 26 The Pentose Phosphate
Pathway 473
Chapter 4 Protein Three-Dimensional Structure 47
Chapter 5 Techniques in Protein Biochemistry 69 SECTION 12 Fatty Acid and Lipid Metabolism 487
Chapter 27 Fatty Acid Degradation 489
SECTION 3 Basic Concepts and Kinetics of
Enzymes 95 Chapter 28 Fatty Acid Synthesis 507
Chapter 6 Basic Concepts of Enzyme Action 97 Chapter 29 Lipid Synthesis: Storage Lipids,
Phospholipids, and Cholesterol 523
Chapter 7 Kinetics and Regulation 111
Chapter 8 Mechanisms and Inhibitors 131 SECTION 13 The Metabolism of Nitrogen-
Chapter 9 Hemoglobin, an Allosteric Protein 149 Containing Molecules 549
Chapter 30 Amino Acid Degradation and
SECTION 4 Carbohydrates and Lipids 165
the Urea Cycle 551
Chapter 10 Carbohydrates 167
Chapter 31 Amino Acid Synthesis 571
Chapter 11 Lipids 189
Chapter 32 Nucleotide Metabolism 585
SECTION 5 Cell Membranes, Channels,
Pumps, and Receptors 203 PART III
Chapter 12 Membrane Structure and Function 205 Synthesizing the Molecules of Life
Chapter 13 Signal-Transduction Pathways 225 SECTION 14 Nucleic Acid Structure
and DNA Replication 605
PART II Chapter 33 The Structure of Informational
Transducing and Storing Energy Macromolecules: DNA and RNA 607
SECTION 6 Basic Concepts and Design Chapter 34 DNA Replication 627
of Metabolism 245 Chapter 35 DNA Repair and Recombination 643
Chapter 14 Digestion: Turning a Meal into
SECTION 15 RNA Synthesis, Processing,
Cellular Biochemicals 247
and Regulation 657
Chapter 15 Metabolism: Basic Concepts
Chapter 36 RNA Synthesis and Regulation
and Design 257
in Bacteria 659
SECTION 7 Glycolysis and Gluconeogenesis 281 Chapter 37 Gene Expression in Eukaryotes 675
Chapter 16 Glycolysis 283 Chapter 38 RNA Processing in Eukaryotes 691
Chapter 17 Gluconeogenesis 313
SECTION 16 Protein Synthesis and
SECTION 8 The Citric Acid Cycle 329 Recombinant DNA Techniques 705
Chapter 18 Preparation for the Cycle 331 Chapter 39 The Genetic Code 707
Chapter 19 Harvesting Electrons from the Chapter 40 The Mechanism of Protein
Cycle 343 Synthesis 721
Chapter 41 Recombinant DNA Techniques 743
SECTION 9 Oxidative Phosphorylation 361
Chapter 20 The Electron-Transport Chain 363
Chapter 21 The Proton-Motive Force 383

xv
Contents

PART I SECTION 2
The Molecular Design of Life Protein Composition and Structure 35

SECTION 1 Chapter 3 Amino Acids 37

Biochemistry Helps Us to Understand Our World 1 Two Different Ways of Depicting Biomolecules
Will Be Used 38
Chapter 1 Biochemistry and the Unity of Life 3 3.1 Proteins Are Built from a Repertoire of
1.1 Living Systems Require a Limited Variety of Atoms 20 Amino Acids 38
and Molecules 4 Most Amino Acids Exist in Two Mirror-Image Forms 38
1.2 There Are Four Major Classes of Biomolecules 5 All Amino Acids Have at Least Two Charged Groups 38
Proteins Are Highly Versatile Biomolecules 5 3.2 Amino Acids Contain a Wide Array of
Nucleic Acids Are the Information Molecules of the Cell 6 Functional Groups 39
Lipids Are a Storage Form of Fuel and Serve as a Barrier 6 Hydrophobic Amino Acids Have Mainly
Carbohydrates Are Fuels and Informational Molecules 7 Hydrocarbon Side Chains 39
1.3 The Central Dogma Describes the Basic Principles Polar Amino Acids Have Side Chains That Contain an
of Biological Information Transfer 7 Electronegative Atom 41
1.4 Membranes Define the Cell and Carry Out Cellular Positively Charged Amino Acids Are Hydrophilic 42
Functions 8 Negatively Charged Amino Acids Have Acidic
Side Chains 43
Biochemical Functions Are Sequestered in Cellular
Compartments 11 The Ionizable Side Chains Enhance Reactivity and
Bonding 43
Some Organelles Process and Sort Proteins and Exchange
Material with the Environment 12 3.3 Essential Amino Acids Must Be Obtained from
Clinical Insight Defects in Organelle Function the Diet 44
May Lead to Disease 14 Clinical Insight Pathological Conditions Result
If Protein Intake Is Inadequate 44
Chapter 2 Water, Weak Bonds, and the
Generation of Order Out of Chaos 17 Chapter 4 Protein Three-Dimensional
2.1 Thermal Motions Power Biological Interactions 18 Structure 47
2.2 Biochemical Interactions Take Place 4.1 Primary Structure: Amino Acids Are Linked
in an Aqueous Solution 18 by Peptide Bonds to Form Polypeptide Chains 48
Proteins Have Unique Amino Acid Sequences
2.3 Weak Interactions Are Important Biochemical
Specified by Genes 49
Properties 20
Polypeptide Chains Are Flexible Yet Conformationally
Electrostatic Interactions Are Between Electrical Charges 20
Restricted 50
Hydrogen Bonds Form Between an Electronegative
Atom and Hydrogen 21
4.2 Secondary Structure: Polypeptide Chains
Can Fold into Regular Structures 52
van der Waals Interactions Depend on Transient
Asymmetry in Electrical Charge 21 The Alpha Helix Is a Coiled Structure Stabilized by
Intrachain Hydrogen Bonds 52
Weak Bonds Permit Repeated Interactions 22
Beta Sheets Are Stabilized by Hydrogen Bonding
2.4 Hydrophobic Molecules Cluster Together 22 Between Polypeptide Strands 53
Membrane Formation Is Powered by the Polypeptide Chains Can Change Direction by
Hydrophobic Effect 23 Making Reverse Turns and Loops 55
Protein Folding Is Powered by the Hydrophobic Effect 24 Fibrous Proteins Provide Structural Support for
Functional Groups Have Specific Chemical Properties 24 Cells and Tissues 55
2.5 pH Is an Important Parameter of Clinical Insight Defects in Collagen Structure
Biochemical Systems 26 Result in Pathological Conditions 57
Water Ionizes to a Small Extent 26 4.3 Tertiary Structure: Water-Soluble Proteins Fold
An Acid Is a Proton Donor, Whereas a Base Is a into Compact Structures 57
Proton Acceptor 27 Myoglobin Illustrates the Principles of Tertiary Structure 57
Acids Have Differing Tendencies to Ionize 27 The Tertiary Structure of Many Proteins Can Be
Buffers Resist Changes in pH 28 Divided into Structural and Functional Units 59
Buffers Are Crucial in Biological Systems 29 4.4 Quaternary Structure: Multiple Polypeptide
Making Buffers Is a Common Laboratory Practice 30 Chains Can Assemble into a Single Protein 59

xvi
 Contents xvii
4.5 The Amino Acid Sequence of a Protein 6.4 Enzymes Facilitate the Formation of
Determines Its Three-Dimensional Structure 60 the Transition State 103
Proteins Fold by the Progressive Stabilization of The Formation of an Enzyme–Substrate Complex Is
Intermediates Rather Than by Random Search 61 the First Step in Enzymatic Catalysis 103
Some Proteins Are Inherently Unstructured and Can The Active Sites of Enzymes Have Some Common Features 104
Exist in Multiple Conformations 62 The Binding Energy Between Enzyme and Substrate Is
Clinical Insight Protein Misfolding and Aggregation Important for Catalysis 105
Are Associated with Some Neurological Diseases 63 Transition-State Analogs Are Potent Inhibitors of Enzyme 106
Chapter 5 Techniques in Protein Biochemistry 69
Chapter 7 Kinetics and Regulation 111
5.1 The Proteome Is the Functional Representation
7.1 Kinetics Is the Study of Reaction Rates 112
of the Genome 70
7.2 The Michaelis–Menten Model Describes
5.2 The Purification of a Protein Is the First Step in
the Kinetics of Many Enzymes 113
Understanding Its Function 70
Clinical Insight Variations in KM Can Have
Proteins Can Be Purified on the Basis of Differences in
Physiological Consequences 114
Their Chemical Properties 71
KM and Vmax Values Can Be Determined by Several Means 115
Proteins Must Be Removed from the Cell to Be Purified 71
KM and Vmax Values Are Important Enzyme Characteristics 115
Proteins Can Be Purified According to Solubility, Size,
Charge, and Binding Affinity 72 kcat/KM Is a Measure of Catalytic Efficiency 116
Proteins Can Be Separated by Gel Electrophoresis and Most Biochemical Reactions Include Multiple Substrates 117
Displayed 74 7.3 Allosteric Enzymes Are Catalysts and Information
A Purification Scheme Can Be Quantitatively Evaluated 77 Sensors 118
5.3 Immunological Techniques Are Used to Purify Allosteric Enzymes Are Regulated by Products of
and Characterize Proteins 78 the Pathways Under Their Control 120
Centrifugation Is a Means of Separating Proteins 78 Allosterically Regulated Enzymes Do Not Conform to
Gradient Centrifugation Provides an Assay for the Michaelis–Menten Kinetics 121
Estradiol–Receptor Complex 79 Allosteric Enzymes Depend on Alterations in Quaternary
Antibodies to Specific Proteins Can Be Generated 80 Structure 121
Monoclonal Antibodies with Virtually Any Desired Regulator Molecules Modulate the R m T Equilibrium 122
Specificity Can Be Readily Prepared 81 The Sequential Model Also Can Account for
The Estrogen Receptor Can Be Purified by Allosteric Effects 123
Immunoprecipitation 83 Clinical Insight Loss of Allosteric Control May
Proteins Can Be Detected and Quantified with Result in Pathological Conditions 123
the Use of an Enzyme-Linked Immunosorbent Assay 84 7.4 Enzymes Can Be Studied One Molecule at a Time 123
Western Blotting Permits the Detection of Proteins
Separated by Gel Electrophoresis 84 Chapter 8 Mechanisms and Inhibitors 131
5.4 Determination of Primary Structure Facilitates 8.1 A Few Basic Catalytic Strategies Are Used by
an Understanding of Protein Function 86 Many Enzymes 131
Mass Spectrometry Can Be Used to Determine a 8.2 Enzyme Activity Can Be Modulated by
Protein’s Mass, Identity, and Sequence 88 Temperature, pH, and Inhibitory Molecules 132
Amino Acids Are Sources of Many Kinds of Insight 90 Temperature Enhances the Rate of Enzyme-Catalyzed
Reactions 132
SECTION 3
Most Enzymes Have an Optimal pH 133
Basic Concepts and Kinetics of Enzymes 95
Enzymes Can Be Inhibited by Specific Molecules 134
Chapter 6 Basic Concepts of Enzyme Action 97 Reversible Inhibitors Are Kinetically Distinguishable 135
6.1 Enzymes Are Powerful and Highly Specific Catalysts 97 Irreversible Inhibitors Can Be Used to Map
Proteolytic Enzymes Illustrate the Range of Enzyme the Active Site 137
Specificity 98 Clinical Insight Penicillin Irreversibly Inactivates a
There Are Six Major Classes of Enzymes 98 Key Enzyme in Bacterial Cell-Wall Synthesis 138
6.2 Many Enzymes Require Cofactors for Activity 99 8.3 Chymotrypsin Illustrates Basic Principles of
6.3 Gibbs Free Energy Is a Useful Thermodynamic Catalysis and Inhibition 140
Function for Understanding Enzymes 100 Serine 195 Is Required for Chymotrypsin Activity 140
The Free-Energy Change Provides Information About Chymotrypsin Action Proceeds in Two Steps Linked by a
the Spontaneity but Not the Rate of a Reaction 100 Covalently Bound Intermediate 141
The Standard Free-Energy Change of a Reaction Is The Catalytic Role of Histidine 57 Was Demonstrated by
Related to the Equilibrium Constant 101 Affinity Labeling 142
Enzymes Alter the Reaction Rate but Not the Reaction Serine Is Part of a Catalytic Triad That Includes
Equilibrium 102 Histidine and Aspartic Acid 142
xviii Contents
Chapter 9 Hemoglobin, an Allosteric Protein 149 Biological Insight Blood Groups Are Based on
9.1 Hemoglobin Displays Cooperative Behavior 150 Protein Glycosylation Patterns 181
9.2 Myoglobin and Hemoglobin Bind Oxygen in Clinical Insight Lack of Glycosylation Can Result
in Pathological Conditions 182
Heme Groups 150
Clinical Insight Functional Magnetic Resonance 10.4 Lectins Are Specific Carbohydrate-Binding
Imaging Reveals Regions of the Brain Processing Proteins 182
Sensory Information 152 Lectins Promote Interactions Between Cells 183
9.3 Hemoglobin Binds Oxygen Cooperatively 152 Clinical Insight Lectins Facilitate Embryonic
Development 183
9.4 An Allosteric Regulator Determines the
Oxygen Affinity of Hemoglobin 154 Clinical Insight Influenza Virus Binds to
Sialic Acid Residues 183
Clinical Insight Hemoglobin’s Oxygen Affinity Is
Adjusted to Meet Environmental Needs 154
Chapter 11 Lipids 189
Biological Insight Hemoglobin Adaptations Allow
Oxygen Transport in Extreme Environments 155 11.1 Fatty Acids Are a Main Source of Fuel 190
9.5 Hydrogen Ions and Carbon Dioxide Promote the Fatty Acids Vary in Chain Length and Degree of
Unsaturation 191
Release of Oxygen 155
The Degree and Type of Unsaturation Are Important
9.6 Mutations in Genes Encoding Hemoglobin
to Health 192
Subunits Can Result in Disease 156
11.2 Triacylglycerols Are the Storage Form of
Clinical Insight Sickle-Cell Anemia Is a Disease
Caused by a Mutation in Hemoglobin 157
Fatty Acids 193
NEW Clinical Insight Thalassemia is Caused by an 11.3 There Are Three Common Types of
Imbalanced Production of Hemoglobin Chains 159 Membrane Lipids 194
Phospholipids Are the Major Class of
SECTION 4 Membrane Lipids 194
Carbohydrates and Lipids 165 Membrane Lipids Can Include Carbohydrates 196
Chapter 10 Carbohydrates 167 Steroids Are Lipids That Have a Variety of Roles 196
Biological Insight Membranes of Extremophiles
10.1 Monosaccharides Are the Simplest Carbohydrates 168
Are Built from Ether Lipids with Branched Chains 197
Many Common Sugars Exist in Cyclic Forms 169
Membrane Lipids Contain a Hydrophilic and
NEW Pyranose and Furanose Rings Can Assume a Hydrophobic Moiety 197
Different Conformations 171
Some Proteins Are Modified by the Covalent
NEW Clinical Insight Glucose Is a Reducing Sugar 171 Attachment of Hydrophobic Groups 198
Monosaccharides Are Joined to Alcohols and Clinical Insight Premature Aging Can Result from
Amines Through Glycosidic Bonds 172 the Improper Attachment of a Hydrophobic Group
Biological Insight Glucosinolates Protect Plants to a Protein 199
and Add Flavor to Our Diets 173
10.2 Monosaccharides Are Linked to Form Complex SECTION 5
Carbohydrates 173
Cell Membranes, Channels, Pumps, and
Specific Enzymes Are Responsible for Oligosaccharide
Assembly 173
Receptors 203
Sucrose, Lactose, and Maltose Are the Common
Disaccharides 174
Chapter 12 Membrane Structure and
Glycogen and Starch Are Storage Forms of Glucose 175 Function 205
Cellulose, a Structural Component of Plants, Is 12.1 Phospholipids and Glycolipids Form
Made of Chains of Glucose 175 Bimolecular Sheets 206
10.3 Carbohydrates Are Attached to Proteins to Clinical Insight Lipid Vesicles Can Be Formed
Form Glycoproteins 177 from Phospholipids 207
Carbohydrates May Be Linked to Asparagine, Serine, or Lipid Bilayers Are Highly Impermeable to Ions and
Threonine Residues of Proteins 177 Most Polar Molecules 207
Clinical Insight The Hormone Erythropoietin Is a 12.2 Membrane Fluidity Is Controlled by Fatty Acid
Glycoprotein 178 Composition and Cholesterol Content 208
Proteoglycans, Composed of Polysaccharides and 12.3 Proteins Carry Out Most Membrane Processes 209
Protein, Have Important Structural Roles 178 Proteins Associate with the Lipid Bilayer in
Clinical Insight Proteoglycans Are Important a Variety of Ways 209
Components of Cartilage 179 Clinical Insight The Association of Prostaglandin H2
Clinical Insight Mucins Are Glycoprotein Synthase-l with the Membrane Accounts for
Components of Mucus 180 the Action of Aspirin 211
 Contents xix
12.4 Lipids and Many Membrane Proteins Diffuse The Activated Insulin-Receptor Kinase Initiates a Kinase
Laterally in the Membrane 211 Cascade 237
12.5 A Major Role of Membrane Proteins Is to Insulin Signaling Is Terminated by the Action of
Function As Transporters 212 Phosphatases 238
The Na+–K+ ATPase Is an Important Pump in 13.5 Calcium Ion Is a Ubiquitous Cytoplasmic
Many Cells 213 Messenger 238
Clinical Insight Multidrug Resistance Highlights 13.6 Defects in Signaling Pathways Can Lead to
a Family of Membrane Pumps with ATP-Binding Diseases 239
Domains 214 Clinical Insight The Conversion of
Clinical Insight Harlequin Ichthyosis Is a Dramatic Proto-oncogenes into Oncogenes Disrupts
Result of a Mutation in an ABC Transporter Protein 214 the Regulation of Cell Growth 239
Secondary Transporters Use One Concentration Clinical Insight Protein Kinase Inhibitors May
Gradient to Power the Formation of Another 214 Be Effective Anticancer Drugs 240
Clinical Insight Digitalis Inhibits the Na+-K+ Pump
by Blocking Its Dephosphorylation 215 PART II
Specific Channels Can Rapidly Transport Ions Across Transducing and Storing Energy
Membranes 216
Biological Insight Venomous Pit Vipers Use Ion SECTION 6
Channels to Generate a Thermal Image 216 Basic Concepts and Design of Metabolism 245
The Structure of the Potassium Ion Channel Reveals
the Basis of Ion Specificity 216
Chapter 14 Digestion: Turning a Meal into
The Structure of the Potassium Ion Channel Explains
Cellular Biochemicals 247
Its Rapid Rate of Transport 218 14.1 Digestion Prepares Large Biomolecules for
Use in Metabolism 247
Chapter 13 Signal-Transduction Pathways 225 Most Digestive Enzymes Are Secreted as Inactive
13.1 Signal Transduction Depends on Molecular Precursors 248
Circuits 225 14.2 Proteases Digest Proteins into Amino Acids and
13.2 Receptor Proteins Transmit Information into Peptides 248
the Cell 227 NEW Clinical Insight Protein Digestion Begins in the
Seven-Transmembrane-Helix Receptors Change Stomach 248
Conformation in Response to Ligand Binding and NEW Protein Digestion Continues in the Intestine 249
Activate G Proteins 227 NEW Clinical Insight Celiac Disease Results from
Ligand Binding to 7TM Receptors Leads to the the Inability to Properly Digest Certain Proteins 251
Activation of G Proteins 228 14.3 Dietary Carbohydrates Are Digested by
Activated G Proteins Transmit Signals by Binding to Alpha-Amylase 251
Other Proteins 229 14.4 The Digestion of Lipids Is Complicated by
Cyclic AMP Stimulates the Phosphorylation of Their Hydrophobicity 252
Many Target Proteins by Activating Protein Kinase A 229 Biological Insight Snake Venoms Digest from
NEW Clinical Insight Mutations in Protein Kinase A the Inside Out 254
Can Cause Cushing’s Syndrome 230
G Proteins Spontaneously Reset Themselves Chapter 15 Metabolism: Basic Concepts and
Through GTP Hydrolysis 230 Design 257
Clinical Insight Cholera and Whooping Cough Are 15.1 Energy Is Required to Meet Three
Due to Altered G-Protein Activity 231 NEW Fundamental Needs 258
The Hydrolysis of Phosphatidylinositol Bisphosphate by 15.2 Metabolism Is Composed of Many
Phospholipase C Generates Two Second Messengers 232 Interconnecting Reactions 258
13.3 Some Receptors Dimerize in Response to Ligand Metabolism Consists of Energy-Yielding Reactions and
Binding and Recruit Tyrosine Kinases 233 Energy-Requiring Reactions 259
Receptor Dimerization May Result in Tyrosine Kinase A Thermodynamically Unfavorable Reaction Can
Recruitment 233 Be Driven by a Favorable Reaction 260
Clinical Insight Some Receptors Contain Tyrosine 15.3 ATP Is the Universal Currency of Free Energy 260
Kinase Domains Within Their Covalent Structures 235
ATP Hydrolysis Is Exergonic 261
Ras Belongs to Another Class of Signaling G Proteins 236
ATP Hydrolysis Drives Metabolism by Shifting
13.4 Metabolism in Context: Insulin Signaling the Equilibrium of Coupled Reactions 261
Regulates Metabolism 236 The High Phosphoryl-Transfer Potential of
The Insulin Receptor Is a Dimer That Closes Around ATP Results from Structural Differences Between
a Bound Insulin Molecule 236 ATP and Its Hydrolysis Products 263
xx Contents
Phosphoryl-Transfer Potential Is an Important Form of Clinical Insight Galactose Is Highly Toxic If the
Cellular Energy Transformation 264 Transferase Is Missing 298
Clinical Insight Exercise Depends on Various 16.4 The Glycolytic Pathway Is Tightly Controlled 299
Means of Generating ATP 265 Glycolysis in Muscle Is Regulated by Feedback
Phosphates Play a Prominent Role in Inhibition to Meet the Need for ATP 299
Biochemical Processes 266 The Regulation of Glycolysis in the Liver
15.4 The Oxidation of Carbon Fuels Is an Corresponds to the Biochemical Versatility of
Important Source of Cellular Energy 266 the Liver 300
Carbon Oxidation Is Paired with a Reduction 266 A Family of Transporters Enables Glucose to Enter and
Compounds with High Phosphoryl-Transfer Potential Leave Animal Cells 303
Can Couple Carbon Oxidation to ATP Synthesis 267 NEW Clinical Insight Aerobic Glycolysis Is a
Property of Rapidly Growing Cells 304
15.5 Metabolic Pathways Contain Many Recurring
Motifs 268 Clinical Insight Cancer and Exercise Training Affect
Glycolysis in a Similar Fashion 305
Activated Carriers Exemplify the Modular Design and
Economy of Metabolism 268 16.5 Metabolism in Context: Glycolysis Helps
Clinical Insight Lack of Activated Pantothenate
Pancreatic Beta Cells Sense Glucose 305
Results in Neurological Problems 271 Chapter 17 Gluconeogenesis 313
Many Activated Carriers Are Derived from Vitamins 271 17.1 Glucose Can Be Synthesized from
15.6 Metabolic Processes Are Regulated in Noncarbohydrate Precursors 314
Three Principal Ways 273 Gluconeogenesis Is Not a Complete Reversal of
The Amounts of Enzymes Are Controlled 274 Glycolysis 314
Catalytic Activity Is Regulated 274 The Conversion of Pyruvate into Phosphoenolpyruvate
The Accessibility of Substrates Is Regulated 275 Begins with the Formation of Oxaloacetate 316
Oxaloacetate Is Shuttled into the Cytoplasm and
SECTION 7 Converted into Phosphoenolpyruvate 317
Glycolysis and Gluconeogenesis 281 The Conversion of Fructose 1,6-bisphosphate into
Fructose 6-phosphate and Orthophosphate Is an
Chapter 16 Glycolysis 283 Irreversible Step 318
16.1 Glycolysis Is an Energy-Conversion Pathway 284 The Generation of Free Glucose Is an Important
Hexokinase Traps Glucose in the Cell and Control Point 319
Begins Glycolysis 284 Six High-Transfer-Potential Phosphoryl Groups Are
Fructose 1,6-bisphosphate Is Generated from Glucose Spent in Synthesizing Glucose from Pyruvate 319
6-phosphate 286 17.2 Gluconeogenesis and Glycolysis Are
Clinical Insight The Six-Carbon Sugar Is Cleaved Reciprocally Regulated 320
into Two Three-Carbon Fragments 287 Energy Charge Determines Whether Glycolysis or
The Oxidation of an Aldehyde Powers the Formation Gluconeogenesis Will Be More Active 320
of a Compound Having High Phosphoryl-Transfer The Balance Between Glycolysis and Gluconeogenesis
Potential 288 in the Liver Is Sensitive to Blood-Glucose
ATP Is Formed by Phosphoryl Transfer from Concentration 321
1,3-Bisphosphoglycerate 289 Clinical Insight Insulin Fails to Inhibit
Additional ATP Is Generated with the Formation Gluconeogenesis in Type 2 Diabetes 323
of Pyruvate 290 Clinical Insight Substrate Cycles Amplify
Two ATP Molecules Are Formed in the Conversion Metabolic Signals 323
of Glucose into Pyruvate 291 17.3 Metabolism in Context: Precursors Formed by
16.2 NAD+ Is Regenerated from the Metabolism of Muscle Are Used by Other Organs 324
Pyruvate 291
SECTION 8
Fermentations Are a Means of Oxidizing NADH 292
The Citric Acid Cycle 329
Biological Insight Fermentations Provide Usable
Energy in the Absence of Oxygen 294 Chapter 18 Preparation for the Cycle 331
16.3 Fructose and Galactose Are Converted into 18.1 Pyruvate Dehydrogenase Forms Acetyl
Glycolytic Intermediates 294 Coenzyme A from Pyruvate 332
NEW Fructose Is Converted into Glycolytic Intermediates The Synthesis of Acetyl Coenzyme A from
by Fructokinase 295 Pyruvate Requires Three Enzymes and
NEW Clinical Insight Excessive Fructose Five Coenzymes 333
Consumption Can Lead to Pathological Conditions 295 Flexible Linkages Allow Lipoamide to Move Between
NEW Galactose Is Converted into Glucose 6-phosphate 296 Different Active Sites 335
Clinical Insight Many Adults Are Intolerant of Milk 18.2 The Pyruvate Dehydrogenase Complex Is
Because They Are Deficient in Lactase 297 Regulated by Two Mechanisms 337
 Contents xxi
Clinical Insight Defective Regulation of Pyruvate The Electron-Transport Chain Is a Series of
Dehydrogenase Results in Lactic Acidosis 338 Coupled Oxidation–Reduction Reactions 368
Clinical Insight Enhanced Pyruvate NEW Clinical Insight Loss of Iron-Sulfur Cluster
Dehydrogenase Kinase Activity Facilitates the Results in Friedreich’s Ataxia 371
Development of Cancer 339
20.3 The Respiratory Chain Consists of Proton
Clinical Insight The Disruption of Pyruvate Pumps and a Physical Link to the Citric
Metabolism Is the Cause of Beriberi 339
Acid Cycle 371
The High-Potential Electrons of NADH Enter
Chapter 19 Harvesting Electrons from the Respiratory Chain at NADH-Q Oxidoreductase 371
the Cycle 343 Ubiquinol Is the Entry Point for Electrons from
19.1 The Citric Acid Cycle Consists of Two Stages 344 FADH2 of Flavoproteins 373
19.2 Stage One Oxidizes Two Carbon Atoms to Electrons Flow from Ubiquinol to Cytochrome c
Gather Energy-Rich Electrons 344 Through Q-Cytochrome c Oxidoreductase 373
Citrate Synthase Forms Citrate from Oxaloacetate and The Q Cycle Funnels Electrons from a Two-Electron
Acetyl Coenzyme A 344 Carrier to a One-Electron Carrier and Pumps Protons 374
The Mechanism of Citrate Synthase Prevents Cytochrome c Oxidase Catalyzes the Reduction of
Undesirable Reactions 345 Molecular Oxygen to Water 375
Citrate Is Isomerized into Isocitrate 346 Biological Insight The Dead Zone: Too Much
Isocitrate Is Oxidized and Decarboxylated to Respiration 377
Alpha-Ketoglutarate 346 Toxic Derivatives of Molecular Oxygen Such As Superoxide
Succinyl Coenzyme A Is Formed by the Oxidative Radical Are Scavenged by Protective Enzymes 377
Decarboxylation of Alpha-Ketoglutarate 347
19.3 Stage Two Regenerates Oxaloacetate and
Chapter 21 The Proton-Motive Force 383
Harvests Energy-Rich Electrons 347
21.1 A Proton Gradient Powers the Synthesis of ATP 384
A Compound with High Phosphoryl-Transfer
Potential Is Generated from Succinyl Coenzyme A 347 ATP Synthase Is Composed of a Proton-Conducting
Unit and a Catalytic Unit 385
Succinyl Coenzyme A Synthetase Transforms
Types of Biochemical Energy 348 Proton Flow Through ATP Synthase Leads to the
Oxaloacetate Is Regenerated by the Oxidation of Release of Tightly Bound ATP 386
Succinate 349 Rotational Catalysis Is the World’s Smallest
The Citric Acid Cycle Produces High-Transfer-Potential Molecular Motor 387
Electrons, an ATP, and Carbon Dioxide 349 Proton Flow Around the c Ring Powers ATP
19.4 The Citric Acid Cycle Is Regulated 352 Synthesis 388
The Citric Acid Cycle Is Controlled at Several Points 352 21.2 Shuttles Allow Movement Across
The Citric Acid Cycle Is a Source of Biosynthetic Mitochondrial Membranes 390
Precursors 353 Electrons from Cytoplasmic NADH Enter
The Citric Acid Cycle Must Be Capable of Being Rapidly Mitochondria by Shuttles 390
Replenished 353 The Entry of ADP into Mitochondria Is Coupled to
Clinical Insight Defects in the Citric Acid Cycle the Exit of ATP 392
Contribute to the Development of Cancer 354 Mitochondrial Transporters Allow Metabolite Exchange
19.5 The Glyoxylate Cycle Enables Plants and Between the Cytoplasm and Mitochondria 393
Bacteria to Convert Fats into Carbohydrates 355 21.3 Cellular Respiration Is Regulated by
the Need for ATP 393
SECTION 9 The Complete Oxidation of Glucose Yields About
Oxidative Phosphorylation 361 30 Molecules of ATP 393
The Rate of Oxidative Phosphorylation Is Determined
Chapter 20 The Electron-Transport Chain 363 by the Need for ATP 395
20.1 Oxidative Phosphorylation in Eukaryotes
NEW Clinical Insight ATP Synthase Can Be
Takes Place in Mitochondria 364
Regulated 395
Mitochondria Are Bounded by a Double Membrane 364
Biological Insight Mitochondria Are the Biological Insight Regulated Uncoupling Leads to
Result of an Endosymbiotic Event 365 the Generation of Heat 396

20.2 Oxidative Phosphorylation Depends on Electron Clinical Insight Oxidative Phosphorylation Can Be
Transfer 366 Inhibited at Many Stages 398
The Electron-Transfer Potential of an Electron Is Clinical Insight Mitochondrial Diseases Are Being
Measured as Redox Potential 366 Discovered in Increasing Numbers 399
Electron Flow Through the Electron-Transport Power Transmission by Proton Gradients Is a
Chain Creates a Proton Gradient 367 Central Motif of Bioenergetics 400
xxii Contents
SECTION 10 Thioredoxin Plays a Key Role in Regulating
The Light Reactions of Photosynthesis and the Calvin Cycle 435
the Calvin Cycle 405 Rubisco Also Catalyzes a Wasteful Oxygenase Reaction 436
The C4 Pathway of Tropical Plants Accelerates
Chapter 22 The Light Reactions 407 Photosynthesis by Concentrating Carbon Dioxide 436
22.1 Photosynthesis Takes Place in Chloroplasts 408 Crassulacean Acid Metabolism Permits Growth in Arid
Biological Insight Chloroplasts, Like Mitochondria, Ecosystems 438
Arose from an Endosymbiotic Event 409
SECTION 11
22.2 Photosynthesis Transforms Light Energy into
Glycogen Metabolism and the Pentose
Chemical Energy 409
Phosphate Pathway 443
Chlorophyll Is the Primary Receptor in Most
Photosynthetic Systems 410 Chapter 24 Glycogen Degradation 445
Light-Harvesting Complexes Enhance the Efficiency
24.1 Glycogen Breakdown Requires Several Enzymes 446
of Photosynthesis 411
Phosphorylase Cleaves Glycogen to Release Glucose
Biological Insight Chlorophyll in Potatoes
1-phosphate 446
Suggests the Presence of a Toxin 413
A Debranching Enzyme Also Is Needed for
22.3 Two Photosystems Generate a Proton the Breakdown of Glycogen 447
Gradient and NADPH 413
Phosphoglucomutase Converts Glucose 1-phosphate
Photosystem I Uses Light Energy to Generate Reduced into Glucose 6-phosphate 448
Ferredoxin, a Powerful Reductant 414
Liver Contains Glucose 6-phosphatase,
Photosystem II Transfers Electrons to a Hydrolytic Enzyme Absent from Muscle 448
Photosystem I and Generates a Proton Gradient 415
24.2 Phosphorylase Is Regulated by Allosteric
Cytochrome b6 f Links Photosystem II to
Interactions and Reversible Phosphorylation 449
Photosystem I 416
Liver Phosphorylase Produces Glucose for Use by
The Oxidation of Water Achieves Oxidation–Reduction Other Tissues 449
Balance and Contributes Protons to the Proton
Muscle Phosphorylase Is Regulated by
Gradient 416
the Intracellular Energy Charge 450
22.4 A Proton Gradient Drives ATP Synthesis 418
Biochemical Characteristics of Muscle Fiber Types Differ 451
The ATP Synthase of Chloroplasts Closely Resembles
NEW Phosphorylation Promotes the Conversion of
That of Mitochondria 418
Phosphorylase b to Phosphorylase a 451
NEW The Activity of Chloroplast ATP Synthase Is
Phosphorylase Kinase Is Activated by
Regulated 419
Phosphorylation and Calcium Ions 452
Cyclic Electron Flow Through Photosystem I Leads
Clinical Insight Hers Disease Is Due to a
to the Production of ATP Instead of NADPH 419
Phosphorylase Deficiency 453
The Absorption of Eight Photons Yields One O2 ,
Two NADPH, and Three ATP Molecules 420
24.3 Epinephrine and Glucagon Signal
the Need for Glycogen Breakdown 453
The Components of Photosynthesis Are
Highly Organized 421 G Proteins Transmit the Signal for the Initiation
of Glycogen Breakdown 453
Biological Insight Many Herbicides Inhibit the
Light Reactions of Photosynthesis 421 Glycogen Breakdown Must Be Rapidly Turned
Off When Necessary 455
Chapter 23 The Calvin Cycle 427 Biological Insight Glycogen Depletion Coincides
with the Onset of Fatigue 455
23.1 The Calvin Cycle Synthesizes Hexoses from
Carbon Dioxide and Water 428 Chapter 25 Glycogen Synthesis 459
Carbon Dioxide Reacts with Ribulose
25.1 Glycogen Is Synthesized and Degraded by
1,5-bisphosphate to Form Two Molecules of
3-Phosphoglycerate 429
Different Pathways 459
UDP-Glucose Is an Activated Form of Glucose 460
Hexose Phosphates Are Made from
Phosphoglycerate, and Ribulose 1,5-bisphosphate Glycogen Synthase Catalyzes the Transfer of
Is Regenerated 430 Glucose from UDP-Glucose to a Growing Chain 460
Three Molecules of ATP and Two Molecules of A Branching Enzyme Forms Alpha-1,6 Linkages 461
NADPH Are Used to Bring Carbon Dioxide to Glycogen Synthase Is the Key Regulatory Enzyme
the Level of a Hexose 430 in Glycogen Synthesis 461
Biological Insight A Volcanic Eruption Can Affect Glycogen Is an Efficient Storage Form of Glucose 462
Photosynthesis Worldwide 432 25.2 Metabolism in Context: Glycogen Breakdown
Starch and Sucrose Are the Major Carbohydrate and Synthesis Are Reciprocally Regulated 462
Stores in Plants 433 Protein Phosphatase 1 Reverses the Regulatory
Biological Insight Why Bread Becomes Stale: Effects of Kinases on Glycogen Metabolism 462
The Role of Starch 434 Insulin Stimulates Glycogen Synthesis by Inactivating
23.2 The Calvin Cycle Is Regulated by the Environment 434 Glycogen Synthase Kinase 464
 Contents xxiii
Glycogen Metabolism in the Liver Regulates NEW Clinical Insight Ketogenic Diets May Have
the Blood-Glucose Concentration 465 Therapeutic Properties 498
Clinical Insight Diabetes Mellitus Results from Animals Cannot Convert Fatty Acids into Glucose 498
Insulin Insufficiency and Glucagon Excess 466 27.4 Metabolism in Context: Fatty Acid Metabolism
Clinical Insight A Biochemical Understanding of Is a Source of Insight into Various
Glycogen-Storage Diseases Is Possible 467 Physiological States 499
Clinical Insight Diabetes Can Lead to a
Chapter 26 The Pentose Phosphate
Life-Threatening Excess of Ketone-Body Production 499
Pathway 473
Clinical Insight Ketone Bodies Are a Crucial
26.1 The Pentose Phosphate Pathway Yields Fuel Source During Starvation 500
NADPH and Five-Carbon Sugars 474
NEW Clinical Insight Some Fatty Acids May Contribute
Two Molecules of NADPH Are Generated in to the Development of Pathological Conditions 501
the Conversion of Glucose 6-phosphate into
Ribulose 5-phosphate 474
The Pentose Phosphate Pathway and Glycolysis Chapter 28 Fatty Acid Synthesis 507
Are Linked by Transketolase and Transaldolase 474 28.1 Fatty Acid Synthesis Takes Place in Three Stages 507
26.2 Metabolism in Context: Glycolysis and Citrate Carries Acetyl Groups from Mitochondria
the Pentose Phosphate Pathway Are to the Cytoplasm 508
Coordinately Controlled 478 Several Sources Supply NADPH for Fatty Acid Synthesis 508
The Rate of the Pentose Phosphate Pathway Is The Formation of Malonyl CoA Is the Committed
Controlled by the Level of NADP+ 478 Step in Fatty Acid Synthesis 509
The Fate of Glucose 6-phosphate Depends on Fatty Acid Synthesis Consists of a Series of
the Need for NADPH, Ribose 5-phosphate, and ATP 478 Condensation, Reduction, Dehydration, and
NEW Clinical Insight The Pentose Phosphate Reduction Reactions 510
Pathway Is Required For Rapid Cell Growth 481 The Synthesis of Palmitate Requires 8 Molecules of
26.3 Glucose 6-phosphate Dehydrogenase Acetyl CoA, 14 Molecules of NADPH, and
7 Molecules of ATP 512
Lessens Oxidative Stress 481
Fatty Acids Are Synthesized by a Multifunctional
Clinical Insight Glucose 6-phosphate
Enzyme Complex in Animals 512
Dehydrogenase Deficiency Causes a Drug-Induced
Hemolytic Anemia 481 Clinical Insight Fatty Acid Metabolism Is Altered in
Tumor Cells 513
Biological Insight A Deficiency of Glucose
6-phosphate Dehydrogenase Confers an Clinical Insight A Small Fatty Acid That Causes
Evolutionary Advantage in Some Circumstances 483 Big Problems 513
28.2 Additional Enzymes Elongate and Desaturate
SECTION 12 Fatty Acids 514
Fatty Acid and Lipid Metabolism 487 Membrane-Bound Enzymes Generate Unsaturated
Fatty Acids 514
Chapter 27 Fatty Acid Degradation 489
Eicosanoid Hormones Are Derived from
27.1 Fatty Acids Are Processed in Three Stages 489 Polyunsaturated Fatty Acids 514
Clinical Insight Triacylglycerols Are Hydrolyzed Clinical Insight Aspirin Exerts Its Effects by
by Hormone-Stimulated Lipases 490 Covalently Modifying a Key Enzyme 515
NEW Free Fatty Acids and Glycerol Are Released into 28.3 Acetyl CoA Carboxylase Is a Key Regulator of
the Blood 491 Fatty Acid Metabolism 516
Fatty Acids Are Linked to Coenzyme A Before Acetyl CoA Carboxylase Is Regulated by Conditions
They Are Oxidized 491 in the Cell 516
Clinical Insight Pathological Conditions Result if Acetyl CoA Carboxylase Is Regulated by a Variety of
Fatty Acids Cannot Enter the Mitochondria 493 Hormones 516
Acetyl CoA, NADH, and FADH2 Are Generated by
28.4 Metabolism in Context: Ethanol Alters Energy
Fatty Acid Oxidation 493
Metabolism in the Liver 517
The Complete Oxidation of Palmitate Yields
106 Molecules of ATP 495
27.2 The Degradation of Unsaturated and Chapter 29 Lipid Synthesis: Storage Lipids,
Odd-Chain Fatty Acids Requires Additional Steps 495 Phospholipids, and Cholesterol 523
An Isomerase and a Reductase Are Required for the 29.1 Phosphatidate Is a Precursor of Storage
Oxidation of Unsaturated Fatty Acids 495 Lipids and Many Membrane Lipids 523
Odd-Chain Fatty Acids Yield Propionyl CoA in the Triacylglycerol Is Synthesized from Phosphatidate in
Final Thiolysis Step 497 Two Steps 524
27.3 Ketone Bodies Are Another Fuel Source Phospholipid Synthesis Requires Activated Precursors 524
Derived from Fats 497 NEW Clinical Insight Phosphatidylcholine Is an
Ketone-Body Synthesis Takes Place in the Liver 497 Abundant Phospholipid  526
xxiv Contents
Sphingolipids Are Synthesized from Ceramide 526 30.2 Ammonium Ion Is Converted into Urea in Most
Clinical Insight Gangliosides Serve as Binding Terrestrial Vertebrates 555
Sites for Pathogens 527 NEW Carbamoyl Phosphate Synthetase Is the Key
Clinical Insight Disrupted Lipid Metabolism Regulatory Enzyme for Urea Synthesis  556
Results in Respiratory Distress Syndrome and NEW Carbamoyl Phosphate Reacts with Ornithine to Begin the
Tay–Sachs Disease 528 Urea Cycle  556
Phosphatidic Acid Phosphatase Is a Key The Urea Cycle Is Linked to Gluconeogenesis 557
Regulatory Enzyme in Lipid Metabolism 529 Clinical Insight Metabolism in Context:
29.2 Cholesterol Is Synthesized from Acetyl Inherited Defects of the Urea Cycle Cause
Coenzyme A in Three Stages 529 Hyperammonemia 558
The Synthesis of Mevalonate Initiates the Synthesis of Biological Insight Hibernation Presents Nitrogen
Cholesterol 530 Disposal Problems 558
Squalene (C30) Is Synthesized from Six Molecules of Biological Insight Urea Is Not the Only Means of
Isopentenyl Pyrophosphate (C5) 530 Disposing of Excess Nitrogen 559
Squalene Cyclizes to Form Cholesterol 532 30.3 Carbon Atoms of Degraded Amino Acids
29.3 The Regulation of Cholesterol Synthesis Emerge as Major Metabolic Intermediates 559
Takes Place at Several Levels 532 Pyruvate Is a Point of Entry into Metabolism 560
29.4 Lipoproteins Transport Cholesterol and Oxaloacetate Is Another Point of Entry into
Triacylglycerols Throughout the Organism 534 Metabolism 561
Low-Density Lipoproteins Play a Central Role in Alpha-Ketoglutarate Is Yet Another Point of Entry into
Cholesterol Metabolism 535 Metabolism 561
Clinical Insight The Absence of the LDL Receptor Succinyl Coenzyme A Is a Point of Entry for
Leads to Familial Hypercholesterolemia and Several Nonpolar Amino Acids 562
Atherosclerosis 536 The Branched-Chain Amino Acids Yield Acetyl
NEW Clinical Insight Cycling of the LDL Receptor Coenzyme A, Acetoacetate, or Succinyl Coenzyme A 562
Is Regulated 537 Oxygenases Are Required for the Degradation of
Clinical Insight HDL Seems to Protect Against Aromatic Amino Acids 563
Atherosclerosis 537 Methionine Is Degraded into Succinyl Coenzyme A 565
NEW Clinical Insight The Clinical Management of Clinical Insight Inborn Errors of Metabolism
Cholesterol Levels Can Be Understood at a Can Disrupt Amino Acid Degradation 565
Biochemical Level 538 NEW Clinical Insight Determining the Basis of the
29.5 Cholesterol Is the Precursor of Steroid Neurological Symptoms of Phenylketonuria
Hormones 539 Is an Active Area of Research 566
NEW Clinical Insight Bile Salts Facilitate Lipid
Absorption 539 Chapter 31 Amino Acid Synthesis 571
Steroid Hormones Are Crucial Signal Molecules 539 31.1 The Nitrogenase Complex Fixes Nitrogen 572
Vitamin D Is Derived from Cholesterol by The Molybdenum–Iron Cofactor of Nitrogenase
the Energy of Sunlight 540 Binds and Reduces Atmospheric Nitrogen 573
Clinical Insight Vitamin D Is Necessary for Bone Ammonium Ion Is Incorporated into an Amino
Development 541 Acid Through Glutamate and Glutamine 573
Clinical Insight Androgens Can Be Used to 31.2 Amino Acids Are Made from Intermediates
Artificially Enhance Athletic Performance 542 of Major Pathways 574
Oxygen Atoms Are Added to Steroids by Human Beings Can Synthesize Some Amino Acids
Cytochrome P450 Monooxygenases 542 but Must Obtain Others from the Diet 574
Metabolism in Context: Ethanol Also Is Processed by Some Amino Acids Can Be Made by Simple
the Cytochrome P450 System 543 Transamination Reactions 575
SECTION 13 Serine, Cysteine, and Glycine Are Formed from
The Metabolism of Nitrogen-Containing 3-Phosphoglycerate 576
Molecules 549 Clinical Insight Tetrahydrofolate Carries
Activated One-Carbon Units 576
Chapter 30 Amino Acid Degradation and S-Adenosylmethionine Is the Major Donor of
the Urea Cycle 551 Methyl Groups 578
30.1 Nitrogen Removal Is the First Step in Clinical Insight High Homocysteine Levels
the Degradation of Amino Acids 552 Correlate with Vascular Disease 578
Alpha-Amino Groups Are Converted into Ammonium 31.3 Feedback Inhibition Regulates Amino Acid
Ions by the Oxidative Deamination of Glutamate 552 Biosynthesis 579
NEW Clinical Insight Blood Levels of The Committed Step Is the Common Site
Amonitransferases Serve a Diagnostic Function 553 of Regulation 579
NEW Serine and Threonine Can Be Directly Deaminated 553 Branched Pathways Require Sophisticated
Peripheral Tissues Transport Nitrogen to the Liver 554 Regulation 579
 Contents xxv
Chapter 32 Nucleotide Metabolism 585 33.2 Nucleic Acid Strands Can Form a Double-Helical
32.1 An Overview of Nucleotide Biosynthesis and Structure 611
Nomenclature 586 The Double Helix Is Stabilized by Hydrogen
Bonds and the Hydrophobic Effect 611
32.2 The Pyrimidine Ring Is Assembled and
The Double Helix Facilitates the Accurate
Then Attached to a Ribose Sugar 587
Transmission of Hereditary Information 613
CTP Is Formed by the Amination of UTP 589
Meselson and Stahl Demonstrated That Replication Is
Kinases Convert Nucleoside Monophosphates into Semiconservative 614
Nucleoside Triphosphates 589
The Strands of the Double Helix Can Be Reversibly
NEW Clinical Insight Salvage Pathways Recycle Separated 615
Pyrimidine Bases 589
33.3 DNA Double Helices Can Adopt Multiple Forms 615
32.3 The Purine Ring Is Assembled on Ribose
Z-DNA Is a Left-Handed Double Helix in Which
Phosphate 590 Backbone Phosphoryl Groups Zigzag 616
AMP and GMP Are Formed from IMP 590 The Major and Minor Grooves Are Lined by
Clinical Insight Enzymes of the Purine-Synthesis Sequence-Specific Hydrogen-Bonding Groups 616
Pathway Are Associated with One Another in Vivo 592 Double-Stranded DNA Can Wrap Around Itself to Form
Bases Can Be Recycled by Salvage Pathways 593 Supercoiled Structures 617
32.4 Ribonucleotides Are Reduced to 33.4 Eukaryotic DNA Is Associated with Specific
Deoxyribonucleotides 593 Proteins 619
Thymidylate Is Formed by the Methylation of Nucleosomes Are Complexes of DNA and Histones 619
Deoxyuridylate 594 Eukaryotic DNA Is Wrapped Around Histones to Form
Clinical Insight Several Valuable Anticancer Drugs Nucleosomes 620
Block the Synthesis of Thymidylate 595 Clinical Insight Damaging DNA Can Inhibit
32.5 Nucleotide Biosynthesis Is Regulated by Cancer-Cell Growth 622
Feedback Inhibition 596 33.5 RNA Can Adopt Elaborate Structures 622
Pyrimidine Biosynthesis Is Regulated by Aspartate
Transcarbamoylase 596 Chapter 34 DNA Replication 627
The Synthesis of Purine Nucleotides Is Controlled by 34.1 DNA Is Replicated by Polymerases 628
Feedback Inhibition at Several Sites 596 DNA Polymerase Catalyzes Phosphodiester-Linkage
NEW Clinical Insight The Synthesis of Formation 628
Deoxyribonucleotides Is Controlled by the The Specificity of Replication Is Dictated by the
Regulation of Ribonucleotide Reductase 597 Complementarity of Bases 630
32.6 Disruptions in Nucleotide Metabolism Can Clinical Insight The Separation of DNA Strands
Cause Pathological Conditions 598 Requires Specific Helicases and ATP Hydrolysis 630
Clinical Insight The Loss of Adenosine Deaminase Topoisomerases Prepare the Double Helix for
Activity Results in Severe Combined Unwinding 632
Immunodeficiency 598 Clinical Insight Bacterial Topoisomerase Is a
Clinical Insight Gout Is Induced by High Serum Therapeutic Target 632
Levels of Urate 599 Many Polymerases Proofread the Newly Added
Clinical Insight Lesch–Nyhan Syndrome Is a Bases and Excise Errors 633
Dramatic Consequence of Mutations in a 34.2 DNA Replication Is Highly Coordinated 633
Salvage-Pathway Enzyme 600
DNA Replication in E. coli Begins at a Unique Site 634
Clinical Insight Folic Acid Deficiency Promotes
An RNA Primer Synthesized by Primase Enables DNA
Birth Defects Such As Spina Bifida 600
Synthesis to Begin 634
One Strand of DNA Is Made Continuously and
PART III the Other Strand Is Synthesized in Fragments 635
Synthesizing the Molecules of Life DNA Replication Requires Highly Processive
Polymerases 635
Section 14 The Leading and Lagging Strands Are Synthesized in a
Coordinated Fashion 636
Nucleic Acid Structure and DNA Replication 605
DNA Synthesis Is More Complex in Eukaryotes
Than in Bacteria 638
Chapter 33 The Structure of Informational
Telomeres Are Unique Structures at the Ends of
Macromolecules: DNA and RNA 607 Linear Chromosomes 638
33.1 A Nucleic Acid Consists of Bases Linked to Clinical Insight Telomeres Are Replicated by
a Sugar–Phosphate Backbone 608 Telomerase, a Specialized Polymerase That
DNA and RNA Differ in the Sugar Component and Carries Its Own RNA Template 639
One of the Bases 608
Nucleotides Are the Monomeric Units of Nucleic Acids 609 Chapter 35 DNA Repair and Recombination 643
DNA Molecules Are Very Long and Have Directionality 610 35.1 Errors Can Arise in DNA Replication 644
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