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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
quotation. Thinking about biochemistry and then putting those thoughts into
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,
dedicated, caring people who have taught us much about how to present science
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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
xxvi Contents
Clinical Insight Some Genetic Diseases Are Caused
Chapter 37 Gene Expression in Eukaryotes 675
by the Expansion of Repeats of Three Nucleotides 644 37.1 Eukaryotic Cells Have Three Types of RNA
Bases Can Be Damaged by Oxidizing Agents, Polymerases 676
Alkylating Agents, and Light 645 37.2 RNA Polymerase II Requires Complex
35.2 DNA Damage Can Be Detected and Repaired 647 Regulation 678
The Presence of Thymine Instead of Uracil in The Transcription Factor IID Protein Complex Initiates
DNA Permits the Repair of Deaminated Cytosine 649 the Assembly of the Active Transcription Complex 679
Clinical Insight Many Cancers Are Caused by Enhancer Sequences Can Stimulate Transcription at
the Defective Repair of DNA 650 Start Sites Thousands of Bases Away 679
Clinical Insight Many Potential Carcinogens Clinical Insight Inappropriate Enhancer Use
Can Be Detected by Their Mutagenic Action May Cause Cancer 680
on Bacteria 650 Multiple Transcription Factors Interact with Eukaryotic
35.3 DNA Recombination Plays Important Roles in Promoters and Enhancers 680
Replication and Repair 651 Clinical Insight Induced Pluripotent Stem Cells
Double Strand Breaks Can Be Repaired by Can Be Generated by Introducing Four Transcription
Recombination 652 Factors into Differentiated Cells 680
DNA Recombination Is Important in a Variety of 37.3 Gene Expression Is Regulated by Hormones 681
Biological Processes 652 Nuclear Hormone Receptors Have Similar Domain
Structures 681
Nuclear Hormone Receptors Recruit Coactivators and
Corepressors 682
SECTION 15 Clinical Insight Steroid-Hormone Receptors
RNA Synthesis, Processing, and Regulation 657 Are Targets for Drugs 683
Chapter 36 RNA Synthesis and Regulation 37.4 Histone Acetylation Results in Chromatin
in Bacteria 659 Remodeling 684
Metabolism in Context: Acetyl CoA Plays a Key Role in
36.1 Cellular RNA Is Synthesized by RNA Polymerases 659
the Regulation of Transcription 684
Genes Are the Transcriptional Units 660
Histone Deacetylases Contribute to Transcriptional
RNA Polymerase Is Composed of Multiple Subunits 661 Repression 686
36.2 RNA Synthesis Comprises Three Stages 661
Transcription Is Initiated at Promoter Sites on the DNA Chapter 38 RNA Processing in Eukaryotes 691
Template 661 38.1 Mature Ribosomal RNA Is Generated by
Sigma Subunits of RNA Polymerase Recognize the Cleavage of a Precursor Molecule 692
Promoter Sites 662 38.2 Transfer RNA Is Extensively Processed 692
RNA Strands Grow in the 5’-to-3’ Direction 663 38.3 Messenger RNA Is Modified and Spliced 693
Elongation Takes Place at Transcription Bubbles Sequences at the Ends of Introns Specify Splice Sites
That Move Along the DNA Template 664 in mRNA Precursors 694
An RNA Hairpin Followed by Several Uracil Residues Small Nuclear RNAs in Spliceosomes Catalyze
Terminates the Transcription of Some Genes 664 the Splicing of mRNA Precursors 695
The Rho Protein Helps Terminate the Transcription of Clinical Insight Mutations That Affect Pre-mRNA
Some Genes 665 Splicing Cause Disease 696
Precursors of Transfer and Ribosomal RNA Are Clinical Insight Most Human Pre-mRNAs Can
Cleaved and Chemically Modified After Transcription 666 Be Spliced in Alternative Ways to Yield Different
Clinical Insight Some Antibiotics Inhibit Proteins 697
Transcription 667 The Transcription and Processing of mRNA
36.3 The lac Operon Illustrates the Control of Are Coupled 698
Bacterial Gene Expression 668 Biological Insight RNA Editing Changes
An Operon Consists of Regulatory Elements and the Proteins Encoded by mRNA 698
Protein-Encoding Genes 668 38.4 RNA Can Function as a Catalyst 699
Ligand Binding Can Induce Structural Changes in
Regulatory Proteins 669 SECTION 16
Transcription Can Be Stimulated by Proteins Protein Synthesis and Recombinant DNA
That Contact RNA Polymerase 669 Techniques 705
Clinical and Biological Insight Many Bacterial Cells
Release Chemical Signals That Regulate Gene Chapter 39 The Genetic Code 707
Expression in Other Cells 670 39.1 The Genetic Code Links Nucleic Acid and
Some Messenger RNAs Directly Sense Metabolite Protein Information 708
Concentrations 670 The Genetic Code Is Nearly Universal 708
 Contents xxvii
Transfer RNA Molecules Have a Common Design 709 Protein Synthesis Begins on Ribosomes That Are
Some Transfer RNA Molecules Recognize More Free in the Cytoplasm 733
Than One Codon Because of Wobble Signal Sequences Mark Proteins for Translocation
in Base-Pairing 711 Across the Endoplasmic Reticulum Membrane 733
The Synthesis of Long Proteins Requires a Low Error 40.6 Protein Synthesis Is Regulated by a Number of
Frequency 712 Mechanisms 735
39.2 Amino Acids Are Activated by Attachment to Messenger RNA Use Is Subject to Regulation 735
Transfer RNA 712 The Stability of Messenger RNA Also Can Be
Amino Acids Are First Activated by Adenylation 713 Regulated 736
Aminoacyl-tRNA Synthetases Have Highly Small RNAs Can Regulate mRNA Stability and Use 736
Discriminating Amino Acid Activation Sites 714
Proofreading by Aminoacyl-tRNA Synthetases Chapter 41 Recombinant DNA Techniques 743
Increases the Fidelity of Protein Synthesis 714
41.1 Nucleic Acids Can Be Synthesized from
Synthetases Recognize the Anticodon Loops and Protein-Sequence Data 744
Acceptor Stems of Transfer RNA Molecules 714
Protein Sequence Is a Guide to Nucleic Acid
39.3 A Ribosome Is a Ribonucleoprotein Particle Information 744
Made of Two Subunits 715 DNA Probes Can Be Synthesized by Automated
Ribosomal RNAs Play a Central Role in Protein Methods 744
Synthesis 715
41.2 Recombinant DNA Technology Has
Messenger RNA Is Translated in the 5’-to-3’ Revolutionized All Aspects of Biology 745
Direction 716
Restriction Enzymes Split DNA into Specific
Fragments 745
Chapter 40 The Mechanism of
Restriction Fragments Can Be Separated by Gel
Protein Synthesis 721 Electrophoresis and Visualized 746
40.1 Protein Synthesis Decodes the Information in Restriction Enzymes and DNA Ligase Are Key Tools for
Messenger RNA 722 Forming Recombinant DNA Molecules 747
Ribosomes Have Three tRNA-Binding Sites That 41.3 Eukaryotic Genes Can Be Manipulated with
Bridge the 30S and 50S Subunits 722 Considerable Precision 748
The Start Signal Is AUG Preceded by Complementary DNA Prepared from mRNA Can Be
Several Bases That Pair with 16S Ribosomal RNA 722 Expressed in Host Cells 748
Bacterial Protein Synthesis Is Initiated by Estrogen-Receptor cDNA Can Be Identified by
Formylmethionyl Transfer RNA 723 Screening a cDNA Library 749
Formylmethionyl-tRNAf Is Placed in the P Site of Complementary DNA Libraries Can Be Screened for
the Ribosome in the Formation of the 70S Initiation Synthesized Protein 750
Complex 724
Specific Genes Can Be Cloned from Digests of
Elongation Factors Deliver Aminoacyl-tRNA to Genomic DNA 750
the Ribosome 724
DNA Can Be Sequenced by the Controlled
40.2 Peptidyl Transferase Catalyzes Peptide-Bond Termination of Replication 751
Synthesis 725
Clinical and Biological Insight Next-Generation
The Formation of a Peptide Bond Is Followed by the Sequencing Methods Enable the Rapid
GTP-Driven Translocation of tRNAs and mRNA 725 Determination of a Complete Genome Sequence 753
Protein Synthesis Is Terminated by Release Factors Selected DNA Sequences Can Be Greatly Amplified by
That Read Stop Codons 728 the Polymerase Chain Reaction 754
40.3 Bacteria and Eukaryotes Differ in the Initiation Clinical and Biological Insight PCR Is a Powerful
of Protein Synthesis 728 Technique in Medical Diagnostics, Forensics, and
Clinical Insight Mutations in Initiation Factor 2 Studies of Molecular Evolution 756
Cause a Curious Pathological Condition 730 Gene-Expression Levels Can Be Comprehensively
40.4 A Variety of Biomolecules Can Inhibit Protein Examined 756
Synthesis 730
Clinical Insight Some Antibiotics Inhibit Protein Appendices A1
Synthesis 730
Glossary B1
Clinical Insight Diphtheria Toxin Blocks Protein
Synthesis in Eukaryotes by Inhibiting Translocation 731 Answers to Problems C1
Clinical Insight Ricin Fatally Modifies
28S Ribosomal RNA 732 Index D1
40.5 Ribosomes Bound to the Endoplasmic Reticulum Selected Readings
Manufacture Secretory and Membrane Proteins 733 (online at www.whfreeman.com/tymoczko3e) E1
this page left intentionally blank
 SECTION 1

Biochemistry Helps Us to
Understand Our World

T he ultimate goal of all scientific endeavors is to develop a deeper, richer

understanding of ourselves and the world in which we live. Biochemistry
has had and will continue to have an extensive role in helping us to develop
this understanding. Biochemistry, the study of living organisms at the molecular
level, has shown us many of the details of the most fundamental processes of
life. For instance, biochemistry has shown us how information flows from genes
to molecules that have functional capabilities. In recent years, biochemistry has
also unraveled some of the mysteries of the molecular generators that provide
the energy that powers living organisms. The realization that we can understand
Chap ter 1
Biochemistry and the such essential life processes has significant philosophical implications. What
Unity of Life does it mean, biochemically, to be human? What are the biochemical differences
between a human being, a chimpanzee, a mouse, and a fruit fly? Are we more
similar than we are different?
The understanding achieved through biochemistry is greatly influencing
medicine and other fields. Although we may not be accustomed to thinking of illness
in relation to molecules, illness is ultimately some sort of malfunction at the molecular
level. The molecular lesions causing sickle-cell anemia, cystic fibrosis, hemophilia,
and many other genetic diseases have been elucidated at the biochemical level.
Biochemistry is also contributing richly to clinical diagnostics. For example, elevated
levels of heart enzymes in the blood reveal whether a patient has recently had a
Chap ter 2
Water, Weak Bonds, and myocardial infarction (heart attack). Agriculture, too, is employing biochemistry
the Generation of Order to develop more effective, environmentally safer herbicides and pesticides and to
Out of Chaos create genetically engineered plants that are, for example, more resistant to insects.

1
 In this section, we will learn some of the key concepts that structure the
study of biochemistry. We begin with an introduction to the molecules of
biochemistry, followed by an overview of the fundamental unit of biochemistry
and life itself—the cell. Finally, we examine the weak reversible bonds that
enable the formation of biological structures and permit the interplay between
molecules that makes life possible.

✓ By the end of this section, you should be able to:

✓ 1 Describe the key classes of biomolecules and differentiate between
them.
✓ 2 List the steps of the central dogma.

✓ 3 Identify the key features that differentiate eukaryotic cells from

prokaryotic cells.
✓ 4 Describe the chemical properties of water and explain how water
affects biochemical interactions.
✓ 5 Describe the types of noncovalent, reversible interactions and explain
why reversible interactions are important in biochemistry.
✓ 6 Define pH and explain why changes in pH may affect biochemical
systems.

2
 chapter 1
Biochemistry and the
Unity of Life

1.1 Living Systems Require a Limited

Variety of Atoms and Molecules
1.2 There Are Four Major Classes of
Biomolecules
1.3 The Central Dogma Describes
the Basic Principles of Biological
Information Transfer Despite their vast differences in mass—the African elephant has a mass 3 × 1018 times as
great as that of the bacterium E. coli—and complexity, the biochemical workings of these
1.4 Membranes Define the Cell and two organisms are remarkably similar. [E. coli: Eye of Science/Science Source. Elephant: John
Carry Out Cellular Functions Michael Evan Potter/Shutterstock.]

A
key goal of biochemistry, one that has been met with striking success, is to
understand what it means to be alive at the molecular level. Another goal
is to extend this understanding to the organismic level—that is, to under-
stand the effects of molecular manipulations on the life that an organism leads. For
instance, understanding how the hormone insulin works at the molecular level
illuminates how the organism controls the levels of common fuels—glucose and
fats—in its blood. Often, such understanding facilitates an understanding of dis-
ease states, such as diabetes, which results when insulin signaling goes awry. In
turn, this knowledge can be a source of insight into how the disease can be treated.
Biochemistry has been an active area of research for more than a century.
Much knowledge has been gained about how a variety of organisms manipulate
energy and information. However, one of the most exciting outcomes of bio-
chemical research has been the realization that all organisms have much in com-
mon biochemically. Organisms are remarkably uniform at the molecular level.
This observation is frequently referred to as the unity of biochemistry, but, in real-
ity, it illustrates the unity of life. French biochemist Jacques Monod encapsulated
this idea in 1954 with the phrase “Anything found to be true of [the bacterium]
E. coli must also be true of elephants.” This uniformity reveals that all organisms on
Earth have arisen from a common ancestor. A core of essential biochemical
­processes, common to all organisms, appeared early in the evolution of life. The
3
4 1 Biochemistry and the Unity of Life
diversity of life in the modern world has been generated by ­evolutionary pro-
cesses acting on these core processes through millions or even billions of years.
We begin our study of biochemistry by looking at commonalities. We will
examine the molecules and molecular constituents that are used by all life forms
and will then consider the rules that govern how biochemical information is ac-
cessed and how it is passed from one generation to the next. Finally, we will take
an overview of the fundamental unit of life—the cell. This is just the beginning.
All of the molecules and structures that we see in this chapter we will meet again
and again as we explore the chemical basis of life.

1.1 Living Systems Require a Limited Variety of

Atoms and Molecules
Ninety naturally occurring elements have been identified, yet only three—­
oxygen, hydrogen, and carbon—make up 98% of the atoms in an organism.
Moreover, the abundance of these three elements in life is vastly different from
their abundance in Earth’s crust (Table 1.1). What can account for the disparity
between what is available and what organisms are made of?
One reason that oxygen and hydrogen are so common is the ubiquity of
­water, or “the matrix of life,” as biochemist Albert Szent-Györgi called it. This tiny
molecule—consisting of only three atoms—makes life on Earth possible. Indeed,
current belief is that all life requires water, which is why so much effort has been
made in recent decades to determine whether Mars had water in the past and
whether it still does. The importance of water for life is so crucial that its presence
is tantamount to saying that life could be present. We will consider the properties
of water and how these properties facilitate biochemistry in Chapter 2.
After oxygen and hydrogen, the next most-common element in living
organisms is carbon. Most large molecules in living systems are made up
­
­predominantly of carbon. Fuel molecules are made entirely of carbon, hydrogen,

Table 1.1 Chemical compositions as percentage of total number of atoms

Composition in
Element Human beings (%) Seawater (%) Earth’s crust (%)
Hydrogen 63 66 0.22
Oxygen 25.5 33 47
Carbon 9.5 0.0014 0.19
Nitrogen 1.4 <0.1 <0.1
Calcium 0.31 0.006 3.5
Phosphorus 0.22 <0.1 <0.1
Chloride 0.03 0.33 <0.1
Potassium 0.06 0.006 2.5
Sulfur 0.05 0.017 <0.1
Sodium 0.03 0.28 2.5
Magnesium 0.01 0.003 2.2
Silicon <0.1 <0.1 28
Aluminum <0.1 <0.1 7.9
Iron <0.1 <0.1 4.5
Titanium <0.1 <0.1 0.46
All others <0.1 <0.1 <0.1

Note: Because of rounding, total percentages do not equal 100%.

Source: Data from E. Frieden, The chemical elements of life, Sci. Am. 227(1), 1972, p. 54.
 1.2 There Are Four Major Classes of Biomolecules 5
and oxygen. Biological fuels, like the fuels that power machinery, react with oxy-
gen to produce carbon dioxide and water. In regard to biological fuels, this reac-
tion, called combustion, provides the energy to power the cell. As a means of
seeing why carbon is uniquely suited for life, let us compare it with silicon, its
nearest elemental relative. Silicon is much more plentiful than carbon in Earth’s
crust (Table 1.1), and, like carbon, can form four covalent bonds—a property
crucial to the construction of large molecules. However, carbon-to-carbon bonds
are stronger than silicon-to-silicon bonds. This difference in bond strength has
two important consequences. First, large molecules can be built with the use of
carbon–carbon bonds as the backbone because of the stability of these bonds.
Second, more energy is released when carbon–carbon bonds undergo combus-
tion than when silicon reacts with oxygen. Thus, carbon-based molecules are
stronger construction materials and are better fuels than silicon-based molecules.
Carbon even has an advantage over silicon after it has undergone combustion.
Carbon dioxide is readily soluble in water and can exist as a gas; thus, it remains
in biochemical circulation, given off by one tissue or organism to be used by an-
other tissue or organism. In contrast, silicon is essentially insoluble after reaction
with oxygen. After it has combined with oxygen, it is permanently out of circula-
tion. Quartz is a common form of silicon dioxide.
Other elements have essential roles in living systems—notably, nitrogen,
phosphorus, and sulfur. Moreover, some of the trace elements, although present
in tiny amounts compared with oxygen, hydrogen, and carbon, are absolutely
vital to a number of life processes. We will see specific uses of these elements as
we proceed with our study of biochemistry.

1.2 There Are Four Major Classes of Biomolecules ✓ 1 Describe the key classes of
biomolecules and differentiate
Living systems contain a dizzying array of biomolecules. However, these biomol- between them.
ecules can be divided into just four classes: proteins, nucleic acids, lipids, and
carbohydrates.

Proteins Are Highly Versatile Biomolecules

Much of our study of biochemistry will revolve around proteins. Proteins are con-
structed from 20 building blocks, called amino acids, linked by peptide bonds to
form long unbranched polymers (Figure 1.1). These polymers fold into precise
three-dimensional structures that facilitate a vast array of biochemical functions.
Proteins serve as signal molecules (e.g., the hormone insulin signals that fuel is in
the blood) and as receptors for signal molecules. Receptors convey to the cell that
a signal has been received and initiates the cellular response. Thus, for example,
insulin binds to its particular receptor, called the insulin receptor, and initiates
the biological response to the presence of fuel in the blood. Proteins also play
structural roles, allow mobility, and provide defenses against environmental

1 2 3

Amino acids Amino acid sequence Protein

Figure 1.1 Protein folding. The three-dimensional structure of a protein is dictated by the
sequence of amino acids that constitute the protein.
6 1 Biochemistry and the Unity of Life
NH2 ­ angers. Perhaps the most prominent role of proteins is that
d
2– O –
O
–
O
N of catalysts—agents that enhance the rate of a chemical reac-
N
tion without being permanently affected themselves. Protein
H2
O
P P P C N catalysts are called enzymes. Every process that takes place in
O O O O
O O O N living systems depends on enzymes.

Nucleic Acids Are the Information Molecules of the Cell

HO
Adenosine triphosphate
(ATP)
Figure 1.2 The structure of a
nucleotide. A nucleotide (in this case,
adenosine triphosphate) consists of a base
(shown in blue), a five-carbon sugar (black),
and at least one phosphoryl group (red).
OH
As information keepers of the cell, the primary function of nu-
cleic acids is to store and transfer information. They contain the
instructions for all cellular functions and interactions. Like
proteins, nucleic acids are linear molecules. However, nucleic acids are constructed
from only four building blocks called nucleotides. A nucleotide is made up of a five-
carbon sugar, either a deoxyribose or a ribose, attached to a heterocyclic ring struc-
ture called a base and at least one phosphoryl group (Figure 1.2).
There are two types of nucleic acid: deoxyribonucleic acid (DNA) and ribo-
nucleic acid (RNA). Genetic information is stored in DNA—the “parts list” that
determines the nature of an organism. DNA is constructed from four deoxyri-
bonucleotides, differing from one another only in the ring structure of the
­bases—adenine (A), cytosine (C), guanine (G), and thymine (T). The i­ nformation
content of DNA is the sequence of nucleotides linked together by phosphodies-
ter linkages. DNA in all higher organisms exists as a double-stranded helix
(Figure 1.3). In the double helix, the bases interact with one another—A with
T and C with G.

Figure 1.3 The double helix. Two

individual chains of DNA interact to form a
double helix. The sugar–phosphate backbone
of one of the two chains is shown in red; the
other is shown in blue. The bases are shown
in green, purple, orange, and yellow.

RNA is a single-stranded form of nucleic acid. Some regions of DNA are

copied as a special class of RNA molecules called messenger RNA (mRNA).
mRNA is a template for the synthesis of proteins. Unlike DNA, mRNA is fre-
quently broken down after use. RNA is similar to DNA in composition with two
exceptions: the base thymine (T) is replaced by the base uracil (U), and the sugar
component of the ribonucleotides contains an additional hydroxyl (—OH) group.

Lipids Are a Storage Form of Fuel and Serve as a Barrier

Among the key biomolecules, lipids are much smaller than proteins or nucleic
acids. Whereas proteins and nucleic acids can have molecular weights of thou-
sands to millions, a typical lipid has a molecular weight of 1300 g mol−1. More-
over, lipids are not polymers made of repeating units, as are proteins and nucleic
acids. A key characteristic of many biochemically important lipids is their dual
chemical nature: part of the molecule is hydrophilic, meaning that it can dissolve
in water, whereas the other part, made up of one or more hydrocarbon chains, is
hydrophobic and cannot dissolve in water (Figure 1.4). This dual nature allows
lipids to form barriers that delineate the cell from its environment and to estab-
lish intracellular compartments. In other words, lipids allow the development of
“inside” and “outside” at a biochemical level. The hydrocarbon chains cannot in-
teract with water and, instead, interact with those of other lipids to form a barrier,
or membrane, whereas the water-soluble components interact with the aqueous
environment on either side of the membrane. Lipids are also an important stor-
age form of energy. As we will see, the hydrophobic component of lipids can un-
dergo combustion to provide large amounts of cellular energy. Lipids are crucial
signal molecules as well.
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 DANCE ON STILTS AT THE GIRLS’ UNYAGO, NIUCHI

Newala, too, suffers from the distance of its water-supply—at least

the Newala of to-day does; there was once another Newala in a lovely
valley at the foot of the plateau. I visited it and found scarcely a trace
of houses, only a Christian cemetery, with the graves of several
missionaries and their converts, remaining as a monument of its
former glories. But the surroundings are wonderfully beautiful. A
thick grove of splendid mango-trees closes in the weather-worn
crosses and headstones; behind them, combining the useful and the
agreeable, is a whole plantation of lemon-trees covered with ripe
fruit; not the small African kind, but a much larger and also juicier
imported variety, which drops into the hands of the passing traveller,
without calling for any exertion on his part. Old Newala is now under
the jurisdiction of the native pastor, Daudi, at Chingulungulu, who,
as I am on very friendly terms with him, allows me, as a matter of
course, the use of this lemon-grove during my stay at Newala.
 FEET MUTILATED BY THE RAVAGES OF THE “JIGGER”
(Sarcopsylla penetrans)

The water-supply of New Newala is in the bottom of the valley,

some 1,600 feet lower down. The way is not only long and fatiguing,
but the water, when we get it, is thoroughly bad. We are suffering not
only from this, but from the fact that the arrangements at Newala are
nothing short of luxurious. We have a separate kitchen—a hut built
against the boma palisade on the right of the baraza, the interior of
which is not visible from our usual position. Our two cooks were not
long in finding this out, and they consequently do—or rather neglect
to do—what they please. In any case they do not seem to be very
particular about the boiling of our drinking-water—at least I can
attribute to no other cause certain attacks of a dysenteric nature,
from which both Knudsen and I have suffered for some time. If a
man like Omari has to be left unwatched for a moment, he is capable
of anything. Besides this complaint, we are inconvenienced by the
state of our nails, which have become as hard as glass, and crack on
the slightest provocation, and I have the additional infliction of
pimples all over me. As if all this were not enough, we have also, for
the last week been waging war against the jigger, who has found his
Eldorado in the hot sand of the Makonde plateau. Our men are seen
all day long—whenever their chronic colds and the dysentery likewise
raging among them permit—occupied in removing this scourge of
Africa from their feet and trying to prevent the disastrous
consequences of its presence. It is quite common to see natives of
this place with one or two toes missing; many have lost all their toes,
or even the whole front part of the foot, so that a well-formed leg
ends in a shapeless stump. These ravages are caused by the female of
Sarcopsylla penetrans, which bores its way under the skin and there
develops an egg-sac the size of a pea. In all books on the subject, it is
stated that one’s attention is called to the presence of this parasite by
an intolerable itching. This agrees very well with my experience, so
far as the softer parts of the sole, the spaces between and under the
toes, and the side of the foot are concerned, but if the creature
penetrates through the harder parts of the heel or ball of the foot, it
may escape even the most careful search till it has reached maturity.
Then there is no time to be lost, if the horrible ulceration, of which
we see cases by the dozen every day, is to be prevented. It is much
easier, by the way, to discover the insect on the white skin of a
European than on that of a native, on which the dark speck scarcely
shows. The four or five jiggers which, in spite of the fact that I
constantly wore high laced boots, chose my feet to settle in, were
taken out for me by the all-accomplished Knudsen, after which I
thought it advisable to wash out the cavities with corrosive
sublimate. The natives have a different sort of disinfectant—they fill
the hole with scraped roots. In a tiny Makua village on the slope of
the plateau south of Newala, we saw an old woman who had filled all
the spaces under her toe-nails with powdered roots by way of
prophylactic treatment. What will be the result, if any, who can say?
The rest of the many trifling ills which trouble our existence are
really more comic than serious. In the absence of anything else to
smoke, Knudsen and I at last opened a box of cigars procured from
the Indian store-keeper at Lindi, and tried them, with the most
distressing results. Whether they contain opium or some other
narcotic, neither of us can say, but after the tenth puff we were both
“off,” three-quarters stupefied and unspeakably wretched. Slowly we
recovered—and what happened next? Half-an-hour later we were
once more smoking these poisonous concoctions—so insatiable is the
craving for tobacco in the tropics.
Even my present attacks of fever scarcely deserve to be taken
seriously. I have had no less than three here at Newala, all of which
have run their course in an incredibly short time. In the early
afternoon, I am busy with my old natives, asking questions and
making notes. The strong midday coffee has stimulated my spirits to
an extraordinary degree, the brain is active and vigorous, and work
progresses rapidly, while a pleasant warmth pervades the whole
body. Suddenly this gives place to a violent chill, forcing me to put on
my overcoat, though it is only half-past three and the afternoon sun
is at its hottest. Now the brain no longer works with such acuteness
and logical precision; more especially does it fail me in trying to
establish the syntax of the difficult Makua language on which I have
ventured, as if I had not enough to do without it. Under the
circumstances it seems advisable to take my temperature, and I do
so, to save trouble, without leaving my seat, and while going on with
my work. On examination, I find it to be 101·48°. My tutors are
abruptly dismissed and my bed set up in the baraza; a few minutes
later I am in it and treating myself internally with hot water and
lemon-juice.
Three hours later, the thermometer marks nearly 104°, and I make
them carry me back into the tent, bed and all, as I am now perspiring
heavily, and exposure to the cold wind just beginning to blow might
mean a fatal chill. I lie still for a little while, and then find, to my
great relief, that the temperature is not rising, but rather falling. This
is about 7.30 p.m. At 8 p.m. I find, to my unbounded astonishment,
that it has fallen below 98·6°, and I feel perfectly well. I read for an
hour or two, and could very well enjoy a smoke, if I had the
wherewithal—Indian cigars being out of the question.
Having no medical training, I am at a loss to account for this state
of things. It is impossible that these transitory attacks of high fever
should be malarial; it seems more probable that they are due to a
kind of sunstroke. On consulting my note-book, I become more and
more inclined to think this is the case, for these attacks regularly
follow extreme fatigue and long exposure to strong sunshine. They at
least have the advantage of being only short interruptions to my
work, as on the following morning I am always quite fresh and fit.
My treasure of a cook is suffering from an enormous hydrocele which
makes it difficult for him to get up, and Moritz is obliged to keep in
the dark on account of his inflamed eyes. Knudsen’s cook, a raw boy
from somewhere in the bush, knows still less of cooking than Omari;
consequently Nils Knudsen himself has been promoted to the vacant
post. Finding that we had come to the end of our supplies, he began
by sending to Chingulungulu for the four sucking-pigs which we had
bought from Matola and temporarily left in his charge; and when
they came up, neatly packed in a large crate, he callously slaughtered
the biggest of them. The first joint we were thoughtless enough to
entrust for roasting to Knudsen’s mshenzi cook, and it was
consequently uneatable; but we made the rest of the animal into a
jelly which we ate with great relish after weeks of underfeeding,
consuming incredible helpings of it at both midday and evening
meals. The only drawback is a certain want of variety in the tinned
vegetables. Dr. Jäger, to whom the Geographical Commission
entrusted the provisioning of the expeditions—mine as well as his
own—because he had more time on his hands than the rest of us,
seems to have laid in a huge stock of Teltow turnips,[46] an article of
food which is all very well for occasional use, but which quickly palls
when set before one every day; and we seem to have no other tins
left. There is no help for it—we must put up with the turnips; but I
am certain that, once I am home again, I shall not touch them for ten
years to come.
Amid all these minor evils, which, after all, go to make up the
genuine flavour of Africa, there is at least one cheering touch:
Knudsen has, with the dexterity of a skilled mechanic, repaired my 9
× 12 cm. camera, at least so far that I can use it with a little care.
How, in the absence of finger-nails, he was able to accomplish such a
ticklish piece of work, having no tool but a clumsy screw-driver for
taking to pieces and putting together again the complicated
mechanism of the instantaneous shutter, is still a mystery to me; but
he did it successfully. The loss of his finger-nails shows him in a light
contrasting curiously enough with the intelligence evinced by the
above operation; though, after all, it is scarcely surprising after his
ten years’ residence in the bush. One day, at Lindi, he had occasion
to wash a dog, which must have been in need of very thorough
cleansing, for the bottle handed to our friend for the purpose had an
extremely strong smell. Having performed his task in the most
conscientious manner, he perceived with some surprise that the dog
did not appear much the better for it, and was further surprised by
finding his own nails ulcerating away in the course of the next few
days. “How was I to know that carbolic acid has to be diluted?” he
mutters indignantly, from time to time, with a troubled gaze at his
mutilated finger-tips.
 Since we came to Newala we have been making excursions in all
directions through the surrounding country, in accordance with old
habit, and also because the akida Sefu did not get together the tribal
elders from whom I wanted information so speedily as he had
promised. There is, however, no harm done, as, even if seen only
from the outside, the country and people are interesting enough.
The Makonde plateau is like a large rectangular table rounded off
at the corners. Measured from the Indian Ocean to Newala, it is
about seventy-five miles long, and between the Rovuma and the
Lukuledi it averages fifty miles in breadth, so that its superficial area
is about two-thirds of that of the kingdom of Saxony. The surface,
however, is not level, but uniformly inclined from its south-western
edge to the ocean. From the upper edge, on which Newala lies, the
eye ranges for many miles east and north-east, without encountering
any obstacle, over the Makonde bush. It is a green sea, from which
here and there thick clouds of smoke rise, to show that it, too, is
inhabited by men who carry on their tillage like so many other
primitive peoples, by cutting down and burning the bush, and
manuring with the ashes. Even in the radiant light of a tropical day
such a fire is a grand sight.
Much less effective is the impression produced just now by the
great western plain as seen from the edge of the plateau. As often as
time permits, I stroll along this edge, sometimes in one direction,
sometimes in another, in the hope of finding the air clear enough to
let me enjoy the view; but I have always been disappointed.
Wherever one looks, clouds of smoke rise from the burning bush,
and the air is full of smoke and vapour. It is a pity, for under more
favourable circumstances the panorama of the whole country up to
the distant Majeje hills must be truly magnificent. It is of little use
taking photographs now, and an outline sketch gives a very poor idea
of the scenery. In one of these excursions I went out of my way to
make a personal attempt on the Makonde bush. The present edge of
the plateau is the result of a far-reaching process of destruction
through erosion and denudation. The Makonde strata are
everywhere cut into by ravines, which, though short, are hundreds of
yards in depth. In consequence of the loose stratification of these
beds, not only are the walls of these ravines nearly vertical, but their
upper end is closed by an equally steep escarpment, so that the
western edge of the Makonde plateau is hemmed in by a series of
deep, basin-like valleys. In order to get from one side of such a ravine
to the other, I cut my way through the bush with a dozen of my men.
It was a very open part, with more grass than scrub, but even so the
short stretch of less than two hundred yards was very hard work; at
the end of it the men’s calicoes were in rags and they themselves
bleeding from hundreds of scratches, while even our strong khaki
suits had not escaped scatheless.

NATIVE PATH THROUGH THE MAKONDE BUSH, NEAR

MAHUTA

I see increasing reason to believe that the view formed some time
back as to the origin of the Makonde bush is the correct one. I have
no doubt that it is not a natural product, but the result of human
occupation. Those parts of the high country where man—as a very
slight amount of practice enables the eye to perceive at once—has not
yet penetrated with axe and hoe, are still occupied by a splendid
timber forest quite able to sustain a comparison with our mixed
forests in Germany. But wherever man has once built his hut or tilled
his field, this horrible bush springs up. Every phase of this process
may be seen in the course of a couple of hours’ walk along the main
road. From the bush to right or left, one hears the sound of the axe—
not from one spot only, but from several directions at once. A few
steps further on, we can see what is taking place. The brush has been
cut down and piled up in heaps to the height of a yard or more,
between which the trunks of the large trees stand up like the last
pillars of a magnificent ruined building. These, too, present a
melancholy spectacle: the destructive Makonde have ringed them—
cut a broad strip of bark all round to ensure their dying off—and also
piled up pyramids of brush round them. Father and son, mother and
son-in-law, are chopping away perseveringly in the background—too
busy, almost, to look round at the white stranger, who usually excites
so much interest. If you pass by the same place a week later, the piles
of brushwood have disappeared and a thick layer of ashes has taken
the place of the green forest. The large trees stretch their
smouldering trunks and branches in dumb accusation to heaven—if
they have not already fallen and been more or less reduced to ashes,
perhaps only showing as a white stripe on the dark ground.
This work of destruction is carried out by the Makonde alike on the
virgin forest and on the bush which has sprung up on sites already
cultivated and deserted. In the second case they are saved the trouble
of burning the large trees, these being entirely absent in the
secondary bush.
After burning this piece of forest ground and loosening it with the
hoe, the native sows his corn and plants his vegetables. All over the
country, he goes in for bed-culture, which requires, and, in fact,
receives, the most careful attention. Weeds are nowhere tolerated in
the south of German East Africa. The crops may fail on the plains,
where droughts are frequent, but never on the plateau with its
abundant rains and heavy dews. Its fortunate inhabitants even have
the satisfaction of seeing the proud Wayao and Wamakua working
for them as labourers, driven by hunger to serve where they were
accustomed to rule.
But the light, sandy soil is soon exhausted, and would yield no
harvest the second year if cultivated twice running. This fact has
been familiar to the native for ages; consequently he provides in
time, and, while his crop is growing, prepares the next plot with axe
and firebrand. Next year he plants this with his various crops and
lets the first piece lie fallow. For a short time it remains waste and
desolate; then nature steps in to repair the destruction wrought by
man; a thousand new growths spring out of the exhausted soil, and
even the old stumps put forth fresh shoots. Next year the new growth
is up to one’s knees, and in a few years more it is that terrible,
impenetrable bush, which maintains its position till the black
occupier of the land has made the round of all the available sites and
come back to his starting point.
The Makonde are, body and soul, so to speak, one with this bush.
According to my Yao informants, indeed, their name means nothing
else but “bush people.” Their own tradition says that they have been
settled up here for a very long time, but to my surprise they laid great
stress on an original immigration. Their old homes were in the
south-east, near Mikindani and the mouth of the Rovuma, whence
their peaceful forefathers were driven by the continual raids of the
Sakalavas from Madagascar and the warlike Shirazis[47] of the coast,
to take refuge on the almost inaccessible plateau. I have studied
African ethnology for twenty years, but the fact that changes of
population in this apparently quiet and peaceable corner of the earth
could have been occasioned by outside enterprises taking place on
the high seas, was completely new to me. It is, no doubt, however,
correct.
The charming tribal legend of the Makonde—besides informing us
of other interesting matters—explains why they have to live in the
thickest of the bush and a long way from the edge of the plateau,
instead of making their permanent homes beside the purling brooks
and springs of the low country.
“The place where the tribe originated is Mahuta, on the southern
side of the plateau towards the Rovuma, where of old time there was
nothing but thick bush. Out of this bush came a man who never
washed himself or shaved his head, and who ate and drank but little.
He went out and made a human figure from the wood of a tree
growing in the open country, which he took home to his abode in the
bush and there set it upright. In the night this image came to life and
was a woman. The man and woman went down together to the
Rovuma to wash themselves. Here the woman gave birth to a still-
born child. They left that place and passed over the high land into the
valley of the Mbemkuru, where the woman had another child, which
was also born dead. Then they returned to the high bush country of
Mahuta, where the third child was born, which lived and grew up. In
course of time, the couple had many more children, and called
themselves Wamatanda. These were the ancestral stock of the
Makonde, also called Wamakonde,[48] i.e., aborigines. Their
forefather, the man from the bush, gave his children the command to
bury their dead upright, in memory of the mother of their race who
was cut out of wood and awoke to life when standing upright. He also
warned them against settling in the valleys and near large streams,
for sickness and death dwelt there. They were to make it a rule to
have their huts at least an hour’s walk from the nearest watering-
place; then their children would thrive and escape illness.”
The explanation of the name Makonde given by my informants is
somewhat different from that contained in the above legend, which I
extract from a little book (small, but packed with information), by
Pater Adams, entitled Lindi und sein Hinterland. Otherwise, my
results agree exactly with the statements of the legend. Washing?
Hapana—there is no such thing. Why should they do so? As it is, the
supply of water scarcely suffices for cooking and drinking; other
people do not wash, so why should the Makonde distinguish himself
by such needless eccentricity? As for shaving the head, the short,
woolly crop scarcely needs it,[49] so the second ancestral precept is
likewise easy enough to follow. Beyond this, however, there is
nothing ridiculous in the ancestor’s advice. I have obtained from
various local artists a fairly large number of figures carved in wood,
ranging from fifteen to twenty-three inches in height, and
representing women belonging to the great group of the Mavia,
Makonde, and Matambwe tribes. The carving is remarkably well
done and renders the female type with great accuracy, especially the
keloid ornamentation, to be described later on. As to the object and
meaning of their works the sculptors either could or (more probably)
would tell me nothing, and I was forced to content myself with the
scanty information vouchsafed by one man, who said that the figures
were merely intended to represent the nembo—the artificial
deformations of pelele, ear-discs, and keloids. The legend recorded
by Pater Adams places these figures in a new light. They must surely
be more than mere dolls; and we may even venture to assume that
they are—though the majority of present-day Makonde are probably
unaware of the fact—representations of the tribal ancestress.
 The references in the legend to the descent from Mahuta to the
Rovuma, and to a journey across the highlands into the Mbekuru
valley, undoubtedly indicate the previous history of the tribe, the
travels of the ancestral pair typifying the migrations of their
descendants. The descent to the neighbouring Rovuma valley, with
its extraordinary fertility and great abundance of game, is intelligible
at a glance—but the crossing of the Lukuledi depression, the ascent
to the Rondo Plateau and the descent to the Mbemkuru, also lie
within the bounds of probability, for all these districts have exactly
the same character as the extreme south. Now, however, comes a
point of especial interest for our bacteriological age. The primitive
Makonde did not enjoy their lives in the marshy river-valleys.
Disease raged among them, and many died. It was only after they
had returned to their original home near Mahuta, that the health
conditions of these people improved. We are very apt to think of the
African as a stupid person whose ignorance of nature is only equalled
by his fear of it, and who looks on all mishaps as caused by evil
spirits and malignant natural powers. It is much more correct to
assume in this case that the people very early learnt to distinguish
districts infested with malaria from those where it is absent.
This knowledge is crystallized in the
ancestral warning against settling in the
valleys and near the great waters, the
dwelling-places of disease and death. At the
same time, for security against the hostile
Mavia south of the Rovuma, it was enacted
that every settlement must be not less than a
certain distance from the southern edge of the
plateau. Such in fact is their mode of life at the
present day. It is not such a bad one, and
certainly they are both safer and more
comfortable than the Makua, the recent
intruders from the south, who have made USUAL METHOD OF
good their footing on the western edge of the CLOSING HUT-DOOR
plateau, extending over a fairly wide belt of
country. Neither Makua nor Makonde show in their dwellings
anything of the size and comeliness of the Yao houses in the plain,
especially at Masasi, Chingulungulu and Zuza’s. Jumbe Chauro, a
Makonde hamlet not far from Newala, on the road to Mahuta, is the
most important settlement of the tribe I have yet seen, and has fairly
spacious huts. But how slovenly is their construction compared with
the palatial residences of the elephant-hunters living in the plain.
The roofs are still more untidy than in the general run of huts during
the dry season, the walls show here and there the scanty beginnings
or the lamentable remains of the mud plastering, and the interior is a
veritable dog-kennel; dirt, dust and disorder everywhere. A few huts
only show any attempt at division into rooms, and this consists
merely of very roughly-made bamboo partitions. In one point alone
have I noticed any indication of progress—in the method of fastening
the door. Houses all over the south are secured in a simple but
ingenious manner. The door consists of a set of stout pieces of wood
or bamboo, tied with bark-string to two cross-pieces, and moving in
two grooves round one of the door-posts, so as to open inwards. If
the owner wishes to leave home, he takes two logs as thick as a man’s
upper arm and about a yard long. One of these is placed obliquely
against the middle of the door from the inside, so as to form an angle
of from 60° to 75° with the ground. He then places the second piece
horizontally across the first, pressing it downward with all his might.
It is kept in place by two strong posts planted in the ground a few
inches inside the door. This fastening is absolutely safe, but of course
cannot be applied to both doors at once, otherwise how could the
owner leave or enter his house? I have not yet succeeded in finding
out how the back door is fastened.

MAKONDE LOCK AND KEY AT JUMBE CHAURO

 This is the general way of closing a house. The Makonde at Jumbe
Chauro, however, have a much more complicated, solid and original
one. Here, too, the door is as already described, except that there is
only one post on the inside, standing by itself about six inches from
one side of the doorway. Opposite this post is a hole in the wall just
large enough to admit a man’s arm. The door is closed inside by a
large wooden bolt passing through a hole in this post and pressing
with its free end against the door. The other end has three holes into
which fit three pegs running in vertical grooves inside the post. The
door is opened with a wooden key about a foot long, somewhat
curved and sloped off at the butt; the other end has three pegs
corresponding to the holes, in the bolt, so that, when it is thrust
through the hole in the wall and inserted into the rectangular
opening in the post, the pegs can be lifted and the bolt drawn out.[50]

MODE OF INSERTING THE KEY

With no small pride first one householder and then a second

showed me on the spot the action of this greatest invention of the
Makonde Highlands. To both with an admiring exclamation of
“Vizuri sana!” (“Very fine!”). I expressed the wish to take back these
marvels with me to Ulaya, to show the Wazungu what clever fellows
the Makonde are. Scarcely five minutes after my return to camp at
Newala, the two men came up sweating under the weight of two
heavy logs which they laid down at my feet, handing over at the same
time the keys of the fallen fortress. Arguing, logically enough, that if
the key was wanted, the lock would be wanted with it, they had taken
their axes and chopped down the posts—as it never occurred to them
to dig them out of the ground and so bring them intact. Thus I have
two badly damaged specimens, and the owners, instead of praise,
come in for a blowing-up.
The Makua huts in the environs of Newala are especially
miserable; their more than slovenly construction reminds one of the
temporary erections of the Makua at Hatia’s, though the people here
have not been concerned in a war. It must therefore be due to
congenital idleness, or else to the absence of a powerful chief. Even
the baraza at Mlipa’s, a short hour’s walk south-east of Newala,
shares in this general neglect. While public buildings in this country
are usually looked after more or less carefully, this is in evident
danger of being blown over by the first strong easterly gale. The only
attractive object in this whole district is the grave of the late chief
Mlipa. I visited it in the morning, while the sun was still trying with
partial success to break through the rolling mists, and the circular
grove of tall euphorbias, which, with a broken pot, is all that marks
the old king’s resting-place, impressed one with a touch of pathos.
Even my very materially-minded carriers seemed to feel something
of the sort, for instead of their usual ribald songs, they chanted
solemnly, as we marched on through the dense green of the Makonde
bush:—
 “We shall arrive with the great master; we stand in a row and have
no fear about getting our food and our money from the Serkali (the
Government). We are not afraid; we are going along with the great
master, the lion; we are going down to the coast and back.”
With regard to the characteristic features of the various tribes here
on the western edge of the plateau, I can arrive at no other
conclusion than the one already come to in the plain, viz., that it is
impossible for anyone but a trained anthropologist to assign any
given individual at once to his proper tribe. In fact, I think that even
an anthropological specialist, after the most careful examination,
might find it a difficult task to decide. The whole congeries of peoples
collected in the region bounded on the west by the great Central
African rift, Tanganyika and Nyasa, and on the east by the Indian
Ocean, are closely related to each other—some of their languages are
only distinguished from one another as dialects of the same speech,
and no doubt all the tribes present the same shape of skull and
structure of skeleton. Thus, surely, there can be no very striking
differences in outward appearance.
 Even did such exist, I should have no time
to concern myself with them, for day after day,
I have to see or hear, as the case may be—in
any case to grasp and record—an
extraordinary number of ethnographic
phenomena. I am almost disposed to think it
fortunate that some departments of inquiry, at
least, are barred by external circumstances.
Chief among these is the subject of iron-
working. We are apt to think of Africa as a
country where iron ore is everywhere, so to
speak, to be picked up by the roadside, and
where it would be quite surprising if the
inhabitants had not learnt to smelt the
material ready to their hand. In fact, the
knowledge of this art ranges all over the
continent, from the Kabyles in the north to the
Kafirs in the south. Here between the Rovuma
and the Lukuledi the conditions are not so
favourable. According to the statements of the
Makonde, neither ironstone nor any other
form of iron ore is known to them. They have
not therefore advanced to the art of smelting
the metal, but have hitherto bought all their
THE ANCESTRESS OF
THE MAKONDE
iron implements from neighbouring tribes.
Even in the plain the inhabitants are not much
better off. Only one man now living is said to
understand the art of smelting iron. This old fundi lives close to
Huwe, that isolated, steep-sided block of granite which rises out of
the green solitude between Masasi and Chingulungulu, and whose
jagged and splintered top meets the traveller’s eye everywhere. While
still at Masasi I wished to see this man at work, but was told that,
frightened by the rising, he had retired across the Rovuma, though
he would soon return. All subsequent inquiries as to whether the
fundi had come back met with the genuine African answer, “Bado”
(“Not yet”).
 BRAZIER

Some consolation was afforded me by a brassfounder, whom I

came across in the bush near Akundonde’s. This man is the favourite
of women, and therefore no doubt of the gods; he welds the glittering
brass rods purchased at the coast into those massive, heavy rings
which, on the wrists and ankles of the local fair ones, continually give
me fresh food for admiration. Like every decent master-craftsman he
had all his tools with him, consisting of a pair of bellows, three
crucibles and a hammer—nothing more, apparently. He was quite
willing to show his skill, and in a twinkling had fixed his bellows on
the ground. They are simply two goat-skins, taken off whole, the four
legs being closed by knots, while the upper opening, intended to
admit the air, is kept stretched by two pieces of wood. At the lower
end of the skin a smaller opening is left into which a wooden tube is
stuck. The fundi has quickly borrowed a heap of wood-embers from
the nearest hut; he then fixes the free ends of the two tubes into an
earthen pipe, and clamps them to the ground by means of a bent
piece of wood. Now he fills one of his small clay crucibles, the dross
on which shows that they have been long in use, with the yellow
material, places it in the midst of the embers, which, at present are
only faintly glimmering, and begins his work. In quick alternation
the smith’s two hands move up and down with the open ends of the
bellows; as he raises his hand he holds the slit wide open, so as to let
the air enter the skin bag unhindered. In pressing it down he closes
the bag, and the air puffs through the bamboo tube and clay pipe into
the fire, which quickly burns up. The smith, however, does not keep
on with this work, but beckons to another man, who relieves him at
the bellows, while he takes some more tools out of a large skin pouch
carried on his back. I look on in wonder as, with a smooth round
stick about the thickness of a finger, he bores a few vertical holes into
the clean sand of the soil. This should not be difficult, yet the man
seems to be taking great pains over it. Then he fastens down to the
ground, with a couple of wooden clamps, a neat little trough made by
splitting a joint of bamboo in half, so that the ends are closed by the
two knots. At last the yellow metal has attained the right consistency,
and the fundi lifts the crucible from the fire by means of two sticks
split at the end to serve as tongs. A short swift turn to the left—a
tilting of the crucible—and the molten brass, hissing and giving forth
clouds of smoke, flows first into the bamboo mould and then into the
holes in the ground.
The technique of this backwoods craftsman may not be very far
advanced, but it cannot be denied that he knows how to obtain an
adequate result by the simplest means. The ladies of highest rank in
this country—that is to say, those who can afford it, wear two kinds
of these massive brass rings, one cylindrical, the other semicircular
in section. The latter are cast in the most ingenious way in the
bamboo mould, the former in the circular hole in the sand. It is quite
a simple matter for the fundi to fit these bars to the limbs of his fair
customers; with a few light strokes of his hammer he bends the
pliable brass round arm or ankle without further inconvenience to
the wearer.
SHAPING THE POT

SMOOTHING WITH MAIZE-COB

CUTTING THE EDGE

 FINISHING THE BOTTOM

LAST SMOOTHING BEFORE

BURNING

FIRING THE BRUSH-PILE

 LIGHTING THE FARTHER SIDE OF
THE PILE

TURNING THE RED-HOT VESSEL

NYASA WOMAN MAKING POTS AT MASASI

Pottery is an art which must always and everywhere excite the
interest of the student, just because it is so intimately connected with
the development of human culture, and because its relics are one of
the principal factors in the reconstruction of our own condition in
prehistoric times. I shall always remember with pleasure the two or
three afternoons at Masasi when Salim Matola’s mother, a slightly-
built, graceful, pleasant-looking woman, explained to me with
touching patience, by means of concrete illustrations, the ceramic art
of her people. The only implements for this primitive process were a
lump of clay in her left hand, and in the right a calabash containing
the following valuables: the fragment of a maize-cob stripped of all
its grains, a smooth, oval pebble, about the size of a pigeon’s egg, a
few chips of gourd-shell, a bamboo splinter about the length of one’s
hand, a small shell, and a bunch of some herb resembling spinach.
 Nothing more. The woman scraped with the
shell a round, shallow hole in the soft, fine
sand of the soil, and, when an active young
girl had filled the calabash with water for her,
she began to knead the clay. As if by magic it
gradually assumed the shape of a rough but
already well-shaped vessel, which only wanted
a little touching up with the instruments
before mentioned. I looked out with the
MAKUA WOMAN closest attention for any indication of the use
MAKING A POT. of the potter’s wheel, in however rudimentary
SHOWS THE a form, but no—hapana (there is none). The
BEGINNINGS OF THE embryo pot stood firmly in its little
POTTER’S WHEEL
depression, and the woman walked round it in
a stooping posture, whether she was removing
small stones or similar foreign bodies with the maize-cob, smoothing
the inner or outer surface with the splinter of bamboo, or later, after
letting it dry for a day, pricking in the ornamentation with a pointed
bit of gourd-shell, or working out the bottom, or cutting the edge
with a sharp bamboo knife, or giving the last touches to the finished
vessel. This occupation of the women is infinitely toilsome, but it is
without doubt an accurate reproduction of the process in use among
our ancestors of the Neolithic and Bronze ages.
There is no doubt that the invention of pottery, an item in human
progress whose importance cannot be over-estimated, is due to
women. Rough, coarse and unfeeling, the men of the horde range
over the countryside. When the united cunning of the hunters has
succeeded in killing the game; not one of them thinks of carrying
home the spoil. A bright fire, kindled by a vigorous wielding of the
drill, is crackling beside them; the animal has been cleaned and cut
up secundum artem, and, after a slight singeing, will soon disappear
under their sharp teeth; no one all this time giving a single thought
to wife or child.
To what shifts, on the other hand, the primitive wife, and still more
the primitive mother, was put! Not even prehistoric stomachs could
endure an unvarying diet of raw food. Something or other suggested
the beneficial effect of hot water on the majority of approved but
indigestible dishes. Perhaps a neighbour had tried holding the hard
roots or tubers over the fire in a calabash filled with water—or maybe
an ostrich-egg-shell, or a hastily improvised vessel of bark. They
became much softer and more palatable than they had previously
been; but, unfortunately, the vessel could not stand the fire and got
charred on the outside. That can be remedied, thought our
ancestress, and plastered a layer of wet clay round a similar vessel.
This is an improvement; the cooking utensil remains uninjured, but
the heat of the fire has shrunk it, so that it is loose in its shell. The
next step is to detach it, so, with a firm grip and a jerk, shell and
kernel are separated, and pottery is invented. Perhaps, however, the
discovery which led to an intelligent use of the burnt-clay shell, was
made in a slightly different way. Ostrich-eggs and calabashes are not
to be found in every part of the world, but everywhere mankind has
arrived at the art of making baskets out of pliant materials, such as
bark, bast, strips of palm-leaf, supple twigs, etc. Our inventor has no
water-tight vessel provided by nature. “Never mind, let us line the
basket with clay.” This answers the purpose, but alas! the basket gets
burnt over the blazing fire, the woman watches the process of
cooking with increasing uneasiness, fearing a leak, but no leak
appears. The food, done to a turn, is eaten with peculiar relish; and
the cooking-vessel is examined, half in curiosity, half in satisfaction
at the result. The plastic clay is now hard as stone, and at the same
time looks exceedingly well, for the neat plaiting of the burnt basket
is traced all over it in a pretty pattern. Thus, simultaneously with
pottery, its ornamentation was invented.
Primitive woman has another claim to respect. It was the man,
roving abroad, who invented the art of producing fire at will, but the
woman, unable to imitate him in this, has been a Vestal from the
earliest times. Nothing gives so much trouble as the keeping alight of
the smouldering brand, and, above all, when all the men are absent
from the camp. Heavy rain-clouds gather, already the first large
drops are falling, the first gusts of the storm rage over the plain. The
little flame, a greater anxiety to the woman than her own children,
flickers unsteadily in the blast. What is to be done? A sudden thought
occurs to her, and in an instant she has constructed a primitive hut
out of strips of bark, to protect the flame against rain and wind.
This, or something very like it, was the way in which the principle
of the house was discovered; and even the most hardened misogynist
cannot fairly refuse a woman the credit of it. The protection of the
hearth-fire from the weather is the germ from which the human
dwelling was evolved. Men had little, if any share, in this forward
step, and that only at a late stage. Even at the present day, the
plastering of the housewall with clay and the manufacture of pottery
are exclusively the women’s business. These are two very significant
survivals. Our European kitchen-garden, too, is originally a woman’s
invention, and the hoe, the primitive instrument of agriculture, is,
characteristically enough, still used in this department. But the
noblest achievement which we owe to the other sex is unquestionably
the art of cookery. Roasting alone—the oldest process—is one for
which men took the hint (a very obvious one) from nature. It must
have been suggested by the scorched carcase of some animal
overtaken by the destructive forest-fires. But boiling—the process of
improving organic substances by the help of water heated to boiling-
point—is a much later discovery. It is so recent that it has not even
yet penetrated to all parts of the world. The Polynesians understand
how to steam food, that is, to cook it, neatly wrapped in leaves, in a
hole in the earth between hot stones, the air being excluded, and
(sometimes) a few drops of water sprinkled on the stones; but they
do not understand boiling.
To come back from this digression, we find that the slender Nyasa
woman has, after once more carefully examining the finished pot,
put it aside in the shade to dry. On the following day she sends me
word by her son, Salim Matola, who is always on hand, that she is
going to do the burning, and, on coming out of my house, I find her
already hard at work. She has spread on the ground a layer of very
dry sticks, about as thick as one’s thumb, has laid the pot (now of a
yellowish-grey colour) on them, and is piling brushwood round it.
My faithful Pesa mbili, the mnyampara, who has been standing by,
most obligingly, with a lighted stick, now hands it to her. Both of
them, blowing steadily, light the pile on the lee side, and, when the
flame begins to catch, on the weather side also. Soon the whole is in a
blaze, but the dry fuel is quickly consumed and the fire dies down, so
that we see the red-hot vessel rising from the ashes. The woman
turns it continually with a long stick, sometimes one way and
sometimes another, so that it may be evenly heated all over. In
twenty minutes she rolls it out of the ash-heap, takes up the bundle
of spinach, which has been lying for two days in a jar of water, and
sprinkles the red-hot clay with it. The places where the drops fall are
marked by black spots on the uniform reddish-brown surface. With a
sigh of relief, and with visible satisfaction, the woman rises to an
erect position; she is standing just in a line between me and the fire,
from which a cloud of smoke is just rising: I press the ball of my
camera, the shutter clicks—the apotheosis is achieved! Like a
priestess, representative of her inventive sex, the graceful woman
stands: at her feet the hearth-fire she has given us beside her the
invention she has devised for us, in the background the home she has
built for us.
At Newala, also, I have had the manufacture of pottery carried on
in my presence. Technically the process is better than that already
described, for here we find the beginnings of the potter’s wheel,
which does not seem to exist in the plains; at least I have seen
nothing of the sort. The artist, a frightfully stupid Makua woman, did
not make a depression in the ground to receive the pot she was about
to shape, but used instead a large potsherd. Otherwise, she went to
work in much the same way as Salim’s mother, except that she saved
herself the trouble of walking round and round her work by squatting
at her ease and letting the pot and potsherd rotate round her; this is
surely the first step towards a machine. But it does not follow that
the pot was improved by the process. It is true that it was beautifully
rounded and presented a very creditable appearance when finished,
but the numerous large and small vessels which I have seen, and, in
part, collected, in the “less advanced” districts, are no less so. We
moderns imagine that instruments of precision are necessary to
produce excellent results. Go to the prehistoric collections of our
museums and look at the pots, urns and bowls of our ancestors in the
dim ages of the past, and you will at once perceive your error.
MAKING LONGITUDINAL CUT IN
BARK

DRAWING THE BARK OFF THE LOG

REMOVING THE OUTER BARK

 BEATING THE BARK

WORKING THE BARK-CLOTH AFTER BEATING, TO MAKE IT

SOFT

MANUFACTURE OF BARK-CLOTH AT NEWALA

To-day, nearly the whole population of German East Africa is
clothed in imported calico. This was not always the case; even now in
some parts of the north dressed skins are still the prevailing wear,
and in the north-western districts—east and north of Lake
Tanganyika—lies a zone where bark-cloth has not yet been
superseded. Probably not many generations have passed since such
bark fabrics and kilts of skins were the only clothing even in the
south. Even to-day, large quantities of this bright-red or drab
material are still to be found; but if we wish to see it, we must look in
the granaries and on the drying stages inside the native huts, where
it serves less ambitious uses as wrappings for those seeds and fruits
which require to be packed with special care. The salt produced at
Masasi, too, is packed for transport to a distance in large sheets of
bark-cloth. Wherever I found it in any degree possible, I studied the
process of making this cloth. The native requisitioned for the
purpose arrived, carrying a log between two and three yards long and
as thick as his thigh, and nothing else except a curiously-shaped
mallet and the usual long, sharp and pointed knife which all men and
boys wear in a belt at their backs without a sheath—horribile dictu!
[51]
Silently he squats down before me, and with two rapid cuts has
drawn a couple of circles round the log some two yards apart, and
slits the bark lengthwise between them with the point of his knife.
With evident care, he then scrapes off the outer rind all round the
log, so that in a quarter of an hour the inner red layer of the bark
shows up brightly-coloured between the two untouched ends. With
some trouble and much caution, he now loosens the bark at one end,
and opens the cylinder. He then stands up, takes hold of the free
edge with both hands, and turning it inside out, slowly but steadily
pulls it off in one piece. Now comes the troublesome work of
scraping all superfluous particles of outer bark from the outside of
the long, narrow piece of material, while the inner side is carefully
scrutinised for defective spots. At last it is ready for beating. Having
signalled to a friend, who immediately places a bowl of water beside
him, the artificer damps his sheet of bark all over, seizes his mallet,
lays one end of the stuff on the smoothest spot of the log, and
hammers away slowly but continuously. “Very simple!” I think to
myself. “Why, I could do that, too!”—but I am forced to change my
opinions a little later on; for the beating is quite an art, if the fabric is
not to be beaten to pieces. To prevent the breaking of the fibres, the
stuff is several times folded across, so as to interpose several
thicknesses between the mallet and the block. At last the required
state is reached, and the fundi seizes the sheet, still folded, by both
ends, and wrings it out, or calls an assistant to take one end while he
holds the other. The cloth produced in this way is not nearly so fine
and uniform in texture as the famous Uganda bark-cloth, but it is
quite soft, and, above all, cheap.
Now, too, I examine the mallet. My craftsman has been using the
simpler but better form of this implement, a conical block of some
hard wood, its base—the striking surface—being scored across and
across with more or less deeply-cut grooves, and the handle stuck
into a hole in the middle. The other and earlier form of mallet is
shaped in the same way, but the head is fastened by an ingenious
network of bark strips into the split bamboo serving as a handle. The
observation so often made, that ancient customs persist longest in
connection with religious ceremonies and in the life of children, here
finds confirmation. As we shall soon see, bark-cloth is still worn
during the unyago,[52] having been prepared with special solemn
ceremonies; and many a mother, if she has no other garment handy,
will still put her little one into a kilt of bark-cloth, which, after all,
looks better, besides being more in keeping with its African
surroundings, than the ridiculous bit of print from Ulaya.
MAKUA WOMEN