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cesses within living organisms, is the bedrock
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New to
This Edition
A NEW CHEMISTRY PRIMER
This helpful in-text resource reviews foundational general chemistry and organic chemistry topics, getting students up to
speed so that they can master the biochemical concepts to come
General and Organic Chemistry Review Primer P-13
In theChemistry
methane molecule
(FigureP-11
6), each of the four sp hybrid orbitals overlaps
General and Organic
Review Primer
3
with the 1s orbital of hydrogen to form a sigma bond. A sigma bond (s), which is
formed by the overlapping by the outermost orbitals of two atoms, is the strongest
type of covalent bond.
WORKED PROBLEM 2
What is the Lewis electron dot formula for formaldehyde (H2C=O)?
SOLUTION
H
The valence electrons for hydrogen, carbon, and oxygen are 2 (1 for each atom),
4, and 6, respectively, for a total of 12 electrons. Single bonds between the elements account for 6 electrons, leaving 6 electrons unaccounted for. Group the
remaining 6 electrons around the most electronegative atom (oxygen) until a total
of 8 electrons (bonding and nonbonding) is reached. Using one pair of these
electrons to form a double bond between carbon and oxygen completes the
carbon octet. The final Lewis structure is given below.
sp3
sp3
H
FIGUR E 6
Structure of Methane
sp3
Methane (CH4) has a tetrahedral
geometry with four s bonds
formed by the overlap of four sp3
orbitals of carbon with four 1s
orbitals of hydrogen atoms.
H
sp3
H
H
C O
Each of the two carbon atoms in the molecule ethene (H2C5CH2) is bonded
to three atoms in trigonal planar geometry. Carbon’s 2s orbital mixes with two of
the three available 2p orbitals to form three sp2 orbitals.
H
Ascertaining a molecule’s three-dimensional shape begins with a correct
Lewis dot structure. The molecule’s geometry is then determined based on the
number of bonding and nonbonding electrons on the central atom (Figure 4). If
there are two electron pairs, the molecule has a linear shape. Carbon dioxide
(CO2), for example, is a linear molecule with two electron groups. Its bond angle
is 180o. Formaldehyde (H2C5O), with three electron groups, has trigonal planar
geometry with bond angles of 120o. Molecules with a central atom with four pairs
of electrons have a tetrahedral shape. Methane (CH4), with its four carbon-hydrogen
bonds, has bond angles of 109.5o. If one of the four electron groups in a tetrahedron is a lone pair, the molecular shape is trigonal pyramidal. Because of the
strong repulsion of the lone pair, bond angles are less than 109.5o. For example,
the lone pair in NH3 forces the NH bonding electron pairs closer together with
bond angles of 107.3o.
280
1.3 Is the Living Cell a Chemical Factory?
1s2 2sp2 2sp2 2sp2 2p
Two of the three sp2 orbitals of each carbon atom overlap the orbital of a hydrogen atom, forming a total of four s bonds. The third sp2 orbital of the two carbon
atoms overlap to form a carbon-carbon s bond. The p orbitals, one on each
carbon, overlap to form a pi (p) bond (Figure
7). A double bond
O in molecules
O
O
such as ethene consists of a s bond and a p bond.
R
H
C
C
120°
H
O−
C
C
H
120°
P
−
HO
Fatty Acid
H
H
120°
O−
CH2CH2C
H
σ bond
(b)
H
O
P
O−
O
15
NH2
N
N
O
N
O
P
N
CH 2
FIGUR E 7 O
O−Ethene Structure
(a) Each carbon atom in ethane
(also known as ethylene) has
ATPthree sp2 orbitals with bond
OH
OH
angles of 120˚, which have a
NHgeometry.
trigonal planar
2
2
(b) Two
O
N of the sp orbitals of O
each carbon (green)
7. Phosphoryl group transfer. In this reaction ATP is synthesized as phosN overlap with
π
H
H
an s orbital of hydrogen
+ (red)
O− P
O−
P
O
phoglycerate kinase catalyzes the transfer
of the
high-energy phosphoryl
FIGUR
E
4
Linear
Trigonal planar
forming a total of 4 s bonds.
C σ C
O
O
group of glycerate-1,3-bisphosphate to Common
ADP: Molecular
−
N
2
N
−
The remaining two sp orbitals, O
O
H
H
π
Geometrics
one from each carbon, overlapPyrophosphate
to
O
P
O
CoASH
C
R
CH2CH2
CH 2
O
O
O form a carbon-carbon s bond.
These structures illustrate
(c)
O−
(c) Two p orbitals (blue), one
O the spatial orientations of
109.5°
C
O
P
O−
from each carbon atom, overlap
electron groups. Note that
Phosphoglycerate
Fatty Acid - AMP
−
kinase
to form a π bond.
electrons(C
are2H2) is a molecule with a triple bond with each carbon bonded to
O Acetylene
C unpaired
O−
indicated
by anatoms
enlarged
two other
in a linear geometry. Carbon’s 2s orbital
H
C
OH
O
H
ATP
O
H
ADP
+
+
O
O
C
O
H
H
representation of an
2+
Mg
Tetrahedral
Trigonal pyramidal
Bent (V shaped)
orbital.
CHAPTER EIGHT
CH 2
180°
Carbohydrate
Metabolism
120°
O
P
(a)
O−
CH 2
O
P
O−
1s2
sp
sp
2p
2p
AMP
O− also affects molecular polarity. In polar covalent
O−
Three-dimensional shape
O
bonds thereGlycerate-1,3-bisphosphate
is an unequal sharing of electrons because the atoms have different Glycerate-3-phosphate
mixes with one 2p orbital to form 2 sp hybrid orbitals. Each carbon also possesses
electronegativities. This separation of charge is called a dipole. Although a polar
S CoA
C
R
CH2CH2
two
unhybridized
2p
orbitals.
Acetylene
has
a
triple
bond
consisting
of
one s
molecule always contains polar bonds, someThe
molecules
with
polar
bonds
are
terminal phosphoryl group of ADP acting as a nucleophile attacks
bond
and two p bonds. The carbon-carbon
s bond is formed by the overlap of an
nonpolar. Molecular polarity requires an asymmetric
distribution
of polar
bonds.
the phosphorus
of the
phosphoanhydride
of glycerate-1,3-bisphosphate
to
FIGUR
E
1.14
bonds.
Carbon dioxide is aReaction
nonFor example, CO2 contains two C—O dipoleyield
glycerate-3-phosphate.
7 is an example of a substrate-level
Activation of a Fatty Acid
polar molecule because of its linear shape (i.e.,phosphorylation.
its bond dipoles Because
are symmetrical
the synthesis of ATP is endergonic, it requires
and cancel each other out). Water, which alsoanhas
two
polar
bonds
(two
O—H
Before a fatty acid can be degraded to yield energy or used in the synthesis of a triacylglycerol,
energy source. In substrate-level phosphorylations, ATP is produced
it must first be activated. In the first step the carboxylate ion attacks a phosphate of ATP to form
by the transfer of a phosphoryl group from a substrate with a high phosphoryl transfer potential (glycerate-1,3-bisphosphate) (refer to Table 4.1) atofatty acyl-AMP intermediate and pyrophosphate (PPi). In the second step the fatty acyl-AMP
is attacked by the thiol group of coenzyme A (CoASH) to form the thioester fatty acyl-SCoA
produce a compound with a lower transfer potential (ATP) and therefore
and AMP. The rapid hydrolysis of PPi to form two phosphates (Pi) drives the reaction forward.
McKee_Primer.indd 13
DG , 0. Because two molecules
of glycerate-1,3-bisphosphate are formed
for every glucose molecule, this reaction produces two ATP molecules,
hydroxyl
oxygen on carbon 6 of the sugar molecule is the nucleophile and phosand the investment of phosphate bond energy is recovered. ATP synthesis
McKee_Primer.indd 11
14/05/15 2:24 AM
phorus is the electrophile. Adenosine diphosphate is the leaving group.
later in the pathway represents a net gain.
8. The interconversion of glycerate-3-phosphate and glycerate-2phosphate. Glycerate-3-phosphate has a low phosphoryl group transfer
ELIMINATION REACTIONS In elimination reactions a double bond is formed
potential. As such, it is a poor candidate for further ATP synthesis (DG89 for
when atoms in a molecule are removed.
ATP synthesis is –30.5 kJ/mol). Cells convert glycerate-3-phosphate with
H
H
H
H
its energy-poor phosphate ester to phosphoenolpyruvate (PEP), which has
−
an exceptionally high phosphoryl group transfer potential. (The standard
C
C
H
C
H
H + A+ + B
C
H
free energies of hydrolysis of glycerate-3-phosphate and PEP are 212.6
B
A
and 261.9 kJ/mol, respectively.) In the first step in this conversion (reaction 8), phosphoglycerate mutase catalyzes the conversion of a C-3 phosphorylated compound to a C-2 phosphorylated compound through a The removal of H2O from biomolecules containing alcohol functional groups
is a commonly encountered reaction. A prominent example is the dehydration of
two-step addition/elimination cycle.
2-phosphoglycerate, a reaction in glycolysis, which is a biochemical pathway in
carbohydrate metabolism (Figure 1.17). As illustrated on pp. P-33–P-34, this
reaction occurs via an E1cB mechanism. Other products of elimination reactions
O
include ammonia (NH3), amines (RNH2), and alcohols (ROH).
14/05/15 2:25 AM
DEEPER CHEMISTRY
Expanded chemical explanation and emphasis on the chemistry of reactions
O
C
H
C
CH 2
O−
OH
O
H
+
O−
C
O
O−
O−
Glycerate-3-phosphate
Phosphoglycerate
mutase
O
H2O
O−
O
CH 2
O
Pi
O
O−
P
Pi
O
P
C
P
O−
O−
Glycerate-2,3-bisphosphate
Phosphoglycerate
mutase
H
C
O−
C
O
O
P
O−
01-McKee-Chap01.indd 15
O−
CH 2
OH
Glycerate-2-phosphate
9. Dehydration of glycerate-2-phosphate. Enolase catalyzes the dehydration of glycerate-2-phosphate to form PEP:
14/05/15
716
CHAPTER EIGHTEEN
Genetic Information
FIGUR E 18.54
Gene
Viral
dsRNA
mi-RNA and si-RNA Processing
RNAP II
Dicer
In posttranscriptional gene silencing, the
primary transcript of a miRNA gene, pripri-miRNA
miRNA, is processed by microprocessor, a
siRNA
protein complex containing pasha and
19.3 The Proteostasis Network 763
Microprocessor
drosha, and dicer to form miRNA. The
miRNA guide strand is then incorporated
into the RISC ribonucleoprotein complex
pre-miRNA
where it binds a complementary sequence in
Transport into
the 39 UTR
its target
mRNA.and
Because
Within
the of
highly
crowded
dynamic interior of living cells,
millions of procytoplasm
these perform
two sequences
arearray
not perfectly
teins
a vast
of functions such as DNA replication
and transcripDicer
complementary,
mRNA is silenced,
butresponses, cell cycle control,
tion,
cell signal the
transduction,
immune
and molecular
not degraded.
In depends
RNA interference,
a
transport.
Life
on the proper
function of proteins, which in
turn requires
miRNA
foreign dsRNA is cleaved by dicer to yield
that
these linear macromolecules fold into their “native states” yet retain some
the ds-RNA molecule siRNA. Once the
degree
of conformational flexibility. As a result, many proteins, especially those
RISC
guide strand of the siRNA has been
that
are composed
100 itorbinds
moretoamino
acids or are completely or even partially
positioned
within theof
RISC,
its
mRNA
unstructured,
are
marginally
stable
and
therefore
prone
to
misfolding.
Misfolded
complementary sequence on the viral
or
partially
folded
oftenare
have exposed hydrophobic patches that may
mRNA.
Because
theseproteins
two sequences
interact
other molecules
form amorphous aggregates. In addition, some
perfectlywith
complementary,
the slicertoactivity
of the RISCmolecules
proceeds to may
cleaverearrange
the mRNA to form
misfolded
the b-strandsinto
of aamyloid
fibrillar complex called RISC. The other miRNA
is incorporated
ribonucleoprotein
into pieces. The proteome is also challenged
aggregates.
by a (the
constant
barrage
of metabolic
strand
passenger
strand)
is degraded. A RISC protein called argonaute posi-
19.3 THE PROTEOSTASIS NETWORK
Biochemistry
UPDATED CONTENT
New discussions of RNA interference, epigenetics, metabolic
regulation, and proteostasis
17.2 RNA
641
IN PERSPECTIVE
Degradation
Chaperones
and environmental stresses (e.g., heat or heavy
metals
exposure,
acidthe
sidetarget mRNA, thereby inactivating it.
tions
the miRNA
so itamino
can bind
chain oxidation, hypoxia, and toxins) that canMiRNA-mediated
damage them. When
gene combined
silencing utilizes components of RNA interference,
with the incidence of random errors in protein
synthesis,
proteotoxic
a process
originally
believed stressto be limited to protection against viruses and
Epigenetics
andto the
related protein misfolding and other types of
damage areCells
a severe
threat
cell si-RNAs to recognize and then degrade
transposons.
use double-stranded
function.
target
mRNAs. siRNAsGenetic
are the products of dicer-induced cleavage of larger NH
Epigenome:
NH2
2
Healthy young cells maintain proteostasisRNA
withmolecules
a robust and
highly
conserved
(e.g.,
a viral
RNA genome). Once the guide siRNA is incorpoCH3
beyond
DNA
interconnected network of pathways, referredrated
toInheritance
as into
the proteostasis
network
RISC (Figure
18.54),(PN)
it binds
to its complementary sequence on the
N
N
(Figure 19.23). Using stress-responsive signaling
pathways,
the PN
monitors match exactly, slicer (an enzymatic activtarget
mRNA.
Because
the sequences
Base
Sequences
proteins from their synthesis by ribosomes, ity
through
folding,ofrefolding,
transport,
in a domain
argonaute)
cleaves the mRNA into pieces.
O
O
N
N
and degradation when their useful life is over or
they
damaged.
PN processes
How
doare
covalent
modifications
of DNA and histones affect
O
O
TRANSPORT
transport out of the nucleus, a highly regulated
are accomplished with the aid of molecularRNA
chaperones
(p. 165), mRNA
stress-response
How do the more
the
functions
of
multicellular
organisms?
occurs inprocesses
three phases:
processing reactions, docking and passage
transcription factors, detoxifying enzymes,process,
and degradation
such as
than 200 cell types in humans arise from a fertilized egg? Life
through
NPC (p. 55),
into the cytoplasm. In the first phase pre-mRNA
the ubiquitin-proteosomal system (p. 556) and
autophagy
558).and
Therelease
resources
scientists have known for many years that the transformation of
5-Methyl cytosine
molecules
are simultaneously
into mRNAs and packagedCytosine
into
that are devoted to proteome protection indicate
the importance
of the PN. processed
For
a single cell into a multicellular organism is the result of cell
ribonucleoprotein
complexes
(mRNPs). mRNP proteins (e.g., capFIGUR
bindingEprotein,
example, the human PN involves about 2000
genes. Under stressful
conditions
17A
specialization effected by gene expression changes that occur
andthat
poly(A)-binding
protein)
that allow
NPC
PN processes can be activated throughout EJCs,
the cell,
is, cytoplasm and
the recruit export factors Cytosine
Methylation
during the developmental process. Early signal mechanisms
targeting. The capping and splicing proteins allow binding to TREX, an export
must “instruct” cells, each with an identical genetic blueprint, to Cytosine residues in CpG dinucleotides are methylated by specific
414 CHAPTER ELEVEN Lipids and Membranes
protein complex. Once mRNPs are linked via a TREX subunit to Nxf1-Nxt1, a
progress down separate developmental pathways to yield termi- methyltransferases.
heterodimer nuclear export receptor, they move through the NPC. When an
differentiated
cells plasma
such as membrane
red blood cells,
neurons, orcalled cystic fibrosis
anally
missing
or defective
glycoprotein
mRNP
complex
reaches the
cytoplasm, the release
of export proteins triggers the
The methylation
of CpG islands, which are located upskeletal muscle cells.
In recent yearsregulator
it has become apparent CFTR
that bases.
Ribosomeremodeling
transmembrane
conductance
(Figure
11.33),
of the complex
that in turn directs(CFTR).
transport to its final
destination
KEY CONCEPTS
Translation
stream of
constitutively expressed (continuously produced)
this
process,
the
result
of
sequential,
programmed
whichtranslation
functions as
a chloride
channel in epithelialchanges
cells, isina member
ofmost
a family
where
will
occur.
• Membrane transport mechanisms are
genes
and
some
regulated
genes, represses gene expression.
FIGUR
E
19.23
the
pattern
of
expressed
and
silenced
genes
in
each
cell
type,
of proteins referred to as ABC transporters. (ABC transporters are so named
classified as passive or active according to
There are two classes of CpG methylating enzymes: maintedoes noteach
depend
on genetic
information segment
(DNA
base sequences)
The Proteostasis
Nascent
because
contains
a polypeptide
anNetwork
ATP-binding
TRANSLATIONAL
CONTROL
Eukaryotic
cells called
can respond
to variouscassette.)
stimuli
whether they require energy.
nance
methyltransferases
and
de novo methyltransferases. Mainalone.
Rather,
development
is the result
ofThe
chromatin
remodelpolypeptide
proteostasis
consists
of contains
moThe
CFTR
gene
on
chromosome
codes
the CFTR
protein,
which
(e.g.,
heat shock,
viral
infections, 7and
cellfor
cycle
phasenetwork
changes)
by selectively
• In passive transport, solutes moving across
tenance
methyltransferases
recognize methylated CpGs in the
ing domains.
that is effected
by two mechanisms:
DNA
methylation
and
lecular
chaperones
that assist
proteins
in
five
Two
domains
(MSD1
andmodification
MSD2),
each
containing
six
membraneng their concentration
altering
protein
synthesis.
The
covalent
of
several
translation
factors
i
k
membranes move
down
ic
parentalthrough
DNA
and then catalyze the methylation of cytohistone covalent
modifications.
covalent
–
de novo
folding
and in
maintaining
them strand
inthe
aff
channel
pore.modification–
Chloride
transport
spanning
helices,
form
theassist
ClBecause
proteins
that
in
the translation
process)
has
been observed
to
Ag (nonribosomal
gradient. ing/tr nes
sinesoccur
in
the corresponding
CpGs in the newly synthesized strand.
induced
gene activations
and
are
heritable
but
notwhich
grepore
their
native states.
The
network
also
ld
ero
is overall
controlled
by synthesis
the repressions
otherrate
three
domains
(alldo
on the
Folding
alter
protein
and/or
enhance
theof
translation
of includes
specific
ga the
Fo transport,
ap
• In active
energy Intermediate
derived directly
tio
It
is
this
process
that
is responsible for the stable inheritance of
enzymes
and
protein
complexes
that
degrade
change
DNA
base
sequences,
this
phenomenon
is
referred
to
as
Ch
n
g
Ch
cytoplasmic
side of the
plasma
membrane).
Two
nucleotide-binding
domains
mRNAs.
For example,
when
cellular
iron levels
areare
low,
a repressor
protein
binds
to
Amorphous
or indirectly from ATP
din hydrolysis or another
misfolded,
damaged,
and DNA
obsolete
proteins. patterns between cell generations. The addiDis aper epigenetics
methylation
[epi
(Gk)
5
over
or
above].
Epigenetic
modificafol
n
and
NBD
) that
andprotein
hydrolyze
ATPWhen
and use
released
energy to
coding
for2the
ironbind
storage
ferritin.
ironthe
levels
rise
sufficiently
n(NBD1aggregates
energy source isU required to move an ionagorgr omRNAs
As
each
nascentheteropolypeptide
emerges
from
s
eg etions
of methyl
groups to previously unmodified CpGs is catalyzed
convert affected DNA
sequences
within
facultative
athe
conformational
changes
in the
pore.
The regulatory
(R)tion
domain
contains
binding
of iron to the
repressor
protein
a conformational
change
that
tiodrive
molecule against its concentration
thetriggers
exit tunnel,
ribosomenchromatin
de novo methyltansferases, usually in response to various
intoacid
transcriptionally
euchromatin
orit encounters
viceby by
several
amino
residues
thatactive
must
be
phosphorylated
cAMP-dependent
gradient.
causes
it to
dissociate
from
mRNA.
The
ferrritin
mRNA
can
then
be
translated.
associated
chaperones.
If
necessary,
Autophagy
signal
transduction
mechanisms. The mechanism whereby CpGs
versa.
DNA
methylation
is
also
a
means
whereby
cells
silence
proteinOligomers
kinase (PKA) for chloride transport
to occur.
Native
additional
folding assistance is provided by
are
demethylated
is still obscure.
transposable
elements.
Each
cellabsorption
type has unique
protein
n
Un
channel
is differentiated
vital
proper
of All
salt
(NaCl)
and
SIGNAL
TRANSDUCTION
ANDfor
GENE
EXPRESSION
cells
respond
downstream
molecular
chaperones
such water
as to
tioThe chloride
fold
aepigenetic
Chaperones
g
modifications
that
are
referred
to
as
its
epigenome.
ing
the apical
membrane
epithelial
cells
that
line
ducts
and
greacross from
hsp70s
and hsp90s
and
their
associated
their(top)
environment
in surface
partthe
byof
altering
gene
expression
patterns.
Ag signals
Afterin
a brief
description
of
epigenetic
theand
role sweat
of
proteins.
Misfolded
proteins
are degraded
by
tubes
tissues
such asDegradation
lungs,
liver, modifications,
small
intestine,
glands.
Chloride
Histone
Modifications
epigenetics
is discussed
interface to
between
genomes
and cAMP.
a acombination
of chaperones
andThe
E3 ubiquichannel
opening
occursasinanresponse
signal
molecule,
cAMPthe environment.
Misfolded
Histones
a featured role in epigenetic gene expression
tin ligases
that together
recognize
target
dependent
kinase PKA then phosphorylates
specific
residues
in the and
Rhave
domain,
UPS
state
them
for destruction
by the
(ubiquitinregulation.
Covalent modification of histone N-terminal tails
s
causing a change in its conformation that
triggers
the binding
ofUPS
ATP
molecules
ne
proteosome domains
system). Aggregated
proteins
ero tion
(Figure
17B)
can
occur at specific amino acid residues because
p
and
NBD
.
The
two
nucleotide-binding
then
form
a
head-toto
NBD
a
2
a
DNA1Amyloid
Methylation
Ch grad
that resist digestion by proteasomes
are
theinside
unstructured
tails protrude outward from the nucleosome
fibrils
tail heterodimer-like
structure with the ATP-binding
sites on the
surfaces.
De
removed
by
autophagy.
wherechannel
they aregate
accessible
enzymes. The most
In aDNA
methylation
reactions a methyl
group is donated
As
result
of these intramolecular
rearrangements,
thebychloride
18-McKee-Chap18.indd 716
14/05/15 to
3:32modifying
AM
commonly
observed
SAM and
(p. 531)
to carbon-5
of cytosine
residues
(Figure 17A).
opens
chloride
ions flow
down their
concentration
gradient.
Hydrolysis
of modifications are methylation, acetylation,
ubiquitinylation
In mammals,
methylatedATP
cytosines
occurcauses
predominantly
in and that
one
of the NBD-bound
molecules
dimer disruption
results in of lysine, methylation of arginine, and
phosphorylation
of serine. (Histone modifications are desig59-CG-39closing.
sequences,
referred
dinucleotides
channel
Thewhich
NBDare
dimer
actstoasasaCpG
timing
device in that
the rate of ATP
nated by histone type followed by a one-letter symbol of the
or CpGs. The
C-5 methyl
residues
protrudeis open.
hydrolysis
determines
thegroups
lengthofofcytosine
time that
the channel
MORE RELEVANT
CONNECTIONS
Greater emphasis on the
relationship between
biochemistry and human biology
▼
19-McKee-Chap19.indd 763
into the major groove where they prevent binding of certain modified amino acid [Table 5.1, p. 134] and an abbreviation of
DNA-binding proteins (i.e., transcription factors). They also the modification type. For example, mono- and dimethyl modiOligosaccharide
Outside
enable the binding of proteins with methyl-CpG binding
dochains
of fications of lysine 4 on histone 3 are referred to as H3K4me and
According to the histone code hypothmains, called methyl-CpG-binding proteins (MeCPs), that
pro- H3K4me2, respectively.)
14/05/15 10:31 AM
glycoprotein
mote heterochromatin formation. CpGs are relatively rare in esis, the pattern of histone modifications within each DNA
sequence
regulates
gene
expression
by serving as a platform for
mammalian genomes. However, there are CpG-rich regions,
called CpG islands, in which CpGs are typically about 50% of the binding of specific accessory proteins. Once they are bound
NH3+
17-McKee-Chap17.indd 641
NBD1
14/05/15 3:31 AM
NBD2
Phe508
COO–
Inside
R domain
FIGUR E 11.33
The Cystic Fibrosis Transmembrane Conductance Regulator (CFTR)
CFTR is a chloride channel composed of two domains (each with six membrane-spanning
helices) that constitute the Cl2 pore, two nucleotide-binding domains (NBD), and a regulatory (R) domain. Transport of Cl2 through the pore, driven by ATP hydrolysis, occurs when
specific amino acid residues on the R domains are phosphorylated. The most commonly
observed CF-causing mutation is a deletion of Phe508 in NBD1, which prevents proper targeting of CFTR-containing vesicles to the plasma membrane. The precise structural relationships among the pore-forming helices remain unclear.
11-McKee-Chap11.indd 414
14/05/15 10:20 AM
Short Answer
61. Why are eukaryotic cells so much larger than prokaryotic
cells?
62. How does soap kill bacteria?
63. What would happen if the cell membrane was covalently
linked rather than held together by relatively weak van der
Waals forces?
64. Suggest a reason why phospholipids are constituents of cell
membranes rather than carboxylic acids.
65. Suggest a reason why some eukaryotic cells lack cell walls.
Thought Questions
285 NEW
END-OF-CHAPTER
REVIEW QUESTIONS
These questions are designed to reinforce your understanding of all of the key concepts discussed in the book so far, including this
chapter and the chapter before it. They may not have one right answer! The authors have provided possible solutions to these
questions in the back of the book and in the accompanying Study Guide for your reference.
66. Cyst formation causes a catastrophic loss of function in
form of FH, in which patients have no functional LDL receppolycystic kidney disease. Genetic research has linked this
tors, heart attacks begin at about age 8, with death occurring
disease to defects in genes that code for primary cilium
a few years later. Based on what you have learned in this
proteins. Describe in general terms how malfunctioning
chapter, briefly describe the cellular processes that are defecprimary cilia cause the formation of kidney cysts.
tive in FH.
67. Primary cilia have evolved as primary sensory organelles for 71. Mycoplasmas are unusual bacteria that lack cell walls. With
vertebrate cells. What structural features of these cilia make
a diameter of 0.3 mm, they are believed to be the smallest
them ideal for this purpose?
known free-living organisms. Some species are pathogenic
to humans. For example, Mycoplasma pneumoniae causes a
68. Several pathogenic bacteria (e.g., Bacillus anthracis, the cause
very serious form of pneumonia. Assuming that mycoplasof anthrax) produce an outermost mucoid layer called a capmas are spherical, calculate the volume of an individual cell.
sule. Capsules may be composed of polysaccharide or protein.
Compare the volume of a mycoplasma with that of E. coli.
What effect do you think this “coat” would have on a bacterium’s interactions with a host animal’s immune system?
72. The dimensions of prokaryotic ribosomes are approximately
14 nm by 20 nm. If ribosomes occupy 20% of the volume of
69. In addition to providing support, the cytoskeleton immobia bacterial cell, calculate how many ribosomes are in a typilizes enzymes and organelles in the cytoplasm. What advancal cell such as E. coli. Assume that the shape of a ribosome
tage does this immobilization have over allowing the cell
is approximately that of a cylinder.
contents to freely diffuse in the cytoplasm?
73. The E. coli cell is 2 mm long and 1 mm in diameter, whereas a
70. Familial hypercholesterolemia (FH) is an inherited disease
typical eukaryotic cell is 20 mm in diameter. Assuming that the
characterized by high blood levels of cholesterol, xanthomas
E. coli cell is a perfect cylinder and the eukaryotic cell is a per(lipid-laden nodules that develop under the skin near tenfect sphere, calculate the surface-to-volume ratio for each cell
dons), and early-onset atherosclerosis (the formation of
type (cylinder volume, V 5 pr2h; cylinder area A 5 2pr2 1
yellowish plaques within arteries). In the milder form of this
2prh; sphere volume, V 5 4/3(pr3); sphere area, A 5 4pr2).
disease, patients have half the plasma membrane low-density
FIGUR E 16.6
What do these numbers tell you about the evolutionary changes
lipoprotein (LDL) receptors needed for cells to bind to and
that would have to occur to generate an efficient eukaryotic
The Adenylate Cyclase Second Messenger System That Controls
internalize LDL (a plasma lipoprotein particle that transports
cell, considering that most biochemical processes depend on
Glycogenolysis
cholesterol and other lipids to tissues). These patients have
membrane-bound transport processes?
GDPfirst heart attacks in young adulthood. In the severe
When the receptor is unoccupied, the Gs protein a s subunit hastheir
LigandLigand
Adenylate
bound and is complexed with the bg dimer. The binding of hormone
binding
molecule
cyclase
(1) activates the receptor and leads to replacement of GDP with GTP by a
site
(inactive)
GEF (not shown) (2). The activated a-subunit interacts with and activates
Outside
adenylate cyclase. (3) The cAMP produced binds to and activates
of cell
cAMP-dependent protein kinase. Signal transduction ends when the
ligand leaves the receptor, the bound GTP is hydrolyzed to GDP by
the GTPase activity within the a s subunit, and the a s 02-McKee-Chap02.indd 74
Plasma
membrane
subunit dissociates from adenylate cyclase. Cyclic
γ
GTP
αs
AMP is deactivated by hydrolysis to AMP, a reaction
1
β
catalyzed by phosphodiesterase. (4) The a s subunit
GDP
then reassociates with the bg dimer. Glycogen
Inside
GDP
of cell
breakdown is initiated when cAMP-dependent
Receptor
protein kinase activates phosphorylase
G
protein
(inactive)
Ligand-receptor complex
s
kinase, which in turn activates (via
phosphorylation) the glycogendegrading enzyme glycogen
phosphorylase. The active subunits
of cAMP-dependent protein kinase (PKA)
move into the nucleus, where they
αs
activate the transcription factor CREB,
γ
allowing it to bind to CREs
2
β
(cAMP-response elements)
GTP
in combination with the coactivator
CBP. As a result, cAMP-inducible
Gs protein (active)
genes are transcribed.
The most robust and
complete set of review problems of any text,
with more than 1,250 end-of-chapter exercises
STUNNING ART
PROGRAM
More than fifty new illustrations
Adenylate cyclase (active)
Pi
3
γ
αs
β
GTP
ATP
cAMP-dependent
protein kinase
(inactive)
cAMP
γ
(+)
H2O
cAMP-dependent
protein kinase
(active)
Phosphorylase
kinase
(inactive)
αs
β
AMP
GDP
4
Cyclic AMP
Phosphodiesterase
Cytoplasm
(+)
Phosphorylase
kinase
(active)
ATP
Nucleus
ADP
αs
ADP
Coactivator
ATP
CREB
CRE
γ
β
CREB
Transcription
GDP
590
16-McKee-Chap16.indd 590
14/05/15 1:20 PM
14/05/15 2:44 AM
EngAgIng pEdAgOgY
A Review of Basic Principles
To ensure that all students are sufficiently prepared to acquire a meaningful understanding of biochemistry, the first four chapters—now streamlined for easier coverage and self-study assessment—review the principles of relevant topics like organic functional groups, noncovalent bonding, thermodynamics, and cell structure.
Chemical and Biological Principles in Balance
Comprehensive coverage offers each instructor the flexibility to decide how much chemistry or biology should be presented. Chemical mechanisms are always presented within the physiological context of the organism.
Real-World Relevance
Because students who take the survey of biochemistry course come from a range of backgrounds and 492 CHAPTER THIRTEEN Photosynthesis
have diverse career goals, the sixth edition consistently demonstrates the fascinating connections between biochemical principles and the fields of medicine, nutrition, agriculture, The
bioengineering,
andanforensics.
Calvin cycle (p. 493) requires
ATP:NADPH ratio of 3:2. However,
ATP is also used for processes other than carbohydrate synthesis. Consequently,
both noncyclic and cyclic photophosphorylation pathways are required for sufficient ATP synthesis during photosynthesis.
KEY CONCEPTS
• Eukaryotic photosynthesizing cells
possess two photosystems, PSI and
PSII, which are connected in series in
a mechanism referred to as the Z scheme.
• The water-oxidizing clock component of
PSII generates O2.
• The protons are used in the synthesis of
ATP in a chemiosmotic mechanism.
• PSI is responsible for the synthesis of
NADPH.
The Most Robust Problem-Solving Program
Available
WORKED PROBLEM 13.1
Calculate DG89 for the four-electron oxidation of H2O by NADP1 in the light
reactions.
• In-chapter “Worked Problems” illustrate how quantitative problems are solved and provide students with opportunities to put their knowledge into action right when new concepts are introduced
SOLUTION
The overall reaction is
2 H2O 1 2 NADP1 Æ O2 1 2 NADPH 1 2 H1
The reduction potentials (DE 89) for the two half reactions are
1/2 O2 1 2 H1 1 2e2 Æ H2O (DE 89 5 1 0.82 V)
NADP1 1 H1 1 2e2 Æ NADPH 1 H1 (DE 89 5 20.32 V)
DG89 is calculated using the equation DG 5 2nFDE 89
Substituting the DE89 values for the two half reactions
• Dozens of checkpoint questions are interspersed throughout 284 CHAPTER EIGHT Carbohydrate Metabolism
DG89 5 24 (96.5 kJ/V ? mol) [20.32 V2 (0.82 V)]
the chapters, motivating students to think critically about (386 kJ/Vmuscle
? mol) (21.14
V) demand for energy is high. After the O
Glyceraldehyde-3Lactate
In rapidly5contracting
cells, the
phosphate
5 2440 lactic
kJ/molacid fermentation provides sufficient NAD to allow glyhigh-interest topics
supply is depleted,
+
2
1
NAD
colysis (with its low level of ATP production) to continue for a short time (Figure 8.8).
Pi
QUESTION 13.5
QUESTION 8.1
Describe the role of each of the following molecules in photosynthesis:
Most molecules of ethanol are detoxified in the liver by two reactions. In the first,
a. plastocyanin
d. plastoquinone
ethanol
is oxidized to form acetaldehyde.
This reaction, catalyzed by ADH, produces
amounts of NADH:
b. large
b-carotene
e. pheophytin a
c. ferredoxin
f. lutein
O
• Hundreds of multiple-choice and short-answer questions at NADH
the end of the chapters test students’ knowledge, develop their +
Pyruvate
Glycerate-1,3conceptual understanding, and encourage them
to apply
what
bisphosphate
+
H
they have learned
FIGUR E 8.8
CH3
Currency
O
C
C
+
NAD
ADH
CH3 C
H
+
NADH
+
+
H
dria, the thylakoid membrane is permeable to Mg21 and Cl–. Therefore, Mg21 and
In –yeast
certain
bacterialmembrane,
species, pyruvate
decarboxylated
to form
ac- as
moveand
across
the thylakoid
therebyisdissipating
electrical
potential
Cl
etaldehyde,
which
is then across
reduced
NADH toduring
form ethanol.
(In a decarboxylprotons are
transported
thebymembrane
the light reaction.
The electroation
reaction,
an organic
loses a carboxyl
group
CO2.)ATP synthesis therechemical
gradient
acrossacid
the thylakoid
membrane
thatasdrives
fore consists mainly of a proton gradient that may be as great as 3.5 pH units.
1
Alcohol
Experimental
measurements of H :ATP ratios indicate that the movement
Pyruvate
dehydrogenase
O
CH 2
OH
decarboxylase
across
the thylakoid membrane
of about 12 protons in noncyclic photophosphorO−
ylation yields three molecules
of
ATP.
The
synthesis of these ATPs is made
C
H
O
CH3
Visit the companion website
at www.oup.com/us/mckee to read the
Biochemistry in Perspective essay on
+
photophosphorylation.
It is apparent from the preceding discussions that there are
O
many similarities between mitochondrial and chloroplast
ATP synthesis. For exAldehyde
+
H2Othat are encountered in aerobic
+ terms
H + molecules
CH3 of Cthe same
NAD
ample, many
and
dehydrogenase
respiration (Chapter 10) are also relevant to discussions of photosynthesis. Although there are Oa variety of differences between aerobic respiration and photosynthesis, the essential difference between the two processes
is the conversion of light
NADH
+(Recall
2 H+
CHredox
C energy
O− +
3
energy into
by chloroplasts.
that mitochondria produce redox
energy by extracting high-energy electrons from food molecules.) Another critical
One
commoninvolves
effect ofthe
alcohol
intoxication
is the accumulation
of lactate
in memthe
difference
permeability
characteristics
of mitochondrial
inner
blood.
explainmembrane.
why this effect
occurs?to the inner membrane of mitochonbraneCan
andyou
thylakoid
In contrast
Pyruvate
13-McKee-Chap13.indd 492
OH
Soon
after photosynthesis
its production, acetaldehyde
is converted
to acetate
by aldehyde
dehy- is
During
light energy captured
by an
organism’s
photosystems
drogenase,
which
a reaction
thatenergy.
also produces
NADH: is referred to as
transduced
intocatalyzes
ATP phosphate
bond
This conversion
The NADH produced during the conversion
of glyceraldehyde-3-phosphate to glycerate-1,
3-bisphosphate is oxidized when pyruvate is
converted to lactate. This process allows the
cell to continue producing ATP under anaerobic conditions as long as glucose is available.
With a goal of providing balanced and thorough coverage of chemistry within a biological context, the sixth edition has been
thoroughly updated to present recent developments in the field. It remains focused on the “big-picture” principles that are the cornerstone of the one-term biochemistry course.
CH2
Photophosphorylation
Recycling of NADH during Anaerobic
Glycolysis
CO2
CH3
Acetaldehyde
NADH
+
H
+
+
NAD
CH 3
Ethanol
This process, called alcoholic fermentation, is used commercially to produce
wine, beer, and bread. Certain bacterial species produce organic molecules other
than ethanol. For example, Clostridium acetobutylicum, an organism related
14/05/15 3:23 AM
Adopt the Text and Access
a Powerful Teaching Package
For Instructors
Ancillary Resource Center (ARC)
The McKee ARC (www.oup-arc.com/mckee) contains a wide range of lecture assessment and additional
resources for instructors, including:
• A new Video and Animation Guide, with links to freely available and high-quality
animated biochemical processes
• Powerpoint-based images in enhanced electronic format
• Lecture Notes Slides for each chapter of the text
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exercises from the text that are not included in the book itself. Each
solution has been independently checked for accuracy by a panel of
expert reviewers.
• NEW!
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