Appendix

Solutions
Chapter 1: End-of-Chapter Questions c. photoautotroph—organisms that transform the energy
of the sun into energy
Review Questions d. chemoheterotroph—consume preformed food mole-
cules as their energy source
2
e. photoheterotroph—use both light and organic biomole­
a. functional group—group of atoms within a molecule
cules as their energy source
with distinct chemical properties
b. R-group—group of atoms that make up a side chain in 13
amino acids A few examples of life science fields that require a solid un-
c. carboxyl group—functional group consisting of derstanding of biochemistry include agronomy, forensics,
R-C(5O)OH or R-COOH. marine biology, plant biology, pharmacology, plant or animal
d. amino group—functional group consisting of R-NH2 genetics, environmental science, and wildlife biology.
e. hydroxyl group—functional group consisting of
16
R-OH
Amino acids occur in peptides and proteins. Sugars occur
4 in oligosaccharides and polysaccharides. Nucleotides are
a. fatty acid—monocarboxylic acids represented by the the components of nucleic acids. Fatty acids are compo-
formula R-COOH in which R is an alkyl group that nents of several types of lipid molecules, e.g., triacylglyc-
contains carbon and hydrogen erols and phospholipids.
b. saturated fatty acid—fatty acid that contains no
carbon-carbon double bonds 18
c. unsaturated fatty acid—fatty acid that contains one or Cells use oxidation-reduction reactions to convert bond
more carbon-carbon double bonds energy in biomolecules into higher energy ATP bonds.
d. triacylglycerol—esters containing glycerol and three Energy is captured as electrons are transferred from
fatty acids ­reduced molecules to more oxidized ones.
e. phosphoglyceride—esters containing glycerol and two 20
fatty acids Catabolic pathways convert nutrients to small-molecule
7 starting materials. Anabolic pathways utilize the small-
a. mRNA—messenger RNA molecule precursors to synthesize complex structure and
b. tRNA—transfer RNA function.
c. rRNA—ribosomal RNA 22
d. siRNA—small interfering RNA Examples of reactions involving acyl transfer nucleophilic
e. miRNA—micro RNA substitution include the formation of thioesters such as
9 acyl-SCoA molecules from acyl monophosphate and co-
a. elimination reaction—a double bond is formed when enzyme A, the reaction of a carboxylic acid with an alco-
atoms in a molecule are removed hol to form an ester (e.g., ethyl acetate is the product of
b. hydrolysis—nucleophilic substitution reactions in the reaction between acetic acid and ethanol), and the
which the oxygen of water serves as the nucleophile ­hydrolysis of the amide bonds in protein molecules to
c. addition reaction—two molecules combine to form a yield amino acids.
single product 25
d. dehydration reaction—removal of water from biomole­ The molecules belong to the following classes:
cules containing alcohol functional groups a. amino acid
e. hydration reaction—water is added to an alkene b. sugar
producing an alcohol c. fatty acid
11 d. nucleotide
a. autotroph—organisms that transform the energy of the 27
sun into energy Important ions found in living organisms are Na1, K1,
b. chemoautotroph—organisms that transform the energy Ca21, and Cl-. Many polyatomic ions are also common,
of the various chemicals into energy such as NH41, PO432, and CO322.
A -1

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 A-2 Appendix

29 By dividing the volume of the hepatocyte by the volume of

The functions of polypeptides include transport, structural the prokaryotic cell (4200 mm3 /1.57 mm3) the number of
composition, defence, storage, regulation, movement, and prokaryotic cells that would fit within the heptocyte is
catalysis. ­obtained: 2700.
32 2.2
Examples of waste products produced by animals include Without a means of disposal, the lipid molecules will
carbon dioxide, ammonia, urea, uric acid, and water. accumulate in the cells. Cell function is eventually compro-
mised and the cells die.
34
Complex control mechanisms and protective systems 2.3
allow living organisms to withstand various physical and/or Ten percent of 70 kg is 7 kg, which can be expressed as 7 3
chemical challenges, e.g., fluctuations in temperature, 106 mg. To calculate the weight of a single ‘average’ mito-
availability of nutrients, and energy needs. As such, living chondrion, divide the estimated total weight of mitochondria
organisms are robust, yet they are fragile in their vulner- by the estimated number of mitochondria (1 3 1016):
ability to unusual or rare events that cause irreparable 7 3 106 mg
damage. For ­example, a bleeding cut will clot and heal,   1 3 1016
but extended ­exposure to high levels of carbon monoxide The answer (i.e., the weight of an average mitochondrion) is
causes death. approximately
7 3 10210 mg (1 mg 5 1 3 1026 kg)
Thought Questions
2.4
36 Cell division involves the highly organized restructuring of
The leaving group in nucleophilic acyl substitution reac- the microtubules that form the mitotic spindle during the
tions involving thioesters is RS2. When the thioester in- phases of mitosis. Microtubule function depends on dynamic
volved contains coenzyme A, the leaving group is CoAS2. instability, that is, the capacity to rapidly shorten and lengthen
38 via polymerization/depolymerization reactions. Cell division,
The smaller the pKa value of a chemical group, the better which is unregulated in cancerous cells, is suppressed by taxol
it functions as a leaving group. In other words, its anion because this drug stabilizes microtubule structure.
is more stable.
Chapter 2: End-of-Chapter Questions
40
In the normally functioning system the lipid molecule is not Review Questions
particularly toxic (i.e., its presence at normal levels does not
3
interfere with brain function). In individuals that lack the
a. supramolecular complex—composed of molecules
key enzyme, this lipid begins to accumulate within neurons
held together by noncovalent intermolecular forces
and other brain cells. Its physical presence interferes with
b. ribosome—protein-synthesizing unit composed
the way nerve tracts are laid down. Neurological systems
of protein and RNA
that require integration of brain functions (e.g., motor con-
c. channel protein—membrane protein that transports
trol and intelligence) begin to fail.
­specific ions
42 d. carrier protein—membrane protein that transports
Both normal and tumour cells are robust, i.e., they remain ­specific molecules
alive despite perturbations. The genetic instability of e. receptor – proteins with binding sites for extracellular
tumour cells facilitates the survival of the tumour. Out of ligands
the millions of cells in a tumour, there is a distinct possibil-
ity that one or more will express the P-glycoprotein. Under 5
the selection pressure of the drug, these cells will survive. a endotoxin—molecule that is released from membrane-
Cells not expressing P-glycoprotein or another means of bound lipids when the cell disintegrates
detoxifying the drug will die. b. periplasmic space—the region between the outer mem-
brane and the plasma membrane
Chapter 2: In-Chapter Questions c. biofilm—disorganized accumulations of polysaccha-
rides that form during adherence to surfaces and growth
2.1 d. slime layer—also known as biofilm, disorganized
The volume of a prokaryotic cell is calculated as follows: accumulations of polysaccharides that form during
pr 2h 5 3.14 3 (0.5 mm)2 3 2 mm 5 1.57 mm3 ­adherence to surfaces and growth
e. bacterial capsule—some pathogenic bacteria possess
The volume of a eukaryotic cell is calculated as follows: ­secreted polysaccharides and proteins that allow the
4/3 pr 3 5 4 3 (3.14 3 103)/3 5 4200 mm3 bacteria to avoid detection by the host immune system

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 Appendix
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7 23
a. glycocalyx—eukaryotic carbohydrate coat on the outside The components of the endomembrane system are the
of the plasma membrane plasma membrane, endoplasmic reticulum, Golgi appara-
b. extracellular matrix—secreted structural proteins and tus, nucleus, and lysosomes. All of these control transport
complex carbohydrates to form a gelatinous material that of ions and molecules across its membrane. Each mem-
binds cells together brane encloses an internal space that requires such control
c. cell cortex—three-dimensional meshwork of proteins on to function properly, i.e., for key biochemical reactions to
the inner surface of eukaryotic plasma membranes take place. The compartments of the endomembrane
d. endoplasmic reticulum—a system of interconnected system are connected via membranous vesicles that bud
membranous tubules, vesicles, and sacs off from a donor membrane in one component in the
e. ER lumen—space enclosed by the ER membrane system and fuse with the membrane of another compo-
nent. For example, proteins synthesized in the RER are
9 transferred via vesicles to the Golgi apparatus for further
a. nucleoplasm—subcellular region surrounded by the processing reactions.
­nuclear envelope that harbours chromatin
b. chromatin fibre—uncondensed chromosomes 25
c. nuclear matrix—functions as a scaffold that organizes Mitochondrial fission and fusion processes promote
loops of DNA healthy mitochondrial function. Fission facilitates the pro-
d. nucleolus—site of rRNA synthesis and ribosome assembly duction of additional energy when the cell’s requirements
e. nuclear envelope—membrane that functions to separate are high and the segregation of damaged portions of mito-
DNA replication and transcription from the cytoplasm chondria prior to their destruction. Fusion facilitates the
rescue of mitochondria with minor damage by allowing
12 the mixing of their contents with that of healthy
a. mitochondrion—organelle that is the site of aerobic mitochondria.
respiration
b. aerobic respiration—process in which chemical bond 27
energy is used to synthesize ATP The nucleus is the repository of the cell’s hereditary infor-
c. apoptosis—programmed cell death pathway mation. The nucleus also exerts a profound influence over
d. outer mitochondrial membrane—porous smooth mem- all the cell’s metabolic activities through the expression of
brane of the mitochondrion that information.
e. inner mitochondrial membrane—membrane of the
mitochondrion that is impermeable to ions 29
The function of the Golgi apparatus is the processing,
14 ­packaging, and distribution of cell products, such as
a. cytoskeleton—supportive network of fibres, filaments glycoproteins.
and proteins inside the cell
b. microtubule—filaments formed by reversible polymer- 31
ization of tubulin dimers The nuclear pore complex (NPC) is a large 120-MDa
c. MAP—microtubule-associated proteins structure with a diameter of 120 nm that consists of
d. IFT—intraflagellar transport process about 100 proteins known as the nucleoporins. Filaments
e. primary cilium—nonmotile form of cilia that extend from the cytoplasmic and nucleoplasmic side
of the NPC function as docking sites for large molecules
16 that will be transported through the pore in a GTP-­
Microorganisms are required for human health with regard dependent ­manner. Small substances such as ions and
to improved digestion, vitamin synthesis, pathogen growth small proteins (40 kDa or less) readily diffuse through
repression and robust immune system development. the NPC. Large molecules are restricted from passing
through the pore.
19
Examples of factors that promote protein misfolding in- 33
clude metabolic stress (e.g., illness), oxidative stress (oxygen Peroxisomes are small spherical membranous organelles
radical formation), inflammatory signalling processes, and that contain oxidative enzymes. Primary functions of
genetic factors (e.g., a gene mutation that results in the syn- ­peroxisomes are the generation and degradation of perox-
thesis of a defective protein). ides and the oxidation of toxic molecules. Additional func-
tions include the synthesis of certain membrane lipids and
21 the degradation of fatty acids and purine bases. To form
Macromolecules of each type usually are present in low peroxisomes, nuclear genes code for the enzymes and
numbers. The concentration of any one macromolecule is ­membrane proteins, which are synthesized on cytoplasmic
low but adds to the overall number of molecules. This ribosomes and then imported into preperoxisomes. The ER
­results in crowding. provides the peroxisomal membrane, and peroxins (a group

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 A-4 Appendix

of proteins) assemble the peroxisomes. [Peroxisomes are the number of unshared electron pairs. Because of the abil-
also involved in photorespiration in plants (Chapter 13 of ity of each ammonia molecule to form a hydrogen bond
your text.)] with a neighbouring molecule, ammonia ‘ice’ would be
­expected to be less dense than liquid ammonia.
35
Hepatocyte SER functions include synthesis of the lipid 3.2
components of very-low-density lipoproteins (VLDL), and From left to right in the illustration, the noncovalent
biotransformation reactions, which convert water-insoluble ­interactions are ionic, hydrogen bonding, and van der
metabolites and xenobiotics into more soluble products for Waals interactions.
excretion. Striated muscle SER is called the sarcoplasmic
3.3
reticulum (SR) and is a reservoir for calcium ions, the
Tendons and ligaments contain large amounts of collagen
signal that triggers muscle contraction.
and other molecules that bind substantial amounts of
structured water molecules. Water is an incompressible
Thought Questions substance; that is, it cannot be forced to occupy a smaller
38 space. As a result, structures containing large amounts of
The genes that are mutated in polycystic kidney disease water can absorb relatively large amounts of force without
encode a mechanoreceptor that monitors fluid flow in the damage.
kidney. When these genes are mutated cell division stimu- 3.4
lation results in cyst formation. The equilibrium shifts to the right to replace lost bicarbon-
40 ate, and the acid concentration increases. The resulting
The immobilization of enzymes and organelles on the cyto- ­condition is called acidosis.
skeleton facilitates the highly organized set of living pro-
cesses required to sustain the living state. For example, the Chapter 3: End-of-Chapter Questions
close proximity of immobilized enzymes in a biochemical
Review Questions
pathway allows the rapid delivery of the product of one
enzyme to the active site of the next. This circumstance re- 3
quires lower concentrations of reactant molecules than the a. osmosis—spontaneous passage of solvent molecules
time-consuming diffusion process. through a semipermeable membrane that separates a
solution of low solute concentration from one with high
43
solute concentration
The volume of a ribosome is calculated as follows:
b. osmotic pressure—the pressure required to stop the net
pr 2h 5 (3.14)(0.007 mm)2(0.02 mm) 5 3 3 1026 mm3 flow of water across a membrane
The volume of a bacterial cell (from question 2.42) is c. isotonic solution—solution that contains the same
1.6 mm3. The number of ribosomes that can fit in a bacterial ­concentration of solute and water on both sides of
cell is 1.6/3 3 1026 5 5 3 105, but because they occupy a selectively permeable membrane
only 20% of the cell’s volume, divide by 5 to give 1 3 105 d. membrane potential—asymmetry of charge distribution
ribosomes per bacterial cell. on the surfaces of cell membranes that create an electrical
gradient
e. hydronium ion—H3O1
Chapter 3: In-Chapter Questions
5
3.1 Both c and d are weak acid – conjugate base pairs.
The tetrahedral structures of the three molecules are as
follows: 7
Osmolarity 5 molarity 3 the extent of ionization (i, the
H number of ions produced per ionic compound). Na3PO4
­dissociates into four ions. Assuming 85% ionization, the
O N C osmolarity of a 1.3 M solution of Na3PO4 would therefore
H H H H H H be 1.3 3 4 3 0.85 5 4.4
H H
Water Ammonia Methane 9
One, CH3 – OH - - - - O – H(CH3)
In the solid state of water, the oxygen atom has two electron
pairs that form hydrogen bonds with neighbouring water 12
molecules. The nitrogen atom in ammonia has one un- π 5 iMRT where π 5 0.01 atm
shared electron pair that can form a hydrogen bond with a i 5 1
neighbouring ammonia molecule and methane has none. R 5 0.0821 L atm/mol K
Note that the heats of fusion for these substances parallel T 5 298 K

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 Appendix
A-5

Solving for M: 22
0.01 atm 5 (1) (0.0821 L atm/mol K) (298 K) (M) In a mixture of one mole of benzoic acid (‘HA’) and one
M 5 4.08 3 10 −4 mol/L mole of sodium benzoate (A2), [HA] 5 [A2], and so
Solving for the molecular weight of the protein: [A2]/[HA] 5 1. Since log(1) 5 0, the Henderson-
0.056 g/0.030 L 5 1.867 g/L Hasselbalch equation simplifies to pH 5 pKa 5 4.2.
1.867 g 5 4.08 3 10 −4 mol [A2]
1 mol of the protein 5 4575.98 g 5 4600 g pH 5 pKa 1 log   pH 5 4.2 1 log(1)  pH 5 4.2
[HA]
14 25
Carbon dioxide is present in the blood in sufficient quantities When H1 (HCl) is added to an acetic acid/acetate buffer,
to make it effective as a buffer. Phosphate concentration in the H1 will react with the acetate (A2) to form more acetic
blood is too low for this compound to be an effective buffer. acid (HA).
Within cells, the phosphate concentration is much higher, and # moles H1 (HCl) added 5 (1 3 1023 L)(1 M) 5 1 3 1023
it can therefore act as an effective buffer. mol H1 added
# moles of HA and A2 initially present: (1 L)(1 M HA)
16
5 1 mol HA 5 1 mol A2
H2CO3 and HCO32 are both present at pH 6.4. H2CO3,
H1 1 A2 « HA
HCO32 and CO322 are present at pH 8. HCO32 and CO322
are present at pH 13. The number of moles of HA will increase:
1 mol HA (initial) 1 0.001 mol HA (from the added HCl)
18 5 1.001 mol HA
Hyperventilation drives the transfer of carbon dioxide from
the blood. This process, which shifts the following equilib- The number of moles of A2 will decrease:
rium to the left, consumes protons, thereby making the 1 mol A2 (initial) 2 0.001 mol A2 (that reacted with HCl) 5
blood more alkaline. 0.999 mol A2

20 (Note that it’s not necessary to calculate the total volume

Ascorbic acid is the weak acid (HA) and sodium hydrogen and the molarity, since the volume would be in both the
ascorbate is its conjugate base (A2). Note that a more accu- ­numerator and the denominator, and would cancel.)
[A2]
rate representation is H2A and HA2. pH 5 pKa 1 log
The number of moles of hydrogen ascorbate initially: [HA]
pH 5 4.75 1 log [(0.999 mol A2)/(1.001 mol HA)]
(300 mL)(0.25 M) 5 75 mmol HA2
pH 5 4.75 1 (20.0009) 5 4.7491 ≈ 4.75
The number of moles of HCl added: (150 mL)(0.2 M) 5 30
mmol HCl Compare this insignificant pH change, upon the addition of
HCl to a buffer, with the addition of the same amount of
Since HCl reacts completely with the hydrogen ascorbate, HCl to water (pH 3).
30 mmol HCl added 5 30 mmol HA2 that react with
HCl to form H2A Thought Questions
The number of moles of H2A remaining after addition is:
75 mmol HA2 – 30 mmol that react with HCl 5 27
45 mmol H2A left over. The gelatin will dehydrate as the salt becomes hydrated by
30 mmol of ascorbic acid were formed. the water in the gelatin.
Next, use the Henderson-Hasselbalch equation (pKa1 5 4.04): 29
or The cell will undergo haemolysis. Because of the large influx
[HAscorbate] [HA2]
pH 5 pKa 1 log or pH 5 pKa 1 log of sodium ions the cell becomes hypertonic relative to blood.
[H2Ascorbate] [H2A]
[45 mmol] 32
pH 5 4.04 1 log The salts dissolved in the seawater (a hypertonic solution)
[30 mmol]
pull water out of plants and will cause them to die. This is
5 4.04 1 0.18 5 4.22 the reverse of the normal flow of water from the environ-
ment into a plant.
Does a pH of 4.22 make sense? Yes, because we have
more base than acid present, and 4.22 is more basic than 34
4.04, the pKa. Note that this method included a shortcut: In a liquid, the molecules must be free to move over one
millimoles rather than molarity was used. This is another. In the gelatin solution, each water molecule
valid because the total volume is the same and would ­hydrogen-bonds with two segments of the protein, locking
cancel out. To use molarity, divide both the numerator the protein chains and the water together. Because the
(0.0045 mol) and the denominator (0.0030 mol) by the water molecules are no longer able to move freely, the
total volume (0.450 L). ­mixture becomes semirigid.

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 A-6 Appendix

36 Amount of glucose required to produce 100 kcal through

The conversion of glycogen to glucose creates an increase ATP
in osmotic pressure, and water would flow into the cell. 5 (100 kcal)/(.40)(686 kcal/mol)
To offset this rise in osmotic pressure, ions such as 5 100 kcal/274.4 kcal/mol
sodium and potassium are pumped out of the cell. These 5 0.36 mol
ions would be followed by water, thus restoring cell 5 0.36 mol 3 180 g/mol 5 65.6 g of glucose
volume.
Chapter 4: End-of-Chapter Questions
38
Sugars contain many –OH (alcohol) groups per molecule. Review Questions
Alcohols are structurally similar to water (ROH vs. HOH)
and have similar chemical properties. The OH groups of 2
the alcohols ‘hydrate’ the proteins and prevent them from a. exergonic reaction—chemical reactions that release
aggregating. energy (i.e., have a negative free energy charge)
b. endergonic reaction—chemical reactions that absorb
40 energy (i.e., have a positive free energy charge)
The syrup is actually a mixture of the sugar and small c. phosphoryl group transfer potential—the tendency of
amounts of water that remain tightly held by hydrogen phosphorylated molecules such as ATP to undergo
bonding to the OH groups of the sugars. Such tightly held hydrolysis
water molecules prevent the direct hydrogen bonding be- d. dissipative system—requires that continuous work
tween –OH groups in the sugar molecules required for be done on the system because otherwise all natural
crystallization. ­processes will proceed towards equilibrium
42 e. phosphoanhydride bond—a bond formed from two
The equation is set up as follows: ­molecules of phosphoric acid with the release of a water
molecule.
69.9 J/g(1g) 1 1.03 J/g(1g)(85.5259.955) 1 549 J/g(1g) 5 646.6 J
5
The energy required to vaporize water is 4.7 times that of For a reaction to proceed to completion the total overall
hydrogen sulfide. Most of this difference is in the heat of DG°9 must be negative, and there must be a common inter-
vaporization. In water, strong hydrogen bonds must be mediate, in this case Pi. This is true of reaction b and e.
broken. Hydrogen sulfide does not have strong hydrogen
7
bonds to break, hence the energy requirement is less.
The principle of coupled reactions.
44
Oxygen is a smaller atom than nitrogen. As a result, the 9
­hydrogens of the water molecule can approach the oxygen ATP 1 glutamate 1 NH3 Æ ADP 1 Pi 1 glutamine
more closely to form stronger bonds. Oxygen is also more ATP 1 H2O Æ ADP 1 Pi DG°9 5 −30.5 kJ/mol
electronegative than nitrogen, resulting in an O–H bond
Glutamine 1 H2O Æ glutamate 1 NH3 DG°9 5 −14.2
being more polar than an N–H bond.
kj/mol
Chapter 4: In-Chapter Questions Reverse the second equation and add the DG°9 values.
ATP 1 H2O Æ ADP 1 Pi DG°9 5 −30.5 kJ/mol
4.1 Glutamate 1 NH3 Æ glutamine 1 H2O DG°9 5 114.2
DG9 5 DG89 1 RT ln ([ADP][Pi]/[ATP]) kJ/mol
where R 5 8.315 3 1023 kJ/mol • K
ATP 1 glutamate 1 NH3 Æ ADP 1 Pi 1 glutamine
      T 5 310 K
DG°9 5 −16.3 kJ/mol
  [ADP] 5 0.00135 M, [ATP] 5 0.004 M,
     [Pi] 5 0.00465 M 11
  DG89 5 230.5 kJ/mol Under standard conditions the following statements are
true: a and e.
DG9 5 230.5 kJ/mol 1 (8.315  J/mol • K)(310)
      ln(0.00135 M)(0.00465 M)/(0.004 M) 13
DG9 5 230.5 1 2.577 (ln 0.00157) Under standard conditions the following statements are
  5 230.5 2 16.64 true: b, d, and e.
  5 247.14 kJ/mol 5 247.1 kJ/mol
15
4.2 The reduction of CO2 to methane by Methanococcus
Amount of ATP required to walk a mile janaschii, a hyperthermophile, is possible due to the high
5 (100 kcal/mi)/7.3 kcal/mol temperatures and pressures of the hydrothermal vent envi-
5 13.7 mol/mi 3 507 g/mol 5 6945.2 g/mi 5 6950 g/mi ronments in which the organism thrives. This reduction is

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 Appendix
A-7

thermodynamically favourable under these conditions, but 28

not at ambient temperature and pressure. Note that using a Using Einstein’s equation E 5 mc2:
coupled reaction to drive CO2 reduction ­forwards would c 5 3.0 3 108 m/s2
result in a favourable DG for the overall process, but would
not change the DG for the reduction reaction alone. In other E 5 (0.001) 3 (3.0 3 108 m/s)2
words, a coupled reaction can provide the energy to drive E 5 9 3 1013 joules
CO2 reduction, but cannot convert an energy-­requiring re- Coal yields 393.3 kJ/mol 5 393,300 joules/mol
action into an energy-producing reaction. This is the inher-   5 9 3 1013 joules 3 (1/393,300 joules/mol)
ent difference between an organism using ATP hydrolysis, (1g/mol)(1kg/1000g)
for example, to drive CO2 reduction forwards, and an or-
ganism that obtains energy from CO2 reduction to synthe-   5 228,832 kg
size ATP. 30
17 The balanced equation is
In the absence of Mg21, increased repulsion between a­ djacent C17H35COOH 1 26O2 Æ 18CO2 1 18H2O
negative charges of ATP would cause it to have less stability DH 5 DHproducts − DHreactants
than ATP with Mg21 present. 5 18 mol(−94 kcal/mol) 1 18 mol(−68.4 kcal/mol) −
19 (1 mol)(−211.4 kcal/mol)
[glucose] 5 [Pi] 5 4.8 mM 5 4.8 x 1023 M 5 −1692 kcal − 1231.2 kcal 1 211.4 kcal
[glucose-6-phosphate] 5 0.25 mM 5 −2711.8 kcal 5 −2712 kcal

Keq 5 Keq 5
[glucose][Pi] 32
[glucose-6-phosphate] The sulfur of the thioester is larger than oxygen of the
(4.8 3 1023M)(4.8 3 1023M) ­alcohol. So sulfur can stabilize the unshared electron pairs
Keq 5 more easily. Consequently, there is a larger difference in
(2.5 3 1024M)
energy between the reactants and products, which translates
Keq 5 9.2 3 1022 M into a larger DG.
Thought Questions
22
Chapter 5: In-Chapter Questions
A newly identified bacterial strain that could grow in the 5.1
presence of arsenate opens a new debate over whether Amino acids a and b are neutral, nonpolar, c is basic, and d
­arsenate can substitute for phosphate in living organisms. is an acidic amino acid.
Arsenic and phosphorus have similar oxidative states and
5.2
its most common form 51 (V) oxides such as arsenate
Bacteria with surface polypeptides composed of d-amino
(HAsO422) has similar pKa values to those of phosphate.
acids are resistant to degradation because the proteases,
The major argument against arsenate substituting for phos-
the enzymes that immune system cells use to degrade
phate is arsenate-esters and arsenate-diesters are extremely
protein in foreign cells, can only catalyse the hydrolysis
unstable in aqueous solutions. This higher reactivity with
of peptide bonds between l-amino acids. In other words,
water would become problematic for long-term stability of
the active sites of proteases are stereospecific; that is, they
the genome of arsenate containing nucleic acids.
can only effectively bind peptides composed of l-amino
24 acids.
DG9 5 2RT ln Keq 5.3
216,700 J/mol 5 2(8.315J/mol•K)(298 K)ln Keq The isoelectric point for the tripeptide valylcysteinyltrypto-
phan is calculated as follows: The pKa values are (1) valyl
216,700 5 2 2478 ln Keq amino group 5 2.32; (2) tryptophan carboxylate group
16,700/2478 5 ln Keq 5 9.39; and (3) cysteine side chain 5 8.33. The electrically
6.74 5 ln Keq neutral species of this tripeptide would contain a positively
charged amino group and a negatively charged carboxylate
Keq 5 851 [ATP][G-6-P]/[ATP] [glucose]
group. The pI is calculated by adding the pKa values for the
26 amino and carboxylate groups and dividing by two, i.e.,
DG is the most useful criterion of spontaneity because it 2.32 1 9.39/2 5 5.86. Since the pK R for the cysteinyl side
reflects the change in entropy, which must increase for a chain is more than two pH units away from the pI, it
reaction to be spontaneous. ­remains largely uncharged.

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 A-8 Appendix

5.4
The structure of the penicillamine-cysteine disulfide is

O O

C OH C OH

H C NH2 H C NH2

H3C C S S C H

CH3 H

5.5
The complete structure of oxytocin is

NH2
CH3 CH3
NH2 O C CH
CH2
O C O CH2 H O H H O CH2 CH2 O CH2 O
H
CH2
C C N C C N C C N C C N C CH2 NH2
CH2 N
C H CH2 H H H
H
O C S

N H S
CH3 C H H H CH2
CH
C N C C N C C OH
CH2
CH3 O CH2 O H O

OH

At pH 4 the terminal amino group of the glycine would be vasopressin. If the arginine residue of vasopressin is re-
protonated to give the molecule a 11 charge. The isoelec- placed by a lysine residue, it is expected that there will be
tric point of oxytocin is 5.6. Therefore at pH 7.3 and pH 9 a decrease in the molecule’s binding properties because of
the molecule will have a net negative charge. the structural differences between the two side chains. This
decrease would probably not be large, since the side chains
5.6 are similar in length and are both positively charged.
The partial overlap in the biological properties of vasopres-
sin and oxytocin can be explained in part by the Ile residue 5.7
at position 3 of oxytocin. Presumably, given the overall The trait is recessive, and two copies of the aberrant gene
similarities in size and the identical nature of six of the are required for full expression of the disease. Primaquine
eight amino acid residues in the two molecules, the hydro- induces the production of excess amounts of the strong oxi-
phobic side chain of this Ile can reach and partially fit into dizing agent hydrogen peroxide. In the absence of sufficient
the hydrophobic pocket of the vasopressin receptor. The amounts of the reducing agent NADPH, the peroxide mole­
degree of functional overlap between the two ­peptides is cules cause e­ xtensive damage to the cell. No, a higher than
reduced by the leucine residue at position 8 of oxytocin normal peroxide level in blood cells is damaging to the
because the side chain of this residue is not only neutral malarial parasite and is selected for in ­geographical regions
but smaller than the positively charged arginine residue of where malaria occurs.

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 Appendix
A-9

5.8
The solution to the first two illustrations is
Greek key -helix

-pleated sheet

4
5
8
7
6
2
C 1 3

N
-meander

The solution to the third illustration is

-helix
3
2

4 1

8
-pleated 5
strand

7
6

N
C

This protein is an example of an a/b-barrel structure.

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 A-10 Appendix

5.9
Arginine Aspartate
H H O H H O

N C C N C C
Serine Glutamate
CH2 CH2
H H O H H O Threonine Serine
CH2 C O H H O H H O
N C C N C C –O
CH2 N C C N C C
CH2 CH2
H N H C O CH2
O H CH2
+ Salt bridge
C NH2 CH3 H H O
Hydrogen bond O C
NH2 NH2 Hydrogen bond
(a) (b) (c)

Glutamate Aspartate
H H O H H O Tryptophan

N C C N C C H
Phenylalanine
CH2 CH2 N H
C O
O C C
CH2 C O
–O
H C CH2
C H
O N
H N
Hydrogen bond
H Hydrophobic interaction
(d) (e)

5.10 c. holoprotein—a protein that is combined with its

Collagen is a major structural protein found in connective prosthetic group
­tissues. Consequently, the failure of collagen molecules to d. intrinsically unstructured protein—a protein with partial
form properly weakens these tissues causing diverse symp- or complete lack of ordered structure
toms. Examples include cataracts, easily deformed bones, e. kinesin—motor protein that moves vesicles and organ-
torn tendons and ­ligaments, and ruptured blood vessels. elles along microtubules
5.11 5
BPG stabilizes deoxyhaemoglobin. In the absence of a. aldimine—Schiff bases formed by an amino group
BPG, ­oxyhaemoglobin forms more easily. Fetal haemoglo- reacting with an aldehyde group
bin binds BPG poorly and, therefore, has a greater affinity b. heat shock protein—a group of conserved proteins that
for oxygen. assist in protein folding by preventing inappropriate
protein-protein interactions.
5.12
c. multifunction protein—a protein with multiple and often
Myoglobin, composed of a single polypeptide, binds oxygen
unrelated functions
in a simple pattern—it binds the molecule tightly and re-
d. protein family—composed of protein molecules that are
leases it only when the cells’ oxygen concentration is very
related by amino acid sequence similarity
low. The binding of oxygen by haemoglobin, a tetramer, has
e. protein superfamily—proteins more distantly related
a more complicated sigmoidal pattern that is made possible
by the noncovalent interactions among its four subunits. 7
a. salt bridge—noncovalent bonds that occur between ionic
groups of opposite charge
Chapter 5: End-of-Chapter Questions b. oligomer—multisubunit proteins
c. allosteric transition—ligand-induced conformation
Review Questions
changes
3 d. protein denaturation—the process of structural disrup-
a. metalloprotein—proteins that contain metal ions tion of a protein
b. hormone—chemical signal molecules produced in one e. amphipathic molecule—a molecule that contains both
cell that regulates the function of other cells hydrophobic and hydrophilic components

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 Appendix
A-11

9 chains. Of the noncovalent interactions that are possible,

A polypeptide is a polymer containing more than 50 amino hydrophobic interactions are particularly important. (Recall
acid residues. A protein is composed of one or more poly- that hydrophobic interactions are driven in part by the
peptide chains. A peptide is a polymer with fewer than ­increase in entropy in the surrounding water molecules.)
50 amino acid residues. 21
11 The pKa of the amino group of Gly is 9.60 and the pKa
The name of the molecule is cysteinylglycyltyrosine. Its of the carboxyl group of Alanine is 2.34. (9.6012.34)/2 5
­abbreviated structure is: 5.97 5 pI of the dipeptide Gly-Ala. Remember the carboxyl
1
H3N–Cys–Gly–Tyr–COO – group of Gly no longer contributes to the charge of the
­dipeptide because it reacted with the amino end of Ala to
13 form a peptide bond.
a. The amino acid sequence is a polypeptide’s primary
structure. Thought Questions
b. A b-pleated sheet is one type of secondary structure.
c. Inter- and intra-chain hydrogen bonds between N–H 24
groups and carbonyl groups of peptide bonds are the During hyperventilation, oxyhaemoglobin significantly
principal feature of secondary structure. Hydrogen decreases.
bonds formed between polar side chains are important 26
in tertiary and quaternary structure. The structure of each protein is different. More complex
d. Disulfide bonds are strong covalent bonds that multi-domain proteins tend to require assistance. Simple
contribute to tertiary and quaternary structure. single-domain proteins such as ribonuclease A spontaneous
15 fold without the help of molecular chaperones.
a. heat—hydrogen bonding (secondary and tertiary 28
structure) The large size of enzymes is required to stabilize the shape
b. strong acid—hydrogen bonding (secondary and tertiary and functional properties of the active site and to shield it
structure) and salt bridges (secondary and tertiary from extraneous molecules. In addition, structural features
structure) of the protein may function in recognition processes in
c. saturated salt solution—salt bridges (tertiary structure) ­signalling or binding to cellular structures.
d. organic solvents—hydrophobic interactions (tertiary
structure) 30
The hydrophobic amino acid side chains are excluded from
17 the water and tend to cluster together. This clustering holds
The first step in the isolation of a specific protein is the portions of the polypeptides in a particular conformation.
­development of an assay, which allows the investigator to
detect it during the purification protocol. Next, the protein, 34
as well as other substances, are released from source tissue The hydrophobic amino acids glycine, phenylalanine,
by cell disruption and homogenization. Preliminary purifica- ­methionine, valine, and leucine should all seek the
tion techniques include salting out, in which large amounts ­relatively water-free interior of the decapeptide.
of salt are used to induce protein precipitation, and dialysis, 36
in which salts and other low molecular weight material are The extended a-helix probably contains amino acids with
removed. Further purification methods, which are adapted nonpolar side chains such as lysine, leucine, and phenylala-
to each research effort at the discretion of the investigator, nine. These need to be replaced by amino acids such as
include various types of chromatography and electrophore- glycine and proline. Glycine’s small R group permits a con-
sis. Three chromatographic methods are: ion-exchange tiguous proline to assume a cis orientation, resulting in a
chromatography, gel-filtration chromatography, and affinity tight turn in the peptide chain.
chromatography. Gel electrophoresis may be used to purify
a protein and/or to assess the purity of a protein. 38
Serotonin is derived from tryptophan; dopamine comes
19 from tyrosine.
The primary driving force in protein folding is the require-
ment to achieve a low-energy state despite the decrease in
entropy that occurs as the protein’s three-dimensional
Chapter 6: In-Chapter Questions
structure becomes more ordered. Key considerations in- 6.1
clude the energy associated with different bond angles and The amino acid residues forming the three-dimensional
bond rotation, the chemical properties of the amino acid structure of the active site are chiral. As a result, the active
side chains (e.g., whether or not the side chain will be site is chiral. It can bind only one isomeric form of a hexose
charged at the cellular pH), and interactions between side sugar, in this case the d-isomer.

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 A-12 Appendix

6.2 6.5
a. isomerase Dialysis removes the formaldehyde, formic acid, and meth-
b. transferase anol that build up in the bloodstream. The bicarbonate neu-
c. lyase tralizes the acid produced and helps offset the resultant
d. oxidoreductase acidosis. The ethanol competitively binds with the alcohol
e. ligase dehydrogenase. This slows the dehydrogenation of the
f. hydrolase methanol and allows time for the kidneys to excrete it.
6.3 6.6
The products of the degradation are the following Menkes’ syndrome—injections of copper salts into the
compounds: blood would avoid intestinal malabsorption and provide the
copper necessary to form adequate levels of ceruloplasmin
O and offset the symptoms of the disease.

C OH 6.7
Wilson’s disease—zinc induces the synthesis of metallo-
O CH2 O thionein, which has a high affinity for copper. Some organ
CH3OH H2N CH C OH H2N C C OH damage can be averted because metallothionein sequesters
copper and prevents this toxic metal from binding to and
CH2 H inactivating susceptible proteins and enzymes. Penicilla-
mine forms a complex with copper in the blood. This com-
plex is transported to the kidneys, where it is excreted.
6.8
Methanol Phenylalanine Aspartic acid
a. cofactor
b. holoenzyme
Cleavage of the ester bond is catalysed by an esterase; the c. apoenzyme
amide bond is cleaved by a peptidase. d. coenzyme
e. coenzyme
6.4 f. none of these
O O

Enzyme SH + I CH2 C NH2 Enzyme S CH2 C NH2

6.9 5
The patient that failed to show improvement probably had a a. proenzyme—an inactive precursor of an enzyme
higher level of acetylating enzymes. The patient’s dosage b. positive cooperativity—the mechanism in which the
should be based on capacity to process the drug and not on binding of one ligand to a target molecule increases the
body weight. likelihood of subsequent ligand binding
c. negative cooperativity—the binding of one ligand to a
Chapter 6: End-of-Chapter Questions target molecule, decreasing the likelihood of subsequent
ligand binding
Review Questions d. zymogen—an inactive form of a proteolytic enzyme
3 e. free radical—an atom or molecule that has an unpaired
a. reaction order—the sum of the exponents on the concen- electron
tration terms in the rate expression for a reaction; allows 7
an experimenter to draw certain conclusions regarding Factors that contribute to enzyme catalysis include proxim-
the reactions mechanism ity and strain effects, electrostatic effects, acid-base cataly-
b. turnover number—the number of molecules of sub- sis, and covalent catalysis. Refer to pp. 197–200 for an
strate converted to product in each second per mole explanation of each.
of enzyme
c. double-displacement reaction—a reaction in which the 9
first product is released before the second substrate a. oxidoreductase—an enzyme that catalyses an oxidation-
binds; also referred to as a ‘ping pong’ mechanism reduction reaction.
d. inhibitor—a molecule that reduces an enzyme’s activity b. lyase—an enzyme that catalyses an addition or elimina-
e. reaction mechanism—step-by-step description of a tion reaction, adding a molecule across a double bond or
chemical reaction process removing a molecule to form a double bond.

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 Appendix
A-13

c. ligase—an enzyme that catalyses the joining of two mol- d. In silico—resulting from computer simulation or com-
ecules, often using ATP for energy. puter modelling.
d. transferase—an enzyme that catalyses the transfer of a e. metabolic flux—the rate of flow of metabolites, such as
functional group from one molecule to another. substrates, products, and intermediates, along biochemi-
e. hydrolase—an enzyme that catalyses a nucleophilic cal pathways.
substitution reaction where water is the nucleophile,
19
­resulting in a cleaved bond.
Compartmentation within eukaryotic cells is the physical
f. isomerase—an enzyme that catalyses the conversion of
separation of enzymes by a membrane (i.e., by containing
one isomer to another.
certain enzymes within an organelle), or by attachment of
11 enzymes to membranes or cytoskeletal filaments. Compart-
Transition metal ions are useful as enzyme cofactors be- mentation (1) prevents competing reactions from occurring
cause they have concentrations of positive charge, can act simultaneously and allows them to be regulated separately
as Lewis acids, and can bind to two or more ligands at the (‘divide and control’), (2) reduces or removes diffusion
same time. barriers by locating enzymes and metabolites close to
13 each other, (3) provides specialized reaction conditions
At the start of a reaction, the concentrations of the reactants (e.g., low pH) that would not be possible otherwise, and
and products can be known precisely. Because equilibrium (4) protects other cellular components from potentially
has not yet been established presumably only the forward toxic reaction products (‘damage control’).
reaction is taking place. 22
15 Amino acids that are capable of acting as acids or bases
Enzymes lower the activation energy of a reaction by low- in enzyme catalysis are aspartic acid, glutamic acid, histi-
ering the free energy of the transition state. The active site dine, cysteine, tyrosine, lysine, and arginine. Of these
of the enzyme described most likely contains amino acid amino acids, histidine is the most likely to be able to func-
residues that stabilize the transition state with some or all tion as either an acid or a base, since its pKR value, 6.0, is
of the following: electrostatic effects and noncovalent inter- relatively close to physiological pH. At pH 7.6, histidine’s
actions, a shape that accepts the substrate yet eases strain in R group would be completely ionized in aqueous solution.
the transition state, and participation in the catalytic mech- However, the pKa may shift depending upon the environ-
anism (e.g., by providing an acidic, basic, or ­nucleophilic ment of the active site. A relatively nonpolar active site
residue to assist in acid-base or covalent ­catalysis). The would lower the pKa to favour the neutral form of the
active site should also place the substrate and reactants in R group (which could act as a base), while a polar active
close proximity to each other and in the proper orientation. site would raise the pKa to favour the charged form (which
could act as an acid).
17
a. metabolon—a complex of enzymes that share intermedi- 23
ates of a metabolic pathway so that the product of one The ratio kcat/Km, called the specificity constant, is the
enzyme is in close proximity to the active site of the next ­second-order rate constant for a reaction in which
enzyme in the pathway. [S] << Km. An enzyme’s specificity constant reflects the
b. In vivo—in a living cell or organism. ­relationship between catalytic rate and substrate binding
c. In vitro—in ‘glass’ (i.e., a test tube); taking place under affinity. The upper limit for the enzymes kcat/Km value
controlled laboratory conditions as opposed to within a ­cannot exceed the maximal rate at which the enzyme can
living cell or organism. bind to a substrate molecule.

27
The energy diagrams for the hypothetical reaction are as follows:
Transition state

Transition state
Free energy

Expected result
in absence of
tunneling

Reactant Reactant
Tunneling
Product Product

Progress of reaction Progress of reaction

Hypothetical reaction without enzyme Hypothetical reaction
with enzyme and tunneling phenomenon

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 A-14 Appendix

29
The conversion of the ketone functional group-containing
dihydroxyacetone phosphate to the aldehyde functional
group-containing glyceraldehyde-3-phosphate involves
acid/base catalysis. The intermediate is an enediol.
H

C OH

C OH O

CH2 O P O–

O–
Enediol intermediate

Thought Questions
32
0.3

1
Intercept, horizontal axis = –
0.2 Km

1
Intercept, vertical axis =
1 Vmax
v
Km
Slope =
Vmax
0.1

No inhibitor The type of inhibition being observed is

noncompetitive

0 0.1 0.2
1
[S]

34 38
The kcat/Km: values for the alcohols are as follows: Crowding will tend to raise activity coefficients. If the
substances are not allowed to diffuse from the reaction centre
alcohol Kcat/km (M–1s–1) the concentration in terms of moles per litre can be quite low
Ethanol 0.5 but the local concentration can be considerably higher.
1-Butanol 1.0
40
1-Hexanol 2.6
The magnesium ion has vacant d orbitals that can act as
12-Hydroxydodecanoate 2.9
electron pair acceptors
All-trans-retinol 3.9
Benzyl alcohol 0.2 42
2-Butanol 1.1 3 10 –3 rate 5 k[A]2[B]
Cyclohexanol 3.9 3 10 –3 [A] [B] Rate
0.1 0.01 1 3 106
Based on the kcat/km values of these alcohols, all-trans-­ 0.1 0.02 2 3 106
retinol is the most easily metabolized alcohol by ADH. 0.2 0.01 4 3 106
0.2 0.02 8 3 106

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 Appendix
A-15

44 7.3
CH2OH CH3
H O
O O C H
O
–
O H H OH H C C O−
N+ N HO
+ NH3 O
Asp
OH

His 7.4 CH2OH

CH2OH
O
The histidine protonates the OH of the alcohol making it a O
better leaving group. OH
46 HO
a. no OH
b. if a was less than 1 the reaction would be faster than the
uninhibited reaction Carbohydrate Aglycone

Chapter 7: In-Chapter Questions 7.5

a. glucose—reducing sugar
7.1
b. fructose—reducing sugar
a. Aldotetrose,  b. Ketopentose,  c. Ketohexose
c. a-methyl-d-glucoside—nonreducing
7.2 d. sucrose—nonreducing
CH2OH CH2OH Sugars a and b are capable of mutarotation.
HO O HO O OH 7.6
The larger, insoluble glycogen molecule makes a negligible
OH OH contribution to the osmotic pressure of the cell. In contrast,
OH
each molecule of an equivalent number of glucose molecules
OH OH contributes to osmotic pressure. If the glucose molecules
α-D-Galactose β-D-Galactose were not linked to form glycogen, the cell would burst.
(a) 7.7
COOH COOH CHO In an analogue system, information is encoded as a continu-
ous signal. For example, in old-fashioned clocks the hands
H C OH H C OH H C OH
move continuously and not in small steps. In analogue sys-
HO C H HO C H HO C H tems, small fluctuations in information processing can be
meaningful. The sugar code is an analogue system because
HO C H HO C H HO C H of micro­heterogeneity, the continuous spectrum of carbohy-
drate structures that cells can synthesize to encode biologi-
H C OH H C OH H C OH
cally relevant signalling information. In a digital system,
CH2OH COOH COOH information is represented by discrete values (‘digits’) of a
physical quantity. Digital clocks display time as a progres-
Aldonic acid Aldaric acid Uronic acid
sion of discrete n­ umbers with no intermediate values. The
(b) DNA code is a digital system composed of four digits
CH2OH (bases). During protein synthesis, each DNA base triplet
that ultimately codes for an amino acid has a specific
H C OH
meaning.
CH2OH
HO C H
HO O Chapter 7: End-of-Chapter Questions
HO C H
OH
O
Review Questions
H C OH
3
CH2OH OH a. aldonic acid—the product of the oxidation of the
­aldehyde group of a monosaccharide
Galactitol δ-Lactone of galactonic acid
b. uronic acid—the product formed when the terminal
(c) (d) CH2OH group of a monosaccharide is oxidized

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 A-16 Appendix

c. aldaric acid—the product formed when the aldehyde 13

and CH2OH groups of a monosaccharide are oxidized CH2OH CH2OH
to carboxylic acids O O
d. lactone—a cyclic ester OH
O OH
e. reducing sugar—a sugar that can be oxidized by weak HO OH
oxidizing agents OH NH2

5 15
a. Maillard reaction—the nonenzymatic glycation of a. Carboxylate, sulfate and hydroxyl groups bind large
­protein; the nucleophilic attack of an amino nitrogen amounts of water.
on the anomeric carbon of a reducing sugar b. Hydrogen bonding is the primary type of bonding
b. Schiff base—the imine product of a reaction between a ­between water and glycosaminoglycans.
primary amino group and a carbonyl group
c. Amadori product—a stable ketoamine formed from the 17
rearrangement of a Schiff base; an intermediate in glyca- A reducing sugar reduces Cu(II) in Benedict’s reagent. This
tion processes that produce advanced glycation end reduction takes place because the hemiacetal portion of a
products sugar can form an aldehyde functional group, which can be
d. adduct—the product of an addition reaction oxidized to a carboxylic acid.
e. reactive carbonyl-containing product—highly reactive 19
molecules produced from Amadori products that cause a. D-erythrose and D-threose are epimers.
protein cross-linkages and adduct formation; the dicar- b. D-glucose and D-mannose are epimers.
bonyl compound glyoxal (CHOCHO) is an example c. D-ribose and L-ribose are enantiomers.
7 d. D-allose and D-galactose are diastereomers.
a. glycogen—a glucose storage molecule in vertebrates; a e. D-glyceraldehyde and dihydroxyacetone are an
branched polymer containing a(1,4) and a(1,6) glyco- aldose-ketose pair.
sidic linkages
b. cellulose—an unbranched structural polymer produced Thought Questions
by plants that is composed of D-glucopyranose residues 22
linked by b(1,4)-glycosidic linkages The thick proteoglycan coat acts to protect bacteria by pre-
c. N-glycan—an oligosaccharide linked to a protein via a venting the binding of antibodies to their surface antigens.
b-glycosidic bond between the core N-acetylglucos-
amine anomeric carbon and a side chain amide 24
nitrogen of an asparagine residue CH2OH CH2OH
d. O-glycan—an oligosaccharide linked to a protein via O O
an b-glycosidic bond to the hydroxyl oxygen of serine
O OH O OH
or threonine residues
e. glycosaminoglycan—a long unbranched heteropolysac-
charide chain composed of disaccharide repeating NH NH
units C O C O
9 CH3 CH3
a. Glucose and mannose are examples of epimers.
b. 26
CH2OH a.
glycosidic
O linkage
COOH O
OH
HO O CH3 O
HO OH OH
COOH
c. Glucose is a reducing sugar. O
O
d. Ribose is a monosaccharide.
e. a- and b-Glucose are anomers. OH OH
COOH
f. D-ribose and D-arabinose are diastereomers
O O
11
Heteroglycans are made up of more than one type of OH OH
­monosaccharide residue but homoglycans have only one.
Examples of homoglycans and heteroglycans are starch O
and hyaluronic acid, respectively.

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 Appendix
A-17

b. The polymer acts to immobilize water through e­ xtensive

hydrogen bonding
28
The complete structures of the Type A and Type B antigens
are as follows:
CH2OH CH2OH CH2OH
O
HO O O HO O
O
CH2OH
OH
HO O OH

OH NH OH
O
O H3C C O
NH
O
H3C C O
CH3
OH
HO

OH

Type A

CH2OH CH2OH CH2OH

O
HO O O HO O
O
OH
OH
CH2OH
O
NH OH
HO O
O H3C C O
OH
O
OH CH3
OH
HO

OH Type B

30 34
The conversion of glucose to fructose occurs via enol-keto Assuming a D family sugar, two structures are possible
tautomerism. Refer to Figure 7.16, p. 226.
O OH O OH
32 C C
The sulfate group has several negatively charged oxygens
that are capable of hydrogen bonding. Conjugation of sul- H C OH H C OH
fate with the hydrophobic molecule enhances solubility be-
cause of hydrogen bonding between the sulfate oxygens and H C OH HO C H
water molecules in tissue fluids.
H C OH HO C H

H C OH H C OH

CH2OH CH2OH

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 A-18 Appendix

36 8.5
Three a-anomeric ring forms of 3-ketoglucose are shown. In gluconeogenesis pyruvate is converted to oxaloacetate.
The pyranose form is the most stable because the bond NADH and H1 are required to reduce glycerate 1,3-bisphos-
angles are less strained. phate to glyceraldehyde-3-phosphate. NAD1 is the oxidized
O form of NADH also produced in this reaction. ATP is needed
CH2OH to provide the energy to carboxylate pyruvate to oxaloacetate
C OH
CH2OH and phosphorylate glyceraldehyde-3-phosphate to glycerate-
O H C OH H C OH 1,3-bisphosphate. Both of these reactions also produce ADP
O O
and Pi. GTP is hydrolysed in the conversion of oxaloacetate to
OH OH OH
phosphoenolpyruvate to yield GDP and Pi. Water is involved
OH
OH
in the hydrolysis reactions of ATP to ADP and Pi, the conver-
O OH O OH OH
sion of phosphoenolpyruvate to 2-phosphoglycerate, and the
38 hydrolysis of glucose-6-phosphate to glucose. Six p­ rotons are
The structure of olestra is as follows: formed when four molecules of ATP and two ­molecules of
O O GTP are hydrolysed.
C CH2
O
8.6
R
O Without glucose-6-phosphatase activity, the individual
cannot release glucose into the blood. Blood glucose levels
O C
must be maintained by frequent consumption of carbohy-
O O R
C drate. Excess glucose-6-phosphate is converted to pyruvate,
O O
which is then reduced by NADH to form lactate.
R C
O 8.7
R
O The enzyme deficiencies prevent the breakdown of
C O CH2 O glycogen. Because the synthetic enzymes are active, some
O glycogen continues to be produced and causes liver enlarge-
R
C O ment. Because of the liver’s strategic role in maintaining
R CH2 O
blood glucose, defective debranching enzyme causes
O
­hypoglycaemia (low blood sugar).
C O
C O R
R Chapter 8: End-of-Chapter Questions
Review Questions
Chapter 8: In-Chapter Questions
3
8.1 a. tautomerization—chemical reaction by which two
The large excess of NADH that is produced by these reac- tautomers are interconverted by the movement of a
tions ­drives the conversion of pyruvate to lactate. ­hydrogen atom and a double bond
8.2 b. tautomer—an isomer that differs from another in the
Chromium is acting as a cofactor. ­location of a hydrogen atom and a double bond (e.g.,
keto-enol-tautomers)
8.3 c. amphibolic pathway—a metabolic pathway that func-
In the absence of O2, energy is produced only through gly- tions in both anabolism and catabolism
colysis, an anaerobic process. Glycolysis produces less d. electron transport system—a series of electron carrier
energy per glucose molecule than does aerobic respiration. proteins that bind reversibly to electrons at different
Consequently, more glucose molecules must be metabo- energy levels
lized to meet the energy needs of the cell. When O2 is e. decarboxylation reaction—the removal of a carboxylic
present, the flux of glucose through glycolysis is reduced. group from a carboxylic acid as carbon dioxide
8.4
5
At three strategic points, glycolytic and gluconeogenic reac-
Phosphorylation of glucose upon its entry into the cells pre-
tions are catalysed by different enzymes. For example,
vents leakage of the molecule out of the cell and facilitates
phosphofructokinase and fructose-l,6-diphosphatase ca-
its binding to the active sites of enzymes.
talyse opposing reactions. If both reactions occur simulta-
neously (i.e., in a futile cycle) to a significant extent, ATP 7
hydrolysis in the reaction catalysed by phosphofructokinase The early activation of nutrient molecules in these pathways
releases large amounts of heat. If the heat is not quickly dis- allows ATP production under varying substrate and product
sipated, an affected individual could die of hyperthermia. concentration.

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 Appendix
A-19

9 whose product, cAMP, initiates a reaction cascade that

The unique reactions in gluconeogenesis are (1) synthesis of activates the glycogen-degrading enzyme glycogen
phosphoenolpyruvate, catalysed by pyruvate carboxylase phosphorylase.
and PEP carboxylated, (2) conversion of fructose 1,6-bis­ 17
phosphate to fructose-6-phosphate, catalysed by fructose- Gluconeogenesis occurs mainly in the liver. It is
1-6-bisphophatase, and (3) the formation of glucose from activated by processes that deplete blood glucose,
glucose-6-phosphate, catalysed by glucose-6-phosphatase. such as fasting and exercise. Futile cycles are
11 prevented by having the forward and reverse reactions
The three principal hormones that regulate the body’s levels catalysed by different enzymes, both independently
of glucose are insulin, glucagon, and epinephrine. Insulin is regulated.
an anabolic hormone that causes target cells to take up glu- 19
cose from the blood and stimulates glycogenesis in liver and Glucose can be a substrate or a product of a number of
muscle and glycolysis in the liver. Glucagon is released key metabolic pathways depending upon the needs of the
when blood glucose levels are low. It stimulates liver glyco- cell, and as such, glucose plays a central role in carbohy-
genolysis and gluconeogenesis, both of which produce glu- drate metabolism. When energy is needed, glucose un-
cose, which is then released into the blood. Epinephrine, dergoes glycolysis to form pyruvate, which can be
released under stressful conditions, raises blood glucose oxidized further either aerobically via the citric acid
levels by triggering liver glycogenolysis. cycle and the electron transport chain to produce ATP, or
13 anaerobically to form lactate (or ethanol in yeast cells
Substrate-level phosphorylation is the synthesis of ATP (from and some bacteria). When energy is abundant, glucose is
ADP and Pi) that is coupled to the exergonic breakdown of a converted to glycogen via glycogenesis, or it may enter
high-energy organic substrate. Examples of this process in the pentose phosphate pathway to form pentose and other
glycolysis are the conversions of glycerate-1,3-bisphosphate to sugars. Also, pyruvate formed from glucose may react to
glycerate-3-phosphate (by phosphoglycerate kinase) and phos- form acetyl-CoA, a precursor for fatty acid synthesis as
phoenolpyruvate to pyruvate (by pyruvate kinase). well as the citric acid cycle. Glucose may also be synthe-
sized from pyruvate via gluconeogenesis, or from certain
15
amino acids.
Epinephrine promotes the conversion of glycogen to
glucose by activating adenylate cyclase, an enzyme 21
O

HO CH2 CH2OH HO CH2 CH2 O P O–

O O
Fructokinase
O–
OH OH
OH OH
ATP
OH ADP OH
Fructose Fructose-1-phosphate

O
O
CH2 OH
–
HO CH2 CH2 O P O
O Fructose-1-phosphate C H
aldolase C O O
O– +
OH
H C OH
OH CH2 O P O–

ATP CH2OH
OH
ADP O–
Fructose-1-phosphate DHAP Glyceraldehyde

O C H

C H Glyceraldehyde
H C OH O
kinase
H C OH O–
CH2 O P

CH2OH ATP O–
ADP
Glyceraldehyde Glyceraldehyde-3-phosphate

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 A-20 Appendix

23 38
In glycolysis, a dehydration occurs in the conversion of Both glycogen and triacylglycerols are energy sources.
2-phosphoglycerate to phosphoenolpyruvate, catalysed by One difference between the two molecules is in the speed
enolase. with which energy can be mobilized. Glycogen can be
converted to glucose and diverted to energy production
25 very quickly (instant energy). It takes longer to mobilize
Insulin is released in response to high blood glucose levels. the fat reserves, but once activated they provide the energy
In the liver, insulin leads to the inhibition of glycogenolysis for sustained effort.
and the activation of glycogenesis, resulting in a decrease in
blood glucose levels. Insulin also causes an increased cel- 40
lular uptake (adipocytes and muscle cells) of glucose. Glu- Refer to Figures 8.14a and 8.14b, which illustrate the
cagon is released in response to low blood glucose levels. In pentose phosphate pathway. Note that the 14C label at
the liver, glucagon leads to the inhibition of glycogenesis C-2 of glucose-6-phosphate is C-1 of ribulose-5-phos-
and the activation of glycogenolysis, resulting in the release phate as the result of a decarboxylation reaction. When
of glucose into the bloodstream. ribulose-5-phosphate enters the nonoxidative phase of
the pentose phosphate pathway the radioactive label
27 will appear as C-1 of ribose-5-phosphate, xylulose-
The fate of pyruvate under anaerobic conditions is fermen- 5-phosphate, sedoheptulose-7-phosphate and
tation. In muscle cells, lactate is the only product, in yeast fructose-6-phosphate.
cells the products are ethanol and CO2 and some microor-
ganisms produce lactate and other acids or alcohols. All of Chapter 9: In-Chapter Questions
these fermentation reactions result in the regeneration of
NAD1 so that glycolysis can continue. The fate of pyruvate 9.1
under aerobic conditions is to be oxidized completely to With a DE 09 value of 20.345 V, the oxidation of NO22 is
form CO2 and H2O. not spontaneous as written. The oxidation of ethanol is
spontaneous as written because its DE 09 value is positive
Thought Questions (10.275 V).
30 9.2
Glucokinase (GK) acts as a glucose sensor because of its rela- Reactions 3, 4, and 5 are redox reactions. In reaction 3,
tively low affinity for glucose. Since it does not usually work ­lactate is the reducing agent and NAD1 is the oxidizing
at high velocity GK is sensitive to small changes in blood glu- agent. In reaction 4, cyt b (Fe21) is the reducing agent and
cose levels. In each cell type in which GK occurs it is linked NO22 the oxidizing agent. In reaction 5, NADH is the
to a signal transduction pathway. For example, in pancreatic ­reducing agent and CH3CHO is the o­ xidizing agent.
b-cells, GK-catalysed glucose phosphorylation, which occurs 9.3
when blood glucose levels are high, triggers insulin release. The oxidation states of the functional group carbon (indi-
32 cated in bold) are:
In liver, fructose is metabolized more rapidly than glucose CH3CH2OH      0 2 1 2 1 1 1 5 2 1
because its metabolism bypasses two regulatory steps in CH3CHO   0 2 1 1 2 5 11
the glycolytic pathway: the conversion of glucose to CH3COOH      0 1 1 1 2 5 13
glucose-6-phosphate and fructose-6-phosphate to fructose- 9.4
1,6-bisphosphate. Recall that fructose-1-phosphate is split As it is incorporated into an organic molecule, the carbon
into glyceraldehyde and DHAP, both of which are sub­ atom in CO2 is reduced.
sequently converted to glyceraldehyde-3-phosphate.
9.5
34 Because of its symmetrical structure, a molecule of succi-
If gluconeogenesis and glycolysis were exactly the reverse nate derived from a 14C-labelled acetyl-CoA is converted
of one another, futile cycles would be established and much into two forms of oxaloacetate, one with a labelled
energy would be wasted. In addition, it would be impossible ­methylene group and one with a labelled carbonyl group.
for the body to store glycogen or release glucose into the 14
C-labelled CO2 is not released until the third turn of the
blood as needed. cycle when one-half of the original labelled c­ arbon is lost
(the carbonyl group derived from acetyl-CoA). The labelled
36
carbon is further scrambled when succinyl-CoA is converted
In high concentrations fructose can bypass most of the reg-
to succinate during the third and fourth turns of the cycle.
ulatory steps of the glycolytic cycle. Instead of being stored
in glycogen molecules, the carbon skeletons of excess fruc- 9.6
tose molecules are converted through pyruvate and acetyl- Pyruvate carboxylase converts pyruvate to oxaloacetate.
CoA to fatty acids in triacylglycerol molecules. If the enzyme is inactive, concentrations of pyruvate in the

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 Appendix
A-21

system rise and pyruvate is converted by NADH to lactate. 5

Excess lactate is then excreted in the urine. Contracting muscle converts large amounts of ATP to ADP
in the muscle cells. The drop in ATP concentration stimu-
Chapter 9: End-of-Chapter Questions lates two key regulatory enzymes of the citric acid cycle.
(1) Citrate synthetase catalyses the condensation of acetyl-
Review Questions CoA and oxaloacetate to give citrate. ATP is an allosteric
3 inhibitor of this enzyme. As concentrations of ATP drop,
a. amphibolic pathway—a metabolic pathway that func- this enzyme becomes more active. (2) Isocitrate dehydroge-
tions in both anabolism and catabolism nase, which converts isocitrate to a-ketoglutarate, is inhib-
b. anaplerotic reaction—a reaction that replenishes a sub- ited by high concentrations of ATP and activated by high
strate needed for a biochemical pathway concentrations of ADP. A reduced ATP concentration
c. glyoxylate cycle—a modification of the citric acid cycle also stimulates the conversion of pyruvate to acetyl-CoA
that occurs in plants, bacteria, and other eukaryotes; catalysed by pyruvate dehydrogenase.
allows growth in these organisms from two carbon sub- 7
strates such as ethanol, acetate, and acetyl-CoA The first two reactions of the glyoxylate cycle, catalysed by
d. reduction potential—redox potential – a measure of the citrate synthase and aconitase, also occur in the citric acid
tendency of an electron donor in a redox pair to lose an cycle. In the next two reactions isocitrate is split into suc-
electron cinate and glyoxylate. Glyoxylate reacts with acetyl-CoA to
e. conjugate redox pair—in a half-reaction an electron form malate. The cycle is completed when malate is con-
donor (e.g., Cu1) and an electron acceptor (e.g., Cu12) verted to oxaloacetate by malate dehydrogenase.

9
The balanced equations for each of the reactions of the citric acid cycle are:
1. C2H3O-SCoA 1 C4H2O522 1 H2O Æ CoASH 1 C6H5O732 1 H1
   Acetyl-CoA   oxaloacetate        citrate
2. C6H5O732 Æ C6H5O732
   citrate  isocitrate
3. C6H5O732 1 NAD1 Æ C5H4O522 1 NADH 1 CO2
   isocitrate     a-ketoglutarate
4. C5H4O522 1 NAD1 1 CoASH Æ C4H4O332–SCoA 1 NADH 1 CO2
   a-ketoglutarate               succinyl-CoA
5. C4H4O332–SCoA 1 GDP 1 HPO422 Æ C4H4O422 1 GTP (or ATP) 1 CoASH
   succinyl-CoA   (or ADP)   Pi      succinate
6. C4H4O422 1 FAD Æ C4H2O422 1 FADH2
   succinate         fumarate
7. C4H2O422 1 H2O Æ C4H4O522
   fumarate          L-malate
8. C4H4O522 1 NAD1 Æ C4H2O522 1 NADH 1 H1
   L-malate          L-Oxaloacetate

11 would also impact the two key regulatory enzymes that uti-
The biochemical process required to obtain energy from lize NAD1 as a substrate.
glucose when oxygen is available are glycolysis, the conver-
15
sion of pyruvate to acetyl-CoA, which then enters the citric
The roles of each enzyme, cofactor, and coenzyme of
acid cycle. The reduced coenzyme products of the cycle,
the pyruvate dehydrogenase complex are as follows.
NADH and FADH2 then donate electrons to the electron
(1) Pyruvate decarboxylase (also called pyruvate dehy-
transport system in which oxygen is the terminal electron
drogenase) decarboxylates pyruvate via the coenzyme TPP
acceptor. The energy captured by the electron transport
(thiamine pyrophosphate), to form HETPP (hydroxyethyl
system is then used in the synthesis of ATP.
TPP) and CO2. (2) Dihydrolipoyl transacetylase cataly-
13 ses the transfer of an acetyl group from HETPP to the
Oxygen is required for the electron transport chain (ETC): coenzyme lipoic acid to regenerate TPP and form acetyl
lipoic acid. A second transfer of this acetyl group from
O2 1 NADH 1 H1 Æ H2O 1 NAD1
acetyl lipoic acid to the coenzyme CoASH forms acetyl
Without oxygen, the ETC shuts down, and NADH accumu- CoA and dihydrolipoic acid. (3) Dihydrolipoyl dehydro-
lates at the expense of NAD1. Both high NADH and low genase reoxidizes the dihydrolipoic acid to regenerate
NAD1 levels inhibit the citric acid cycle. Low NAD1 levels lipoic acid.

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 A-22 Appendix

17 28
Unlike organisms that are capable of the glyoxylate path- Inhibition of pyruvate dehydrogenase kinase, an enzyme
way, animals cannot use two-carbon molecules as precur- that contributes to the regulation of pyruvate dehydroge-
sors in gluconeogenesis. One pathway to gluconeogenesis nase, has the effect of increasing the conversion of pyruvate
begins with pyruvate reacting to form oxaloacetate, then molecules to acetyl-CoA, thereby decreasing lactate levels.
phosphoenolpyruvate. Since the decarboxylation of pyru-
30
vate to form acetyl-CoA is irreversible, and there is no bio-
synthetic ­pathway from acetyl-CoA to pyruvate, it cannot DG8 5 –nF DE8
be formed from two-carbon molecules. Gluconeogenesis The half cells for the two reactions are:  E
may use oxaloacetate as a precursor. However, oxaloacetate  S 1 2H1 1 2e2 Æ H2S 20.23V
cannot be synthesized solely from acetyl-CoA. When 1
­acetyl-CoA enters the citric acid cycle by reacting with oxa- O 1 2H1 1 2e2 Æ H2O 10.82V
2 2
loacetate, it adds two carbons to the cycle. However, two        NADH Æ NAD 1 H 1 2e 10.32V
1 1 2

carbons are removed as CO2 in subsequent reactions. Thus, For the formation of hydrogen sulfide the reaction
there is no net addition of carbon atoms to the cycle. If oxa- would be:
loacetate is used for gluconeogenesis, it must be replenished
via a citric acid cycle intermediate larger than acetyl-CoA, S 1 H1 1 NADH Æ H2S 1 NAD1 5 109V
or by its synthesis from certain amino acids. The glyoxylate DE8 5 223 V 1 0.32 V 5 10.09 V
cycle, not present in animals, does allow gluconeogenesis DG8 5 2(0.96485 J/ mol V)(09) 5 17,367 J
from 2-carbon molecules because it bypasses the citric acid
cycle reactions that liberate CO2. For the formation of water the reaction would be
1
19 O 1 H1 1 NADH Æ H2O 1 NAD1 5 11.14 V
2 2
Biosynthetic pathways that utilize citric acid cycle intermedi- DE8 5 10.82V 1 0.32V 5 1.14 V
ates as precursors include the syntheses of: glucose from ox-
aloacetate; pyrimidines from oxaloacetate, purines from DG8 5 2(96485 J/ mol V)(1.14 V) 5 219985 J
a-ketoglutarate, fatty acids and cholesterol from citrate; por- The difference in energy yield is 219985 2 17367 5
phyrin, haem, or chlorophyll from succinyl-CoA; the amino 20618 kJ or 200 kJ
acids Asp, Lys, Thr, Ile, and Met from oxaloacetate; and the
amino acids Glu, Gln, Pro, and Arg from a-ketoglutarate.
Chapter 10: In-Chapter Questions
Thought Questions 10.1
22 a. NADH
In substrate-level phosphorylation, ADP is converted to b. FADH2
ATP by the direct transfer of a phosphoryl group from a c. Cyt b (reduced)
high energy compound. The only reaction in the citric acid d. NADH
cycle that involves this type of reaction is the cleavage of e. NADH
succinyl-CoA to form succinate, CoASH, and GTP. An- 10.2
other example of a substrate level phosphorylation is the DNP is a lipophilic molecule that binds reversibly with
glycolytic reaction that converts phosphoenolpyruvate and protons. It dissipates the proton gradient in mitochondria
ADP to pyruvate and ATP. by transferring protons across the inner membrane. The
24 uncoupling of electron transport from oxidative phosphor-
Three enzymes that require thiamine are pyruvate dehydro- ylation causes the energy from food to be dissipated as
genase, a-ketoglutarate dehydrogenase and transketolase. heat. DNP causes liver failure because of insufficient ATP
Thiamine is involved in decarboxylation and acyl group synthesis in a metabolically demanding organ.
transfer reactions. Absence of decarboxylation reactions 10.3
would prevent pyru­vate from being decarboxylated to No, for ATP synthesis to occur, the proton concentration
­acetyl-CoA. The body would then lack two carbon units for must be higher within the inside-out mitochondrial particles.
synthesis and energy production. Pyruvate accumulates as ATP synthesis requires that protons move down a concentra-
lactate. The overall results of thiamine deficiency are lack tion gradient through the base of the ATP synthetase across
of energy, muscle wasting and acidosis the membrane.
26 10.4
Carboxylation of pyruvate produces oxaloacetate, a citric Disregarding proton leakage and assuming that the g­ lycerol
acid cycle intermediate. Increasing the concentration of one phosphate shuttle is in operation, 38 ATP would be produced
of the intermediates stimulates the cycle and more energy is from the aerobic oxidation of a glucose molecule. If the malate
produced. shuttle is in operation, only 36 ATP would be produced.

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 Appendix
A-23

10.5 7
Sucrose is a disaccharide composed of glucose and fructose. a. radical—an atom or molecule with an unpaired electron
As described (p. 333) the oxidation of 1 mol of glucose yields b. ROS—reactive oxygen species – a reactive derivative of
a maximum of 31 mol of ATP. Fructose, which like glucose molecular oxygen
is also partially degraded by the glycolytic pathway, also c. RNS—reactive nitrogen species—nitrogen-containing
yields a maximum of 31 mol ATP. The total maximum radicals
energy yield is 62 mol of ATP per mol of sucrose. d. GSH—glutathione—an intracellular reducing agent
10.6 e. SOD—superoxide dismutase—an enzyme that catalyses
The larger selenium atom holds its electrons less tightly the conversion of superoxide radical to hydrogen
than s­ ulfur. Selenium is more easily oxidized and therefore ­peroxide and oxygen
acts as a better s­ cavenger for oxygen than does sulfur. 9
10.7 Principal sources of electrons for the mitochondrial
The SH groups reduce hydrogen peroxide or trap hydroxyl ­electron transport system are NADH and FADH2.
­radicals to form water. An example of a nonsulfhydryl
11
group–containing molecule that should be capable of this
The translocation of three protons is required to drive ATP
activity is vitamin C or any of a number of other antioxi-
synthesis. The fourth proton drives the transport of ADP
dants (carotenoids, flavonoids, tocopherols, etc.).
and Pi.
10.8
The phenolic groups of both molecules are responsible for 13
their antioxidant activity because of the ease of formation In small quantities ROS act as signal molecules. Excessive
of phenoxy radicals with subsequent neutralization of elec- amounts of dietary antioxidants such as vitamin E compro-
tron-deficient ROS. mise ROS-triggered defence mechanisms that induce in-
creased synthesis of antioxidant enzymes.

Chapter 10: End-of-Chapter Questions 16

The major enzyme defences against oxidative stress
Review Questions are provided by superoxide dismutase, catalase, and
glutathione peroxidase.
3
a. chemiosmotic coupling theory—ATP synthesis is cou- 18
pled to electron transport by the electrochemical proton The advantage of dioxygen over the charged oxidizing
gradient across a membrane agents, such as NO3−, Fe31, and SO42−, is that O2 readily
b. uncoupler—a molecule that uncouples ATP synthesis diffuses across cell membranes. Unlike CO2, which also
from electron transport; it collapses a proton gradient by diffuses across cell membranes, dioxygen is highly reac-
transporting protons across the membrane tive and readily accepts electrons. Finally, O2 is found
c. ionophore—a substance that transports cations across a almost everywhere on Earth’s surface, and as such, is
membrane much more readily accessible than oxidizing agents such
d. submitochondrial particle—small membranous vesicles as sulfur.
formed when mitochondria are subjected to sonication;
used to investigate ATP synthesis 20
e. a,b hexmer—a component of the F1 unit of mitochon- There are four protein complexes in the mitochondrial
drial ATP synthesis; catalyses ATP synthesis ETC. Complex I (NADH dehydrogenase complex) cataly-
ses the transfer of electrons from NADH to UQ. ­Complex
5 II (succinate dehydrogenase complex) mediates the trans-
a. reactive oxygen species (ROS)—a reactive derivative of fer of electrons from succinate, an intermediate in the
molecular oxygen, including superoxide radical, hydro- citric acid cycle, via FAD to UQ. Complex III
gen peroxide, the hydroxyl radical, and singlet oxygen ­(cytochrome bc1 complex) transfers electrons from UQH2
b. antioxidant—a substance that prevents the oxidation of to cytochrome c, a mobile electron carrier protein loosely
other molecules associated with the outer face of the inner mitochondrial
c. oxidative stress—excessive production of reactive membrane. Complex IV (cytochrome oxidase) transfers
oxygen species the electrons donated by cytochrome c that reduce oxygen
d. respiratory burst—an oxygen-consuming process in to yield water.
scavenger cells such as macrophages in which ROS are
generated and used to kill foreign or damaged cells 22
e. reactive nitrogen species (RNS)—nitrogen containing The net reaction of the electron transport system is
radicals often classified as ROS; examples include nitric highly exergonic. Using a series of oxidations instead
oxide, nitrogen dioxide, and peroxynitrite of one reaction allows a more controlled, more efficient

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 A-24 Appendix

capture of this energy, avoiding the liberation of a great steroids because it shuts down only a portion of eico-
deal of heat. sanoid synthetic pathways.
24 11.2
NADH dehydrogenase (Complex I) oxidizes NADH to The product of complete hydrogenation would be hard and
NAD1. When Complex I is inhibited, NADH accumulates therefore not useful as a margarine.
(resulting in an increased NADH:NAD1 ratio) and FADH2, 11.3
which is oxidized in Complex II, is unaffected. When soap and grease are mixed, the hydrophobic hydro-
carbon tails of the soap insert (or dissolve) into the oil drop-
Thought Questions let. The oil droplet becomes coated with soap molecules.
27 The hydrophilic portion of the soap molecules allows the
Low levels of G-6-PD in combination with a high level of soap-oil complex to be dispersed in water.
oxidized GSH cause high oxidative stress. Without antioxi- 11.4
dant protection, red cell membranes become fragile, a con- The phospholipid of the surfactant, which possesses a
dition that eventually causes haemolytic anaemia. polar head group and two hydrophobic acyl groups, dis-
29 rupts some of the ­intermolecular hydrogen bonds of the
Dinitrophenol collapses the proton gradient across the mi- water, thereby decreasing the ­surface tension.
tochondrial inner membrane. The energy normally used to 11.5
drive ATP synthesis is lost as heat. Carvone and camphor are monoterpenes; abscisic acid is a
31 sesquiterpene.
Cyanide binds to cytochrome oxidase irreversibly. All the 11.6
cytochromes in the ETC become reduced, and ATP synthe- Bile salts are structurally similar to soap in that they contain
sis ceases. In the case of dinitrophenol, the acidic phenol a polar head group (e.g., the charged amino acid residue gly-
disrupts the proton gradient by shuttling protons across the cine) and a hydrophobic tail (the steroid ring system).
membrane. None of the parts of the electron transport
11.7
system are irreversibly altered by dinitrophenol. Removal
a. simple diffusion
of the phenol allows the system to restore itself.
b. secondary active transport or facilitated diffusion
33 c. primary active transport or exchanger protein
If the cytochrome complexes were not embedded in the mi- d. primary active transport or gated channel
tochondrial inner membrane the proton gradient could not e. fat molecules (triacylglycerols) are not directly transported
be established and ATP synthesis would not occur. across cell membranes; they must be hydrolysed first.
f. simple diffusion.
35
If oxygen is used as the electron acceptor for the ETC, the 11.8
difference in voltage between NADH and water is 1.14 V. The main stabilizing feature of biological membranes is
The complete reduction of nitrate by NADH would be hydrophobic interactions among the molecules in the lipid
11.18 V. This is almost exactly the same as for oxygen. bilayer. The phospholiqids in the lipid bilayer orientate
It would be reasonable to assume that the same amount themselves so that their polar head groups interact with
of ATP would be produced. water. Proteins in the lipid bilayer interact favourably in
their hydrophobic milieu because they typically have hy-
37
drophobic amino acid residues on their outer surfaces.
The carbon radicals generated by the attack of oxygen on
an amino acid can dimerize to produce a crosslink between 11.9
two amino acids. The transport mechanisms discussed in the chapter fit into
2R9CHCONHÆRCH(CONH)-CH(CONH)R the ­following categories:
sodium channel: uniporter
Chapter 11: In-Chapter Questions glucose permease: passive uniporter
Na 1 -K 1 -ATPase: antiporter
11.1
Because steroids inhibit the release of arachidonic acid, Chapter 11: End-of-Chapter Questions
their use shuts down the synthesis of most if not all eico-
sanoid molecules, hence their reputation as potent anti- Review Questions
inflammatory agents. Aspirin inactivates cyclooxygenase 3
and prevents the conversion of ­arachidonic acid to PGG2 a. prostaglandin—an arachidonic acid derivative that con-
the precursor of prostaglandins and thromboxanes. Aspi- tains a cylcopentane ring with hydroxyl groups at C-11
rin is not as effective an anti-inflammatory agent as the and C-15

20-McKee-Appendix.indd 24 09/04/16 1:47 PM

 Appendix
A-25

b. thromboxane—a derivative of arachidonic acid that con- 11

tains a cyclic ester a. botulism—a form of muscle paralysis caused by a pro-
c. leukotriene—a derivative of arachidonic acid; linear tein toxin produced by Clostridium botulinum
molecules whose synthesis is initiated by peroxidation b. botulinum toxin—a protein produced by Clostridium
catalysed by lipooxygenase botulinum that causes muscle paralysis; prevents the re-
d. autocrine—refers to a hormone-like molecule that is lease of the neurotransmitter acetylcholine from the pre-
active within the cell in which it is produced synaptic axon of motor neurons
e. anaphylaxis—an unusually severe allergic reaction trig- c. t-SNARE—target membrane specific soluble N-ethyl-
gered when an allergen binds to IgE antibodies on the maleimide sensitive factor attachment protein receptors
surface of mast cells —a component of the fusion machinery required for
5 exocytosis at nerve terminals
a. phosphoglyceride—a membrane lipid composed of glyc- d. v-SNARE—vesicle specific SNARE
erol linked to two fatty acids, phosphate, and a polar e. membrane fusion—the merging of two lipid bilayers
group 13
b. sphingolipid—a membrane lipid that contains a long- The protein component of plasma lipoproteins serves to
chain amino alcohol and ceramide (a fatty acid deriva- solubilize the lipoproteins in the blood. It also binds to
tive of sphingosine) cell surface receptors that permit uptake of lipoproteins
c. GPI anchor—a glycolipid (glycosylphosphatidylinositol) by body cells.
used to link certain proteins to membranes, preferen-
tially in lipid rafts 15
d. glycolipids—a glycosphingolipid; a molecule in which a Bile salts are used to emulsify dietary fat and oils so they
carbohydrate group is attached to ceramide through an may be digested and then absorbed.
O-glycosidic linkage 17
e. sphingomyelin—a type of phospholipid; the 1-hydroxyl For a phospholipid to move from one side of the bilayer to
group of ceramide is esterified to the phosphate group of the other, the polar head must move through the hydropho-
phosphatidylcholine or phosphatidylethanoloamine and bic portion of the phospholipid membrane. This process
the amino group of sphingosine is in an amide linkage requires a significant amount of energy and is therefore
with a fatty acid relatively slow.
7 19
a. prenylation—the covalent attachment of prenyl groups Prostaglandins have major recognized roles in all the
(e.g., farnesyl and geranylgeranyl groups) to protein ­following processes: reproduction, respiration, and inflam-
molecules mation. (Note: Thromboxanes promote blood clotting,
b. steroid—a derivative of triterpenes; contains four fused while prostaglandins inhibit platelet aggregation, thus in-
rings hibiting blood clotting. Some prostaglandins also have va-
c. digitalis—a type of cardiac glycoside; a molecule that sodilating or vasoconstricting activity, which may affect
increases the force of cardiac muscle contractions blood pressure.)
d. lipoprotein—a conjugated protein in which lipid mol-
ecules are the prosthetic groups; a protein-lipid complex 21
that transports water-insoluble lipids in the blood The indicated compounds are classified as follows:
e. apolipoprotein—the protein component of a lipoprotein a. monoterpene    d. polyterpene
b. monoterpene    e. diterpene
9 c. sesquiterpene   f. triterpene
a. peripheral protein—a protein that is not embedded in the
membrane but attached either by a covalent bond to a 23
lipid molecule or by a noncovalent interaction with a To increase a cell’s resistance to mechanical stress,
membrane protein or lipid increase the content of cholester­ol and cardiolipin (two
b. integral protein—a protein that is embedded within a phospholipids linked by a glycerol) in the cell membrane.
membrane 25
c. lipid raft—a specialized microdomain in the external The three proteins that facilitate the movement of phospho-
leaflet of eukaryotic plasma membrane lipid molecules from one side of a membrane to another are
d. passive transport—transport of a substance across mem- as follows. Flippase transfers phospholipids from the outer
branes that requires no direct input of energy to the inner membrane leaflet. Floppase transfers phospho-
e. active transport—the energy-requiring movement of lipids from the inner to the outer leaflet. Scramblase is a
molecules across a membrane against a concentration nonspecific, energy-independent redistributor of phospho-
gradient lipids across membranes.

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 A-26 Appendix

27 In the presence of water these materials would either dis-

a. In primary active transport, ATP provides energy to solve or swell. Waxes on the other hand are composed of
transport a substance against a concentration gradient. hydrophobic molecules that are resistant to the penetration
The Na1-K1 ATPase pump is a primary transporter, since of water from the leaf interior. A relatively thick wax layer
it transports substances across a membrane from lower to prevents insect penetration.
higher concentration. Secondary active transport uses the 38
concentration gradients that were generated by p­ rimary Boric acid is a hard crystalline solid. One of the ways that
active transport to drive the transport of a different sub- this abrasive molecule kills insects is that when it contacts
stance against its concentration gradient. An example of the exoskeleton the crystals cut into the wax coat. These
secondary active transport is the use of the gradient cre- gaps allow water to escape and the insect dies of dehydra-
ated by the Na1-K1 ATPase pump to transport glucose. tion. (Boric acid is also an internal poison in insects. When
b. Passive transport is the general term for the transport of insects, which are covered with boric acid powder, groom
substances across a membrane by diffusion. Since passive themselves, they ingest the boric acid crystals. Boric acid
transport occurs down (or with) a concentration gradient interferes with the digestion of food, thereby causing
(i.e., from an area of high concentration to low concentra- starvation.)
tion), no energy is required. Facilitated diffusion is the
passive transport of substances such as ions or polar mol-
ecules that are unable to cross the membrane alone and
Chapter 12: In-Chapter Questions
require the presence of a protein channel or carrier. For 12.1
example, nonpolar organic molecules (such as steroid hor- The triacylglycerols are emulsified in the small intestine by
mones) and carbon dioxide cross cell membranes by pas- bile salts. They are then digested by lipases, the most im-
sive diffusion. The red blood cell glucose transporter is an portant of which is pancreatic lipase. The products, fatty
example of a carrier, and Na1 may diffuse through a acids and mono­acylglycerol, are transported into entero-
membrane only through specific Na1 channel proteins. cytes and reconverted to triacylglycerol. Triacylglycerol is
c. Both carrier-mediated and channel-mediated transport subsequently incorporated into chylomicrons, which are
are examples of facilitated diffusion. In channel-­ then transported into lymph via ­exocytosis and finally into
mediated transport, an integral protein forms a channel the bloodstream for transport to the fat cells.
through which a specific substance may pass. In carrier-
mediated transport, the substance to be transported 12.2
binds to the carrier protein and causes a conformational Although there is no cure for MCAD, symptoms can be
change. This change results in the substance crossing managed primarily by ensuring that frequent feeding
the membrane, where it is then released by the carrier occurs, i.e., there are no prolonged fasts. This can be a
protein. See (b) for examples. ­challenge in patients who often manifest a poor appetite so
intravenous feeding with glucose may be necessary. Since
29 toxic products of fatty acid metabolites can accumulate,
Detergents disrupt membranes and extract membrane the diet must be low in fat. Daily consumption of carnitine
proteins by solubilizing both their hydrophobic and their ­supplements may also be beneficial because acyl-carnitine
hydrophilic components, effectively dispersing them derivatives are excreted in urine.
throughout the aqueous solvent.
12.3
a. phospholipid
Thought Questions
b. acyl-CoA
32 c. carnitine
Most of the cholesterol in plaque results from the ingestion
12.4
of LDL by the foam cells that line the arteries. High blood
Unlike the oxidation of glucose to form pyruvate, fatty
plasma LDL therefore promotes atherosclerosis. Because
acid oxidation, which involves the citric acid cycle and the
the coronary arteries are narrow, they are especially prone
electron transport system, cannot operate in the absence
to occlusion by atherosclerotic plaque.
of O2.
34
12.5
The hooves and lungs are subjected to much lower tempera-
The yield from the oxidation of stearyl-CoA is calculated as
tures than the rest of the body. At these low temperatures,
­follows:
the membrane must be modified so that the membranes
8 FADH2 3 1.5 ATP/FADH2 5 12 ATP
remain fluid. This can be done by increasing the unsatura-
8 NADH 3 2.5 ATP/NADH 5 20 ATP
tion of the nonpolar tails of the membrane phospholipids.
9 Acetyl-CoA 3 10 ATP/Acetyl-CoA 5       90 ATP
36 122 ATP
Both carbohydrates and proteins contain large numbers of Two ATP are required to form stearyl-CoA from stearate to
atoms capable of hydrogen bonding (oxygen and nitrogen). give a total of 120 ATP.

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 Appendix
A-27

12.6 b. mixed function oxidase—one of a group of enzymes that

Propionyl-CoA can be reversibly converted to succinyl-CoA, catalyse reactions in which one oxygen is consumed (re-
an intermediate in the citric acid cycle. Oxaloacetate, a duced) per substrate molecule, one oxygen atom appear-
downstream intermediate of this cycle can be converted to ing in the product and the other in a molecule of water;
PEP. PEP is then converted to glucose via gluconeogenesis. also referred to as monooxygenases
c. flavin-containing monooxygenase—one of a group of
12.7 ­enzymes that catalyse an NADPH and oxygen-requiring
Adipic acid undergoes one round of b-oxidation to yield oxidation of molecules (primarily xenobiotics) bearing func-
acetyl-CoA and succinyl-CoA. Succinyl-CoA is sequen- tional groups containing nitrogen, sulfur, or phosphorus
tially converted to oxaloacetate, PEP, and then to glucose. d. detoxication—the process by which a toxic molecule is
12.8 converted to a more soluble and usually less toxic product
Following the hydrolysis of sucrose, both monosaccharide e. detoxification—correction of a state of toxicity; the
products enter the bloodstream and travel to the liver, where chemical reactions that produce sobriety in an inebriated
fructose is ­converted to fructose-1-phosphate. Recall that person
the conversion of fructose-1-phosphate to glyceraldehyde- 7
3-phosphate bypasses two regulatory steps. Consequently, Peroxisomes have b-oxidation enzymes that are specific for
more glycerol-phosphate and acetyl-CoA (the substrates for long chain fatty acids, whereas mitochondria possess en-
triacylglycerol synthesis) are produced. High blood glucose zymes that are specific for short and moderate chain length
concentrations that result from this c­ onsumption of exces- fatty acids. In addition, the first reaction in the peroxisomal
sive amounts of sucrose trigger the release of larger than pathway is catalysed by a different enzyme than the mito-
normal amounts of insulin. One of the functions of insulin chondrial pathway. The FADH2 produced in the first per-
is to promote fat synthesis. oxisomal reaction donates its electrons to oxygen directly
12.9 (forming hydrogen peroxide instead of UQ as in mitochon-
a. b-Hydroxybutyrate is a product of ketone body dria). The processes are similar in that acetyl-CoA is de-
metabolism. rived from the oxidation of fatty acids.
b. Malonyl-CoA is the product of the reaction of acetyl-CoA 9
and carboxybiotin that occurs during fatty acid systhesis. Because of the presence of the methyl substituent on the
c. Biotin is a carrier of CO2 in fatty acid synthesis and sev- b-carbon, the fatty acid first undergoes one cycle of
eral other reactions. a-oxidation. The resulting molecule, now shorter by one
d. Acetyl ACP delivers acetate to the synthetic machinery carbon atom, then undergoes one cycle of b-oxidation.
of fatty acid synthesis. The products of the latter process are two molecules of
12.10 propionyl-CoA.
The higher activity of HMG-CoA reductase in obese 11
­patients in combination with a high-calorie diet increases The yield of ATP from the oxidation of stearic acid is 122
the synthesis of cholesterol. (8 FADH2 3 1.5 ATP, 8 NADH 3 2.5 ATP and 9 acetyl-
CoA x 10 ATP). Since the formation of stearoyl-CoA re-
Chapter 12: End-of-Chapter Questions quires two ATP equivalents the net synthesis is 120 ATP.
Stearic acid yields 120/18 or 6.6 ATP per carbon atom.
Review Questions Recall that the ratio for glucose is 5.2 ATP per carbon atom.
3 13
a. adipocytes—TG-storing cells in adipose tissue After the TG content of VLDL (very low density lipopro-
b. MCAD—medium-chain acyl-CoA dehydrogenase – a teins) has been depleated, the lipoprotein is referred to as
mitochondrial enzyme that catalyses the first reaction an IDL (intermediate density) lipoprotein.
in the b-oxidation cycle 15
c. ACP—acyl carrier protein—a component of fatty acid Enoyl-CoA isomerase converts the naturally occurring cis
synthase double bond at D 3 to a trans double bond at D 2, the correct
d. a-oxidation—a mechanism for degrading branched- position for the next round of b-oxidation.
chain fatty acid molecules such as phytanic acid
e. odd chain oxidation—oxidation of fatty acids with an 17
odd number of carbons; proceeds via b-oxidation to The indicated bond is cleaved by glucocerebrosidase.
yield acetyl-CoA molecules and one propionyl-CoA CH2OH
5 CH3(CH2)12 CH CH CH CH CH2 O O
a. cytochrome P450 —one of a group of haemoproteins that OH NH OH
when complexed with carbon monoxide absorb light at a C OH
wavelength of 450 nm; oxidizes a wide variety of hydro- R O OH
phobic molecules

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 A-28 Appendix

19 phosphate, which is a substrate for the synthesis of glucose,

Review Figure 12.31 on p 428. The bile salts are emulsify- phospholipids, and triacylglycerols.
ing agents that facilitate fat digestion. 31
21 Of the four reactions in b-oxidation, only reactions 1 and 3
The components of the cytochrome P450 electron transport are oxidation reactions:
system are: 1) cytochrome P450, which contains haem, and 1) Acyl-CoA 1 FAD Æ trans-a,b-Enoyl-CoA 1 FADH2
2) NADPH-cytochrome P450 reductase, a flavoenzyme that 3) L-b-Hydroxyacyl-CoA 1 NAD1 Æ b-Ketoacyl-CoA 1
contains both FAD and FMN. Cyt P450 catalyses oxidation NADH 1 H1
reactions involving a wide variety of hydrophobic sub-
strates. A hydroxyl group appears in each reaction. The Thought Questions
electrons required for each Cyt P450-catalysed reaction
are donated by Cyt P450 reductase. 34
a. Hydrophobic interactions are probable between the
23 enzyme and the lipid in the micelle.
The inability of peroxisomal thiolase to bind medium-chain b. For phospholipases to be drawn into the micelle, they
acyl-CoA requires the final three-to-six b-oxidation cycles must have a hydrophobic surface.
of every fatty acid to take place in one organelle, the mito-
chondria. This is an advantage to the cell because it allows 36
for tighter regulation of the b-oxidation of fatty acids to Membrane phospholipids are synthesized on the cytoplas-
form acetyl-CoA molecules. Efficiency is also increased mic side of SER membrane. Because the polar head groups
since acetyl-CoA produced in mitochondria may enter the of phospholipid molecules make transport across the hydro-
citric acid cycle without needing to be transported across phobic core of a membrane an unlikely event, a transloca-
membranes. Similarly, the NADH and FADH2 may enter tion mechanism is used to transfer phospholipids across the
the ETC directly. Otherwise, there would be an energy cost membrane to ensure balanced growth. Choline-containing
associated with transporting acetyl-CoA from the peroxi- phospholipids are found in high concentration on the lume-
somes to the mitochondria. The maximum number of ATP nal side of ER membrane because a prominent phospho-
could not be realized from a fatty acid molecule in a per- lipid translocator protein called flippase preferentially
oxisome, since the NADH and FADH2 produced there transfers this class of molecule.
would not be able to enter the mitochondria to enter the 38
ETC. A further consideration is the additional regulation The reaction for the oxidation of one mole of palmitic acid is:
by compartmentation made possible by the requirement of
b-oxidation to be completed in mitochondria. For example, CH3(CH2)14COOH 1 23 O2 Æ 16 CO2 1 16 H2O
to prevent fatty acid synthesis from occurring at the same One mole of palmitic acid produces a yield of 16 moles
time as b-oxidation in the liver, the transport of fatty acids of water molecules. From this number must be subtracted
into mitochondria is inhibited when fatty acid synthesis is 8 moles of water of which 7 moles are used in the hydration
taking place in the cytoplasm. If b-oxidation could go to reaction in each round of the b-oxidation spiral and 1 mole
completion in peroxisomes, it would negate this control is used for the hydrolysis of pyrophosphate, the reaction
mechanism. that drives the activation of the palmitic acid molecule to
completion. The net reaction, therefore, yields a total of
25 8 molecules of metabolic water.
NADH donates electrons to an electron transport system
composed of cytochrome b5 reductase (a flavoprotein) and 40
cytochrome b5 (which contains haem). An oxygen-depen- Fatty acids are assembled from two carbon acid synthase
dent desaturase uses these electrons (from NADH) to acti- which ends the process at C-16. Although there is a robust
vate O2. The activated O2 oxidizes the fatty acyl-CoA to capacity to elongate fatty acids, the most abundant fatty
create an alkene in its hydrocarbon chain, and is reduced to acids are C16 and C18, the product of one round of elonga-
form two molecules of water. tion process.
27
Since the 14CO2 that is added to acetyl-CoA is removed in Chapter 13: In-Chapter Questions
the reaction of malonyl-ACP with acetyl synthase to form 13.1
acetoacetyl-ACP, no 14C label appears in the eventual fatty
Refer to Figure 13.4 for an illustration of the relative loca-
acid products.
tions of CFoCF1, P700 (in PSI), and P680 (in PSII) within
29 thylakoid membrane. The Calvin cycle reactions occur in the
Glycerol (generated from the lipolysis of adipocyte triacyl- stroma, the gel-like substance that surrounds the external
glycerols) is released into the blood and transported to the surface of thylakoid membrane. CFoCF1 is the ATP synthase
liver, where glycerol kinase converts it to glycerol-3- that utilizes the transmembrane proton gradient to drive ATP

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 Appendix
A-29

synthesis. P700 is the term used to indicate the special pair and pyruvate kinase, enzymes required to channel carbon
of chlorophyll a molecules in the reaction centre of PSI that skeletons into the citric acid cycle.
absorbs light energy and then donates the energized electrons
that eventually reduce NADP1. P680 is a special pair of chlo- Chapter 13: End-of-Chapter Questions
rophyll a molecules in PSII that absorbs light energy and
then donates energized electrons eventually to plastoquinone. Review Questions
The Calvin cycle enzymes are responsible for utilizing ATP 3
and NADPH generated by the light reactions to incorporate a. phylloquinone (A1)—one of several electron carriers
C02 into carbohydrate molecules. that transfers the PSI P700* energized electron to
ferredoxin
13.2 b. lutein—a light absorbing and antioxidant carotenoid
The energy of a photon is proportional to its frequency. found in thylakoid membrane
Blue light has a higher frequency than green light and c. QA—an electron carrier bound to protein in PSII; a
therefore has higher energy. plastoquinone
13.3 d. PQH2—plastoquinol, the reduced form of platoquinone;
The presence of antenna pigments allows the light-harvesting oxidized to supply two electrons to plastocyanin
systems of chloroplasts to collect energy from a wider range e. carotenoids—isoprenoid molecules that function as
of frequencies than those absorbed by the chlorophylls. Be- light-harvesting pigments and antioxidants
cause their absorption spectra overlap, the energy absorbed 5
by the antenna ­pigments is quickly transferred to the critical a. cytochrome b6f complex—a multisubunit protein
chlorophylls of PSI and PSII. complex in thylakoid membrane that is similar in
13.4 structure and function to cytochrome bc1 complex
Excessive light promotes the formation of ROS, which in mitochon­drial inner membrane; delivers electrons
damage proteins such as D1. b-Carotene is an antioxidant donated by plastoquinol to the water-soluble protein
that prevents some of this damage. plastocyanin
b. CF0 —a membrane-spanning protein complex in the
13.5 chloroplast ATP synthase that contains a proton
a. Plastocyanin is a component of the cytochrome b6f com- channel
plex; a copper-containing protein that accepts electrons c. CF1—the ATP synthesizing component of the chloro-
from plastoquinone. plast ATP synthase
b. b-Carotene is a carotenoid pigment that protects d. LCHII—light-harvesting complex II – a trimer of light-
­chlorophyll molecules from ROS. harvesting proteins bound to chlorophyll a and b mol-
c. Ferredoxin is a mobile, water-soluble protein that ecules; detachable from PSII
­donates ­electrons to a flavoprotein called ferredoxin- e. Mn4CaO5—a component of the oxygen-evolving com-
NADP oxidoreductase. plex; found on the luminal side of PSII
d. Plastoquinone is a component of photosystem II that
­accepts electrons from pheophytin a to become 7
plastoquinol. The most significant contribution of early photosyn­
e. Pheophytin a is a molecule similar in structure to thesizing organisms to the earth’s environment was the con-
­chlorophyll that is a component of the electron trans- version of a reducing atmosphere (ammonia and methane)
port pathway between PSII and PSI. to an oxidizing atmosphere.
f. Lutein is a carotenoid that is a component of light-­ 9
harvesting complexes. Excited molecules can return to its ground state in 4 ways:
(1) fluorescence in which a molecule’s excited state decays
13.6
as it emits a photon; (2) resonance energy transfer in which
Of the herbicides discussed, paraquat and DCMU are most
excitation energy is transferred to neighbouring chromo-
hazardous to humans. Paraquat generates free radicals that
phores through interaction between adjacent molecuar or-
can attack cell components. DCMU poisons the electron
bitals; (3) oxidation-reduction in which an excited electron
transport complex.
is transferred to a neighbouring molecule; and (4) radiation-
13.7 less decay into heat. The most important of these mecha-
The hydrolysis of glycerate-l,3-bisphosphate generates nisms in photosynthesis are resonance energy transfer,
1 mol of ATP. Recall that aerobic respiration is stimulated which plays an important role in the harvesting of light
by relatively high ADP concentrations and inhibited by rel- energy and oxidation-reduction, which is illustrated by the
atively high ATP concentrations. Any measurable increase Z scheme. Fluorescence is used as a protective mechanism
in ATP concentration has the effect of depressing aerobic in which photons are reemitted when light absorption by a
respiration. Also recall that ATP is an inhibitor of PFK-1 photosystem is excessive.

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 A-30 Appendix

11 34
The ultimate goal of artificial photosynthesis research is to Only light of a particular energy can be absorbed by
devise a cost-effective means of generating fuel such as H2 photosynthetic pigments. Increasing the intensity of the
and methane. In addition, these research efforts provide light increases the number of photons present and hence
­insight into the intricacies of the natural process. can improve the rate of photosynthesis. Increasing the
16 energy level of the light, that is, the energy of the photons,
A special pair is composed of two special chlorophyll a decreases the rate of photosynthesis by shifting the photons
molecules that reside within a reaction centre. In PSI the to energy levels that are not absorbed by the photosystems.
special pair is referred to as P700, because it absorbs light 36
at 700 nm. In PSII the special pair of chlorophyll a mol- If sufficient carbon dioxide is already present to saturate all
ecules are referred to as P680. of the ribulose-1,5-bisphosphate carboxylase molecules, the
18 presence of additional carbon dioxide molecules will not
Deforestation has numerous negative effects on the local increase the rate of photosynthesis. In addition, photosyn-
environment. Among these are a disrupted water cycle thesis is depressed by low light levels.
(the local climate becomes drier because of the loss of 38
transpiration by trees), significantly increased water Under conditions of high temperature, the carbon dioxide
runoff and erosion (tree roots absorb rain water and compensation point of C3 plants rises because the oxygen-
groundwater), and a degraded environment with reduced ase activity of rubisco increases more rapidly than the
biodiversity. ­carboxylase activity.
22
The Z scheme is a mechanism whereby electrons are 40
transferred from water to NADP1. This process produces Chloroplasts must be relatively large to intercept the light
the reducing agent NADPH required for fixing carbon di- necessary to carry out photosynthesis
oxide in the light-independent reactions of photosynthesis. 42
Removal of the electrons from water also results in the Because of extensive photorespiration, which competes with
production of oxygen. As electrons flow from PSII to PSI, photosynthesis, C3 plants expend more energy per gram of
protons are pumped across the thylakoid membrane, a pro- carbon fixed. As a result C4 plants are more efficient.
cess that establishes the proton gradient that drives ATP
synthesis.
Chapter 14: In-Chapter Questions
27
The term triose phosphate is used to describe the molecules 14.1
glyceraldehyde-3-phosphate and dihydroxyacetone phos- a. CH3NH2
phate. Formed during the Calvin cycle, the triose phos- b. NH3
phates are used in plants in biosynthetic processes such as c. CH3CH3
the formation of sucrose, polysaccharides, fatty acids and 14.2
amino acids. As their names suggest, haemoglobin and leghaemoglobin
29 are p­ roteins in the globin superfamily. Recall that haemo-
When hydrogen sulfide is the source of hydrogen atoms, the globin is an oxygen transport protein that contains a haem
end products of photosynthesis are glucose and elemental group, which binds reversibly with O2. The haem in leghae-
sulfur. (The carbon and oxygen atoms in glucose are from moglobin also binds to O2. The function of leghaemoglo-
carbon dioxide molecules.) bin, the sequestration of oxygen molecules, can be deduced
from the irreversible inactivation of the nitrogenase com-
plex in root nodules by O2.
Thought Questions
14.3
32
Because of its close structural similarity to folic acid, meth-
There was a significant shift from hydrogen sulfide based
otrexate is a competitive inhibitor of the enzyme dihydrofo-
photosynthesis to that which oxidizes water, because water
late reductase. (Recall that this enzyme converts folic acid
is an abundant resource, whereas hydrogen sulfide is found
to its biologically active form, THF.) Rapidly dividing cells
only in relatively small quantities.
require large amounts of folic acid. Methotrexate prevents

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 Appendix
A-31

the synthesis of THF, the one-carbon carrier required in Chapter 14: End-of-Chapter Questions
nucleotide and amino acid synthesis. It is therefore toxic to
rapidly dividing cells, especially those of certain tumours Review Questions
and normal cells that divide frequently such as hair and GI
3
tract cells.
a. biogenic amine—an amino acid derivative that acts as a
14.4 neurotransmitter (e.g., GABA and the catecholamines)
b. catecholamine—one of a class of neurotransmitters de-
HO N-Acetyltransferase
CH 2 CH 2
+
NH 3 rived from tyrosine; includes dopamine, norepinephrine,
and epinephrine
N c. pyridoxal phosphate (PLP)—a coenzyme required in trans-
amination reactions; derived from pyridoxine ­(vitamin B6)
H
d. urea—the major nitrogen waste molecule in mammals
Serotonin
e. L-Dopa—3,4-dihydroxyphenylalanine – the precursor
O
molecule in the synthesis of the catecholamines; formed
HO O-Methyltransferase by the hydroxylation of tyrosine catalysed by tyrosine
CH2CH2NH C CH 3
SAM hydroxylase
N
5
H a. synaptic vesicle—a membrane-bound structure in neu-
5-Hydroxy-N-acetyltryptamine rons that contains neurotransmitter molecules
b. thioredoxin—a small protein with two thiol groups that
O
mediates the transfer of electrons from NADPH to
CH3 O
CH2CH2NH C CH3 reduce another molecule, e.g., the reduction of ribonucle-
otides in the synthesis of deoxyribonucleotides
N c. orotic aciduria—a rare genetic disease caused by defec-
H
tive UMP synthase; excessive urinary excretion of orotic
Melatonin
acid; symptoms include anaemia and growth retardation

14.5
The reaction sequence is as follows:
Note that the secondary amino nitrogen alkylates more easily
than the primary amino nitrogen in the guanidoacetate
molecule.

O
+
H3N CH C O–
O
(CH2)3 AGAT NH2 O
+ +
+ H3N CH2 C O– H2N C
NH NH CH2 C O–
Glycine
+ O Guanidoacetate
C NH2 +
H3N CH C O–
NH2
(CH2)3
Arginine
+NH
3

Ornithine

NH2 O NH2 O
+
H2N C H2N C
GAMT
NH CH2 C O– NH CH2 C O–
Guanidoacetate
CH3
SAM SAH Creatine

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 A-32 Appendix

d. anti-adenosine—the conformation of the nucleotide serine to manufacture glucose for transport. Since gluta-
­adenosine in which the base adenine is rotated out- mine (b) is a primary energy source for enterocytes, the
wards away from the 69-CH2OH group of the ribose concentration of glutamine is predicted to be higher in the
moiety nutrient pool entering the enterocytes. (Note: Recall that
e. PRPP - 59- phospho-a-D-ribosyl-1-pyrophosphate—the BCAA 5 branched chain amino acids and EAA are es-
precursor molecule in the synthesis of molecules such as sential amino acids.)
histidine and purine nucleotides
13
7 a. alanine belongs to the pyruvate family
a. methotrexate—an analogue of folate; used to treat b. phenylalanine belongs to the aromatic family
­several types of cancer and autoimmune diseases c. methionine belongs to the aspartate family
b. circadian rhythms—patterns of biological function d. trypthophan belongs to the aromatic family
associated with light and dark such as sleep/wake e. histidine belongs to the histidine family
cycles f. serine belongs to the serine family
c. calmodulin (CAM)—a small calcium-binding protein
that regulates a variety of enzymes 15
d. Lesch-Nyhan syndrome—a fatal X-linked disease The ten essential amino acids in humans are isoleucine,
caused by HGPRT (hypoxanthine guaninephosphoribos- leucine, lysine, methionine, phenylalanine, threonine, tryp-
yltransferase) deficiency; excessive production of uric tophan, and valine. In addition, histidine and arginine are
acid causes severe neurological symptoms essential for infants. These amino acids are essential be-
e. thioredoxin reductase—the dithiol-containing enzyme cause they cannot be synthesized in required amounts by
that transfers electrons from NADPH to thioredoxin humans and must be included in the diet.

9 17
Nitrogen-fixing organisms solve the problem of oxygen The following intermediates occur during the reduction of
inactivation in several ways. These are: (1) anaerobic or- nitrogen to yield ammonia diimine (HN5NH) and hydra-
ganisms live only in anaerobic soil and are not faced with zine (H2N-NH2).
the problem of oxygen inactivation, and (2) other organ- 19
isms physically separate oxygen from the nitrogenase com- Glutamate plays a central role in amino acid metabolism
plex. For example, many of the cyanobacteria produce because it and a-ketoglutarate constitute one of the most
specialized nitrogenase-containing cells called hetero- common a-amino acid/a-keto acid pairs used in trans-
cysts. The thick cell walls of the heterocysts isolate the amination reactions. Glutamate also serves as a precur-
enzymes from atmospheric oxygen. In addition, legumes sor of several amino acids and as a component of
produce an oxygen binding protein called leghaemoglobin, polypeptides. Glutamine serves as the amino group
which traps oxygen before it can interact with the nitroge- donor in numerous biosynthetic reactions (e.g., purine,
nase complex. pyrimidine, and amino sugar synthesis), as a safe storage
11 and transport form of ammonia and as a component of
The concentrations of isoleucine (a) and valine (d) are polypeptides.
typically higher in the blood leaving the liver than in the 21
nutrient pool entering enterocytes because the liver prefer- The biologically active form of folic acid, referred to as tet-
entially exports these essential amino acids. The amino rahydrofolate or THF, is shown below. It is formed by the
nitrogens of BCAA are used by other tissues for the syn- reduction of folic acid with NADPH, in two reactions cata-
thesis of the nonessential amino acids. (Note that this lysed by dihydrofolate reductase.
question concerns concentrations, not total amounts. Since
the liver draws amino acids from the blood to synthesize H
proteins, and the liver cannot replenish these EAA via H2N N N
synthesis, lower numbers of Ile, Leu, and Val molecules O
leave the liver than enter enterocytes. However, since the H
N
N CH2 N C N Glu
liver transports BCAA preferentially, their concentration O H H H
in the blood flowing from the liver is higher.) The concen-
trations of serine (c) and alanine (e) are typically higher in 23
the nutrient pool entering the enterocytes than in the The carbon at position 2 of the uracil ring is derived from
blood leaving the liver because the liver uses alanine and carbon dioxide.

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 Appendix
A-33

26 35
The source of the hydrogen gas produced by the nitrogen The conversion of cytosine to uracil occurs as follows:
reductase system is the same as the source of electrons:
NH2 NH HO NH2 O
NAD(P)H.
N NH H2O NH NH
Thought Questions
N O N
29 N O N O O

Tyrosine becomes an essential amino acid if its precursor H H H H

the EAA phenylalanine is excluded from the diet or if the Cytosine Uracil
enzyme phenylalanine-4-monooxygenase is missing or
­defective or the coenzyme BH4 is not available. Chapter 15: In-Chapter Questions
31
15.1
Glutamate is an excitatory neurotransmittor with stimulat-
In newborn animals arginine will be an essential amino
ing effects on neurons that regulate bodily function such as
acid if the urea cycle is not yet fully functional.
blood pressure and body temperature. Individuals who dis-
play symptoms after consuming monosodium glutamate 15.2
apparently possess efficient mechanisms for transporting Certain intestinal bacteria can release ammonia from urea
glutamate across the blood-brain barrier. molecules that diffuse across the membrane into the intesti-
nal lumen. Treatment with antibiotics kills these organisms,
33
thereby reducing blood ammonia concentration.
Arginine is normally synthesized by the urea cycle. In
small children, the urea cycle is not fully functional. 15.3
Consequently, arginine must be obtained from external +NH O
sources. 3
Decarboxylation
−O S CH2 CH C O−
2

Cysteine Sulfate +
−O S CH2 CH2 NH3 + CO2
2

+ Oxidation
−O S CH2 CH2 NH3
2
−O S +
3 CH2 CH2 NH3
Taurine

15.4
The reactions are as follows:
NADP+ O2 H2O
NADPH 2H+ O2− Cl−

−
O2 O2 H2O2 HOCl
SOD MPO

Superoxide Hydrogen Hypochlorite

peroxide

+ +
H3N CH2 CH2 SO3− + HOCl H2N CH2 CH2 SO3−

Cl

Taurine Tau-Cl

15.5 15.6
Gout is caused by high levels of uric acid. Animals that do a. Urea is formed from ammonia, CO2, and aspartate in the
not suffer from gout possess the enzyme urate oxidase, urea cycle.
which converts uric acid to allantoin. Unlike uric acid, b. Uric acid is the oxidation product of purines.
which is relatively insoluble in blood, allantoin readily c. β -Alanine is produced in the degradative pathway of
dissolves and is easily excreted. ­pyrimidines

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 A-34 Appendix

15.7
Suggested catabolic reactions of b-alanine and
b-aminoisobu­tyrate:
O O O O O

O− O− −O O−
Deamination Oxidation
CH2 CH2 C H C CH2 C C CH2 C
+NH
3
β-Alanine
O CoASH O
Decarboxylation
CH3 C O− CH3 C SCoA

Acetyl-CoA
ATP ADP + Pi

CH3 O O CH3 O O CH3 O

O− O−
Deamination Oxidation −O
CH2 CH2 C H C CH C C CH C O−
+NH
3
β-Aminoisobutyrate
O O O
Decarboxylation Carboxylation
CH3 CH2 C O− −O C CH2 CH2 C O−

Succinate
CoASH
O O
−O C CH2 CH2 C SCoA

Succinyl-CoA
ATP ADP + Pi

Chapter 15: End-of-Chapter Questions d. PAPS—39-phosphoadenosine-59-phosphosulfate—a high

energy sulfate donor molecule used in the synthesis of
Review Questions the sulfatides and proteoglycans
e. S-adenosylmethionine (SAM)—a methyl donor
3
­molecule; an intermediate in the methylation and
a. L-amino acid oxidase—one of several FMN-requiring
­transsulfuration pathways.
liver and kidney enzymes that convert some amino acids
to a-keto acids, ammonium ion and hydrogen peroxide. 7
b. serine dehydratase—a hepatic pyridoxal-requiring a. MAO—monoamine oxidase—an enzyme that catalyses
enzyme that converts serine to pyruvate the oxidation of epinephrine, norepinephrine and dopa-
c. bacterial urease—an enzyme produced by intestinal bac- mine, thereby inactivating them
teria that hydrolyses urea circulating in the bloodstream b. PNMT—phenylethanolamine-N-methyltransferase – the
to form ammonia. SAM-requiring enzyme that catalyses the methylation of
d. adenosine deaminase—an enzyme that releases ammon­ norepinephrine to form epinephrine
ium ion from the adenine ring of AMP in a nucleotide c. COMT—catechol-O-methyltransferase—an enzyme that
catabolic pathway inactivates catecholamines (epinephrine, norepinephrine
e. glutaminase—a liver enzyme that hydrolyses glutamine and dopamine) by catalysing methylation reactions
to form glutamate and ammonium ion d. NPC—Niemann-Pick disease Type C—a disease caused
by the accumulation of cholesterol and glycolipids that is
5 linked to a defective transmembrane protein; symptoms
a. transsulfuration pathway—the biochemical reactions include liver and/or spleen enlargement and progressive
that convert methionine to cysteine neurological problems
b. cystathionine—an intermediate in the transsulfuration path- e. TB—tuberculosis—an infectious disease caused by
way; the product of the reaction of homocysteine and serine. ­Mycobacteriau tuberculosis; damage to the lungs is
c. homocysteine—an intermediate in both the transsulfura- ­associated with the formation of tubercles, which are
tion and methylation pathways. aggregates of infected macrophages

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9 d. NH41—aquatic animals
a. T cells—a T lymphocyte—a white blood cell that bears e. allantoin—some mammals
antibody-like molecules on its surface and binds to and 23
destroys foreign cells in cellular immunity A vegetarian diet excludes taurine. Since domestic cats
b. B cells—a B lymphocyte—a white blood cell that pro- cannot synthesize taurine, they must obtain it by consum-
duces and secrets antibodies, the proteins that bind to ing meat. Without taurine, domestic cats become listless
foreign substances thereby initiating their destruction in and die prematurely.
the humoral immune response
c. cellular immunity—immune system processes mediated 25
by T cells Excess amino acids present after a high protein meal are
d. humoral immunity—the immunity that results from the eventually converted to glutamate in the liver (see the solu-
presence of antibodies in blood and tissue fluid; also re- tion for Review Question 24). Excess glutamate is converted
ferred to as antibody-mediated immunity to N-acetylglutamate, which is an allosteric activator for
e. myoadenylate deaminase deficiency—deficiency of the carbamoyl phosphate synthetase I, the most critical enzyme
skeletal muscle purine nucleotide cycle enzyme myoad- of the urea cycle in that NH41 is one of its substrates. Since
enylate deaminase (AMP deaminase); affected individu- all five enzymes are controlled by substrate concentrations,
als exhibit exercise–induced muscle fatigue higher levels of aspartate would activate argininosuccinate
synthase. (A continued high protein diet results in the acti-
11 vation of the synthesis of all five urea cycle enzymes.)
The structural features that apparently mark proteins for
destruction are: (1) certain N-terminal amino acid residues 27
(e.g., methionine or alanine), (2) peptide motif sequences Tryptophan is ketogenic because its catabolic pathway re-
(e.g., amino acid sequences with proline, glutamic acid, sults in the formation of a-ketoadipate, which reacts further
serine and threonine), and (3) oxidized residues (amino acid to form acetoacetyl-CoA, and then acetyl-CoA. Tryptophan
residues whose side chains have been oxidized by oxidases is glucogenic in that one of its catabolic reactions along this
or ROS). pathway also produces alanine, which is converted to pyru-
vate (a substrate for gluconeogenesis) via a transamination
13 reaction.
Purines are degraded to xanthine, which is oxidized to uric
acid. Note that the structure of uric acid retains the original 29
purine ring, which cannot be degraded by humans. A sig- Humans cannot excrete waste nitrogen atoms as ammonia
nificant percentage of uric acid is excreted in the urine. because of its toxicity. Urea is also toxic but much less so
than ammonia. The conversion of ammonia to urea not
15 only allows the nitrogen to be transported and excreted in
The first two reactions in the biochemical pathway that con- much less toxic form but also prevents the large water
verts ammonium ions to urea (i.e. the formation of carbam- loss that would be required by the excretion of ammonia.
oyl phosphate and citrulline) occur in the mitochon­drial
matrix. Subsequent reactions that convert citrulline to orni- Thought Questions
thine and urea occur in the cytosol. Both citrulline and or-
32
nithine are transported across the inner membrane by
The energy requirements of the urea cycle are closely
specific carriers.
linked to the energy-generating citric acid cycle. Recall that
17 fumarate, a product of the urea cycle, is easily converted to
Individuals with PKU lack phenylalanine hydroxylase (phe- oxaloacetate, the molecule that reacts with incoming acetyl-
nylalanine-4-monooxygenase) activity, so they cannot syn- CoA molecules. Both pathways, together referred to as the
thesize tyrosine from phenylalanine. Tyrosine is therefore Krebs bicycle, occur within the mitochondrial matrix.
an essential amino acid for these patients.
34
19 Tetrahydrobiopterin is a cofactor in the oxidation of phenyl-
The branched chain amino acids (leu, ile, val) are metabo- alanine to form tyrosine. The sustained absence of this
lized primarily in muscle tissue, where they are principally ­cofactor would result in a buildup of phenylalanine and
used to synthesize nonessential amino acids. the appearance of the symptoms of PKU.
21 36
a. uric acid— birds, reptiles and insects Because of the structural similarities to purine, caffeine is
b. urea—mammals converted to a variety of derivatives by xanthine oxidase
c. allantoate—bony fish (e.g., 1-methyluric acid and 7-methylxanthine).

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38
The pathway whereby uracil is converted to b-alanine is as
follows
O O
O O
4 4
H—N 3 5 H—N 3 5
H2N C—NH—CH2CH2—C—O–
2 6 2 6 3 2 1 6 5 4
1 1
O N O N
b-Ureido-propionate
H H

Uracil Dihydrouracil

H2N—CH2CH2—C—O–
1 6 5 4

b-Alanine

The atoms in each molecule are numbered as indicated. 16.4

40 The inhibition of GTP hydrolysis causes the subunit of Gs
In the absence of insulin and/or insulin receptors, target protein to continue activating adenylate cyclase. In intestinal
tissues generate energy by means other than metabolizing cells, this enzyme activity opens chloride channels, causing
glucose. Muscle proteins are degraded to amino acids, loss of large amounts of chloride ions and water. The mas-
which are then used to generate energy for muscle contrac- sive diarrhoea caused by this process quickly leads to seri-
tion via the citric acid cycle. ous dehydration and electrolyte loss.
16.5
Chapter 16: In-Chapter Questions Both DAG and phorbol esters promote the activity of pro-
tein kinase C, which promotes cell growth and division.
16.1 Phorbol esters provide initiated cells with a sustained
Several series of signal transduction components are illus- growth advantage over normal cells. This condition is an
trated in Figure 8.20. A prominent example series consist early stage in carcinogenesis.
of glucagon ­(primary signal), glucagon receptor (receptor),
adenylate cyclase (transducer), and activated protein kinase 16.6
(response). The high blood glucose levels in untreated diabetics result
in the loss of increasingly large amounts of glucose along
16.2 with water in the urine, a condition that causes dehydration.
cAMP molecules would be produced by the binding of a In the absence of usable glucose, the body rapidly degrades
single ­hormone molecule before it diffused away from the fats and proteins to generate energy, Hence Aretaeus’s ob-
receptor site. The amplification factor for the hormone mol- servation that in this disease excessive weight loss and ex-
ecule is 350; that is, 350 cAMP molecules are produced for cessive urination are related.
every hormone-receptor binding event.
16.7
16.3 Long-term fasting or low-calorie diets arc interpreted by
Approximately 100,000 (or 105) molecules of target mol- the brain as starvation. The brain responds by lowering the
ecule (ER) can be activated by a single molecule of hor- body’s BMR. The majority of the energy is derived from
mone. cAMP is generated from ATP by adenylate cyclase fatty acid oxidation. The ­glucose needed for glucose-­
when a hormone molecule binds to its receptor. The inter- dependent tissues is generated via gluconeogenesis at the
action between the receptor and adenylate cyclase is medi- expense of muscle protein.
ated by a G protein, Gs. As a consequence of hormone
binding and the resulting conformational change, the recep- 16.8
tor interacts with a nearby Gs protein. As Gs binds to the As blood glucose and insulin levels in blood drop back to
receptor, GDP dissociates. Then the binding of GTP to Gs normal, glucagon is released from the pancreas. Glucagon
allows one of its subunits to interact and stimulate adenyl- acts on the liver to prevent hypoglycaemia by promoting
ate cyclase, thus initiating cAMP synthesis. cAMP must glycogenolysis and gluconeogenesis. Glucagon stimulates
break down quickly so the signalling mechanism can be glycogenolysis by triggering the synthesis of cAMP, which
precisely controlled. in turn initiates a cascade of reactions that lead to the

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activation of glycogen phosphorylase. Increased lipolysis, and malic enzyme, is used as a reducing agent in a wide
hydrolysis of fat molecules, provides glycerol molecules variety of synthetic reactions (e.g. amino acids, fatty acids,
that are substrates for gluconeogenesis. sphingolipids and cholesterol). The degradation of some of
these molecules (e.g., fatty acids and the carbon skeletons of
the amino acids) results in the synthesis of NADH, a major
Chapter 16: End-of-Chapter Questions source of cellular energy via the mitochondrial electron
Review Questions transport system.

3 11
a. G Protein—one of a set of heterotrimeric GTP binding For several weeks after the onset of fasting, blood glucose
proteins; a protein that binds GTP, which activates the levels are maintained via gluconeogenesis. During most of
protein to perform a function this period, amino acids derived from the breakdown of
b. GPCR—G protein–coupled receptor—a cell surface re- muscle proteins are the major substrates for this process,
ceptor that transduces the binding of a hormone or other Eventually, as muscle becomes depleted, the brain switches
signal molecule into an intracellular response via the to ketone bodies as an energy source. Consequently, the
­activation of a G protein production of urea (the molecule used to dispose of the
c. RTK—receptor tyrosine kinase—a transmembrane re- amino groups of the amino acids) declines.
ceptor that contains a cytoplasmic domain with tyrosine 13
kinase activity that is activated when a ligand is bound One consequence of physical activity is the activation of the
to the external domain sympathetic nervous system, which in turn stimulates the
d. growth factor—an extracellular polypeptide that stimu- adrenal gland to secrete epinephrine and norepinephrine.
lates cells to grow and/or undergo cell division These hormones then activate the adipocytes enzyme hor-
e. cytokine—one of a set of hormone-like polypeptides and mone–sensitive lipase, which catalyses the hydrolysis of
proteins that may stimulate or inhibit cell growth or pro- triacylglycerol molecules to form the fatty acids used to
liferation; traditionally used in reference to proteins pro- drive muscle contraction.
duced by blood-forming cells and immune system cells
15
5 In Alzheimer’s disease there is progressive mental deterio-
a. metabolic syndrome—a cluster of clinical disorders that ration that is characterized by loss of memory, language
includes obesity, hypertension, dyslipidaemia and insulin skills and behavioural changes. Alzheimer’s disease is a
resistance form of dementia in which brain damage is associated with
b. hyperuricaemia—high blood levels of uric acid aggregated b-amyloid protein outside and around neurons
c. hypothalamus—an area of the brain that controls body and aggregated tau protein inside neurons. In type 2 diabe-
temperature and electrolyte balance, monitors nutrient tes mellitus, pancreatic b-cell function is eventually com-
levels, and contributes to feeding behaviour regulation promised by aggregates of misfolded proteins.
d. anorexigenic—appetite inhibiting
e. orexigenic—appetite stimulating 17
HbA1c formation is a consequence of nonenzymatic glyca-
7 tion of haemoglobin that occurs in the presence of high
a. tumour promoter—a molecule that provides cells with a blood glucose levels. In the Maillard reaction, the aldehyde
growth advantage over nearby cells group of glucose condenses with a free amino group in a
b. guanine nucleotide exchange factor (GEF)—a protein protein to form a Schiff base, the Amadori product. The
that mediates a conformational change in the transmem- Amadori product subsequently destabilizes to form a reac-
brane region of a G-protein-coupled receptor that leads tive carbonyl-containing product that reacts with haemoglo-
to GDP/GTP exchange during G-protein activation bin molecules to form an adduct such as HbA1c.
c. DAG—diacylglycerol, a second messenger molecule
generated when PIP2 is cleaved by phospholipase C; 19
­activates protein kinase C In type 1 diabetes (insulin-dependent diabetes mellitus),
d. steady state—a phase in an organism’s life when the rate no insulin is produced and the action of glucagon is unop-
of anabolic processes is approximately equal to that of posed. Glucagon causes an increase in lipolysis in adipo-
catabolic processes cytes, leading to an excess of acetyl-CoA molecules, which
e. IP3—inositol-1,4,5-trisphosphate; a second messenger are converted to ketone bodies. Ketoacidosis (an excess of
molecule generated when PIP2 is cleaved by phospholi- ketone bodies in the blood with low blood pH) is rare in
pase C; binds to IP3 receptor, a calcium channel type 2 diabetes (insulin-independent diabetes mellitus) in
which blood levels of insulin are normal or elevated but
9 cells are resistant to insulin. Since the action of glucagon is
NADPH, which is formed during the pentose phosphate not completely unopposed, and there is some (although re-
pathway and reactions catalysed by isocitrate dehydrogenase duced) glucose uptake by cells, lipolysis is not activated as

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 A-38 Appendix

it is in type 1 diabetes, and the excess production of ketone received the vesicles fuse with plasma membrane and (via
bodies does not occur. exocytosis) release their contents into the bloodstream.
21 32
In addition to water loss, contributing factors to the relatively Appetite regulation in humans is a set of complex and
rapid weight loss during the first week of a prolonged diet are robust mechanisms that involve several areas of the brain,
depletion of glycogen stores, loss of muscle protein, and li- such as the hypothalamus. In response to calorie restriction
polysis of triacylglycerol in adipocytes. Large amounts of which is interpreted as starvation, the appetite centres of
amino acids from muscle protein are needed to provide glu- the brain respond by stimulating appetite, lowering the
cose (via gluconeogenesis in the liver), the preferred energy body’s BMR (to conserve energy), lowering energy expen-
source for the brain. Lipolysis releases fatty acids to provide ditures (resulting in lethargy). As a result of these and
an alternate energy source to glucose. Regarding the water other hormone- and peptide-triggered responses, continued
loss, note that water bound by glycogen will be lost when gly- achievement of weight loss and maintenance of a reduced
cogen is depleted. Also a molecule of water is required to hy- weight over time becomes very difficult, if not impossible.
drolyse each glycosidic, ester and peptide bond.
34
23 mTORC1 is a central metabolic sensor that integrates hor-
a. The intestine digests foods into nutrients that are small monal activity, nutrient availability, energy status and
enough to be absorbed (e.g., sugars, fatty acids, and amino stress. It stimulates anabolic processes such as protein syn-
acids). The small intestine, as well as the stomach, pro- thesis. When levels of ATP, nutrients, and oxygen are low,
duces ghrelin, a hormone that stimulates nutrient intake. AMPK inhibits mTORC1.
b. The liver has numerous roles in nutrient metabolism.
Among these are monitoring blood nutrient levels, distri- 36
bution of nutrients to the body’s tissues (e.g., amino In a signal cascade the initial signal can be present in low
acids), and regulation of blood glucose via gluconeogen- concentrations. The message can then be amplified as the
esis and glycogenolysis. cascade progresses. In addition, an intricate multistage cas-
c. Skeletal muscle consumes glucose and fatty acids, cade mechanism provides opportunities for the integration
energy sources that drive muscle contraction. During of numerous cellular processes
fasting skeletal muscle protein is degraded to yield ala- 38
nine, which is delivered to the liver for gluconeogenesis. Exercise promotes insulin-independent glucose uptake by
Cardiac muscle relies primarily on glucose and fatty muscle cells, which facilitates blood glucose control.
acids for energy.
d. Adipose tissue cells store TGs, and release fatty acids 40
and glycerol into the blood for delivery to other organs. During prolonged starvation ketone body levels will even-
e. The kidney uses fatty acids and glucose to meet its tually rise to levels that cause acidosis, a condition that
energy needs. It disposes of the water-soluble products of causes kidney damage.
nutrient metabolism (e.g., urea). 42
f. The brain uses glucose as its sole fuel. During prolonged The unregulated conversion of fructose to triose phosphate
starving, the brain can adapt to use ketone bodies as an promotes liver lipogenesis and VLDL synthesis and
energy source. secretion.

Thought Questions Chapter 17: In-Chapter Questions

26 17.1
The second messenger is an effector molecule synthesized The cytosine-guanine base pair with its three hydrogen
when a hormone (the first messenger) binds. It stimulates bonds is more stable than the adenine-thymine base pair.
the cell to respond to the original signal. Second messen- The more CG bp there are, the more stable the DNA mol-
gers also allow the signal to be amplified. ecule. Structure b, with the fewest CG bp, will therefore
28 denature first.
Increased mobilization of fatty acids provides an alternate 17.2
energy source for muscle, thereby sparing glucose for the a. Ethanol will disrupt the hydrogen bonding in the base
brain. In addition, glucagon stimulates gluconeogenesis, a pairs and denature the DNA.
pathway that utilizes amino acids derived from muscle. b. Heat, which easily disrupts hydrogen bonds, will cause
30 DNA chains to separate and denature.
The storage of preformed hormone molecules in secretory c. Dimethylsulfate is an alkylating agent that can cause
vesicles allows for a rapid response of the producing cells to transversion and transition mutations.
metabolic signals. As soon as the appropriate signal is d. Nitrous acid deaminates bases.

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A-39

17.3 39-GCAUUCGAAUUGCAGACUCCUGCAAUUCGGCAA
The brain is especially sensitive to oxidative stress because U-59.
it uses a greater proportion of oxygen than other tissues.
17.8
Consequently, the chance of oxidative damage is also high.
In the original central dogma, the flow of genetic informa-
In addition, when most types of brain cells are irreversibly
tion is in one direction only, that is, from DNA to the RNA
damaged by ROS, they cannot be replaced. In addition to
molecules, which then direct protein synthesis. The altered
hydroxyl radicals, other ROS that can contribute to oxida-
diagram indicates that the RNA genome of some viruses
tive stress in the brain include superoxide, hydrogen perox-
can replicate their RNA genomes (using a viral enzyme
ide, and singlet oxygen.
activity referred to as RNA-directed RNA polymerase) or
17.4 undergo reverse transcription (i.e., synthesize DNA from
In A-DNA, the dehydrated form of DNA, the base pairs an RNA sequence).
are no longer at right angles to the helical axis. Instead,
they tilt 20 degrees away from the horizontal as compared Chapter 17: End-of-Chapter Questions
to B-DNA. The distance between adjacent base pairs is
slightly reduced, with 11 bp per helical turn instead of the Review Questions
10.4 bp that occurs in the B-form. Each turn of the double
helix of A-DNA occurs in 2.5 nm instead of the 3.4 nm of 3
B-DNA. The diameters of A-DNA and B-DNA are 2.6 and a. point mutation—a change in a single nucleotide base in a
2.4 nm, respectively. The significance of A-DNA is unclear. DNA sequence
It has been observed that its overall appearance resembles b. transition mutation—a DNA mutation that involves the
that of RNA duplexes and the RNA-DNA hybrids that form substitution of a purine base by a different purine, or the
during ­transcription. substitution of a pyrmidine by a different pyrmidine
With a diameter of 1.8 nm, Z-DNA is considerably c. transversion mutation—a type of point mutation in which
slimmer than B-DNA. It is twisted into a left-handed spiral a pyrimidine is substituted for a purine and vice versa
with 12 bp per turn, each of which occurs in 4.5 nm instead d. silent mutatio—a point mutation that has no discernable
of the 3.4 observed in B-DNA. Segments with alternating effect on a polypeptide’s function
purine and pyrimidine bases are most likely to adopt the e. missense mutation—a point mutation that results in an
Z-DNA configuration. In Z-DNA the bases stack in a left- amino acid substitution resulting in a change in a poly-
handed, staggered pattern that gives this form its flattened, peptide’s function
non-grooved surface and zigzag appearance. The signifi- 5
cance of Z-DNA is unresolved. a. Chargaff’s rules—a set of rules describing the base com-
17.5 position of DNA; posits the equality of the concentration
The genome is the total set of DNA-encoded genetic infor- of adenine and thymine and of cytosine and guanine
mation in an organism. A chromosome is a DNA molecule, b. constitutive heterochromatin—sections of DNA in
usually complexed with certain proteins. Chromatin is the ­eukaryotes that is permanently highly condensed and
partially decondensed form of eukaryotic chromosomes. transcriptionally silent; occurs at centromeres, telomeres,
Nucleosomes are the repeating structural units of eukary- transposons and repetitive sequences.
otic chromosomes formed by the interaction of DNA with c. bacteriophage—a type of virus that infects bacteria
the histones. A gene is a DNA sequence that codes for a d. replication-dependent histones—histones that are
polypeptide or an RNA molecule. ­synthesized during S phase of the cell cycle in
­coordination with DNA synthesis.
17.6 e. replication-independent histones—histones that are
The genomes of prokaryotes are substantially smaller than ­synthesized in small amounts throughout the cell cycle.
those of eukaryotes. For example, the genome sizes of
E. coli and humans are 4.6 and 30 Mb, respectively. Pro- 7
karyotic genomes are compact and continuous; that is, there a. histones—a group of basic proteins found in all eukary-
are few, if any, noncoding DNA sequences. In contrast, eu- otes that bind to DNA to form nucleosomes
karyotic DNA contains enormous amounts of noncoding b. heterochromatin—highly condensed chromatin that is
sequences. Other distinguishing features of prokaryotic and transcriptionally inactive; constitutive heterochromatin is
eukaryotic DNA are the linkages of genes into operons in permanently condensed; facultative herterochromatin
prokaryotes and intervening sequences in eukaryotic genes. may be decompressed in specific cell types
c. euchromatin—a less condensed form of chromatin with
17.7 varying levels of transcriptional activity
The antisense DNA sequence is 39-CGTAAGCT d. intergenic sequences—DNA sequences in which
TAACGTCTGAGGACGTTAAGCCGTTA-59; the mRNA ­multiple copies are arranged next to each other.
sequence is 39-CGUAAGCUUAACGUCUGAGGACGU e. tandem repeats—DNA sequences in which multiple
UAAGCCGUUA-59, The antisense RNA sequence is copies are arranged next to each other

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9 21
a. DNA typing—a DNA analysis technique used to iden- The Env trimer (a complex of three gp120/gp41 heterodi-
tify individuals; involves the analysis of several highly mers) is a fusion machine that enables HIV to attach to and
variable sequences called markers fuse with the plasma membrane of target cells. Fusion of
b. short tandem repeats—DNA sequences with between the HIV envelope with a target cell plasma membrane is the
2 and 4 bp repeats; can be used to generate DNA profiles initiating event in the infection of the target cell.
that distinguish among individuals
23
c. DNA profile—a unique DNA pattern of repeats of target
Water stabilizes DNA structure by binding to phosphate
sequences that is separated in an electrophoresis gel;
groups, deoxyribose 39- and 59-oxygen atoms, and electro-
used to identify individuals
negative atoms in the nucleotide bases. Also, the increased
d. ribozyme—catalytic RNA molecules; catalyses self-
entropy of surrounding water molecules drives the hydropho-
cleavage or the cleavage of other RNA molecules
bic interactions between the nucleotide bases within the helix
e. noncoding RNA—types of RNA other than the RNAs
involved in protein synthesis (i.e. tRNAs, rRNAs and 25
mRNAs) that act as an extensive genome regulatory According to the histone code hypothesis, the pattern of
network histone modification within each DNA sequence regulates
gene expression by serving as a platform for the binding of
11
proteins that inhibit or facilitate transcription.
Eukaryotic genomes are larger than those of prokaryotes.
In contrast to prokaryotic genomes, which consist entirely 27
of genes, the majority of eukaryotic DNA sequences do not Ethyl chloride is an alkylating agent that can react with
appear to have coding functions. Unlike prokaryotic genes, DNA bases to form ethyl derivatives.
most eukaryotic genes are not continuous (i.e. they usually
contain introns). Thought Questions
13 30
RNA molecules differ from DNA in the following ways: The major and minor grooves of DNA arise because the
(1) RNA contains ribose instead of deoxyribose, (2) the glycosidic bonds in the two hydrogen bonded strands are
­nitrogenous bases in RNA differ from those of DNA not exactly opposite to each other.
(e.g., uracil replaces thymine and several RNA bases are
chemically modified), and (3) in contrast to the double 32
helix of DNA, RNA is single-stranded. The electron withdrawing effect of the bromine increases
the likelihood of enol formation of uracil. This enol mimics
15 the hydrogen bonding pattern of cytosine. Therefore this
There are approximately 6 million base pairs in a single base can be paired with guanine.
human cell. Assuming that there are 1014 body cells, the
total length of the DNA in the human body is approxi- 34
mately 2 3 1011 km. This estimated length is about 1000 The histones act to shield the DNA from the action of
time greater than the distance for the earth to the sun. nucleases.
(Note that 1 nm is 1029 m.) 36
17 At the crime scene, a forensic expert collects biological
Before the publication of the Watson-Crick paper in 1953, specimens such as blood, hair, and saliva. Once these
research efforts were focused on proving that DNA is the specimens are delivered to the lab, they are analysed and
genetic material and more recently to discover its structure. compared with the DNA of the victim. Any DNA not
Beginning with the Watson-Crick paper, research efforts belonging to the victim is assumed to belong to a person,
rapidly shifted to the functional properties of DNA and re- or persons, present during the time when the crime was
lated cell processes. This work was eventually referred to committed. If a suspect is identified, his or her DNA
as molecular biology. profile (obtained from a swab of cheek cells or from a court-
ordered blood sample) is compared with that obtained from
19 crime scene specimens. If there is no obvious suspect, the
The stable inheritance of DNA methylation patterns from crime scene specimens can be compared to the DNA pro-
one cell generation to the next is made possible by a class files in the statewide database. This strategy has been re-
of enzymes called the maintenance methyltransferases. markably successful in the identification of individuals later
They methylate the cytosines in CpG-rich regions in newly found guilty not only of recent murders, but also those from
synthesized DNA strands. The enzymes methylate the ‘cold cases’ in which crime scene specimens had been pre-
­cytosines on the new strand at sites opposite to the served. The technology that makes this success possible
­methylated cytosines on the parental strand. includes PCR, RFLP, and STR-DNA analysis.

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38 18.3
The hydrogen bonds to water molecules formed by the When antibiotics are used in large quantities, the bacterial
atoms in a phosphodiester linkage are as follows: cells that possess resistance genes (acquired through spon-
taneous mutations or through intermicrobial DNA transfer
CH2 BASE
O
mechanisms such as conjugation, transduction, and trans-
formation) survive and even flourish. Because of antibiotic
H O use, which acts as a selection pressure, resistant organisms
H (once only a minor constituent of a microbial population)
become the dominant cells in their ecological niche.
O O 18.4
H H Most gene duplications are apparently a consequence of
P accidents during genetic recombination. Examples of pos-
O O
H H H H sible causes of gene duplication are unequal crossing over
O
C BASE
during synapses and transposition. After a gene has been
O
O H O duplicated, random mutations and genetic recombination
H
H O H
may introduce variations.
H O 18.5
H Because phytochrome has been demonstrated to mediate
H
numerous light-induced plant processes, it appears reason-
able to assume that it does so in part by interacting with
O light-response elements (LRE) in plant cell genomes. Pre-
sumably, phytochrome influences gene expression by bind-
ing, either alone or as part of a complex, to various LREs
40 when its chromophore is activated by light.
DNA degrades with time. Ancient fossils would have little
if any intact DNA with which to reconstruct the organisms. Chapter 18: End-of-Chapter Questions
In addition, although intact DNA is vitally important for
Review Questions
organismal function, it is only the operating system of an
organism. Without access to a living example of such an 3
organism, it would be impossible to reconstitute the physi- a. replicons—a unit of the genome that contains an origin
ological structure and functional properties that are unique for initiating replication
to a species. b. Okazaki fragment—any of a series of deoxyribonucleo-
tide segments that are formed during discontinuous rep-
Chapter 18: In-Chapter Questions lication of one DNA strand as the other strand is
continuously replicated
18.1 c. ter region—a segment of the E. coli chromosome that
Briefly, prokaryotic DNA replication consists of DNA un- contains DNA replication termination sequences
winding, RNA primer formation, DNA synthesis catalysed d. tus protein—a protein that when bound to a ter sequence
by DNA polymerase and the joining of Okazaki fragments facilitates DNA replication termination
by DNA ligase. Prokaryotic DNA replication differs from e. preinitiation complex—the eukaryotic replication com-
the eukaryotic process in that prokaryotic replication is plex (preRC) whose formation is the first major step in
faster, the Okazaki fragments are longer and there is usu- DNA replication
ally only one origin of replication per chromosome (eukary-
5
otes have many per chromosome).
a. transposition—the movement of a DNA sequence from
18.2 one site in a genome to another
In excision repair short damaged sequences (e.g., thymine b. transposable element—a DNA sequence that excises
dimers) are excised and replaced with correct sequences. itself and then inserts at another site
After an ­endonuclease deletes the damaged single-stranded c. bacterial transformation—a process in which DNA
sequence, a DNA ­polymerase activity synthesizes a replace- fragments enter a bacterial cell and are introduced into
ment sequence using the undamaged strand as a template. the bacterial genome
In photoreactivation repair a photoreactivating enzyme uses d. transduction—the transfer of DNA segments between
light energy to repair pyrimidine dimers. In recombina- bacteria by bacteriophages
tional repair damaged sequences are deleted. Repair in- e. conjugation—unconventional sexual mating between
volves an exchange of an appropriate segment of the bacterial cells; a donor cell transfers a DNA segment
homologous DNA molecule. into a recipient cell through a specialized pilus.

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 A-42 Appendix

9 17
a PCR – polymerase chain reaction—a method for obtain- In bacteria general recombination is involved in transfor-
ing large numbers of DNA copies; uses Taq polymerase, mation (DNA from one cell enters another cell and is sub-
a heat stable DNA polymerase sequently integrated into the recipient cell’s genome),
b. DNA microarray—a DNA chip used to analyse the ex- transduction (a bacteriophage synthesized in a bacterial cell
pression of thousands of genes simultaneously inadvertently carries a bacterial DNA fragment to a bacte-
c. chromosomal jumping—a technique used to isolate rial cell that the virus infects), and conjugation (unconven-
clones that contain discontinuous sequences for the same tional sexual mating in which DNA from one cell enters a
chromosome second cell via a sex pilus).
d. genome project—the process of determining the entire 19
set of DNA base sequences of a particular organism Because DNA is constantly exposed to disruptive pro-
e. bioinformatics—the computer–based field that facilitates cesses, its structural integrity is highly dependent on ef-
the analysis of biological sequence data ficient repair mechanisms. The life span of an organism is
9 dependent on the health of its constituent cells, which is in
a. gene silencing—a form of posttranscriptional gene regu- turn dependent on the timely and accurate expression of
lation in higher eukaryotes, involves short 22-nt RNAs genetic information. Consequently, the capacity of the
called microRNAs ­organisms in a species to maintain the integrity of DNA
b. RNA interference—a cellular mechanism in which RNA molecules is an important factor in determining life span.
molecules are degraded; functions in gene expression
regulation and in defence against viral RNA genomes 21
c. tumour suppressor gene—one of a set of genes that code a. Transcription factors are proteins that regulate or initiate
for proteins that actively protect cells from progressing RNA synthesis by binding to specific DNA sequences
towards cancer called response elements.
d. protooncogene—a normal gene that codes for a protein b. RNA polymerase is an enzyme that transcribes a DNA
involved in cell cycle regulation; promotes carcinogen- sequence into an RNA product.
esis if mutated c. A promoter is a DNA sequence immediately before a
e. GEF—guainine nucleotide exchange factor - a protein gene that is recognized by RNA polymerase and signals
that causes GTPases to release GDP and then bind GTP the start point and direction of transcription.
d. A sigma factor is a bacterial protein that facilitates the
11 binding of the core enzyme of RNA polymerase to the
The poly A tail facilitates the transport of mRNAs out of the initiation site during transcription.
nucleus and their subsequent translation by ribosomes. The e. An enhancer is a DNA regulatory sequence that when
poly A tail also serves as a timing device. As an mRNA’s bound to an appropriate transcription factor increases
poly A tail becomes shorter, it eventually becomes vulnerable the likelihood that nearby genes will be transcribed.
to degradation, a circumstance that limits its functional life. f. The TATA box is the best researched example of a
13 ­eukaryotic core promoter element.
The incorporation of a nucleotide into a DNA strand: 23
The amplification of a single DNA molecule during 5
5' 5' O CH2
cycles yields 25 or 32 molecules.
O CH2 N1
N1 O
O
25
Refer to Figure 18.18
O H
27
O H
O P O – O P O
O CH2 In species that possess DNA photolyase, light energy cap-
O CH2 N2
O
N2 O tured by this enzyme’s flavin and pterin chromophores is
used to break the cyclobutane ring in a thymine dimer, thus
PPi
3' HO H O H converting the dimer back to two thymine monomers. The
O P O phosphodiester bond is not affected. (Humans do not
O O O O CH2 N3
­possess this enzyme.)
O P O P O P O CH2 O
O O O O
N3 29
The function of telomere end-binding proteins is to bind to
3' HO H
HO H GT-rich telomere sequences as part of the process that se-
15 questers and stabilizes telomeres.
‘Jumping genes’ is the popular name for transposons. 31
First discovered by Barbara McClintock, transposons A tetragametic chimera is an individual that developed
(transposable elements) are DNA sequences that can move from the fusion of two nonidentical zygotes formed from
around the genome. four genetically distinct gametes (two eggs and two sperm).

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 Appendix
A-43

Thought Questions Therefore the amino acid sequences past the mutation are
different. In (d) no frame shift occurs because three bases
34 are deleted. In this case, the only difference between the
DNA sequence changing processes such as genetic recombi- normal polypeptide and the mutated version is the dele-
nation, gene splicing, and alternate RNA splicing can allow tion of a single amino acid.
cells to alter gene expression and expand their repertoire of
proteins. Their best-best known example is antibody produc- 19.2
tion in lymphocytes. The rearrangement of several possible Assuming that the DNA sequence given is the coding strand,
choices for each of a number of antibody gene segments by the mRNA sequence is 59-GGUUUA-39 and the anticodons
a site-specific recombination results in the generation of an are 59-UAA-39 and 59-ACC-39. If the DNA sequence is the
extremely large number of different antibody molecules. template strand, the mRNA sequence is 59-UAAACC-39 and
the anticodons are 59-GGU-39 and 59-UUA-39.
36
The tanning process which occurs in response to overexpo- 19.3
sure to sunlight, is triggered by DNA damage. DNA damage The possible choices for mRNA codon base sequences for
in skin cells causes an accelerated ageing process that is man- the ­peptide are:
ifested as a thickened and wrinkled skin. DNA damage may Tyr—Leu—Thr—Ala—
also inactivate tumour suppressor genes and/or cause muta- 59-UAU-39 CUU ACU GCU
tions in protooncogenes, thus increasing skin cancer risk. UAC CUC ACC GCC
CUA ACA GCA
38 CUG ACG GCG
Because the Rb gene codes for a tumour suppressor, retino- UUA
blastoma occurs only when both copies have been damaged UUG
or deleted. Usually a long period of time is required for
random mutations to cause this event. In hereditary retino- The possible choices for the DNA sequences that code for
blastoma, in which an affected individual possesses only the ­peptide are:
one functional Rb gene, the time necessary for a random Tyr—Leu—Thr—Ala—
mutation to inactivate the second Rb gene is significantly 39-ATA-59 GAA TGA CGA
less than that required for the inactivation of both genes ATG GAG TGG CGG
that cause the nonhereditary version of the disease. GAT TGT CGT
GAC TGC CGC
40 AAT
Once DNA has been extracted from the cells of an organ- AAC
ism it is digested and a genomic library is created using
shotgun cloning. The DNA sequence in each clone is then The possible choices for the tRNA anticodons that code for
sequenced. Chromosome walking is used to determine the ­peptide are:
overlapping sequences. Tyr—Leu—Thr—Ala—
39-AUA-59 GAA UGA CGA
42 AUG GAG UGG CGG
The RNA ‘copies’ of the DNA can be altered to generate GAU UGU CGU
protein diversity without changing the DNA template se- GAC UGC CGC
quence. In addition, RNA molecules can be used repeatedly AAU
and then disposed of without damaging the original DNA. AAG
If the DNA were used directly, the master molecule could
be damaged or destroyed. In addition RNA molecules can 19.4
easily leave the nucleoid or nucleus to travel to another part The formation of an ADP-ribosylated derivative of eEF-2
of the cell. affects the three-dimensional structure of this protein
factor. Presumably protein synthesis is arrested because
the ability of eEF-2 to interact with or bind to one or more
Chapter 19: In-Chapter Questions ribosomal components is altered.
19.1 19.5
The amino acid sequence of the beginning of the polypep- After the synthesis of the plastocyanin precursor in cyto-
tide is Met–Ser–Pro–Thr–Ala–Asp–Glu–Gly– Arg–Arg– plasm, the first import signal mediates the transport of the
Trp–Leu–Ile–Met–Phe. The mutation types in the altered protein into the chloroplast stroma. After this signal has
mRNA sequences are (a) insertion of one base, (b) dele- been removed by a protease, a second import signal medi-
tion of one base, (c) insertion of two bases, (d) deletion of ates the transfer of the protein into the thylakoid lumen.
three bases. The consequences of these mutations are al- Plastocyanin then binds a copper atom, folds into its final
tered amino acid sequences of the polypeptides produced three-dimensional structure, and associates with the thyla-
from mRNA. In (a), (b), and (c) a frame shift occurs. koid membrane.

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 A-44 Appendix

Chapter 19: End-of-Chapter Questions c. mRNP—messenger ribonucleoprotein; mRNA bound to

proteins that are involved in splicing, export from the
Review Questions nucleus and translation
d. mTORC1—mammalian target of rapamycin complex 1;
3
a protein complex that functions as a cellular sensor for
a. decoding centre—the position in the 30S ribosomal sub-
nutrient, energy and redox and controls protein synthesis
unit where an mRNA codon is matched to an incoming
e. NMD—nonstop-mediated mRNA decay; an mRNA
tRNA anticodon
­surveillance system that detects and rescues stalled
b. peptidyl transferase centre—a set of overlapping binding
ribosomes
sites on the 50S subunit for translation factors with
GTPase activity 11
c. GTPase associated centre—a set of overlapping binding The major differences between prokaryotic and eukaryotic
sites on the 50S subunit for translation factors with translation are speed (the prokaryotic process is signifi-
GTPase activity cantly faster), location (the eukaryotic process is not di-
d. guanine nucleotide exchange factor—a protein that rectly coupled to transcription as prokaryotic translation is),
­removes GDP from a protein and then facilitates complexity (because of their complex life styles, eukaryotes
GTP binding possess complex mechanisms for regulatory protein synthe-
e. proton shuttle mechanism—the reaction mechanism sis, e.g., eukaryotic translation involves a significantly
whereby a peptide bond is formed by the nucleophilic larger number of protein factors than prokaryotic transla-
attack of the a-amino nitrogen on the A-site aminoacyl tion), and posttranslational modifications (eukaryotic
group carbonyl carbon ­reactions appear to be considerably more complex and
varied than those observed in prokaryotes).
5
a. proprotein—an inactive precursor protein 13
b. preproprotein—an inactive precursor protein with a A preproprotein is the inactive precursor of a protein with a
­removable signal peptide removable signal peptide. A proprotein is an inactive pre-
c. disulfide exchange—a mechanism that facilitates the cursor protein. A protein is a fully functional product of
formation of appropriate disulfide bridges in newly translation.
­synthesized proteins
15
d. proline hydroxylation—the ascorbic acid-requiring reac-
The major differences between prokaryotic and eukaryotic
tion that converts proline residues in certain connective
translation control mechanisms are related to the complexity
tissue proteins to hydroxylated derivatives; required for
of eukaryotic gene expression. Features that distinguish eu-
structural integrity of connective tissue
karyotic expression include mRNA export (spatial separation
e. proteolytic cleavage—a posttranslational removal of
of transcription and translation), mRNA stability (the half
peptide segments by proteases; used to regulate the
lives of mRNA can be modulated), negative translational
­activity of certain polypeptides
control (the translation of certain mRNAs can be blocked by
7 the binding of specific repressor proteins), initiation factor
a. tmRNA—a bacterial RNA molecule containing a phosphorylation (mRNA translation rates are altered by cer-
tRNA- like domain and an mRNA-like domain that tain circumstances when eIF-2 is phosphorylated), and trans-
­rescues ribosomes bound to damaged mRNAs lational frameshifting (certain mRNAs can be frameshifted
b. SECIS element—selenocysteine insertion sequence—a so that a different polypeptide is synthesized).
sequence element required in order to code for seleno- 17
cysteine and located in the 39-UTR of the mRNA for a GTP hydrolysis provides the energy that drives the move-
selenocysteine-containing polypeptide ment of the peptidyl-tRNA from the A site to the P site in
c. initiation—the beginning phase of translation the ribosome. During elongation GTP hydrolysis is required
d. elongation—the polypeptide growth phase during trans- for the incoming aminoacyl-tRNA to bind in the A site.
lation of an mRNA in a ribosome.
e. termination—the phase of translation in which newly 19
synthesized polypeptides are released from the r­ ibosome The large subunit contains the catalytic site for peptide
bond formation. The small subunit serves as a guide for the
9
translation factors required to regulate protein synthesis.
a. proteostasis network—proteins that work together as a
Together the two subunits come together and form a mo-
system to control protein conformation through interac-
lecular machine that polymerizes amino acids in a sequence
tions of the proteome with molecular chaperones and
specified by the base sequence in the mRNA molecule.
degradation mediated by the ubiquitin proteasome system
b. heat shock response—the cellular response to heat and 21
other forms of stress that involves up-regulation of genes To ensure that proteins end up in a location appropriate to
coding for heat shock proteins as a component of a cell’s their function in a timely and predictable way, it is necessary
repair mechanism to have a targeting mechanism. The signalling process begins

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 Appendix
A-45

with specific signal sequences, which determine where trans- 27

lation will be completed. Specific localization sequences and/ The three letter sequences listed below each amino acid in
or posttranslational modification of the product protein then the first table are the possible mRNA sequences that code
ensures delivery of the protein to its target location. for that specific amino acid. For example, any of the four
mRNA sequences listed below Ala will code for Ala.
23 Thus, there are many correct answers to this question.
Elongation involves three basic steps: (1) Binding of an Choose one three-letter sequence from each column to
aminoacyl-tRNA in the A site, which is effected by build an mRNA sequence that will code for the peptide.
eEF1a-GTP; (2) transpeptidation, the nucleophilic attack For example, one possible answer is:
of the A site a-amino group on the carbonyl carbon of
the P-site in which eEF2-GTP binds to the ribosome. mRNA  59-GCU UCU UUU UAU UCU AAA AAA UAA
GTP hydrolysis drives conformational changes needed GCU GAU GUU AUU-39
to physically move the ribosome along the mRNA. cDNA  
39-CGA AGA AAA ATA AGA TTT TTT ATT
CGA CTA CAA TAA-59
25
Neurons of patients with Alzheimer’s disease are sur- Note that the sequence order must be reversed to write the
rounded with aggregated b-amyloid. The protein huntingtin sequence as ‘59 Æ 39’:
is aggregated in Huntington’s disease. Amylin is the
59 2 ATT AAC CTA AGC TAA TTT TTT AGA ATA
protein that forms aggregates in the b-cells of patients
AAA AGA AGC -39
with type 2 diabetes.

59 Æ 39 Possible Choices for mRNA Codon Base Sequences

for this Peptide

59-Ala Ser Phe Tyr Ser Lys Lys Leu Ala Asp Val Ile-39

GCU UCU UUU UAU UCU AAA AAA UUA GCU GAU GUU AUU

GCC UCC UUC UAC UCC AAG AAG UUG GCC GAC GUC AUC

GCA UCA UAC UCA

GCA GUA
AUA

GCG UCG UCG UCG

GCG GUG

AGU AGU AGU

AGC AGC AGC

39 Æ 59 Possible Choices for the DNA Sequences for this

Polypeptide

Ala Ser Phe Tyr Ser Lys Lys Leu Ala Asp Val Ile

39CGA AGA AAA ATA AGA TTT TTT AAT CGA CTA CAA TAA

3CGG AGG AAG ATG AGG TTC TTC AAC CGG CTG TAG

3CGT AGT AGT GAA CGT CAG TAT

3CGC AGC AGC GAG CGC CAT

TCA TCA GAT CAC

TCG TCG GAC

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 A-46 Appendix

29 34
Features of eukaryotic protein synthesis that help to ac- When errors in amino acid–tRNA binding do occur, they
count for the increased time required (as opposed to pro- are usually the result of similarities in amino acid structure.
karyotic translation) include the greater quantity, variety Several aminoacyl-tRNA synthetases possess a separate
and functioning of eukaryotic translation factors (e.g., at proofreading site that binds the incorrect aminoacyl–tRNA
least 12 IF’s vs 3 for prokaryotes): additional processing of products and hydrolyses them.
mRNA (addition of a cap and a poly(A) tail; removal of in-
36
trons); and the increased quantity and variety of eukaryotic
Posttranslational modification reactions prepare polypep-
posttranslational modifications, such as hydroxylation, and
tides to serve their specific functions and direct them to
disulfide bond formation. Also, because eukaryotic mRNA
specific cellular or extracellular locations. Examples of
lacks Shine-Dalgarno sequences, eukaryotic ribosomes
these modifications include proteolytic processing (e.g., re-
must search for a translation start site by binding to the
moval of signal proteins), glycosylation, methylation, phos-
capped 59 end and scan towards the 39 end.
phorylation, hydroxylation, lipophilic modifications (e.g.,
N-myristoylation and prenylation), and disulfide bond
Thought Questions formation.
32 38
The coding reassignment mechanisms for selenocysteine Sets of amino acids which may require proofreading in-
and pyrolysine are similar in many respects (e.g., the use of clude phenylalanine/tyrosine, serine/threonine, aspartate/
the reassignment sequences SECIS and PYLIS, and specific glutamate, asparagine/glutamine, isoleucine/leucine, and
tRNAs and acyl-tRNA synthetases). A major difference be- glycine/alanine.
tween these two examples of coding reassignment is the
mechanism whereby the two nonstandard amino acids are 40
linked to their respective tRNAs. Selenocysteine-tRNA is A two subunit ribosome is essential to ensure that all of the
produced from a specialized seryl-tRNA. The seryl group required elements are in place before the translational pro-
is converted after linkage to the tRNA to a selenocysteinyl cess begins. This is a physical ordering process much like
group. In contrast pyrolysine is synthesized before it is an assembly line; the parts must be in place before the en-
linked to its tRNA. zymatic activities are set in motion.

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