Bioc 202.

951 T1 (2017)

Problem Sets
Note:
Problem sets are optional but highly recommended. It is up to you how many problems you complete.

Pages refer to Lehninger Principles of Biochemistry 5th edition and 6th edition. Nelsen, D.L., Cox,
M.M. Freeman and Company 2008 and 2013, respectively.

To give you more practice, several questions are included from the 7th edition of Biochemistry by
Berg, Tymoczko, and Stryer. Freeman and Company 2012.

These textbooks and their accompanying student study guides (which contain expanded
answers to the chapter questions) can be found in the reserve section of the Woodward library.

Problem set 1
Basic Chemistry, Acids/Bases & Water

Lehninger 5th edition Lehninger 6th edition

Chapter 1 Q. 8, 11 p. 37-40 Q. 8, 11 p. 41-43
Chapter 2 Q. 1-29 & 31 p. 67-70 Q. 1-33 & 35 p. 71-74

Note:
For Acid/Base questions, these are review questions from first year chemistry. There will
be some sort of acid/base question on the exam, but it is up to you to decide how may of
these questions you want to complete. Ive listed all the questions that I expect you to be
able to answer.

Dr. MJ Krisinger. Department of Biochemistry & Molecular Biology 1

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 Bioc 202.951 T1 (2017)

Also try:
1. Given the following reaction for which the pKa is 7.21

H2PO4- H+ + HPO42-

a) What would the molar ratio of [H2PO4-] to [HPO42-] be in order to have a pH of

7.4?

b) Define the term buffer. Would this be a good buffer system at pH 7.2? Why or
why not?

Problem set 2
Amino acids, Peptides and Proteins & 3-D Structure of Proteins

Lehninger 5th edition Lehninger 6th edition

Chapter 3 Q. 1, 2(all except m), 4-7, 11a, Q. 1, 2(all except m), 4-7, 11a,
14, 18 p. 108-112 14, 18 p. 110-114
Chapter 4 Q. 1, 3-5 p. 149-152 Q. 1, 3-5, 10 p. 152-156

Note:
Q18. 1-fluoro-2,4-dinitrobenzene will attach a 2,4-dinitrophenyl group to the N-
terminus of a polypeptide. Chymotrypsin hydrolyzes peptide bonds after (or that
are on the C-terminal side of) large hydrophobic residues including Phe, Tyr, Trp,
Met and Leu.

Also try:
1. Hydrophobic amino acids tend to group themselves in the cores of proteins

a) What interaction is mediating this? Explain how it occurs.

b) List four amino acids you would expect to find in the core of proteins. Include
structures and abbreviations.

c) What is the rational that the R groups of the amino acids you listed above are of
different shapes?

Dr. MJ Krisinger. Department of Biochemistry & Molecular Biology 2

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 Bioc 202.951 T1 (2017)

2. The amino acid glutamate is also used as a neurotransmitter. It is released from one
nerve cell, crosses the synaptic cleft and binds to a glutamate receptor on a second nerve
cell, triggering a response.

a) Draw the structure of glutamate

b) In order for glutamate to interact with the receptor, it must form multiple
interactions within the binding site. For each of the functional groups on
glutamate, indicate which groups of amino acids (including a representative
example) could be present in the receptor to bind specifically glutamate. Make
sure to include two different types of interactions.

c) Would you expect to see a large number of high-energy interactions?

Stryer 7th edition

Chapter 2 Q. 1-7, 9-10, 12-13, 15, 17-23, 28-29 p. 63-64
Chapter 5 Q. 5 p. 217

Note:
Q1: Your text answers this in absolutes. I would expect a little more rationalization
here.
Q7: You will need to use Table 2.1 on page 32 to answer this.
Q13a: The average amino acid residue in a polypeptide is 110 Da.
Q13b: For a 4-residue hairpin turn, assume that 2 of the residues are in -strands.

A couple of questions that really stand out are:

Chapter 2, Q15, p.63-64
A mutation that changes an A to V in the interior of a protein is found to lead to a loss of
activity. However, activity is regained when a second mutation at a different location
changes an I to G. How might this second mutation lead to a restoration of activity?

Chapter 2, Q29, p.64

Would you expect Pro-X peptide bonds to tend to have cis conformations like those of X-
Pro bonds? Why or why not? Note that X is the abbreviation for any amino acid.

Chapter 5, Q5, p.217

The pKa of an acid depends partly on its environment. Predict the effect of each of the
following environmental changes on the pKa of a glutamic acid side chain.
a) A Lys side chain is brought into proximity.
b) The terminal carboxyl group of the protein is brought into proximity.
c) The Glu side chain is shifted from the outside of the protein to a non-polar
site inside.

Dr. MJ Krisinger. Department of Biochemistry & Molecular Biology 3

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 Bioc 202.951 T1 (2017)

Problem set 3
Enzyme Thermodynamics and Kinetics & Chymotrypsin

Lehninger 5th edition Lehninger 6th edition

Chapter 6 Q. 1, 4-5, 7-8, 9a&b, 10a&b, Q. 1, 4-5, 7-8, 9a&b, 10a&b,
11(see note), 12-15, 19, 21(see 11(see note), 12-15, 19, 21(see
note), 23(see note) p. 229-233 note), 23(see note) p. 238-242

Note:
Q11: Normally, an approximation of Vmax and Km by inspection is not a good idea.
Why?
Q21: Lysozyme (an enzyme, found in your tears, that breaks down bacterial cell walls)
normally requires Glu35 to be protonated and Asp52 to be deprotenated for
effective catalysis.
Q23: This is an excellent question! The structure of oxaloacetate can be found in Fig
16-7, page 621 (5th edition)/ Fig 16-7, page 639 (6th edition). It is essentially the
carboxylated form of pyruvate.

Also, when you are solving for Km and kcat , ask yourself "What are these values telling
me about the enzyme? What useful information does it provide?"

Note: the mouse icon found throughout Lehninger 6th edition textbook indicates the availability of a
living graph, molecular structure tutorial or other problem solving video.
To access this helpful resource, log on to:
BioChemPortal (http://courses.bfwpub.com/lehninger6e.php?errCode=11)
Go to ! Resources (top tab)
! e.g. problem solving video e.g. Chapter 6 Enzymes
! gives insight and help with e.g. Q8, Q10, Q13, Q15

Lehninger does not provide any questions about chymotrypsin. You may wish to check
Chapter 9 of Stryer.

Stryer 7th edition

Chapter 8 Q. 1-2, 5-8, 10, 15, 17-18, 20a&b, 23-28, 31 p. 249-252
Chapter 9 Q. 2-4, 10-11, 15 p. 286-288

Note:
Chapter 8
Q17: The expanded answer in the student companion is incorrect (it refers to an entirely
different question). The back of the book answer is correct.
Q24: The expanded answer in the student companion is incorrect. It does the
calculation for 1/10 Km (instead of 10 Km). The correct answer is 1.1 mole/min.

Chapter 9
Q2: Subtilisin is also a serine protease with His64 being the equivalent to His57 in
chymotrypsin

Dr. MJ Krisinger. Department of Biochemistry & Molecular Biology 4

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 Bioc 202.951 T1 (2017)

Q11: Choose from chymotrypsin, trypsin, or elastase. Explain your choice.

Q15: See figure 9.17 page 264.

Problem set 4
Hemoglobin

Lehninger 5th edition Lehninger 6th edition

Chapter 5 Q. 3, 5-6, 7a&c, 8 p. 180-182 Q. 3, 6-7, 8a&c, 9 p. 184-187

Stryer 7th edition

Chapter 7 Q. 1, 8-11, 13, 15-16 p. 216-218

Note:
Q13: P. falciparum is a causative agent of malaria. In sickle-cell anemia, hemoglobin
molecules in the T-state can polymerize, forming long fibers. This leads to the
traditional sickle shape seen in red blood cells. Sickled red blood cells have a
much shorter half-life than normal red blood cells. Why are people with sickle cell
anemia resistant to malarial infection?

Dr. MJ Krisinger. Department of Biochemistry & Molecular Biology 5

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 Bioc 202.951 T1 (2017)

Problem set 5
Metabolism and Thermodynamics

Lehninger 5th edition Lehninger 6th edition

Chapter 13 Q. 2-7, 9, 11-15, 19-21 p. 522- Q. 2-7, 9, 11-15, 19-21 p. 538-
526 542

Note:
Q11: Answer at the end of textbook and study guide are based on 25 C and are thus
incorrect! They should be calculated and based on 37 C as stated in the question.
Q13: Answer at the end of textbook and study guide are based on 25 C and thus are
incorrect! Physiological temperature is 37 C (or 310K) and thus should be used
to calculate the answer.
Q15: G'o synthesis of ATP is 30.5 kJ/mole. It's the reverse of the ATP hydrolysis.
Q19: The molecular weight of ATP is 503 g/mole
Q21: Errors in the question!
G'o hydrolysis of Acetyl CoA to acetate and CoASH (CoA) is 31.4 kJ/mole,
not 32.2 kJ/mole.
G'o hydrolysis of ATP to AMP is 45.6 kJ/mole, not 30.5 kJ/mole.
Thus, the answers in the back of the book for Q21 are incorrect.

Stryer 7th edition

Chapter 15 Q. 2-3, 5, 7-12, 14, 16-18, 21-22 p. 449-451

Note:
Q12: Just calculate G'o.
Q14: G'o hydrolysis of ATP to AMP is 45.6 kJ/mole.
G'o hydrolysis of Acetyl CoA to acetate and CoASH (CoA) is 31.4 kJ/mole.
Q21: G'o hydrolysis of ATP to ADP is 30.5 kJ/mole.
The answers in the back of the book for Q21 are slightly off.

A note about Q:
Lehninger refers to the ratio of products/reactants at non-equilibrium conditions as the
mass action ratio (Q). Therefore, G = Go' + RT ln (products/reactants) becomes
G = G'o + RT ln Q

A note about K'eq:

K'eq is equal to the ratio of products over reactants at equilibrium
([C]eq[D]eq/[A]eq[B]eq).
Furthermore, the G of a reaction at equilibrium is 0.

the formula G = G'o + RT ln (products/reactants) simplifies to:

Dr. MJ Krisinger. Department of Biochemistry & Molecular Biology 6

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 Bioc 202.951 T1 (2017)

0 = G'o + RT ln K'eq
G'o = -RT ln K'eq

Now, why do we care so much about K'eq? Because, it is the ratio of products to
reactants where G = 0. If we decrease ratio of products/reactants ever so slightly
(below K'eq), G' becomes negative and the forward reaction becomes spontaneous. If
we increase the ratio of products/reactants ever so slightly (above K'eq), G' becomes
positive and the forward reaction becomes non-spontaneous. In fact, the reaction will
start running in the reverse direction. I.E., the ratio of products to reactants at
equilibrium (K'eq) provides a crossover point (if you will) that tells you what ratio of
products to reactants you need to make the reaction spontaneous (or non-spontaneous).

Also try:
Consider the following two reactions:

ADP + Pi ! ATP + H2O G'o = 30.5 kJ/mole

Creatine + Pi ! Creatine phosphate G'o = 43.1 kJ/mole

The enzyme creatine kinase can transfer the phosphate from ATP to creatine, thus
generating creatine phosphate. Creatine phosphate can be used as a source of
phosphate in muscle cells.

a) Write the equation for the reaction in which creatine phosphate is synthesized (as
described above). What is the G'o for this reaction? Would you consider this
reaction to spontaneous or non-spontaneous at standard state?

b) In a recovering muscle cell, the following concentrations are observed:

Metabolite Concentration (mM)

ATP 8.0
ADP 0.02
Pi 3.0
Creatine 9.0
Creatine phosphate 16.0

Calculate the G for creatine phosphate formation in these cells at 37o C. Is the
reaction spontaneous in recovering muscle cells?

c) Is the G calculated in b) different from the G'o that you calculated in a)? Why
or why not?

d) During the first few seconds of heavy exercise in muscle cells, the ATP levels can
drop to 0.8 mM and the ADP levels can increase to 0.2mM. What effect would
this have on the spontaneity of the reaction in b)? What would you predict to
happen to the reaction in a)? What is the significance of this?

Dr. MJ Krisinger. Department of Biochemistry & Molecular Biology 7

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 Bioc 202.951 T1 (2017)

Problem set 6
Carbohydrates

Lehninger 5th edition Lehninger 6th edition

Chapter 7 Q. 1-6, 7b-c, 10-12, 13a-b, 14, Q. 1-5, 6b-c, 7, 9, 11a-b, 12-13
15 p. 267-270 p. 278-280

Note:
Q5 (5th)/Q4 (6th): Ignore the chair conversion
Q11 (5th): Fehling's solution turns red in the presence of reducing sugars.
Maltose has a formula of glucose(14)glucose.
Q11 (6th): Specific Rotation: The optical activity of a stereoisomer is expressed
quantitatively by its optical rotation (the number of degrees by which
plane polarized light is rotated on passage through a given path length
of a solution of a compound at a given concentration.)

Stryer 7th edition

Chapter 11 Q. 1, 3(a-d, f), 5-6, 9, 11, 14-15 p. 342-344

Note:
Q3: Refer to figure 11.6
Q6: Prove it remember your math for solving two variables.
Q7: Remember your organic chemistry!!!

Also try:
Youre a biochemist hired by NASA to study the results of a probe sent to Rhea, an
earth sized planet several light years away. There is a large amount of excitement
over Rhea as it contains several primitive life forms resembling plants that contain
carbohydrates and proteins! It is currently hypothesized that these plants could
provide a source of nutrients for any future manned missions to Rhea. The most
recent plant data from the probe is listed below:

Carbohydrates:
Two disaccharides detected:
-L-glucopyranose linked to -L-fructofuranose in an 1-2 arrangement.
-L-galactopyranose linked to -L-glucopyranose in an 1-4 arrangement.

Protein amino acid composition:

D-glycine 7.5%
D-alanine 7.2%
D-serine 5.7%
More data in next transmission.

Armed with this, you dash into your supervisors office!!!

What have you learned from this latest dataset from the probe? Why is it important?

Dr. MJ Krisinger. Department of Biochemistry & Molecular Biology 8

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 Bioc 202.951 T1 (2017)

Problem set 7
Glycolysis

Lehninger 5th edition Lehninger 6th edition

Chapter 14 Q. 1, 2, 5-16, 26 p. 565-568 Q. 1, 2, 5-16, 26 p. 582-585

Note:
Q2: Back of book answer is INCORRECT.
Net reaction: 2 GAP + 2 Pi + 4 ADP ! 2 lactate + 4 ATP + 2 H2O G'o = -113.5 kJ/mol

Stryer 7th edition

Chapter 16 Q. 1, 3(a-c), 5-7, 9-11, 14, 16, 18, 21, 33(a-b, d), 37-39
p. 493-496

Note:
Q16: Is tough and a lot of work for a one-word answer... but if you can answer it, you
probably have a good grasp of the material.
Q18: Requires data from table 16.1, page 466-467
Q21: Typo in the question hydrogen atom at C-5 (not G-5).
Q39: Can help you understand why AMP is used instead of ADP to allosterically
inhibit PFK.

Also try (without your notes):

Given the following reversible reaction:

a) Identify A and B, as well as the enzyme that catalyzes this reaction.

b) What is the significance of this reaction? When would it occur (give an

example)?

c) Suppose the G'o of the above reaction is -25 kJ/mole. What is the highest ratio
of products to reactants that would allow this reaction to go forward in the cell?

d) There are some very rare cases where the enzyme catalyzing the above reaction is
mutated and inactive. These patients suffer from exertional myoglobinuria (the
presence of myoglobin in the urine during exercise) and fatigue upon heavy
exercise. Explain these symptoms (hint: Where is myoglobin normally found?).

Dr. MJ Krisinger. Department of Biochemistry & Molecular Biology 9

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 Bioc 202.951 T1 (2017)

Problem set 8
Krebs Cycle

Lehninger 5th edition Lehninger 6th edition

Chapter 16 Q. 1-9, 10a-b, 11-19, 22, 26a-b, Q. 1-9, 10a-b, 11-19, 22, 26a-b,
30-34 p. 642-646 30-34 p. 661-665

Note:
Q2: Back of book answer does not include H2O or H+ in stoichiometry. There
should be 2 H2O as reactant and 8 H+ as product.
Q3b: Needs H2O as reactant to balance reaction.
Q4: Hexanoic acid = C6H12O2 and NOT C6H14O2 as stated.
Q5d: Needs H2O as reactant to balance reaction.
Q9: Note: The oxaloacetate concentration is the limiting factor for the TCA cycle.
Q13: See Fig 16-15, p.632 (5th edition) or Fig 16-16, p.651 (6th edition)
Q15: Malonate is COO- CH2 COO-
Q16-18: It is unlikely that a tracing question would be on the final, but it is very helpful
to understand the cycle.
Q16b: Answer in guide is INCORRECT. After the 2nd round 0% of label is lost, after
the 3rd round 50%, after the 4th round 25%, 5th round 12.5%, etc
Q26: Error in question: Pyruvate Dehydrogenase Complex (PDC) is active when
unphosphorylated and inactive when phosphorylated.

Stryer 7th edition

Chapter 17 Q. 1-4, 5 (tough), 8, 9 (tough), 10-11, 13, 15-16, 18, 20-
25, 27, 29-30 p. 521-523

Note:
Q1: Back of book answer is incorrect: It should state: Dihydrolipoyl Dehydrogenase
(E3) catalyzes the oxidation of the reduced lipoic acid (lipoyllysine).
Q9: The hydrogen on the carbon between the nitrogen and the sulfur atoms can be lost
as a proton, forming a carbanion. Formation of the carbanion is ESSENTIAL for
TPP function!
Q16: Back of book answer is incorrect. Lowest ratio of malate/OAA = 9615

Dr. MJ Krisinger. Department of Biochemistry & Molecular Biology 10

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 Bioc 202.951 T1 (2017)

Also try:
The amino acid glutamate can be converted into ketoglutarate by glutamate
dehydrogenase as shown below (note: you are not responsible for this reaction).

a. Can the ketoglutarate formed in the above reaction enter the Krebs cycle?
Write out the balanced equation for the conversion of glutamate to oxaloacetate.
Would this result in a net production of oxaloacetate?

b. The above reaction is reversible, i.e. ketoglutarate can be converted to

glutamate. What effect would the synthesis of glutamate by this reaction have on
the overall rate of the Krebs cycle? Explain your answer.

c. Could an increase in the concentration of acetyl CoA overcome the effect

observed in b?

Dr. MJ Krisinger. Department of Biochemistry & Molecular Biology 11

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 Bioc 202.951 T1 (2017)

Problem set 9
Oxidative Phosphorylation

Lehninger 5th edition Lehninger 6th edition

Chapter 19 Q. 1-7, 8a-b, 9-11, 13-14, 19-23 Q. 1-7, 8a-b, 9-11, 13-14, 19-23
p. 768-772 p. 793-795

Note:
Q3: Calculate G'o for both electron transfers.
Q4: For Q4d, I would accept an answer of "a mixture of oxidized and reduced carriers"
Q6: It is not the lack of ATP that kills, rather it is heat production

Stryer 7th edition

Chapter 18 Q. 1-5, 7-13, 15, 17(a-d, f), 19-23, 26, 28-30, 38, 40-41 p.
562-564

Note:
Q7: Assume the value of the FAD-FADH2 is 0.05V (even though table 18.1 states
0.22V as remember the environment can alter E'o).
You do not have to memorize E'o as listed in table 18.1.
Q17: Book answers assume either brain or skeletal muscle tissue (i.e. use of glycerol-3-
phosphate shuttle to account for cytoplasmic NADH).
Q17b: Back of book answer is incorrect. The ATP yield from lactate is 11 ATP (using
the glycerol-3-phosphate shuttle) or as this more appropriately occurs in the liver
10 ATP (using the Asp-Malate shuttle).
Q23: This is an excellent question! If you can answer it, you have a good
understanding of oxidative phosphorylation!
Oligomycin blocks ATP synthase.
Rotenone blocks electron transfer from complex I to coenzyme Q.
The answer diagrammed in the student companion is incorrect!
Q28: Read the question carefully and determine what it is asking. Its not nearly as
hard as it looks!

Also try:
Given the following table of standard reduction potentials: Electron Carrier E'o
+
NAD -0.320 V

Calculate the change in Gibbs free energy that results from Complex I
transferring two electrons from QH2 to O2. FMN
Fe-S
-0.300 V
-0.170 V

Ubiquinone +0.045 V

Complex III
Cytochrome b +0.077 V

Cytochrome c +0.254 V

Complex IV
Cytochrome a +0.290 V
Cytochrome a3 +0.350 V
Dr. MJ Krisinger. Department of Biochemistry & Molecular Biology
Not to be copied, used, or revised without explicit written permission from the copyright owner O2 +0.820 V12
 Bioc 202.951 T1 (2017)

Problem set 10
Glycogen Metabolism

Lehninger 5th edition Lehninger 6th edition

Chapter 15 Q. 3, 5-6, 10 p. 611-613 Q. 3, 5-6, 10 p. 629-631

Stryer 7th edition

Chapter 21 Q. 2-3, 6, 9, 11, 21-22, 27 p. 637-638

Note:
Q6: People with von Gierke disease (type I glycogen storage disorder) fail to make
functional glucose-6-phosphatase in the liver.

Problem set 11
Gluconeogenesis

Lehninger 5th edition Lehninger 6th edition

Chapter 14 Q. 17, 19-23, 24a-d, 27-28 p. Q. 17, 19-23, 24a-d, 27-28 p.
565-568 582-585
Chapter 16 Q. 20-21 p. 644 Q. 20-21 p. 663

Stryer 7th edition

Chapter 16 Q. 9-10, 24-27, 29-32, 34, 40 p. 493-496
Chapter 17 Q. 19 p. 522

Also try:
1a. Draw out the reactions catalyzed by phosphofructokinase (PFK1) and fructose-1,6-
bisphosphatase (FBPase1). Include the names and structures of the substrates and
products. Where do these reactions occur in the body? In the cell?

1b. List each of the molecules that regulate PFK1 and FBPase1. Provide a brief rationale
for the role of each molecule listed and explain (at the local level) how PFK1 and
FBPase1 are reciprocally regulated. Why is it important that these two pathways be
reciprocally regulated?

Dr. MJ Krisinger. Department of Biochemistry & Molecular Biology 13

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 Bioc 202.951 T1 (2017)

Problem set 12
Integration of Carbohydrate Metabolism

Lehninger 5th edition Lehninger 6th edition

Chapter 14 Q. 3 p. 565 Q. 3 p. 582
Chapter 15 Q. 4, 8, 14-15 p. 611-613 Q. 4, 8, 14-15 p. 629-631
Chapter 23 Q. 6, 11-12, 15, 21 p. 942-944 Q. 6, 11-12, 15, 21 p. 973-975

Dr. MJ Krisinger. Department of Biochemistry & Molecular Biology 14

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