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MCMP 208 Exam I - 1
Examination I
MCMP 208 – Biochemistry for Pharmaceutical Sciences I
February 8, 2016
Name:______________________________________________
Instructions
1.
Check your exam to make certain that it has 10 pages including this cover page. Ask for a new copy
of the exam if you are missing any pages.
2.
Use a pencil for filling in the answer sheet for computerized grading.
3.
Write your name on the line above (this page) AND on the answer sheet for computerized grading.
Also write your student number on the answer sheet. Fill in the circles underneath where you write
your name and student number. Do NOT place any identification or signature anywhere on this
exam or on the answer sheet. Also, do NOT fill in anything for “section number” and do NOT write
your name on the back of the exam.
4.
Your answers to problems 1 through 25 will be graded by computer. All computer-graded questions
will be worth three points each. Put your answers for these problems on the answer sheet and fill in
the appropriate circle using a pencil. It is your responsibility to be certain that the answers for
these problems are correctly marked on the answer sheet at the time you hand in your
completed exam. You are strongly encouraged to double check this at the time you submit the
answer sheet, as no points will be given for having mistakenly marked your answer sheet. The
computer grading answer sheets will not be returned to the students, so you are encouraged to record
your answers to the computer-graded questions on this exam as well as on the answer sheet.
However, the computerized grading of your answers to these questions will be done solely on the
basis of the optically scanned answer sheet, not on what is recorded on your exam. The course policy
is that there will be no re-grading of the computer answer sheets.
5.
Examination problems 26 through 30 are to be answered with short answers, brief essays, or
drawings. Put your answer to each of these directly on this exam, in the space provided below each of
these questions.
6.
After completing your exam, both the exam and the answer sheet must be submitted for grading and
both must be identified only with your name.
7.
This is a closed-book, closed-notes exam. Calculators and electronic devices of any kind that can
store information or communicate (cell phones, smart watches, computers, tablets, headphones)
are not allowed to be used during this exam. Any electronic device that is not in a backpack,
bookbag, purse, pocket, etc, will be considered to be in use, so put away all electronic devices
including cell phones and calculators. Anyone observed to be using a calculator, any book,
handouts, notes, printed or handwritten material of any kind, or the exam or answer sheet of any other
student will be considered to have committed an act of academic dishonesty. Students that do so will
not be allowed to complete the exam and will be given a zero for this exam. Also remember that the
first instance of academic dishonesty also results in a grade of "F" in this course and reporting this
episode to the Pharmacy Dean and the Dean of Students office.
MCMP 208 Exam I - 2
MULTIPLE CHOICE. For problems 1 to 25, select from the list immediately following each question the
single most correct choice to complete the statement, solve the problem, or answer the question. Mark that
answer on your answer sheet. [3 points each]
1. Certain nucleoside triphosphates (NTPs), which have the same structure as ATP except with a different
base instead of adenine, are used in sugar metabolism via a series of enzyme-catalyzed reactions shown
generically below. Note the sugar-phosphate bond in the starting metabolite and the sugar-beta phosphate
bond (in NDP) are relatively low energy phosphoester bonds and the bond linking the acceptor to the
sugar in the final product has a similar (low) energy of hydrolysis.
Reaction 1: sugar-phosphate + NTP  NDP-sugar + inorganic pyrophosphate
Reaction 2a: inorganic pyrophosphate + water  2 phosphate
Reaction 2b: acceptor + NDP-sugar  NDP + acceptor-sugar
What is a true statement you can make about the energetics of this metabolic pathway?
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The pathway is energetically unfavorable as written.
The pathway is energetically close to neutral, and does not favor either the reactants or products.
The pathway releases energy from two high energy phospho-anhydride bonds
Reactions 1 and 2b are energetically close to neutral, while 2a is highly favorable.
Reaction 1 is highly energetically unfavorable but reactions 2a and 2b are highly favorable.
Reaction 1 is highly energetically favorable but reactions 2a and 2b are highly unfavorable.
2. A pathway that converts glucose, a simple 6 carbon sugar, to carbon dioxide and reducing energy in the
form of NADPH is best described as what kind of pathway?
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signaling
energy transfer
transport
macromolecule synthesis (polymerization)
macromolecule breakdown (depolymerization)
anabolism
catabolism
3. The primary function of all membranes in a cell is
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to surround the cell protecting it from the extracellular environment
to act as an attachment point for the cytoskeleton of the cell
to create a surface for the construction of a cell wall
to allow the contents and conditions inside the cell or organelle to be controlled
to bind and localize some specific proteins that carry out very specific biochemical reactions at the
membrane
 to contain the osmotic pressure
 to control the pH by restricting the flow of protons across the membrane
4. When molecules of carbon dioxide are added to an aqueous solution, this results (at equilibrium) in
 the solution becoming slightly more acidic
 the solution becoming slightly more alkaline
 no change in the pH of the solution
MCMP 208 Exam I - 3
5. Exocytosis is
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when a cell moves from one location to another
when molecules are moved across any membrane in a cell
when a cell releases molecules that had previously been held in an intracellular vessicle
when a cell divides, creating two cells from one previous cell
when a mitochondrion divides, creating two mitochondria from the previous mitochondrion
the process of attachment of a cell to its substratum via its glycocalyx
the process by which a cell becomes detached from its substratum as a result of a change in cell shape
when a cell dies via programmed cell death
when a cell moves molecules from one side to the other side of its plasma membrane
6. Water is accurately described as being highly structured. This is because
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water easily dissolves many molecules
water is a weak electrolyte
water is a strong electrolyte
water cannot dissolve hydrophobic molecules
each molecule of water forms several dipole bonds
the molecules of water do not have much motion
the molecules of water exhibit a single most-stable structure which can be crystallized
7. Which amino acid contains sulfur but cannot participate in disulfide bonds?
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
tyr
asp
cys
ser
leu
trp
met
sec
lys
arg
8. In an aqueous solution of two molecules, A and B, the following reaction occurs:
A + B  A~B where the ~ symbol represents one or more non-covalent interactions.
What does this information tell you about A and B?
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Either A or B must be an enzyme
A and B can form a non-covalent complex
The complex formed that involves A and B is extremely stable
The complex formed that involves A and B is extremely unstable
The energy of activation of this reaction is very low
At equilibrium there is more complex than there are free A and B molecules
At equilibrium there is less complex than there are free A and B molecules
At equilibrium about half of the A and B molecules are associated in a complex
MCMP 208 Exam I - 4
9. The most unusual aspect of hydrophobic interactions, compared to other non-covalent bonds, is that
 hydrophobic interactions do not require participation by a hydrogen atom
 hydrophobic interactions only occurs in the presence of ions
 hydrophobic interactions appear to be bonding together of similar structures but actually result from a
common inability to interact with water
 hydrophobic interactions always involve organic solvents, such as hexane
 hydrophobic interactions can be disrupted at higher temperatures
 hydrophobic interactions can involve only a part of a molecule, rather than the whole molecule
10. Nucleolin is a eukaryotic protein containing 710 amino acids that is abundantly expressed in nearly all
human cells. About half the nucleolin in cells is in the nucleolus, and the remainder is in the cytosol, on
the cell membrane, associated with the cytoskeleton, and outside of cells. It is not possible to crystallize
nucleolin. Its sequence includes four adjacent copies of a sequence motif (each one 74 to 78 amino acids
long and with spacer sequences of 10 to 20 amino acids between them) from amino acids 307 to 648.
This repeated sequence motif is known to have RNA-binding ability, which is supported by the NMRdetermined solution structure of a protein that represents just one of those four sequence motif regions.
The structure of the remainder of nucleolin is unknown. The protein is known to participate in the
generation of ribosomes. But nucleolin also interacts with DNA and a large number of proteins, where it
has roles as a DNA-binding transcription regulator, a regulator of chromatin remodeling, and a DNA
unwinding protein (helicase). It has important protein-binding functions in the cytoplasm and also on the
outside surface of the cell plasma membrane. Nucleolin is an excellent example of
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a highly regulated enzyme
a protein that is largely or completely intrinsically unstructured
a moonlighting protein
a protein that is largely or completely intrinsically unstructured that is also a moonlighting protein
a protein that would fail to refold from a fully denatured conformation
a protein with quaternary structure that is stabilized by disulfide bonds
a fibrous protein
11. Because of their high amount of stabilization energy, intermediates in the folding of larger globular
domains of proteins consists primarily of
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salt bridges
hydrogen bonds between polar side chains of amino acids
beta-sheets
alpha-helices
hydrophobic interactions
any kind of secondary structure
12. Intrinsically unstructured proteins is a significant (but relatively recent) concept because it shifted
thinking about what paradigm of protein science?
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Proteins are polymers of amino acids
All amino acids in proteins are bonded together by the peptide bond
Proteins have one structure and one function
Protein structure determines protein function
Protein structure is very rigid and inflexible
Protein structure is static and has no dynamics associated with it
MCMP 208 Exam I - 5
13. One characteristic of fibrous proteins that is very different from globular proteins, is that fibrous proteins
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are very easily denatured
frequently are post-translationally modified
frequently contain cross-links between polypeptide chains
are fully comprised of secondary structure elements but have very little tertiary structure
are much longer polypeptides
contain only one kind of secondary structure element in any one protein
contain almost no secondary structure elements
14. The locus of the gene polymorphisms responsible for causing cystic fibrosis are located in a gene that
encodes a transport protein that is located in the plasma membrane. The mutations that cause cystic
fibrosis either result in the protein misfolding and never getting to the plasma membrane or in a loss of its
transport function. This evidence supports what important concept or paradigm about proteins?
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Misfolded proteins must be degraded or else they can cause serious diseases.
Primary structure determines higher order structure
Function produces structure
Globular proteins are easily misfolded
Moonlighting proteins
Intrinsically unstructured proteins
Proteins with a single polypeptide can have multiple globular domains
Membrane proteins cannot be degraded by the proteasome
15. X-ray crystallography of a protein usually is one of the last analyses done on a protein, so the sequence
of the protein is known by the time crystallography is done. What new information is provided by x-ray
studies of a protein crystal?
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The molecular weight of the protein
The primary (or only) function of the protein
The moonlighting functions of the protein
The amino acid composition of the protein
An electron density map of the repeating unit in the crystal
The capability of certain regions of the protein to move
The most likely subcellular location for the protein
16. In the induced-fit model of enzyme action, a _______ must bind to the enzyme's______ for the enzyme
to assume its catalytically active conformation.
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catalyst; activation energy
product; prosthetic group
water molecule; cofactor
coenzyme; N-terminus
substrate; active site
cofactor; allosteric site
MCMP 208 Exam I - 6
17. A novel biochemical activity was discovered and a test-tube method for measuring (assaying) that novel
activity was developed. Using this assay method the activity was highest in the cytosolic fraction of cells, so
cellular cytosol was prepared and one-fifth of this cytosol preparation was separated by each of 5 different
types of liquid chromatography. For each type of chromatography, the eluted material was collected into
numerous distinct fractions (based on time of elution during the running of the liquid chromatography). The
fractions were assayed for activity. For each type of chromatography, the fraction with the most activity was
analyzed by sodium dodecyl-sulfate polyacrylamide gel electrophoresis, which allowed determination of the
number of distinct sizes of polypeptides in each sample analyzed. The results are shown in the table below.
What can you conclude from this experimental comparison of various types of liquid chromatograph and its
results?
Number of distinct
polypeptide sizes
detected
70
45
15
7
40
LC type
Sephadex 200
Sephpac HPLC
DEAE cellulose
Hydroxyapatite
IMAC
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The protein with the novel activity has quaternary structure.
Spehadex 200 produces the largest amount of the protein with the novel activity.
Hydroxyapatite produces the largest amount of the protein with the novel activity.
The protein with the novel activity is negatively charged.
The protein with the novel activity is globular.
The protein with the novel activity has multiple globular domains.
The protein with the novel activity is fibrous.
Sephadex 200 is the best of these 5 methods for purifying the protein with the novel activity.
Hydroxyapatite is the best of these 5 methods for purifying the protein with the novel activity.
18. The enzyme that catalyzes the reaction below is best classified as a
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Oxidoreductase
Transferase
Hydrolase
Lyase
Isomerase
Ligase
O
O
O
P
O O
P
O
O
6
5
O
2
HO
O
O
O
4
3
O
HO
O
OH
19. The catalytic activity of alcohol dehydrogenase is dependent on which metal cofactor.
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Fe2+
Cu2+
Mg2+
K+
Mo
Zn2+
Mn2+
O
O
P
O
1
+
4
H
O
O
6
5
1
OH
P
2
O
3
OH
MCMP 208 Exam I - 7
20. The enzyme propionyl-CoA carboxylase catalyzes the carboxylation of propionyl CoA and requires an
enzyme bound molecule called biotin, or vitamin B7. The protein molecule lacking biotin is called
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a coenzyme
an apoenzyme
a holoenzyme
a prosthetic group
a heme group
a substrate
a ligase
a lyase
21. The following data were obtained for an enzyme that can
be described by the Michaelis-Menton equation.
Compound X is not a substrate, but does affect enzyme
activity. What is the best estimate of the Km for the
enzyme and most accurate description of Compound X?
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Km = 8 mM; coenzyme
Km = 1000 mM; coenzyme
Km = 1000 mM; competitive inhibitor
Km = 8 mM; heterotropic activator
Km = 8 mM; competitive inhibitor
Km = 8 mM; noncompetitive inhibitor
Km = 8 mM; uncompetitive inhibitor
Km = 500 mM; uncompetitive inhibitor
2
25
5
4
50
8
8
100
13
100
190
25
200
195
26
800
198
26
1000
202
27
22. The transition state for a chemical reaction best defined as
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the minimum energy required to cause the reaction
the free energy difference of the reactants and products
the species that exists for a finite length of time during the reaction and is then transformed to product
the enzyme-substrate (ES) complex
the structural form of reactant molecule that has the highest energy along the reaction coordinate
a reaction intermediate
23. See the Lineweaver-Burk plot below, where the activity of an enzyme is measured alone and in the
presence of an inhibitor at two different concentrations. This behavior of inhibition is characteristic of a
_________ inhibitor. The apparent Km value ____________ with increasing inhibitor concentration.
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competitive; decreases
competitive; increases
competitive; stays the same
noncompetitive; decreases
noncompetitive; increases
noncompetitive; stays the same
uncompetitive; decreases
uncompetitive; increases
uncompetitive; stays the same
MCMP 208 Exam I - 8
24. A zymogen is an example of an enzyme that relies primarily on which mechanism for regulation of
activity.
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Genetic control
Enzyme induction
Covalent modification
Compartmentation
Allosteric regulation
Cooperativity
H
N
25. In the step in the mechanism of an aspartic acid protease shown
here, what is the role of the Asp side chain on the right?
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intermediate
stabilizing the transition state
general acid
general base
covalent catalysis
increasing the effective concentration of substrates
O
H
Asp
OH
O
O
H
O
Asp
O
ESSAY PROBLEMS. Write your answers to problems 26 to 30 in the space immediately below each
problem.
26. [6 points] In a protein, there is a short internal segment that contains two amino acyl residues, which are
different. Each of the amino acyl residues in the segment can be phosphorylated to cause a change in the
functioning of the protein. Without phosphorylation, this segment is moderately hydrophobic.
a. [4 points] Draw the structure of this 2-amino acyl residue long segment when it is unphosphorylated
using any amino acids that are consistent with the information given in this problem. Do not draw a
peptide, but a segment, indicating where the rest of the protein is attached to this segment. Your
structure should show any ionizations that are predominant at physiological pH. You do not need to
be concerned about dihedral bond angles in your drawing. In your protein, indicate the end of your
segment that is closest (along the backbone) to the amino terminus of the protein.
b. [2 points] Redraw your 2-amino acyl residue sequence, but this time draw the resonance structure
that restricts rotation of the omega dihedral angle and be sure to show this dihedral angle as it would
be in the lowest energy state.
MCMP 208 Exam I - 9
27. [5 points] In a protein there is an alpha-helix composed of 11 amino acyl residues. In the folded protein,
this alpha-helix lays next to a flat region of a beta-sheet that has hydrophobic amino acids on the surface
nearest the alpha-helix. The other side of the alpha-helix is exposed to solvent on the surface of the
protein. Using the cartoon of an alpha-helix below to indicate the arrangement of these 11 amino acyl
residues as they would be in this protein. First, draw a large box around the part of the cartoon below that
you think is sufficient for the 11 amino acyl residues, then on the cartoon part that is inside this box, put
numbers (1 through 11) on the ribbon where the alpha carbons of the 11 amino acyl residues are located
along the alpha helix (if the location is hidden use an arrow to indicate the location). Then, in the spaces
provided below the diagram indicate the sequence of amino acids for this alpha helix based on the
locations of the amino acids in the drawing and the indicated locations of the beta-sheet and protein
surface. You may use any amino acids that are consistent with this overall structure.
------------------------------------------------ protein surface -----------------------------------
------------------------------------------------ β-sheet surface ----------------------------------Sequence (1 to 11) – one letter codes: __ __ __ __ __ __ __ __ __ __ __
1 2 3 4 5 6 7 8 9 10 11
28. [5 points] A protein with two globular domains is composed of a single polypeptide chain that is 500
amino acids long. The catalytic domain is composed of residues 170 to 500, while the regulatory domain
is composed of residues 1 to 155. An allosteric activator, A, binds to the regulatory domain. In the
absence of A, the regulatory domain interacts strongly with the catalytic domain, inhibiting its catalytic
activity. This inhibitor inter-domain interaction is lost when A is bound to the regulatory domain. Draw
two cartoons of this protein, with one showing this protein in the inactive state and the other cartoon
showing it in the active state. Label the state shown by each cartoon, active or inactive. The domains
should be drawn approximately to scale as circles or ellipses but remember to indicate the entire protein
in your drawing. Also, in your cartoons, show how A is bound to this protein (A should be represented
by a small circle labeled as “A”).
MCMP 208 Exam I - 10
29. [5 points total]
a. [3 points] Draw a graph of substrate concentration ([S]) vs. initial velocity (vo) for an enzyme that can
be described using the Michaelis Menton equation. Label both axes appropriately and also label the
Vmax and Km on the graph.
b. [2 points] Show how the curve would change if a competitive inhibitor were added to the reaction.
Draw a single plot with 2 curves. Label one as the uninhibited reaction and the other as the inhibited
reaction.
30. [4 points total]
a. [2 points] Based on your understanding of the substrate preferences of chymotrypsin, describe the
type of amino acids that line the specificity pocket and give an example of one such amino acid.
b. [2 points] Another homologous, serine protease, trypsin, contains an Asp in its specificity pocket.
After which amino acid(s) would you expect trypsin to cleave?