, Question 1
A cell maintains a cytosolic ATP/ADP ratio of ~10. Which statement best
explains why a 10-fold increase in ADP concentration can stimulate glycolysis
more than a 10-fold increase in AMP?
A. ADP directly activates phosphofructokinase-1 by binding to its
allosteric site, whereas AMP inhibits it.
B. AMP is rapidly deaminated to IMP, reducing its regulatory role, while
ADP is stable.
C. ADP is a substrate for both glycolysis and oxidative phosphorylation,
so its increase reflects a higher energy demand.
D. The adenylate kinase reaction (2 ADP -> ATP + AMP) amplifies small
changes in ADP into larger relative changes in AMP, but ADP itself also
directly regulates key enzymes.
Correct Answer: D - The adenylate kinase reaction (2 ADP ->
ATP + AMP) amplifies small changes in ADP into larger relative
changes in AMP, but ADP itself also directly regulates key
enzymes.
RATIONALE
Adenylate kinase maintains the equilibrium 2 ADP -> ATP + AMP, so
a small rise in ADP causes a much larger relative rise in AMP, which
is a potent allosteric activator of PFK-1. However, ADP also directly
regulates enzymes like PFK-1 and is a substrate for ATP synthesis.
Thus, both nucleotides contribute, but the amplification via adenylate
kinase makes AMP a more sensitive signal.
Question 2
In a patient with a mutation in the gene encoding the mitochondrial uncoupling
protein UCP1, which of the following would be the most likely direct
consequence for brown adipose tissue?
A. Increased ATP synthesis due to a higher proton gradient.
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, B. Decreased heat production and increased reactive oxygen species
(ROS) generation.
C. Enhanced fatty acid oxidation due to increased substrate availability.
D. Shift from oxidative phosphorylation to glycolysis for ATP
production.
Correct Answer: B - Decreased heat production and increased
reactive oxygen species (ROS) generation.
RATIONALE
UCP1 dissipates the proton gradient to generate heat (non-shivering
thermogenesis) without ATP synthesis. Loss of UCP1 would reduce
heat production and cause a higher proton motive force, leading to
increased electron leak and ROS production. ATP synthesis would not
increase because the gradient is not used for ATP; instead, it may be
less efficiently regulated.
Question 3
A researcher measures the rate of O2 consumption by isolated mitochondria in
the presence of excess substrate, ADP, and an inhibitor of Complex III. Which
of the following would be observed?
A. O2 consumption continues at a high rate because Complex IV can still
reduce O2.
B. O2 consumption ceases because the electron transport chain is
blocked, but ATP synthesis continues via substrate-level phosphorylation.
C. O2 consumption decreases sharply, and the proton gradient collapses,
halting ATP synthesis.
D. O2 consumption increases due to a compensatory increase in Complex
IV activity.
Correct Answer: B - O2 consumption ceases because the electron
transport chain is blocked, but ATP synthesis continues via
substrate-level phosphorylation.
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, RATIONALE
Inhibition of Complex III blocks electron transfer to cytochrome c,
halting O2 reduction at Complex IV. However, substrate-level
phosphorylation (e.g., from succinyl-CoA synthetase in the TCA
cycle) can still produce some ATP if substrates are available. The
proton gradient would eventually collapse, but ATP synthesis via
oxidative phosphorylation stops.
Question 4
Which of the following best explains why the G°' for the hydrolysis of ATP is
more negative than that of glucose-6-phosphate?
A. ATP has a higher phosphoryl transfer potential due to resonance
stabilization of the products and electrostatic repulsion in the reactant.
B. Glucose-6-phosphate is a larger molecule, so its hydrolysis releases
more energy.
C. ATP hydrolysis is coupled to endergonic reactions, lowering its G.
D. Glucose-6-phosphate hydrolysis produces glucose, which is rapidly
metabolized, driving the reaction forward.
Correct Answer: A - ATP has a higher phosphoryl transfer
potential due to resonance stabilization of the products and
electrostatic repulsion in the reactant.
RATIONALE
ATP has a high phosphoryl transfer potential because the products
(ADP and Pi) are stabilized by resonance and the reactant has
electrostatic repulsion among phosphate groups. Glucose-6-phosphate
has a lower transfer potential because its hydrolysis products are less
stabilized. This difference explains why ATP can phosphorylate
glucose.
Page 4
A cell maintains a cytosolic ATP/ADP ratio of ~10. Which statement best
explains why a 10-fold increase in ADP concentration can stimulate glycolysis
more than a 10-fold increase in AMP?
A. ADP directly activates phosphofructokinase-1 by binding to its
allosteric site, whereas AMP inhibits it.
B. AMP is rapidly deaminated to IMP, reducing its regulatory role, while
ADP is stable.
C. ADP is a substrate for both glycolysis and oxidative phosphorylation,
so its increase reflects a higher energy demand.
D. The adenylate kinase reaction (2 ADP -> ATP + AMP) amplifies small
changes in ADP into larger relative changes in AMP, but ADP itself also
directly regulates key enzymes.
Correct Answer: D - The adenylate kinase reaction (2 ADP ->
ATP + AMP) amplifies small changes in ADP into larger relative
changes in AMP, but ADP itself also directly regulates key
enzymes.
RATIONALE
Adenylate kinase maintains the equilibrium 2 ADP -> ATP + AMP, so
a small rise in ADP causes a much larger relative rise in AMP, which
is a potent allosteric activator of PFK-1. However, ADP also directly
regulates enzymes like PFK-1 and is a substrate for ATP synthesis.
Thus, both nucleotides contribute, but the amplification via adenylate
kinase makes AMP a more sensitive signal.
Question 2
In a patient with a mutation in the gene encoding the mitochondrial uncoupling
protein UCP1, which of the following would be the most likely direct
consequence for brown adipose tissue?
A. Increased ATP synthesis due to a higher proton gradient.
Page 2
, B. Decreased heat production and increased reactive oxygen species
(ROS) generation.
C. Enhanced fatty acid oxidation due to increased substrate availability.
D. Shift from oxidative phosphorylation to glycolysis for ATP
production.
Correct Answer: B - Decreased heat production and increased
reactive oxygen species (ROS) generation.
RATIONALE
UCP1 dissipates the proton gradient to generate heat (non-shivering
thermogenesis) without ATP synthesis. Loss of UCP1 would reduce
heat production and cause a higher proton motive force, leading to
increased electron leak and ROS production. ATP synthesis would not
increase because the gradient is not used for ATP; instead, it may be
less efficiently regulated.
Question 3
A researcher measures the rate of O2 consumption by isolated mitochondria in
the presence of excess substrate, ADP, and an inhibitor of Complex III. Which
of the following would be observed?
A. O2 consumption continues at a high rate because Complex IV can still
reduce O2.
B. O2 consumption ceases because the electron transport chain is
blocked, but ATP synthesis continues via substrate-level phosphorylation.
C. O2 consumption decreases sharply, and the proton gradient collapses,
halting ATP synthesis.
D. O2 consumption increases due to a compensatory increase in Complex
IV activity.
Correct Answer: B - O2 consumption ceases because the electron
transport chain is blocked, but ATP synthesis continues via
substrate-level phosphorylation.
Page 3
, RATIONALE
Inhibition of Complex III blocks electron transfer to cytochrome c,
halting O2 reduction at Complex IV. However, substrate-level
phosphorylation (e.g., from succinyl-CoA synthetase in the TCA
cycle) can still produce some ATP if substrates are available. The
proton gradient would eventually collapse, but ATP synthesis via
oxidative phosphorylation stops.
Question 4
Which of the following best explains why the G°' for the hydrolysis of ATP is
more negative than that of glucose-6-phosphate?
A. ATP has a higher phosphoryl transfer potential due to resonance
stabilization of the products and electrostatic repulsion in the reactant.
B. Glucose-6-phosphate is a larger molecule, so its hydrolysis releases
more energy.
C. ATP hydrolysis is coupled to endergonic reactions, lowering its G.
D. Glucose-6-phosphate hydrolysis produces glucose, which is rapidly
metabolized, driving the reaction forward.
Correct Answer: A - ATP has a higher phosphoryl transfer
potential due to resonance stabilization of the products and
electrostatic repulsion in the reactant.
RATIONALE
ATP has a high phosphoryl transfer potential because the products
(ADP and Pi) are stabilized by resonance and the reactant has
electrostatic repulsion among phosphate groups. Glucose-6-phosphate
has a lower transfer potential because its hydrolysis products are less
stabilized. This difference explains why ATP can phosphorylate
glucose.
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