1. A 60-year-old man is admitted to the hospital with confusion, fatigue, and muscle weakness. His symptoms suggest mitochondrial dysfunction, potentially caused by exposure to a toxin that inhibits the electron transport chain. Laboratory tests reveal a disruption in ATP production, and the medical team suspects inhibition at Complex I. Which of the following is an inhibitor of Complex I?
A. BAL
B. Cyanide
C. H₂S
D. Malonate
E. Rotenone
Correct Option:
E. Rotenone: Rotenone is a well-known inhibitor of Complex I (NADH-CoQ reductase) in the electron transport chain. It blocks the transfer of electrons from NADH to ubiquinone, impairing the generation of ATP. This inhibition leads to energy deficiency in cells, resulting in symptoms like fatigue and muscle weakness.
Incorrect Options:
A. BAL (British Anti-Lewisite): BAL inhibits Complex III (cytochrome bc1 complex), disrupting electron transfer between ubiquinone and cytochrome c, but it does not affect Complex I.
B. Cyanide: Cyanide inhibits Complex IV (cytochrome c oxidase) by blocking the transfer of electrons to oxygen, resulting in severe metabolic crisis and respiratory failure.
C. H₂S (Hydrogen sulfide): Hydrogen sulfide also inhibits Complex IV, similar to cyanide, by interfering with oxygen binding, disrupting ATP production.
D. Malonate: Malonate is a competitive inhibitor of Complex II (succinate dehydrogenase) and does not affect Complex I.
2. Out of the following respiratory chain components, which one is a mobile carrier of electrons?
A. Cytochrome c oxidase
B. Cytochrome bc1-c reductase
C. NADH-CoQ reductase
D. Succinate dehydrogenase
E. Ubiquinone
Correct Option: E. Ubiquinone: Ubiquinone (also known as Coenzyme Q) is a mobile electron carrier in the electron transport chain (ETC). It transfers electrons between Complex I (NADH-CoQ reductase) or Complex II (succinate dehydrogenase) and Complex III (cytochrome bc1 complex). Ubiquinone’s mobility within the mitochondrial inner membrane allows it to shuttle electrons efficiently.
Incorrect Options:
A. Cytochrome c oxidase: This refers to Complex IV, which is a stationary complex and not a mobile carrier.
B. Cytochrome bc1-c reductase: This is another name for Complex III of ETC but is also not a mobile electron carrier.
C. NADH-CoQ reductase: Complex I of the electron transport chain is a large, fixed enzyme complex that transfers electrons to ubiquinone but does not move within the membrane.
D. Succinate dehydrogenase: This is Complex II, involved in both the ETC and the citric acid cycle. While it participates in electron transfer to ubiquinone, it is not a mobile carrier.
3. A child has accidentally ingested a chemical and presents with a high fever. The chemical is known to affect ATP formation in the electron transport chain. Which of the following could cause similar manifestations?
A. 2,4-Dinitrophenol
B. Atractyloside
C. Cyanide
D. Malonate
E. Rotenone
Correct Option: A. 2,4-Dinitrophenol: 2,4-Dinitrophenol (DNP) is an uncoupler of oxidative phosphorylation, meaning it disrupts the proton gradient across the inner mitochondrial membrane. Although the electron transport chain continues to operate, ATP production is impaired because protons bypass ATP synthase. This uncoupling generates heat, leading to high fever and hyperthermia, similar to what might occur in the scenario described.
Incorrect Options:
B. Atractyloside: Atractyloside inhibits the ADP/ATP translocase, preventing the exchange of ATP and ADP across the mitochondrial membrane. Although it impairs ATP formation, it is not typically associated with hyperthermia.
C. Cyanide: Cyanide inhibits Complex IV (cytochrome c oxidase) of the electron transport chain, blocking electron flow and halting ATP production. This can cause severe hypoxia and metabolic acidosis, but it is more commonly associated with respiratory failure than high fever.
D. Malonate: Malonate is a competitive inhibitor of succinate dehydrogenase (Complex II). It slows down the ETC, leading to reduced ATP production, but does not typically cause hyperthermia.
E. Rotenone: Rotenone inhibits Complex I (NADH-CoQ reductase), blocking electron flow from NADH to ubiquinone. While this reduces ATP production, it is not known to cause significant fever or hyperthermia.
4. A 32-year-old female working in a laboratory consumed cyanide and was rushed to the hospital. She was declared dead upon arrival. Cyanide is a known inhibitor of the electron transport chain (ETC). Which complex of the ETC might have been inhibited?
A. Cytochrome bc1-c reductase
B. Cytochrome c oxidase
C. NADH-CoQ reductase
D. Succinate dehydrogenase
E. Ubiquinone
Correct Option: B. Cytochrome c oxidase: Cyanide inhibits cytochrome c oxidase (Complex IV) of the ETC by binding to the iron in heme groups, blocking the transfer of electrons to oxygen. This halts cellular respiration and ATP production, leading to severe cellular hypoxia and metabolic failure, which can rapidly result in death, as seen in this case.
Incorrect Options:
A. Cytochrome bc1-c reductase refers to Complex III, which transfers electrons from ubiquinol to cytochrome c. While critical to the ETC, Complex III is not targeted by cyanide.
C. NADH-CoQ reductase: Also known as Complex I, this enzyme transfers electrons from NADH to ubiquinone. It is not directly affected by cyanide, though its function is indirectly impacted when the ETC stops functioning.
D. Succinate dehydrogenase: This is Complex II, which is involved in both the citric acid cycle and the ETC. It transfers electrons from succinate to ubiquinone. Cyanide does not inhibit Complex II directly.
E. Ubiquinone: Ubiquinone is a mobile electron carrier that transfers electrons between Complex I/II and Complex III. While essential for the ETC, cyanide does not act on ubiquinone itself.
5. Patients with inherited mitochondrial defects involving components of the respiratory chain and oxidative phosphorylation typically present with which of the following conditions except?
A. Encephalopathy
B. Hepatomegaly
C. Lactic acidosis
D. Myopathy
E. Stroke
Correct Option: B. Hepatomegaly: Mitochondrial disorders primarily affect tissues with high energy demands, such as the brain, muscles, and heart. Hepatomegaly (enlarged liver) is not a common feature in most mitochondrial disorders, though some metabolic diseases may affect the liver. In classical mitochondrial diseases, neurological and muscular symptoms are more prominent.
Incorrect Options:
A. Encephalopathy: Mitochondrial dysfunction in the brain often leads to encephalopathy, which manifests as confusion, developmental delays, or seizures due to impaired energy metabolism.
C. Lactic acidosis: Lactic acidosis occurs as cells shift toward anaerobic metabolism, leading to an accumulation of lactate when mitochondrial ATP production is insufficient.
D. Myopathy: Myopathy (muscle weakness) is a hallmark feature of mitochondrial disease, as muscles require a constant supply of energy from oxidative phosphorylation.
E. Stroke: Stroke-like episodes, particularly in syndromes such as MELAS (Mitochondrial Encephalopathy, Lactic Acidosis, and Stroke-like episodes), occur due to energy production deficits in the brain.
6. A 45-year-old patient with a history of metabolic disorders presents with symptoms of muscle fatigue and weakness. Laboratory tests suggest impaired oxidative phosphorylation. Given the suspicion of mitochondrial dysfunction affecting ATP production, the medical team examines the ATP synthase complex for potential issues. All of the following statements about the ATP synthase complex are true, except:
A. F₀ spans the membrane and forms a proton channel.
B. F₀ is inhibited by oligomycin.
C. F₁ contains the phosphorylation mechanism.
D. F₁ projects into the intermembranous space.
Correct Option: D. F₁ projects into the intermembranous space: The F₁ subunit of ATP synthase is located on the matrix side of the inner mitochondrial membrane, not in the intermembranous space. It is responsible for catalyzing the synthesis of ATP from ADP and inorganic phosphate. The intermembranous space is where protons accumulate during electron transport to create a gradient, but the F₁ subunit does not project into this space.
Incorrect Options:
A. F₀ spans the membrane and forms a proton channel: The F₀ subunit of ATP synthase spans the inner mitochondrial membrane and serves as a channel for protons to flow back into the matrix, powering ATP synthesis.
B. F₀ is inhibited by oligomycin: Oligomycin is a well-known inhibitor of the F₀ subunit. It blocks proton movement through the channel, thereby halting ATP production.
C. F₁ contains the phosphorylation mechanism: The F₁ subunit is responsible for ATP synthesis, where the chemical reaction of adding phosphate to ADP occurs, completing the phosphorylation process.
7. A 27-year-old woman is brought to the emergency department after an intentional overdose of aspirin. She presents with confusion, rapid breathing, a high fever (hyperthermia), and sweating. Laboratory results reveal metabolic acidosis with an increased anion gap. The attending physician suspects aspirin toxicity, which affects mitochondrial function. Which of the following best describes the biochemical basis of hyperthermia associated with aspirin toxicity?
A. Elevated ATP consumption
B. Increased fatty acid oxidation
C. Increased glycolysis
D. Increased muscular activity
E. Uncoupling of oxidative phosphorylation
Correct Option: E. Uncoupling of oxidative phosphorylation: Aspirin (salicylate) toxicity leads to the uncoupling of oxidative phosphorylation, disrupting the proton gradient in mitochondria. Although the electron transport chain remains active, the protons leak back into the matrix without driving ATP synthesis. As a result, the energy is released as heat, causing hyperthermia. This uncoupling contributes to the patient’s elevated body temperature and metabolic acidosis seen in aspirin overdose.
Incorrect Options:
A. Elevated ATP consumption: While ATP consumption increases in some pathological states, it is not the primary mechanism of hyperthermia in aspirin toxicity. The main issue lies in the inability to produce ATP efficiently due to mitochondrial uncoupling.
B. Increased fatty acid oxidation: Although aspirin can influence metabolism, increased fatty acid oxidation is not the direct cause of hyperthermia. Fatty acid metabolism typically occurs in response to energy needs but does not explain the heat production from mitochondrial dysfunction.
C. Increased glycolysis: Glycolysis increases in certain conditions, such as anaerobic metabolism, but it is not directly responsible for hyperthermia in aspirin toxicity, which stems from mitochondrial uncoupling rather than glycolytic pathways.
D. Increased muscular activity: Although increased muscular activity can cause hyperthermia, it is unrelated to aspirin toxicity. The fever in this scenario is metabolic, stemming from the uncoupling of oxidative phosphorylation rather than muscle exertion.
8. A 55-year-old man with a history of mitochondrial myopathy presents with muscle weakness and fatigue. His physician explains that the condition involves impaired electron transport within mitochondria. Specifically, the patient’s test results indicate a defect in the pathway through which electrons flow from Complex I to Complex III. Which of the following molecules or complexes facilitates this electron transfer?
A. Complex II
B. Complex III
C. Complex IV
D. Ubiquinone
Correct Option: D. Ubiquinone: Ubiquinone (Coenzyme Q) is the mobile electron carrier that transfers electrons from Complex I (NADH-CoQ reductase) to Complex III (cytochrome bc1 complex) in the electron transport chain. Ubiquinone accepts electrons from both Complex I and Complex II and then shuttles them to Complex III, allowing the continuation of electron flow in the chain.
Incorrect Options:
A. Complex II: Complex II (succinate dehydrogenase) also transfers electrons to ubiquinone, but it does not directly transfer electrons from Complex I to Complex III.
B. Complex III: Complex III receives electrons from ubiquinone but is not involved in transferring electrons directly from Complex I to itself.
C. Complex IV: Complex IV (cytochrome c oxidase) is the final complex in the electron transport chain, where it transfers electrons to oxygen, but it does not play a role in the electron transfer between Complex I and Complex III.
9. Which of the following best describes the mechanism of toxicity associated with Atractyloside?
A. Inhibits ATP synthase
B. Inhibits the ATP/ADP transporter
C. Acts as a proton ionophore
D. Uncouples oxidative phosphorylation
E. Inhibits Complex IV of the electron transport chain
Correct Option: B. Inhibits the ATP/ADP transporter: Atractyloside inhibits adenine nucleotide translocase (ANT), which is essential for the exchange of ATP and ADP between the mitochondrial matrix and the cytosol. This inhibition disrupts energy production, causing cellular dysfunction.
Incorrect Options:
A. Inhibits ATP synthase: ATP synthase catalyzes the synthesis of ATP from ADP and inorganic phosphate, and its inhibition by compounds like oligomycin leads to energy failure, though this is not the mechanism of atractyloside toxicity.
C. Acts as a proton ionophore: Proton ionophores, such as valinomycin, make membranes permeable to protons, collapsing the proton gradient. Atractyloside does not act as a proton ionophore.
D. Uncouples oxidative phosphorylation: Uncouplers like 2,4-dinitrophenol (DNP) allow protons to bypass ATP synthase, dissipating energy as heat. Atractyloside, however, does not uncouple oxidative phosphorylation.
E. Inhibits Complex IV of the electron transport chain: Complex IV (cytochrome c oxidase) is inhibited by substances like cyanide and carbon monoxide, leading to impaired oxygen consumption. This is not the mechanism of action of atractyloside.
10. A 50-year-old patient presents with profound muscle weakness and fatigue. Laboratory investigations reveal mitochondrial dysfunction impairing ATP production. The physician explains that energy production in cells relies on the electron transport chain (ETC) within mitochondria, where protons are pumped across the inner mitochondrial membrane, creating a gradient that drives ATP synthesis. For each H₂O molecule formed during the ETC, approximately how many protons are pumped into the intermembranous space?
A. 2
B. 4
C. 6
D. 8
E. 10
Correct Option: E. 10. For every pair of electrons that pass through the ETC, one molecule of water (H₂O) is formed as electrons are transferred to oxygen at Complex IV. During this process:
o 4 protons are pumped by Complex I,
o 4 protons are pumped by Complex III,
o 2 protons are pumped by Complex IV.
Thus, a total of 10 protons are pumped into the intermembranous space for every H₂O molecule formed, establishing the proton gradient needed for ATP synthesis.
Incorrect Options:
A. 2: Only Complex IV pumps 2 protons, but this is a partial step, not the total proton output for each water molecule formed.
B. 4: Complex I or Complex III alone pumps 4 protons, but this does not account for the full ETC process involving all complexes.
C. 6: While multiple complexes contribute to proton pumping, 6 protons is an incorrect total for the entire process involving Complexes I, III, and IV.
D. 8: Some steps pump 8 protons collectively, but the complete flow from electron input to water formation results in the pumping of 10 protons into the intermembranous space.
