Introduction: Inhibitors of ETC are vital for B.Pharm students to understand drug actions, toxicology, and experimental tools targeting the electron transport chain. This concise guide explains key electron transport chain inhibitors—Complex I inhibitors (rotenone, amytal), Complex III blockers (antimycin A), Complex IV poisons (cyanide, carbon monoxide), and ATP synthase inhibitors (oligomycin)—and highlights effects on oxidative phosphorylation, ATP synthesis, proton motive force, oxygen consumption, and reactive oxygen species. Knowing mechanisms, laboratory uses, clinical implications, and antidotes enhances pharmacology and toxicology competence. Now let’s test your knowledge with 50 MCQs on this topic.
Q1. Which inhibitor specifically blocks electron transfer from NADH to ubiquinone at Complex I?
- Antimycin A
- Rotenone
- Oligomycin
- Cyanide
Correct Answer: Rotenone
Q2. Which compound inhibits Complex III by binding to the Qi site and prevents ubiquinol oxidation?
- Myxothiazol
- Antimycin A
- Rotenone
- Oligomycin
Correct Answer: Antimycin A
Q3. Cyanide inhibits which component of the electron transport chain?
- Complex I
- Ubiquinone (CoQ)
- Cytochrome c oxidase (Complex IV)
- ATP synthase (Complex V)
Correct Answer: Cytochrome c oxidase (Complex IV)
Q4. Oligomycin inhibits ATP synthesis by directly blocking which structure?
- F0 proton channel of ATP synthase
- NADH dehydrogenase active site
- Cytochrome b binding site
- Cytochrome c release
Correct Answer: F0 proton channel of ATP synthase
Q5. Which of the following is an example of a classical Complex I inhibitor used experimentally?
- Antimycin A
- Rotenone
- Azide
- Oligomycin
Correct Answer: Rotenone
Q6. Carbon monoxide (CO) exerts toxicity by competitive binding to which site?
- Iron-sulfur centers in Complex I
- Heme a3 in cytochrome c oxidase
- ATP synthase catalytic site
- Ubiquinone binding pocket
Correct Answer: Heme a3 in cytochrome c oxidase
Q7. Which inhibitor increases NADH/NAD+ ratio by blocking electron exit from Complex I?
- Antimycin A
- Cyanide
- Rotenone
- Dinitrophenol (DNP)
Correct Answer: Rotenone
Q8. Antimycin A primarily causes which change in mitochondrial respiration?
- Increased ATP synthesis with decreased O2 consumption
- Decreased electron flux at Complex III and decreased O2 consumption
- Uncoupling of oxidative phosphorylation increasing heat production
- Increased proton pumping across inner membrane
Correct Answer: Decreased electron flux at Complex III and decreased O2 consumption
Q9. Which inhibitor blocks electron flow between cytochrome b and cytochrome c1 at Complex III?
- Myxothiazol
- Antimycin A
- Rotenone
- Azide
Correct Answer: Antimycin A
Q10. Which toxic agent binds irreversibly to cytochrome c oxidase and can be treated with hydroxocobalamin?
- Cyanide
- Carbon monoxide
- Rotenone
- Oligomycin
Correct Answer: Cyanide
Q11. Which inhibitor is known as a protonophore and uncouples oxidative phosphorylation rather than inhibiting electron transport directly?
- 2,4-Dinitrophenol (DNP)
- Antimycin A
- Rotenone
- Oligomycin
Correct Answer: 2,4-Dinitrophenol (DNP)
Q12. Inhibition of Complex IV by cyanide results in which immediate cellular effect?
- Enhanced ATP production
- Impaired reduction of oxygen to water
- Increased proton pumping by Complex IV
- Activation of ATP synthase
Correct Answer: Impaired reduction of oxygen to water
Q13. Which agent inhibits ATP synthase by covalently modifying a conserved carboxyl residue in F0?
- Oligomycin
- Dicyclohexylcarbodiimide (DCCD)
- Rotenone
- Cyanide
Correct Answer: Dicyclohexylcarbodiimide (DCCD)
Q14. Which inhibitor would most directly increase production of reactive oxygen species (ROS) at Complex I?
- Oligomycin
- Rotenone
- Cyanide
- Azide
Correct Answer: Rotenone
Q15. Which inhibitor competes with oxygen at the heme copper center causing cellular hypoxia despite normal oxygen tension?
- Carbon monoxide
- Antimycin A
- Rotenone
- Oligomycin
Correct Answer: Carbon monoxide
Q16. Malonate acts as an inhibitor of which enzyme linked to the electron transport chain?
- Succinate dehydrogenase (Complex II)
- NADH dehydrogenase (Complex I)
- Cytochrome c oxidase (Complex IV)
- ATP synthase (Complex V)
Correct Answer: Succinate dehydrogenase (Complex II)
Q17. Which statement best distinguishes uncouplers like DNP from ETC inhibitors?
- Uncouplers block electron flow at specific complexes
- Uncouplers dissipate proton gradient without blocking electron flow
- Uncouplers inhibit ATP synthase directly
- Uncouplers increase ATP synthesis efficiency
Correct Answer: Uncouplers dissipate proton gradient without blocking electron flow
Q18. Which experimental inhibitor blocks electron transfer from ubiquinol to the Rieske iron-sulfur protein at Complex III?
- Myxothiazol
- Antimycin A
- Rotenone
- Azide
Correct Answer: Myxothiazol
Q19. Azide inhibits cytochrome c oxidase by binding to which component?
- Iron-sulfur centers of Complex I
- Heme iron in cytochrome a3
- ATP synthase F1 catalytic subunit
- Ubiquinone head group
Correct Answer: Heme iron in cytochrome a3
Q20. Which inhibitor would decrease the proton motive force and ATP synthesis but not immediately stop electron flow?
- Oligomycin
- Uncouplers like DNP
- Rotenone
- Antimycin A
Correct Answer: Uncouplers like DNP
Q21. Which inhibitor is commonly used to study ATP synthase by blocking proton translocation through F0?
- Rotenone
- Oligomycin
- Antimycin A
- Cyanide
Correct Answer: Oligomycin
Q22. In the presence of rotenone, what happens to oxygen consumption in state 3 respiration?
- It increases markedly
- It decreases due to inhibited electron flow
- It becomes independent of ADP
- It converts to anaerobic respiration
Correct Answer: It decreases due to inhibited electron flow
Q23. Which inhibitor would cause accumulation of reduced cytochrome b and oxidation of cytochrome c?
- Antimycin A
- Rotenone
- Cyanide
- Oligomycin
Correct Answer: Antimycin A
Q24. Which therapeutic agent is used as an antidote for cyanide poisoning by binding free cyanide?
- Hydroxocobalamin
- Nitroglycerin
- Atropine
- Probenecid
Correct Answer: Hydroxocobalamin
Q25. Which inhibitor interferes with electron transfer at Complex II by acting as a succinate analogue?
- Malonate
- DNP
- Rotenone
- Azide
Correct Answer: Malonate
Q26. Inhibition of Complex IV leads to which change in cytochrome c redox state?
- Cytochrome c becomes highly oxidized
- Cytochrome c becomes highly reduced
- Cytochrome c is degraded
- No change occurs
Correct Answer: Cytochrome c becomes highly reduced
Q27. Which inhibitor is often used experimentally to block mitochondrial electron transport at the Q-cycle by binding the Qo site?
- Myxothiazol
- Rotenone
- Cyanide
- Oligomycin
Correct Answer: Myxothiazol
Q28. Which industrial chemical can cause cyanide-like inhibition of cytochrome c oxidase leading to lactic acidosis?
- Hydrogen sulfide
- Sodium azide
- Phenol
- Ammonia
Correct Answer: Sodium azide
Q29. Which of the following decreases the P:O ratio by allowing electron flow without ATP synthesis?
- Rotenone
- Uncouplers such as DNP
- Antimycin A
- Oligomycin
Correct Answer: Uncouplers such as DNP
Q30. Which poison leads to cherry-red skin coloration due to impaired oxygen utilization?
- Cyanide
- Carbon monoxide
- Rotenone
- Antimycin A
Correct Answer: Carbon monoxide
Q31. Which inhibitor would prevent ATP synthesis yet maintain a high proton gradient because proton re-entry is blocked?
- Oligomycin
- DNP
- Rotenone
- Antimycin A
Correct Answer: Oligomycin
Q32. Inhibition at Complex I by rotenone would be expected to:
- Decrease NADH levels
- Increase NADH/NAD+ ratio
- Oxidize the mitochondrial matrix completely
- Increase ATP synthesis
Correct Answer: Increase NADH/NAD+ ratio
Q33. Which agent blocks electron transfer at Complex IV and is associated with smoke inhalation from house fires?
- Antimycin A
- Carbon monoxide
- Rotenone
- DNP
Correct Answer: Carbon monoxide
Q34. Which experimental inhibitor specifically blocks the Qo site of Complex III preventing formation of semiquinone at that site?
- Myxothiazol
- Antimycin A
- Rotenone
- Azide
Correct Answer: Myxothiazol
Q35. The therapeutic use of nitrites in cyanide poisoning works by converting hemoglobin to what form to sequester cyanide?
- Carboxyhemoglobin
- Methemoglobin
- Oxyhemoglobin
- Deoxyhemoglobin
Correct Answer: Methemoglobin
Q36. Which inhibitor blocks ATP synthase by binding to the c subunit ring in F0 and preventing rotation?
- Oligomycin
- Rotenone
- Antimycin A
- Azide
Correct Answer: Oligomycin
Q37. Which of the following is NOT a direct inhibitor of the electron transport chain complexes?
- Antimycin A
- Rotenone
- Dinitrophenol (DNP)
- Cyanide
Correct Answer: Dinitrophenol (DNP)
Q38. In mitochondria treated with oligomycin, what is the expected effect on oxygen consumption?
- Oxygen consumption increases due to stimulated electron flow
- Oxygen consumption is reduced because ATP synthesis and ADP recycling are limited
- Oxygen consumption is unaffected
- Oxygen becomes the electron donor
Correct Answer: Oxygen consumption is reduced because ATP synthesis and ADP recycling are limited
Q39. Which compound blocks electron flow by binding to the quinone reduction site of Complex I?
- Piericidin
- Antimycin A
- Oligomycin
- Cyanide
Correct Answer: Piericidin
Q40. Which statement about rotenone toxicity is TRUE?
- Rotenone causes direct inhibition of Complex IV
- Rotenone is associated with increased ROS and has been used to model Parkinsonism in animals
- Rotenone acts as an uncoupler increasing heat production
- Rotenone is an antidote for cyanide poisoning
Correct Answer: Rotenone is associated with increased ROS and has been used to model Parkinsonism in animals
Q41. Which inhibitor would be most useful to distinguish between defects in ATP synthase and defects in the electron transport chain in an experimental assay?
- Rotenone
- Oligomycin followed by uncoupler addition
- Antimycin A alone
- Cyanide alone
Correct Answer: Oligomycin followed by uncoupler addition
Q42. Which of the following increases oxygen consumption but reduces ATP production in mitochondria?
- Rotenone
- Uncouplers such as DNP
- Antimycin A
- Oligomycin
Correct Answer: Uncouplers such as DNP
Q43. Which inhibitor blocks electron transfer by binding to the cytochrome c binding site on Complex IV?
- Azide
- Cyanide
- CO
- None of the above specifically block the cytochrome c binding site
Correct Answer: None of the above specifically block the cytochrome c binding site
Q44. Which effect is expected when antimycin A is added to isolated mitochondria with succinate as substrate?
- Succinate-supported respiration continues normally
- Electron flow is blocked at Complex III and respiration halts
- Complex I becomes hyperactive
- ATP synthesis increases
Correct Answer: Electron flow is blocked at Complex III and respiration halts
Q45. Which agent is used experimentally to probe superoxide generation by inhibiting reverse electron flow into Complex I?
- Rotenone
- Oligomycin
- Antimycin A
- Cyanide
Correct Answer: Rotenone
Q46. Which inhibitor would most rapidly cause cessation of mitochondrial oxygen consumption when added to active isolated mitochondria?
- DNP
- Cyanide
- Oligomycin
- Malonate
Correct Answer: Cyanide
Q47. Which of the following is TRUE about antimycin A-induced blockade?
- It increases electron flow through Complex III
- It causes accumulation of reduced upstream carriers and decreases downstream reduction
- It acts at Complex I exclusively
- It uncouples oxidative phosphorylation
Correct Answer: It causes accumulation of reduced upstream carriers and decreases downstream reduction
Q48. Which clinical sign is most characteristic of acute cyanide poisoning affecting ETC?
- Hypothermia with bradycardia
- Rapid onset of lactic acidosis and altered mental status
- Hyperactivity and euphoria
- Delayed muscle weakness over weeks
Correct Answer: Rapid onset of lactic acidosis and altered mental status
Q49. Which mitochondrial inhibitor is reversible and often used to probe Complex IV function in vitro?
- Cyanide (reversible at low concentration)
- Antimycin A (irreversible)
- DCCD (irreversible)
- Rotenone (irreversible)
Correct Answer: Cyanide (reversible at low concentration)
Q50. Which statement best describes the pharmacological importance of ETC inhibitors for B.Pharm students?
- They have no relevance beyond toxicology
- They serve as tools to dissect mitochondrial function, model disease, and highlight risks of environmental toxins and therapeutic exposures
- They are only used to increase ATP production therapeutically
- They are exclusively used as pesticides with no biomedical implications
Correct Answer: They serve as tools to dissect mitochondrial function, model disease, and highlight risks of environmental toxins and therapeutic exposures
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