Oxidative phosphorylation – mechanism MCQs With Answer

Oxidative phosphorylation – mechanism MCQs With Answer

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Oxidative phosphorylation – mechanism MCQs With Answer

Oxidative phosphorylation is the final, ATP-generating stage of cellular respiration where the electron transport chain (ETC) and ATP synthase convert energy from NADH/FADH2 into ATP. This mechanism relies on the chemiosmotic theory, proton gradient across the mitochondrial inner membrane, and coordinated function of complexes I–IV and Coenzyme Q and cytochrome c. B. Pharm students must master concepts like proton motive force (Δψ and ΔpH), P/O ratios, inhibitors (cyanide, rotenone, oligomycin), uncouplers (2,4-DNP), and ROS generation to understand drug action and mitochondrial pathophysiology. Now let’s test your knowledge with 50 MCQs on this topic.

Q1. Which component directly synthesizes ATP using the proton motive force in oxidative phosphorylation?

  • Complex I (NADH dehydrogenase)
  • Complex II (Succinate dehydrogenase)
  • ATP synthase (F1F0-ATPase)
  • Cytochrome c oxidase (Complex IV)

Correct Answer: ATP synthase (F1F0-ATPase)

Q2. The chemiosmotic theory of oxidative phosphorylation was proposed by which scientist?

  • Hans Krebs
  • Peter Mitchell
  • Otto Warburg
  • Albert Szent-Györgyi

Correct Answer: Peter Mitchell

Q3. Which complex of the mitochondrial electron transport chain directly transfers electrons from NADH to ubiquinone (CoQ)?

  • Complex I
  • Complex II
  • Complex III
  • Complex IV

Correct Answer: Complex I

Q4. Which carrier transfers electrons between Complex III and Complex IV?

  • Coenzyme Q (Ubiquinone)
  • Cytochrome c
  • FMN
  • Iron-sulfur proteins

Correct Answer: Cytochrome c

Q5. What is the main difference in electron entry into the ETC between NADH and FADH2?

  • NADH donates to Complex II, FADH2 to Complex I
  • NADH donates to Complex I, FADH2 to Complex II
  • Both donate to Complex III directly
  • Both donate electrons only to CoQ

Correct Answer: NADH donates to Complex I, FADH2 to Complex II

Q6. Which statement best describes the proton motive force (PMF)?

  • It is solely the pH gradient across the outer mitochondrial membrane
  • It is the combined membrane potential (Δψ) and proton concentration gradient (ΔpH) across the inner membrane
  • It is the electron gradient along the ETC
  • It is the concentration gradient of ATP across the inner membrane

Correct Answer: It is the combined membrane potential (Δψ) and proton concentration gradient (ΔpH) across the inner membrane

Q7. Which inhibitor specifically blocks Complex IV (cytochrome c oxidase)?

  • Rotenone
  • Antimycin A
  • Cyanide
  • Oligomycin

Correct Answer: Cyanide

Q8. Oligomycin inhibits which part of oxidative phosphorylation?

  • Electron transfer at Complex III
  • ATP synthase proton channel (F0)
  • ADP/ATP translocase
  • Coenzyme Q reduction

Correct Answer: ATP synthase proton channel (F0)

Q9. Which of the following is an uncoupler of oxidative phosphorylation?

  • Antimycin A
  • 2,4-Dinitrophenol (2,4-DNP)
  • Rotenone
  • Oligomycin

Correct Answer: 2,4-Dinitrophenol (2,4-DNP)

Q10. The P/O ratio refers to:

  • Protons pumped per oxygen atom reduced
  • ATP molecules produced per pair of electrons from NADH
  • ATP produced per oxygen atom reduced
  • Phosphate consumed per oxygen molecule

Correct Answer: ATP produced per oxygen atom reduced

Q11. Which complex contains the cytochrome a and a3 and the copper centers essential for O2 reduction?

  • Complex I
  • Complex II
  • Complex III
  • Complex IV

Correct Answer: Complex IV

Q12. Antimycin A inhibits which electron transport component?

  • Electron transfer from Complex I to CoQ
  • Electron transfer within Complex III (cytochrome b to c1)
  • Complex IV active site
  • ATP synthase catalytic site

Correct Answer: Electron transfer within Complex III (cytochrome b to c1)

Q13. Where are the complexes of the electron transport chain located?

  • Mitochondrial outer membrane
  • Mitochondrial inner membrane
  • Cytosol
  • Endoplasmic reticulum lumen

Correct Answer: Mitochondrial inner membrane

Q14. Which prosthetic group is present in Complex I and plays a role in FMN-mediated electron transfer?

  • Heme a
  • Flavin mononucleotide (FMN)
  • Copper A
  • Ubiquinone

Correct Answer: Flavin mononucleotide (FMN)

Q15. Coenzyme Q (ubiquinone) is unique because it:

  • Is a small water-soluble cytochrome
  • Shuttles electrons and protons within the inner membrane and is lipid-soluble
  • Directly reduces oxygen to water
  • Is part of ATP synthase complex

Correct Answer: Shuttles electrons and protons within the inner membrane and is lipid-soluble

Q16. Which of the following increases ATP synthesis by increasing ADP availability?

  • High ATP/ADP ratio
  • Low ADP concentration
  • High ADP concentration (respiratory control)
  • Oligomycin treatment

Correct Answer: High ADP concentration (respiratory control)

Q17. Which experimental evidence supported chemiosmotic theory?

  • Demonstration that ATP synthase does not require a proton gradient
  • Observation that formation of a proton gradient across liposomes drives ATP synthesis
  • Finding that electrons flow without proton translocation
  • Discovery that ATP is synthesized solely by substrate-level phosphorylation

Correct Answer: Observation that formation of a proton gradient across liposomes drives ATP synthesis

Q18. Which protein exchanges matrix ATP for cytosolic ADP across the inner mitochondrial membrane?

  • Porin
  • ADP/ATP translocase (ANT)
  • ATP synthase F1 subunit
  • Cytochrome c

Correct Answer: ADP/ATP translocase (ANT)

Q19. Reactive oxygen species (ROS) production in mitochondria commonly arises from which complexes?

  • Complex I and Complex III
  • Complex II only
  • ATP synthase and Complex IV
  • Complexes located in the outer membrane

Correct Answer: Complex I and Complex III

Q20. Which statement best distinguishes substrate-level phosphorylation from oxidative phosphorylation?

  • Substrate-level uses PMF; oxidative uses enzyme catalysis
  • Substrate-level directly transfers a phosphate to ADP; oxidative uses an electrochemical gradient and ATP synthase
  • Both are identical processes occurring in mitochondria
  • Oxidative phosphorylation does not produce ATP

Correct Answer: Substrate-level directly transfers a phosphate to ADP; oxidative uses an electrochemical gradient and ATP synthase

Q21. The F0 portion of ATP synthase is primarily responsible for:

  • Catalyzing ATP formation from ADP and Pi
  • Proton translocation across the membrane
  • Binding ADP and Pi in the matrix
  • Electron transfer to oxygen

Correct Answer: Proton translocation across the membrane

Q22. Which inhibitor blocks Complex I and is used as a pesticide?

  • Rotenone
  • Antimycin A
  • Oligomycin
  • Cyanide

Correct Answer: Rotenone

Q23. In isolated mitochondria, what happens to oxygen consumption when ADP is added (state 3 respiration)?

  • Oxygen consumption decreases
  • Oxygen consumption increases due to stimulated ATP synthesis
  • Oxygen consumption is unchanged
  • Oxygen consumption stops completely

Correct Answer: Oxygen consumption increases due to stimulated ATP synthesis

Q24. Which molecule accepts electrons from Complex II?

  • Cytochrome c
  • Coenzyme Q (ubiquinone)
  • Oxygen directly
  • ATP synthase

Correct Answer: Coenzyme Q (ubiquinone)

Q25. The term “respirasome” refers to:

  • A single isolated complex I protein
  • Supercomplex assembly of ETC complexes that enhance electron transfer efficiency
  • The ATP synthase monomer only
  • The mitochondrial DNA encoding respiratory enzymes

Correct Answer: Supercomplex assembly of ETC complexes that enhance electron transfer efficiency

Q26. Which of the following decreases ATP synthesis by collapsing the proton gradient without inhibiting electron flow?

  • Rotenone
  • Oligomycin
  • Uncouplers such as 2,4-DNP
  • Antimycin A

Correct Answer: Uncouplers such as 2,4-DNP

Q27. Which ion movement primarily generates the electrical component (Δψ) of the proton motive force?

  • Sodium ions pumping across the outer membrane
  • Proton movement across the inner mitochondrial membrane
  • Movement of glucose into mitochondria
  • Chloride ion flux through porins

Correct Answer: Proton movement across the inner mitochondrial membrane

Q28. Which clinical condition is most directly linked to defects in oxidative phosphorylation?

  • Lysosomal storage disorders
  • Mitochondrial myopathies and encephalopathies
  • Hemophilia
  • Scurvy

Correct Answer: Mitochondrial myopathies and encephalopathies

Q29. Which experimental inhibitor would you use to block ATP synthesis but allow continued electron transport and oxygen consumption?

  • Oligomycin (blocks ATP synthase)
  • Cyanide (blocks Complex IV)
  • Rotenone (blocks Complex I)
  • Antimycin A (blocks Complex III)

Correct Answer: Oligomycin (blocks ATP synthase)

Q30. What is the role of cytochrome c in apoptosis related to mitochondria?

  • It synthesizes ATP in the cytosol
  • Release of cytochrome c into cytosol activates caspases and apoptosis
  • It inhibits Complex IV activity
  • It transports ADP into mitochondria

Correct Answer: Release of cytochrome c into cytosol activates caspases and apoptosis

Q31. Which statement about Complex II is true?

  • Complex II pumps protons across the inner membrane
  • Complex II contains succinate dehydrogenase and feeds electrons to CoQ without proton translocation
  • Complex II reduces oxygen to water
  • Complex II is the main site of proton leak

Correct Answer: Complex II contains succinate dehydrogenase and feeds electrons to CoQ without proton translocation

Q32. Which redox center in Complex III participates in the Q-cycle?

  • Flavin mononucleotide (FMN)
  • Heme groups (cytochromes b and c1) and iron-sulfur (Rieske) protein
  • Copper B center only
  • Succinate

Correct Answer: Heme groups (cytochromes b and c1) and iron-sulfur (Rieske) protein

Q33. Reverse electron transport, generating superoxide, is most likely when:

  • CoQ is highly reduced and Δψ is large
  • Oxygen is absent
  • ATP synthase is hyperactive
  • Matrix NAD+ is very low

Correct Answer: CoQ is highly reduced and Δψ is large

Q34. In intact cells, what primarily limits the rate of oxidative phosphorylation under normal conditions?

  • Availability of oxygen only
  • ATP synthase catalytic activity only
  • ADP availability and demand for ATP (acceptor control)
  • Outer membrane permeability

Correct Answer: ADP availability and demand for ATP (acceptor control)

Q35. Which molecule functions as both an electron and proton carrier and can accept electrons from multiple dehydrogenases?

  • Cytochrome c
  • Ubiquinone (CoQ)
  • ATP
  • Oxygen

Correct Answer: Ubiquinone (CoQ)

Q36. The F1 portion of ATP synthase contains:

  • The proton channel embedded in membrane
  • Catalytic sites for ATP synthesis/hydrolysis
  • CoQ binding site
  • Cytochrome c binding domain

Correct Answer: Catalytic sites for ATP synthesis/hydrolysis

Q37. Which type of mitochondrial membrane permeability leads to uncoupling and loss of membrane potential?

  • Permissive outer membrane porin activity only
  • Formation of the mitochondrial permeability transition pore (mPTP)
  • Specific import of ADP via ANT
  • Increased cytochrome c binding to Complex IV

Correct Answer: Formation of the mitochondrial permeability transition pore (mPTP)

Q38. What effect does hypoxia (low oxygen) have on oxidative phosphorylation?

  • Increases ATP production by oxidative phosphorylation
  • Decreases electron flow to oxygen, reducing ATP synthesis and increasing anaerobic glycolysis
  • Uncouples proton gradient to increase heat production
  • Has no effect because oxygen is not required

Correct Answer: Decreases electron flow to oxygen, reducing ATP synthesis and increasing anaerobic glycolysis

Q39. How does cyanide poisoning rapidly cause cellular failure?

  • By binding to Complex I and preventing NADH oxidation
  • By inhibiting Complex IV, blocking electron transfer to oxygen and halting ATP synthesis
  • By acting as an uncoupler to dissipate ΔpH
  • By blocking ATP synthase directly

Correct Answer: By inhibiting Complex IV, blocking electron transfer to oxygen and halting ATP synthesis

Q40. Which parameter is commonly measured to assess mitochondrial respiratory activity in vitro?

  • Glucose concentration only
  • Oxygen consumption rate (OCR)
  • Membrane cholesterol content
  • pH of the cytosol only

Correct Answer: Oxygen consumption rate (OCR)

Q41. Which metal ion is essential in cytochrome c oxidase for the reduction of O2?

  • Magnesium
  • Calcium
  • Copper and iron
  • Zinc only

Correct Answer: Copper and iron

Q42. P/O ratio for NADH is approximately:

  • 0.5 ATP per O atom
  • 2.5 ATP per pair of electrons to O (approx. 2.5 per NADH)
  • 1 ATP per NADH
  • 4 ATP per NADH always

Correct Answer: 2.5 ATP per pair of electrons to O (approx. 2.5 per NADH)

Q43. Which statement about proton leak is correct?

  • Proton leak always increases ATP synthesis efficiency
  • Proton leak reduces coupling efficiency and can generate heat
  • Proton leak is identical to ATP synthase activity
  • Proton leak is only observed in bacterial cells

Correct Answer: Proton leak reduces coupling efficiency and can generate heat

Q44. Which drug interferes with electron flow between Complex I and CoQ by binding to the NADH dehydrogenase site?

  • Antimycin A
  • Rotenone
  • Oligomycin
  • 2,4-DNP

Correct Answer: Rotenone

Q45. What is the immediate electron acceptor for Complex IV to complete reduction of oxygen to water?

  • Cytochrome c
  • Oxygen directly accepts electrons within Complex IV active site and is reduced to water
  • Ubiquinone (CoQ)
  • ATP

Correct Answer: Oxygen directly accepts electrons within Complex IV active site and is reduced to water

Q46. Which technique can be used to measure ATP production linked to oxidative phosphorylation?

  • Western blot of cytochrome c only
  • Luciferase-based ATP assay
  • Measurement of DNA content
  • Protein glycosylation assay

Correct Answer: Luciferase-based ATP assay

Q47. During the Q-cycle at Complex III, ubiquinone is:

  • Oxidized and reduced in a mechanism that contributes to proton translocation
  • Permanently reduced to ubiquinol without recycling
  • Transported into the matrix to synthesize ATP
  • Converted directly into cytochrome c

Correct Answer: Oxidized and reduced in a mechanism that contributes to proton translocation

Q48. Which physiological process uses mitochondrial uncoupling proteins to generate heat?

  • Shivering thermogenesis
  • Non-shivering thermogenesis in brown adipose tissue via UCP1
  • ATP-dependent muscle contraction
  • Gluconeogenesis

Correct Answer: Non-shivering thermogenesis in brown adipose tissue via UCP1

Q49. Which of the following best describes how oxidative phosphorylation is regulated?

  • Fixed rate independent of cellular energy status
  • Primarily regulated by ADP availability, substrate supply (NADH/FADH2), and oxygen
  • Regulated exclusively by mitochondrial DNA expression
  • Regulated by cytosolic calcium only

Correct Answer: Primarily regulated by ADP availability, substrate supply (NADH/FADH2), and oxygen

Q50. Which of the following is NOT a typical consequence of impaired oxidative phosphorylation?

  • Decreased cellular ATP levels
  • Increased lactic acid production due to anaerobic glycolysis
  • Excessive ROS generation and oxidative damage
  • Enhanced oxidative ATP production leading to hyperactive metabolism

Correct Answer: Enhanced oxidative ATP production leading to hyperactive metabolism

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