Hexose monophosphate (HMP) shunt, also known as the pentose phosphate pathway (PPP), is a vital cellular route that generates reducing power and biosynthetic precursors. For B. Pharm students, understanding HMP shunt fundamentals — NADPH production, ribose-5-phosphate synthesis, oxidative and non-oxidative phases, and regulation — is essential for pharmacology, drug metabolism, and biochemical pathway integration. This concise review highlights enzyme functions (glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, transketolase), clinical correlations, and metabolic flux under oxidative stress. Targeted practice with pathway MCQs reinforces key concepts, mechanism details, and clinical significance to prepare you for exams and applied pharmaceutical problems. Now let’s test your knowledge with 50 MCQs on this topic.
Q1. What are the primary products of the oxidative phase of the HMP shunt?
- NADH and ATP
- NADPH and ribose-5-phosphate
- Pyruvate and ATP
Correct Answer: NADPH and ribose-5-phosphate
Q2. Which enzyme catalyzes the first and rate-limiting step of the oxidative pentose phosphate pathway?
- Transketolase
- Glucose-6-phosphate dehydrogenase
- Ribose-5-phosphate isomerase
- 6-Phosphogluconate dehydrogenase
Correct Answer: Glucose-6-phosphate dehydrogenase
Q3. How many molecules of NADPH are produced per molecule of glucose-6-phosphate oxidized through the oxidative phase?
- One
- Two
- Three
- Four
Correct Answer: Two
Q4. Which cofactor is required by transketolase in the non-oxidative phase?
- NADH
- Thiamine pyrophosphate (TPP)
- Biotin
- FAD
Correct Answer: Thiamine pyrophosphate (TPP)
Q5. Which metabolite enters the HMP shunt as the starting substrate?
- Glucose
- Fructose-6-phosphate
- Glucose-6-phosphate
- Pyruvate
Correct Answer: Glucose-6-phosphate
Q6. Which cellular location hosts the HMP shunt in mammalian cells?
- Mitochondrial matrix
- Cytosol
- Nucleus
Correct Answer: Cytosol
Q7. A deficiency of which enzyme leads to the most common inherited disorder affecting the HMP shunt?
- Transaldolase
- Glucose-6-phosphate dehydrogenase
- Ribulose-5-phosphate epimerase
- 6-Phosphogluconolactonase
Correct Answer: Glucose-6-phosphate dehydrogenase
Q8. What clinical condition is most commonly associated with G6PD deficiency when exposed to oxidant drugs or fava beans?
- Microcytic anemia
- Hemolytic anemia
- Aplastic anemia
- Iron deficiency anemia
Correct Answer: Hemolytic anemia
Q9. Which product of the HMP shunt is essential for nucleotide (purine and pyrimidine) synthesis?
- Fructose-6-phosphate
- Ribose-5-phosphate
- Glyceraldehyde-3-phosphate
- Sedoheptulose-7-phosphate
Correct Answer: Ribose-5-phosphate
Q10. Which molecule is a direct feedback inhibitor of glucose-6-phosphate dehydrogenase?
- NADH
- ATP
- NADPH
- ADP
Correct Answer: NADPH
Q11. Which enzyme catalyzes the oxidative decarboxylation that releases CO2 in the HMP shunt?
- Ribose-5-phosphate isomerase
- 6-Phosphogluconate dehydrogenase
- Transketolase
- Glucose-6-phosphate isomerase
Correct Answer: 6-Phosphogluconate dehydrogenase
Q12. The non-oxidative phase of the HMP shunt is characterized by what type of reactions?
- Irreversible oxidations
- Reversible sugar interconversions
- ATP-generation steps
- Oxidative phosphorylation
Correct Answer: Reversible sugar interconversions
Q13. Which two glycolytic intermediates directly interconvert with the non-oxidative PPP products?
- Glucose and fructose
- Fructose-6-phosphate and glyceraldehyde-3-phosphate
- 3-Phosphoglycerate and phosphoenolpyruvate
- Pyruvate and oxaloacetate
Correct Answer: Fructose-6-phosphate and glyceraldehyde-3-phosphate
Q14. Why do erythrocytes heavily rely on the HMP shunt?
- To produce ATP by oxidative phosphorylation
- To generate NADPH for maintaining reduced glutathione and protect against oxidative damage
- To synthesize proteins
- To perform beta-oxidation of fatty acids
Correct Answer: To generate NADPH for maintaining reduced glutathione and protect against oxidative damage
Q15. Which test is commonly used as a screening method for G6PD deficiency in the laboratory?
- Glucose tolerance test
- Fluorescent spot test
- Coombs test
- Schilling test
Correct Answer: Fluorescent spot test
Q16. Which enzyme converts ribulose-5-phosphate to ribose-5-phosphate?
- Ribose-5-phosphate isomerase
- Ribulose kinase
- Transaldolase
- Phosphopentose epimerase
Correct Answer: Ribose-5-phosphate isomerase
Q17. Which enzyme catalyzes the epimerization of ribulose-5-phosphate to xylulose-5-phosphate?
- Ribulose-5-phosphate epimerase
- Transketolase
- 6-Phosphogluconate dehydrogenase
- Ribose-5-phosphate isomerase
Correct Answer: Ribulose-5-phosphate epimerase
Q18. In tissues requiring large amounts of NADPH for fatty acid synthesis, which pathway is especially active?
- Glycogenolysis
- HMP shunt (pentose phosphate pathway)
- Urea cycle
- Beta-oxidation
Correct Answer: HMP shunt (pentose phosphate pathway)
Q19. Which vitamin deficiency impairs transketolase activity and can be detected by measuring erythrocyte transketolase activation?
- Vitamin B1 (thiamine)
- Vitamin B2 (riboflavin)
- Vitamin B6 (pyridoxine)
- Vitamin B12 (cobalamin)
Correct Answer: Vitamin B1 (thiamine)
Q20. Which of the following best describes the role of NADPH generated by the HMP shunt in drug metabolism?
- NADPH donates electrons to cytochrome P450 reductase supporting phase I detoxification
- NADPH is used as an energy source for active drug transport
- NADPH directly conjugates drugs in phase II reactions
- NADPH inhibits cytochrome P450 enzymes
Correct Answer: NADPH donates electrons to cytochrome P450 reductase supporting phase I detoxification
Q21. Which metabolic change would stimulate flux through the oxidative pentose phosphate pathway?
- High ATP and low NADP+ concentration
- High NADPH levels
- Elevated demand for NADPH (e.g., oxidative stress)
- Increased AMP-activated protein kinase activity
Correct Answer: Elevated demand for NADPH (e.g., oxidative stress)
Q22. Sedoheptulose-7-phosphate is produced during which phase of the HMP shunt?
- Oxidative phase
- Non-oxidative phase
- Glycolytic phase
- TCA cycle
Correct Answer: Non-oxidative phase
Q23. Which statement about the non-oxidative pentose phosphate pathway is correct?
- It produces NADPH directly
- It involves irreversible decarboxylation reactions
- It allows interconversion of sugars of different chain lengths
- It generates ATP
Correct Answer: It allows interconversion of sugars of different chain lengths
Q24. Which enzyme transfers a three-carbon unit (aldol transfer) during the non-oxidative PPP?
- Transketolase
- Transaldolase
- Ribose-5-phosphate isomerase
- Glucose-6-phosphate dehydrogenase
Correct Answer: Transaldolase
Q25. Which carbon of glucose is released as CO2 during the oxidative pentose phosphate pathway?
- Carbon 1 (C1)
- Carbon 2 (C2)
- Carbon 3 (C3)
- Carbon 6 (C6)
Correct Answer: Carbon 1 (C1)
Q26. In rapidly proliferating cells requiring nucleotides, which HMP shunt mode predominates?
- High oxidative flux only to produce NADPH
- Non-oxidative interconversion to supply ribose-5-phosphate without producing much NADPH
- Complete shutdown of PPP
- Direct conversion of pyruvate to ribose
Correct Answer: Non-oxidative interconversion to supply ribose-5-phosphate without producing much NADPH
Q27. Which of the following enzymes is NOT part of the pentose phosphate pathway?
- Glucose-6-phosphate dehydrogenase
- Phosphofructokinase-1
- Transketolase
- Ribulose-5-phosphate epimerase
Correct Answer: Phosphofructokinase-1
Q28. How does a cell that needs both NADPH and ATP typically coordinate HMP shunt and glycolysis?
- Shunt all G6P into PPP and stop glycolysis
- Use non-oxidative PPP to convert pentoses back to glycolytic intermediates for ATP production while oxidative PPP supplies NADPH
- Rely solely on mitochondrial NADPH production
- Convert ATP to NADPH directly
Correct Answer: Use non-oxidative PPP to convert pentoses back to glycolytic intermediates for ATP production while oxidative PPP supplies NADPH
Q29. Which cofactor is used by 6-phosphogluconate dehydrogenase?
- NAD+
- NADP+
- FAD
- CoA
Correct Answer: NADP+
Q30. Which of the following best explains why G6PD-deficient individuals are susceptible to oxidative drug-induced hemolysis?
- They cannot metabolize drugs in the liver
- They have reduced NADPH generation, impairing glutathione recycling required to neutralize reactive oxygen species
- They lack hemoglobin altogether
- They overproduce NADPH leading to redox imbalance
Correct Answer: They have reduced NADPH generation, impairing glutathione recycling required to neutralize reactive oxygen species
Q31. Which pentose phosphate pathway enzyme deficiency can be used as a functional assay for thiamine status?
- Transketolase
- 6-Phosphogluconate dehydrogenase
- Glucose-6-phosphate dehydrogenase
- Ribose-5-phosphate isomerase
Correct Answer: Transketolase
Q32. Which molecule produced by the HMP shunt is critical for maintaining reduced glutathione levels?
- ATP
- NADPH
- FADH2
- Coenzyme A
Correct Answer: NADPH
Q33. Which enzyme directly converts 6-phosphogluconolactone to 6-phosphogluconate?
- 6-Phosphogluconolactonase
- Glucose-6-phosphate dehydrogenase
- Ribulose-5-phosphate isomerase
- Transaldolase
Correct Answer: 6-Phosphogluconolactonase
Q34. The PPP provides NADPH for which biosynthetic process?
- Glycogen breakdown
- Fatty acid and cholesterol synthesis
- Protein translation
- Urea synthesis
Correct Answer: Fatty acid and cholesterol synthesis
Q35. Which sugar phosphate produced in the non-oxidative PPP contains seven carbons?
- Sedoheptulose-7-phosphate
- Ribose-5-phosphate
- Xylulose-5-phosphate
- Glyceraldehyde-3-phosphate
Correct Answer: Sedoheptulose-7-phosphate
Q36. Which PPP enzyme deficiency is most likely to present clinically with neonatal jaundice or hemolysis?
- Glucose-6-phosphate dehydrogenase deficiency
- Transaldolase deficiency
- Ribulose-5-phosphate epimerase deficiency
- 6-Phosphogluconolactonase deficiency
Correct Answer: Glucose-6-phosphate dehydrogenase deficiency
Q37. During oxidative stress, the HMP shunt activity increases primarily to supply which protective factor?
- ATP for repair enzymes
- Reduced glutathione via NADPH
- FADH2 for electron transport
- Oxygen radicals to signal apoptosis
Correct Answer: Reduced glutathione via NADPH
Q38. Which statement is true about the pentose phosphate pathway in bacteria and plants?
- PPP is found only in animals
- PPP is absent in bacteria
- PPP operates in most organisms including bacteria and plants
- PPP functions only in chloroplasts
Correct Answer: PPP operates in most organisms including bacteria and plants
Q39. Which molecule directly donates reducing equivalents for glutathione reductase to regenerate GSH?
- NADH
- NADPH
- FADH2
- ATP
Correct Answer: NADPH
Q40. Which of the following conditions would decrease flux through G6PD?
- Increased NADP+ availability
- High oxidative stress
- Accumulation of NADPH
- Rapid cell proliferation requiring nucleotides
Correct Answer: Accumulation of NADPH
Q41. Which product is formed when ribulose-5-phosphate is isomerized?
- Fructose-6-phosphate
- Ribose-5-phosphate
- Glyceraldehyde-3-phosphate
- Pyruvate
Correct Answer: Ribose-5-phosphate
Q42. Which HMP shunt enzyme activity increases during insulin-stimulated lipogenesis?
- Transaldolase
- Glucose-6-phosphate dehydrogenase
- Ribulose-5-phosphate epimerase
- Pyruvate kinase
Correct Answer: Glucose-6-phosphate dehydrogenase
Q43. Which of these is a correct application of PPP knowledge in pharmacology?
- Predicting drug solubility in lipids
- Understanding NADPH-dependent drug metabolism and oxidative drug toxicity
- Designing peptide bond formation inhibitors
- Estimating oral bioavailability of antibiotics
Correct Answer: Understanding NADPH-dependent drug metabolism and oxidative drug toxicity
Q44. Which enzyme links pentose phosphates back to glycolysis by producing fructose-6-phosphate?
- Transketolase and transaldolase in combination
- 6-Phosphogluconate dehydrogenase alone
- Pyruvate kinase
- Glucose-6-phosphate dehydrogenase
Correct Answer: Transketolase and transaldolase in combination
Q45. Which metabolic fate best describes ribose-5-phosphate generated by the HMP shunt in proliferating tissues?
- Used for amino acid catabolism
- Converted to ATP in mitochondria
- Used for nucleotide and nucleic acid synthesis
- Exported as CO2
Correct Answer: Used for nucleotide and nucleic acid synthesis
Q46. Which of the following enzymes requires no vitamin-derived cofactor?
- Transketolase
- Glucose-6-phosphate dehydrogenase
- Pyruvate dehydrogenase
- Biotin-dependent carboxylase
Correct Answer: Glucose-6-phosphate dehydrogenase
Q47. Which PPP reaction is irreversible under physiological conditions?
- Transaldolase reactions
- Oxidative dehydrogenation of glucose-6-phosphate by G6PD
- Interconversion of sugar phosphates by transketolase
- Isomerization of ribulose-5-phosphate
Correct Answer: Oxidative dehydrogenation of glucose-6-phosphate by G6PD
Q48. What is the primary consequence in hepatocytes when PPP-derived NADPH is insufficient?
- Enhanced gluconeogenesis
- Impaired fatty acid and cholesterol synthesis and reduced detoxification capacity
- Increased ketone body formation
- Excessive glycogen storage
Correct Answer: Impaired fatty acid and cholesterol synthesis and reduced detoxification capacity
Q49. Which reaction in the PPP results in production of xylulose-5-phosphate?
- Ribose-5-phosphate isomerization
- Ribulose-5-phosphate epimerization
- 6-Phosphogluconate decarboxylation to ribulose-5-phosphate
- Transaldolase transferring three-carbon unit
Correct Answer: Ribulose-5-phosphate epimerization
Q50. Which of the following accurately summarizes the role of the HMP shunt in cellular physiology?
- Produces ATP and NADH for energy
- Generates NADPH for reductive biosynthesis and antioxidant defense, and provides ribose-5-phosphate for nucleotide synthesis
- Directly oxidizes fatty acids to acetyl-CoA
- Stores glucose as glycogen
Correct Answer: Generates NADPH for reductive biosynthesis and antioxidant defense, and provides ribose-5-phosphate for nucleotide synthesis
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