HMP shunt – significance MCQs With Answer

HMP shunt – significance MCQs With Answer

The HMP shunt, also called the hexose monophosphate pathway (HMP) or pentose phosphate pathway (PPP), is a central metabolic route B.Pharm students must master. It produces NADPH for biosynthetic reactions and antioxidant defense, and ribose‑5‑phosphate for nucleotide synthesis. Located in the cytosol, the pathway links to glycolysis via fructose‑6‑phosphate and glyceraldehyde‑3‑phosphate. Key enzymes like glucose‑6‑phosphate dehydrogenase and transketolase determine flux, while clinical aspects—G6PD deficiency, drug‑induced hemolysis, cancer metabolism—have direct pharmaceutical relevance. Understanding regulation, clinical implications, and assay methods enhances pharmacology, toxicology and therapeutics competence. Now let’s test your knowledge with 50 MCQs on this topic.

Q1. What is another common name for the HMP shunt?

  • Glycolytic pathway
  • Tricarboxylic acid cycle
  • Pentose phosphate pathway
  • Urea cycle

Correct Answer: Pentose phosphate pathway

Q2. What are the primary biochemical products of the oxidative phase of the HMP shunt?

  • ATP and CO2
  • NADH and ribose‑5‑phosphate
  • NADPH and ribose‑5‑phosphate
  • FADH2 and glycerol

Correct Answer: NADPH and ribose‑5‑phosphate

Q3. In which cellular compartment does the HMP shunt primarily occur?

  • Mitochondrial matrix
  • Cytosol
  • Lysosome
  • Endoplasmic reticulum lumen

Correct Answer: Cytosol

Q4. Which enzyme catalyzes the first and rate‑limiting step of the oxidative HMP shunt?

  • Transketolase
  • 6‑Phosphogluconate dehydrogenase
  • Glucose‑6‑phosphate dehydrogenase
  • Phosphoglucose isomerase

Correct Answer: Glucose‑6‑phosphate dehydrogenase

Q5. Which cofactor is produced by the HMP shunt and is essential for fatty acid synthesis?

  • ATP
  • NADH
  • NADPH
  • CoA

Correct Answer: NADPH

Q6. Which enzyme links the pentose phosphate pathway to thiamine status in the body?

  • Transketolase
  • Glucose‑6‑phosphate dehydrogenase
  • Pyruvate kinase
  • 6‑Phosphogluconolactonase

Correct Answer: Transketolase

Q7. Which vitamin is a required cofactor for transketolase activity?

  • Vitamin B12
  • Vitamin B1 (thiamine)
  • Vitamin B6 (pyridoxine)
  • Vitamin C (ascorbic acid)

Correct Answer: Vitamin B1 (thiamine)

Q8. Ribose‑5‑phosphate produced by the HMP shunt is directly used for:

  • Fatty acid elongation
  • Cholesterol esterification
  • Nucleotide and nucleic acid synthesis
  • Protein glycosylation

Correct Answer: Nucleotide and nucleic acid synthesis

Q9. Which enzyme deficiency is classically associated with hemolytic anemia triggered by oxidative drugs?

  • Transaldolase deficiency
  • Glucose‑6‑phosphate dehydrogenase deficiency
  • Phosphofructokinase deficiency
  • Hexokinase deficiency

Correct Answer: Glucose‑6‑phosphate dehydrogenase deficiency

Q10. How does NADPH protect red blood cells from oxidative damage?

  • By producing superoxide radicals
  • By regenerating reduced glutathione via glutathione reductase
  • By directly binding hemoglobin
  • By increasing ATP synthesis

Correct Answer: By regenerating reduced glutathione via glutathione reductase

Q11. Which enzyme hydrolyzes 6‑phosphogluconolactone to 6‑phosphogluconate?

  • 6‑Phosphogluconolactonase
  • 6‑Phosphogluconate dehydrogenase
  • Glucose‑6‑phosphate dehydrogenase
  • Ribulose‑5‑phosphate epimerase

Correct Answer: 6‑Phosphogluconolactonase

Q12. Which enzyme catalyzes a decarboxylation that produces CO2 in the oxidative phase of the HMP shunt?

  • Glucose‑6‑phosphate dehydrogenase
  • 6‑Phosphogluconate dehydrogenase
  • Transketolase
  • Ribose‑5‑phosphate isomerase

Correct Answer: 6‑Phosphogluconate dehydrogenase

Q13. When a cell needs only NADPH and not ribose‑5‑phosphate, the non‑oxidative reactions of PPP:

  • Convert ribose‑5‑phosphate into glycolytic intermediates that can be recycled to glucose‑6‑phosphate
  • Irreversibly degrade ribose‑5‑phosphate to CO2
  • Divert all carbons to the TCA cycle
  • Produce large amounts of ATP

Correct Answer: Convert ribose‑5‑phosphate into glycolytic intermediates that can be recycled to glucose‑6‑phosphate

Q14. Which non‑oxidative enzyme transfers two‑carbon units between sugar phosphates?

  • Transaldolase
  • Transketolase
  • Ribose‑5‑phosphate isomerase
  • Glucose‑6‑phosphate dehydrogenase

Correct Answer: Transketolase

Q15. The HMP shunt is especially active in tissues with high demands for NADPH. Which tissue is a prime example?

  • Skeletal muscle during exercise
  • Red blood cells and liver (lipogenesis)
  • Brain neurons at rest
  • Cardiac myocytes under ischemia

Correct Answer: Red blood cells and liver (lipogenesis)

Q16. Which statement best explains why rapidly dividing cells often upregulate the HMP shunt?

  • To increase ATP production for mitosis
  • To supply ribose‑5‑phosphate for nucleotide synthesis and NADPH for biosynthesis
  • To oxidize fatty acids faster
  • To produce more CO2 for buffering

Correct Answer: To supply ribose‑5‑phosphate for nucleotide synthesis and NADPH for biosynthesis

Q17. The activity of glucose‑6‑phosphate dehydrogenase is stimulated by:

  • High NADPH concentrations
  • Low NADP+ concentrations
  • High NADP+ concentrations
  • Low glucose‑6‑phosphate levels

Correct Answer: High NADP+ concentrations

Q18. Which genetic pattern describes the inheritance of classic G6PD deficiency?

  • Autosomal dominant
  • Autosomal recessive
  • X‑linked recessive
  • Mitochondrial inheritance

Correct Answer: X‑linked recessive

Q19. Which laboratory finding is characteristic of G6PD deficiency after oxidative stress?

  • Increased reduced glutathione
  • Presence of Heinz bodies and bite cells in peripheral smear
  • Elevated NADPH levels
  • Increased hemoglobin concentration

Correct Answer: Presence of Heinz bodies and bite cells in peripheral smear

Q20. Which drug class is known to precipitate hemolysis in G6PD‑deficient patients?

  • Benzodiazepines
  • Sulfonamides and certain antimalarials (e.g., primaquine)
  • ACE inhibitors
  • Statins

Correct Answer: Sulfonamides and certain antimalarials (e.g., primaquine)

Q21. NADPH generated by the HMP shunt is used by which enzyme system in phagocytes for the respiratory burst?

  • NADPH oxidase
  • Cytochrome c oxidase
  • ATP synthase
  • Glutathione peroxidase

Correct Answer: NADPH oxidase

Q22. Which metabolite is the direct substrate that enters the HMP shunt?

  • Fructose
  • Glucose‑6‑phosphate
  • Pyruvate
  • Acetyl‑CoA

Correct Answer: Glucose‑6‑phosphate

Q23. Ribulose‑5‑phosphate can be converted into which two pentose sugars in the non‑oxidative phase?

  • Glucose and fructose
  • Ribose‑5‑phosphate and xylulose‑5‑phosphate
  • Glyceraldehyde and dihydroxyacetone
  • Sucrose and lactose

Correct Answer: Ribose‑5‑phosphate and xylulose‑5‑phosphate

Q24. Which enzyme interconverts ribulose‑5‑phosphate and ribose‑5‑phosphate?

  • Ribose‑5‑phosphate isomerase
  • Transketolase
  • G6PD
  • Pyruvate dehydrogenase

Correct Answer: Ribose‑5‑phosphate isomerase

Q25. Which metabolic need would drive flux through the non‑oxidative phase in the direction of glycolytic intermediates?

  • High need for ribose‑5‑phosphate and low NADPH demand
  • High NADPH requirement with no need for ribose‑5‑phosphate
  • Complete absence of glucose
  • Excess ATP synthesis requirement

Correct Answer: High NADPH requirement with no need for ribose‑5‑phosphate

Q26. A pharmacology student learns that cytochrome P450 monooxygenases require NADPH. Which pathway supplies much of this NADPH in hepatocytes?

  • Glycolysis
  • HMP shunt (PPP)
  • TCA cycle
  • Beta‑oxidation

Correct Answer: HMP shunt (PPP)

Q27. Which enzyme transfers a three‑carbon unit between sugars in the non‑oxidative phase?

  • Transketolase
  • Transaldolase
  • Ribulose‑5‑phosphate epimerase
  • 6‑Phosphogluconate dehydrogenase

Correct Answer: Transaldolase

Q28. Increased cellular demand for fatty acid synthesis would most directly increase flux through which part of the HMP shunt?

  • Non‑oxidative phase only
  • Oxidative phase to generate NADPH
  • Only pentose interconversion enzymes
  • Complete shutdown of PPP

Correct Answer: Oxidative phase to generate NADPH

Q29. Which laboratory assay is commonly used to assess HMP shunt activity or G6PD function?

  • Serum creatinine measurement
  • G6PD enzyme activity assay measuring NADPH formation
  • Hemoglobin A1c test
  • Serum amylase

Correct Answer: G6PD enzyme activity assay measuring NADPH formation

Q30. Which statement best describes the energy yield of the HMP shunt?

  • It directly produces large amounts of ATP
  • It does not generate ATP but provides reducing power and ribose
  • It produces both ATP and FADH2
  • It is the main source of ATP in erythrocytes

Correct Answer: It does not generate ATP but provides reducing power and ribose

Q31. Which enzyme converts ribulose‑5‑phosphate into xylulose‑5‑phosphate?

  • Ribulose‑5‑phosphate epimerase
  • Ribose‑5‑phosphate isomerase
  • Transaldolase
  • Transketolase

Correct Answer: Ribulose‑5‑phosphate epimerase

Q32. In thiamine deficiency, which HMP enzyme‑linked activity is decreased and may affect carbohydrate metabolism?

  • Glucose‑6‑phosphate dehydrogenase activity
  • Transketolase activity
  • Ribose‑5‑phosphate isomerase activity
  • 6‑Phosphogluconate dehydrogenase activity

Correct Answer: Transketolase activity

Q33. Which metabolic intermediate from glycolysis can enter the non‑oxidative PPP reversibly?

  • Phosphoenolpyruvate
  • Glyceraldehyde‑3‑phosphate
  • Lactate
  • Oxaloacetate

Correct Answer: Glyceraldehyde‑3‑phosphate

Q34. Which enzyme in the HMP shunt is most directly inhibited by high NADPH levels?

  • Transaldolase
  • Glucose‑6‑phosphate dehydrogenase
  • Transketolase
  • Ribose‑5‑phosphate isomerase

Correct Answer: Glucose‑6‑phosphate dehydrogenase

Q35. Which of the following best describes the clinical importance of PPP activity in the liver?

  • Supports gluconeogenesis only
  • Provides NADPH for lipogenesis and drug detoxification by cytochrome P450
  • Is the major source of mitochondrial ATP
  • Produces bile salts directly

Correct Answer: Provides NADPH for lipogenesis and drug detoxification by cytochrome P450

Q36. A B.Pharm student studying anticancer strategies learns targeting PPP can limit nucleotide synthesis. Which PPP product is most directly linked to nucleotide biosynthesis?

  • Xylulose‑5‑phosphate
  • Ribose‑5‑phosphate
  • Fructose‑6‑phosphate
  • Glyceraldehyde‑3‑phosphate

Correct Answer: Ribose‑5‑phosphate

Q37. Which compound provides the activated ribose donor PRPP used in nucleotide synthesis and is derived from PPP product?

  • Ribose‑5‑phosphate via ribose‑phosphate diphosphokinase
  • Fructose‑1,6‑bisphosphate
  • Acetyl‑CoA
  • Phosphoenolpyruvate

Correct Answer: Ribose‑5‑phosphate via ribose‑phosphate diphosphokinase

Q38. Which of these drugs is known to inhibit G6PD experimentally and used in research to study NADPH depletion?

  • 6‑Aminonicotinamide
  • Metformin
  • Atorvastatin
  • Propranolol

Correct Answer: 6‑Aminonicotinamide

Q39. In conditions of oxidative stress, what happens to the cellular ratio of NADP+ to NADPH and PPP flux?

  • NADP+ decreases and PPP flux decreases
  • NADP+ increases and PPP flux increases
  • NADPH increases and PPP flux decreases
  • No change in ratio or flux

Correct Answer: NADP+ increases and PPP flux increases

Q40. Which pathology is directly linked to impaired NADPH production in RBCs?

  • Sickle cell disease
  • G6PD deficiency–related hemolytic anemia
  • Polycythemia vera
  • Iron deficiency anemia

Correct Answer: G6PD deficiency–related hemolytic anemia

Q41. Transketolase and transaldolase reactions in the non‑oxidative PPP primarily allow cells to:

  • Generate ATP from pentoses
  • Interconvert sugars of different chain lengths between PPP and glycolysis
  • Export pentoses out of the cell
  • Oxidize NADPH to NADP+

Correct Answer: Interconvert sugars of different chain lengths between PPP and glycolysis

Q42. Which of the following is NOT a physiological use of NADPH?

  • Fatty acid synthesis
  • Cholesterol biosynthesis
  • Oxidative phosphorylation to make ATP
  • Glutathione regeneration

Correct Answer: Oxidative phosphorylation to make ATP

Q43. Which intermediate generated by the non‑oxidative PPP can reenter glycolysis?

  • Ribose‑5‑phosphate only
  • Fructose‑6‑phosphate and glyceraldehyde‑3‑phosphate
  • Glucose‑1‑phosphate
  • Citrate

Correct Answer: Fructose‑6‑phosphate and glyceraldehyde‑3‑phosphate

Q44. Which enzyme deficiency would most directly impair the production of ribose‑5‑phosphate from glucose‑6‑phosphate?

  • Hexokinase deficiency
  • Glucose‑6‑phosphate dehydrogenase deficiency
  • Pyruvate kinase deficiency
  • Citrate synthase deficiency

Correct Answer: Glucose‑6‑phosphate dehydrogenase deficiency

Q45. Which clinical scenario is most likely to increase PPP activity in hepatocytes?

  • Fasting state with high glucagon
  • Fed state with high insulin and active lipogenesis
  • Starvation with muscle breakdown
  • Prolonged exercise with depleted glycogen

Correct Answer: Fed state with high insulin and active lipogenesis

Q46. Which laboratory change indicates impaired antioxidant capacity due to PPP dysfunction?

  • Increased NADPH and increased reduced glutathione
  • Decreased NADPH and decreased reduced glutathione
  • Elevated ATP and increased reduced glutathione
  • Decreased lactate only

Correct Answer: Decreased NADPH and decreased reduced glutathione

Q47. Which enzyme in the PPP is commonly assayed to diagnose chronic thiamine deficiency by measuring its activity boost after thiamine addition?

  • Glucose‑6‑phosphate dehydrogenase
  • Transketolase
  • Ribose‑5‑phosphate isomerase
  • 6‑Phosphogluconate dehydrogenase

Correct Answer: Transketolase

Q48. How does the HMP shunt influence drug metabolism in the liver?

  • Provides NADPH for cytochrome P450 reactions required for phase I metabolism
  • Directly conjugates drugs in phase II reactions
  • Breaks down drugs into amino acids
  • Exports drugs unchanged to bile

Correct Answer: Provides NADPH for cytochrome P450 reactions required for phase I metabolism

Q49. Which metabolic fate occurs when cells require both NADPH and ribose‑5‑phosphate simultaneously?

  • Oxidative phase produces NADPH and ribose‑5‑phosphate directly
  • Only glycolysis is used
  • PPP is suppressed
  • Cells produce only ATP from glucose

Correct Answer: Oxidative phase produces NADPH and ribose‑5‑phosphate directly

Q50. Targeting PPP enzymes is being explored as an anticancer strategy because:

  • Cancer cells do not use NADPH
  • PPP provides ribose for nucleotides and NADPH for anabolic growth, supporting proliferation
  • PPP is the principal source of mitochondrial ATP in tumors
  • Inhibiting PPP increases blood glucose levels to starve tumors

Correct Answer: PPP provides ribose for nucleotides and NADPH for anabolic growth, supporting proliferation

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