Biosynthesis of purine nucleotides MCQs With Answer
The biosynthesis of purine nucleotides is a core topic for B. Pharm students, covering enzymes, intermediates, regulation and clinical implications. This concise, student-focused resource includes MCQs on PRPP synthesis, the committed step by amidophosphoribosyltransferase, N10-formyl-THF roles, IMP formation, branch pathways to AMP and GMP, salvage enzymes like HGPRT/APRT, and drug targets (allopurinol, 6-mercaptopurine, methotrexate). Emphasis is on mechanism, feedback regulation and pharmacological relevance to diseases such as gout and Lesch-Nyhan syndrome. Ideal for exam preparation and deeper conceptual understanding of purine biosynthesis and therapeutic interventions. Now let’s test your knowledge with 50 MCQs on this topic.
Q1. Which enzyme synthesizes PRPP from ribose-5-phosphate?
- Glucose-6-phosphate dehydrogenase
- PRPP synthetase (ribose-phosphate diphosphokinase)
- Phosphoribosylpyrophosphate amidotransferase
- Transketolase
Correct Answer: PRPP synthetase (ribose-phosphate diphosphokinase)
Q2. What is the committed (first regulatory) step in de novo purine biosynthesis?
- Conversion of IMP to AMP
- Synthesis of PRPP from ribose-5-phosphate
- Amidation of PRPP to 5-phosphoribosylamine by amidophosphoribosyltransferase
- Formylation of GAR by GAR transformylase
Correct Answer: Amidation of PRPP to 5-phosphoribosylamine by amidophosphoribosyltransferase
Q3. Which amino acid provides the amide nitrogen in the reaction catalyzed by amidophosphoribosyltransferase?
- Glutamine
- Asparagine
- Glycine
- Aspartate
Correct Answer: Glutamine
Q4. Which cofactor donates formyl groups during formation of FGAR and FGAM steps?
- Biotin
- NADH
- N10-formyl-tetrahydrofolate (N10-formyl-THF)
- S-adenosylmethionine (SAM)
Correct Answer: N10-formyl-tetrahydrofolate (N10-formyl-THF)
Q5. GAR synthetase catalyzes which reaction?
- Conversion of IMP to XMP
- Condensation of glycine with 5-phosphoribosylamine to form GAR
- Removal of formyl group from FGAR
- Formation of PRPP from ribose-5-phosphate
Correct Answer: Condensation of glycine with 5-phosphoribosylamine to form GAR
Q6. The enzyme that converts IMP to AMP requires which nucleotide as an energy source?
- ATP
- GTP
- CTP
- UTP
Correct Answer: GTP
Q7. Conversion of IMP to GMP involves which initial enzyme activity?
- Adenylosuccinate synthetase
- IMP dehydrogenase that oxidizes IMP to XMP
- GMP reductase
- AMP deaminase
Correct Answer: IMP dehydrogenase that oxidizes IMP to XMP
Q8. Purine biosynthesis consumes N10-formyl-THF twice. These reactions produce which intermediates?
- GAR and AIR
- FGAR and FGAM
- FGAR and GAR transformylated products yielding formyl groups at two positions (GAR→FGAR and AICAR→FAICAR)
- PRA and IMP
Correct Answer: FGAR and GAR transformylated products yielding formyl groups at two positions (GAR→FGAR and AICAR→FAICAR)
Q9. Which drug inhibits dihydrofolate reductase and indirectly affects purine biosynthesis?
- Allopurinol
- Methotrexate
- Colchicine
- Febuxostat
Correct Answer: Methotrexate
Q10. Which enzyme salvages hypoxanthine to IMP using PRPP?
- HGPRT (hypoxanthine-guanine phosphoribosyltransferase)
- APRT (adenine phosphoribosyltransferase)
- Xanthine oxidase
- AMP deaminase
Correct Answer: HGPRT (hypoxanthine-guanine phosphoribosyltransferase)
Q11. Lesch-Nyhan syndrome results from deficiency of which enzyme?
- PRPP synthetase
- HGPRT
- IMP dehydrogenase
- GAR transformylase
Correct Answer: HGPRT
Q12. Which molecule is an allosteric inhibitor of phosphoribosylpyrophosphate amidotransferase?
- PRPP
- ATP
- IMP, AMP and GMP (purine nucleotides)
- ADP only
Correct Answer: IMP, AMP and GMP (purine nucleotides)
Q13. PRPP synthetase is activated by which metabolite?
- Inorganic phosphate (Pi)
- ATP exclusively
- AMP exclusively
- Urate
Correct Answer: Inorganic phosphate (Pi)
Q14. 6-Mercaptopurine (6-MP) primarily targets which aspect of purine metabolism?
- Salvage pathway activation
- De novo purine synthesis by inhibiting amidophosphoribosyltransferase after conversion to thio-IMP
- Enhancement of HGPRT activity
- Direct inhibition of xanthine oxidase
Correct Answer: De novo purine synthesis by inhibiting amidophosphoribosyltransferase after conversion to thio-IMP
Q15. Which enzyme converts adenine to AMP in the salvage pathway?
- HGPRT
- APRT (adenine phosphoribosyltransferase)
- Adenosine deaminase
- Xanthine oxidase
Correct Answer: APRT (adenine phosphoribosyltransferase)
Q16. Which intermediate is the branch point leading to IMP formation after several steps in purine biosynthesis?
- GAR
- AICAR (or AICAR ribotide)
- SAICAR
- FGAM
Correct Answer: AICAR (or AICAR ribotide)
Q17. IMP is converted to adenylosuccinate by which enzyme?
- Adenylosuccinate synthetase
- GMP synthetase
- IMP dehydrogenase
- Purine nucleoside phosphorylase
Correct Answer: Adenylosuccinate synthetase
Q18. The source of one-carbon units for purine rings is primarily:
- Formate only
- Tetrahydrofolate derivatives (N10-formyl-THF)
- S-adenosylmethionine
- Biotin
Correct Answer: Tetrahydrofolate derivatives (N10-formyl-THF)
Q19. IMP dehydrogenase is a key enzyme targeted for immunosuppression because it blocks synthesis of which nucleotide?
- ATP
- CTP
- GMP (and thus GTP)
- UMP
Correct Answer: GMP (and thus GTP)
Q20. Which enzyme catalyzes the conversion of hypoxanthine to xanthine in purine degradation?
- Xanthine oxidase
- HGPRT
- Adenosine deaminase
- Methyltransferase
Correct Answer: Xanthine oxidase
Q21. Allopurinol reduces uric acid production by inhibiting:
- PRPP synthetase
- Xanthine oxidase
- HGPRT
- AMP deaminase
Correct Answer: Xanthine oxidase
Q22. Which intermediate is directly converted into IMP in the final step of purine de novo synthesis?
- Inosine monophosphate is formed from AICAR-related intermediate (FAICAR) by ring closure
- GAR
- PRPP
- GMP
Correct Answer: Inosine monophosphate is formed from AICAR-related intermediate (FAICAR) by ring closure
Q23. Which enzyme provides the amino group when glutamine is used in purine biosynthesis beyond the committed step?
- Phosphoribosylformylglycinamidine synthase (FGAM synthetase)
- Gar transformylase
- IMP dehydrogenase
- Xanthine oxidase
Correct Answer: Phosphoribosylformylglycinamidine synthase (FGAM synthetase)
Q24. Which nucleotide is required as an energy source for GMP synthesis from XMP?
- GTP
- CTP
- ATP
- UTP
Correct Answer: ATP
Q25. Overactivity of PRPP synthetase can lead to increased purine synthesis and predispose to:
- Megaloblastic anemia
- Gout due to hyperuricemia
- Hypouricemia
- Renal tubular acidosis
Correct Answer: Gout due to hyperuricemia
Q26. Which enzyme deficiency causes increased de novo purine synthesis due to lack of feedback inhibition and may cause gout?
- Adenylosuccinate lyase deficiency
- HGPRT deficiency (Lesch-Nyhan) leading to PRPP accumulation and increased de novo synthesis
- Xanthine oxidase deficiency
- PRPP synthetase deficiency
Correct Answer: HGPRT deficiency (Lesch-Nyhan) leading to PRPP accumulation and increased de novo synthesis
Q27. Which enzyme catalyzes the conversion of SAICAR to AICAR in purine biosynthesis?
- Adenylosuccinate synthetase
- SAICAR synthetase followed by SAICAR lyase (adenylosuccinate lyase)
- IMP dehydrogenase
- HGPRT
Correct Answer: SAICAR synthetase followed by SAICAR lyase (adenylosuccinate lyase)
Q28. Which intermediate is directly used to form the purine ring atoms contributed by glycine?
- GAR (glycinamide ribotide)
- PRA
- AICAR
- IMP
Correct Answer: GAR (glycinamide ribotide)
Q29. Which pharmacologic agent is a selective xanthine oxidase inhibitor distinct from allopurinol?
- Febuxostat
- Probenecid
- Methotrexate
- 6-Mercaptopurine
Correct Answer: Febuxostat
Q30. Which cofactor is essential for conversion steps that transfer one-carbon units in purine biosynthesis and must be regenerated by dihydrofolate reductase?
- Biotin
- Folate (THF derivatives)
- Pyridoxal phosphate
- Flavin adenine dinucleotide (FAD)
Correct Answer: Folate (THF derivatives)
Q31. AMP synthesis from IMP proceeds via adenylosuccinate; this step is inhibited by which product?
- GMP
- ATP
- AMP (feedback inhibition)
- IMP itself
Correct Answer: AMP (feedback inhibition)
Q32. The enzyme adenylosuccinate lyase deficiency leads to accumulation of which metabolites associated with neurological symptoms?
- SAICAR and adenylosuccinate (S-Ado)
- IMP and GMP
- PRPP and PRA
- Xanthine and urate
Correct Answer: SAICAR and adenylosuccinate (S-Ado)
Q33. Which of the following enzymes is a target for immunosuppressive drug mycophenolate mofetil?
- IMP dehydrogenase
- Adenylosuccinate synthetase
- GAR transformylase
- HGPRT
Correct Answer: IMP dehydrogenase
Q34. Which ribonucleotide is produced directly by salvage of guanine via HGPRT?
- GMP
- GTP
- Guanosine
- IMP
Correct Answer: GMP
Q35. Which purine biosynthetic enzyme requires ATP for activation of carboxyl group in adenylosuccinate formation?
- Adenylosuccinate synthetase (requires GTP for IMP→AMP branch, but uses GTP/ATP interplay)
- IMP dehydrogenase
- GMP synthetase (uses ATP in conversion of XMP to GMP)
- PRPP synthetase
Correct Answer: GMP synthetase (uses ATP in conversion of XMP to GMP)
Q36. Which enzyme deficiency causes immunodeficiency due to toxic accumulation of deoxyATP from adenosine metabolism?
- Adenosine deaminase (ADA) deficiency
- HGPRT deficiency
- Adenylosuccinate lyase deficiency
- IMP dehydrogenase deficiency
Correct Answer: Adenosine deaminase (ADA) deficiency
Q37. Which compound directly stimulates de novo purine synthesis by activating amidophosphoribosyltransferase?
- IMP
- PRPP (substrate activation)
- GMP
- AMP
Correct Answer: PRPP (substrate activation)
Q38. Which enzyme links purine salvage to PRPP availability and is inhibited when PRPP is low?
- HGPRT and APRT (both require PRPP and are sensitive to PRPP concentration)
- Xanthine oxidase
- IMP dehydrogenase
- Phosphoribosylpyrophosphate amidotransferase
Correct Answer: HGPRT and APRT (both require PRPP and are sensitive to PRPP concentration)
Q39. A drug that mimics folate and inhibits GAR transformylase would primarily affect which process?
- Purine de novo synthesis (formyl transfer steps)
- Pyrimidine degradation
- Protein glycosylation
- Lipid biosynthesis
Correct Answer: Purine de novo synthesis (formyl transfer steps)
Q40. Which enzyme catalyzes the conversion of inosine monophosphate (IMP) to xanthosine monophosphate (XMP) precursor for GMP?
- IMP dehydrogenase
- GMP synthetase
- Adenylosuccinate synthetase
- HGPRT
Correct Answer: IMP dehydrogenase
Q41. Which metabolite accumulates when xanthine oxidase is inhibited by allopurinol?
- Uric acid
- Xanthine and hypoxanthine (more soluble than urate)
- Guanine
- Adenine
Correct Answer: Xanthine and hypoxanthine (more soluble than urate)
Q42. Purine ring atoms derived from aspartate are incorporated at which step?
- Formation of GAR from PRA
- Aspartate contributes a nitrogen at the adenylosuccinate step (via adenylosuccinate synthetase) and also in purine ring as a nitrogen donor for one position
- During IMP to GMP conversion
- PRPP formation
Correct Answer: Aspartate contributes a nitrogen at the adenylosuccinate step (via adenylosuccinate synthetase) and also in purine ring as a nitrogen donor for one position
Q43. Which enzyme deficiency causes increased urinary excretion of orotic acid but is in pyrimidine pathway (included to test integration of nucleotide metabolism)?
- Orotic aciduria due to UMP synthase deficiency (pyrimidine pathway)
- HGPRT deficiency
- IMP dehydrogenase deficiency
- PRPP synthetase deficiency
Correct Answer: Orotic aciduria due to UMP synthase deficiency (pyrimidine pathway)
Q44. Which enzyme converts guanosine monophosphate (GMP) to guanosine and ultimately to guanine in degradation?
- GMP reductase
- Nucleotidase and nucleoside phosphorylase
- Xanthine oxidase
- HGPRT
Correct Answer: Nucleotidase and nucleoside phosphorylase
Q45. In purine biosynthesis, which step is directly coupled to ATP hydrolysis for activation when converting XMP to GMP?
- IMP to adenylosuccinate
- XMP to GMP by GMP synthetase (requires ATP and glutamine)
- PRA formation
- PRPP synthesis
Correct Answer: XMP to GMP by GMP synthetase (requires ATP and glutamine)
Q46. Which enzyme activity is fused in human cells to create multifunctional purinosome complexes that increase efficiency of purine biosynthesis?
- Single isolated enzymes only
- Multi-enzyme complexes involving GAR synthetase, FGAM synthetase and other enzymes in de novo pathway (purinosome assembly)
- Xanthine oxidase complexes
- HGPRT/APRT fusion
Correct Answer: Multi-enzyme complexes involving GAR synthetase, FGAM synthetase and other enzymes in de novo pathway (purinosome assembly)
Q47. Which metabolic intermediate links purine biosynthesis with AMP biosynthesis and urea cycle-intermediate aspartate contributions?
- AICAR only
- Adenylosuccinate (link between IMP and AMP; aspartate contributes)
- PRPP alone
- Xanthine
Correct Answer: Adenylosuccinate (link between IMP and AMP; aspartate contributes)
Q48. Which analytical lab parameter increases in overproduction of purines and is the primary marker for gout risk?
- Serum uric acid
- Serum creatinine
- Serum ALT
- Plasma ammonia
Correct Answer: Serum uric acid
Q49. Which enzyme converts ribose-5-phosphate to PRPP and uses which energy molecule?
- PRPP synthetase uses GTP
- PRPP synthetase uses ATP
- Phosphoribosyltransferase uses ATP
- PRPP synthetase uses NADH
Correct Answer: PRPP synthetase uses ATP
Q50. Which genetic defect leads to hyperactivity of de novo purine synthesis via increased PRPP and results in gout and neurodevelopmental problems?
- HGPRT overexpression
- Partial deficiency of HGPRT or PRPP synthetase gain-of-function mutations leading to increased PRPP availability
- Xanthine oxidase deficiency
- Adenylosuccinate synthetase deficiency
Correct Answer: Partial deficiency of HGPRT or PRPP synthetase gain-of-function mutations leading to increased PRPP availability

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