Synthesis of purine MCQs With Answer
The synthesis of purine nucleotides is a core topic for B. Pharm students, covering de novo purine pathway, salvage pathways, key enzymes like PRPP synthetase and amidophosphoribosyltransferase, intermediates (GAR, AIR, IMP), and one‑carbon donors such as N10‑formyl‑THF. This introduction reviews regulation by end‑product inhibition (AMP, GMP), clinical links (Lesch‑Nyhan, methotrexate effects), and drug targets (IMP dehydrogenase, antifolates). Understanding enzymatic steps, cofactors, and branching to AMP/GMP is essential for therapeutics and drug design. Clear grasp of these mechanisms strengthens pharmacology, medicinal chemistry, and clinical correlations. Now let’s test your knowledge with 50 MCQs on this topic.
Q1. Which molecule is the activated ribose donor that initiates de novo purine synthesis?
- Ribose-5-phosphate
- 5-Phosphoribosyl-1-pyrophosphate (PRPP)
- Adenosine monophosphate (AMP)
- Inosine monophosphate (IMP)
Correct Answer: 5-Phosphoribosyl-1-pyrophosphate (PRPP)
Q2. What is the first committed enzyme of de novo purine biosynthesis?
- PRPP synthetase
- Amidophosphoribosyltransferase (PRPP amidotransferase)
- GAR transformylase
- IMP dehydrogenase
Correct Answer: Amidophosphoribosyltransferase (PRPP amidotransferase)
Q3. Which amino acid provides the nitrogen that forms the first amine in purine ring formation?
- Glycine
- Glutamine
- Aspartate
- Serine
Correct Answer: Glutamine
Q4. Which intermediate contains the glycine residue incorporated into the purine ring?
- FGAM
- GAR (glycinamide ribonucleotide)
- AICAR
- IMP
Correct Answer: GAR (glycinamide ribonucleotide)
Q5. How many one‑carbon formyl transfers from N10‑formyl‑THF are required in de novo purine synthesis to make IMP?
- One
- Two
- Three
- None
Correct Answer: Two
Q6. Which enzyme catalyzes the conversion of IMP to XMP during GMP biosynthesis?
- Adenylosuccinate synthetase
- IMP dehydrogenase
- GMP synthetase
- Xanthine oxidase
Correct Answer: IMP dehydrogenase
Q7. Which nucleotide(s) exert feedback inhibition on amidophosphoribosyltransferase?
- Only ATP
- Only GTP
- Both AMP and GMP
- Only IMP
Correct Answer: Both AMP and GMP
Q8. Which cofactor is required by IMP dehydrogenase for oxidation of IMP to XMP?
- FAD
- NAD+
- NADP+
- ATP
Correct Answer: NAD+
Q9. Conversion of IMP to AMP requires which nucleotide as a source of energy/regulation?
- ATP
- GTP
- CTP
- UTP
Correct Answer: GTP
Q10. Which enzyme catalyzes the salvage of hypoxanthine to IMP?
- HGPRT (hypoxanthine-guanine phosphoribosyltransferase)
- APRT (adenine phosphoribosyltransferase)
- Xanthine oxidase
- Nucleoside phosphorylase
Correct Answer: HGPRT (hypoxanthine-guanine phosphoribosyltransferase)
Q11. Deficiency of HGPRT leads to which clinical syndrome?
- Gout due to xanthine oxidase deficiency
- Lesch‑Nyhan syndrome
- Adrenoleukodystrophy
- Severe combined immunodeficiency (SCID)
Correct Answer: Lesch‑Nyhan syndrome
Q12. Methotrexate inhibits which enzyme that indirectly reduces purine synthesis by depleting N10‑formyl‑THF?
- Dihydrofolate reductase (DHFR)
- IMP dehydrogenase
- Adenylosuccinate synthetase
- PRPP synthetase
Correct Answer: Dihydrofolate reductase (DHFR)
Q13. Mycophenolic acid (mycophenolate) inhibits which enzyme in purine metabolism?
- PRPP synthetase
- IMP dehydrogenase
- Adenine deaminase
- HGPRT
Correct Answer: IMP dehydrogenase
Q14. Which substrate provides the atoms that become the C4, C5 and N7 of the purine ring?
- Glycine
- Formyl‑THF
- CO2
- Aspartate
Correct Answer: Glycine
Q15. The enzyme that synthesizes PRPP from ribose-5-phosphate is called:
- PRPP amidotransferase
- PRPP synthetase (ribose-phosphate diphosphokinase)
- Ribokinase
- Phosphoribosyltransferase
Correct Answer: PRPP synthetase (ribose-phosphate diphosphokinase)
Q16. Which compound is the first fully formed purine nucleotide produced by de novo synthesis?
- AMP
- GMP
- IMP (inosine monophosphate)
- XMP
Correct Answer: IMP (inosine monophosphate)
Q17. Adenylosuccinate synthetase converts IMP to adenylosuccinate using which cosubstrate?
- ATP
- GTP
- UTP
- ADP
Correct Answer: GTP
Q18. Which enzyme uses glutamine as an ammonia donor to convert XMP to GMP?
- GMP synthetase
- IMP cyclohydrolase
- Adenylosuccinate lyase
- HGPRT
Correct Answer: GMP synthetase
Q19. Which drug directly inhibits dihydrofolate reductase causing reduced N10‑formyl‑THF and impaired purine synthesis?
- Allopurinol
- Methotrexate
- Mycophenolate mofetil
- Azathioprine
Correct Answer: Methotrexate
Q20. Purine ring atoms originate from several sources. Which provides a carbon atom via CO2 fixation?
- Formyl-THF
- Carbon dioxide via carboxylation of AIR to CAIR
- Glycine
- Glutamine
Correct Answer: Carbon dioxide via carboxylation of AIR to CAIR
Q21. Which enzyme deficiency leads to accumulation of SAICAR and S‑Adenosyl compounds and neurodevelopmental issues?
- Adenylosuccinate lyase deficiency
- HGPRT deficiency
- PRPP synthetase deficiency
- IMP dehydrogenase deficiency
Correct Answer: Adenylosuccinate lyase deficiency
Q22. The salvage enzyme APRT converts adenine to:
- IMP
- AMP
- GMP
- Adenosine
Correct Answer: AMP
Q23. Which enzyme couples glutamine hydrolysis to form the first purine ring nitrogen during de novo synthesis?
- GAR synthetase
- Amidophosphoribosyltransferase
- GMP synthetase
- AICAR transformylase
Correct Answer: Amidophosphoribosyltransferase
Q24. Inhibition of which enzyme would most directly block GMP synthesis but not AMP synthesis?
- IMP dehydrogenase
- Adenylosuccinate synthetase
- PRPP synthetase
- HGPRT
Correct Answer: IMP dehydrogenase
Q25. Which molecule stimulates GMP synthesis by providing the energy source for GMP branch?
- ATP
- GTP
- CTP
- UTP
Correct Answer: ATP
Q26. Which intermediate is directly converted by AICAR transformylase during purine ring formation?
- GAR
- AICAR (5-aminoimidazole-4-carboxamide ribonucleotide)
- FGAM
- SAICAR
Correct Answer: AICAR (5-aminoimidazole-4-carboxamide ribonucleotide)
Q27. PRPP synthetase activity depends on which substrate derived from the pentose phosphate pathway?
- Fructose-6-phosphate
- Ribose-5-phosphate
- Glucose-6-phosphate
- Sedoheptulose-7-phosphate
Correct Answer: Ribose-5-phosphate
Q28. Which inhibitor is known to target glutamine amidotransferases involved in purine biosynthesis?
- Azaserine
- Allopurinol
- Probenecid
- Colchicine
Correct Answer: Azaserine
Q29. Which folate derivative provides formyl groups in two separate reactions during purine ring assembly?
- N5,N10‑Methylene‑THF
- N10‑Formyl‑THF
- 5‑Methyl‑THF
- Dihydrofolate
Correct Answer: N10‑Formyl‑THF
Q30. A gain‑of‑function mutation in PRPP synthetase would most likely lead to:
- Decreased purine synthesis and immunodeficiency
- Overproduction of purines and hyperuricemia (gout)
- Impaired nucleotide salvage with anemia
- Increased thymidine synthesis
Correct Answer: Overproduction of purines and hyperuricemia (gout)
Q31. Which enzyme converts GAR to FGAR by addition of a formyl group?
- GAR synthetase
- GAR transformylase (GAR Tfase)
- FGAM synthetase
- AICAR transformylase
Correct Answer: GAR transformylase (GAR Tfase)
Q32. What is the immediate product formed after addition of aspartate to IMP during AMP biosynthesis?
- Adenylosuccinate
- AICAR
- SAICAR
- AMP
Correct Answer: Adenylosuccinate
Q33. Which enzyme is targeted by ribavirin’s active metabolites affecting purine metabolism in viruses?
- IMP dehydrogenase
- PRPP synthetase
- HGPRT
- GMP synthetase
Correct Answer: IMP dehydrogenase
Q34. Which purine intermediate accumulates when ADSL (adenylosuccinate lyase) is deficient?
- SAICAR and adenylosuccinate (S‑Ado)
- IMP only
- GMP only
- PRPP
Correct Answer: SAICAR and adenylosuccinate (S‑Ado)
Q35. Which enzyme catalyzes conversion of AIR to CAIR by carboxylation?
- AIR carboxylase (phosphoribosylaminoimidazole carboxylase)
- GAR synthetase
- IMP cyclohydrolase
- Adenylosuccinate synthetase
Correct Answer: AIR carboxylase (phosphoribosylaminoimidazole carboxylase)
Q36. Inhibition of which pathway component reduces availability of N10‑formyl‑THF and therefore inhibits purine synthesis?
- Serine hydroxymethyltransferase or DHFR (folate cycle)
- PRPP synthetase
- HGPRT
- Xanthine oxidase
Correct Answer: Serine hydroxymethyltransferase or DHFR (folate cycle)
Q37. Which enzyme cyclizes FAICAR to form IMP at the final step of purine ring assembly?
- IMP cyclohydrolase
- GAR synthetase
- AICAR transformylase
- Glycinamide ribonucleotide transformylase
Correct Answer: IMP cyclohydrolase
Q38. Which metabolite is a branch point connecting purine de novo synthesis to nucleotide salvage and degradation?
- PRPP
- IMP
- ATP
- Glycine
Correct Answer: IMP
Q39. Which therapeutic agent reduces lymphocyte proliferation by inhibiting IMP dehydrogenase?
- Azathioprine
- Mycophenolate mofetil
- Methotrexate
- Allopurinol
Correct Answer: Mycophenolate mofetil
Q40. Which enzyme uses PRPP to salvage guanine into GMP?
- APRT
- HGPRT
- Nucleotidase
- Guanine deaminase
Correct Answer: HGPRT
Q41. Formation of FGAM (formylglycinamidine ribonucleotide) requires which substrate and cofactor?
- GAR and ATP
- GAR and glutamine
- GAR, glutamine, and ATP
- GAR and NAD+
Correct Answer: GAR, glutamine, and ATP
Q42. Which enzyme converts adenylosuccinate to AMP and fumarate?
- Adenylosuccinate lyase
- Adenylosuccinate synthetase
- AMP deaminase
- IMP dehydrogenase
Correct Answer: Adenylosuccinate lyase
Q43. What is the primary fate of excess purine nucleotides in humans?
- Conversion to uric acid via xanthine oxidase
- Conversion to pyrimidines
- Storage as nucleoproteins
- Excretion as adenine
Correct Answer: Conversion to uric acid via xanthine oxidase
Q44. The drug allopurinol primarily reduces uric acid by inhibiting:
- PRPP synthetase
- Xanthine oxidase
- HGPRT
- IMP dehydrogenase
Correct Answer: Xanthine oxidase
Q45. Which purine biosynthetic enzyme is part of a multifunctional polypeptide in mammalian cells (purinosome concept)?
- Separate monofunctional enzymes only
- GAR transformylase as part of multifunctional protein
- Xanthine oxidase in purinosome
- HGPRT in purinosome
Correct Answer: GAR transformylase as part of multifunctional protein
Q46. Which vitamin deficiency would impair de novo purine synthesis by reducing one‑carbon donors?
- Vitamin B6
- Folate (vitamin B9)
- Vitamin B12 only
- Vitamin C
Correct Answer: Folate (vitamin B9)
Q47. Which enzyme is responsible for converting IMP to GMP’s immediate precursor XMP?
- IMP dehydrogenase
- GMP synthetase
- Adenylosuccinate lyase
- PRPP synthetase
Correct Answer: IMP dehydrogenase
Q48. Which metabolite signals high cellular GTP levels to downregulate de novo purine synthesis?
- GTP via feedback inhibition of amidophosphoribosyltransferase
- ATP only
- cAMP
- IMP only
Correct Answer: GTP via feedback inhibition of amidophosphoribosyltransferase
Q49. Salvage of nucleobases conserves energy because it bypasses which costly step?
- Synthesis of ribose-5-phosphate
- De novo ring assembly on PRPP
- Glycolysis
- Mitochondrial ATP production
Correct Answer: De novo ring assembly on PRPP
Q50. Inhibition of folate metabolism reduces availability of N10‑formyl‑THF and therefore specifically impairs which two steps in purine biosynthesis?
- GAR to FGAR and AICAR to FAICAR (formylation steps)
- IMP to XMP and XMP to GMP
- PRPP formation and HGPRT activity
- Adenylosuccinate formation and cleavage
Correct Answer: GAR to FGAR and AICAR to FAICAR (formylation steps)

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