Biosynthesis of pyrimidine nucleotides MCQs With Answer offers B. Pharm students a focused review of pyrimidine biosynthesis, covering de novo synthesis, salvage pathways, and clinical relevance. This set emphasizes key enzymes (CPS II, aspartate transcarbamoylase, dihydroorotate dehydrogenase, UMP synthase), intermediates (carbamoyl phosphate, orotate, UMP), regulation by UTP and PRPP, and links to thymidylate and folate metabolism. Expect questions on enzymatic mechanisms, cellular localization, feedback inhibition, disorders like orotic aciduria, and pharmacologic inhibitors such as 5‑fluorouracil and leflunomide. Clear MCQs with answers will strengthen your understanding of nucleotide metabolism, drug targets, and practical B.Pharm applications. Now let’s test your knowledge with 50 MCQs on this topic.
Q1. Which enzyme catalyzes the first committed step in de novo pyrimidine biosynthesis?
- Carbamoyl phosphate synthetase I (CPS I)
- Carbamoyl phosphate synthetase II (CPS II)
- Aspartate transcarbamoylase (ATCase)
- Orotate phosphoribosyltransferase (OPRT)
Correct Answer: Carbamoyl phosphate synthetase II (CPS II)
Q2. Where does de novo pyrimidine biosynthesis occur in eukaryotic cells?
- Mitochondrial matrix
- Rough endoplasmic reticulum
- Golgi apparatus
- Cytosol
Correct Answer: Cytosol
Q3. What is the primary nitrogen donor for carbamoyl phosphate synthesis by CPS II?
- Ammonium ion (NH4+)
- Glutamine
- Glutamate
- Asparagine
Correct Answer: Glutamine
Q4. Which reaction is catalyzed by aspartate transcarbamoylase (ATCase)?
- Formation of UMP from OMP
- Formation of carbamoyl aspartate from carbamoyl phosphate and aspartate
- Oxidation of dihydroorotate to orotate
- Conversion of UMP to UDP
Correct Answer: Formation of carbamoyl aspartate from carbamoyl phosphate and aspartate
Q5. Which enzyme oxidizes dihydroorotate to orotate and where is it located?
- Dihydroorotase in the cytosol
- Dihydroorotate dehydrogenase in the mitochondria (uses ubiquinone)
- Orotate phosphoribosyltransferase in the nucleus
- OMP decarboxylase in the endoplasmic reticulum
Correct Answer: Dihydroorotate dehydrogenase in the mitochondria (uses ubiquinone)
Q6. Which enzyme converts orotate and PRPP into orotidine-5′-monophosphate (OMP)?
- OMP decarboxylase
- Orotate phosphoribosyltransferase (OPRT)
- UMP kinase
- PRPP synthetase
Correct Answer: Orotate phosphoribosyltransferase (OPRT)
Q7. OMP decarboxylase catalyzes which step in pyrimidine biosynthesis?
- OMP to UMP
- UTP to CTP
- Carbamoyl phosphate formation
- PRPP synthesis
Correct Answer: OMP to UMP
Q8. Which enzyme phosphorylates UMP to UDP during pyrimidine nucleotide activation?
- UMP kinase (uridine monophosphate kinase)
- Nucleoside diphosphate kinase
- Thymidylate synthase
- PRPP synthetase
Correct Answer: UMP kinase (uridine monophosphate kinase)
Q9. Which enzyme catalyzes the reduction of ribonucleotides (e.g., UDP) to their corresponding deoxyribonucleotides (e.g., dUDP) for DNA synthesis?
- Ribonucleotide reductase
- Thymidylate synthase
- DNA polymerase
- Ribonuclease H
Correct Answer: Ribonucleotide reductase
Q10. Which enzyme synthesizes dTMP from dUMP and what one‑carbon donor does it use?
- Thymidylate synthase using N5,N10-methylene-tetrahydrofolate
- Dihydrofolate reductase using NADPH
- Ribonucleotide reductase using thioredoxin
- Uridine kinase using ATP
Correct Answer: Thymidylate synthase using N5,N10-methylene-tetrahydrofolate
Q11. Which folate derivative provides the methyl group required for thymidylate synthesis?
- NADH
- N5,N10-methylene tetrahydrofolate
- Tetrahydrobiopterin
Correct Answer: N5,N10-methylene tetrahydrofolate
Q12. Which nucleotide provides feedback inhibition to CPS II in pyrimidine biosynthesis?
- ATP
- GTP
- UTP
- CTP
Correct Answer: UTP
Q13. PRPP (phosphoribosyl pyrophosphate) is synthesized from which substrate(s)?
- Glucose-6-phosphate and ATP
- Ribose-5-phosphate and ATP
- Ribulose-5-phosphate and GTP
- Fructose-6-phosphate and ADP
Correct Answer: Ribose-5-phosphate and ATP
Q14. Which enzyme catalyzes the salvage reaction that converts free uracil to UMP?
- Uridine phosphorylase
- Uracil phosphoribosyltransferase (UPRT)
- Thymidine kinase
- Pyrimidine nucleoside phosphorylase
Correct Answer: Uracil phosphoribosyltransferase (UPRT)
Q15. Orotic aciduria is most commonly due to deficiency of which enzyme(s)?
- UMP synthase (bifunctional OPRT and OMP decarboxylase)
- Carbamoyl phosphate synthetase I (CPS I)
- Dihydroorotate dehydrogenase
- Thymidylate synthase
Correct Answer: UMP synthase (bifunctional OPRT and OMP decarboxylase)
Q16. A characteristic clinical feature of hereditary orotic aciduria includes:
- Hyperammonemia due to CPS I deficiency
- Orotic aciduria with megaloblastic anemia that improves with uridine
- Excess uric acid and gouty arthritis
- Severe hypokalemia and muscle weakness
Correct Answer: Orotic aciduria with megaloblastic anemia that improves with uridine
Q17. Which anticancer drug acts primarily by inhibiting thymidylate synthase?
- Methotrexate
- 5-Fluorouracil (5-FU)
- Azathioprine
- Cisplatin
Correct Answer: 5-Fluorouracil (5-FU)
Q18. Methotrexate inhibits which enzyme, thereby impairing thymidylate synthesis indirectly?
- Dihydrofolate reductase (DHFR)
- Thymidylate synthase
- Ribonucleotide reductase
- Orotate phosphoribosyltransferase
Correct Answer: Dihydrofolate reductase (DHFR)
Q19. How is pyrimidine ring assembly different from purine ring assembly?
- Pyrimidine ring is assembled on PRPP; purine is assembled first then attached to PRPP
- Pyrimidine ring is assembled first and then attached to PRPP; purine ring is assembled on PRPP
- Both pyrimidine and purine rings are assembled on PRPP
- Neither pathway uses PRPP
Correct Answer: Pyrimidine ring is assembled first and then attached to PRPP; purine ring is assembled on PRPP
Q20. Which enzyme is considered the rate-limiting and committed regulator of de novo pyrimidine biosynthesis?
- PRPP synthetase
- OMP decarboxylase
- Carbamoyl phosphate synthetase II (CPS II)
- Thymidylate synthase
Correct Answer: Carbamoyl phosphate synthetase II (CPS II)
Q21. Dihydroorotate dehydrogenase is associated with which cellular location?
- Cytosolic ribosomes
- Mitochondrial inner membrane
- Golgi lumen
- Nucleolus
Correct Answer: Mitochondrial inner membrane
Q22. In mammals, the multifunctional CAD protein includes which enzymatic activities?
- CPS II, aspartate transcarbamoylase, and dihydroorotase
- OMP decarboxylase and OPRT
- Thymidylate synthase and DHFR
- PRPP synthetase and UMP kinase
Correct Answer: CPS II, aspartate transcarbamoylase, and dihydroorotase
Q23. Dihydroorotase catalyzes which transformation in the pyrimidine pathway?
- Conversion of UMP to UDP
- Cyclization of carbamoyl aspartate to dihydroorotate
- Oxidation of dihydroorotate to orotate
- Carboxylation of orotate to OMP
Correct Answer: Cyclization of carbamoyl aspartate to dihydroorotate
Q24. Which enzyme supplies carbamoyl phosphate for the urea cycle (distinct from CPS II)?
- Carbamoyl phosphate synthetase I (CPS I)
- Carbamoyl phosphate synthetase II (CPS II)
- Arginase
- Ornithine transcarbamylase
Correct Answer: Carbamoyl phosphate synthetase I (CPS I)
Q25. What is an effective treatment for hereditary orotic aciduria due to UMP synthase deficiency?
- Allopurinol therapy
- High protein diet
- Uridine supplementation
- Pyridoxine (vitamin B6) supplementation
Correct Answer: Uridine supplementation
Q26. PRPP provides what critical component for nucleotide formation?
- Activated adenine base
- Activated ribose-phosphate
- Activated methyl group
- Activated phosphate donor for DNA ligase
Correct Answer: Activated ribose-phosphate
Q27. What is the first ribonucleotide produced in the de novo pyrimidine pathway?
- UMP (uridine monophosphate)
- AMP (adenosine monophosphate)
- GMP (guanosine monophosphate)
- CTP (cytidine triphosphate)
Correct Answer: UMP (uridine monophosphate)
Q28. Which enzyme converts UTP to CTP and what is its amino‑nitrogen source?
- CTP synthase using glutamine as nitrogen donor
- CTP kinase using ammonia as nitrogen donor
- ATP-dependent cytidine deaminase using asparagine
- UMP kinase using glutamate
Correct Answer: CTP synthase using glutamine as nitrogen donor
Q29. In the pyrimidine salvage pathway, which enzyme phosphorylates uridine to UMP?
- Uridine kinase
- Thymidine kinase
- Uracil phosphoribosyltransferase
- UDP-glucuronosyltransferase
Correct Answer: Uridine kinase
Q30. Which fluorinated metabolite of 5‑fluorouracil directly inhibits thymidylate synthase?
- Fluorouridine
- Fluorodeoxyuridine monophosphate (FdUMP)
- Fluorouracil glucuronide
- Fluorouridine triphosphate (FUTP)
Correct Answer: Fluorodeoxyuridine monophosphate (FdUMP)
Q31. Which chemotherapeutic agent inhibits ribonucleotide reductase?
- Hydroxyurea
- 5-Fluorouracil
- Methotrexate
- Leucovorin
Correct Answer: Hydroxyurea
Q32. Which enzyme converts dCMP to dUMP in the pathway used to produce dTMP?
- dCMP deaminase
- dTMP kinase
- dUTPase
- Thymidine phosphorylase
Correct Answer: dCMP deaminase
Q33. Which reaction produces orotic acid during pyrimidine biosynthesis?
- Carbamoyl phosphate formation
- Oxidation of dihydroorotate by dihydroorotate dehydrogenase
- Decarboxylation of OMP to UMP
- Phosphorylation of orotate to OMP
Correct Answer: Oxidation of dihydroorotate by dihydroorotate dehydrogenase
Q34. In bacteria, which nucleotide acts as an allosteric inhibitor of ATCase?
- ATP activates and CTP inhibits ATCase
- GTP inhibits ATCase
- UTP activates ATCase
- ADP inhibits ATCase
Correct Answer: ATP activates and CTP inhibits ATCase
Q35. Which enzyme catalyzes the reversible conversion between uridine and uracil plus ribose-1-phosphate?
- Uridine phosphorylase
- Uracil phosphoribosyltransferase
- Uridine kinase
- Thymidine kinase
Correct Answer: Uridine phosphorylase
Q36. Deficiency of folate (vitamin B9) primarily impairs which step in nucleotide metabolism?
- Reduction of ribonucleotides to deoxyribonucleotides
- Methylation of dUMP to dTMP due to lack of N5,N10-methylene-THF
- Conversion of orotate to OMP
- Formation of PRPP
Correct Answer: Methylation of dUMP to dTMP due to lack of N5,N10-methylene-THF
Q37. Leflunomide, used in rheumatoid arthritis, inhibits which enzyme in pyrimidine biosynthesis?
- Thymidylate synthase
- Dihydroorotate dehydrogenase (DHODH)
- OMP decarboxylase
- Uridine kinase
Correct Answer: Dihydroorotate dehydrogenase (DHODH)
Q38. PRPP exerts which effect on CPS II activity?
- Inhibition
- No effect
- Activation
- Irreversible degradation
Correct Answer: Activation
Q39. Which small redox protein provides reducing equivalents to ribonucleotide reductase in many cells?
- Thioredoxin
- Glutathione peroxidase
- Catalase
- SOD (superoxide dismutase)
Correct Answer: Thioredoxin
Q40. Folate deficiency can cause megaloblastic anemia primarily because of decreased synthesis of which nucleotide?
- ATP
- dTMP (thymidylate)
- GTP
- UTP
Correct Answer: dTMP (thymidylate)
Q41. Which enzyme activity is contained within the UMP synthase polypeptide?
- OMP decarboxylase and orotate phosphoribosyltransferase
- Carbamoyl phosphate synthetase II and dihydroorotase
- Thymidylate synthase and DHFR
- Ribonucleotide reductase and thioredoxin reductase
Correct Answer: OMP decarboxylase and orotate phosphoribosyltransferase
Q42. Which nucleotides inhibit PRPP synthetase as feedback regulators?
- ATP and GTP
- ADP and GDP
- UTP and CTP
- AMP and CMP
Correct Answer: ADP and GDP
Q43. Pemetrexed, a cancer drug, targets folate-dependent enzymes. Which pathway is thereby most directly affected?
- De novo pyrimidine synthesis (thymidylate synthesis)
- Glycolysis
- TCA cycle
- Fatty acid oxidation
Correct Answer: De novo pyrimidine synthesis (thymidylate synthesis)
Q44. Which enzyme phosphorylates UDP to UTP?
- UMP kinase
- Nucleoside diphosphate kinase (NDP kinase)
- Thymidylate synthase
- Ribonucleotide reductase
Correct Answer: Nucleoside diphosphate kinase (NDP kinase)
Q45. The committed step in CTP biosynthesis from UTP is catalyzed by which enzyme?
- CTP synthase
- CTP kinase
- UMP kinase
- Thymidylate synthase
Correct Answer: CTP synthase
Q46. Which intermediate accumulates and is excreted in classic orotic aciduria?
- Uric acid
- Carbamoyl phosphate
- Orotic acid
- Orotidine-5′-monophosphate (OMP)
Correct Answer: Orotic acid
Q47. Which enzyme supplies carbamoyl phosphate for pyrimidine biosynthesis in the cytosol?
- CPS I (mitochondrial)
- CPS II (cytosolic)
- Ornithine transcarbamylase
- Argininosuccinate synthetase
Correct Answer: CPS II (cytosolic)
Q48. Which enzyme is also known as ribose-phosphate diphosphokinase and synthesizes PRPP?
- PRPP synthetase (ribose-phosphate diphosphokinase)
- Phosphoribosyltransferase
- UMP synthase
- Ribokinase
Correct Answer: PRPP synthetase (ribose-phosphate diphosphokinase)
Q49. In the thymidine salvage pathway, which enzyme phosphorylates thymidine to thymidine monophosphate (TMP)?
- Thymidine kinase
- Uridine kinase
- Thymidylate synthase
- Thymidine phosphorylase
Correct Answer: Thymidine kinase
Q50. Which enzymatic process provides the deoxyribonucleotide precursors required for DNA replication?
- Reduction of ribonucleotides by ribonucleotide reductase
- Salvage phosphorylation by nucleoside kinases only
- Synthesis of purines on PRPP exclusively
- Methylation of dUMP by thymidylate synthase only
Correct Answer: Reduction of ribonucleotides by ribonucleotide reductase
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