Biochemistry Nucleotide Chemistry and Metabolism 2 — Questions and Answers
Question 1: Which enzyme catalyzes the committed (first unique) step of pyrimidine biosynthesis?
- PRPP synthetase
- Carbamoyl phosphate synthetase II (CPS II)
- Aspartate transcarbamoylase (ATCase) (Correct answer)
- Dihydroorotase
Correct answer: Aspartate transcarbamoylase (ATCase)
ATCase (aspartate transcarbamoylase) catalyzes the condensation of carbamoyl phosphate with aspartate, forming carbamoyl aspartate, which is the committed step unique to pyrimidine biosynthesis.
Question 2: Which nucleotide intermediate serves as the branch point from which both AMP and GMP are synthesized in the purine de novo pathway?
- XMP
- PRPP
- IMP (inosine monophosphate) (Correct answer)
- Adenylosuccinate
Correct answer: IMP (inosine monophosphate)
IMP is the first complete purine nucleotide formed in de novo synthesis and serves as the branch-point intermediate from which AMP and GMP diverge via separate enzymatic routes.
Question 3: PRPP (5-phosphoribosyl-1-pyrophosphate) is best described as which of the following?
- The final catabolic product of both purines and pyrimidines
- An activated ribose donor used in both de novo synthesis and salvage pathways (Correct answer)
- A substrate exclusive to pyrimidine de novo synthesis
- An allosteric inhibitor of purine salvage enzymes
Correct answer: An activated ribose donor used in both de novo synthesis and salvage pathways
PRPP donates the activated ribose-5-phosphate moiety in both de novo nucleotide synthesis and salvage pathways for purines (HGPRT, APRT) and pyrimidines (OPRT).
Question 4: Orotic aciduria type I is caused by a deficiency of which bifunctional enzyme?
- CPS II
- ATCase
- UMP synthase (UMPS) (Correct answer)
- Dihydroorotate dehydrogenase
Correct answer: UMP synthase (UMPS)
UMP synthase possesses both orotate phosphoribosyltransferase and OMP decarboxylase activities; its deficiency blocks the last two steps of pyrimidine synthesis, causing orotic acid accumulation and megaloblastic anemia.
Question 5: 5-Fluorouracil (5-FU) exerts its anticancer activity primarily by inhibiting which enzyme?
- Ribonucleotide reductase
- Thymidylate synthase (Correct answer)
- Dihydrofolate reductase
- CTP synthetase
Correct answer: Thymidylate synthase
5-FU is converted to 5-FdUMP, which forms a covalent ternary complex with thymidylate synthase and N5,N10-methyleneTHF, irreversibly blocking dTMP synthesis and depleting the thymidine pool for DNA replication.
Question 6: PRPP amidotransferase, which catalyzes the first committed step of de novo purine synthesis, is allosterically inhibited by which molecules?
- Carbamoyl phosphate and aspartate
- AMP, ADP, ATP, GMP, GDP, and GTP (Correct answer)
- Orotate and UMP
- IMP and XMP only
Correct answer: AMP, ADP, ATP, GMP, GDP, and GTP
PRPP amidotransferase is subject to cumulative feedback inhibition by the end-product purine nucleotides (AMP/ADP/ATP and GMP/GDP/GTP), ensuring synthesis shuts down when purine pools are replete.
Question 7: In the pyrimidine salvage pathway, uridine is converted directly to UMP by which enzyme?
- Uridine kinase (Correct answer)
- UMP synthase
- Uridine phosphorylase
- CTP synthetase
Correct answer: Uridine kinase
Uridine kinase phosphorylates uridine (using ATP) to produce UMP in the salvage pathway, allowing cells to recycle preformed pyrimidine nucleosides without de novo synthesis.
Biochemistry Nucleotide Chemistry and Metabolism 2
Which enzyme catalyzes the committed (first unique) step of pyrimidine biosynthesis?