Nucleotide Metabolism and Disorders (Purine/Pyrimidine, Gout, Lesch-Nyhan, ADA-SCID) MCQs

Biochemistry · 22 free questions with answers & explanations.

1. A 3-year-old boy exhibits self-mutilating behavior, choreoathetosis, intellectual disability, and elevated serum uric acid. His red blood cells show nearly absent HGPRT activity. Which salvage pathway substrate accumulates to drive hyperuricemia?
2. Adenosine deaminase (ADA) deficiency causes SCID primarily because accumulation of which metabolite is selectively toxic to lymphocytes?
3. A 55-year-old man with chronic tophaceous gout is started on allopurinol. The drug works by inhibiting xanthine oxidase. Which statement about the resulting metabolic change is CORRECT?
4. A child presents with megaloblastic anemia, orotic aciduria, and poor growth. There is no hyperammonemia. Which enzyme deficiency is MOST likely responsible?
5. A 4-year-old boy presents with self-mutilating behaviour, hyperuricaemia, and choreoathetosis. His urine shows orange crystals. The enzyme deficient in this condition is:
6. Allopurinol treats gout by inhibiting xanthine oxidase. Which ADDITIONAL biochemical effect of allopurinol reduces de novo purine synthesis?
7. In ADA-SCID, the toxic accumulator that primarily kills lymphocytes is:
8. Orotic aciduria with megaloblastic anaemia unresponsive to B12/folate, WITHOUT hyperammonaemia, points to a deficiency of:
9. Which enzyme converts xanthine to uric acid AND hypoxanthine to xanthine in purine catabolism?
10. A 3-year-old boy presents with severe combined immunodeficiency (SCID), recurrent infections, and absent B and T lymphocytes. Enzyme assay reveals near-absent adenosine deaminase (ADA) activity. Which toxic metabolite accumulates and selectively destroys lymphocytes?
11. Allopurinol reduces uric acid production by inhibiting xanthine oxidase. In a patient with Lesch-Nyhan syndrome on allopurinol, what secondary metabolic effect would be expected regarding PRPP and purine de novo synthesis?
12. Which enzyme catalyzes the committed, rate-limiting step of pyrimidine de novo synthesis, and which two substrates does it combine?
13. A 55-year-old man with gout is prescribed febuxostat. How does febuxostat differ mechanistically from allopurinol in reducing uric acid production?
14. A 3-year-old boy presents with self-mutilation, choreoathetosis, hyperuricemia, and intellectual disability. Enzyme deficiency responsible for this condition catalyses which reaction?
15. Adenosine deaminase (ADA) deficiency causes SCID by accumulation of which toxic metabolite selectively lethal to lymphocytes?
16. Orotic acid is excreted in large amounts in a child who develops megaloblastic anemia not responding to B12 or folate. Deficiency of which enzyme is responsible?
17. Allopurinol treats gout by inhibiting xanthine oxidase. This results in accumulation of which metabolites that are more soluble than uric acid?
18. A 6-year-old boy with intellectual disability, self-mutilation (lip/finger biting), choreoathetosis, and gout is found to have markedly elevated serum uric acid. Hypoxanthine-guanine phosphoribosyltransferase (HGPRT) activity in erythrocytes is virtually absent. The biochemical mechanism linking HGPRT deficiency to hyperuricemia is:
19. 5-Fluorouracil (5-FU), used in colorectal cancer chemotherapy, is a pyrimidine antimetabolite. Its active metabolite 5-fluoro-2'-deoxyuridine-5'-monophosphate (FdUMP) acts as an irreversible ('suicide') inhibitor of which enzyme?
20. Methotrexate (MTX) inhibits dihydrofolate reductase (DHFR), depleting tetrahydrofolate (THF) and blocking de novo purine and thymidylate synthesis. Leucovorin rescue after high-dose MTX works because leucovorin is:
21. Allopurinol is used to treat gout and to prevent tumour lysis syndrome during chemotherapy. Allopurinol is a prodrug — it undergoes conversion by xanthine oxidase to alloxanthine (oxypurinol), which then inhibits xanthine oxidase. This pattern of inhibition (where the substrate is converted to an inhibitor by the target enzyme) is called:
22. During tumour lysis syndrome (TLS) following chemotherapy, massive cell death releases intracellular contents. The metabolic consequences include hyperkalemia, hyperphosphatemia, hypocalcemia, and hyperuricemia. The mechanism causing hypocalcemia in TLS specifically is: