Nucleotide drugs: fluorouracil: practice question

A Biochemistry question in the style of the NEET PG paper. Answer it first, then read why the right option is right and why each of the others is wrong.

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Biochemistry · Nucleotide drugs: fluorouracil

Sample item

A patient with colorectal cancer receives fluorouracil. The active metabolite FdUMP forms a covalent complex with thymidylate synthase. Which intracellular change is expected?

Original practice item, not a recalled exam question. Nothing here is recorded.

The answer and the reasoning

B. Decreased dTMP with accumulation of dUMP

Thymidylate synthase converts dUMP to dTMP using N5,N10-methylene tetrahydrofolate as the methyl donor. FdUMP traps the enzyme in a ternary complex, so dTMP falls and dUMP accumulates, causing so-called thymineless death in dividing cells. Leucovorin stabilises the complex and enhances the effect.

Option by option

  • A. Decreased dUMP with accumulation of dTMP

    This is the reverse of the effect, since dUMP is the substrate and builds up.

  • B. Decreased dTMP with accumulation of dUMP (correct)

    Correct. Blocking thymidylate synthase lowers the product dTMP and raises its substrate dUMP.

  • C. Decreased dCDP with accumulation of CDP

    dCDP and CDP changes would arise from ribonucleotide reductase inhibition, as with hydroxyurea.

  • D. Decreased IMP with accumulation of PRPP

    IMP and PRPP changes would arise from blocking purine synthesis, as with 6-mercaptopurine.

Source note: Original NextPrep sample item — pending expert review. This item is original practice material awaiting independent expert review, so confirm important facts in a standard textbook.

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Questions about this Biochemistry question

What is the answer to this Biochemistry question?

The best answer is B, Decreased dTMP with accumulation of dUMP. Thymidylate synthase converts dUMP to dTMP using N5,N10-methylene tetrahydrofolate as the methyl donor.

Why is "Decreased dUMP with accumulation of dTMP" not the answer?

This is the reverse of the effect, since dUMP is the substrate and builds up.

Why is "Decreased dCDP with accumulation of CDP" not the answer?

dCDP and CDP changes would arise from ribonucleotide reductase inhibition, as with hydroxyurea.

Why is "Decreased IMP with accumulation of PRPP" not the answer?

IMP and PRPP changes would arise from blocking purine synthesis, as with 6-mercaptopurine.

What concept does this question test?

It tests Nucleotide drugs: fluorouracil in Biochemistry. FdUMP traps the enzyme in a ternary complex, so dTMP falls and dUMP accumulates, causing so-called thymineless death in dividing cells. Leucovorin stabilises the complex and enhances the effect.

How hard is this question?

We tag it as a multi-step question: it asks you to combine more than one idea. The tag is our own editorial judgement, not an official difficulty rating, so read the reason for every option, not only the answer.

How should I study Nucleotide drugs: fluorouracil?

Build one table of enzyme deficiency, disease, inheritance and key finding, then revise it by spaced recall. Then use the flashcards and the other Biochemistry questions on this site to test what stuck.

Is this a real NEET PG question?

No. It is an original practice item (editorial status: sample, version 1). NextPrep does not publish recalled or leaked questions, and independent faculty review of this item has not been completed yet, so confirm important facts in a standard textbook.