Nucleotide metabolism: pemetrexed: 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 metabolism: pemetrexed

Sample item

A patient with malignant pleural mesothelioma receives pemetrexed with folic acid and vitamin B12 supplementation to reduce toxicity. Pemetrexed is a folate analogue that inhibits several folate-dependent enzymes. Which effect is expected?

AImpaired synthesis of only purine nucleotidesBImpaired synthesis of only thymidylateCImpaired conversion of orotate to UMPDImpaired synthesis of both thymidylate and purines

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

The answer and the reasoning

D. Impaired synthesis of both thymidylate and purines

Pemetrexed is a multitargeted antifolate that inhibits thymidylate synthase, dihydrofolate reductase and glycinamide ribonucleotide formyltransferase. This blocks both thymidylate and de novo purine synthesis, so rapidly dividing cells cannot make DNA. Folate and B12 supplements reduce its toxicity.

Option by option

A. Impaired synthesis of only purine nucleotides
Only purines would be affected if the sole target were the formyltransferase step.
B. Impaired synthesis of only thymidylate
Only thymidylate is affected by fluorouracil, which targets one enzyme.
C. Impaired conversion of orotate to UMP
Orotate conversion to UMP uses UMP synthase, which is not folate-dependent.
D. Impaired synthesis of both thymidylate and purines (correct)
Correct. It inhibits enzymes in both the thymidylate and purine pathways.

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.

Questions about this Biochemistry question

What is the answer to this Biochemistry question?

The best answer is D, Impaired synthesis of both thymidylate and purines. Pemetrexed is a multitargeted antifolate that inhibits thymidylate synthase, dihydrofolate reductase and glycinamide ribonucleotide formyltransferase.

Why is "Impaired synthesis of only purine nucleotides" not the answer?

Only purines would be affected if the sole target were the formyltransferase step.

Why is "Impaired synthesis of only thymidylate" not the answer?

Only thymidylate is affected by fluorouracil, which targets one enzyme.

Why is "Impaired conversion of orotate to UMP" not the answer?

Orotate conversion to UMP uses UMP synthase, which is not folate-dependent.

What concept does this question test?

It tests Nucleotide metabolism: pemetrexed in Biochemistry. This blocks both thymidylate and de novo purine synthesis, so rapidly dividing cells cannot make DNA. Folate and B12 supplements reduce its toxicity.

How hard is this question?

We tag it as an application question: it asks you to use a fact on a patient or a finding. 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 metabolism: pemetrexed?

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.