Nucleotide drugs: methotrexate rescue: 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.

Try it

Biochemistry · Nucleotide drugs: methotrexate rescue

Sample item

A patient on weekly methotrexate for rheumatoid arthritis presents with mouth ulcers, macrocytosis and neutropenia after a dosing error. Which agent best rescues normal cells, and why?

ALeucovorin, because it is a reduced folate that bypasses the blocked dihydrofolate reductaseBUridine, because it restores pyrimidine salvageCCyanocobalamin, because it restores methionine synthase activityDFolic acid, because it enters one-carbon metabolism without reduction

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

The answer and the reasoning

A. Leucovorin, because it is a reduced folate that bypasses the blocked dihydrofolate reductase

Methotrexate inhibits dihydrofolate reductase, so tetrahydrofolate is not regenerated and thymidylate and purine synthesis fail, hitting marrow and mucosa. Leucovorin (folinic acid) is already a reduced folate and supplies one-carbon carriers downstream of the block. Plain folic acid needs dihydrofolate reductase to be reduced, so it is not reliable for rescue.

Option by option

A. Leucovorin, because it is a reduced folate that bypasses the blocked dihydrofolate reductase (correct)
Correct. A reduced folate by-passes the enzyme block.
B. Uridine, because it restores pyrimidine salvage
Uridine rescue is used in orotic aciduria and with some pyrimidine analogues, not for methotrexate toxicity.
C. Cyanocobalamin, because it restores methionine synthase activity
Vitamin B12 does not correct the dihydrofolate reductase block.
D. Folic acid, because it enters one-carbon metabolism without reduction
Folic acid needs reduction by the inhibited enzyme before it can act, so it does not rescue reliably.

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 A, Leucovorin, because it is a reduced folate that bypasses the blocked dihydrofolate reductase. Methotrexate inhibits dihydrofolate reductase, so tetrahydrofolate is not regenerated and thymidylate and purine synthesis fail, hitting marrow and mucosa.

Why is "Uridine, because it restores pyrimidine salvage" not the answer?

Uridine rescue is used in orotic aciduria and with some pyrimidine analogues, not for methotrexate toxicity.

Why is "Cyanocobalamin, because it restores methionine synthase activity" not the answer?

Vitamin B12 does not correct the dihydrofolate reductase block.

Why is "Folic acid, because it enters one-carbon metabolism without reduction" not the answer?

Folic acid needs reduction by the inhibited enzyme before it can act, so it does not rescue reliably.

What concept does this question test?

It tests Nucleotide drugs: methotrexate rescue in Biochemistry. Leucovorin (folinic acid) is already a reduced folate and supplies one-carbon carriers downstream of the block. Plain folic acid needs dihydrofolate reductase to be reduced, so it is not reliable for rescue.

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 drugs: methotrexate rescue?

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.