Pyrimidine synthesis: leflunomide: 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 · Pyrimidine synthesis: leflunomide

Sample item

A woman with rheumatoid arthritis takes leflunomide. Its active metabolite, teriflunomide, preferentially suppresses activated lymphocytes because it inhibits which enzyme?

ADihydroorotate dehydrogenase, a step in de novo pyrimidine synthesisBDihydrofolate reductaseCXanthine oxidaseDIMP dehydrogenase in de novo purine synthesis

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

The answer and the reasoning

A. Dihydroorotate dehydrogenase, a step in de novo pyrimidine synthesis

Dihydroorotate dehydrogenase, located on the inner mitochondrial membrane, oxidises dihydroorotate to orotate. Activated lymphocytes depend heavily on de novo pyrimidine synthesis because their salvage capacity is limited, so inhibition arrests their proliferation; uridine can partially rescue cells. Hepatotoxicity and teratogenicity are important adverse effects.

Option by option

A. Dihydroorotate dehydrogenase, a step in de novo pyrimidine synthesis (correct)
Blocking dihydroorotate dehydrogenase starves proliferating lymphocytes of pyrimidines.
B. Dihydrofolate reductase
Dihydrofolate reductase is inhibited by methotrexate, which is a different disease-modifying drug.
C. Xanthine oxidase
Xanthine oxidase is inhibited by allopurinol and febuxostat in gout.
D. IMP dehydrogenase in de novo purine synthesis
IMP dehydrogenase inhibition is the mechanism of mycophenolate and affects guanine nucleotides.

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, Dihydroorotate dehydrogenase, a step in de novo pyrimidine synthesis. Dihydroorotate dehydrogenase, located on the inner mitochondrial membrane, oxidises dihydroorotate to orotate.

Why is "Dihydrofolate reductase" not the answer?

Dihydrofolate reductase is inhibited by methotrexate, which is a different disease-modifying drug.

Why is "Xanthine oxidase" not the answer?

Xanthine oxidase is inhibited by allopurinol and febuxostat in gout.

Why is "IMP dehydrogenase in de novo purine synthesis" not the answer?

IMP dehydrogenase inhibition is the mechanism of mycophenolate and affects guanine nucleotides.

What concept does this question test?

It tests Pyrimidine synthesis: leflunomide in Biochemistry. Activated lymphocytes depend heavily on de novo pyrimidine synthesis because their salvage capacity is limited, so inhibition arrests their proliferation; uridine can partially rescue cells. Hepatotoxicity and teratogenicity are important adverse effects.

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 Pyrimidine synthesis: leflunomide?

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.