Nucleotide metabolism: activation of 6-mercaptopurine: 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 metabolism: activation of 6-mercaptopurine

Sample item

6-Mercaptopurine is a prodrug. It inhibits de novo purine synthesis only after conversion to a thioinosine monophosphate nucleotide by an enzyme of the purine salvage pathway. A tumour that has lost this enzyme would be resistant. Which enzyme is this?

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

The answer and the reasoning

D. Hypoxanthine-guanine phosphoribosyltransferase

HGPRT transfers ribose phosphate from PRPP onto mercaptopurine, forming thio-IMP. This nucleotide inhibits the committed enzyme glutamine-PRPP amidotransferase and the conversion of IMP to AMP and GMP, and it is incorporated into nucleic acids. Loss of HGPRT is a recognised cause of thiopurine resistance.

Option by option

  • A. Orotate phosphoribosyltransferase

    This pyrimidine pathway enzyme acts on orotate, not on purine analogues.

  • B. Adenosine deaminase

    Adenosine deaminase deaminates adenosine and deoxyadenosine and does not activate thiopurines.

  • C. Thiopurine methyltransferase

    This methyltransferase inactivates the drug and would not be needed for activation.

  • D. Hypoxanthine-guanine phosphoribosyltransferase (correct)

    Correct. Conversion to the nucleotide by the salvage transferase generates the active inhibitor.

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.

More Biochemistry questions

Questions about this Biochemistry question

What is the answer to this Biochemistry question?

The best answer is D, Hypoxanthine-guanine phosphoribosyltransferase. HGPRT transfers ribose phosphate from PRPP onto mercaptopurine, forming thio-IMP.

Why is "Orotate phosphoribosyltransferase" not the answer?

This pyrimidine pathway enzyme acts on orotate, not on purine analogues.

Why is "Adenosine deaminase" not the answer?

Adenosine deaminase deaminates adenosine and deoxyadenosine and does not activate thiopurines.

Why is "Thiopurine methyltransferase" not the answer?

This methyltransferase inactivates the drug and would not be needed for activation.

What concept does this question test?

It tests Nucleotide metabolism: activation of 6-mercaptopurine in Biochemistry. This nucleotide inhibits the committed enzyme glutamine-PRPP amidotransferase and the conversion of IMP to AMP and GMP, and it is incorporated into nucleic acids. Loss of HGPRT is a recognised cause of thiopurine resistance.

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 metabolism: activation of 6-mercaptopurine?

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.