Purine synthesis: PRPP synthetase superactivity: 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 · Purine synthesis: PRPP synthetase superactivity

Sample item

A 22-year-old man has gout, uric acid urolithiasis and sensorineural hearing loss. HGPRT activity is normal, but PRPP synthetase shows increased activity (X-linked). Which mechanism causes the hyperuricaemia?

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

The answer and the reasoning

C. Excess PRPP drives amidophosphoribosyltransferase and increases de novo purine synthesis

PRPP is the substrate and a positive effector of amidophosphoribosyltransferase, the committed step of purine synthesis. Overactive or feedback-resistant PRPP synthetase raises PRPP and thus the flux through de novo synthesis and uric acid production. The condition also features neurological features such as deafness.

Option by option

  • A. Reduced renal urate excretion through URAT1 overactivity

    Renal underexcretion is the commonest cause of gout in general but does not explain this enzyme finding.

  • B. Overactive xanthine oxidase converting hypoxanthine to uric acid

    Xanthine oxidase activity is not the primary abnormality and would not be raised in this disorder.

  • C. Excess PRPP drives amidophosphoribosyltransferase and increases de novo purine synthesis (correct)

    Raised PRPP accelerates the committed step of purine synthesis, so purines and uric acid are overproduced.

  • D. Absent purine salvage because of HGPRT deficiency

    HGPRT is stated to be normal, so salvage failure (Lesch-Nyhan syndrome) is not responsible.

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 C, Excess PRPP drives amidophosphoribosyltransferase and increases de novo purine synthesis. PRPP is the substrate and a positive effector of amidophosphoribosyltransferase, the committed step of purine synthesis.

Why is "Reduced renal urate excretion through URAT1 overactivity" not the answer?

Renal underexcretion is the commonest cause of gout in general but does not explain this enzyme finding.

Why is "Overactive xanthine oxidase converting hypoxanthine to uric acid" not the answer?

Xanthine oxidase activity is not the primary abnormality and would not be raised in this disorder.

Why is "Absent purine salvage because of HGPRT deficiency" not the answer?

HGPRT is stated to be normal, so salvage failure (Lesch-Nyhan syndrome) is not responsible.

What concept does this question test?

It tests Purine synthesis: PRPP synthetase superactivity in Biochemistry. Overactive or feedback-resistant PRPP synthetase raises PRPP and thus the flux through de novo synthesis and uric acid production. The condition also features neurological features such as deafness.

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 Purine synthesis: PRPP synthetase superactivity?

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.