Molecular biology and genetics: NAT2 and isoniazid: 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 · Molecular biology and genetics: NAT2 and isoniazid

Sample item

A man with tuberculosis develops peripheral neuropathy on standard-dose isoniazid. Genotyping shows variants that reduce hepatic N-acetylation of the drug. Which pharmacogenetic phenotype does he have?

ACYP2D6 poor metaboliserBSlow NAT2 acetylatorCFast NAT2 acetylatorDTPMT deficiency

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

The answer and the reasoning

B. Slow NAT2 acetylator

Slow acetylators clear isoniazid more slowly, leading to higher drug levels and more neuropathy and pyridoxine depletion. Fast acetylators have lower levels and may have reduced efficacy. TPMT and CYP2D6 govern thiopurines and drugs such as codeine, not isoniazid.

Option by option

A. CYP2D6 poor metaboliser
CYP2D6 does not metabolise isoniazid appreciably.
B. Slow NAT2 acetylator (correct)
Correct. Reduced N-acetylation prolongs isoniazid exposure and increases neuropathy.
C. Fast NAT2 acetylator
Fast acetylation would lower drug levels and reduce the risk of neuropathy.
D. TPMT deficiency
TPMT deficiency affects thiopurine handling.

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 B, Slow NAT2 acetylator. Slow acetylators clear isoniazid more slowly, leading to higher drug levels and more neuropathy and pyridoxine depletion.

Why is "CYP2D6 poor metaboliser" not the answer?

CYP2D6 does not metabolise isoniazid appreciably.

Why is "Fast NAT2 acetylator" not the answer?

Fast acetylation would lower drug levels and reduce the risk of neuropathy.

Why is "TPMT deficiency" not the answer?

TPMT deficiency affects thiopurine handling.

What concept does this question test?

It tests Molecular biology and genetics: NAT2 and isoniazid in Biochemistry. Fast acetylators have lower levels and may have reduced efficacy. TPMT and CYP2D6 govern thiopurines and drugs such as codeine, not isoniazid.

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 Molecular biology and genetics: NAT2 and isoniazid?

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.