Amino acid metabolism: glutathione: 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 · Amino acid metabolism: glutathione

Sample item

A 20-year-old woman presents 6 hours after ingesting about 30 tablets of paracetamol. Intravenous N-acetylcysteine is started. What is its biochemical basis?

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

The answer and the reasoning

B. It supplies cysteine to restore hepatic glutathione, which neutralises the toxic metabolite NAPQI

At therapeutic doses paracetamol is mainly glucuronidated and sulfated, with a small fraction oxidised by CYP2E1 to NAPQI, which glutathione conjugates. In overdose the conjugation pathways saturate, more NAPQI forms and glutathione is exhausted, so NAPQI binds hepatocyte proteins and causes centrilobular necrosis. Glutathione is the tripeptide gamma-glutamyl-cysteinyl-glycine, and cysteine supply is rate limiting, which N-acetylcysteine provides.

Option by option

  • A. It increases renal excretion of unchanged paracetamol

    N-acetylcysteine does not meaningfully increase urinary excretion of unchanged drug.

  • B. It supplies cysteine to restore hepatic glutathione, which neutralises the toxic metabolite NAPQI (correct)

    Correct. N-acetylcysteine replenishes cysteine and hence glutathione for NAPQI detoxification.

  • C. It competitively inhibits cytochrome P450 2E1 to stop NAPQI formation

    Cytochrome P450 inhibition is not the antidote's mechanism; its action is mainly on the glutathione side.

  • D. It activates glucuronosyltransferase to speed conjugation of paracetamol

    Glucuronosyltransferase is saturated in overdose and N-acetylcysteine does not activate it.

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 B, It supplies cysteine to restore hepatic glutathione, which neutralises the toxic metabolite NAPQI. At therapeutic doses paracetamol is mainly glucuronidated and sulfated, with a small fraction oxidised by CYP2E1 to NAPQI, which glutathione conjugates.

Why is "It increases renal excretion of unchanged paracetamol" not the answer?

N-acetylcysteine does not meaningfully increase urinary excretion of unchanged drug.

Why is "It competitively inhibits cytochrome P450 2E1 to stop NAPQI formation" not the answer?

Cytochrome P450 inhibition is not the antidote's mechanism; its action is mainly on the glutathione side.

Why is "It activates glucuronosyltransferase to speed conjugation of paraceta…" not the answer?

Glucuronosyltransferase is saturated in overdose and N-acetylcysteine does not activate it.

What concept does this question test?

It tests Amino acid metabolism: glutathione in Biochemistry. In overdose the conjugation pathways saturate, more NAPQI forms and glutathione is exhausted, so NAPQI binds hepatocyte proteins and causes centrilobular necrosis. Glutathione is the tripeptide gamma-glutamyl-cysteinyl-glycine, and cysteine supply is rate limiting, which N-acetylcysteine provides.

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 Amino acid metabolism: glutathione?

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.