Amino acid metabolism: gamma-glutamyl cycle and 5-oxoproline: 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: gamma-glutamyl cycle and 5-oxoproline

Sample item

A malnourished 60-year-old woman on regular paracetamol for chronic pain is admitted with sepsis and a high anion gap metabolic acidosis. Lactate, ketones, osmolal gap and renal function are normal. Urine organic acid analysis shows markedly raised pyroglutamic acid (5-oxoproline). Which mechanism explains this?

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

The answer and the reasoning

A. Glutathione depletion removes feedback inhibition of gamma-glutamylcysteine synthetase, causing overproduction of 5-oxoproline

Glutathione normally inhibits gamma-glutamylcysteine synthetase. When glutathione is consumed by conjugating paracetamol metabolites, especially in malnutrition with low cysteine, the feedback is lost. Excess gamma-glutamylcysteine is converted into 5-oxoproline faster than 5-oxoprolinase can process it, causing high anion gap acidosis.

Option by option

  • A. Glutathione depletion removes feedback inhibition of gamma-glutamylcysteine synthetase, causing overproduction of 5-oxoproline (correct)

    Correct. Loss of glutathione feedback drives the gamma-glutamyl cycle and 5-oxoproline accumulation.

  • B. Inhibition of pyruvate dehydrogenase from thiamine deficiency

    Thiamine deficiency causes lactic acidosis, and lactate is normal here.

  • C. Block of methylmalonyl-CoA mutase from cobalamin deficiency

    Cobalamin deficiency raises methylmalonic acid, not 5-oxoproline.

  • D. Direct acid formation from the toxic metabolite NAPQI

    NAPQI depletes glutathione and injures hepatocytes but is not itself an organic acid causing the gap.

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 A, Glutathione depletion removes feedback inhibition of gamma-glutamylcysteine synthetase, causing overproduction of 5-oxoproline. Glutathione normally inhibits gamma-glutamylcysteine synthetase.

Why is "Inhibition of pyruvate dehydrogenase from thiamine deficiency" not the answer?

Thiamine deficiency causes lactic acidosis, and lactate is normal here.

Why is "Block of methylmalonyl-CoA mutase from cobalamin deficiency" not the answer?

Cobalamin deficiency raises methylmalonic acid, not 5-oxoproline.

Why is "Direct acid formation from the toxic metabolite NAPQI" not the answer?

NAPQI depletes glutathione and injures hepatocytes but is not itself an organic acid causing the gap.

What concept does this question test?

It tests Amino acid metabolism: gamma-glutamyl cycle and 5-oxoproline in Biochemistry. When glutathione is consumed by conjugating paracetamol metabolites, especially in malnutrition with low cysteine, the feedback is lost. Excess gamma-glutamylcysteine is converted into 5-oxoproline faster than 5-oxoprolinase can process it, causing high anion gap acidosis.

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 Amino acid metabolism: gamma-glutamyl cycle and 5-oxoproline?

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.