Amino acid metabolism: valproate and hyperammonaemia: 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 · Amino acid metabolism: valproate and hyperammonaemia

Sample item

A child on sodium valproate for epilepsy becomes lethargic and vomits. Liver enzymes are normal but ammonia is raised, and carbamoyl phosphate synthetase I activity is reduced. Which mechanism links the drug to the urea cycle?

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

The answer and the reasoning

B. Reduced N-acetylglutamate formation, so carbamoyl phosphate synthetase I is not activated

Valproate metabolites reduce the supply of acetyl-CoA and inhibit N-acetylglutamate synthase, so N-acetylglutamate, the obligatory activator of carbamoyl phosphate synthetase I, falls. The urea cycle then slows and ammonia accumulates. Carnitine depletion adds to the problem, and the treatment is to stop the drug and give carglumic acid or carnitine.

Option by option

  • A. Depletion of aspartate needed for argininosuccinate synthetase

    Aspartate depletion would affect a later step and would not reduce CPS-I activity.

  • B. Reduced N-acetylglutamate formation, so carbamoyl phosphate synthetase I is not activated (correct)

    Correct. Lack of the allosteric activator N-acetylglutamate leaves CPS-I inactive.

  • C. Inhibition of arginase in the cytosol

    Arginase is not the target, and its inhibition would raise arginine rather than reduce CPS-I.

  • D. Direct inhibition of ornithine transcarbamylase

    Valproate does not directly inhibit ornithine transcarbamylase.

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 B, Reduced N-acetylglutamate formation, so carbamoyl phosphate synthetase I is not activated. Valproate metabolites reduce the supply of acetyl-CoA and inhibit N-acetylglutamate synthase, so N-acetylglutamate, the obligatory activator of carbamoyl phosphate synthetase I, falls.

Why is "Depletion of aspartate needed for argininosuccinate synthetase" not the answer?

Aspartate depletion would affect a later step and would not reduce CPS-I activity.

Why is "Inhibition of arginase in the cytosol" not the answer?

Arginase is not the target, and its inhibition would raise arginine rather than reduce CPS-I.

Why is "Direct inhibition of ornithine transcarbamylase" not the answer?

Valproate does not directly inhibit ornithine transcarbamylase.

What concept does this question test?

It tests Amino acid metabolism: valproate and hyperammonaemia in Biochemistry. The urea cycle then slows and ammonia accumulates. Carnitine depletion adds to the problem, and the treatment is to stop the drug and give carglumic acid or carnitine.

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: valproate and hyperammonaemia?

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.