Amino acid metabolism: propionic acidaemia: 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: propionic acidaemia

Sample item

A 4-day-old breastfed neonate has vomiting, poor feeding and lethargy, with high anion gap metabolic acidosis and hyperammonaemia. Urine organic acid analysis shows 3-hydroxypropionate and methylcitrate, while methylmalonic acid is not raised. Which enzyme is deficient?

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

The answer and the reasoning

C. Propionyl-CoA carboxylase

Propionyl-CoA, derived from isoleucine, valine, methionine, threonine and odd-chain fatty acids, is carboxylated to methylmalonyl-CoA by the biotin-dependent enzyme propionyl-CoA carboxylase. When it is deficient, propionyl-CoA backs up and alternative products such as 3-hydroxypropionate and methylcitrate appear, with ketoacidosis and secondary hyperammonaemia. Methylmalonic acid is normal because the block lies before its formation.

Option by option

  • A. Branched-chain alpha-ketoacid dehydrogenase

    Branched-chain ketoacid dehydrogenase deficiency causes maple syrup urine disease with raised branched-chain amino acids.

  • B. Isovaleryl-CoA dehydrogenase

    Isovaleryl-CoA dehydrogenase deficiency gives isovalerylglycine and a sweaty-feet odour.

  • C. Propionyl-CoA carboxylase (correct)

    Correct. A block before methylmalonyl-CoA explains propionate metabolites with normal methylmalonic acid.

  • D. Methylmalonyl-CoA mutase

    Methylmalonyl-CoA mutase deficiency would raise methylmalonic acid.

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, Propionyl-CoA carboxylase. Propionyl-CoA, derived from isoleucine, valine, methionine, threonine and odd-chain fatty acids, is carboxylated to methylmalonyl-CoA by the biotin-dependent enzyme propionyl-CoA carboxylase.

Why is "Branched-chain alpha-ketoacid dehydrogenase" not the answer?

Branched-chain ketoacid dehydrogenase deficiency causes maple syrup urine disease with raised branched-chain amino acids.

Why is "Isovaleryl-CoA dehydrogenase" not the answer?

Isovaleryl-CoA dehydrogenase deficiency gives isovalerylglycine and a sweaty-feet odour.

Why is "Methylmalonyl-CoA mutase" not the answer?

Methylmalonyl-CoA mutase deficiency would raise methylmalonic acid.

What concept does this question test?

It tests Amino acid metabolism: propionic acidaemia in Biochemistry. When it is deficient, propionyl-CoA backs up and alternative products such as 3-hydroxypropionate and methylcitrate appear, with ketoacidosis and secondary hyperammonaemia. Methylmalonic acid is normal because the block lies before its formation.

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: propionic acidaemia?

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.