Amino acid metabolism: isolated methylmalonic 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: isolated methylmalonic acidaemia

Sample item

A 5-day-old neonate is vomiting and lethargic with tachypnoea, a high anion gap metabolic acidosis, ketonuria and hyperammonaemia. Urine organic acids show grossly raised methylmalonic acid. Maternal and infant vitamin B12 levels and plasma homocysteine are normal. Which enzyme is most likely defective?

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

The answer and the reasoning

A. Methylmalonyl-CoA mutase

Methylmalonyl-CoA mutase converts methylmalonyl-CoA to succinyl-CoA using adenosylcobalamin. A mutase defect with normal B12 and normal homocysteine points to the isolated enzyme defect, with methylmalonic acid accumulating behind the block. Propionyl-CoA carboxylase deficiency raises propionate metabolites instead.

Option by option

  • A. Methylmalonyl-CoA mutase (correct)

    Correct. A block at the mutase step lets methylmalonyl-CoA and its acid build up while B12 and homocysteine stay normal.

  • B. Propionyl-CoA carboxylase

    Deficiency of this enzyme blocks the step before methylmalonyl-CoA, so propionic acid and 3-hydroxypropionate accumulate rather than methylmalonic acid.

  • C. Isovaleryl-CoA dehydrogenase

    Deficiency of this leucine pathway enzyme causes isovaleric acid accumulation and a sweaty-feet odour, not methylmalonic acid.

  • D. Methionine synthase

    Deficiency of methionine synthase raises homocysteine, which is normal here, and does not 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 A, Methylmalonyl-CoA mutase. Methylmalonyl-CoA mutase converts methylmalonyl-CoA to succinyl-CoA using adenosylcobalamin.

Why is "Propionyl-CoA carboxylase" not the answer?

Deficiency of this enzyme blocks the step before methylmalonyl-CoA, so propionic acid and 3-hydroxypropionate accumulate rather than methylmalonic acid.

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

Deficiency of this leucine pathway enzyme causes isovaleric acid accumulation and a sweaty-feet odour, not methylmalonic acid.

Why is "Methionine synthase" not the answer?

Deficiency of methionine synthase raises homocysteine, which is normal here, and does not raise methylmalonic acid.

What concept does this question test?

It tests Amino acid metabolism: isolated methylmalonic acidaemia in Biochemistry. A mutase defect with normal B12 and normal homocysteine points to the isolated enzyme defect, with methylmalonic acid accumulating behind the block. Propionyl-CoA carboxylase deficiency raises propionate metabolites instead.

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: isolated methylmalonic 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.