Amino acid metabolism: remethylation defect MTHFR: 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: remethylation defect MTHFR

Sample item

A 3-year-old with developmental delay and seizures has raised plasma and urinary homocysteine with low plasma methionine. There is no marfanoid habitus or lens dislocation, and urinary methylmalonic acid is normal. A defect in which enzyme is most likely?

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

The answer and the reasoning

B. Methylenetetrahydrofolate reductase

Methylenetetrahydrofolate reductase makes 5-methyltetrahydrofolate, the methyl donor for methionine synthase. When it is deficient, homocysteine cannot be remethylated, so homocysteine rises while methionine is low. Classic cystathionine beta-synthase deficiency instead raises methionine and gives lens dislocation and a marfanoid build.

Option by option

  • A. Methylmalonyl-CoA mutase

    Methylmalonyl-CoA mutase deficiency raises methylmalonic acid, which is normal here.

  • B. Methylenetetrahydrofolate reductase (correct)

    Correct. Without 5-methyltetrahydrofolate, homocysteine is not remethylated to methionine, giving high homocysteine and low methionine.

  • C. Homogentisate oxidase

    Homogentisate oxidase deficiency is alkaptonuria, which does not raise homocysteine.

  • D. Cystathionine beta-synthase

    Cystathionine beta-synthase deficiency raises methionine and typically causes ectopia lentis and marfanoid features.

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, Methylenetetrahydrofolate reductase. Methylenetetrahydrofolate reductase makes 5-methyltetrahydrofolate, the methyl donor for methionine synthase.

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

Methylmalonyl-CoA mutase deficiency raises methylmalonic acid, which is normal here.

Why is "Homogentisate oxidase" not the answer?

Homogentisate oxidase deficiency is alkaptonuria, which does not raise homocysteine.

Why is "Cystathionine beta-synthase" not the answer?

Cystathionine beta-synthase deficiency raises methionine and typically causes ectopia lentis and marfanoid features.

What concept does this question test?

It tests Amino acid metabolism: remethylation defect MTHFR in Biochemistry. When it is deficient, homocysteine cannot be remethylated, so homocysteine rises while methionine is low. Classic cystathionine beta-synthase deficiency instead raises methionine and gives lens dislocation and a marfanoid build.

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: remethylation defect MTHFR?

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.