Amino acid metabolism: homocysteine with methylmalonate: 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: homocysteine with methylmalonate

Sample item

Two patients have macrocytic anaemia with raised plasma homocysteine. Methylmalonic acid is raised in the first patient and normal in the second. What is the best interpretation?

AFirst has cobalamin deficiency; second has folate deficiencyBBoth have cobalamin deficiencyCFirst has pyridoxine deficiency; second has niacin deficiencyDFirst has folate deficiency; second has cobalamin deficiency

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

The answer and the reasoning

A. First has cobalamin deficiency; second has folate deficiency

Homocysteine rises in both folate and cobalamin deficiency, because methionine synthase needs methyl-tetrahydrofolate and methylcobalamin. Methylmalonic acid rises only in cobalamin deficiency, because the mutase also needs adenosylcobalamin.

Option by option

A. First has cobalamin deficiency; second has folate deficiency (correct)
Correct. A raised methylmalonic acid marks cobalamin deficiency, while folate deficiency leaves it normal.
B. Both have cobalamin deficiency
Cobalamin deficiency in the second patient would have raised methylmalonic acid, which is normal.
C. First has pyridoxine deficiency; second has niacin deficiency
Pyridoxine and niacin deficiency do not typically cause macrocytic anaemia with a raised homocysteine pattern like this.
D. First has folate deficiency; second has cobalamin deficiency
This reverses the logic; folate is not a cofactor of the mutase, so methylmalonic acid cannot rise from folate lack.

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.

Questions about this Biochemistry question

What is the answer to this Biochemistry question?

The best answer is A, First has cobalamin deficiency; second has folate deficiency. Homocysteine rises in both folate and cobalamin deficiency, because methionine synthase needs methyl-tetrahydrofolate and methylcobalamin.

Why is "Both have cobalamin deficiency" not the answer?

Cobalamin deficiency in the second patient would have raised methylmalonic acid, which is normal.

Why is "First has pyridoxine deficiency; second has niacin deficiency" not the answer?

Pyridoxine and niacin deficiency do not typically cause macrocytic anaemia with a raised homocysteine pattern like this.

Why is "First has folate deficiency; second has cobalamin deficiency" not the answer?

This reverses the logic; folate is not a cofactor of the mutase, so methylmalonic acid cannot rise from folate lack.

What concept does this question test?

It tests Amino acid metabolism: homocysteine with methylmalonate in Biochemistry. Methylmalonic acid rises only in cobalamin deficiency, because the mutase also needs adenosylcobalamin.

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: homocysteine with methylmalonate?

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.