Vitamins and minerals: holocarboxylase synthetase deficiency: 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 · Vitamins and minerals: holocarboxylase synthetase deficiency

Sample item

A 3-week-old infant has a scaly erythematous rash, alopecia, hypotonia, vomiting and ketolactic acidosis. Urine contains 3-hydroxyisovalerate and methylcitrate, and biotinidase activity is normal. Large oral doses of biotin produce dramatic improvement. Which enzyme is defective?

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

The answer and the reasoning

A. Holocarboxylase synthetase

Holocarboxylase synthetase attaches biotin to the apoenzymes of the four carboxylases, so its deficiency causes multiple carboxylase deficiency with organic aciduria. A high Km for biotin explains the response to pharmacological doses. Biotinidase deficiency gives a similar picture but biotinidase activity is low.

Option by option

  • A. Holocarboxylase synthetase (correct)

    Correct. Without this enzyme, biotin cannot be attached to the carboxylases, and large biotin doses overcome the defect.

  • B. Methylmalonyl-CoA mutase

    A mutase defect causes isolated methylmalonic aciduria and does not respond to biotin.

  • C. Propionyl-CoA carboxylase apoenzyme

    A defect confined to this one apoenzyme would not impair the other biotin-dependent carboxylases or respond to biotin.

  • D. Biotinidase

    Biotinidase activity is stated to be normal in this infant.

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, Holocarboxylase synthetase. Holocarboxylase synthetase attaches biotin to the apoenzymes of the four carboxylases, so its deficiency causes multiple carboxylase deficiency with organic aciduria.

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

A mutase defect causes isolated methylmalonic aciduria and does not respond to biotin.

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

A defect confined to this one apoenzyme would not impair the other biotin-dependent carboxylases or respond to biotin.

Why is "Biotinidase" not the answer?

Biotinidase activity is stated to be normal in this infant.

What concept does this question test?

It tests Vitamins and minerals: holocarboxylase synthetase deficiency in Biochemistry. A high Km for biotin explains the response to pharmacological doses. Biotinidase deficiency gives a similar picture but biotinidase activity is low.

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 Vitamins and minerals: holocarboxylase synthetase deficiency?

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.