Amino acid metabolism: nitisinone in alkaptonuria: 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: nitisinone in alkaptonuria

Sample item

A man with alkaptonuria is given nitisinone, which lowers his urinary homogentisic acid. What is its site of action?

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

The answer and the reasoning

D. Inhibits 4-hydroxyphenylpyruvate dioxygenase, upstream of the block

Homogentisate accumulates because homogentisate oxidase is missing. Nitisinone blocks 4-hydroxyphenylpyruvate dioxygenase, the enzyme that makes homogentisate, so less pigment precursor reaches the block. In tyrosinaemia type I the same drug prevents toxic downstream metabolites.

Option by option

  • A. Inhibits fumarylacetoacetate hydrolase, downstream of the block

    Blocking this downstream enzyme would cause accumulation of toxic metabolites, as in tyrosinaemia type I, and would not reduce homogentisate.

  • B. Activates tyrosine aminotransferase to speed tyrosine breakdown

    Activating tyrosine transamination would not stop the block and is not how the drug works.

  • C. Inhibits phenylalanine hydroxylase to reduce tyrosine formation

    Inhibiting phenylalanine hydroxylase would induce hyperphenylalaninaemia without removing homogentisate.

  • D. Inhibits 4-hydroxyphenylpyruvate dioxygenase, upstream of the block (correct)

    Correct. Blocking homogentisate formation lowers the substrate of the deficient enzyme.

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 D, Inhibits 4-hydroxyphenylpyruvate dioxygenase, upstream of the block. Homogentisate accumulates because homogentisate oxidase is missing.

Why is "Inhibits fumarylacetoacetate hydrolase, downstream of the block" not the answer?

Blocking this downstream enzyme would cause accumulation of toxic metabolites, as in tyrosinaemia type I, and would not reduce homogentisate.

Why is "Activates tyrosine aminotransferase to speed tyrosine breakdown" not the answer?

Activating tyrosine transamination would not stop the block and is not how the drug works.

Why is "Inhibits phenylalanine hydroxylase to reduce tyrosine formation" not the answer?

Inhibiting phenylalanine hydroxylase would induce hyperphenylalaninaemia without removing homogentisate.

What concept does this question test?

It tests Amino acid metabolism: nitisinone in alkaptonuria in Biochemistry. Nitisinone blocks 4-hydroxyphenylpyruvate dioxygenase, the enzyme that makes homogentisate, so less pigment precursor reaches the block. In tyrosinaemia type I the same drug prevents toxic downstream metabolites.

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: nitisinone in alkaptonuria?

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.