Amino acid metabolism: asparagine depletion therapy: 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: asparagine depletion therapy

Sample item

A child with acute lymphoblastic leukaemia is treated with L-asparaginase. What explains the selective toxicity of this enzyme to the leukaemic lymphoblasts?

AThey have little asparagine synthetase and depend on circulating asparagineBThey overproduce asparagine synthetase and exhaust the aspartate poolCThey lack glutamine synthetase and depend on circulating glutamineDThey cannot transaminate oxaloacetate and so lack aspartate

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

The answer and the reasoning

A. They have little asparagine synthetase and depend on circulating asparagine

Normal cells make asparagine from aspartate and glutamine using asparagine synthetase. Many lymphoblasts express little of this enzyme and rely on plasma asparagine, so depleting it halts their protein synthesis while normal cells cope.

Option by option

A. They have little asparagine synthetase and depend on circulating asparagine (correct)
Correct. Low asparagine synthetase leaves the blasts dependent on plasma asparagine, which the drug removes.
B. They overproduce asparagine synthetase and exhaust the aspartate pool
Overproduction would make the cells resistant to the drug, the opposite of what happens.
C. They lack glutamine synthetase and depend on circulating glutamine
The enzyme acts on asparagine, not glutamine, so this does not explain its selectivity.
D. They cannot transaminate oxaloacetate and so lack aspartate
Leukaemic cells can transaminate oxaloacetate; their problem is the final amidation step to asparagine.

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, They have little asparagine synthetase and depend on circulating asparagine. Normal cells make asparagine from aspartate and glutamine using asparagine synthetase.

Why is "They overproduce asparagine synthetase and exhaust the aspartate pool" not the answer?

Overproduction would make the cells resistant to the drug, the opposite of what happens.

Why is "They lack glutamine synthetase and depend on circulating glutamine" not the answer?

The enzyme acts on asparagine, not glutamine, so this does not explain its selectivity.

Why is "They cannot transaminate oxaloacetate and so lack aspartate" not the answer?

Leukaemic cells can transaminate oxaloacetate; their problem is the final amidation step to asparagine.

What concept does this question test?

It tests Amino acid metabolism: asparagine depletion therapy in Biochemistry. Many lymphoblasts express little of this enzyme and rely on plasma asparagine, so depleting it halts their protein synthesis while normal cells cope.

How hard is this question?

We tag it as an application question: it asks you to use a fact on a patient or a finding. 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: asparagine depletion therapy?

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.