Amino acid metabolism: hyperinsulinism-hyperammonaemia syndrome: 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: hyperinsulinism-hyperammonaemia syndrome

Sample item

A 9-month-old has recurrent hypoglycaemia after protein-rich meals and fasting, with inappropriately high insulin and persistent mild hyperammonaemia of about 2 to 3 times normal. Which enzyme abnormality explains the combination?

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

The answer and the reasoning

D. Gain-of-function of glutamate dehydrogenase

Activating mutations in glutamate dehydrogenase remove the inhibition normally exerted by GTP. Increased oxidative deamination of glutamate in beta cells raises ATP and promotes insulin release, and increased deamination in liver releases ammonia. Leucine, which activates the enzyme, provokes hypoglycaemia.

Option by option

  • A. Deficiency of glucose-6-phosphatase

    Glucose-6-phosphatase deficiency causes fasting hypoglycaemia with low insulin and lactic acidosis.

  • B. Loss of function of glucokinase

    Glucokinase loss of function raises the glucose threshold for insulin secretion and does not give hypoglycaemia.

  • C. Deficiency of carbamoyl phosphate synthetase I

    CPS I deficiency causes severe hyperammonaemia without hyperinsulinism.

  • D. Gain-of-function of glutamate dehydrogenase (correct)

    Correct. An overactive enzyme releases ammonia and stimulates insulin secretion in response to amino acids.

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, Gain-of-function of glutamate dehydrogenase. Activating mutations in glutamate dehydrogenase remove the inhibition normally exerted by GTP.

Why is "Deficiency of glucose-6-phosphatase" not the answer?

Glucose-6-phosphatase deficiency causes fasting hypoglycaemia with low insulin and lactic acidosis.

Why is "Loss of function of glucokinase" not the answer?

Glucokinase loss of function raises the glucose threshold for insulin secretion and does not give hypoglycaemia.

Why is "Deficiency of carbamoyl phosphate synthetase I" not the answer?

CPS I deficiency causes severe hyperammonaemia without hyperinsulinism.

What concept does this question test?

It tests Amino acid metabolism: hyperinsulinism-hyperammonaemia syndrome in Biochemistry. Increased oxidative deamination of glutamate in beta cells raises ATP and promotes insulin release, and increased deamination in liver releases ammonia. Leucine, which activates the enzyme, provokes hypoglycaemia.

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: hyperinsulinism-hyperammonaemia syndrome?

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.