Biomolecules and enzymes: aquaporin-2 and lithium: 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 · Biomolecules and enzymes: aquaporin-2 and lithium

Sample item

A man with bipolar disorder on long-term lithium passes large volumes of dilute urine. After water deprivation and after desmopressin, urine osmolality remains low. Which molecular change in the collecting duct best explains this?

AReduced expression and apical insertion of aquaporin-2 water channelsBFailure of vasopressin synthesis in the supraoptic nucleusCLoss of the thiazide-sensitive sodium-chloride cotransporterDExcess aldosterone-driven sodium reabsorption

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

The answer and the reasoning

A. Reduced expression and apical insertion of aquaporin-2 water channels

Lithium enters principal cells through sodium channels and interferes with vasopressin signalling, reducing aquaporin-2 expression and its insertion into the apical membrane. The kidney then cannot concentrate urine despite normal or high vasopressin, which is nephrogenic diabetes insipidus. Failure to respond to desmopressin separates it from central diabetes insipidus.

Option by option

A. Reduced expression and apical insertion of aquaporin-2 water channels (correct)
Correct. Fewer aquaporin-2 channels at the apical membrane prevent water reabsorption despite desmopressin.
B. Failure of vasopressin synthesis in the supraoptic nucleus
Failed vasopressin synthesis is central diabetes insipidus, which would correct with desmopressin.
C. Loss of the thiazide-sensitive sodium-chloride cotransporter
Loss of the thiazide-sensitive cotransporter (Gitelman syndrome) causes hypokalaemia and salt wasting, not a failure of water channels.
D. Excess aldosterone-driven sodium reabsorption
Excess aldosterone retains sodium and water, and does not cause dilute polyuria.

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, Reduced expression and apical insertion of aquaporin-2 water channels. Lithium enters principal cells through sodium channels and interferes with vasopressin signalling, reducing aquaporin-2 expression and its insertion into the apical membrane.

Why is "Failure of vasopressin synthesis in the supraoptic nucleus" not the answer?

Failed vasopressin synthesis is central diabetes insipidus, which would correct with desmopressin.

Why is "Loss of the thiazide-sensitive sodium-chloride cotransporter" not the answer?

Loss of the thiazide-sensitive cotransporter (Gitelman syndrome) causes hypokalaemia and salt wasting, not a failure of water channels.

Why is "Excess aldosterone-driven sodium reabsorption" not the answer?

Excess aldosterone retains sodium and water, and does not cause dilute polyuria.

What concept does this question test?

It tests Biomolecules and enzymes: aquaporin-2 and lithium in Biochemistry. The kidney then cannot concentrate urine despite normal or high vasopressin, which is nephrogenic diabetes insipidus. Failure to respond to desmopressin separates it from central diabetes insipidus.

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 Biomolecules and enzymes: aquaporin-2 and lithium?

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.