Question:medium
Hyperammonaemia inhibits the TCA cycle by depleting which intermediate?
Hyperammonaemia inhibits the TCA cycle by depleting which intermediate?
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Ammonia is mopped up as glutamate, drawing this TCA intermediate away.
Updated On: Jun 23, 2026
- Succinate
- Alpha ketoglutarate
- Malate
- Fumarate
Show Solution
The Correct Option is B
Solution and Explanation
Step 1: Excess ammonia is toxic, so the cell converts it into the harmless carrier glutamine. The first trap for ammonia is the formation of glutamate.
Step 2: Glutamate is built by adding ammonia onto a TCA-cycle carbon skeleton, namely $\alpha$-ketoglutarate. The sequence runs $\alpha\text{-ketoglutarate} + NH_4^+ \rightarrow \text{glutamate} \rightarrow \text{glutamine}$.
Step 3: Because $\alpha$-ketoglutarate is being siphoned off for ammonia disposal, less of it remains to keep the citric acid cycle turning. The cycle is therefore throttled by loss of this single intermediate, not by succinate, malate, or fumarate.\[\boxed{Alpha\ ketoglutarate}\]
Step 2: Glutamate is built by adding ammonia onto a TCA-cycle carbon skeleton, namely $\alpha$-ketoglutarate. The sequence runs $\alpha\text{-ketoglutarate} + NH_4^+ \rightarrow \text{glutamate} \rightarrow \text{glutamine}$.
Step 3: Because $\alpha$-ketoglutarate is being siphoned off for ammonia disposal, less of it remains to keep the citric acid cycle turning. The cycle is therefore throttled by loss of this single intermediate, not by succinate, malate, or fumarate.\[\boxed{Alpha\ ketoglutarate}\]
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