Question:
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
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The Correct Option is B
Solution and Explanation
Step 1: The urea cycle and the citric acid (TCA) cycle are separate pathways but are linked through shared intermediates.
Step 2: In hyperammonaemia, the body tries to detoxify excess ammonia by forming glutamate and then glutamine. Glutamate is generated from alpha-ketoglutarate by reductive amination/transamination: alpha-ketoglutarate + NH4+ → glutamate → glutamine.
Step 3: This pulls alpha-ketoglutarate out of the TCA cycle. With alpha-ketoglutarate depleted, the cycle slows down. Succinate, malate, and fumarate are downstream of alpha-ketoglutarate and are not the directly consumed substrate, so the answer is alpha-ketoglutarate.
Step 2: In hyperammonaemia, the body tries to detoxify excess ammonia by forming glutamate and then glutamine. Glutamate is generated from alpha-ketoglutarate by reductive amination/transamination: alpha-ketoglutarate + NH4+ → glutamate → glutamine.
Step 3: This pulls alpha-ketoglutarate out of the TCA cycle. With alpha-ketoglutarate depleted, the cycle slows down. Succinate, malate, and fumarate are downstream of alpha-ketoglutarate and are not the directly consumed substrate, so the answer is alpha-ketoglutarate.
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