Question

Hyperammonaemia inhibit TCA cycle by depleting?

• A. succinate
• B. a keto glutarate
• C. malate
• D. fumarate

Answer 1

The Correct Option is B

Hyperammonaemia can inhibit the Tricarboxylic Acid (TCA) cycle primarily by depleting α-ketoglutarate. This occurs because excess ammonia (NH₃) reacts with α-ketoglutarate to form glutamate and subsequently glutamine. This process impacts the TCA cycle as follows:

• α-ketoglutarate consumption: Ammonia is detoxified primarily in the liver where it combines with α-ketoglutarate in a reaction catalyzed by glutamate dehydrogenase to form glutamate:

α-ketoglutarate + NH₃ + NAD(P)H ⇌ glutamate + NAD(P)⁺ + H₂O

• Further conversion of glutamate to glutamine by the addition of another ammonia molecule results in the depletion of α-ketoglutarate:

glutamate + NH₃ + ATP → glutamine + ADP + Pi

• Impact on TCA cycle: As α-ketoglutarate is a key intermediate in the TCA cycle, its depletion reduces the cycle's efficiency, limiting the production of energy and essential metabolites.
• Conclusion: The depletion of α-ketoglutarate is the primary inhibitory effect of hyperammonaemia on the TCA cycle.