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​The figure below depicts the feedback regulation in the biosynthesis pathway of three branched-chain amino acids (BCAA) - Leu, Val, and Ile, acting a
Question

The figure below depicts the feedback regulation in the biosynthesis pathway of three branched-chain amino acids (BCAA) - Leu, Val, and Ile, acting at three major steps catalyzed by enzymes AHAS, IPMS, and TD. The activity of AHAS is feedback regulated by the synergistic combination of Leu and Val. IPMS activity is regulated exclusively by Leu. Ile regulates TD activity, while Val can relax this feedback regulation on TD by Ile.

Which one of the following possibilities of BCAA pools is likely to occur in the RNAi knockdown of IPMS?

A.

Both Leu and Val will decrease.

B.

Leu will decrease, and Val remains unchanged.

C.

Leu will decrease, and both Val and Ile will increase.

D.

Only Leu will decrease.

Correct option is C

Explanation:

  • IPMS knockdown reduces Leu biosynthesis, so Leu decreases.

  • Because Leu negatively regulates AHAS, lower Leu levels release AHAS from inhibition, causing increased flux towards Val and Ile biosynthesis.

  • Consequently, Val and Ile levels increase due to increased AHAS activity and enhanced precursor flow into their pathways.

  • This exemplifies feedback regulation and pathway branching.

Information Booster:

  • AHAS is the common upstream enzyme producing precursors for Val, Leu, and Ile.

  • Leu acts as a feedback inhibitor of both AHAS and IPMS.

  • Reduction of Leu reduces feedback inhibition, increasing AHAS activity and boosting Val and Ile synthesis.

  • This metabolic regulation maintains BCAA balance.

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