How does malonyl-CoA regulate fatty acid oxidation and synthesis to prevent futile cycling?

• A. Malonyl-CoA inhibits CPT I, preventing mitochondrial fatty entry for oxidation while enabling cytosolic fatty acid synthesis.
• B. Malonyl-CoA activates CPT I, increasing oxidation.
• C. Malonyl-CoA inhibits acetyl-CoA carboxylase.
• D. Malonyl-CoA is not involved in regulation of fatty acid metabolism.

Answer: (A)

Malonyl-CoA acts as a switch that coordinates fatty acid synthesis with oxidation. It inhibits CPT I, the enzyme that imports long-chain fatty acyl-CoA into mitochondria for beta-oxidation, so fatty acids aren’t oxidized while they’re being synthesized. At the same time, malonyl-CoA is the substrate for cytosolic fatty acid synthesis, formed by acetyl-CoA carboxylase. When synthesis is active, malonyl-CoA levels rise and oxidation is blocked, preventing futile cycling. In energy-demanding states, signals like AMPK lower malonyl-CoA by inhibiting acetyl-CoA carboxylase, freeing CPT I to drive oxidation.