Malonyl CoA

Definition

Malonyl CoA is a key intermediate in the biosynthesis of fatty acids. It is the activated form of malonic acid, which serves as the two-carbon building block for the elongation of fatty acid chains.

5 Must Know Facts For Your Next Test

1. Malonyl CoA is produced from acetyl CoA by the enzyme acetyl-CoA carboxylase, which adds a carboxyl group to acetyl CoA.
2. The carboxylation of acetyl CoA to malonyl CoA is an irreversible, rate-limiting step in fatty acid biosynthesis.
3. Malonyl CoA serves as the two-carbon extender unit that is repeatedly added to the growing fatty acid chain by fatty acid synthase.
4. The concentration of malonyl CoA is tightly regulated, as it is both an essential precursor and an inhibitor of fatty acid oxidation.
5. Acetyl-CoA carboxylase is allosterically regulated by citrate (an activator) and palmitoyl CoA (an inhibitor), allowing the cell to modulate fatty acid synthesis based on energy and nutrient status.

Review Questions

• Explain the role of malonyl CoA in the biosynthesis of fatty acids.
  • Malonyl CoA is a crucial intermediate in the biosynthesis of fatty acids. It serves as the two-carbon extender unit that is repeatedly added to the growing fatty acid chain by the fatty acid synthase complex. The carboxylation of acetyl CoA to malonyl CoA, catalyzed by acetyl-CoA carboxylase, is the rate-limiting and irreversible step in fatty acid synthesis. This ensures that malonyl CoA is available as the building block for the elongation of fatty acid chains.
• Describe how the regulation of malonyl CoA levels affects fatty acid metabolism.
  • The concentration of malonyl CoA is tightly regulated, as it plays a dual role in fatty acid metabolism. Malonyl CoA is an essential precursor for fatty acid biosynthesis, but it also acts as an allosteric inhibitor of carnitine palmitoyltransferase I, the enzyme that facilitates the transport of fatty acids into the mitochondria for β-oxidation. This allows the cell to modulate fatty acid synthesis and oxidation based on its energy and nutrient status, as signaled by the levels of regulatory molecules like citrate (an activator of acetyl-CoA carboxylase) and palmitoyl CoA (an inhibitor).
• Analyze the significance of the carboxylation of acetyl CoA to malonyl CoA in the context of fatty acid biosynthesis.
  • The carboxylation of acetyl CoA to malonyl CoA, catalyzed by acetyl-CoA carboxylase, is a critical and irreversible step in the biosynthesis of fatty acids. This reaction adds a carboxyl group (CO2-) to acetyl CoA, creating the two-carbon extender unit that is then used by the fatty acid synthase complex to elongate the growing fatty acid chain. The regulation of this carboxylation step, through allosteric modulation of acetyl-CoA carboxylase, allows the cell to fine-tune fatty acid synthesis in response to its energy and nutrient status. This highlights the pivotal role of malonyl CoA as a key metabolic intermediate that links the regulation of fatty acid synthesis and oxidation pathways.

Related terms

Acetyl CoA: Acetyl CoA is the primary input molecule for the fatty acid biosynthesis pathway, providing the initial two-carbon unit.

Fatty Acid Synthase: Fatty acid synthase is the multi-enzyme complex that catalyzes the stepwise addition of malonyl CoA units to the growing fatty acid chain.

Carboxylation: Carboxylation is the process of adding a carboxyl group (CO2-) to a molecule, which in the case of malonyl CoA, is catalyzed by acetyl-CoA carboxylase.