Acetyl-CoA Carboxylase

Definition

Acetyl-CoA carboxylase is an important enzyme that catalyzes the conversion of acetyl-CoA to malonyl-CoA, a crucial step in fatty acid synthesis. This enzyme plays a central role in regulating lipid metabolism by controlling the availability of malonyl-CoA, which not only serves as a building block for fatty acids but also inhibits fatty acid oxidation. The activity of acetyl-CoA carboxylase is influenced by various metabolic states, highlighting its significance in energy storage and utilization.

5 Must Know Facts For Your Next Test

1. Acetyl-CoA carboxylase exists in two main isoforms: ACC1 and ACC2, which are found in different tissues and have distinct regulatory mechanisms.
2. The enzyme is activated by citrate, which signals an abundance of substrates for fatty acid synthesis, while it is inhibited by long-chain fatty acyl-CoAs indicating sufficient fatty acid levels.
3. Acetyl-CoA carboxylase plays a dual role in metabolism by not only providing malonyl-CoA for fatty acid synthesis but also inhibiting mitochondrial fatty acid oxidation.
4. Hormonal regulation affects the activity of acetyl-CoA carboxylase; insulin promotes its activity to facilitate fat storage, while glucagon and epinephrine inhibit it to enhance fat breakdown.
5. Deficiencies or mutations in acetyl-CoA carboxylase can lead to metabolic disorders, affecting the body's ability to store and utilize fats properly.

Review Questions

• How does the regulation of acetyl-CoA carboxylase reflect changes in metabolic states, such as fed versus fasting?
  • In the fed state, acetyl-CoA carboxylase is activated by insulin and citrate, promoting fatty acid synthesis and fat storage. Conversely, during fasting, glucagon and epinephrine inhibit the enzyme's activity, facilitating fatty acid oxidation for energy production. This regulatory mechanism ensures that the body effectively manages energy storage and utilization based on nutrient availability.
• Discuss the interplay between acetyl-CoA carboxylase and other enzymes involved in lipid metabolism, including how they integrate metabolic pathways.
  • Acetyl-CoA carboxylase works closely with fatty acid synthase to ensure a steady supply of malonyl-CoA for fatty acid synthesis. Additionally, malonyl-CoA produced by this enzyme inhibits carnitine palmitoyltransferase 1 (CPT1), which prevents the transport of fatty acids into mitochondria for oxidation. This interplay highlights how acetyl-CoA carboxylase integrates anabolic and catabolic pathways to balance lipid metabolism.
• Evaluate the implications of altered acetyl-CoA carboxylase activity on metabolic health and potential therapeutic targets for metabolic disorders.
  • Alterations in acetyl-CoA carboxylase activity can significantly impact metabolic health, leading to conditions such as obesity or insulin resistance. For instance, excessive activity may promote fat accumulation, while insufficient activity could impair lipid storage and lead to fat mobilization issues. Understanding its regulatory mechanisms offers potential therapeutic targets; for example, modulating its activity through small molecules or gene therapy could restore metabolic balance in individuals with dysregulated lipid metabolism.

Related terms

Malonyl-CoA: Malonyl-CoA is a key intermediate in fatty acid synthesis that is formed from acetyl-CoA through the action of acetyl-CoA carboxylase.

Fatty Acid Synthase: Fatty acid synthase is a multi-enzyme complex that synthesizes fatty acids from acetyl-CoA and malonyl-CoA, playing a crucial role in lipid metabolism.

AMP-activated Protein Kinase (AMPK): AMPK is an energy-sensing enzyme that regulates acetyl-CoA carboxylase activity in response to cellular energy levels, promoting fatty acid oxidation when energy is low.