Acetyl-CoA Carboxylase

Definition

Acetyl-CoA carboxylase is an enzyme that catalyzes the conversion of acetyl-CoA to malonyl-CoA, a crucial step in the biosynthesis of fatty acids. This enzyme plays a pivotal role in regulating lipid metabolism and is considered a key control point for fatty acid synthesis, influencing both energy storage and membrane formation.

5 Must Know Facts For Your Next Test

1. Acetyl-CoA carboxylase is an allosteric enzyme that is activated by citrate and inhibited by long-chain fatty acyl-CoAs, allowing for fine-tuned regulation of fatty acid synthesis based on metabolic needs.
2. The enzyme requires biotin as a cofactor, which is essential for its carboxylation reaction that adds a carbon dioxide molecule to acetyl-CoA to form malonyl-CoA.
3. Acetyl-CoA carboxylase exists in two isoforms: ACC1 and ACC2, with ACC1 primarily found in lipogenic tissues and ACC2 associated with oxidative tissues.
4. The regulation of acetyl-CoA carboxylase is critical for metabolic health; dysregulation can lead to disorders such as obesity and type 2 diabetes due to altered fatty acid metabolism.
5. Acetyl-CoA carboxylase plays a role in the integration of carbohydrate and lipid metabolism, responding to insulin signaling and energy availability in the body.

Review Questions

• How does acetyl-CoA carboxylase function within the context of fatty acid synthesis?
  • Acetyl-CoA carboxylase initiates fatty acid synthesis by converting acetyl-CoA into malonyl-CoA, which serves as a key substrate for the fatty acid synthase complex. This enzymatic reaction not only sets the stage for the elongation of fatty acids but also acts as a regulatory point. The activity of acetyl-CoA carboxylase thus directly impacts the overall rate of fatty acid production in response to cellular energy levels.
• Discuss the regulatory mechanisms that control the activity of acetyl-CoA carboxylase.
  • The activity of acetyl-CoA carboxylase is regulated by several mechanisms, including allosteric modulation and covalent modification. Citrate acts as an allosteric activator, signaling that there are ample substrates available for fatty acid synthesis. In contrast, long-chain fatty acyl-CoAs inhibit its activity, preventing excess fatty acid production when lipid levels are sufficient. Additionally, phosphorylation by AMP-activated protein kinase (AMPK) leads to inactivation of the enzyme during energy deficit conditions.
• Evaluate the implications of dysregulation of acetyl-CoA carboxylase in metabolic disorders.
  • Dysregulation of acetyl-CoA carboxylase can have significant consequences for metabolic health, particularly leading to obesity and type 2 diabetes. When acetyl-CoA carboxylase is overly active, it promotes excessive fatty acid synthesis, contributing to increased lipid accumulation and insulin resistance. Conversely, insufficient activity can disrupt normal lipid metabolism and energy homeostasis. Understanding these pathways provides insight into potential therapeutic targets for managing metabolic diseases.

Related terms

Fatty Acid Synthase: A multi-enzyme complex that catalyzes the synthesis of fatty acids from malonyl-CoA and acetyl-CoA, elongating the carbon chain to produce long-chain fatty acids.

Malonyl-CoA: A three-carbon molecule that acts as a building block in fatty acid synthesis, formed from acetyl-CoA by the action of acetyl-CoA carboxylase.

Citrate: A six-carbon compound that can activate acetyl-CoA carboxylase by increasing its activity, signaling the presence of sufficient energy and resources for fatty acid synthesis.