ACSF - Acyl-CoA Synthetase Family Member | Elisa - Clia - Antibody - Protein

Background

The Acyl-CoA Synthetase Family (ACSF) includes a group of enzymes that play essential roles in lipid metabolism by catalyzing the activation of fatty acids. These enzymes convert free fatty acids into acyl-CoA derivatives, which are pivotal intermediates in various metabolic pathways, including fatty acid degradation, lipid biosynthesis, and energy production. Fatty acids are incorporated into membranes and signaling molecules and have roles in energy storage and metabolism. These essential functions require activation of the fatty acid by acyl-coenzyme A (CoA) synthetases, such as ACSF2, which form an activating thioester linkage between the fatty acid and CoA. ACSF3 IS localized to mitochondria, has high specificity for malonate and methylmalonate and possesses malonyl-CoA synthetase activity.

Protein Structure

The structure of ACSF enzymes includes several key domains and motifs:

• ATP Binding Domain: Critical for binding and hydrolyzing ATP, providing the energy necessary for the activation of fatty acids.
• Fatty Acid Binding Site: Specific regions that bind to fatty acids, positioning them for acylation.
• Catalytic Core: Contains essential residues involved in the formation of acyl-CoA from fatty acids and coenzyme A (CoA).

Classification and Subtypes

The ACSF family is classified based on substrate specificity and tissue distribution. Key members of this family include:

• ACSF1: Involved in the activation of medium- to long-chain fatty acids.
• ACSF2: Known for its role in the activation of short-chain fatty acids.
• ACSF3: Specialized in the activation of dicarboxylic acids.
• ACSF4 and ACSF5: Other members with distinct yet less well-characterized roles in fatty acid metabolism.

Function and Biological Significance

ACSF enzymes have critical functions in various metabolic processes:

1. Fatty Acid Activation: Catalyze the conversion of free fatty acids into acyl-CoA derivatives, which are necessary for subsequent metabolic processes.
2. Energy Production: Facilitate the breakdown of fatty acids via β-oxidation in mitochondria and peroxisomes, contributing to cellular energy production.
3. Lipid Biosynthesis: Participate in the synthesis of complex lipids, including triglycerides and phospholipids.
4. Metabolic Regulation: Play a role in the regulation of metabolic pathways by controlling the availability of acyl-CoA derivatives.

Interactions

ACSF enzymes interact with various molecules and metabolic pathways:

1. Coenzyme A (CoA): A crucial co-substrate in the formation of acyl-CoA.
2. ATP: Provides the energy required for the activation of fatty acids.
3. Fatty Acid β-Oxidation Pathway: Interact with enzymes involved in the breakdown of fatty acids for energy production.
4. Lipid Biosynthesis Pathways: Engage with enzymes and substrates involved in the synthesis of complex lipids.

Clinical Significance

Alterations or deficiencies in ACSF enzymes can lead to several metabolic disorders:

1. Inherited Metabolic Disorders: Mutations in ACSF genes can result in specific metabolic syndromes characterized by abnormal fatty acid metabolism.
2. Energy Metabolism Disorders: Impaired function of ACSF enzymes can disrupt normal fatty acid catabolism, leading to energy production deficiencies and related metabolic diseases.
3. Lipid Storage Disorders: Dysregulation of ACSF activity can affect lipid biosynthesis and storage, contributing to conditions such as fatty liver disease and obesity.
4. Potential Therapeutic Targets: ACSF enzymes are potential targets for therapeutic intervention in metabolic diseases due to their central role in lipid metabolism.

Summary

The Acyl-CoA Synthetase Family (ACSF) includes enzymes essential for activating fatty acids by converting them into acyl-CoA derivatives. This activation is critical for fatty acid metabolism, including degradation, lipid biosynthesis, and energy production. Key members such as ACSF1, ACSF2, and ACSF3 each have specific roles in activating different types of fatty acids. Dysfunctions or mutations in these enzymes can lead to metabolic disorders, highlighting their importance in health and disease. Understanding the structure, function, interactions, and clinical implications of ACSF enzymes provides valuable insights into their roles in metabolic processes.