ACSM - Acyl-CoA synthetase medium chain family member | Elisa - Clia - Antibody - Protein

Background

Acyl-CoA Synthetase Medium-Chain (ACSM) family members are enzymes involved in the metabolism of medium-chain fatty acids (MCFAs), typically ranging from 4 to 12 carbon atoms in length. These enzymes catalyze the activation of MCFAs by converting them into acyl-CoA derivatives. This activation step is crucial for the subsequent utilization of fatty acids in various metabolic pathways, including beta-oxidation for energy production or incorporation into cellular membranes for lipid synthesis. They also participate in the glycine conjugation pathway in the detoxification of ibuprofen (ACSM2A)

Protein Structure

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

• ATP Binding Domain: Essential for binding and hydrolyzing ATP, providing the necessary energy for the activation of fatty acids.
• Fatty Acid Binding Site: Regions that specifically bind to medium-chain fatty acids, positioning them for activation.
• Catalytic Core: Contains key residues involved in the formation of acyl-CoA from fatty acids and coenzyme A (CoA).

Classification and Subtypes

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

• ACSM1: Involved in the metabolism of short- to medium-chain fatty acids, widely expressed in various tissues.
• ACSM2A and ACSM2B: Isoforms with distinct but overlapping roles in the metabolism of medium-chain fatty acids, primarily expressed in the liver and kidney.
• ACSM3: Plays a role in the activation of medium-chain dicarboxylic acids, primarily expressed in the liver.
• ACSM4 and ACSM5: Other members with specialized roles in fatty acid metabolism, with specific tissue distributions and substrate specificities.

Function and Biological Significance

ACSM enzymes serve essential functions in various metabolic processes:

1. Fatty Acid Activation: Catalyze the conversion of medium-chain fatty acids into acyl-CoA derivatives, a critical step for their subsequent metabolism.
2. Energy Production: Facilitate the breakdown of medium-chain fatty acids via β-oxidation in mitochondria, contributing to ATP production.
3. Lipid Biosynthesis: Participate in the synthesis of complex lipids, such as triglycerides and phospholipids, for membrane formation and storage.
4. Metabolic Regulation: Regulate the availability of acyl-CoA derivatives, influencing various metabolic pathways and energy homeostasis.

Interactions

ACSM 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 medium-chain 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 ACSM enzymes can lead to several metabolic disorders:

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

Summary

The Acyl-CoA Synthetase Medium-Chain (ACSM) family includes enzymes essential for the activation of medium-chain fatty acids by converting them into acyl-CoA derivatives. This activation is crucial for fatty acid metabolism, including degradation, lipid biosynthesis, and energy production. Key members such as ACSM1, ACSM2A, ACSM2B, ACSM3, ACSM4, and ACSM5 each have specific roles and tissue distributions. Dysfunctions or mutations in these enzymes can lead to various metabolic disorders, emphasizing their importance in maintaining lipid homeostasis and energy balance. Understanding the structure, function, interactions, and clinical implications of ACSM enzymes provides valuable insights into their roles in metabolic processes and potential therapeutic applications.