ACOT - Acyl-CoA Thioesterase | Elisa - Clia - Antibody - Protein

Background

Acyl-CoA thioesterases (ACOTs) are a family of enzymes that catalyze the hydrolysis of acyl-CoA thioesters to free fatty acids and CoA. These enzymes play a crucial role in lipid metabolism by regulating the intracellular levels of acyl-CoA and free fatty acids, which are involved in various metabolic pathways including β-oxidation, lipid biosynthesis, and signaling.Acyl-CoA molecules are intermediates in fatty acid metabolism and are involved in various cellular processes, including energy production and lipid biosynthesis. By cleaving the thioester bond, ACOTs regulate the levels of acyl-CoA substrates and free fatty acids, thereby influencing cellular metabolism. This reaction occurs in a variety of cellular compartments, including the cytoplasm, mitochondria, peroxisomes, and endoplasmic reticulum. Different ACOT isoforms exhibit specificity towards particular acyl-CoA substrates. For example, some ACOTs preferentially hydrolyze long-chain acyl-CoAs, while others may act on medium-chain or short-chain acyl-CoAs. ACOTs play a role in regulating cellular metabolism by controlling the levels of acyl-CoA substrates and free fatty acids. By modulating the availability of these molecules, ACOTs influence pathways such as fatty acid oxidation, lipid biosynthesis, and energy production. Dysregulation of ACOT activity has been associated with metabolic disorders, including obesity, diabetes, and fatty liver disease. Altered expression or activity of ACOTs can disrupt fatty acid metabolism and contribute to metabolic dysfunction.

Protein Structure

ACOTs have a diverse range of structures, reflecting their wide substrate specificity and localization within the cell:

• Catalytic Domain: Contains the active site with residues essential for the hydrolysis reaction. This domain varies among different ACOTs, contributing to their substrate specificity.
• CoA Binding Sites: Specific regions that interact with the CoA moiety of the substrate.
• Substrate Binding Pocket: Accommodates the fatty acid chain of the acyl-CoA substrate.

Classification and Subtypes

ACOTs are classified into different types based on their cellular localization and substrate specificity. There are several subtypes of ACOTs, each with distinct functions and regulatory mechanisms:

• Cytosolic ACOTs: Located in the cytoplasm and involved in regulating cytosolic acyl-CoA and free fatty acid levels.
• Mitochondrial ACOTs: Found in mitochondria, where they play roles in mitochondrial fatty acid metabolism and β-oxidation.
• Peroxisomal ACOTs: Located in peroxisomes and involved in peroxisomal β-oxidation of very-long-chain fatty acids.
• Endoplasmic Reticulum ACOTs: Associated with the endoplasmic reticulum, participating in lipid biosynthesis and metabolism.

Function and Biological Significance

ACOTs serve several critical roles in cellular metabolism:

1. Regulation of Acyl-CoA Levels: Hydrolyze acyl-CoA thioesters to control the levels of acyl-CoA, a key intermediate in various metabolic pathways.
2. Free Fatty Acid Production: Generate free fatty acids, which are important for energy production, lipid signaling, and membrane synthesis.
3. Metabolic Flexibility: Allow cells to switch between different metabolic states by regulating the availability of acyl-CoA and free fatty acids.
4. Signal Transduction: Involved in lipid signaling pathways by producing bioactive lipid molecules.

Interactions

ACOTs interact with various metabolic pathways and molecules:

1. Acyl-CoA Thioesters: The primary substrates for ACOTs, involved in numerous metabolic processes.
2. Free Fatty Acids and CoA: Products of the hydrolysis reaction, which participate in diverse metabolic and signaling pathways.
3. Lipid Metabolism Enzymes: Work in conjunction with other enzymes involved in lipid metabolism, such as fatty acid synthase and carnitine palmitoyltransferase.
4. Signaling Pathways: Influence signaling pathways by modulating the levels of lipid signaling molecules.

Clinical Significance

Alterations in ACOT activity or expression can have significant implications for health and disease:

1. Metabolic Disorders: Dysregulation of ACOT activity is associated with metabolic diseases such as obesity, type 2 diabetes, and fatty liver disease.
2. Cardiovascular Diseases: Changes in lipid metabolism mediated by ACOTs can contribute to the development of atherosclerosis and other cardiovascular conditions.
3. Cancer: Altered lipid metabolism in cancer cells, often involving ACOTs, supports rapid cell proliferation and tumor growth.
4. Neurodegenerative Diseases: Abnormalities in lipid metabolism, potentially involving ACOTs, are implicated in neurodegenerative diseases such as Alzheimer's disease.

Summary

Acyl-CoA thioesterases (ACOTs) are a family of enzymes that hydrolyze acyl-CoA thioesters to produce free fatty acids and CoA, playing essential roles in lipid metabolism. ACOTs are classified based on their cellular localization and substrate specificity, with subtypes found in the cytosol, mitochondria, peroxisomes, and endoplasmic reticulum. They regulate acyl-CoA levels, produce free fatty acids, and participate in metabolic flexibility and signal transduction. Dysregulation of ACOT activity is linked to metabolic disorders, cardiovascular diseases, cancer, and neurodegenerative diseases. Understanding the structure, function, interactions, and clinical implications of ACOTs provides valuable insights into their role in health and disease and highlights their potential as therapeutic targets.