ACOX - Acyl Coenzyme A Oxidase | Elisa - Clia - Antibody - Protein

Background

Acyl-CoA oxidases (ACOXs) are crucial enzymes involved in the first step of peroxisomal β-oxidation, a pathway responsible for the breakdown of very-long-chain fatty acids (VLCFAs), branched-chain fatty acids, and bile acid intermediates. ACOXs catalyze the oxidation of acyl-CoA to trans-2-enoyl-CoA, producing hydrogen peroxide in the process. ACOX catalyzes the first step of the beta-oxidation pathway within peroxisomes. It oxidizes long-chain acyl-CoA molecules, removing two carbons from the fatty acid chain to produce trans-2-enoyl-CoA. This reaction involves the transfer of electrons to molecular oxygen, leading to the formation of hydrogen peroxide (H2O2). Fatty acid beta-oxidation is a crucial pathway for the catabolism of fatty acids, which are important sources of energy for cells. By breaking down fatty acids into acetyl-CoA units, beta-oxidation provides substrates for energy production through processes such as the citric acid cycle and oxidative phosphorylation.Genetic. Mutations in the genes encoding ACOX enzymes can lead to metabolic disorders known as peroxisomal disorders. These conditions are characterized by impaired fatty acid metabolism and can result in a range of clinical manifestations, including neurological abnormalities, developmental delays, and liver dysfunction.

Protein Structure

ACOXs are flavoproteins, containing a flavin adenine dinucleotide (FAD) cofactor essential for their catalytic activity. Key structural features include:

• FAD Binding Domain: Binds FAD, facilitating the transfer of electrons from acyl-CoA to oxygen.
• Substrate Binding Domain: Binds the acyl-CoA substrate and positions it for catalysis.
• Catalytic Residues: Essential amino acids within the active site that participate in the oxidation reaction.

Classification and Subtypes

ACOXs are classified based on substrate specificity and sequence homology. The primary subtypes in mammals include:

• ACOX1: Preferentially oxidizes straight-chain VLCFAs.
• ACOX2: Oxidizes branched-chain fatty acids and bile acid intermediates.
• ACOX3: Oxidizes branched-chain fatty acids, particularly pristanoyl-CoA.

Function and Biological Significance

ACOXs serve several essential functions in cellular metabolism:

1. Fatty Acid β-Oxidation: Initiate the breakdown of VLCFAs and branched-chain fatty acids, providing energy and metabolic intermediates.
2. Detoxification: Generate hydrogen peroxide, which is subsequently detoxified by catalase, preventing oxidative damage.
3. Lipid Homeostasis: Maintain cellular lipid balance by regulating the levels of fatty acids and their derivatives.
4. Peroxisome Function: Integral to peroxisomal metabolism, impacting various metabolic pathways and cellular functions.

Interactions

ACOXs interact with various molecules and pathways:

1. Acyl-CoA Substrates: Oxidize acyl-CoA derivatives as part of the β-oxidation pathway.
2. FAD Cofactor: Essential for their catalytic activity, facilitating electron transfer.
3. Peroxisomal Enzymes: Work in concert with other enzymes in the peroxisome, such as enoyl-CoA hydratase and 3-ketoacyl-CoA thiolase.
4. Catalase: Detoxifies the hydrogen peroxide produced by ACOXs, protecting the cell from oxidative damage.

Clinical Significance

Dysfunction or deficiency of ACOXs can lead to various metabolic and genetic disorders:

1. Peroxisomal Biogenesis Disorders (PBDs): Conditions like Zellweger syndrome involve impaired peroxisomal function, often affecting ACOX activity.
2. X-Linked Adrenoleukodystrophy (X-ALD): Characterized by the accumulation of VLCFAs due to defective peroxisomal β-oxidation, where ACOX1 plays a role.
3. Refsum Disease: A rare disorder caused by defective ACOX3 activity, leading to the accumulation of phytanic acid.
4. Nonalcoholic Fatty Liver Disease (NAFLD): Altered ACOX activity can contribute to lipid accumulation and liver dysfunction.

Summary

Acyl-CoA oxidases (ACOXs) are key enzymes in peroxisomal β-oxidation, catalyzing the initial step in the breakdown of very-long-chain and branched-chain fatty acids. They are classified into subtypes based on substrate specificity: ACOX1, ACOX2, and ACOX3. ACOXs play crucial roles in fatty acid metabolism, detoxification, and lipid homeostasis, with significant implications for peroxisomal function. Dysregulation of ACOX activity is associated with metabolic disorders, genetic conditions, and diseases like X-linked adrenoleukodystrophy and Refsum disease. Understanding the structure, function, and clinical implications of ACOXs is essential for developing therapeutic strategies targeting peroxisomal metabolism and related diseases.