Acyl-coenzyme A oxidase (ACOX)

Molecular Classification

Enzyme, Oxidoreductase, Peroxisomal enzyme

Other Names

Acyl-CoA oxidase, Acyl coenzyme A oxidase, Fatty acyl-CoA oxidase, Fatty acyl-coenzyme A oxidase, Acyl-CoA:oxygen 2-oxidoreductase

Disease Roles

CancerPeroxisomal disorders (e.g., Acyl-CoA oxidase deficiency)Neurodegenerative disease

Acyl-coenzyme A oxidase Overview

Acyl-coenzyme A oxidase is a peroxisomal oxidoreductase enzyme that catalyzes the first and rate-limiting step of the fatty acid beta-oxidation pathway, specifically oxidizing acyl-CoA to 2,3-trans-enoyl-CoA while producing hydrogen peroxide as a byproduct[2][3][5][6]. It is essential for lipid catabolism and energy homeostasis as it enables the breakdown of fatty acids for subsequent cellular utilization. The enzyme uses FAD as a cofactor and exhibits substrate specificity based on side chain length and structure, with different isoforms adapted for various types of fatty acids[1][5]. Acyl-coenzyme A oxidase is vital for normal human physiology; mutations or reduced activity are linked to severe peroxisomal diseases and have been implicated in cancer, neurodegeneration, and aging processes[4]. It is also important in plant biology for hormone biosynthesis and metabolism[2]. While not directly targeted by current therapeutics, its regulation through peroxisomal and metabolic pathways (including PPARs) is of pharmacological interest.

Mechanism of Action

Catalytic oxidation of acyl-CoA to 2,3-trans-enoyl-CoA, producing hydrogen peroxide and supporting peroxisomal fatty acid oxidation Regulated by nuclear receptors including PPARs, which could be modulated by synthetic ligands in disease modulation

Biological Functions

Fatty acid beta-oxidation

Lipid catabolism

Regulation of metabolic pathways

Production of hydrogen peroxide within peroxisomes

Disease Associations

Cancer

Peroxisomal disorders (e.g., Acyl-CoA oxidase deficiency)

Neurodegenerative disease

Aging-related dysfunction

Other (metabolic diseases, especially related to lipid metabolism)

Safety Considerations

Dysfunction or deficiency leads to peroxisomal disorders and severe metabolic conditions, often fatal in infancy (for example, Acyl-CoA oxidase deficiency)
Accumulation of fatty acids and/or hydrogen peroxide may contribute to cellular toxicity[4]
Potential oxidative stress if hydrogen peroxide is not efficiently detoxified in peroxisome

Interacting Drugs

No prominent, widely approved drugs directly targeting acyl-coenzyme A oxidase have been specifically identified in the current search results. Some PPAR agonists (peroxisome proliferator-activated receptor agonists, such as fibrates) may regulate its expression indirectly through peroxisome pathways, but acyl-CoA oxidase itself is not generally a direct drug target[3][4].

Associated Biomarkers

Biomarker
Mutations or decreased activity of acyl-coenzyme A oxidase serve as biomarkers for peroxisomal disorders and some metabolic syndromes
Altered levels or activity in certain cancers or metabolic diseases may have biomarker potential[4]