InterPro domain: IPR012258

Acyl-CoA oxidase (ACO) acts on CoA derivatives of fatty acids with chain lengths from 8 to 18. It catalyses the first and rate-determining step of the peroxisomal beta-oxidation of fatty acids and a major producer of hydrogen peroxide (H2O2) [ 1 , 2 ].

Acyl-CoA oxidase is a homodimer and the polypeptide chain of the subunit is folded into the N-terminal alpha-domain, beta-domain, and C-terminal alpha-domain [ 3 , 3 ]. Functional differences between the peroxisomal acyl-CoA oxidases and the mitochondrial acyl-CoA dehydrogenases are attributed to structural differences in the FAD environments [ 3 ].

Experimental data indicate that in the pumpkin, the expression pattern of ACOX is very similar to that of the glyoxysomal enzyme 3-ketoacyl-CoA thiolase [ 4 ]. In humans, defects in ACOX1 are the cause of pseudoneonatal adrenoleukodystrophy, also known as peroxisomal acyl-CoA oxidase deficiency. Clinical features include mental retardation, leukodystrophy, seizures, mild hepatomegaly and hearing deficit. Pseudo-NALD is characterised by increased plasma levels of very-long chain fatty acids due to a decrease in, or absence of, peroxisome acyl-CoA oxidase activity, despite the peroxisomes being intact and functioning [ 5 ].

1. Three-dimensional structure of the flavoenzyme acyl-CoA oxidase-II from rat liver, the peroxisomal counterpart of mitochondrial acyl-CoA dehydrogenase. J. Biochem. 131, 365-74
2. Loss- or Gain-of-Function Mutations in ACOX1 Cause Axonal Loss via Different Mechanisms. Neuron 106, 589-606.e6
3. Acyl-CoA oxidase 1 from Arabidopsis thaliana. Structure of a key enzyme in plant lipid metabolism. J. Mol. Biol. 345, 487-500
4. Molecular characterization of a glyoxysomal long chain acyl-CoA oxidase that is synthesized as a precursor of higher molecular mass in pumpkin. J. Biol. Chem. 273, 8301-7