Peroxisomal acyl-coenzyme A oxidase 1

Peroxisomal acyl-coenzyme A oxidase 1 (ACOX1) catalyzes the initial, rate-limiting step of peroxisomal beta-oxidation of very-long-chain fatty acids, converting 2,3-saturated acyl-CoAs to 2-trans-enoyl-CoAs while producing hydrogen peroxide (UniProt: Q15067). The enzyme shows highest activity against medium-chain substrates, particularly decanoyl-CoA, and is active against a broad range of fatty acid substrates in vivo.

ACOX1 is a key peroxisomal enzyme whose dysfunction leads to accumulation of very-long-chain fatty acids. Loss-of-function mutations cause pseudoneonatal adrenoleukodystrophy and Mitchell syndrome, both characterized by neurological impairment including intellectual disability, leukodystrophy, and polyneuropathy (UniProt: Q15067).

In Alzheimer's disease, ACOX1 is significantly up-regulated in post-mortem AD brain tissue compared to age-matched controls (mean log2 fold-change: 0.66; Chaparral AD proteomics), suggesting altered fatty acid metabolism may accompany disease pathology. This elevation may reflect compensatory metabolic remodeling or contribute to oxidative stress through increased peroxide generation in the AD brain.