protein
Peroxisomal acyl-coenzyme A oxidase 1
aka AOX
Gene
ACOX1
Organism
Homo sapiens(9606)
Length
660 aa
Mass
74,424 Da
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.
Generated from the curated entity record below. May contain errors — verify against source links.
Proteomics Evidence · AD
↑ Up in ADP3
not detected
P2
not detected
S2
+0.660
S3
not detected
Mean log₂FC across detected fractions: +0.6599 (1 of 4 fractions detected)
Human post-mortem AD brain vs age-matched controls, TMT-labeled, 4 subcellular fractions (P2, P3, S2, S3), DDA proteomics.
Related Publications
Browse all →Tau molecular diversity contributes to clinical heterogeneity in Alzheimer's disease.
Dujardin Simon et al.Nature medicine2020PMID 32572268Deep Multilayer Brain Proteomics Identifies Molecular Networks in Alzheimer's Disease Progression.
Bai Bing et al.Neuron2020PMID 31926610A Multi-network Approach Identifies Protein-Specific Co-expression in Asymptomatic and Symptomatic Alzheimer's Disease.
Seyfried Nicholas T et al.Cell systems2017PMID 27989508Large-scale deep multi-layer analysis of Alzheimer's disease brain reveals strong proteomic disease-related changes not observed at the RNA level.
Johnson Erik C B et al.Nature neuroscience2022PMID 35115731Organization and regulation of gene transcription.
Cramer PatrickNature2019PMID 31462772
Function
Involved in the initial and rate-limiting step of peroxisomal beta-oxidation of straight-chain saturated and unsaturated very-long-chain fatty acids (PubMed:15060085, PubMed:17458872, PubMed:17603022, PubMed:32169171, PubMed:33234382, PubMed:7876265). Catalyzes the desaturation of fatty acyl-CoAs that have a saturated bond between C2 and C3 (2,3-saturated acyl-CoA) to 2-trans-enoyl-CoAs ((2E)-enoyl-CoAs), and donates electrons directly to molecular oxygen (O(2)), thereby producing hydrogen peroxide (H(2)O(2)) (PubMed:17458872, PubMed:17603022, PubMed:7876265)
Shows highest activity against medium-chain fatty acyl-CoAs. Shows optimum activity with a chain length of 10 carbons (decanoyl-CoA) in vitro
Is active against a much broader range of substrates and shows activity towards long-chain fatty acyl-CoAs
Disease associations
Adrenoleukodystrophy, pseudoneonatalPseudo-NALD
A peroxisomal single-enzyme disorder of fatty acid beta-oxidation, resulting in clinical manifestations that remind neonatal adrenoleukodystrophy. Clinical features include intellectual disability, leukodystrophy, seizures, mild hepatomegaly, hearing deficit. Pseudo-NALD is characterized by increased plasma levels of very-long chain fatty acids, due to decreased or absent peroxisome acyl-CoA oxidase activity. Peroxisomes are intact and functioning.
Mitchell syndromeMITCH
A disorder characterized by episodic demyelination, sensorimotor polyneuropathy, and sensorineural hearing loss.
Sources
Last updated 5/8/2026, 6:37:47 AM