Application | Comment | Organism |
---|---|---|
medicine | inhibition of ACOX1 is an effective approach for the treatment of high fat diet or obesity-induced metabolic diseases by improving mitochondrial lipid and reactive oxygen species metabolism | Rattus norvegicus |
nutrition | inhibition of ACOX1 is an effective approach for the treatment of high fat diet or obesity-induced metabolic diseases by improving mitochondrial lipid and reactive oxygen species metabolism | Rattus norvegicus |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
10,12-tricosadiynoic acid-CoA | TDYA-CoA, development of the specific inhibitor of acyl-CoA oxidase-1, the acetylenic acid is a suicide substrate of ACOX1 with high affinity to the target and high selectivity in vivo. TDYA-CoA rapidly inhibits ACOX1 activity in vitro by 92% and in vivo, but only if free TDYA is activated as the CoA thioester, the substrate form. Inhibition of ACOX1 by TDYA-CoA is irreversible, inhibition kinetics parameters KI and kinact are calculated to be 680 nM and 3.18/min, respectively. It is possible that TDYA-CoA forms a covalent bond with a key residue in the catalytic center of ACOX1 and irreversibly inhibits the enzyme. Isozyme ACOX2 activity is not affected by the compound | Rattus norvegicus |
Localization | Comment | Organism | GeneOntology No. | Textmining |
---|---|---|---|---|
peroxisome | - |
Rattus norvegicus | 5777 | - |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
acyl-CoA + O2 | Rattus norvegicus | - |
trans-2,3-dehydroacyl-CoA + H2O2 | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Rattus norvegicus | P07872 | - |
- |
Reaction | Comment | Organism | Reaction ID |
---|---|---|---|
acyl-CoA + O2 = trans-2,3-dehydroacyl-CoA + H2O2 | in the reductive half-reaction, the substrate acyl-CoA isalpha,beta-dehydrogenated into the corresponding 2-trans-enoyl-CoA, with electrons transferred to FAD, which becomes reduced, whereas in the oxidative half-reaction reduced FAD is reoxidized by molecular oxygen, generating hydrogen peroxide | Rattus norvegicus |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
liver | - |
Rattus norvegicus | - |
Specific Activity Minimum [µmol/min/mg] | Specific Activity Maximum [µmol/min/mg] | Comment | Organism |
---|---|---|---|
1.39 | - |
purified recombinant enzyme, pH 7.4, 25°C | Rattus norvegicus |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
acyl-CoA + O2 | - |
Rattus norvegicus | trans-2,3-dehydroacyl-CoA + H2O2 | - |
? |
Synonyms | Comment | Organism |
---|---|---|
ACOX1 | - |
Rattus norvegicus |
acyl-CoA oxidase-1 | - |
Rattus norvegicus |
Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
---|---|---|---|
25 | - |
assay at | Rattus norvegicus |
pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
---|---|---|---|
7.4 | - |
assay at | Rattus norvegicus |
Cofactor | Comment | Organism | Structure |
---|---|---|---|
FAD | - |
Rattus norvegicus |
Organism | Comment | Expression |
---|---|---|
Rattus norvegicus | the hydrogen peroxide-generating enzyme ACOX1 is inducible under conditions of high-fat diet or exposure to PPARalpha ligands, which results in a net increase of hydrogen peroxide in peroxisomes | up |
General Information | Comment | Organism |
---|---|---|
malfunction | specific inhibition of ACOX1 by 10,12-tricosadiynoic acid increases hepatic mitochondrial fatty acid oxidation via activation of the adenosine 5'-monophosphate-activated protein kinase (SIRT1-AMPK) pathway and proliferator activator receptor alpha and reduces hydrogen peroxide accumulation in high fat diet-fed rats, which significantly decreases hepatic lipid and ROS contents, reduces body weight gain, and decreases serum triglyceride and insulin levels. The phosphorylation level of p70S6K (Thr389) in the livers of TDYA-treated rats decreases by 49% compared with the high-fat diet group | Rattus norvegicus |
physiological function | acyl-CoA oxidase-1 (ACOX1) is a flavoenzyme that catalyzes the initial and rate-determining reaction of the classical peroxisomal fatty acid oxidation using straight-chain fatty acyl-CoAs as the substrates, which donates electrons to molecular oxygen generating hydrogen peroxide | Rattus norvegicus |