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Literature summary for 1.3.3.6 extracted from

  • Zeng, J.; Deng, S.; Wang, Y.; Li, P.; Tang, L.; Pang, Y.
    Specific inhibition of acyl-CoA oxidase-1 by an acetylenic acid improves hepatic lipid and reactive oxygen species (ROS) metabolism in rats fed a high fat diet (2017), J. Biol. Chem., 292, 3800-3809 .
    View publication on PubMedView publication on EuropePMC
Search for more literature for 1.3.3.6

Application

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

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

Localization Comment Organism GeneOntology No. Textmining
peroxisome
-
 Rattus norvegicus 5777
-

Natural Substrates/ Products (Substrates)

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

Organism UniProt Comment Textmining
Rattus norvegicus P07872
-
-

Reaction

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
a

Source Tissue

Source Tissue Comment Organism Textmining
liver
-
 Rattus norvegicus
-

Specific Activity [micromol/min/mg]

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 and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
acyl-CoA + O2
-
 Rattus norvegicus trans-2,3-dehydroacyl-CoA + H2O2
-
 ?

Synonyms

Synonyms Comment Organism
ACOX1
-
 Rattus norvegicus
acyl-CoA oxidase-1
-
 Rattus norvegicus

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
25
-
 assay at Rattus norvegicus

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
7.4
-
 assay at Rattus norvegicus

Cofactor

Cofactor Comment Organism Structure
FAD
-
 Rattus norvegicus

Expression

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

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