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Aldehyde oxidase

Aldehyde oxidase
Aldehydoxidase.png
Model of human aldehyde oxidase after PDB: 4UHW​.
Identifiers
EC number 1.2.3.1
CAS number 9029-07-6
Databases
IntEnz IntEnz view
BRENDA BRENDA entry
ExPASy NiceZyme view
KEGG KEGG entry
MetaCyc metabolic pathway
PRIAM profile
PDB structures RCSB PDB PDBe PDBsum
Gene Ontology AmiGO / EGO
aldehyde oxidase 1
Identifiers
Symbol AOX1
Entrez 316
HUGO 553
OMIM 602841
RefSeq NM_001159
UniProt Q06278
Other data
EC number 1.2.3.1
Locus Chr. 2 q33

Aldehyde oxidase (AO) is a metabolizing enzyme, located in the cytosolic compartment of tissues in many organisms. AO catalyzes the oxidation of aldehydes into carboxylic acid, and in addition, catalyzes the hydrozylation of some heterocycles. It can also catalyze the oxidation of both cytochrome P450 (CYP450) and monoamine oxidase (MAO) intermediate products. AO plays a very important role in the metabolization of numerous drugs.

AO catalyzes the conversion of an aldehyde in the presence of oxygen and water to an acid and hydrogen peroxide.

Though the enzyme uses molecular oxygen as an electron acceptor, the oxygen atom that is incorporated into the carboxylate product is from water; however, the exact mechanism of reduction is still not known for AO.

The AO also catalyzes the oxidation of heterocycles, which involves a nucleophilic attack located at the carbon atom beside the heteroatom. This means that susceptibility to nucleophilic attack of a heterocycle determines if that heterocycle is a suitable substrate for AO.

Aldehyde oxidase is a member of the molybd-flavo protein family and has a very complex evolutionary profile—as the genes of AO varies according to animal species. Higher primates, such as humans, have a single functioning AO gene (AOX1), whereas rodents have four separate AOX genes. The human population has both functionally inactive hAOX1 allelic variants and encoding enzyme variants with different catalytic activities. AO activity has been found to be much more active in higher primates (compared to rodents), though many factors may affect this activity, such as gender, age, cigarette smoking, drug usage, and disease states.

Aldehyde oxidase is very concentrated in the liver, where it oxidizes multiple aldehydes and nitrogenous heterocyclic compounds, such as anti-cancer and immunosuppressive drugs. Some AO activity has been located in other parts of the body—including the lungs (epithelial cells and alveolar cells), the kidneys, and the gastrointestinal tract (small and large intestines).

The regulation of expression of AO is still not completely known, though some studies have shown that the AOX1 gene is regulated by the Nrf2 pathway. Some known inhibitors of AO are sterol and phenol compounds, like estradiol. Others include amsacrine, 6,6'-azopurine, chlorpromazine, cimetidine, cyanide, diethylstilbestrol, genestein, isovanillin, and methadone.


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