AOX1 - Aldehyde oxidase - human protein (Function)
 
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Protein
Gene
References

 
AOX1 »  Aldehyde oxidase
 
Gene name:  AOX1
Family name: Xanthine dehydrogenase
Entry whose protein(s) existence is based on evidence at protein level
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GENE REF ISO

Function

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Overview 
Oxidase with broad substrate specificity, oxidizing aromatic azaheterocycles, such as N1-methylnicotinamide and N-methylphthalazinium, as well as aldehydes, such as benzaldehyde, retinal, pyridoxal, and vanillin. Plays a key role in the metabolism of xenobiotics and drugs containing aromatic azaheterocyclic substituents. Participates in the bioactivation of prodrugs such as famciclovir, catalyzing the oxidation step from 6-deoxypenciclovir to penciclovir, which is a potent antiviral agent. Is probably involved in the regulation of reactive oxygen species homeostasis. May be a prominent source of superoxide generation via the one-electron reduction of molecular oxygen. Also may catalyze nitric oxide (NO) production via the reduction of nitrite to NO with NADH or aldehyde as electron donor. May play a role in adipogenesis.  
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  • CuratedUniProtKB
GO molecular function 
2 iron, 2 sulfur cluster bindingdefinition[GO:0051537]  
  • IEAUniProtKB KW
Electron carrier activitydefinition[GO:0009055] silver  
  • IEAInterPro 2 GO
Flavin adenine dinucleotide bindingdefinition[GO:0050660] silver  
  • IEAInterPro 2 GO
Iron ion bindingdefinition[GO:0005506] silver  
  • IEAInterPro 2 GO
Molybdopterin cofactor bindingdefinition[GO:0043546] silver  
  • IEAInterPro 2 GO
NAD bindingdefinition[GO:0051287] silver  
  • IEAInterPro 2 GO
UDP-N-acetylmuramate dehydrogenase activitydefinition[GO:0008762] silver  
  • IEAInterPro 2 GO
Xanthine dehydrogenase activitydefinition[GO:0004854]  
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  • TASPINC
GO biological process 
Inflammatory responsedefinition[GO:0006954]  
1
  • TASPINC
Oxidation-reduction processdefinition[GO:0055114]  
  • IEAUniProtKB KW
Reactive oxygen species metabolic processdefinition[GO:0072593]  
1
  • TASPINC
Enzymatic activity 
This protein acts as an enzyme. It is known to catalyze the following reactions
EC 1.2.3.1: An aldehyde + H(2)O + O(2) a carboxylate + H(2)O(2).  
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  • CuratedUniProtKB
EC 1.17.3.-: Retinal + O(2) + H(2)O retinoate + H(2)O(2).  
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  • CuratedUniProtKB
It requires the following cofactors
Binds 2 2Fe-2S clusters per subunit.  
1
  • CuratedUniProtKB
Binds 1 FAD per subunit.  
1
  • CuratedUniProtKB
Binds 1 molybdenum-molybdopterin (Mo-MPT) cofactor per subunit.  
1
  • CuratedUniProtKB
It is regulated in the following manner
Is very potently inhibited by raloxifene. Also inhibited by estradiol, ethinyl estradiol, hydralazine, menadione, and isovanillin. Not inhibited by allopurinol, a xanthine dehydrogenase potent inhibitor.  
4
  • CuratedUniProtKB
Pathways 
According to KEGG, this protein belongs to the following pathways:
Drug metabolism - cytochrome P450  hsa00982+316  
Metabolic pathways  hsa01100+316  
Nicotinate and nicotinamide metabolism  hsa00760+316  
Tryptophan metabolism  hsa00380+316  
Tyrosine metabolism  hsa00350+316  
Valine, leucine and isoleucine degradation  hsa00280+316  
Vitamin B6 metabolism  hsa00750+316  
According to Reactome, this protein belongs to the following pathway:
Vitamins B6 activation to pyridoxal phosphate  REACT_25012  
 
More information is available from:
Note 
AOX genes evolved from a xanthine oxidoreductase ancestral precursor via a series of gene duplication and suppression/deletion events. Different animal species contain a different complement of AOX genes encoding an equivalent number of AOX isoenzymes. In mammals, the two extremes are represented by certain rodents such as mice and rats, which are endowed with 4 AOX genes, and by humans, whose genome is characterized by a single active gene (PubMed22335465).  
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  • CuratedUniProtKB
Caution 
Was originally (PubMed8248161) thought to be a xanthine dehydrogenase.  
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  • CuratedUniProtKB
 

Biophysicochemical properties

Kinetic parameters
kcat is 6.4 min(-1) for benzaldehyde oxidation, 5.6 min(-1) for phthalazine oxidation, 12.2 min(-1) for phenanthridine oxidation and 5.6 min(-1) for chloroquinazolinone oxidation.
KM 1.3 uM for phthalazine (at 25 degrees Celsius and pH 7.5)
KM 7.1 uM for benzaldehyde (at 25 degrees Celsius and pH 7.5)
KM 0.42 mM for 6-deoxypenciclovir (at 37 degrees Celsius and pH 7)
KM 5.2 uM for chloroquinazolinone (at 25 degrees Celsius and pH 7.5)
KM 3.9 uM for phenanthridine (at 25 degrees Celsius and pH 7.5)
KM 0.15 mM for famciclovir (at 37 degrees Celsius and pH 7)
KM 6.3 uM for N-[(2-dimethylamino)ethyl]acridine-4-carboxamide (at 37 degrees Celsius and pH 7.4)
Vmax 16 nmol/min/mg enzyme with 6-deoxypenciclovir as substrate
Vmax 61 nmol/min/mg enzyme with famciclovir as substrate
Vmax 2.3 nmol/min/mg enzyme with N-[(2-dimethylamino)ethyl]acridine-4-carboxamide as substrate

Keywords

Molecular function 
Oxidoreductase  definition   [KW-0560]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

Enzyme and pathway databases
SABIO-RK: Q06278
Other
GeneWiki: Aldehyde_oxidase_1
GenomeRNAi: 316
PRO: PR:Q06278