Urate oxidase
1081554
181499565
2008-01-02T02:08:52Z
Drphilharmonic
704902
logic
{{protein
| Name = urate oxidase
| caption =
| image =
| width =
| HGNCid = 12575
| Symbol = UOX
| AltSymbols =
| EntrezGene = 7377
| OMIM = 191540
| RefSeq =
| UniProt =
| PDB =
| ECnumber = 1.7.3.3
| Chromosome = 1
| Arm = p
| Band = 22
| LocusSupplementaryData =
}}
The enzyme '''urate oxidase''', or '''UO''', (''[[Aspergillus flavus]]'' enzyme {{PDB|1R4U}}, {{EC number|1.7.3.3}}) catalyzes the [[oxidation]] of [[uric acid]] to [[5-hydroxyisourate]].
:Uric acid + O<sub>2</sub> + H<sub>2</sub>O → 5-hydroxyisourate + [[hydrogen peroxide|H<sub>2</sub>O<sub>2</sub>]]→ allantoin + CO<sub>2</sub>
==Structure==
Urate oxidase is a [[homotetrameric]] enzyme containing four identical active sites situated at the interfaces between its four subunits. UO from A. flavus is made up of 301 residues and has a molecular weight of 33438 [[dalton (unit)|dalton]]. It is unique among the [[oxidase]] in that it does not require a metal atom or an organic co-factor for [[catalysis]].
==Significance of absence in humans==
[[Image:Uric acid.png|thumb|[[Uric acid]]]]
While UO can be found in an extensive variety of organisms, from [[bacteria]] to [[mammals]], and plays different metabolic roles, depending on its host organism, its expression is absent in humans and many [[primates]].
However, humans do have the [[gene]] for UO, but it is nonfunctional, a consequence purported to be due to an occurrence of a sudden mutational event early in primate [[evolution]]. Uric acid is, thus, the final step in the [[catabolism]] of [[purine]]s in humans.
It has also been proposed that the loss of this UO [[protein expression]] has been advantageous to hominoids, since uric acid is a powerful [[antioxidant]] and scavenger of singlet oxygen and [[Radical (chemistry)|radical]]s. Its presence provides the body with protection from [[oxidative]] damage, thus prolonging life and decreasing age-specific cancer rates.
Excessive concentrations of uric acid accumulated in the blood stream, however, leads to [[gout]]. UO has been formulated for the treatment of acute hyperuricaemia as a protein drug (non-proprietary drug name ''[[rasburicase]]'') in patients receiving chemotherapy. A PEGylated form of UO is in clinical development for treatment of chronic hyperuricemia in patients with "treatment-failure gout."
==In legumes==
UO is also an essential enzyme in the ureide pathway, where [[nitrogen fixation]] occurs in the root nodules of [[legume]]s. The fixed nitrogen is converted to [[metabolite]]s that are transported from the roots throughout the plant to provide the needed nitrogen for [[amino acid]] biosynthesis.
{{Nitrogenous donor oxidoreductases}}
{{Nucleotide metabolism}}
[[Category:EC 1.7.3]]
[[de:Uricase]]
[[it:Urato ossidasi]]