Urate oxidase

The enzyme urate oxidase, or UO, (Aspergillus flavus enzyme PDB 1R4U, EC 1.7.3.3) catalyzes the oxidation of uric acid to 5-hydroxyisourate.

Uric acid + O₂ + H₂O → 5-hydroxyisourate + H₂O₂→ allantoin + CO₂

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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. 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

  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 purines 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 radicals. 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 legumes. The fixed nitrogen is converted to metabolites that are transported from the roots throughout the plant to provide the needed nitrogen for amino acid biosynthesis.