| Urate oxidase, pseudogene | |||||
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| Identifiers | |||||
| Symbols | UOX; UOXP; URICASE | ||||
| External IDs | OMIM: 191540 HomoloGene: 7584 GeneCards: UOX Gene | ||||
| EC number | 1.7.3.3 | ||||
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| Orthologs | |||||
| Species | Human | Mouse | |||
| Entrez | 391051 | 22262 | |||
| Ensembl | ENSG00000240520 | ENSMUSG00000028186 | |||
| UniProt | n/a | P25688 | |||
| RefSeq (mRNA) | NR_003927 | NM_009474 | |||
| RefSeq (protein) | n/a | NP_033500 | |||
| Location (UCSC) | Chr 1: 84.83 – 84.87 Mb |
Chr 3: 146.25 – 146.3 Mb |
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| PubMed search | [1] | [2] | |||
The enzyme urate oxidase (UO), or uricase or factor-independent urate hydroxylase, catalyzes the oxidation of uric acid to 5-hydroxyisourate:[1]
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Urate oxidase is mainly localised in the liver, where it forms a large electron-dense paracrystalline core in many peroxisomes.[2] The enzyme exists as a tetramer of identical subunits, each containing a possible type 2 copper-binding site.[3]
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 oxidases in that it does not require a metal atom or an organic co-factor for catalysis. Sequence analysis of several organisms has determined that there are 24 amino acids which are conserved, and of these, 15 are involved with the active site.
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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, it is absent in humans and many other primates.[3]
Humans do have a gene for UO, but it is nonfunctional, a consequence purported to be due to an occurrence of a mutational event early in primate evolution. Uric acid is, thus, the end product of catabolism of purines in humans.
It has also been proposed that the loss of this UO protein expression has been advantageous to hominids, since uric acid is a powerful antioxidant and scavenger of singlet oxygen and radicals.[4] Its presence provides the body with protection from oxidative damage, thus prolonging life and decreasing age-specific cancer rates. However, this is highly unlikely as proteins are capable of being activated only when concentrations exceed a certain amount. Adequate uric acid levels could still be maintained to protect the body while preventing evolutionarily disadvantageous conditions like gout.
Excessive concentration of uric acid in the blood stream, however, leads to gout. UO has been formulated as a protein drug (rasburicase) for the treatment of acute hyperuricemia in patients receiving chemotherapy. A PEGylated form of UO is in clinical development for treatment of chronic hyperuricemia in patients with "treatment-failure gout".
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.
In legumes, 2 forms of uricase are found: in the roots, the tetrameric form; and, in the uninfected cells of root nodules, a monomeric form, which plays an important role in nitrogen-fixation.[5]
This article incorporates text from the public domain Pfam and InterPro IPR002042
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