The enzyme urate oxidase
), or uricase
or factor-independent urate hydroxylase
, absent in humans, catalyzes the oxidation
of uric acid
+ O2 + H2O → 5-hydroxyisourate
+ H2O → allantoin
Urate oxidase is mainly localised in the liver, where it forms a large electron-dense paracrystalline core in many peroxisome
s. The enzyme exists as a tetramer of identical subunits, each containing a possible type 2 copper-binding site.
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 daltons
. It is unique among the oxidase
s 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.
Significance of absence in humans
Of all animals that include meat in their diet, humans are the only animal that is unable to break down uric acid
. This is because humans do not have the necessary enzyme
uricase. This leads to an increased possibility of an accumulation of uric acid in the body when animal products are eaten.
Humans do have a gene
for urate oxidase, but it is nonfunctional. Thus uric acid is the end product of catabolism
s in humans. Excessive concentration of uric acid in the blood stream leads to gout
Urate oxidase is found in nearly all organisms, from bacteria
, and plays different metabolic roles, depending on its host organism. It was lost in early primate evolution
, and so is absent in humans and other higher apes.
It has been proposed that the loss of urate oxidase gene expression
has been advantageous to hominid
s, since uric acid is a powerful antioxidant
and scavenger of singlet oxygen and radical
s. Its presence provides the body with protection from oxidative
damage, thus prolonging life and decreasing age-specific cancer rates.
Urate oxidase is formulated as a protein drug ( rasburicase
) for the treatment of acute hyperuricemia
in patients receiving chemotherapy
. A PEGylated
form of urate oxidase, pegloticase
, was FDA approved in 2010 for the treatment of chronic gout in adult patients refractory to "conventional therapy".
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
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.