Urate oxidase (Uricase) (UOX)

Urate oxidase (uricase) is an enzyme that catalyzes the oxidation of uric acid to 5-hydroxyisourate, which is subsequently converted to allantoin [1]. Allantoin is significantly more water-soluble than uric acid, allowing for efficient renal excretion and preventing the accumulation of urate crystals in joints and tissues [2]. While most mammals possess a functional urate oxidase, humans and higher primates lack this enzyme due to evolutionary gene silencing, making them susceptible to hyperuricemia and gout [3]. Therapeutic urate oxidases, such as the recombinant version WTX221 developed by Worg Pharma, are administered to provide this missing enzymatic activity and rapidly lower serum uric acid levels [4]. These agents are particularly valuable for treating chronic refractory gout and preventing tumor lysis syndrome in patients undergoing chemotherapy [5]. However, as non-human proteins, they are highly immunogenic and can trigger the production of anti-drug antibodies, leading to infusion reactions or reduced efficacy over time [6]. Furthermore, the enzymatic reaction produces hydrogen peroxide as a byproduct, which can cause oxidative stress and hemolytic anemia in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency [2]. WTX221 is a specific recombinant formulation currently under clinical investigation for its potential to manage hyperuricemia with improved pharmacological properties [4].

Other names

UricaseUrate:oxygen oxidoreductaseUrate oxidaseUric acid oxidase

Catalyzes the conversion of uric acid into the more soluble metabolite allantoin, facilitating renal excretion.