Uricase
Greater than 90.0% as determined by SDS-PAGE.
Description
The cDNA coding for urate-oxidase was cloned from a strain of Aspergillus flavus . The monomer protein has no intra- or inter-disulfide bridges.
Product Specs
Urate oxidase, also known as uricase, is an enzyme that plays a crucial role in the breakdown of purines. It catalyzes the oxidation of uric acid, a waste product of purine metabolism, into allantoin. Allantoin is more soluble than uric acid, making it easier for the body to excrete. Humans and other higher primates lack uricase, making them susceptible to conditions like gout, which is characterized by the buildup of uric acid in the body. Uricase is present in many other organisms and is used therapeutically to manage hyperuricemia, elevated uric acid levels, often associated with gout, malignancies, and organ transplantation. Its rapid action and effectiveness in lowering uric acid levels make it a valuable treatment option.
The purity of this product is greater than 90%, as determined by SDS-PAGE analysis.
Product Science Overview
Urate oxidase, also known as uricase (EC 1.7.3.3), is an enzyme that catalyzes the oxidation of uric acid to allantoin, a more soluble and easily excreted compound. This enzyme is naturally present in many organisms, including bacteria, fungi, and lower animals, but is notably absent in humans and higher primates due to evolutionary gene silencing .
The absence of urate oxidase in humans and higher primates is attributed to three specific mutations that have rendered the gene non-functional . This evolutionary change is thought to confer certain advantages, such as the antioxidant properties of uric acid, which may help in reducing oxidative stress and potentially lowering the risk of cancer .
The lack of urate oxidase in humans leads to the accumulation of uric acid, which can result in conditions such as gout and hyperuricemia. Gout is characterized by the formation of monosodium urate crystals in joints and tissues, leading to inflammation and pain . Traditional treatments for gout include medications like allopurinol, but these are not always effective for all patients .
To address the limitations of traditional treatments, recombinant urate oxidase has been developed. This enzyme is produced using genetic engineering techniques, where the urate oxidase gene from organisms like Aspergillus flavus is cloned and expressed in suitable host cells, such as Saccharomyces cerevisiae . The recombinant enzyme, known as rasburicase, is used to treat hyperuricemia, particularly in patients undergoing chemotherapy .
Urate oxidase catalyzes the conversion of uric acid to 5-hydroxyisourate, which subsequently decomposes to allantoin and carbon dioxide . This reaction does not require any cofactors or metal ions, making it a straightforward enzymatic process . The enzyme functions as a homo-tetramer, with each subunit contributing to the active site located at the dimeric interfaces .
Recent advancements have focused on enhancing the stability and efficacy of recombinant urate oxidase. For instance, PAT101, a novel recombinant human albumin-conjugated urate oxidase variant, has shown promising results in preclinical studies . This variant has an extended half-life and reduced immunogenicity compared to traditional formulations, making it a potential candidate for long-term gout management .
