Oxidase urate

Some mammals have urate oxidase, which metabolizes uric acid to a much more soluble product, allantoin. Administration of the enzyme to humans could be useful in the treatment of gout. This assay was designed to measure the activity of urate oxidase bound to polyethylene glycol. 

Urate and allantoin were separated on a /uBondapack CI8 column (3.9 mm x 300 mm). The mobile phase was 50 mM ammonium phosphate (pH 3.0). The effluent was monitored at 290 nm for quantification of uric acid or at 218 nm for detection of allantoin, or mixed in-line with scintillation fluid for quantitation by a flow-through detector. 

The reaction mixture contained in a final volume of 50 fiL 5 to 10 fih of enzyme sample, 35 fih of 0.1 M Na borate (pH 8.5), and 0.25 nCi (4.55 nmol) [2-14C]uric acid, plus unlabeled uric acid to give a final concentration of 300 fxM urate. The reaction was carried out at 37°C and was started by the addition of enzyme or substrate. Reactions were terminated at varying times by adding 20 pL of 1 M perchloric acid. After the tubes had been on ice for 5 minutes, the supemate was analyzed by HPLC The reaction was. linear in 10-minute assays when up to 20% of the substrate was converted to product. 

The enzyme preparation used was uricase modified with polyethylene glycol, from Enzon, or plasma from patients is treated with PEC-uricase. 

23 Glutamine 5-PhosphorlbosyM-pyropho8phate Amldotranaferase (Taha and Oelts, 1993) 

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Rasburicase is a recombinant urate oxidase that catalyzes the conversion of uric acid to allantoin which possesses a greater water-solubility than uric acid. In contrast to allopurinol, rasburicase has also an inhibitory effect on... 

Pharmacologic prevention strategies for tumor lysis syndrome are aimed at low- and high-risk patients (Fig. 96-7). Allopurinol is a xanthine oxidase inhibitor that is used for prevention only because it has no effect on preexisting elevated uric acid. Rasburicase is a recombinant form of urate oxidase that is useful for both prevention and treatment but is extremely expensive (Table 96-12). Although the approved dose is 0.2 mg/kg per day... 

Krystexxa (mammalian urate oxidase) 0 Nonspecific, amine PEGylation 10 2010 (USA)... 

Modified procedure (ACU kit) The plasma sample is preincubated with uricase (urate oxidase) and then quantified in the ACW assay. The method requires 10 pL of plasma. It is also possible to determine the uric acid (UA) portion in ACW UA = ACW - ACU. 

The enzyme urate oxidase has also found medical application for the treatment of acute hype-ruricaemia (elevated plasma uric acid levels), associated with various tumours, particularly during their treatment with chemotherapy. 

Purine metabolism in some mammals is characterized by a further oxidation of uric acid to al-lantoin by the enzyme urate oxidase. Allantoin is significantly more water soluble than uric acid and is also freely excreted via the renal route. 

Administration of urate oxidase to humans suffering from hyperuricaemia results in the reduction of serum uric acid levels through its conversion to allantoin. Urate oxidase purified directly... 

Wu, X., Wakamiya, M., Vaishnav, S. et al. Hyperuricemia and urate nephropathy in urate oxidase-deficient mice Proa Natl Acad. Sci. U.S.A. 91 742-746,1994. 

Urate oxidase 1.7.3.3 Uric acid/oxygen Allantoin Oxygen electrode... 

Rasburicase is a recombinant form of an enzyme, urate oxidase. This enzyme catalyses the conversion of uric acid to allantoin, a more soluble molecule, easily cleared by kidney. Monthly infusions of rasburicase appear to be a possible therapy for severe gout not treatable by other means. The most important adverse events are allergy and the development of antibodies which compromise rasburicase effectiveness. 

Ambartsumian, T. G., Adamian, S. Y., Petrosia, L. S., and Simonian, A. L. (1992). Incorporation of water-soluble enzymes glucose-oxidase and urate oxidase into phosphatidylcholine liposomes. Biol. Membr, 5, 1878-87. 

Uric acid is the excreted end product of purine catabolism in primates, birds, and some other animals. A healthy adult human excretes uric acid at a rate of about 0.6 g/24 h the excreted product arises in part from ingested purines and in part from turnover of the purine nucleotides of nucleic acids. In most mammals and many other vertebrates, uric acid is further degraded to al-lantoin by the action of urate oxidase. In other organisms the pathway is further extended, as shown in Figure 22-45. 

Uracil (Ura, U) 199s, 203 tautomerism of 45 Urate oxidase 886 Urea 82s, 478s Urea carboxylase 730 Urease 478, 877,878... 

Mammals other than primates further oxidize urate by a liver enzyme, urate oxidase. The product, allantoin, is excreted. Humans and other primates, as well as birds, lack urate oxidase and hence excrete uric acid as the final product of purine catabolism. In many animals other than mammals, allantoin is metabolized further to other products that are excreted Allantoic acid (some teleost fish), urea (most fishes, amphibians, some mollusks), and ammonia (some marine invertebrates, crustaceans, etc.). This pathway of further purine breakdown is shown in figure 23.22. 

Degradation of uric acid to excretory products. Mammals other than primates oxidize uric acid further to allantoin. Humans and other primates as well as birds lack urate oxidase and hence excrete uric... 

Stegink, S.J., Vaughan, K.C. Verma, D.P.S. (1987). Antigenic similarity in urate oxidase of major ureide-producing legumes and its correlation with the type of peroxisomes in uninfected cells of nodules. Plant Cell Physiology 28, 387-96. 

Peroxisomes Catalase, D-amino acid oxidase, urate oxidase... 

Akyilmaz E, Sezgintiirk MK, Dinfkaya E (2003) A biosensor based on urate oxidase-peroxidase coupled enzyme system for uric acid determination in urine. Talanta 61 73-79... 

Recombinant urate oxidase catalyzes enzymatic oxidation of uric acid... 

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