Uric acid oxidase

In humans and many other vertebrates, ammonia arising from deamination reactions or other sources is excreted in the form of urea. These animals are called ureo-telic. Fish excrete nitrogen in the form of ammonium ions and are therefore ammonotelic. Animals that need to conserve water excrete their nitrogen in the form of crystalline uric acid. They are uricotelic, or purinotelic. One often finds animals that convert uric acid to allantoin via uric acid oxidase (Figure 20.8). Allan-toin is more water soluble than uric acid. Uric acid oxidase is absent from primates. 

Figure 20.8 Conversion of uric acid to allantoin with uric acid oxidase.

Uricase, or uric acid oxidase, converts uric acid to allantoin (p. 346). The enzyme occurs in the livers of nearly all mammals, and in the kidneys of oxen, pigs, dogs, rats, and frogs. 

Xanthine oxidase, mol wt ca 275,000, present in milk, Hver, and intestinal mucosa (131), is required in the cataboHsm of nucleotides. The free bases guanine and hypoxanthine from the nucleotides are converted to uric acid and xanthine in the intermediate. Xanthine oxidase cataly2es oxidation of hypoxanthine to xanthine and xanthine to uric acid. In these processes and in the oxidations cataly2ed by aldehyde oxidase, molecular oxygen is reduced to H2O2 (133). Xanthine oxidase is also involved in iron metaboHsm. Release of iron from ferritin requires reduction of Fe " to Fe " and reduced xanthine oxidase participates in this conversion (133). 

Deficiency or Toxicity in Humans. Molybdenum deficiency in humans results in deranged metaboHsm of sulfur and purines and symptoms of mental disturbances (130). Toxic levels produce elevated uric acid in blood, gout, anemia, and growth depression. Faulty utiH2ation results in sulfite oxidase deficiency, a lethal inborn error. 

Enzymes are proteins of high molecular weight and possess exceptionally high catalytic properties. These are important to plant and animal life processes. An enzyme, E, is a protein or protein-like substance with catalytic properties. A substrate, S, is the substance that is chemically transformed at an accelerated rate because of the action of the enzyme on it. Most enzymes are normally named in terms of the reactions they catalyze. In practice, a suffice -ase is added to the substrate on which die enzyme acts. Eor example, die enzyme dial catalyzes die decomposition of urea is urease, the enzyme dial acts on uric acid is uricase, and die enzyme present in die micro-organism dial converts glucose to gluconolactone is glucose oxidase. The diree major types of enzyme reaction are ... 

As an inhibitor of xanthine oxidase, allopurinol also markedly decreases oxidation of both hypoxanthine and xanthine itself to the sole source of uric acid (19) in man. This metabolic block thus removes the source of uric acid that in gout causes the painful crystalline deposits in the joints. It is of interest that allopurinol itself is oxidized to the somewhat less effective drug, oxypurinol (21), by xanthine oxidase. 

Anti-gout Drugs. Figure 1 Xanthine oxidase-catalyzed reactions. Xanthine oxidase converts hypoxanthine to xanthine and xanthine to uric acid, respectively. Hypoxanthine and xanthine are more soluble than uric acid. Xanthine oxidase also converts the uricostatic drug allopurinol to alloxanthine. Allopurinol and hypoxanthine are isomers that differ from each other in the substitution of positions 7 and 8 of the purine ring system. Although allopurinol is converted to alloxanthine by xanthine oxidase, allopurinol is also a xanthine oxidase inhibitor. Specifically, at low concentrations, allopurinol acts as a competitive inhibitor, and at high concentrations it acts as a noncompetitive inhibitor. Alloxanthine is a noncompetitive xanthine oxidase inhibitor. XOD xanthine oxidase. 

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... 

Uricostatic drugs inhibit the production of uric acid through the inhibition of xanthine oxidase. Allopurinol is the only therapeutically used uricostatic drug. 

Xanthine oxidase (XOD) is the key enzyme in purine catabolism. XOD catalyses the conversion ofhypoxan-thine to xanthine and of xanthine to uric acid, respectively. The uricostatic drug allopurinol and its major metabolite alloxanthine (oxypurinol) inhibit xanthine oxidase. 

Xanthine oxidase (XO) is not only an important biological source of ROS but also the enzyme responsible for the formation of uric acid associated with gout leading to painful inflammation in the joints. The XO inhibition effect by the enzymatically synthesized poly(catechin) increased as an increasing concentration of catechin units, while the monomeric catechin showed almost negligible inhibition effect in the same concentration range. ° This markedly amplified XO inhibition activity of poly(catechin) was considered to be due to effective multivalent interaction between XO and the condensed catechin units in the poly (catechin). 

Most patients in the United States are treated with allopurinol, which usually is effective if the dosage is titrated appropriately. The drug and its primary active metabolite, oxypurinol, reduce serum uric acid concentrations by inhibiting the enzyme xanthine oxidase, thereby blocking the oxidation of hypoxanthine and xanthine to uric acid. 

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... 

There is no doubt that electrochemically xanthine is initially oxidized to uric acid, which is then further oxidized to a bis-imine that undergoes hydrolysis giving ultimately alloxan, allantoin and urea. There is no single enzyme in man that will bring about such a fragmentation of xanthine. However, there are organisms that possess a combination of enzymes, e.g., xanthine oxidase and certain peroxidases, that under conditions comparable to those employed in the... 

Kamei et al. [45] separated spermine, spermidine, putrescine, and cadav-erine in an ion-pair reversed-phase LC system and detected the hydrogen peroxide formed in the reaction catalyzed by the enzymes putrescine oxidase and polyamine oxidase with POCL. The same analytes were determined in a later study [46], together with the acetyl derivatives. The sensitive determination of uric acid, selectively converted to hydrogen peroxide by uricase, has been investigated by several authors [37, 47],... 

On the other hand, several oxidases are known to generate hydrogen peroxide, acting as an oxidant in the CL system, from corresponding substrates. IMERs in which the oxidases are immobilized on adequate supporting materials such as glass beads have been developed. IMERs are often used for flow injection with CL detection of uric acid and glucose, and are also applicable to the CL determination of acetylcholine, choline, polyamines, enzyme substrates, etc., after online HPLC separation. 

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. 

Uric acid Uricase oxidase, HRP Luminol-H202-HRP 61... 

The answer is c. (Hardman, pp 649—650.) Acute hyperuricemia, which often occurs in patients who are treated with cytotoxic drugs for neoplasic disorders, can lead to the deposition of urate crystals in the kidneys and their collecting ducts. This can produce partial or complete obstruction of the collecting ducts, renal pelvis, or ureter. Allopurinol and its primary metabolite, alloxanthine, are inhibitors of xanthine oxidase, an enzyme that catalyzes the oxidation of hypo xanthine and xanthine to uric acid. The use of allopurinol in patients at risk can markedly reduce the likelihood that they will develop acute uric acid nephropathy. 

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... 

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