Uric acid/urate

For birds, insects, and reptiles, which have an egg stage during development, so that water availability is severely restricted, the synthesis of a highly soluble excretory product would have serious osmotic consequences therefore most of the ammonia is converted to the virtually insoluble uric acid (urate). This product can be safely retained in the egg or excreted as a slurry of fine crystals by the adult. In birds that nest colonially this can accumulate in massive amounts on islands off the coast of Peru cormorants have deposited so much that this guano (hence the name guanine) is collected for use as a fertiliser. Uric acid is less effective as an excretory product, since it has a lower nitrogen content than urea (33%) and is more expensive to synthesise (2.25 molecules ATP per atom of nitrogen). Mammals do produce uric acid but as a product of purine catabolism (see above). 

Lotta Topaigne is being treated with allopurinol for gout, which is caused by an accumulation of sodium urate crystals in joints and joint fluid, particularly in the ankle and great toe. Allopurinol is a suicide inhibitor of the enzyme xanthine oxidase, which is involved in the degradation of purine nucleotides AMP and GMP to uric acid (urate). Although hypoxanthine levels increase in the presence of allopurinol, hypoxanthine does not participate in urate crystal formation and precipitation at this concentration. It is excreted in the urine. 

Fig. 8.19. Allopurinol is a suicide inhibitor of xanthine oxidase. A. Xanthine oxidase catalyzes the oxidation of hyrpoxanthine to xanthine, and xanthine to uric acid (urate) in the pathway for degradation of purine nucleotides. B. The oxidations are performed by a molybdenum-oxo-sul-fide coordination complex in the active site that complexes with the group being oxidized. Oxygen is donated from water. The enzyme can work either as an oxidase (O2 accepts the 2e and is reduced to H2O2) or as a dehydrogenase (NAD accepts the 2e and is reduced to NADH.) C. Xanthine oxidase is able to perform the first oxidation step and convert allopurinol to alloxanthine (oxypurinol). As a result, the enzyme has committed suicide the oxypurinol remains bound in the molybdenum coordination sphere, where it prevents the next step of the reaction.

TABLE 2, Mean (- S,D,) serum uric acid, urate excretion and renal function... 

Fourcroy examined gall stones and calculi. In 1800 Fourcroy and Vauquelin published an important memoir on the composition of urinary calculi, which somewhat extended the publications of Wollaston — which they do not mention — and of Pearson, who changed Scheele s name lithic acid into uric oxide or ouric oxide Fourcroy and Vauquelin called it adde urique. They analysed over 600 calculi and concluded that they are of twelve main species, consisting of the following substances, or mixtures of them uric acid, urate of ammonia, phosphate of lime, phosphate of magnesia and ammonia. 

Hardy-Weinberg law (Hardy-Weinberg equilibrium) Harnsaure (Urat) uric acid (urate)... 

Uric acid first gives white precipitate of copper urate and then reduces. 

Thus, the presence of uric acid crystals in joints triggers a vicious cycle, resulting in an extremely painful inflammation. A typical localization of acute gouty arthritis is the first metatarsal joint of the foot (podagra). The diagnosis of acute gouty arthritis is confirmed by the detection of urate crystals in the joint or tophus. 

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... 

Uric acid is the endproduct of purine metabolism in man. Uric acid has a lower solubility than its progenitor metabolites, hypoxanthine and xanthine. Impaired uric acid elimination and/or increased uric acid production result in hyperuricemia and increase the risk of gouty arthritis. At physiological pH, 99% of the uric acid molecules are actually in the form of the urate salt. A decrease in pH increases the fraction of uric acid molecules relative to urate molecules. Uric acid possesses lower solubility than urate. 

Gout is a form of arthritis in which uric acid accumulates in increased amounts in the blood and often is deposited in the joints. The deposit or collection of urate crystals in the joints causes the symptoms (pain, redness, swelling, joint deformity). 

Allopurinol (Zyloprim) reduces the production of uric acid, thus decreasing serum uric acid levels and the deposit of urate crystals in joints. The exact mechanism of action of colchicine is unknown, but it does reduce the inflammation associated with the deposit of urate crystals in the joints. This probably accounts for its ability to relieve the severe pain of acute gout. Colchicine has no effect on uric acid metabolism. 

In those with gout, the serum uric acid level is usually elevated. Sulfinpyrazone increases the excretion of uric acid by the kidneys, which lowers serum uric acid levels and consequently retards the deposit of urate crystals in the joints. Probenecid (Benemid) works in the same manner and may be given alone or with colchicine as combination therapy when there are frequent, recurrent attacks of gout. Probenecid also has been used to prolong the plasma levels of the penicillins and cephalosporins. 

DRUGS USED FOR GOUT. The nurse encourages a liberal fluid intake and measures the intake and output. The daily urine output should be at least 2 liters. An increase in urinary output is necessary to excrete the urates (uric acid) and prevent urate acid stone formation in the genitourinary tract. 

Humans catabolize purines to uric acid (pA 5.8), present as the relatively insoluble acid at acidic pH or as its more soluble sodium urate salt at a pH near neutrality. Urate crystals are diagnostic of gout. Other disorders of purine catabolism include Lesch-Nyhan syndrome, von Gierke s disease, and hypo-uricemias. 

The solubility of uric acid depends on concentration and temperature. At high serum concentrations, lower body temperature causes the precipitation of monosodium urate crystals. Collections of these crystals (called micro tophi) can form in joint spaces in the distal extremities. 

Allopurinol is well absorbed with a short half-life of 2 to 3 hours. The half-life of oxypurinol approaches 24 hours, allowing allopurinol to be dosed once daily. Oxypurinol is cleared primarily renally and can accumulate in patients with reduced kidney function. Allopurinol should not be started during an acute gout attack because sudden shifts in serum uric acid levels may precipitate or exacerbate gouty arthritis. Rapid shifts in serum uric acid can change the concentration of monosodium urate crystals in synovial fluid, causing more crystals to precipitate. Thus some clinicians advocate a prophylactic dose of colchicine (0.6 mg/day) during initiation of antihyperuricemic therapy. Acute episodes should be treated appropriately before maintenance treatment is started. 

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... 

Gout A group of disorders of purine metabolism, manifested by various combinations of hyperuricemia recurrent acute inflammatory arthritis induced by crystals of monosodium urate monohydrate tophaceous deposits of monosodium urate monohydrate crystals in and around the joints of the extremities, which may lead to crippling destruction of joints and uric acid urolithiasis. 

Monosodium urate A crystallized form of uric acid that can deposit in joints leading to an inflammatory reaction and the symptoms of gout. 

An amperometric urate sensor based on uricase-immobilized silk fibroin membrane was developed by Zhang [256], The biosensor can be used to measure the urate level in human serum or urine and standard additions of uric acid. F or this biosensor, the recoveries of uric acid in human serum and urine are in the range of 94.2 102.6% to 92.5 97.9%, respectively. The relative standard deviations for repeatedly monitoring standard urate solution, human serum, and urine are 2.37, 3.72, and 2.95%, respectively, based on 100 measurements. 

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