Uric acid solubility

Prevention of tumor lysis syndrome generally is achieved by increasing the urine output and preventing accumulation of uric acid. Prophylactic strategies should begin immediately on presentation, preferably 48 hours prior to cytotoxic therapy. Treatment modalities primarily increase uric acid solubility, address electrolyte disturbances, and support renal output. 

Vigorous intravenous hydration with dextrose 5% in water with half-normal saline at 3 L/m2 per day to maintain a urine output of 100 mL/m2 per hour or more is necessary, unless the patient presents with acute renal dysfunction. Alkalinization of the urine to a pH of 7.0 or more with 50 to 100 mEq/L of sodium bicarbonate has been used to promote uric acid solubility for excretion. This measure is controversial because xanthine and hypoxanthine are less soluble at alkaline pH, potentially leading to crystallization, especially during and after allopurinol therapy32 (see Fig. 96-6). Medications that increase serum... 

The story of lithium parallels other stories in medical history where the medicinal value of a substance is discovered accidently. In 1949, John Cade, an Australian psychiatrist, decided to experiment with lithium on guinea pigs. He theorized that uric acid was a cause of manic behavior. Since he needed to keep the uric acid soluble, he used lithium salts as an agent in the solution. The guinea pigs did not become manic as he expected, but instead they responded by becoming extremely calm. 

The use of Harolan can induce a significant decrease of serum uric acid by the simultaneous raising of the urinary pH through better solubility for the increase of uric acid excretion in the first two days. In 24-h-urine and in the circadian rhythm the uric acid solubility graph was never exceeded during the examination. No side effects were observed. 

Treatment in both children involved the use of allopurinol - but at a lesser dosage (5 mg/kg/2hh) because of the retention of the principal metabolite oxipurinol in severe renal failure Careftil monitoring of plasma oxipurinol levels is desirable For the HGPRT deficient child alkali was also given to enhance uric acid solubility It was not prescribed in the APRT deficient child since 2 8-dihyroxy adenine solubility is unaffected by alkali and its use may even be contraindicated ... 

Of the water-soluble vitamins, intakes of nicotinic acid [59-67-6] on the order of 10 to 30 times the recommended daily allowance (RE)A) have been shown to cause flushing, headache, nausea, and moderate lowering of semm cholesterol with concurrent increases in semm glucose. Toxic levels of foHc acid [59-30-3] are ca 20 mg/d in infants, and probably approach 400 mg/d in adults. The body seems able to tolerate very large intakes of ascorbic acid [50-81-7] (vitamin C) without iH effect, but levels in excess of 9 g/d have been reported to cause increases in urinary oxaHc acid excretion. Urinary and blood uric acid also rise as a result of high intakes of ascorbic acid, and these factors may increase the tendency for formation of kidney or bladder stones. AH other water-soluble vitamins possess an even wider margin of safety and present no practical problem (82). 

The presence of sparingly soluble components in human urine, such as calcium oxalate, calcium phosphate, magnesium ammonium phosphate, uric acid and l-cystine. Kidney stones are composed mainly of these compounds. 

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... 

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. 

Humans convert adenosine and guanosine to uric acid (Figure 34-8). Adenosine is first converted to inosine by adenosine deaminase. In mammals other than higher primates, uricase converts uric acid to the water-soluble product allantoin. However, since humans lack uricase, the end product of purine catabofism in humans is uric acid. 

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. 

Gout is caused by an abnormality in uric acid metabolism. Uric acid is a waste product of the breakdown of purines contained in the DNA of degraded body cells and dietary protein. Uric acid is water soluble and excreted primarily by the kidneys, although some is broken down by colonic bacteria and excreted via the gastrointestinal tract. 

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. 

As can be seen, all the water-soluble compounds are capable of quenching CAR + efficiently, with rate constants of the order of 106,107, and 108 M 1 s 1 for ferrulic acid, both ascorbic and uric acids, and Trolox, respectively. 

A typical time course of PCL with luminol as the photosensitizer is shown in Figure 5, as blank. The presence of a water-soluble antioxidant leads to dose-dependent temporary inhibition of PCL. ACW (antioxidant capacity of water-soluble compounds) represents the effect of human blood plasma (2 p.L) on PCL all tested antioxidants, such as ascorbic acid, uric acid, Trolox, taurine, bilirubin, ceruloplasmin, etc., produced the same effects. 

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. 

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). 

The low solubility of uric acid has unfortunate consequences since at higher than normal concentrations it can crystallise in the body. For example, when the urine is unusually acid, calcium urate stones can form in the kidney and bladder. High levels of uric acid in the blood can result in the formation of urate crystals in the joints, which causes a very painful condition, since it results in inflammation in these joints. Gout is unlikely to develop if the urate concentration remains low (<0.4 mmol/L) but any factor that increases the rate of production or decreases that of elimination by the... 

The fact that purine degradation in humans already stops at the uric acid stage can lead to problems, since—in contrast to allantoin—uric acid is poorly soluble in water. When large amounts of uric acid are formed or uric acid processing is disturbed, excessive concentrations of uric acid can develop in the blood hyperuricemia). This can result in the accumulation of uric acid crystals in the body. Deposition of these crystals in the joints can cause very painful attacks of gout. 

Workers at a molybdenum-roasting plant with time-weighted average (TWA) exposures of approximately 9.5mgMo/m to soluble dusts had increased plasma and urine levels of molybdenum the only adverse biochemical findings were large elevations in serum ceruloplasmin levels and some increase in serum uric acid levels. ... 

Uric acid is minimally water-soluble and most cases of gout arise from inadequate excretion by the kidneys (souric acid and precipitation of urate stones In the kidneys and extremities. 

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. 

Allopurinol, in contrast to the uricosuric drugs, reduces serum urate levels through a competitive inhibition of uric acid synthesis rather than by impairing renal urate reabsorption. This action is accomplished by inhibiting xanthine oxidase, the enzyme involved in the metabolism of hypoxanthine and xanthine to uric acid. After enzyme inhibition, the urinary and blood concentrations of uric acid are greatly reduced and there is a simultaneous increase in the excretion of the more soluble uric acid precursors, xanthine and hypoxanthine. 

Gout is a metabolic disease characterized by recurrent episodes of acute arthritis due to deposits of monosodium urate in joints and cartilage. Uric acid renal calculi, tophi, and interstitial nephritis may also occur. Gout is usually associated with hyperuricemia, high serum levels of uric acid, a poorly soluble substance that is the major end product of purine metabolism. In most mammals, uricase converts uric acid to the more soluble allantoin this enzyme is absent in humans. While clinical gouty episodes are associated with hyperuricemia, most individuals with hyperuricemia may never develop a clinical event from urate crystal deposition. 

Dietary purines are not an important source of uric acid. Quantitatively important amounts of purine are formed from amino acids, formate, and carbon dioxide in the body. Those purine ribonucleotides not incorporated into nucleic acids and derived from nucleic acid degradation are converted to xanthine or hypoxanthine and oxidized to uric acid (Figure 36-7). Allopurinol inhibits this last step, resulting in a fall in the plasma urate level and a decrease in the size of the urate pool. The more soluble xanthine and hypoxanthine are increased. 

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