Allantoin solubility

Allantoin was extracted from milk and analyzed on an aminopropyl cohunn (A = 214nm) using a 90/10 acetonitrile/water mobile phase [1087]. The authors note an increase in retention time with increased acetonitrile in the mobile phase. This is most likely due to decreasing allantoin solubility as the acetonitrile level increases. Elution was complete in <4 min and the analyte peak was well resolved fiom other extracted materials. A linear range of 10-50 pM and a detection limit of 1 pM were reported. 

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... 

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. 

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. 

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. 

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. 

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. 

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. 

Uricolytics. Nonprimates are able, via the enzyme urate oxidase, to metabolize uric acid to allantoin, a product with better water solubility and faster renal elimination. Ras-buricase, a recombinant urate oxidase, can be given by infusion in patients with malignant neoplasias, in whom chemotherapy is liable to generate a massive amount of uric acid. 

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. 

The degradation of purines varies with the species. Actually uric acid is excreted as the principal end product of purine metabolism by very few mammals, of which man is unfortunately one. Most nonuricotelio animals possess the enzyme uricase, which converts uric acid to the much more soluble end product allantoin. Man and certain of the higher apes, as well as fowl and reptiles, do not possess this enzyme, so that they must excrete uric acid as the end product of purine metabolism. Despite the fact that it possesses uricase, as do other dogs, the Dalmatian coach hound is peculiar in that it excretes uric acid. This anomaly results from the absence of tubular reabsorption of uric acid in the kidney (Fll). 

In humans, uric acid is the end product of the degradation of purines. Uric acid serves no known physiologic purpose and therefore is regarded as a waste product. In lower animals, the enzyme uricase breaks down uric acid to the more soluble allantoin, and thus uric acid does not accumulate. Gout occurs exclusively in humans in whom a miscible pool of uric acid exists. Under normal conditions, the amount of accumulated uric acid is about 1200 mg in men and about 600 mg in women. The size of the urate pool is increased severalfold in individuals with gout. This excess accumulation may result from either overproduction or underexcretion. 

Rasbnricase is an antimetabolite that catalyzes enzymatic oxidation of nric acid into an inactive and soluble metabolite (allantoin). It is indicated in initial management of plasma nric acid levels in pediatric patients with leukemia, lymphoma, and solid tnmor malignancies who are receiving anticancer therapy expected to result in tumor lysis and snbsequent elevation of plasma uric acid. 

Uric acid, the typical waste product from purines, can cause problems in primates due to its marginal water solubility. Deposits of uric acid in the joints and extremities cause gout (Section 23.8). Other mammals do not have a problem with uric acid because they convert it to allantoin, which is very water-soluble. 

It is well known that uric acid is an end product of only a few mammals man, higher apes, and the Dalmatian coach hound (F5). The Dalmation is an anomaly because its excretion is due to a kidney abnormality (F5). The other mammals that do not excrete uric acid as a primary purine end product, form it as an intermediate, but they possess the enzyme uricase, which degrades vuic acid to allantoin, a more highly water-soluble substance than uric acid, and in some cases this is degraded further. 

See Aluminum chlorohydrate Aluminum chlorhydroxide. See Polyaluminum chloride Aluminum chlorohydrate Aluminum chlorhydroxide alcohol soluble complex. See Aluminum chlorohydrex Aluminum chlorhydroxy allantoinate. See Alcloxa... 

Isoprenosine, a complex of p-acetamidobenzoic acid, N,N-dimethylamino-2-propanol and inosine at a molar ratio of 3 1, is a white crystalhne powder, slightly bitter in taste, soluble in water at room temperature to an extent of 25% (250 mg/ml) and stable in neutral solution. The dosage commonly administered to man is 500 mg tablets (Hadden and Giner-Sorolla 1981). Of particular importance is the metabolic labihty of the inosine moiety of isoprinosine, the half fife of which is 3 min and 50 min, respectively, following intravenous and oral administrations in the rhesus monkey. More than 90 % of the labelled inosine is excreted as allantoin and uric acid. 

Uricase is a hepatic enzyme that converts uric acid into allantoin, which is more easily excreted by the kidney because of its water-soluble compound. In humans, a missense and frame shift mutation during evolution resulted in an inactivated gene encoding uricase. Thus, serum uric acid concentrations in humans are close to the... 

Allantoin is much more soluble than uric acid, the solubility in water being 1 160 at 20° C. Eor this reason it is much more desirable as an end-product of purine metabolism, since it does not form calculi. 

Adenine is converted into hypoxanthine, and guanine is converted into xanthine. Subsequently, by the action of xanthine oxidase both hypoxanthine and xanthine are converted into uric acid. Here the transformation stops in man, the higher apes, the Dalmatian dog, and the birds and reptiles in consequence, uric acid is the characteristic end-product of purine metabolism. Most of the higher animals, however, are able to oxidise uric acid, and by opening part of the purine ring convert it into the more much soluble compound, allantoin, which is readily eliminated as a urinary solute. 

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