Uric acid allantoin from

Structure of Uric Acid.—The formation of allantoine from uric acid is evidence that the latter contains two urea residues, and the formation of alloxan that it contains the arrangement of atoms represented by the symbols,—... 

Moreover, the oxidation of methional to ethylene has been proposed (Beauchamp and Fridovich 1970 Biaglow et al. 1997), and the formation of allantoin (Grootveld and Halliwell 1987 Halliwell et al. 1988) from uric acid as well as the imidazolone derivative from histamine (Ching et al. 1995) have been suggested as an index of OH action in vivo (Halliwell et al. 1988). 

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. 

Lower primates and mammals other than humans carry purine metabolism one step further with the formation of aUantoin from uric acid, a step mediated by uricase ([urate oxygen] oxidoreductase, EC 1.7.3.3). In humans, approximately 75% of uric acid excreted is lost in the urine most of the remainder is secreted mto the gastrointestinal tract, where it is degraded to allantoin and other compounds by bacterial enzymes. 

In many legumes, transportation of N from root to shoot occurs in the form of ureids, allantoin, and allantoic acid, which are synthesized from uric acid, an oxidation product of purine (xanthine). Poor growth of legumes in the presence of Mo deficiency can be ascribed in part to poor upward transport of N because of disturbed xanthine catabolism. In plants, oxidation of xanthine is mediated by another molybdoenzyme, xanthine dehydrogenase (Mendel and Muller, 1976 Nguyen and Feierabend, 1978). This enzyme has a constitution similar to that of the xanthine oxidase found in animals. It has two identical subunits, and each unit contains one Mo atom, one FAD, and four Fe-S groups. 

Fig. 3 (I) Chromatogram of 10-fold diluted sheep urine. (II) Chromatographic separation of standard solutions. Peaks A=allantoin B=uric acid C=hypoxanthine D=aUopurinol (IS) and E creatinine. (From Ref. [25].)...

Fig. 12. Mechanism for formation of allantoins from the methylated uric acid-4,5-diol derived from theobromine and caffeine. Molar amounts of products are those formed in 1 M HOAc...

Formation of methylated allantoins from the uric acid-4,5-diols (IV, X,... 

Fig. 11) would likely proceed by different mechanisms. Protonation of the diol (IV, Fig. 12) derived from theobromine would lead to ring opening at the C6— Cs position giving an imidazole isocyanate (XVI, Fig. 12). This could readily form XVII which after hydrolysis and loss of C02 would give dimethyl-allantoin (XVIII). On the other hand, the uric acid diol derived from caffeine (X, Fig. 12) cannot fragment by this mechanism. Accordingly, either or both of the processes could Occur via the form of the diol hydrated at the C6 carbonyl group (XIX, Fig. 12) which could readily lose C02 to give XX followed by rearrangement to trimethylallantoin (XXI).

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... 

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. 

Allantoin is the excretory product in most mammals other than primates. Most fish hydrolyze allantoin to allantoic acid, and some excrete that compound as an end product. However, most continue the hydrolysis to form urea and glyoxylate using peroxisomal enzymes.336 In some invertebrates the urea may be hydrolyzed further to ammonia. In organisms that hydrolyze uric acid to urea or ammonia, this pathway is used only for degradation of purines from nucleotides. Excess nitrogen from catabolism of amino acids either is excreted directly as ammonia or is converted to urea by the urea cycle (Fig. 24-10). 

One of the first facts observed in regard to uric acid was that on heating it yielded cyanuric acid, (OCNH)3, and ammonia, NH3. As these same products had been obtained by heating urea, OC(NH2)2, it was considered probable that a urea residue was present in uric acid. It was then shown that on oxidation with lead dioxide, one of the ureids, the di-ureid known as allantoin was obtained, together with urea, oxalic acid and carbon dioxide. With other oxidizing agents, such as nitric acid, the products were equal molecules of urea and the two ureids alloxan and parabanic acid. From alloxan there may be obtained, by reduction, two other ureids, viz., barbituric acid and... 

From the facts that uric acid yields the di-ureid allantoin and also equal molecules of alloxan, a mono-ureid, and urea it was concluded that uric acid must contain two urea residues. From the constitution of alloxan and its reduction products, barbituric and dialuric acids, uric acid must likewise contain a three carbon chain linked to a urea residue by the end carbon atoms. Also, as it yields parabanic acid or oxalyl urea, one of the urea residues must be linked to two adjacent carbon atoms in this chain. 

The presence of nucleic acids in yeast is one of the main problems with their use in human foods. Other animals metabolize uric acid to allantoin, which is excreted in the urine. Purines ingested by humans and some other primates are metabolized to uric acid, which may precipitate out in tissue to cause gout (37). The daily human diet should contain no more than about 2 g of nucleic acid, which limits yeast intake to a maximum of 20 g. Thus, the use of higher concentrations of yeast protein in human food requires removal of the nucleic acids. Unfortunately, yields of protein from extracts treated as described are low, and the cost of the protein may more than double. 

The purine catabolic pathway appears in Figure 8,31, The end-product of purine cataboiism in primates, and in some other vertebrates, is uric acid, Purine catabolism differs in other species. Urate oxidase catalyzes the breakdown of uric acid to allantoin. Allantoin can be further broken down to produce urea and glyoxyJate, Allantoin is the purine excretory pixiduct in some mammals and reptiles. Urea is the purine excretory product in fish. Guanine is the purine excretory product in pigs and spiders. Uric acid is used for the packaging and excretion of waste N from amino acids in birds and some reptiles. 

Oxidation of uric acid (LXIV) and its iV-methylated derivatives at a graphite anode produces a quinonoid product (LXV), which adds water or another nucleophile across a C=N double bond to an unstable intermediate (LXVI), which reacts to products. From the oxidation of uric acid can be isolated, depending on pH, allantoin, 5-hydroxyhydan-toin, alloxan, and urea [362, 363] ... 

RP-HPLC procedures for the determination of creatinine and purine metabolites, such as allantoin, uric acid, xanthine, and hypoxanthine in ruminant urine, were described. Chromatography was achieved with a Cig column under isocratic conditions, and detection at 218 nm without allantoin derivatization. The chromatographic conditions were a compromise between the sensitivity and specificity of the measurement of each analyte, analysis time, and resolution of all analyte peaks from interfering compounds.Uremic toxins creatine, creatinine, uric acid, and xanthine were simultaneously determined in human biofluids, simply after dilution, with UV detection at 200 nm. This method was compared, for creatinine and uric acid, with conventional routine methods and did not give significantly different results. 

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. 

Conclusions as to the structure of uric acid have been arrived at from the study of the products formed as the result of the oxidation of the acid. Among the oxidation-products are par-abanic acid and alloxan, which are formed when uric acid is treated with nitric acid, and allantoine, which results from the oxidation of the acid with potassium permanganate. The structure of these substances must be studied before an understanding of the configuration of uric acid can be reached. 

Allantoine, C4H6O3N4, is formed when uric acid is oxidized by potassium permanganate. The products of hydrolysis of allantoine, and its synthesis from glyoxylic acid and urea, lead to the structure which is represented by the formula,—... 

Uric acid 33 (2,6,8-trihydroxypurine) was isolated from urinary calculi by Scheele (1774). After ascertaining its molecular formula (Liebig and Mitscherlich 1834), its structure was established by oxidative degradation and structural correlation with barbituric acid, alloxan, allantoin and hydantoin (Liebig, Wohler, Baeyer) ... 

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