Allantoic acid degradation

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). 

Many animals degrade uric acid further (Figure 15.13). Urate oxidase converts uric acid to allantoin, an excretory product in many mammals. Allantoinase catalyzes the hydration of allantoin to form allantoate, which is excreted by bony fish. Other fish, as well as amphibians, produce allantoicase, which splits allantoic acid into glyoxylate and urea. Finally, marine invertebrates degrade urea to NH4 and COz in a reaction catalyzed by urease. 

Uric acid, the end point of purine degradation in primates, is excreted. Most other animals, however, oxidize uric acid to allantoin, hydrolyze allantoin to allantoic acid and subsequently convert allantoic acid to urea or other possible excretion products, depending on the animal (Figure 22.8). 

In more recent experiments in which the unidentified compound has been detected, it has coelectrophoresed with the ureide, allantoic acid (Figure 8). Allantoin, which is a precursor of allantoic acid in the purine degradation pathway of ureide synthesis, was not labeled significantly. 

In other organisms, inciting most fish and amphibians, allantoin is converted into allantoic acid, which is further degraded in two stages to yield 1 molecule of glyoxylic acid and 2 molecules of urea. 

The so-called ureide plants use allantoin and allantoic acid as a nitrogen store from which ammonia may be liberated by further degradation (E 2.2), In the liver of lungfish a glycine-allantoin cycle (Fig. 182) causes the formation of urea (cf. the formation of urea via L-ornithine derivatives, D 19). 

The uric acid formed from nucleic acid degradation of endogenous or exogenous nucleic acids is excreted as such without chemical alteration in higher apes and man. (In the dalmatian uric acid is partly oxidized and partly excreted.) In all other mammals, uric acid is further oxidized to yield allantoin, and uricase is the enzyme that catalyzes that reaction. In amphibians, fish, and many invertebrates, two more enzymes exist one involved in the oxidation of allantoin to allantoic acid (allantoinase), the other catalyzing the splitting of allantoic acid to yield urea and glyoxylic acid. 

The C02 arises from the methyl carbon and also from the ring-labeled caffeine, proving that the entire molecule can be degraded. AUantoin, allantoic acid, and at least three unidentified compounds have been detected as intermediates (Figures 6.27a and 6.27b). Recently Wanner s group (1975) identified A - and A -methylxanthine as breakdown products. 

N -methylxanthine (II) which is subsequently demethylated at the N -position (III) and remethylated on C-2 to form the methoxy derivative (IV) and oxidized on C-8 (V) which can be converted to compound VI, which is one of the compounds recently isolated (see Fig. 6.27c, Wanner et aL, 1975) (2) the direct conversion to compound VI which can proceed by several alternate pathways. Compound VI can be oxidized to allantoin (VII) and allantoic acid (VIII) and then to CO2 (IX). Caffeine may be degraded by an unknown pathway into allantoin, allantoic acid, and finally, to CO2. 

The degradation of purines in ammonotelic animals and in some ureo-telic animals proceeds to ammonia and urea, respectively. The oxypurines, hypoxanthine and xanthine, are oxidized to uric acid which is in turn oxidized, under the influence of uricase, to allantoin. Hydrolysis of allantoin proceeds in two stages to yield allantoic acid, and finally urea and gly-oxylic acid. In ammonotelic animals urease cleaves the urea into carbon dioxide and ammonia. 

When amino acids are metabolized, the excess nitrogen is concentrated into uric acid, a compound with five amide bonds. A series of enzyme-catalyzed hydrolysis reactions degrade uric acid—one amide bond at a time—all the way to ammonium ion. The extent to which uric acid is degraded depends on the species. Primates, birds, reptiles, and insects excrete excess nitrogen as uric acid. Other mammals excrete excess nitrogen as allantoin. Excess nitrogen in aquatic animals is excreted as allantoic acid, urea, or as ammonium salts. 

Amphibian livers decompose allantoin to urea (278). This process requires two enzymes the first is allantoinase, which hydrolyzes allantoin to allantoic acid, and the second is allantoicase, which cleaves allantoic acid to glyoxylic acid and 2 moles of urea (279-281). Several species of teleost fishes convert allantoin only as far as allantoic acid, but most fishes, amphibia, and fresh water lamellibranchs possess allantoicase as well as allantoinase and degrade allantoin to glyoxylic acid and urea (282). Of interest is the further breakdown of urea to CO2 and NH3, which are the end products of purine catabolism by Crustacea and other lower forms (283). These reactions are shown in Fig. 16. 

Another major deficiency is our lack of understanding about how these ureides are metabolized. Allantoin and allantoic acid are certainly degraded to carbon dioxide and ammonium in leaves and fimits, although the exact pathway of catabolism is not yet clear. Ammonium must be reassimilated before it can be utilized by the plant. On the other hand, metabolism of citrulline may not involve release of ammonium into the cell. A concerted effort using biochemical, molecular, and immunolc cal approaches will be required to address these points. 

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