Xanthine oxidase

 In higher animals nucleotides resulting from degradation of the nucleic acids by the action of nucleases usually undergo enzymatic hydrolysis to yield, ultimately, the free purine and pyramidine bases. If not salvaged and reused, the free bases are degraded further and the end products excreted. In some vertebrates, including the primates, the Dalmatianm dog, birds, and some reptiles, the end product of purine degradation is uric acid, whereas in other mammals and reptiles, and also in mollusks, the end product is allantoin. In fishes, allantoin is broken down to allantoic acid and urea. In aquatic invertebrates ammonia is the major nitrogenous end product of purine catabolism. Curiously, guanine is the excretory form of purines in the spider and the pig. 

The degradation of purines to the end product uric acid in man has been intensively studies, since genetic aberrations of this pathway are known. The major purines adenine and guanine are first converted into xanthine which is then oxidized by the complex flavoprotein xanthine oxidase to uric acid:

Xanthine + H2O + O2 ------------- Uric acid + O2- superoxide

The superoxide radical undergoes conversion to hydrogen peroxide by the action of superoxide dismutase. Isotopic studies on vertebrates that excrete uric acid have shown it to derive from both exogenous and endogenous nucleic acids. Only about 0.5 gm of uric acid is excreted daily by the normal person, although up to 5 gm of free purines are formed daily: evidently the greater part of the free purines is salvaged or recycled. Uric acid is present in blood largely as monosodium urate: however, both the free acid and the urate salts are relatively insoluble in water, with the result that in some individual’s uric acid precipitates and crystallizes in the urine, forming kidney stones and causing damage to this organ. Uric acid deposits are also formed in cartilaginous tissues, to produce the disease gout, which apparantely results from overproduction of uric acid.

Salvage of Purines

Free purines formed from nucleotides are salvaged in vertebrates for reuse in nucleotide and nucleic acid biosynthesis. The major mechanism is by the action of adenine phosphoribosyltransferase and guanine phosphoribosyltransferase. The important enzymes convert free purines into the corresponding purine nucleoside 5- phosphate for reuse. Since up to 90 percent of the free purines formed by man are salvaged and recycled, these salvage pathways, are very important in the purine economy of vertebrates. Deficiency in one of these salvage pathways results in the Lesch-Nyhan syndrome, a rare genetic disorders in which there is a deficiency in the enzyme guanine (hypoxanthine) phosphoribosyltransferase. This enzyme catalyzes the transfer of a ribose phosphate group from PRPP to either guanine or hypoxanthine. When this enzyme is deficient, guanine and hypoxanthine are not salvaged and hence are degraded further to uric acid. Patients with the Lesch-Nyhan syndrome show mental symptoms, including very aggressive behavior and a a bizarre tendency to self-mutilation, as well as massive deposition of uric acid in the kidneys with resulting renal failure.

 Pyrimidine Degradation

In most species pyrimidines are degraded to urea and ammonia. They may also be utilized as precursors in the biosynthesis of β- alanine and thus of co-enzyme A.

Source: - Biochemistry Second Edition, The Molecular Basis of Cell Structure and Function. Albert L. Lehninger, The Johns Hopkins University School of Medicine.

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