Xanthine formation from guanine

Figure 9.119 Time course of formation of xanthine from guanine as measured by guanase activity. The reaction mixture contained, in a final volume of 5 mL, 0.45 mmol of Tris-HCI (pH 8.0), 0.33 puno of guanine, and 20 ftL of guanase solution (4 yxg). A 20 /xL aliquot M of sample was injected. Chromatograms were obtained after incubation for (A) 0 minutes, (B) 12 minutes, and (C) 25 minutes. The S arrows indicate the elution time for the reaction product (xanthine). (From Canepari et aL, 1993.)...

Purine bases are rather less reactive to HOCl than pyrimidines. Thus, in one study, treatment of guanine, adenine, or xanthine (60-62) with 1 or 2 equivalents of HOCl resulted only in high yields of starting material recovery. After prolonged exposure, variable yields of parabanic acid (63) were obtained (Hoyano et al., 1973). This compound has been demonstrated to be formed from both pyrimidines and purines in other high-energy oxidative processes (see, e. g., LeRoux et al. [1969]), but the details of its formation from purines by the HOCl process are not known. 

Figure 34-8. Formation of uric acid from purine nucleosides byway of the purine bases hypoxanthine, xanthine, and guanine. Purine deoxyribonucleosides are degraded by the same catabolic pathwayand enzymes,all of which existin the mucosa of the mammalian gastrointestinal tract.

Figure 10.6 HPLC elution profiles of an incubation mixture made up of. 2 nmol of hypoxanthine/guanine phosphoribosyltransferase, SO fiM guanine (G), SO /xM hypo-xanthine (H), 100 fiM PRibPP, and 1 mM MgCl2 in potassium phosphate (pH 7.4). At time intervals of 0 to 5 minutes, aliquots of the mixture were injected onto the HPLC ion-exchange column and eluted. Inset Time-dependent utilization of H and G and formation of GMP and IMP as determined by the absorbance of each peak at 254 nm. (From Ali and Sloan, 1982.)...

The formation of the anhydride (N2O3) from equation (3) can lead to both direct and indirect DNA damage. Direct action results from nitrosation of primary amines on DNA bases which leads to deamination and at physiological pH, N2O3 has been demonstrated to be the most important species [130]. Indirect actions are due to mutations that can arise from the deamination of bases where guanine deaminates to xanthine, mispairing of which can cause a G C to A T transition which will ultimately lead to single strand breaks [131]. 

Amino-4-imidazole carboxamide ribotide, a precursor only two steps removed (formylation and cycli-zation) from inosinic acid, can be synthesized by the direct condensation of the imidazole with 5-phosphori-bosyl pyrophosphate. The enzyme catalyzing this reaction was purified from an acetone powder of beef liver. The same enzyme (AMP pyrophosphorylase) catalyzes the condensation of adenine, guanine, and hypoxan-thine. Nucleoside phosphorylase is an enzyme that catalyzes the formation of a ribose nucleoside from a purine base and ribose-1-phosphate. Guanine, adenine, xanthine, hypoxanthine, 2,6-diaminopurine, and aminoimidazole carboxamide are known to be converted to their respective nucleosides by such a mechanism. In the presence of a specific kinase and ATP, the nucleoside is then phosphorylated to the corresponding nucleotide. 

Uric Add Formation. In vertebrates purines are oxidized to uric acid. This reaction is catalyzed by xanthine oxidase (or dehydrogenase), which attacks both hypoxanthine and xanthine.Since adenine and guanine nucleotides can give rise to the hydroxylated purines either as the nucleotide, nucleoside, or free base, all of the naturally occurring purines of animals can be converted to uric acid. Adenine may also be oxidized to 2,8-dihydroxy-4-aminopurine, which is excreted in the urine. The formation of uric acid from any of its precursors is followed conveniently spectrophotometrically (Fig. 29). ... 

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