Guanine deaminase

Glantz, M.D. and Lewis, A.S. (1978). Guanine deaminase from rabbit liver. Meth. Enzymol. LI, 512-517. 

GUANINE DEAMINASE GUANOSINE DEAMINASE GUANYATE CYCASE GUANYATE KINASE GUEST... 

Guanine aminohydrolase (guanine deaminase or guanase), present in liver, brain, and other mammalian tissues, provides another pathway to xanthine, this time from guanine. Subsequent oxidation of xanthine to uric acid then occurs. 

A few examples are also available in which the lack of a specific enzyme in some cells in the human body has enabled the development of a therapeutic agent. For example, guanine deaminase is absent from the cells of certain cancers but is abundant in healthy tissue as a result 8-azaguanine can be used therapeutically. 

Aryl-8-azaadenines 300, 8-azahypoxanthine 301, and 6-thiolo-8-azapurines 302 were tested for their inhibitory effect on adenosine deaminase, guanine deaminase, and xanthine oxidase from mammalian sources. Compounds 300 were the most efficient inhibitors of adenosine deaminase and... 

Methoxy-, 6-ethoxy-, and 6-methylthio-9-ribofuranosyl-8-azapurines turned out to be substrates for adenosine kinase, and the first two examples were bound by adenosine deaminase. Their cytotoxic action was attributed to affinity for the kinase. 6-Imino-9-phenyl-l,6-dihydro-8-azapurine was found to be an efficient inhibitor of adenosine deaminase and guanine deaminase. Xanthine oxidase was inhibited by both this compound and 9-aryl-8-azapurin-6-ones. ° ... 

A set of 4-amino-3-aryltriazoles, each one further substituted by a 5-amide, -ester, or -nitrile group, inhibited these enzymes adenosine deaminase, guanine deaminase, and xanthine oxidase. Structure-action relationships were discussed (79MI1 85FES73). 

The anticancer activity of 8-azaguanine was potentiated by administering the triazole 84 with it to mice in which Ehrlich ascites carcinoma had been implanted. Although 84 had no direct action on the tumor, it reinforced the cytotoxic effect of the azapurine by inhibiting the destructive action of guanine deaminase (69CPB539). 

F. F. (2000) Identification, expression, and characterization of Escherichia coli guanine deaminase./. Bacteriol., 182, 4658-4660. 

Xanthine is a product of purine catabolism. It is produced as a result of deamination of guanine (Figure 22.7) by guanine deaminase or by the reaction catalyzed by xanthine oxidase. These reactions are as follows ... 

Phosphoribosyltransferase activity was found for hypoxanthine, guanine and xanthine but not for adenine (2). Adenine and guanine deaminase activities are present. Phosphorylase activities were found for adenosine, guanosine and inosine. Also present were adenosine kinase and a guanosine phosphotransferase neither inosine kinase nor phosphotransferase activity was present. The IMP dehydrogenase differs from the mammalian enzyme in that it does not require for activity and it is more sensitive to inhibition by mycophenolic acid (13). 

In vivo purine flow measured in L. donovani promastigotes confirms the active role of the adenine and guanine deaminases which lead to the production of hypoxanthine and xanthine, respectively (24). These two bases are metabolized to both adenine and guanine nucleotides. For this reason, although three different PRTases exist, the major route of adenine metabolism in promastigotes is through adenine deaminase to... 

Few detailed studies have been done on the purine salvage enzymes of procyclic African trypanosomes. Tb. gambiense has high levels of guanine deaminase and lacks adenine and adenosine deaminase activities (8). Tb. brucei, T.b. gambiense and T.b. rhodesiense convert allopurinol into aminopyrazolopyrimidine nucleotides and incorporates these into RNA (49). This indicates that HPRTase, succino-AMP synthetase, and succino-AMP lyase are present. At least three nucleoside cleavage activities are present (Berens, unpublished results) two are hydrolases, of which one is specific for purine ribonucleosides and the other is specific for purine deoxyribonucleosides. The third nucleoside cleavage activity is a methylthioadenosine/adenosine phosphorylase. The adenosine kinase is similar to that of L. donovani (Berens, unpublished results). 

T.b. gambiense bloodstream forms have APRTase, HGPRTase, adenosine kinase and adenylosuccinate synthetase but lack adenosine deaminase. Two phosphorylase activities have been described for the bloodstream forms of T.b. brucei (42,50). One catalyzes the reversible phosphorolysis of adenosine, inosine and guanosine and the other is specific for adenosine and methylthioadenosine. Guanine deaminase is present whereas both adenosine and adenine deaminase are absent (8). Similar results have been reported for T. congolense (51). T. vivax is unique among the other trypanosomes in that it has an adenine deaminase (51). 

Figure 1. Purine salvage pathways of Leishmania species. Enzymes 1) phosphoribosyltransferase 2) adenine deaminase 3) guanine deaminase 4) adenosine deaminase 5) nucleoside kinase 6, nucleotidase 7) AMP deaminase 8) adenylosuccinate synthetase 9) adenylosuccinate lyase 10) AMP kinase 11) GMP kinase 12) IMP dehydrogenase 13) GMP synthetase 14) GMP reductase.

Figure 3. Compartmentalization of the purine salvage pathway of Leishmania. Abbreviations are as follows AAH, adenine aminohydrolase XPRT, xanthine phosphoribosyltransferase HGPRT, hypoxanthine-guaninephosphoribosyltransferase ADSS, adenylosuccinate synthetase ASL, adenylosuccinate lyase IMPDH, inosine monophosphate dehydrogenase GMPS, gua-nosine monophosphate synthase GDA, guanine deaminase AMPDA, adenosine monophosphate deaminase GMPR, guanosine monophosphate reductase APRT, adenine phosphoribosyltransferase AK, adenosine kinase. Enzymes that have been localized are shown in black and those that are predicted to be in the denoted locations are depicted in gray.

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