Adenine deaminase

Figure 12.2. Pathway for adenine fermentation in C. purinolyticum. AD, adenine deaminase.

SPERMIDINE SYNTHASE Ammonia as a substrate or product, ADENINE DEAMINASE ADENOSINE DEAMINASE [Pg.722]

CpA, UpA Adenine release Coupled assay with adenine deaminase A Ant (423)... 

In some cases the combination of two biocatalysts in a multistep process allows, in an indirect manner, the preparation of some compounds or increases in their yields. Thus, Scheme 10.21 shows that the synthesis of a nucleoside analog containing a hypoxanthine base takes place in a two-step fashion using a combination of both nucleoside phosphorylase and adenine deaminase, obtaining the final analog in high yield. However, the direct preparation of this compound with hypoxanthine takes place with a very low yield due to the low solubility of this base [48]. 

It should therefore be possible to design chemical structures, modeled after known or putative reaction intermediates that resemble postulated transition states. They may exhibit high affinities for the reactive sites of enzymes and therefore function as effective, but reversible, inhibitors. A successful example is the potent and specific cytidine deaminase inhibitor 3,4,5,6-tetrahydrouridine, which effectively blocks the conversion of cytidine to uridine. It was similarly demonstrated that 1,6-dihydro-6-hydroxymethylpurine effectively blocked the deamination of adenine to hypoxanthine by adenine deaminase (Eq. 2.13). 

Leishmania. Leishmania promastigotes convert adenine and inosine into a common intermediate, hypoxanthine, before being used for nucleotide synthesis (6). Adenine is converted into hypoxanthine by adenine deaminase (23). This enzyme is absent in T. cruzi (7), T. b. gambiense or T. b. rhodesiense (8) but has been found in other parasitic protozoans as described below. 

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... 

Although procyclic forms of T. brucei gambiense are incapable of de novo synthesis, the last two enzymes of the pathway are present since the intermediate 5-amino-imidazolo-4-carboxamide ribosylphosphate (AICAR) will maintain viability for over 6 weeks (8). Purine base incorporation is qualitatively identical to that found for T. cruzi both trypanosomes lack the adenine deaminase which is found in Leishmania (Fig. 6.7). Purine ribonucleosides were utilized slightly more efficiently than their corresponding purine bases. 

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). 

Thus with the exception of T. vivax, the African trypanosomes metabolize purines in a manner similar to T. cruzi. The major difference between the trypanosomes and Leishmania is the former s lack of adenine deaminase. 

Leishmania, Toxoplasma has adenine deaminase activity (62), supporting the suggestion that hypoxanthine salvage plays a central role in purine metabolism (61). Consistent with this is the finding that hypoxanthine incorporation is second only to that of adenosine. The majority of adenine, as in Leishmania, is salvaged by deamination to hypoxanthine. 

Kidder, G. W., Dewey, V. C. and Nolan, L. L. (1977) Adenine deaminase of a eukaryotic animal cell, Crithidia fasciculata. Arch. Biochem. Biophys. 183 7-12. 

Vidarabine is deaminated quite rapidly by the enzyme adenine deaminase that is usually found in serum and RBC. Interestingly, this enzyme helps in the conversion of this drug , into its principal metabolite termed as arabinosyl hypoxanthine (ara-HX), which displays weak antiviral activity ... 

The reaction temperature is very important and a key to the synthesis of ara-A. As shown in Fig. 2, by-product hypoxantine is formed from substrate adenine by the reaction of the adenine deaminase of microorganisms in a temperature range of 30 C-50 C, then, ara-A is not formed under these conditions. 

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.

A st e-specific difference in the aaivities of enzymes is another charaaeristic of some Leishmania spiecies, with promastigotes containing adenine deaminase and amastigotes containing adenosine deaminase. IMP formed in the cell can be converted to AMP by adenylosuccinate synthetase and adenylosuccinate lyase whereas XMP is converted to IMP by GMP synthetase and GMP reduaase. Moreover, IMP dehydrogenase has also the ability to convert XMP to GMP. ... 

Adenine deaminase is not found in animal tissues, but is present in some plants and microorganisms. 

Mammalian tissues do not contain adenine deaminase, but specific enzymes able to deaminate adenosine and 5 -adenylic acid have been found in a variety of mammals. Adenosine deaminase activity has been detected in intestine, liver, spleen, brain, kidney, heart, and skeletal muscle. Adenosine deaminase has been partially purified from the intestinal mucosa. The enzyme has a great affinity for adenosine and deoxyadenosine and only low affinity for 2 -AMP and 3, 3 -cyclic AMP. Its activity is lost on dialysis. The enzyme acts optimally at pH 7. 

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