Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.4.2.8 (hypoxanthine-guanine phosphoribosyltransferase)
2,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The enzymes that catalyse the salvage of purines in Entamoeba histolytica trophozoites have been surveyed. Adenine deaminase (EC 3.5.4.2), adenosine deaminase (EC 3.5.4.4), guanine deaminase (EC 3.5.4.3), adenine phosphoribosyltransferase (PRTase) (EC 2.4.2.7), xanthine PRTase (EC 2.4.2.22) and hypoxanthine PRTase (EC 2.4.2.8) were all detected in cell homogenates but only at low activities, whereas AMP deaminase (EC 3.5.4.6) and guanine PRTase (EC 2.4.2.8) were not found. Phosphorylases (EC 2.4.2.1) active in both anabolic and catabolic directions were present and all nucleosides tested were phosphorylated by kinases (EC 2.7.1.15, EC 2.7.1.20, EC 2.7.1.73). 3'-Nucleotidase (EC 3.1.3.6) and 5'-nucleotidase (EC 3.1.3.5) were found, the former being mainly particulate. Nucleotide interconversion enzymes (adenylosuccinate lyase, EC 4.3.2.2; adenylosuccinate synthetase, EC 6.3.4.4; IMP dehydrogenase, EC 1.2.1.14; GMP synthetase, EC 6.3.5.2 and GMP reductase, EC 1.6.6.8) were not detected. The results suggest that in E. histolytica the main route of nucleotide synthesis is from the individual bases through the actions of phosphorylases and kinases.
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PMID:Purine-metabolising enzymes in Entamoeba histolytica. 287 91

Spontaneous and ethyl methanesulfate induced mutants of Saccharomyces cerevisiae, with partial and complete deficiency of adenine phosphoribosyltransferase (APRT, EC 2.4.2.7), were isolated by selection for resistance to 8-azaadenine. Matings between totally deficient mutants and tester strain resulted in diploid heterozygotes that were sensitive to azaadenine. Upon sporulation and tetrad analysis, azaadenine resistance (and APRT deficiency) segregated as expected for a single Mendelian gene. Hypoxanthine-guanine phosphoribosyltransferase (EC 2.4.2.8) activity in the mutants was similar to that in the wild-type cells. There was no detectable activity of adenine aminohydrolase (EC 3.5.4.2) in the wild-type or mutant cells.
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PMID:Mutants of Saccharomyces cerevisiae deficient in adenine phosphoribosyltransferase. 330 56

Mutant promastigotes of Leishmania donovani deficient in adenine phosphoribosyltransferase (APRTase) have been isolated in medium containing 4-aminopyrazolopyrimidine. The generation of APRTase-deficient mutants occurred in two discrete steps. In the first step, clones were isolated with 50% of wildtype levels of APRTase activity. These cells were reselected and colonies totally deficient in APRTase were isolated. Partially and totally APRTase-deficient cells exhibited intermediate and complete resistance to cytotoxic adenine analogs, respectively. Nevertheless, wildtype and mutant cells could salvage adenine and utilize adenine as a purine source equally efficiently, suggesting that the adenine deaminase-HGPRTase pathway plays an important role in promastigote adenine metabolism. Kinetic and thermal inactivation studies of purified APRTase and isoelectric focusing of crude extracts from wildtype and partially APRTase-deficient cells suggested that the latter cells possessed wildtype APRTase activity at half the amount found in wildtype parental cells. These data suggest that Leishmania donovani possess two copies of the APRTase structural gene and that these organisms might be diploid for the APRTase locus.
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PMID:Adenine phosphoribosyltransferase-deficient Leishmania donovani. 376 43

Purine metabolism in Leishmania donovani amastigotes was found to be similar to that of promastigotes with the exception of adenosine metabolism. Adenosine kinase activity in amastigotes is approximately 50-fold greater than in promastigotes. Amastigotes deaminate adenosine to inosine through adenosine deaminase, an enzyme not present in promastigotes. Inosine is cleaved to hypoxanthine and phosphoribosylated by hypoxanthine-guanine phosphoribosyltransferase. Promastigotes cleave adenosine to adenine and deaminate adenine to hypoxanthine via adenase, an enzyme not present in amastigotes. Hypoxanthine is phosphoribosylated by hypoxanthine-guanine phosphoribosyltransferase.
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PMID:Purine metabolism in Leishmania donovani amastigotes and promastigotes. 619 67

Mutants of Saccharomyces cerevisiae deficient in adenine phosphoribosyltransferase (A-PRT, EC 2,4,2,7) have been isolated following selection for resistance to 8-azaadenine in a prototrophic strain carrying the ade4-su allele of the gene coding for amidophosphoribosyltransferase (EC 2,4,2,14). The mutants were recessive and defined a single gene, apt1. They did not excrete purine when combined with ade4+. The mutants appeared to retain some A-PRT activity in crude extracts, and strains of the genotype ade2 apt1 responded to both adenine and hypoxanthine. Mutants deficient in adenine aminohydrolase (EC 3,5,4,2) activity, aah1, and hypoxanthine:guanine phosphoribosyltransferase (EC 2,4,2,8) activity, hpt1, were used to synthesize the genotypes apt1 hpt1 aah+ and apt1 hpt+ aah1. The absence of A-PRT activity in strains with these genotypes confirmed the hypothesis that the residual A-PRT activity of apt1 mutants was due to adenine aminohydrolase and hypoxanthine:guanine phosphoribosyltransferase acting in concert.
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PMID:Adenine phosphoribosyltransferase mutants in Saccharomyces cerevisiae. 639 74

We have isolated numerous mutants containing mutations in the salvage pathways of purine synthesis. The mutations cause deficiencies in adenine phosphoribosyltransferase (adeF), in hypoxanthine-guanine phosphoribosyltransferase (guaF), in adenine deaminase (adeC), in inosine-guanosine phosphorylase, (guaP), and in GMP reductase (guaC). The physiological properties of mutants containing one or more of these mutations and corresponding enzyme measurements have been used to derive a metabolic chart of the purine salvage pathway of Bacillus subtilis.
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PMID:Purine salvage pathways of Bacillus subtilis and effect of guanine on growth of GMP reductase mutants. 640 59

Mutant promastigotes of Leishmania donovani deficient in adenine phosphoribosyltransferase (AP-Rib transferase) have been isolated in medium containing 4-aminopyrazolopyrimidine. The generation of AP-Rib transferase-deficient mutants occurred in two discrete steps. In the first step, clones were isolated with 50% of wild-type levels of AP-Rib transferase activity. These cells were reselected, and colonies totally deficient in AP-Rib transferase were isolated. Wild-type and AP-Rib transferase-deficient cells contained equivalent amounts of other enzymes essential to adenine metabolism such as adenine deaminase and hypoxanthine-guanine phosphoribosyltransferase. Partially and totally AP-Rib transferase-deficient cells exhibited intermediate and complete resistance to cytotoxic adenine analogs, respectively. Nevertheless, wild-type and mutant cells could salvage adenine and utilize adenine as a purine source equally efficiently, suggesting that the adenine deaminase-hypoxanthine-guanine phosphoribosyl-transferase pathway plays an important role in promastigote adenine metabolism. Kinetic and thermal inactivation studies of purified AP-Rib transferase and isoelectric focusing of crude extracts from wild-type and partially AP-Rib transferase-deficient cells suggested that the latter cells possessed wild-type AP-Rib transferase activity at half the amount found in wild-type parental cells. These data suggest that L. donovani possesses two copies of the AP-Rib transferase structural gene and that these organisms might be diploid for the AP-Rib transferase locus.
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PMID:Genetic analysis of adenine metabolism in Leishmania donovani promastigotes. Evidence for diploidy at the adenine phosphoribosyltransferase locus. 650 11

The effects of purine starvation on the ability of the trypanosomatid Crithidia luciliae to accumulate purines were determined. Kinetic studies showed that the uptake of the nucleoside adenosine by purine-starved organisms was approximately 7-fold faster than by nutrient-replete cells. Further, these studies demonstrated that purine-starved organisms accumulated the nucleobases hypoxanthine and adenine at a rate > 100-fold faster than organisms cultivated under replete conditions. Activities of several intracellular purine-salvage enzymes were measured in organisms from both culture conditions. Of those measured, the activities of adenine deaminase and hypoxanthine phosphoribosyltransferase were elevated approximately 4-fold and approximately 11-fold, respectively, in purine-starved organisms. Competitive substrate specificity studies suggested that these elevated enzyme activities were not responsible for the increased rates of uptake by purine-starved cells. The results are consistent with the induction of novel surface membrane purine transporters expressed in response to purine starvation. These studies using C. luciliae may provide insights into the mechanisms of trypanosomatid adaptation to altered environments encountered during the course of the life cycle.
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PMID:Enhanced acquisition of purine nucleosides and nucleobases by purine-starved Crithidia luciliae. 892 13

Leishmania species express three phosphoribosyltransferase enzymes, hypoxanthine-guanine phosphoribosyltransferase (HGPRT), adenine phosphoribosyltransferase (APRT), and xanthine phosphoribosyltransferase (XPRT), which enable this genus to acquire purine nutrients from their hosts. To test whether any of these enzymes is essential for viability, transformation into amastigotes, and infectivity and proliferation within mammalian macrophages, Deltahgprt, Deltaaprt, and Deltaxprt null mutants were created by targeted gene replacement within a virulent background of Leishmania donovani. Each of the three knockout strains was viable as promastigotes and axenic amastigotes and capable of maintaining an infection in bone marrow-derived murine macrophages. These data support the hypothesis that none of the three phosphoribosyltransferases is essential for purine salvage or viability by itself and that purine salvage occurs through multiple anabolic routes in both parasite life cycle stages. In addition these studies revealed the presence of an adenine aminohydrolase enzyme in L. donovani axenic amastigotes, an activity previously thought to be restricted to promastigotes.
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PMID:Leishmania donovani singly deficient in HGPRT, APRT or XPRT are viable in vitro and within mammalian macrophages. 1659 68

To find general metabolic profiles of purine ribo- and deoxyribonucleotides in potato (Solanum tuberosum L.) plants, we looked at the in situ metabolic fate of various (14)C-labelled precursors in disks from growing potato tubers. The activities of key enzymes in potato tuber extracts were also studied. Of the precursors for the intermediates in de novo purine biosynthesis, [(14)C]formate, [2-(14)C]glycine and [2-(14)C]5-aminoimidazole-4-carboxyamide ribonucleoside were metabolised to purine nucleotides and were incorporated into nucleic acids. The rates of uptake of purine ribo- and deoxyribonucleosides by the disks were in the following order: deoxyadenosine > adenosine > adenine > guanine > guanosine > deoxyguanosine > inosine > hypoxanthine > xanthine > xanthosine. The purine ribonucleosides, adenosine and guanosine, were salvaged exclusively to nucleotides, by adenosine kinase (EC 2.7.1.20) and inosine/guanosine kinase (EC 2.7.1.73) and non-specific nucleoside phosphotransferase (EC 2.7.1.77). Inosine was also salvaged by inosine/guanosine kinase, but to a lesser extent. In contrast, no xanthosine was salvaged. Deoxyadenosine and deoxyguanosine, was efficiently salvaged by deoxyadenosine kinase (EC 2.7.1.76) and deoxyguanosine kinase (EC 2.7.1.113) and/or non-specific nucleoside phosphotransferase (EC 2.7.1.77). Of the purine bases, adenine, guanine and hypoxanthine but not xanthine were salvaged for nucleotide synthesis. Since purine nucleoside phosphorylase (EC 2.4.2.1) activity was not detected, adenine phosphoribosyltransferase (EC 2.4.2.7) and hypoxanthine/guanine phosphoribosyltransferase (EC 2.4.2.8) seem to play the major role in salvage of adenine, guanine and hypoxanthine. Xanthine was catabolised by the oxidative purine degradation pathway via allantoin. Activity of the purine-metabolising enzymes observed in other organisms, such as purine nucleoside phosphorylase (EC 2.4.2.1), xanthine phosphoribosyltransferase (EC 2.4.2.22), adenine deaminase (EC 3.5.4.2), adenosine deaminase (EC 3.5.4.4) and guanine deaminase (EC 3.5.4.3), were not detected in potato tuber extracts. These results suggest that the major catabolic pathways of adenine and guanine nucleotides are AMP --> IMP --> inosine --> hypoxanthine --> xanthine and GMP --> guanosine --> xanthosine --> xanthine pathways, respectively. Catabolites before xanthosine and xanthine can be utilised in salvage pathways for nucleotide biosynthesis.
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PMID:Profiles of purine biosynthesis, salvage and degradation in disks of potato (Solanum tuberosum L.) tubers. 1684 29


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