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:2.4.2.7 (adenine phosphoribosyltransferase)
692 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mutations of the resistance to 2,6-diaminopurine (apt), which affect adenine phosphoribosyltransferase, fail to permit the growth of Escherichia coli pur mutants (purine auxotrophs which cannot make inosine monophosphate de novo) on the medium with 2,6-diaminopurine (DAP) as the sole source of purines. Addition of a small amount of hypoxantine, but not guanine, stimulated the growth of mutants of pur apt and pur apt+ genotypes on the medium with DAP. The utilization of DAP as purine source in the presence of hypoxantine is blocked by mutations guaC (guanosine monophosphate reductase), add (adenosine deaminase) and pup (purine necleoside phosphorylase), suggesting that DAP are utilized via purine nucleoside phosphorylase and adenosine deaminase. The drm mutation (that increases the level of pentose-1-phosphate in the cell) does not activate the utilization of DAP. The results indicate that a step, that limits the utilization of DAP as the sole source of purines by pur mutants of E. coli, is the deamination of DAP nucleoside.
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PMID:[Genetic control of Escherichia coli K-12 strains' assimilation of 2,6-diaminopurine as a purine source]. 33 31

Strains of Escherichia coli K-12 defective in purine nucleoside phosphorylase (pup gene) formed on the medium with inosine as the source of carbon and energy phenotypical reversions for the ability of utilizing inosine as source of carbon or purines. The phenotypical suppression of the purine nucleoside phosphorylase deficiency is the result of the mutations (called pnd), which are mapped on the chromosome of E. coli beyond the region of the structural pup-gene location and have phenotypic manifestation distinct from that of pup+ allele: a) pnd mutants divide into some groups for the ability of utilizing several purine nucleosides, including xantosine that cannot be metabolized by pnd+ strains of E. coli; b) pnd mutations do not restore the ability of purine auxotrophs (pur) defective in purine nucleoside phosphorylase (pup) and adenine phosphoribosyltransferase (apt) to grow on the medium with adenine as the sole source of purines. Cell-free extracts of pnd mutants fail to degrade the guanine nucleosides in the absence of phosphate or arsenate ions. These data (and also the ability of pnd mutants to utilize both purine ribonucleosides and deoxyribonucleosides) seem to indicate that the activities induced by pnd mutations are phosphorylase activities.
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PMID:[Escherichia coli K-12 mutants capable of catabolizing purine nucleosides in the absence of purine nucleoside phosphorylase]. 41 Jul 1

Changes in hepatic purine enzyme activities of chicks fed diets containing 11%, 20%, 43% and 80% protein were correlated with protein intake and uric acid production in order to identify those enzymes with activities that parallel closely and may regulate uric acid production. Nucleoside phosphorylase, xanthine dehydrogenase, adenylosuccinate synthetase and adenosine kinase correlated positively with protein intake and uric acid production. Adenosine deaminase, 5'-nucleotidase (AMP), adenylate deaminase and adenine phosphoribosyltransferase correlated negatively with protein intake and uric acid production. Hypoxanthine phosphoribosyltransferase and 5'-nucleotidase (IMP) were unaffected by protein intake and did not correlate with uric acid production. The ratio of adenosine kinase to adenosine deaminase correlated positively with protein intake and uric acid production. The increased activities of adenylosuccinate synthetase and adenosine kinase, along with the reduced activities of 5'-nucleotidase and adenylate deaminase, in liver from chickens fed the 80% compared with the 11% protein diet demonstrate enhanced synthesis of adenine nucleotides. Since adenine nucleotides are essential cofactors for de novo purine synthesis, it is proposed that adenylosuccinate synthetase, adenosine kinase, 5'-nucleotidase and adenylate deaminase are key enzymes involved in the regulation of purine biosynthesis.
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PMID:Protein intake, hepatic purine enzyme levels and uric acid production in growing chicks. 61 42

Incorporation of the adenine moiety of 2'-deoxyadenosine (dAdo) into ATP, consistently observed in human erythrocytes, is a phenomenon which cannot be explained by the operation of any known pathway. We reported previously that this effect was not observed in adenine phosphoribosyltransferase-deficient erythrocytes showing that adenine must be an obligatory intermediate. However, generation of adenine from dAdo was difficult to reconcile with the operation of any known process in human cells, and involvement of S-adenosylhomocysteine hydrolase (SAH-hydrolase) was postulated. The present studies with intact human erythrocytes demonstrate that nucleoside analogues which inhibit SAH-hydrolase caused substantial attenuation of adenine transfer from dAdo into ATP. It was confirmed that dAdo is not a substrate of 5'deoxy-5'methylthioadenosine (5'MT-adenosine) phosphorylase. Inhibition of the transfer of the adenine moiety of dAdo into ATP did not correlate with inhibition of 5'MT-adenosine phosphorylase by nucleoside analogues. This report provides further evidence that the pathway involving nucleoside (adenosine) analogue binding to SAH-hydrolase, release of base and subsequent phosphoribosylation can operate in intact cells. The metabolic significance of this process relates to the possible generation of free bases (adenine) in the human body, ATP synthesis and nucleoside drug interconversions.
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PMID:A novel route of ATP synthesis. 159 94

The specific activity of adenine phosphoribosyltransferase (APRT) (EC 2.4.2.7) and adenosine phosphorylase (EC 2.4.2.-), two enzymes involved in the utilization of exogenous adenine, was measured in extracts of myxamoebae-swarm cells of Physarum flavicomum undergoing growth, microcyst formation (control), and during adenine inhibition of encystment. Both enzymes showed a higher specific activity in adenine-inhibited cells (AIC) compared to normal control (NC) or growing cells (GC). These experiments revealed that the specific activity of APRT was 7.1-, 5.3-, and 1.7-fold higher than that of adenosine phosphorylase in AIC, GC, and NC, respectively. This suggests a predominant role for the enzyme APRT in the salvage of adenine in this organism. The major route for the utilization of adenine thus seems to be by its direct conversion to AMP rather than via its riboside adenosine. HPLC analysis of the ribonucleotide triphosphates in cell extracts of GC, NC, and AIC revealed a 2.6- and a 3.3-fold increase in the ATP and GTP content, respectively, in the AIC compared with the NC cells. The ATP content in the GC was higher by a factor of 2.2 compared with the NC cells, while the GTP content in the GC was only 0.6 times that in the NC cells. UTP levels in AIC and GC were 1.3- and 1.4-fold higher than in the NC cells. In contrast, the CTP level in AIC was lower than in NC cells and was not detectable in the growing cells.
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PMID:Adenine salvage enzymes and intracellular nucleotide triphosphate content in Physarum flavicomum amoebae during growth and development. 250 Oct 17

Cell extracts of Acholeplasma laidlawii B-PG9, Acholeplasma morum S2, Mycoplasma capricolum 14, and Mycoplasma gallisepticum S6 were examined for 37 cytoplasmic enzyme activities involved in the salvage and biosynthesis of purines. All of these organisms had adenine phosphoribosyltransferase activity (EC 2.4.2.7) and hypoxanthine phosphoribosyltransferase activity (EC 2.4.2.8). All of these organisms had purine-nucleoside phosphorylase activity (EC 2.4.2.1) in the synthetic direction using ribose-1-phosphate (R-1-P) or deoxyribose-1-phosphate (dR-1-P); this activity generated ribonucleosides or deoxyribonucleosides, respectively. The pyrimidine nucleobase uracil could also be ribosylated by using either R-1-P or dR-1-P as a donor. The synthesis of deoxyribonucleosides from nucleobases and dR-1-P has been reported from only one other procaryote, Escherichia coli (L. A. Mason and J. O. Lampen, J. Biol. Chem. 193:539-547, 1951). The reverse of this phosphorylase reaction is more widely known, and we found such activity in all mollicutes studied. Some Acholeplasma species but not the Mycoplasma species can phosphorylate deoxyribonucleosides to deoxyribomononucleotides by a PPi-dependent deoxyribonucleoside kinase activity, which was first reported in this group for the ribose analogs (V. V. Tryon and J. D. Pollack, Int. J. Syst. Bacteriol. 35:497-501, 1985). This is the first report of PPi-dependent purine deoxyribonucleoside kinase activity. An ATP-dependent purine deoxyribonucleoside kinase activity is known only in salmon milt extracts (H. L. A. Tarr, Can. J. Biochem. 42:1535-1545, 1964). Deoxyribomononucleotidase activity was also found in cytoplasmic extracts of these mollicutes. This is the first report of deoxyribomononucleotidase activity.
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PMID:Synthesis of deoxyribomononucleotides in Mollicutes: dependence on deoxyribose-1-phosphate and PPi. 303 46

Bacillus subtilis mutants defective in purine metabolism have been isolated by selecting for resistance to purine analogs. Mutants resistant to 2-fluoroadenine were found to be defective in adenine phosphoribosyltransferase (apt) activity and slightly impaired in adenine uptake. By making use of apt mutants and mutants defective in adenosine phosphorylase activity, it was shown that adenine deamination is an essential step in the conversion of both adenine and adenosine to guanine nucleotides. Mutants resistant to 8-azaguanine, pbuG mutants, appeared to be defective in hypoxanthine and guanine transport and normal in hypoxanthine-guanine phosphoribosyltransferase activity. Purine auxotrophic pbuG mutants grew in a concentration-dependent way on hypoxanthine, while normal growth was observed on inosine as the purine source. Inosine was taken up by a different transport system and utilized after conversion to hypoxanthine. Two mutants resistant to 8-azaxanthine were isolated: one was defective in xanthine phosphoribosyltransferase (xpt) activity and xanthine transport, and another had reduced GMP synthetase activity. The results obtained with the various mutants provide evidence for the existence of specific purine base transport systems. The genetic lesions causing the mutant phenotypes, apt, pbuG, and xpt, have been located on the B. subtilis linkage map at 243, 55, and 198 degrees, respectively.
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PMID:Genetic and physiological characterization of Bacillus subtilis mutants resistant to purine analogs. 311 Jan 31

The biological activities of several previously synthesized [J. A. Montgomery et al., J. med. Chem. 17, 1197 (1974)] adenine-substituted analogs of 5'-deoxy-5'-methylthio- or 5'-deoxy-5'-ethyl-thioadenosine, including the 2-fluoroadenine, 2-chloroadenine, 2,6-diaminopurine, 8-azaadenine, and 4-aminopyrazolo [3,4-d]pyrimidine-containing derivatives, have been reexamined. It is demonstrated that many of these analogs are cleaved to their respective free base analogs by 5'-deoxy-5'-methyl-thioadenosine phosphorylase (MTAPase), an enzyme associated with polyamine biosynthesis, and that this reaction is necessary for the cytotoxic action of these MTA analogs to be fully expressed. Evidence to support this includes: (1) the growth of two MTAPase-containing human colon carcinoma cell lines (the HCT-15 and DLD-1 lines) was inhibited by these analogs, whereas an MTAPase-deficient cell line, the CCRF-CEM human T-cell leukemia, was relatively insensitive to their cytotoxic action; (2) extracts of the MTAPase-containing colon carcinoma cell lines were able to cleave these analogs to their respective free base analogs; in contrast, extracts of MTAPase-deficient CCRF-CEM cells were unable to cleave these analogs; (3) intact colon carcinoma cells converted these MTA analogs to their corresponding 5'-phosphorylated analog nucleotides, whereas CCRF-CEM cells did not, at least to detectable levels; and (4) the MTA analog, 5'-deoxy-5'-ethylthio-4-aminopyrazolo [3,4-d]pyrimidine ribonucleoside, which is not a substrate of MTAPase, did not form analog nucleotides and was essentially noncytotoxic to all cell lines tested, whereas the corresponding adenine analog, 4-aminopyrazolo [3,4-d]pyrimidine, readily formed analog nucleotides and was highly cytotoxic to all the lines. It is postulated that the corresponding adenine analog 5'-phosphorylated nucleotides are the primary active metabolites of these MTA analogs, having been formed by the cleavage of these nucleosides to free adenine analogs by MTAPase, followed by the conversion of these base analogs to analog nucleotides by adenine phosphoribosyltransferase and the enzymes of adenine nucleotide phosphorylation. This pathway represents a novel drug-activation system for the synthesis of analog nucleotides and has the potential to be exploited chemotherapeutically.
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PMID:5'-deoxy-5'-methylthioadenosine phosphorylase--II. Role of the enzyme in the metabolism and antineoplastic action of adenine-substituted analogs of 5'-deoxy-5'-methylthioadenosine. 641 Oct 95

The exact source of de novo adenine produced by mammalian cells remain poorly understood, and this prompted the present study. Using a human lymphoblastoid cell line (WI-L2) deficient in adenine phosphoribosyltransferase (EC 2.4.2.7), we have quantitated the rate of adenine synthesis and the relative importance of the phosphorolysis of 5'-methylthioadenosine versus adenosine or 2'-deoxyadenosine in adenine generation. Dividing adenine phosphoribosyltransferase-deficient WI-L2 cells produced adenine at a rate of 0.27 nmol/mg protein/h. This represented approximately 10% of the rate of hypoxanthine production by WI-L2 cells deficient in hypoxanthine phosphoribosyltransferase (EC 2.4.2.8) but was equivalent to the rate of 5'-methylthioadenosine synthesis by human lymphoblastoid CCRF-CEM deficient in 5'-methylthioadenosine, phosphorylase (5'-methylthioadenosine: orthophosphate methylthioribosyltransferase). Up to 97% of adenine, but not hypoxanthine, synthesis was inhibited dose-dependently by the S-adenosylmethionine decarboxylase-inhibitor methylglyoxal bis(guanylhydrazone) and also by spermidine and spermine, but was enhanced by putrescine. The addition of 2-fluoroadenine, a potent competitive inhibitor of methylthioadenosine phosphorylase (Ki = 0.43 microM) to adenine phosphoribosyl-transferase-deficient cells resulted in a progressive accumulation of 5'-methylthioadenosine in the culture medium, and up to an 85% decrease in adenine production at non-toxic concentrations. These results show that de novo adenine synthesis by dividing human cells is considerable, and that 85-97% derives from the cleavage of 5'-methylthioadenosine and hence from polyamine synthesis.
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PMID:Dependence of adenine production upon polyamine synthesis in cultured human lymphoblasts. 679 2

1. Activities of the following enzymes involved in adenine and adenosine metabolism were found in cell-free extracts from Euglena gracilis: acid phosphatase (EC 3.1.3.2), 5'-methylthioadenosine phosphorylase (EC 2.4.2.-), adenine deaminase (EC 3.5.4.2), adenine phosphoribosyltransferase (EC 2.4.2.7) and adenosine kinase (EC 2.7.1.20). 2. The activities occurred both in heterotrophic and photoautotrophic cells and their levels did not change during light-induced chloroplast development. 3. Neither S-adenosylhomocysteinase (EC 3.3.1.1), 5'-methylthioadenosine nucleosidase (EC 3.2.2.9) and nucleoside phosphotransferase (EC 2.7.1.77) nor adenosine degrading enzymes: adenosine deaminase (EC 3.5.4.4), adenosine nucleosidase (EC 3.2.2.7), and purine-nucleoside (adenosine) phosphorylase (EC 2.4.2.1) were found in the Euglena extracts. 4. Comparison of the adenine and adenosine metabolism in Euglena and in other organisms is comprehensively presented. The metabolism in Euglena gracilis differs from that in higher animals and plants.
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PMID:Adenine and adenosine metabolizing enzymes in cell-free extracts from Euglena gracilis. 680 64


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