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Query: UNIPROT:P00492 (hypoxanthine-guanine phosphoribosyltransferase)
 2,385 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The relative rates of the synthetic, interconversion and catabolic reactions of purine metabolism in chopped mouse cerebrum were studied. The rates of incorporation of [(14)C]adenine and [(14)C]hypoxanthine into purine ribonucleotides were much less than the potential activities of adenine phosphoribosyltransferase and hypoxanthine phosphoribosyltransferase, and the rates of incorporation were stimulated by the addition of guanosine to the incubation mixture. The availability of ribose phosphates may be a limiting factor for the formation of ribonucleotides from purine bases. The rate of incorporation of [(14)C]adenosine into purine ribonucleotides was at least seven- to eight-fold higher than that of adenine. The radioactivity in adenine ribonucleotides synthesized from adenine and hypoxanthine was about 100- and ten-fold respectively higher than that in the radioactive guanine ribonucleotides. The conversion of inosinate into guanine ribonucleotides was probably limited by the amount of inosinate available, and the conversion of adenine ribonucleotides into guanine ribonucleotides was probably limited by the activity of adenylate deaminase. The rate of catabolism of [(14)C]adenosine was low in comparison with its rate of utilization for ribonucleotide synthesis. A fraction of the [(14)C]hypoxanthine was catabolized to xanthine and urate. [(14)C]Guanine was completely converted into xanthine, mostly by the guanine deaminase that was released during incubation of chopped mouse cerebrum.
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PMID:Purine ribonucleotide biosynthesis, interconversion and catabolism in mouse brain in vitro. 434 68

To study the activation and cytotoxic mechanism of bredinin (4-carbamoyl-1-beta-D-ribofuranosylimidazolium-5-olate), a novel nucleoside antibiotic with potent cytotoxic and immunosuppressive effects, we isolated in a single-step manner five mutants resistant to 10 microM bredinin from cultured mouse mammary carcinoma FM3A cells mutagenized with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Such resistant (Brdr) mutants were 15- to 19-fold less sensitive to the antibiotic than wild-type cells and maintained stably their resistant phenotypes in the absence of bredinin for more than 3 months. They were cross-resistant to tubercidin, an adenosine analog. Like wild-type cells, Brdr mutants were capable of incorporating radioactivity from ring-labeled adenosine into the acid-insoluble macromolecular fraction. However, hypoxanthine-guanine phosphoribosyltransferase-deficient (HGPRT-) mutants derived from the Brdr cells did not incorporate the radioactivity at all or at a markedly reduced rate, indicating that blockade of the pathway via adenosine deaminase present in the Brdr cells resulted in loss of their ability to utilize adenosine. Enzyme assays using cell-free extracts revealed that all the Brdr mutants had less than 3% of the adenosine kinase (AK) activity found in wild-type cells. These results demonstrate that the bredinin resistance is attributed to a defective AK activity and, therefore, that bredinin is metabolized by AK, which may phosphorylate it to a toxic nucleotide, bredinin 5'-monophosphate (Brd-MP), in sensitive cells. Among exogenously added purine bases, guanine was able to reverse the cytotoxic effect of bredinin on both wild-type cells and F5 cells carrying the vector pSV2-Escherichia coli xanthine-guanine phosphoribosyltransferase (XGPRT) gene, while xanthine was able to do so only in F5 cells because the base was metabolized to XMP by the cells. These results support the mechanism of bredinin cytotoxicity, that Brd-MP formed in sensitive cells exposed to the antibiotic blocks the conversion of IMP to XMP by inhibiting IMP dehydrogenase.
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PMID:Genetic and biochemical studies on the activation and cytotoxic mechanism of bredinin, a potent inhibitor of purine biosynthesis in mammalian cells. 614 13

Rats ingesting high doses of caffeine reproduce the self-destructive behaviour observed in the Lesch-Nyhan syndrome. This syndrome includes a deficit in hypoxanthine-guanine phosphoribosyltransferase. We have observed, however, that the activity of hypoxanthine-guanine phosphoribosyltransferase increases in direct proportion to the concentration of caffeine found in rat brain. It appears, therefore, that the caffeine model is not a true model for the Lesch-Nyhan syndrome, or alternatively, that the deficit in hypoxanthine-guanine phosphoribosyltransferase is coincidental and not a main key to the multifarious aspects of the syndrome, particularly the self-mutilation. The possibility that levels of dopamine are increased in the caffeine model are discussed as a basis for the destructive behaviour. We have found also that ingestion of large amounts of caffeine increases the activities in rat brain of adenosine deaminase, purine nucleoside phosphorylase, aspartate carbamoyl-transferase, dihydroorotase, and dihydroorotate oxidase.
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PMID:Lesch-Nyhan syndrome, caffeine model: increase of purine and pyrimidine enzymes in rat brain. 614 65

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

Previous work in our laboratory led us to postulate that N2a cells release adenosine into growth medium, where it acts at the extracellular adenosine receptors to modulate the sensitivity of the cells to the cyclic AMP-elevating effect of adenosine [Green, RD, J Pharmacol Exp Ther 201:610, 1977]. We have now devised a high-performance liquid chromatographic (HPLC) procedure capable of quantitating the concentrations of adenosine in cells and tissue culture media. Growth media of N2a cells and a variant of N2a cells deficient in hypoxanthine-guanine phosphoribosyltransferase (HGPRT-) contain 10-20 nM adenosine, while that of a variant deficient in adenosine kinase (AK-) is elevated severalfold. It appears that the concentration of adenosine in growth media is determined by both the rate at which it is released by cells into the medium and the rate at which it is metabolized by adenosine deaminase present in the serum in the growth medium. Both N2a and AK- cells release considerable amounts of adenosine into serum-free medium (SFM) over a short period. Adenosine release is greater from AK- cells and is accelerated by erythro-9-(2-hydroxy-3-nonyl)-adenine (EHNA), a potent adenosine deaminase inhibitor. This accelerated release is retarded by dipyridamole and homocysteine. Surprisingly, dipyridamole and 4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone (Ro 20 1724), a potent phosphodiesterase inhibitor, stimulate basal adenosine release from N2a but not from AK- cells. It remains to be determined if this is due to an effect of these compounds on adenosine kinase. These results give further support for the hypothesis that adenosine in growth medium modulates the sensitivity of the cells to the cyclic AMP-elevating affect of adenosine, and furthermore they suggest that adenosine in growth media may tonically stimulate adenylate cyclase and affect processes controlled by the cyclic AMP:cyclic AMP-dependent protein kinase system.
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PMID:Release of adenosine by C1300 neuroblastoma cells in tissue culture. 626 30

Plasmodium falciparum trophozoites were isolated by mechanical rupture of infected human erythrocytes followed by a series of differential centrifugation steps. After lysis with sonication, the 100 000 x g supernatant of parasites and uninfected host cells was used to determine the specific activities of a number of enzymes involved in purine and pyrimidine metabolism. P. falciparum possessed the purine salvage enzymes: adenosine deaminase, purine nucleoside phosphorylase, hypoxanthine-guanine phosphoribosyltransferase (PRTase), xanthine PRTase, adenine PRTase, adenosine kinase. The last two enzymes, however, were present at much lower activity levels. Hypoxanthine was converted (presumably via IMP) into adenine and guanine nucleotides only in the presence both of supernatant and membrane fractions of P. falciparum. Two enzymes involved in the de novo synthesis of pyrimidines, orotic acid PRTase, and orotidine 5'-phosphate decarboxylase, were present in parasite extracts as were the enzymes for pyrimidine nucleotide phosphorylation: UMP-CMP kinase, dTMP kinase, nucleoside diphosphate kinase. Xanthine oxidase, CTP synthetase, cytidine deaminase and several kinases for the salvage of pyrimidine nucleosides were not detected in the parasites. Both phosphoribosyl pyrophosphate synthetase and uracil PRTase were present but at low activity levels. Human erythrocytes displayed similar but not identical enzyme patterns. Enzyme specific activities, however, were generally much lower than those of the corresponding parasite enzymes.
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PMID:Enzymes of purine and pyrimidine metabolism from the human malaria parasite, Plasmodium falciparum. 628 90

We have studied purine metabolism in mononuclear and polymorphonuclear cells from uraemic patients using microradiochemical enzyme assays and high-pressure liquid chromatography. In mononuclear cell lysates the mean activities of adenosine deaminase (EC 3.5.4.4) and 5'-nucleotidase (EC 3.1.3.5) were significantly diminished. The activities of adenylate kinase (EC 2.7.4.3), purine nucleoside phosphorylase (EC 2.4.2.1), adenine phosphoribosyltransferase (EC 2.4.2.7), and hypoxanthine phosphoribosyltransferase (EC 2.4.2.8) were not significantly different in the two groups. The activities of adenosine deaminase and adenine phosphoribosyltransferase were reduced in the polymorphonuclear cell lysates. No clear differences emerged in the concentration of adenine nucleotides in the mononuclear cells. The significance of these changes, which are less marked than those in erythrocytes, is discussed with reference to the immunodeficiency associated with uraemia.
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PMID:Activities of enzymes involved in purine metabolism and some related adenine nucleotide concentrations of leucocytes in renal failure. 629 37

The use of high-performance liquid chromatography to identify and quantitate five purine-metabolizing enzymes from a partially purified subcellular fraction of the eucaryotic microorganism Dictyostelium discoideum is described. All HPLC separations were carried out in an isocratic manner using reverse-phase C18 as the stationary phase. The mobile phase consisted of a phosphate buffer with either methanol or acetonitrile as cosolvent, and optimal separation conditions were attained by varying the organic concentration or the pH of the buffer or by employing paired-ion chromatographic techniques. Substrates and products were detected at either 254 nm for the purines or 295 nm for the formycin analogs. An adenosine kinase activity was identified, and it was demonstrated that formycin A (FoA) could be substituted for adenosine as the phosphate acceptor, yielding FoAMP as the product. With FoA as the substrate an apparent Km of 18.2 microM and an apparent Vmax of 32.4 mmol min-1 mg-1 were observed for the activity. A purine-nucleoside phosphorylase activity was found to cleave adenosine to adenine and ribosylphosphate. FoA was not found to be a substrate for this activity due to the unusual formycin C-glycosyl bond which was not hydrolyzed by enzymes or chemically with either HCl or NaOH. An adenylate deaminase activity was found to be present in the cytosolic S-100 of cells harvested during the onset of development, and this deaminase activity was greatly stimulated by ATP. With FoAMP as the substrate, an apparent Km of 236 microM and Vmax of 2.78 mumol min-1 mg-1 were observed. The deamination of FoAMP could be inhibited by the addition of the natural substrate AMP. An apparent Ki value of 136 microM was determined from initial rate data. An adenylosuccinate synthetase activity was observed to have a Km value for GTP, IMP, and aspartic acid of 23, 34, and 714 microM, respectively. The formycin analog FoIMP was not a substrate with this activity but was a competitive inhibitor of IMP. Finally hypoxanthine-guanine phosphoribosyltransferase was found to have Km and Vmax values for hypoxanthine of 55.5 microM and 34.3 nmol-1 min-1 mg-1. When guanine was used as the substrate, the rate of nucleotide formation was 50% that with hypoxanthine as the substrate. The advantages of using HPLC to examine the interconnecting activities of a multienzyme complex in subcellular fractions are discussed, including the increased sensitivity obtained by using formycin analogs in the assay procedures.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Intermediary purine-metabolizing enzymes from the cytosol of Dictyostelium discoideum monitored by high-performance liquid chromatography. 642 68

Erythrocytes of five strains of mice had ATP concentrations of ca 2.7 mumol/ml packed cells, while those of CBA mice were 23% lower, and those of BALB/C mice were 40% lower. The ratio of the concentrations of ATP and GTP were ca 3.3 in four strains but greater than 27 in three other strains. When erythrocytes from different mouse strains were incubated with radioactive precursors, appreciable strain differences were found in the apparent activities of adenine and hypoxanthine-guanine phosphoribosyltransferase, adenosine kinase, adenosine deaminase, guanine deaminase and xanthine oxidase. The activities of adenosine deaminase and guanine deaminase in sera of mice of different strains also varied.
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PMID:Variation in erythrocyte purine metabolism among mouse strains. 668 81

Adenosine kinase, adenosine deaminase, hypoxanthine phosphoribosyltransferase, inosine-nucleoside phosphorylase, 5'-AMP deaminase and 5'-IMP nucleotidase were identified in cell-free extracts of duckling erythrocytes; no evidence for 5'-AMP nucleotidase and xanthine oxidase activity was found. The Km values for the duckling red cell enzymes were similar to those reported for human erythrocytes. Plasmodium lophurae extracts demonstrated similar enzyme activities except for 5'-AMP deaminase and 5'-IMP nucleotidase which were absent. It is proposed that during infection erythrocytic AMP is catabolized to IMP, inosine and hypoxanthine; the hypoxanthine is taken up by the plasmodium, utilized to form IMP, and this in turn is converted into adenine and guanine nucleotides.
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PMID:Purine metabolizing enzymes of Plasmodium lophurae and its host cell, the duckling (Anas domesticus) erythrocyte. 678 22


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