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)

Extracts of Babesia divergens were examined for the enzymes which catalyse purine salvage. Adenosine deaminase (EC 3.5.4.4), guanine deaminase (EC 3.5.4.3), inosine phosphorylase (EC 2.4.2.1), purine phosphoribosyltransferases (EC 2.4.2.7, EC 2.4.2.8, EC 2.4.2.22) and nucleoside kinases (EC 2.7.1.15, EC 2.7.1.20, EC 2.7.1.73) were all detected at relatively high activities, whereas nucleotide interconverting enzymes were not detected. Coformycin and 4-amino-5-imidazolecarboxamide were found to be potent inhibitors of adenosine deaminase and guanine deaminase, respectively. The results suggest that B. divergens is capable of synthesizing purine nucleotides via two routes, one involving purine phosphoribosyltransferases and the other employing nucleoside kinases.
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PMID:Purine-metabolizing enzymes in Babesia divergens. 303 31

Depressed activities of the following purine enzymes have been shown to result in immunodeficiencies: adenosine deaminase (ADA), hypoxanthine-guanine phosphoribosyltransferase (HGPRT), and purine nucleoside phosphorylase (PNP). These enzymes and adenosine kinase (AK) were measured in cord blood lymphocytes of premature and small-for-gestational age infants since they have partial immunodeficiencies of unknown biochemical etiology which can persist for many years. We also measured these enzymes in 3 infants with various immunodeficiencies. Activities were compared with appropriate matched control groups. The results indicated normal ADA and PNP but significantly depressed AK (P less than 0.05) and HGPRT (P less than 0.001) activities in 10 premature/SGA infants when compared to 35 full-term normal infants. In the 3 immunodeficient children the results were as follows: Child 1 had a 2- to 3-fold decrease in ADA with normal PNP and AK activities; Child 2 had a 2- to 3-fold decrease in AK, 4-fold decrease in HGPRT with normal PNP and ADA activities; Child 3 had confirmed AIDS and a 4-fold decrease in ADA, 6-fold decrease in HGPRT with normal PNP activity. The possible role of these depressed purine enzyme activities found in lymphocytes is discussed in relation to the imparied immunity seen in these infants.
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PMID:Activities of purine metabolising enzymes in lymphocytes of neonates and young children: correlates with immune function. 311 34

Three enzymes catalysing the synthesis of four intermediates (phosphoribosylglycinamide, phosphoribosylaminoimidazole-succinocarboxamide, phosphoribosylaminoimidazole-carboxamide and AMP) in the purine biosynthetic pathway were detected in extracts of Mycobacterium microti and M. avium, even when the organisms had been grown in mice. However only one of the three enzymes, adenylosuccinate AMP-lyase (catalysing the synthesis of the last two of the four intermediates listed above) was detected in M. leprae. Phosphoribosyltransferases, which convert adenine, guanine and hypoxanthine to the corresponding nucleoside monophosphates, and adenosine kinase were the major enzymes for purine scavenging in all mycobacteria studied. In contrast to enzymes in the synthetic pathway, evidence for metabolic regulation of the purine-scavenging enzymes was obtained. In particular, 20-80-fold differences in the activities of guanine phosphoribosyltransferase and adenosine kinase were observed when M. microti was grown in media with or without purines, or in mice. In M. leprae, activities of all phosphoribosyltransferases were low in comparison with activities in M. microti and M. avium (specific activity less than 2% when comparisons were made between extracts of host-grown mycobacteria). However, activity of adenosine kinase was higher in host-grown M. leprae than in host-grown M. microti or M. avium.
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PMID:Enzymes for purine synthesis and scavenging in pathogenic mycobacteria and their distribution in Mycobacterium leprae. 332 71

Long-term bovine lymphocyte cultures were initiated by stimulation with alloantigens and maintained in continuous culture using medium containing recombinant human interleukin-2 (rh IL-2). The development of specific and lectin-dependent killing was monitored following primary alloantigen challenge. Cytolytic activity was barely detectable after 7 days of culture, but gradually increased with peak activity occurring after 21 days of culture. A panel of monoclonal antibodies (MoAb) was used to determine whether a shift in the antigen phenotype of the cell population occurred during culture. The primary cell type that grew in culture was of the T-cell lineage with minimal or no expression of class II antigens. The activities of adenosine deaminase (ADA), purine nucleotide phosphorylase (PNP), adenosine kinase (AK), deoxyadenosine kinase (dAK), deoxycytidine kinase (dCK), 5'-nucleotidase (5'-N), AMP deaminase, hypoxanthine-guanine phosphoribosyl transferase (HGPRT or HPRT), and adenine phosphoribosyl transferase (APRT) were measured by microassay in resting peripheral blood lymphocytes (PBL) and in cells from long-term cultures. Large increases in the activities of PNP and HPRT with a decrease in the activity of ADA were observed. The data show that long-term cultures of lymphocytes can be readily generated, and that sequential changes in antigenic phenotype and function can be monitored and correlated with quantitative changes in enzyme activity.
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PMID:Development and maintenance of bovine cytotoxic lymphocytes with recombinant human interleukin-2. 348 20

Studies with purified enzymes have shown that 2'-deoxycoformycin (dCF) is a potent and selective inhibitor of adenosine deaminase (ADA). Specificity of dCF's effects on adenosine metabolism in intact human skin fibroblasts was investigated by examining the isotopic flux from exogenous [14C] adenosine to metabolic products in hypoxanthine phosphoribosyltransferase deficient (HPRT-) cells which cannot recycle hypoxanthine. Apparent ADA activity (as estimated by isotopic flux to inosine and hypoxanthine) was profoundly inhibited by dCF (with at least 50% inhibition at 10(-8) M and 95% inhibition at 10(-5) M dCF). The degree of inhibition was similar at various exogenous adenosine concentrations ranging from 1 to 400 microM. Some inhibition of isotopic flux to adenine nucleotides (an ADA independent process in HPRT- cells) could be demonstrated, but only in media containing high concentrations of adenosine. Even at 400 microM adenosine, the highest concentration employed, isotopic flux to adenine nucleotides was unaffected by concentrations of dCF below 10(-6) M, and only 30% inhibition was achieved with 10(-5) M dCF. Inhibition of adenosine phosphorylation to AMP appears to be the most likely explanation for dCF inhibition of isotopic flux from [14C] adenosine to adenine nucleotides, probably due to substrate inhibition of adenosine kinase by high levels of intracellular adenosine produced when ADA is inhibited by dCF. No evidence for dCF inhibition of either adenosine transport or phosphorylations within the adenine nucleotide pool (from AMP to ADP or from ADP to ATP) was found. Thus, at physiological levels of exogenous adenosine (0.03 to 2.6 microM), dCF appears to be a potent and highly specific inhibitor of ADA in human skin fibroblasts.
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PMID:Specificity of 2'-deoxycoformycin inhibition of adenosine metabolism in intact human skin fibroblasts. 348 39

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

1. Japanese sumo wrestlers have a diet rich in energy, which results in marked obesity. Their plasma urate and triglyceride levels were significantly elevated. 2. Erythrocyte phosphoribosylpyrophosphate (PRPP) and ATP concentrations in sumo wrestlers were significantly elevated when compared to the levels in control subjects. 3. There were no significant differences in erythrocyte PRPP synthetase (EC 2.7.6.1), purine nucleoside phosphorylase (EC 2.4.2.1) and hypoxanthine guanine phosphoribosyl transferase (EC 2.4.2.8) activities between sumo wrestlers and control subjects. 4. Erythrocyte adenosine kinase (EC 2.7.1.20), adenosine deaminase (EC 3.5.4.4) and adenine phosphoribosyl transferase (EC 2.4.2.7) activities in sumo wrestlers were significantly elevated. 5. It seems that sumo wrestlers have an increased turnover of adenine nucleotides which may contribute to hyperuricaemia.
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PMID:Elevated erythrocyte phosphoribosylpyrophosphate and ATP concentrations in Japanese sumo wrestlers. 618 38

In this study enzyme activities involved in purine metabolism were measured in T and B lymphocytes separated by E and EAC rosetting methods. Adenosine deaminase, purine nucleoside phosphorylase and HGPRTase activities were significantly elevated in T cells, compared to the activities in B cells. There were no significant differences in adenosine kinase and APRTase activities between T and B lymphocytes. In contrast, PRPPsynthetase activities were higher in B cells than in T cells. The uptake of various radiolabeled precursors by mitogen stimulated lymphocytes was studied. The uptake of 14C-formate by the mitogen stimulated lymphocytes was markedly lower, compared to that of 14C-adenosine and or 14C-purine bases. The uptake of 14C-adenosine by PHA stimulated lymphocytes was considerably higher than that of Con A or PWM stimulated lymphocytes. However, the uptake of 14C-hypoxanthine into lymphocytes stimulated with PWM was increased by comparison with unstimulated lymphocytes. From these results it seems that adenosine plays a central role in the metabolism of T cells, and that purine bases are preferentially utilized in B cells.
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PMID:The differences in purine metabolism between T and B lymphocytes. 625 35

A methodology is presented for systemic analysis of purine enzymes in small lymphocyte subfractions. For the determination of 7 different enzymes of purine metabolism *hypoxanthine-guanine phosphoribosyltransferase (HG-PRT), adenine phosphoribosyltransferase (A-PRT), adenosine deaminase (ADA), purine nucleoside phosphorylase (PNP), adenosine kinase (AK), 5'-nucleotidase (5'N), and AMP-deaminase) less than 200,000 peripheral blood lymphocytes are needed. 1000-6000 lyophilised lymphocytes are incubated in micro-incubation vessels (3 microliter) with radioactive substrates for 15-180 min. Separation of substrates and products is achieved by thin-layer chromatography on PEI-cellulose. Addition of BSA to the incubation mixtures results in higher specific enzyme activities and narrower ranges of mean values of a control group.
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PMID:Enzymes of purine nucleotide metabolism in human lymphocytes. 625 89

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


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