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)

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

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

Adenosine deaminase (ADA), purine nucleoside phosphorylase (PNP), 5'nucleotidase (5'NT), ecto-5'NT, hypoxanthine-guanine phosphoribosyltransferase(HGPRT), adenine phosphoribosyltransferase(APRT), adenosine kinase(AK), AMP deaminase (AMPD) and adenylate kinase(AdKin) activities were assayed in leukemic cells from bone marrow and/or peripheral blood of 43 newly diagnosed children with acute lymphoblastic leukemia(ALL). These enzyme activities have been investigated in relation to some immunological markers. ADA activity was higher in E-rosette positive leukemia(E+ ALL), while HGPRT, APRT, PNP, 5'NT, ecto-5'NT and AdKin activities were found to be lower in E+ ALL as compared to E- ALL. In common ALL (cALL) antigen positive leukemia, mean ADA activity was significantly lower as compared to cALL- leukemia, whereas PNP, 5'NT, ecto-5'NT and AdKin activities were significantly higher. cALL cells with cytoplasmic immunoglobulin M(IgM) heavy chains were found to have mean 5'NT activities twice as high as cALL cells lacking cytoplasmic IgM heavy chains. In two patients who had surface immunoglobulins on their cell membranes, low 5'NT activities were found. When measuring enzyme activities after 2-4 days of prednisone monotherapy, only mean ADA and HGPRT activities decreased in non-B, non-T ALL. These decreases were not significant in T-ALL patients. Mean enzyme activities in the leukemic cells of five patients with relapse were comparable to those in newly diagnosed patients, except for 5'NT, which was found to be within the activity range of control peripheral blood lymphocytes. It is concluded that ADA and AdKin activities are suitable as markers for E+ ALL and cALL+ leukemias respectively. 5'NT might help to distinguish between cALL cells having and lacking pre-B characteristics. Since 5'NT activity may also be decreased in B-ALL, it is not suitable as a T-ALL marker. Enzymes of purine metabolism in leukemic relapse need further investigation.
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PMID:Purine metabolism in childhood acute lymphoblastic leukemia: biochemical markers for diagnosis and chemotherapy. 631 Feb 74

Data are presented which indicate that the repression of pur gene expression seen after the addition of preformed purines to cultures of Salmonella typhimurium is the consequence of the presence or the formation of the purine bases, hypoxanthine and guanine. This conclusion is based on the following observations. First, it was impossible to find a correlation between the size of any individual purine nucleotide pool and the level of the first four enzymes in the de novo biosynthetic pathway. Second, adenine plus guanosine served as a perfect source of purine nucleotides, but their presence caused no repression of pur gene expression if the cells lacked purine nucleoside phosphorylase activity. This enzyme is needed to convert adenine and guanosine to hypoxanthine and guanine, but not for their conversion to nucleotides. Third, addition of guanine to a strain lacking guanine phosphoribosyltransferase (gpt) resulted in a repression of the level of the purine de novo biosynthetic enzymes, a reduction of the growth rate, and a fall in the pools of ATP and GTP. Addition of hypoxanthine to a strain lacking hypoxanthine phosphoribosyltransferase (hpt) had a similar, although weaker, effect. If the cells lacked both hypoxanthine and guanine phosphoribosyltransferases (hpt gpt), their basal level of the purine de novo biosynthetic enzymes was repressed in minimal medium. Such cells grow slower than wild-type cells and excrete purines, probably due to the inability to salvage endogenously formed hypoxanthine and guanine.
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PMID:Role of hypoxanthine and guanine in regulation of Salmonella typhimurium pur gene expression. 640 6

1. Phosphorolysis and phosphorylation rates of inosine, guanosine and deoxyguanosine were determined in disrupted and intact human and ovine lymphocytes and rat thymocytes and related with their effect on mitogenic stimulation. 2. Activity of purine nucleoside phosphorylase (EC 2.4.2.1) was about 10 times higher in extracts of human lymphocytes than in those of ovine lymphocytes and rat thymocytes. Apparent Km values for inosine and guanosine were higher in human lymphocytes (about 100 microM) than in ovine lymphocytes (50 microM). Apparent Km values for deoxyguanosine were about 100 microM in the extracts of all three cell types. 3. In extracts of human and ovine lymphocytes the presence of guanosine kinase activity was established. Deoxyguanosine kinase activity was detected in all three cell types. 4. The rate of phosphorylation of deoxyguanosine was much lower than the rate of phosphorolysis both in extracts and in intact cells. 5. Deoxyguanosine, guanosine and inosine were incorporated by intact cells into nucleotides and nucleic acids. This incorporation of deoxyguanosine and guanosine was only partially due to phosphorolysis and subsequent conversion by hypoxanthine-guanine phosphoribosyltransferase (EC 2.4.2.8). The incorporation of inosine appeared to be due completely to this route. 6. Inosine (0.5 mM) did not inhibit thymidine incorporation of phytohemagglutinin-stimulated human and ovine lymphocytes. At the same concentration deoxyinosine caused 50% inhibition, but guanosine and deoxyguanosine inhibited almost completely. Thymidine incorporation of concanavalin A-stimulated rat thymocytes was hardly inhibited by 0.5 mM inosine, deoxyinosine and guanosine, but 50 microM and 0.5 mM deoxyguanosine caused 25% and complete inhibition, respectively.
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PMID:Metabolism of purine nucleosides in human and ovine lymphocytes and rat thymocytes and their influence on mitogenic stimulation. 640 34

Adenosine deaminase (ADA), 5'nucleotidase (5'NT), ecto-5'NT, purine nucleoside phosphorylase (PNP), hypoxanthine-guanine phosphoribosyltransferase (HGPRT), adenine phosphoribosyltransferase (APRT), adenosine kinase (AK), AMP-deaminase (AMPD) and adenylate kinase (AdKin) activities were assayed in peripheral blood lymphoid cells from 20 patients with B-cell type chronic lymphocytic leukemia (CLL). Significantly decreased mean activities of ADA, 5'NT, ecto-5'NT, PNP and AMPD were observed when comparing B-CLL lymphoid cells with control peripheral blood lymphocytes (PBL). AK and AdKin activities however, were found to be higher in B-CLL. Relatively wide ranges of ADA and 5'NT activity were observed. In patients with paraproteinaemia, 5'NT activity was found to be relatively high and in the range of the activities in normal PBL. ADA activity seemed to be slightly higher in patients without paraproteinaemia. No correlation could be found between the enzyme activities and the number of cells rosetting with sheep erythrocytes or bearing surface immunoglobulin (sIg). A relationship was suggested between 5'NT activity and Ig production.
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PMID:Enzymological studies in chronic lymphocytic leukemia. 640 72

A purine nucleotide (inosinate) cycle is demonstrated with human lymphoblasts. The lymphoblast requires approximately 50 nmol of purine/10(6) cell increment. When the inosinate cycle is interrupted by the genetic, severe deficiency of either or both purine nucleoside phosphorylase (PNP) or hypoxanthine phosphoribosyltransferase (HPRT), purine accumulates in the culture medium as inosine, guanosine, deoxyinosine, and deoxyguanosine (PNP deficiency or PNP, HPRT deficiency) or hypoxanthine and guanine (HPRT deficiency). This accumulation represents an additional 25 to 32 nmol of purine which must be synthesized per 10(6) cell increment. PNP-deficient lymphoblasts have PPRibP contents characteristic of normal lymphoblasts, about 20 to 25 pmol/10(6) cells. HPRT-deficient lymphoblasts have four times higher PPRibP contents. The lymphoblast deficient for both PNP and HPRT has only a marginal elevation of PPRibP content, 1.5 times normal values. The elevated PPRibP content of HPRT-deficient cells reflects the efficient, unilateral reutilization of the ribose moiety of purine ribonucleotides and is not a cause of purine overproduction. Purine overproduction characterizing PNP-deficient lymphoblasts appears similar to overproduction from deficiency of HPRT, i.e. a break in the inosinate cycle rather than overactive de novo purine synthesis.
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PMID:Purine nucleotide reutilization by human lymphoblast lines with aberrations of the inosinate cycle. 642 40

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

The synthesis of 6-amino-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (3,7-dideazaguanine, 2) has been accomplished from 3-(ethoxycarbonyl)pyrrole-2-acetonitrile. In contrast to 3-deazaguanine, compound 2 did not show any antitumor, antiviral, or antibacterial properties. Furthermore, it was not a substrate for hypoxanthine-guanine phosphoribosyltransferase or purine nucleoside phosphorylase.
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PMID:Synthesis and biological evaluation of 6-amino-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (3,7-dideazaguanine). 643 21


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