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

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

HL-60 human acute promyelocytic leukemia cells that lack hypoxanthine-guanine phosphoribosyltransferase (HGPRT) activity have been developed by mutagenization and selection. These cells exhibited markedly decreased sensitivity to the cytotoxic action of 6-thioguanine (TG) and, in contrast to parental HL-60 cells, had the capacity to undergo terminal granulocytic differentiation after treatment with this purine antimetabolite. Analysis of extracellular and intracellular metabolites of TG revealed negligible metabolism of TG in these HGPRT- HL-60 cells. These findings are consistent with the concept that inhibition of cellular replication requires generation of analog nucleotide and suggest that TG itself is capable of initiation of differentiation. 6-Thioguanosine (TGuo) had limited activity, while beta-2'-deoxythioguanosine (dTGuo) was inactive, as an inducer of maturation of HGPRT- HL-60 cells. These cells converted relatively large amounts of the nucleosides to the free base TG; the simultaneous exposure of cells to 8-aminoguanosine (AGuo), an inhibitor of purine nucleoside phosphorylase activity, decreased the degradation of TGuo and dTGuo to TG and promoted the intracellular accumulation of TG nucleotides, presumably through the action of nucleoside kinase activities. In a double mutant deficient in both HGPRT and deoxycytidine kinase (DCK) activities, dTGuo was devoid of cytotoxicity and was an effective inducer of maturation. The potency of dTGuo as an inducer in this system was not significantly affected by the presence of AGuo. These results suggested that dTGuo itself was also an active initiator of maturation. Thus, induction of differentiation appeared to be due to the free base, TG, as well as its deoxynucleoside form, dTGuo, whereas the formation of TG nucleotides appeared to antagonize maturation and produce cytotoxicity.
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PMID:Characterization of the metabolic forms of 6-thioguanine responsible for cytotoxicity and induction of differentiation of HL-60 acute promyelocytic leukemia cells. 659 22

The value of the uric acid to creatinine ratio and the uric acid to creatinine clearance ratio in predicting 24-hour urinary uric acid excretion was assessed in 49 patients with normal enzyme activity and 22 patients with purine enzyme deficiencies. A 24-hour urinary uric acid to creatinine ratio greater than 0.75 was found in six of nine patients with a partial deficiency of hypoxanthine-guanine phosphoribosyltransferase and in all patients with Lesch-Nyhan syndrome. A ratio of less than 0.10 suggested xanthinuria or severe purine nucleoside phosphorylase deficiency. Neither ratio calculated from 2-hour timed collections of the 24-hour specimen showed a high correlation with 24-hour urine uric acid excretion in patients with normal enzyme activity, perhaps because of a diurnal variation in urinary uric acid excretion. The spot-urine uric acid to creatinine ratio does not accurately predict the 24-hour urine uric acid excretion in patients with normal enzyme activity.
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PMID:Limited value of uric acid to creatinine ratios in estimating uric acid excretion. 677 79

We have examined the basis for the recently reported, but unexplained deficiency of S-adenosylhomocysteine hydrolase (AdoHcyase) in the erythrocytes of patients with genetic deficiencies of purine nucleoside phosphorylase and hypoxanthine-guanine phosphoribosyltransferase. We found that a hemolysate from a patient with purine nucleoside phosphorylase deficiency had only 7% of control AdoHcyase activity, conforming the original observation. Of the purine nucleosides known to accumulate in nucleoside phosphorylase-deficient patients, inosine alone caused the phosphate-dependent, irreversible inactivation of purified human placental AdoHcyase, and of AdoHcyase in intact erythrocytes and cultured lymphoblastoid cells. Hypoxanthine did not inactivate purified AdoHcyase, but potentiated the effect of inosine in intact hypoxanthine-guanine phosphoribosyltransferase-deficient human lymphoblastoid cells. This presumably resulted from the ability of hypoxanthine to shift the equilibrium of the nucleoside phosphorylase reaction, preventing inosine breakdown. This could account for the partial AdoHcyase deficiency reported in hypoxanthine-guanine phosphoribosyltransferase-deficient patients. We have also demonstrated the AdoHycase-catalyzed synthesis of S-inosylhomocysteine from inosine and L-homocysteine, a reaction which may occur in nucleoside phosphorylase-deficient patients.
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PMID:Proposed explanation for S-adenosylhomocysteine hydrolase deficiency in purine nucleoside phosphorylase and hypoxanthine-guanine phosphoribosyltransferase-deficient patients. 678 20

Several aspects of purine metabolism were studied in peripheral blood mononuclear cells and fibroblasts from a patient with purine nucleoside phosphorylase deficiency and compared to cells from normal controls. Intact cells were incubated with radioactive purine bases and all purine metabolites were extracted and analyzed. Incubation of purine nucleoside phosphorylase-deficient cells with [3H]hypoxanthine and [3H]guanine resulted in the accumulation of large proportions of the incorporated radioactivity into inosine (60-80%) and to lesser extent into guanosine (15-30%), respectively, whereas normal cells accumulated only minor amounts of inosine and guanosine. This observation indicates that purine nucleoside phosphorylase, together with hypoxanthine-guanine phosphoribosyltransferase and nucleoside monophosphate phosphatase, participate in remarkably active inosine and guanosine cycles. These purine nucleoside cycles may play a role in the regulation of intracellular purine nucleotide levels. The absence of these cycles in purine nucleoside phosphorylase-deficient patients may be detrimental to the differentiation of lymphocytes.
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PMID:Evidence for active purine nucleoside cycles in human mononuclear cells and cultured fibroblasts. 681 84

Adenosine deaminase (ADA), purine nucleoside phosphorylase (PNP), and hypoxanthine-guanine phosphoribosyltransferase (HGPRT) activities were measured in normal human B lymphocytes, T lymphocytes, and T gamma and T mu lymphocyte subsets. Total ADA activity in T cells was 5.5U, activity in T gamma and T mu cells was 3.7U and 5.3U, respectively; B cell ADA levels were 3.3U. PNP activity in T cells was 119U, activity in T gamma and T mu cells was 75U and 155U, respectively. B cell PNP activity was 88U. HGPRT activity in T cells was 20.9U; T gamma and T mu HGPRT levels were 13.0U and 52U respectively. B cell HGPRT levels were 46.8U. These data provides further evidence for the biochemical heterogeneity of normal human lymphocytes.
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PMID:Adenosine deaminase, nucleoside phosphorylase and hypoxanthine-guanine phosphoribosyltransferase activity in normal lymphocyte subpopulations. 681 86


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