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)

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

The efficiency of DNA-mediated transfer of the gene (hprt) for hypoxanthine phosphoribosyltransferase (HPRT; IMP: pyrophosphate phosphoribosyltransferase, EC 2.4.2.8) is dependent upon the recipient cell used. hprt has been transferred into mouse TG8 or Chinese hamster CHTG49 cells at a high frequency, similar to the frequency of the gene (tk) for thymidine kinase (TK; ATP:thymidine 5'-phosphotransferase, EC 2.7.1.21) transfer into mouse LMTK- cells (i.e., 10(-6)). In contrast, the frequency of transfer of hprt into mouse A9 cells was about two orders of magnitude less. The identification of efficient recipient cells for hprt transfer permits the use of DNA-mediated transfer as a bioassay for the gene. Cotransfer of the linked tk gene and the gene (galk) for galactokinase (ATP: D-galactose 1-phosphotransferase, EC 2.7.1.6) to LMTK- cells has been detected once among 87 tk transferrents. This suggests that the distance between the tk and galk genes in the Chinese hamster genome may be smaller than was previously thought. Significant differences between chromosome-mediated and DNA-mediated gene transfer were observed with respect to both the size of the transferred functional genetic fragment and the recipient cell specificity.
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PMID:Cotransfer of linked eukaryotic genes and efficient transfer of hypoxanthine phosphoribosyltransferase by DNA-mediated gene transfer. 692 11

Antibody specific for the native form of Chinese hamster hypoxanthine/guanine phosphoribosyltransferase (HPRT; IMP:pyrophosphate phosphoribosyltransferase, EC 2.4.2.8) was used to detect the synthesis of HPRT protein in a rabbit reticulocyte lysate translation system primed with mRNA from Chinese hamster tissues and cultured cells. Electrophoretic analysis of the immunopurified products from the translation of mRNA from wild-type and a series of mutant Chinese hamster cells indicated that HPRT synthesis in vitro qualitatively and quantitatively corresponded to synthesis in vivo. The translation system was used to identify two mRNA sources producing high levels of HPRT protein: Chinese hamster brain and a mouse neuroblastoma HPRT revertant cell line, NBR4. Translation of NBR4 mRNA generated 25-50 times more HPRT protein than mRNA from wild-type cells. The basis for HPRT overproduction is considered in view of an X chromosome alteration found in NBR4 cells.
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PMID:In vitro translation of hypoxanthine/guanine phosphoribosyltransferase mRNA: characterization of a mouse neuroblastoma cell line that has elevated levels of hypoxanthine/guanine phosphoribosyltransferase protein. 694 70

Alterations in several specific enzymes have been associated with increased rates of purine synthesis de novo in human and other mammalian cells. However, these recognized abnormalities in humans account for only a few percent of the clinical cases of hyperuricemia and gout. We have examined in detail the rates of purine production de novo and purine excretion by normal and by mutant (AU-100) murine lymphoma T cells (S49) 80% deficient in adenylosuccinate synthetase [IMP:L-aspartate ligase (GDP-forming), EC 6.3.4.4]. The intracellular ATP concentration of the mutant cells is slightly diminished, but their GTP is increased 50% and their IMP, four-fold. Compared to wild-type cells, the AU-100 cells excrete into the culture medium 30- to 50-fold greater amounts of purine metabolites consisting mainly of inosine. Moreover, the AU-100 cell line overproduces total purines. In an AU-100-derived cell line, AU-TG50B, deficient in adenylosuccinate synthetase and hypoxanthine/guanine phosphoribosyltransferase (IMP:pyrophosphate phosphoribosyltransferase, EC 2.4.2.8), purine nucleoside excretion is increased 50- to 100-fold, and de novo synthesis is even greater than that for AU-100 cells. The overexcretion of purine metabolites by the AU-100 cells seems to be due to the primary genetic deficiency of adenylosuccinate synthetase, a deficiency that requires the cell to increase intracellular IMP in an attempt to maintain ATP levels. As a consequence of elevated IMP pools, large amounts of inosine are secreted into the culture medium. We propose that a similar primary genetic defect may account for the excessive purine excretion in some patients with dominantly inherited hyperuricemia and gout.
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PMID:Purine oversecretion in cultured murine lymphoma cells deficient in adenylosuccinate synthetase: genetic model for inherited hyperuricemia and gout. 695 54

Mouse A9 cells, L-cell-derived mutants deficient in hypoxanthine phosphoribosyltransferase (HPRT; IMP:pyrophosphate phosphoribosyltransferase, EC 2.4.2.8) were found to be incapable of binding (125)I-labeled epidermal growth factor (EGF) to the cell surface. The A9 cells were fused with human diploid fibroblasts (WI-38) possessing EGF-binding ability, and human-mouse cell hybrids (TA series) were isolated after hypoxanthine/aminopterin/thymidine/ouabain selection. Analyses of isozyme markers and chromosomes of four representative clones of TA hybrids indicated that the expression of EGF-binding ability is correlated with the presence of human chromosome 7 or 19. Four subclones were isolated from an EGF-binding-positive line, TA-4, and segregation of EGF-binding was found to be concordant with the expression of human mitochondrial malate dehydrogenase (MDHM; L-malate:NAD(+) oxidoreductase, EC 1.1.1.37), a marker for chromosome 7, but not with glucosephosphate isomerase (GPI; D-glucose-6-phosphate ketol-isomerase, EC 5.3.1.9), a marker for chromosome 19. Furthermore, evidence from 27 clones of AUG hybrids that were produced between A9 and another human fibroblast line, GM1696, carrying an X/7 chromosome translocation indicated that EGF-binding ability segregates together with human MDHM and two X-linked markers, HPRT and glucose-6-phosphate dehydrogenase (G6PD; D-glucose-6-phosphate:NADP(+) 1-oxidoreductase, EC 1.1.1.49), that are located on the translocation chromosome 7p(+). These results permit assignment of the gene, designated EGFS, which is associated with the expression of EGF-binding ability, to human chromosome 7 and its localization to the p22-qter region. Because the EGF receptor is reported to be a glycoprotein the EGFS could be either a structural gene(s) for receptor protein or a gene(s) for modifying the receptor protein through glycosylation.
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PMID:Genetics of cell surface receptors for bioactive polypeptides: binding of epidermal growth factor is associated with the presence of human chromosome 7 in human-mouse cell hybrids. 696 72

An assay procedure, utilizing high pressure liquid chromatography, has been designed which allows both reactions catalyzed by hypoxanthine-guanine phosphoribosyltransferase to be monitored simultaneously. Using this procedure and the theories described by Huang (Huang, C. V. (1979) Methods. Enzymol. 63, 486-500) for alternate substrate kinetic analysis, we have determined that purified hypoxanthine-guanine phosphoribosyltransferase from yeast catalyzes the formations of both IMP and GMP through the use of an Ordered Bi Bi kinetic mechanism, and that guanine is highly preferred over hypoxanthine as substrate in the forward reaction. This proposed kinetic mechanism has been confirmed using flow dialysis experiments in which a binary enzyme-5-phosphoribosyl-alpha-1-pyrophosphate complex was characterized but where enzymic complexes, with either guanine or hypoxanthine, were not detected. Also consistent with this kinetic mechanism was our observation that an exchange of label between [14C]guanine or [14C]hypoxanthine and their respective nucleotides (GMP and IMP) was not catalyzed by hypoxanthine-guanine phosphoribosyltransferase. However, a significant exchange of label between [32P]pyrophosphate and 5-phosphoribosyl-alpha-1-pyrophosphate is observed upon incubation with this enzyme, suggesting that hypoxanthine-guanine phosphoribosyltransferase may exist, in part, as a phosphoribosyl-enzyme complex in the presence of 5-phosphoribosyl-alpha-1-pyrophosphate.
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PMID:Studies of the kinetic mechanism of hypoxanthine-guanine phosphoribosyltransferase from yeast. 703 45

Xanthine phosphoribosyltransferase (XPRTase; EC 2.4.4.22) was found in the promastigotes of four species of Leishmania (L. mexicana, L. donovani, L. braziliensis and L. tarentolae). In no case was there any transribosylation from 5-phosphoribosyl-1-pyrophosphate (PRibPP), forming XMP, in dialyzed preparations, unless activated by a divalent cation. Magnesium and zinc were very low in activation efficiency in all cases, while manganese was optimally efficient. Cobalt was essentially equal to manganese for activation of the enzyme from L. mexicana and L. braziliensis but much less efficient for the enzyme from L. donovani and L. tarentolae. Gel filtration profiles of cell extracts of L. mexicana on Sephadex G-200 indicated that the enzymes catalyzing the transribosylation from PRibPP to guanine, hypoxanthine, and xanthine were inseparable. All were eluted near the void volume. The enzyme for adenine transribosylation was clearly separate. When cell extracts of L. mexicana were applied to Sephadex G-100 columns, the activity toward XMP formation from xanthine eluted with the void volume, together with a portion of that for the formation of GMP and IMP from guanine and hypoxanthine. A second peak of HGPRTase (EC 2.4.2.8) eluted somewhat later and was devoid of XPRTase activity. XPRTase from promastigotes of L. mexicana is heat labile, has rather a broad pH optima, and is stable to freezing when protected by nonspecific cell protein (40,000 g supernate as opposed to 100,000 g supernates).
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PMID:Xanthine phosphoribosyltransferase in Leishmania: divalent cation activation. 713 52

Both enzyme-mediated group translocation and facilitated diffusion have been proposed as mechanisms by which mammalian cells take up purine bases and nucleosides. We have investigated the mechanisms for hypoxanthine and inosine transport by using membrane vesicles from Chinese hamster ovary cells (CHO), Balb/c 3T3 and SV3T3 cells prepared by identical procedures. Uptake mechanisms were characterized by analyzing intravesicular contents, determining which substrates could exchange with the transport products, assaying for hypoxanthine phosphoribosyltransferase activity, and measuring the stimulation of uptake of hypoxanthine by phosphoribosyl pyrophosphate (PRib-PP). We found that the uptake of hypoxanthine in Balb 3T3 vesicles was stimulated 3--4-fold by PRib-PP. The intravesicular product was predominantly IMP. The hypoxanthine phosphoribosyltransferase activity copurified with the vesicle preparation. These results suggest the possible involvement of this enzyme in hypoxanthine uptake in 3T3 vesicles. In contrast to the 3T3 vesicles, CHO vesicles prepared under identical procedures did not retain hypoxanthine phosphoribosyltransferase activity and did not demonstrate PRib-PP-stimulated hypoxanthine uptake. The intravesicular product of hypoxanthine uptake in CHO vesicles was hypoxanthine. These results and data from our kinetic and exchange studies indicated that CHO vesicles transport hypoxanthine via facilitated diffusion. An analogous situation was observed for inosine uptake; CHO vesicles accumulated inosine via a facilitated diffusion mechanism, while in the same experiments SV3T3 vesicles exhibited a purine nucleoside phosphorylase-dependent translocation of the ribose moiety of inosine. Vesicles prepared from a CHO cell line temperature-sensitive for hypoxanthine uptake (Azarts) showed a temperature-sensitivity in Km for uptake parallel to that of the intact cells. This suggests that the defect in Azarts may be caused by a missense mutation in the gene coding for the hypoxanthine transport carrier.
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PMID:Distinct mechanisms of hypoxanthine and inosine transport in membrane vesicles isolated from Chinese hamster ovary and Balb 3T3 cells. 722 83

Tritium suicide was shown to be a highly efficient method for isolating mutants defective in hypoxanthine incorporation in the Chinese hamster lung cell line V79. The tritium suicide procedure consisted of 3 kill cycles. Survivors of one kill cycle were used for the next kill cycle. The kill cycles involved incorporation of [3H]hypoxanthine for 5 or 10 min, followed by storage of 3H-labelled cells at -70 degrees C for 4-10 days. 12 clones that survived the 3rd kill cycle were tested for incorporation of [3H]hypoxanthine and all were found to be defective. At lest 6 of the clones have defective hypoxanthine phosphoribosyltransferase (HPRT) activity. One mutant, H19, chosen for further characterization, had HPRT with a 13-fold elevation in apparent Km for phosphoribosylpyrophosphate (PRPP). Thin-layer chromatography of cell extracts showed that this mutant was incapable of converting intracellular hypoxanthine to IMP or to other purine metabolites. In addition, H19 as resistant to 6-thioguanine.
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PMID:Isolation of hypoxanthine phosphoribosyltransferase-defective mutants in Chinese hamster V79 cells by tritium suicide. 727 70

The metabolic fate of labeled guanine and of prelabeled guanine nucleotides (GuRN) was studied in cultured rat cardiomyocytes. Special attention was given to guanine salvage in comparison to degradation; to the contribution of GuRN to adenine nucleotides (AdRN); to the fluxes from GMP to IMP and from IMP to GMP; and to the degradation pathways of GuRN. In accordance with the 3- to 4-fold higher activity of guanine deaminase (guanase), in comparison to that of hypoxanthine-guanine phosphoribosyltransferase (HGPRT), the rate of guanine deamination to xanthine exceeded that of guanine incorporation into nucleotides (at 4 microM) by 13.2-fold. The label from guanine incorporated into nucleotides was found mainly (81%) in GuRN, but also in IMP and AdRN. The prelabeled GuRN lost 43% of the label in 4 h, reflecting mainly degradation to xanthine (and uric acid) and synthesis of nucleic acids. Blocking nucleoside degradation was associated with a marked accumulation of label in guanosine and inosine (guanosine/inosine labeling ratio is 1.25). The results indicate that in the myocardium guanine is a poor substrate for salvage synthesis of GuRN and that its contribution to the homeostasis of adenine nucleotides is negligible; that GMP degradation to xanthine proceeds through both guanosine and IMP; and that the cardiomyocytes contain the activity of GMP reductase and of the enzymes converting IMP to GMP.
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PMID:Metabolism of guanine and guanine nucleotides in primary rat cardiomyocyte cultures. 758 72


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