Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.4.2.8 (hypoxanthine-guanine phosphoribosyltransferase)
 2,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sealed and unsealed plasma membrane vesicles were prepared from human erythrocytes and lymphocytes. Phosphoribosylpyrophosphate synthetase (PRibPP synthetase), hypoxanthine phosphoribosyltransferase (HPRTase), and adenine phosphoribosyltransferase (APRTase) activities are detectable on both inside-out and right-side-out sealed vesicles. Ghost preparations were about 0.2%, 1%, and 1.2% of the total erythrocyte and 0.5%, 5.3%, and 9.7% of the lymphocyte APRTase, HPRTase, and PRibPP synthetase activities. The rapid decrease in these enzyme activities, upon further purification of the membranes, seemed to suggest that they might be loosely bound extrinsic proteins. Evidence confirming the localization of these enzymes on the cell surface was obtained by measuring production of [14C]AMP by intact cells in medium containing [14C]adenine, ribose 5-phosphate, and Mg2+ATP. The formation of AMP was linear with time and number of cells present. Magnesium and phosphate exerted different effects on the production of extracellular AMP than on intracellular, which involves transport as well as phosphoribosylation. Cytosoluble and membrane-bound APRTase and PRibPP synthetase exhibited different catalytic properties and sensitivities to effectors. Membranes of erythrocytes of HPRTase-deficient patients contain little or no HPRTase activity when assayed in the absence of Triton. Reisolation of these membranes from admixture with normal hemolysates did not result in any bound activity; thus, the membrane-bound activity is not an artifact of the isolation procedure. Lysis with Triton released activity equal to about half that of control membranes. This is further evidence that the enzyme is firmly bound to the membrane.
Biochemistry 1982 Dec 21
PMID:Membrane-associated purine metabolizing enzyme activities of human peripheral blood cells. 629 41

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.
J Med Chem 1984 Dec
PMID:Synthesis and biological evaluation of 6-amino-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (3,7-dideazaguanine). 643 21

We have developed a culture system for detecting and isolating rare hypoxanthine phosphoribosyltransferase-deficient mutants of human epidermal keratinocytes. A thioguanine-resistant variant, 3T3M1, of the Swiss mouse fibroblast line 3T3 was used as a feeder layer to support clonal growth of mutant keratinocytes. A near-diploid, epidermal squamous cell carcinoma line, SCC-13Y, was used as a prototype to determine mutagen treatment conditions, plating density, and phenotypic expression time for maximum mutant recovery. To extend this system to normal keratinocytes, we improved the culture conditions by adding insulin, adenine, and Ham's nutrient mixture F-12, which increased colony-forming efficiencies to 30% in early passage and made feasible the detection of rare mutants in normal epidermal keratinocyte populations. We have quantitated mutation in SCC-13Y and three strains of normal human epidermal keratinocytes after exposure to polycyclic aromatic hydrocarbons, which are activated to their mutagenic forms by cellular mixed-function oxidases. 7,12-Dimethylbenz[a]anthracene and benzo[a]pyrene caused almost no cytotoxicity, but induced thioguanine-resistant mutants at frequencies as much as 50-fold higher than the spontaneous frequency of approximately 10(-6). The mutants were aminopterin-sensitive and possessed no measurable hypoxanthine phosphoribosyltransferase activity; their behavior was indistinguishable from that of keratinocytes cultured from individuals with Lesch-Nyhan syndrome. This mutagenesis assay system should also be applicable to other feeder layer-dependent human epithelial cell types, such as urothelial, mammary, and tracheal epithelial cells.
Proc Natl Acad Sci U S A 1984 Dec
PMID:Polycyclic aromatic hydrocarbon mutagenesis of human epidermal keratinocytes in culture. 644 Jan 45

Mutant promastigotes of Leishmania donovani deficient in adenine phosphoribosyltransferase (AP-Rib transferase) have been isolated in medium containing 4-aminopyrazolopyrimidine. The generation of AP-Rib transferase-deficient mutants occurred in two discrete steps. In the first step, clones were isolated with 50% of wild-type levels of AP-Rib transferase activity. These cells were reselected, and colonies totally deficient in AP-Rib transferase were isolated. Wild-type and AP-Rib transferase-deficient cells contained equivalent amounts of other enzymes essential to adenine metabolism such as adenine deaminase and hypoxanthine-guanine phosphoribosyltransferase. Partially and totally AP-Rib transferase-deficient cells exhibited intermediate and complete resistance to cytotoxic adenine analogs, respectively. Nevertheless, wild-type and mutant cells could salvage adenine and utilize adenine as a purine source equally efficiently, suggesting that the adenine deaminase-hypoxanthine-guanine phosphoribosyl-transferase pathway plays an important role in promastigote adenine metabolism. Kinetic and thermal inactivation studies of purified AP-Rib transferase and isoelectric focusing of crude extracts from wild-type and partially AP-Rib transferase-deficient cells suggested that the latter cells possessed wild-type AP-Rib transferase activity at half the amount found in wild-type parental cells. These data suggest that L. donovani possesses two copies of the AP-Rib transferase structural gene and that these organisms might be diploid for the AP-Rib transferase locus.
J Biol Chem 1984 Dec 10
PMID:Genetic analysis of adenine metabolism in Leishmania donovani promastigotes. Evidence for diploidy at the adenine phosphoribosyltransferase locus. 650 11

We have used liposomes to deliver DNAase I inside normal Syrian hamster embryo (SHE) cells. We showed the entrance of DNAase I inside the cell by dose-dependent cytotoxicity; and the entrance of DNAase I into the nucleus by the induction of chromosomal aberrations and somatic mutation at the HPRT locus (but not at the Na+/K+ ATPase locus). The induction of neoplastic transformation in cultures treated by DNAase I-in-liposomes was manifested by increased saturation density, colony formation at low seeding density, colony formation in 1% serum and 0.3% agar, and tumorigenicity in 100% of injected animals. The acquisition of anchorage-independent growth became apparent only after 39-57 posttreatment population doublings. Thus damage to DNA alone can initiate the neoplastic transformation process; but for full expression of the neoplastic phenotypes, a long progression time is required for the acquisition of anchorage-independent growth and tumorigenicity.
Cell 1984 Dec
PMID:DNAase I encapsulated in liposomes can induce neoplastic transformation of Syrian hamster embryo cells in culture. 650 50

To explore the molecular basis of X chromosome inactivation, we have examined the human locus for glucose-6-phosphate dehydro-genase (G6PD) in various human tissues. Studies of DNA from males and females and from somatic cell hybrids with active or inactive X chromosomes, show that two remarkably dense clusters of CpG dinucleotides in the 3' coding sequences are hypomethylated in active G6PD genes but extensively methylated in inactive ones. Reacquisition of G6PD activity, either spontaneous or induced by 5-azacytidine, is accompanied by demethylation of both clusters; however, the clusters remain methylated in reactivants that express HPRT but not G6PD. Our observations implicate these 3' CpG clusters in the transcription of G6PD and in maintenance of dosage compensation for X linked housekeeping genes.
Nucleic Acids Res 1984 Dec 21
PMID:Complete concordance between glucose-6-phosphate dehydrogenase activity and hypomethylation of 3' CpG clusters: implications for X chromosome dosage compensation. 651 79

Three linear psoralen compounds, 8-methoxypsoralen (8-MOP), 5-methoxypsoralen (5-MOP), 3-carbethoxypsoralen (3-CP), and one angular psoralen, 5-methylangelicin (5-ANG), were tested for their ability to induce both sister chromatid exchanges (SCE) and gene mutations (hypoxanthine-guanine phosphoribosyltransferase locus) in vitro in Chinese hamster ovary cells (CHO line). All the compounds induced both SCE and mutations in the presence of UV irradiation (UVA; peak at 330-380 nm), but no increases were observed in its absence. The frequency of both responses increased with either 1) increasing concentration of compound with a fixed amount of UVA or 2) increasing amount of UVA with a fixed concentration of psoralen. Significant increases in SCE were seen for 8-MOP, 5-MOP, and 5-ANG at concentrations near 1 X 10(-6) M, whereas concentrations near 20 X 10(-6) M of 3-CP were needed before increases in SCE were observed. The induction of gene mutations followed a similar pattern; concentrations of 50-100 X 10(-6) M of 3-CP were needed to induce large increases in mutations, but much lower concentrations of 8-MOP, 5-MOP, and 5-ANG (5-10 X 10(-6) M) were sufficient to induce large increases in mutations. The ratio of induced mutations to induced SCE was similar for 8-MOP, 5-MOP, and 3-CP; that of 5-ANG was much higher, which indicated that the linear furocoumarins produce a different spectrum of DNA damage from that produced by the angular psoralen.
Natl Cancer Inst Monogr 1984 Dec
PMID:Induction of sister chromatid exchanges and gene mutations in Chinese hamster ovary cells by psoralens. 653 Oct 21

Hypoxanthine phosphoribosyltransferase-deficient (HPRT-) F9-derived teratocarcinoma stem cells carrying an SV40 genome (12-16TG cells) were fused with Mus caroli (M. car.) spleen cells, and a stem cell hybrid containing reduced numbers of M. car. chromosomes was isolated (BC6 stem cell). The BC6 cells containing an active X chromosome from each parental cell were induced to differentiate in retinoic acid, and differentiated clones were isolated. Most differentiated clones retained both parental X chromosomes in active form. One differentiated clone, BC6-13, grew equally well in hypoxanthine/aminopterin/thymidine (HAT) selective medium (which requires an active M. car. HPRT (E.C.2.4.2.8) locus) or in 6-thioguanine (6TG, which would require either loss or inactivation of the M. car. HPRT locus). Using cDNA probes for HPRT and phosphoglycerate kinase (PGK) (E.C.2.7.2.3) loci and biochemical assays for HPRT and PGK enzymes, it was shown that BC6-13 cells, whether grown in nonselective medium, HAT medium, or 6TG-containing medium, retain the HPRT and PGK genes of both parental cells, but the M. car. forms of HPRT and PGK were inactivated in cells treated with 6TG. 6-Thioguanine seems to act as an inducer, one effect of which is X chromosome inactivation, which seems to be complete and irreversible as early as 24 h after addition of 6TG to BC6-13 cells.
Cell Differ 1984 Dec
PMID:Activity of X-linked genes in stem and differentiated Mus musculus X Mus caroli hybrid cells. 654 51

The cultured rat embryo undergoing organogenesis (9.5-11.5 days of gestation) together with its associated yolk sac synthesize purine nucleotides via the de novo synthetic pathway. Although both the embryo and its yolk sac contain significant levels of the purine base salvage enzymes adenine phosphoribosyltransferase and hypoxanthine phosphoribosyltransferase, the culture medium that consists largely of rat serum contains no measurable quantities of salvageable purine bases or nucleosides but high activity levels of purine catabolic enzymes. Short-term pulse-chase experiments with adenine and guanine, carried out under virtually serum-free conditions, confirmed that purine base salvage mechanisms were active and that there was no significant net transfer of purines between the embryo and its yolk sac. A comparison between the specific radioactivities of the [14C]glycine added to the culture medium for the studies of the de novo synthetic pathway and the purine bases in both the cellular nucleotides and the nucleic acids indicated the existence of a large glycine pool, which almost certainly was derived from the degradation of medium serum proteins by the yolk sac. Although there are no clear-cut data available on the in vivo plasma levels of purines that could be potentially utilized to meet the demands of the embryo, it is evident that the de novo pathway is adequately developed to meet these needs.
Proc Natl Acad Sci U S A 1983 Dec
PMID:De novo purine synthesis in cultured rat embryos undergoing organogenesis. 658 Jun 49

The effect of human platelet factors and purine derivatives on DNA synthesis has been investigated in mouse fibroblast-like L cells whose growth was arrested by serum starvation. When such cells were exposed to diluted platelet extract (e.g., 35 micrograms of protein per ml), a stimulatory effect on net DNA synthesis was observed. This effect was almost abolished by dialysis of the extract. The stimulation was, however, recovered by supplementing the diluted and dialyzed extract with hypoxanthine or adenosine. Similar phenomena were observed in pulse-labeling experiments performed with [3H]thymidine. In this case, however, there was a marginal stimulatory effect of adenosine or hypoxanthine alone. When the cells were treated with saturating concentrations of pure platelet-derived growth factor (PDGF), a stimulatory effect on pulse labeling was again obtained by the simultaneous presence of hypoxanthine or adenosine. In serum-starved cells of a mutant line of L cells deficient in hypoxanthine phosphoribosyltransferase, there was, however, no stimulatory effect on pulse labeling by hypoxanthine when it was added alone or together with either PDGF or diluted dialyzed platelet extract. It is suggested that the stimulation of DNA synthesis by the purine derivatives in the presence of a certain type of platelet proteins, probably involving PDGF, may be explained by their function as precursors for a purine ribonucleotide pool that is specifically related to DNA synthesis. Treatment of serum-starved L cells with high concentrations of dialyzed platelet extract (e.g., 240 micrograms of protein per ml) showed that platelets contain an additional type of factor that may substitute for the requirement of adenosine or hypoxanthine for DNA synthesis to take place. It is suggested that the effect of this type of factor may be to activate the catabolic activity of the purine salvage pathway.
Proc Natl Acad Sci U S A 1983 Dec
PMID:Both hypoxanthine and adenosine stimulate DNA synthesis independently in serum-starved L cells treated with platelet protein. 658 64


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>