Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00492 (hypoxanthine-guanine phosphoribosyltransferase)
 2,385 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A mutant (HPRT-) cell line was obtained by a series of passages in the medium with 8-azaguanine on the basis of human erythromyeloleukemia K-562 cells. Rapid total death of the cells in a selective medium containing hypoxanthine, aminopterine and thymidine (3 to 4 passages) supported the deficiency as regards hypoxanthine phosphoribosyltransferase. Preliminary experiments aimed at cytotoxicity studies demonstrated that the new mutant cell line lost the property, common to the parent K-562 line, of being sensitive to the attack of natural killers.
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PMID:[Derivation of a mutant (HPRT-) cell line based on K-562 human erythromyeloleukemia]. 657 55

Athetotic cerebral palsy was diagnosed in a 6-month-old boy with no history of perinatal trauma. Lesch-Nyhan syndrome (i.e., complete deficiency of hypoxanthine-guanine phosphoribosyltransferase [HGPRT] ) was diagnosed only when the boy began biting his lower lip at the age of 10 years. It is suggested, on the basis of this case and others like it in the literature, that the delayed onset or absence of self-mutilation in patients with Lesch-Nyhan syndrome may be more common than has been previously suspected. In all males said to have cerebral palsy, HGPRT deficiency must be ruled out, preferably by measuring the ratio of uric acid to creatinine in a random urine specimen.
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PMID:Differential diagnosis of cerebral palsy: Lesch-Nyhan syndrome without self-mutilation. 672 97

We have measured the rate of purine synthesis de novo in blood mononuclear cells in vitro and the activities of the purine salvage enzymes [hypoxanthine phosphoribosyltransferase (HPRT; EC 2.4.2.8), adenine phosphoribosyltransferase (APRT; EC 2.4.2.7)] and ribosephosphate pyrophosphokinase (PP-ribose-P synthetase; EC 2.7.6.1)] and the concentration of phosphoribosylpyrophosphate (PP-ribose-P) in the erythrocytes of affected family members. These subjects belong to families where hyperuricaemia and renal failure occur together early in life, and the genetic transmission follows an autosomal dominant mode of inheritance. We term this syndrome, familial hyperuricaemic nephropathy. No significant differences were detected in either the rates of purine synthesis de novo in vitro between the index patients and the control subjects with respect to the enzyme activities or the PP-ribose-P concentrations. Two groups of controls were used, healthy individuals and patients with a comparable degree of renal failure due to non-immune complex renal disease. Mononuclear cells from patients with Lesch-Nyhan syndrome (congenital HPRT deficiency) showed the expected acceleration of purine synthesis de novo in vitro. The accelerated purine synthesis de novo in vitro associated with phytohaemagglutinin-induced lymphocyte transformation was detectable by the method used. We conclude that familial hyperuricaemic nephropathy is not due to a metabolic lesion which causes accelerated purine synthesis de novo. This suggests that the primary abnormality may be a failure of the renal tubular net excretion of urate.
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PMID:The rate of purine synthesis de nova in blood mononuclear cells in vitro from patients with familial hyperuricaemic nephropathy. 674 92

A significant and reproducible enhancement of purine nucleotide synthesis from hypoxanthine occurs in HAT medium, when communication-competent hypoxanthine-guanine phosphoribosyltransferase (HGPRT+) cells are co-cultured with communication-competent (HGPRT-) LN cells. This enhancement of purine nucleotide synthesis is dependent upon the hypoxanthine concentration and upon the ratio of (HGPRT-): (HGPRT+) cells. Based upon these results a simple biochemical method for the detection of inhibitors of metabolic cooperation between (HGPRT+) cells and (HGPRT-) LN cells is presented. The biochemical method distinguishes inhibitors of metabolic cooperation from inhibitors of hypoxanthine uptake, of hypoxanthine phosphorylation and of nucleic acid synthesis, as well as from general metabolic inhibitors. This method has the advantage that it can be used on a relatively large number of cells, it is simple and not time-consuming, and distinguishes the inhibition of metabolic cooperation by compounds that have a variety of sites of inhibition.
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PMID:Biochemical assay of inhibitors of metabolic cooperation. 685 23

An electrophoretic variation for hypoxanthine phosphoribosyltransferase, HPRT, has been identified in samples of Mus spretus, a field mouse from southern Europe and in M. m. castaneus, a house mouse from southeast Asia. These mice will interbreed with laboratory mice to produce viable, fertile F1 progeny. The variation for HPRT segregates as an X chromosome gene in F1 and backcross progeny. Linkage analysis involving the markers Pgk-1 and Ags indicated a gene order of centromere--Hprt--Pgk-1--Ags in crosses involving both stocks of wild mice.
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PMID:Electrophoretic variation for X chromosome-linked hypoxanthine phosphoribosyl transferase (HPRT) in wild-derived mice. 685 25

We have previously given evidence that the hypoxanthine-guanine phosphoribosyltransferase (HGPRT; EC 2.4.2.8) isozymes in human erythroid cells result from posttranslational modifications of a single gene product [Johnson, G. G., et al. (1982). Biochemistry 21: 960]. In the present work we compare the properties of the unmodified and two major modified isozymes, which collectively account for 90% of the HGPRT enzyme activity in cell lysates. The modified isozymes differ from the parent molecule in the pH dependence of activity and in the relative utilization of the two purine base substrates, hypoxanthine and guanine. In contrast to the changes in the catalytic properties of the enzyme, the modifications have no detectable effects on the heat stability or on the equilibrium between enzyme dimers and enzyme tetramers.
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PMID:Hypoxanthine-guanine phosphoribosyltransferase in human erythroid cells: properties of the isozymes. 686 Feb 91

In a previous report we provided evidence that the three major hypoxanthine-guanine phosphoribosyltransferase (HGPRT; EC 2.4.2.8) isozymes in human erythroid cells are derived by posttranslational modification of a single enzyme [Johnson, G. G. et al. (1982). Biochemistry 21: 960]. In the experiments reported here we provide further evidence that the modified isozymes have a catalytic activity that is at least as great as that of the unmodified enzyme. However, we also show that the total HGPRT activity decrease with red-cell age, by a factor of approximately 4, and that this decrease in activity is paralleled by a loss in HGPRT immunoreactive protein. We estimate that the loss of HGPRT activity and immunoreactive protein as well as the changes in the relative abundances of the major isozymes occur early in the cell's life.
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PMID:Hypoxanthine-guanine phosphoribosyltransferase in human erythroid cells: degradation of the enzyme. 686 Feb 92

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

Somatic cell hybrid clones were derived from the fusion of hypoxanthine phosphoribosyltransferase (HPRT; EC 2.4.2.8)-deficient mouse cells and two different human fibroblast strains, each carrying an X chromosome-autosome translocation. One of these had an X/11 translocation [46,X,t(X;11)(p21;q13)] and the other had an X/19 translocation [46,X,t(X;19)(q22;q13)]. The structurally normal human X chromosome is the late-replicating (genetically inactive) chromosome in these two cell strains; the rearranged X chromosome is early replicating (genetically active). One primary hybrid clone carrying both the translocated X chromosome and the structurally normal X chromosome was isolated in hypoxanthine/aminopterin/thymidine medium from each of these two cell fusion experiments. These clones were then selected in medium containing 8-azaguanine to achieve the loss of the active human HPRT locus. Five subclones from the cell hybrid with the X/11 translocation failed to express two known human X-chromosome markers [glucose-6-phosphate dehydrogenase (G6PD; EC 1.1.1.49) and phosphoglycerate kinase (PGK; EC 2.7.2.3)] but did express human microsomal steroid sulfatase (STS; sterol-sulfate sulfohydrolase, EC 3.1.6.2). Three of these were cytogenetically analyzed and found to contain a structurally normal human X chromosome but not the X/11 translocation. Two subclones were isolated in 8-azaguanine from the hybrid with the X/19 translocation. Cytogenetic analysis of these two clones showed the presence of a structurally normal human X chromosome; the X/19 translocation was not present. They did not express human G6PD, PGK, or HPRT but did express human STS. These results indicate that human STS is expressed from a locus on the inactive human X chromosome and support our earlier finding that the STS locus escapes X-inactivation in man.
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PMID:Expression of an X-linked gene from an inactive human X chromosome in mouse-human hybrid cells: further evidence for the noninactivation of the steroid sulfatase locus in man. 693 82

An established Chinese hamster cell line was fused with microcells isolated from phenotypically stable transferent mouse cells which contained a mouse transgenome coding for an abnormal form of mouse hypoxanthine phosphoribosyltransferase (HPRT, EC. No. 2.4.2.8) (Willecke et al. 1979). Two hybrids were isolated which expressed the abnormal form of mouse HPRT but no mouse alpha-galactosidase (GALA, EC. No. 3.2.1.22). In one of these microcell hybrids the abnormal HPRT activity segregated under counter-selective conditions with mouse chromosome 3. No mouse chromosome or additional mouse gene marker was found in the second microcell hybrid, possibly because of breakage and/or rearrangement of the integrated transgenome during the isolation of this hybrid. We conclude from these results that the transferred mouse HPRT gene is a phenotypically stable clone is not integrated at its homologous site on the host X chromosome. Rather, the transgenome is probably integrated into mouse chromosome 3, possibly due to homologies in repeated DNA sequences which may occur in the transgenome and which are interspersed at many sites in the host genome.
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PMID:DNA-mediated transfer of the mouse gene for hypoxanthine phosphoribosyltransferase into cultured mouse cells: no integration of the transferred gene at its homologous site in the host genome. 694 9


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