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)

This report concerns a three month old infant who was failing to thrive. Renal insufficiency was demonstrated and attributed to aortic coarctation. However, surgical correction of the coarctation failed to correct the renal insufficiency completely and disproportionate hyperuricemia was noted. Excessive urinary excretion of uric acid was found and a moderate deficiency (6% of normal) of hypoxanthine-guanine phosphoribosyltransferase (HGPRT) was demonstrated. When the urate over-production was corrected with allopurinol, renal function returned to normal and the child became well. The importance of over-production of urate and the resultant excessive urinary excretion of uric acid as a treatable cause of acute or persistent renal insufficiency is stressed.
Aust N Z J Med 1984 Dec
PMID:Renal failure in infancy due to over-production of urate. 659 54

The human S11 surface antigens are expressed on fibroblasts and are coded by a gene on the X-chromosome. We have regionally mapped this gene by examining S11 expression on a panel of hybrid lines which had fragmented the X-chromosome either during chromosome-mediated gene transfer, or by interspecies translocation during hybrid cell expansion. using indirect immunofluorescence and the fluorescence-activated cell sorter (FACS), it was possible to isolate antigen-positive and -negative hybrid subpopulations for subsequent genetic analysis. The gene coding S11 could be localized to Xq27-28, between the loci for HPRT and G6PD where genes for the S10 and S12 antigens have been previously mapped. This work demonstrates the value of cell surface antigens and the FACS in somatic cell genetic analysis, and provides evidence for regional clustering of surface antigen loci on the human X-chromosome.
Exp Cell Res 1983 Dec
PMID:The gene coding the human S11 surface antigens maps between the loci for HPRT and G6PD on the X-chromosome. 668 51

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.
Ann Intern Med 1980 Dec
PMID:Limited value of uric acid to creatinine ratios in estimating uric acid excretion. 677 79

The production of hybridomas between immunologically activated T cells and malignant T-cell lines offers a potentially unlimited source of soluble T-cell-derived products. Recently, human T-T hybrids have been described; however, their use has been hampered by slow growth and chromosomal instability due at least in part to the presence of thymidine in the traditional hypoxanthine/aminopterin/thymidine (HAT) selection medium. In this report, we describe the development of a rapidly growing hypoxanthine phosphoribosyltransferase-deficient human T-cell line designated J3R7, the use of azaserine/hypoxanthine (AH) medium as an alternative selection medium to HAT medium, and the production of functional T-T hybrids by using the J3R7 line and the AH selection technique. Hybrids selected in AH medium were 4-fold greater in number and 3-fold faster in growth rate than hybrids grown in HAT medium. No stable clones were obtained from HAT cultures whereas AH-derived hybrids could be readily cloned by the method of limiting dilution. Evidence for hybridization included (i) the presence of approximately twice the number of chromosomes in hybrids than in J3R7 cells; (ii) the presence on hybrid cells of the Leu-3a surface antigen, present on normal helper T cells but not on J3R7 cells; (iii) the expression of HLA antigens of both the normal T-cell partner and the J3R7 line; and (iv) the constitutive secretion of interleukin 2 from multiple hybrid clones but not from the J3R7 cell line. Thus far, these clones have maintained their rapid growth, chromosome number, surface phenotype, and constitutive secretion of interleukin 2 for 4 months.
Proc Natl Acad Sci U S A 1982 Dec
PMID:Production of functional human T-T hybridomas in selection medium lacking aminopterin and thymidine. 698 90

We describe the isolation and characterization of tryptic peptides of human erythrocyte hypoxanthine-guanine phosphoribosyltransferase. The digest was separated by reverse-phase high pressure liquid chromatography into 30 peaks, 26 of which contained purified peptides. The four complex peaks were resolved by high pressure liquid chromatography with a different reverse-phase column. Each peptide predicted from the recently described amino acid sequence of human erythrocyte hypoxanthine-guanine phosphoribosyltransferase was isolated from this peptide map. Sequence analysis of the purified peptides identified two peptides, 14 and 14d, that differed by an Asn/Asp heterogeneity at the position corresponding to residue 106 of the intact protein. Additional studies indicate that this heterogeneity is due to deamidation of the protein in vivo. This post-translational modification appears to be responsible for some of the electrophoretic heterogeneity observed in the normal erythrocyte enzyme.
J Biol Chem 1982 Dec 25
PMID:Human hypoxanthine-guanine phosphoribosyltransferase. Tryptic peptides and post-translational modification of the erythrocyte enzyme. 717 69

1. We have studied purine metabolism in renal failure using high-pressure liquid chromatography to determine metabolite concentrations in erythrocytes and plasma, and microradiochemical assays of enzyme activity in erythrocytes. 2. The mean activities of some of the enzymes involved in purine metabolism were raised in renal failure. Significant elevations of adenylate kinase (EC 2.7.4.3), purine nucleoside phosphorylase (EC 2.4.2.1), hypoxanthine phosphoribosyltransferase (EC 2.4.2.8) and adenosine deaminase (EC 3.5.4.4) but not of adenine phosphoribosyltransferase (EC 2.4.2.7) and ribosephosphate pyrophosphokinase (phosphoribosylpyrophosphate synthetase; EC 2.7.6.1) activities were demonstrated. However, there was an overlap between results from patients with renal failure and normal (control) subjects. Erythrocyte phosphoribosylpyrophosphate levels were also unchanged. 3. Erythrocyte nucleotide concentrations especially those of inosine were raised in renal failure. 4. The plasma inosine was reduced in renal failure. 5. The significance of these changes is discussed.
Clin Sci (Lond) 1981 Dec
PMID:Effect of renal failure on erythrocyte purine nucleotide, nucleoside and base concentrations and some related enzyme activities. 729 37

A large Arab family affected with the rare X-linked Lesch-Nyhan syndrome is reported on. Two hemizygous boys, two and nine years of age, had the classical biochemical and clinical-neurological syndrome. The activity of erythrocyte hypoxanthine-guanine phosphoribosyltransferase (HGPRT) was below the detectable limit (greater than 0.1% of normal). They were mentally and physically retarded and exhibited spasticity and choreoathetosis; the older of the two also exhibited self-mutilation. The mother and three of her seven daughters, all clinically asymptomatic, were proven to be heterozygous for HGPRT deficiency, by demonstration of an increased rate of de novo purine synthesis in cultured skin fibroblasts. Erythrocyte HGPRT activity was normal in the three heterozygous daughters, but was significantly reduced in the mother. However, in all four heterozygotes, erythrocyte HGPRT/adenine phosphoribosyltransferase ratio was lower than in all other family members. All heterozygotes had blood uric acid levels within the normal range, although higher than in the normal women in the family. The ratio uric acid/creatinine concentration in the urine was significantly elevated in one of the heterozygotes, and in the upper normal limit in two others, indicating excessive purine production.
Isr J Med Sci 1981 Dec
PMID:Lesch-Nyhan syndrome in an Arab family. Detection and biochemical manifestation of heterozygosity. 732 17

A highly conserved hypoxanthine phosphoribosyltransferase processed pseudogene (KPH) has been isolated from a female kangaroo (Macropus robustus) lambda EMBL3 genomic library. The pseudogene contains only transcribed material with all of the introns precisely removed and has possible direct repeats at either end of the message. It has a 654-nucleotide open reading frame (ORF) from the Met start codon to the stop codon that contains no additions, deletions or premature stops relative to expressed HPRT genes and, therefore, the possibility exists that it is expressed in vivo. Possible CAAT and GC boxes are present in the region 5' to the ORF and a polyadenylation signal is present in the region 3' to the ORF. If not expressed, the age of the pseudogene is estimated to be 10.7 million years. We propose that integration into the genome occurred specifically in a homocopolymeric region within a highly repeated region unique to the kangaroo genome.
Gene 1994 Dec 15
PMID:Isolation of a potentially functional HPRT processed pseudogene from the hill kangaroo Macropus robustus. 782 7

Competitive polymerase chain reaction (PCR) is a sensitive method for quantification of cytokine mRNA expression. Co-amplification of an internal standard serves as control for comparing the efficiency of PCR in different samples. We have developed a novel control fragment for multiple analyses of rat cytokine gene expression containing primers for IL-1 beta, IL-2, IL-4, IL-5, IL-6, IL-10, TNF-alpha, TGF-beta 1, IFN-gamma and MIP-2. Additional primers were incorporated to analyse the content of T cells (CD3), activated T cells (CD25) and housekeeping genes (beta-actin and HPRT). As an example we demonstrate analysis of IL-2 mRNA expression in small pieces of kidney tissue obtained from rats after kidney allotransplantation. The IL-2 expression decreased tenfold during treatment with an anti-rat CD4 monoclonal antibody as compared to untreated animals.
J Immunol Methods 1994 Dec 28
PMID:A novel multispecific competitor fragment for quantitative PCR analysis of cytokine gene expression in rats. 782 31

Tiazofurin and ribavirin are clinically used inhibitors of IMP dehydrogenase (DH), binding to the NAD and IMP sites, respectively, of the target enzyme. In patients with chronic granulocytic leukemia in blast crisis, daily tiazofurin infusions decreased the high IMP DH activity in blast cells and resulted in 77% response (G. Weber. In: R. A. Harkness et al., Purine and Pyrimidine Metabolism in Man, Vol. VII, Part B, pp. 287-292, 1991). However, patients relapsed in a few weeks with emergence of high IMP DH activity (G. Tricot et al., Int. J. Cell Cloning, 8: 161-170, 1990). The present study showed that the tiazofurin-induced depression of IMP DH activity in rat bone marrow can be maintained by ribavirin injection. Tiazofurin (150 mg/kg, i.p., once a day for 2 days) decreased IMP DH activity to 10% and ribavirin (250 mg/kg, i.p., once a day for the subsequent 3 days) maintained the enzymic activity at 20 to 30% of control values. In control rats where no ribavirin was given, IMP DH activity of the tiazofurin-treated rats rapidly returned to the range of untreated animals. The decrease of IMP DH activity (t1/2 = 2.6 h) sharply preceded that of the bone marrow cellularity (t1/2 = 17.4 h). In addition to the target enzyme, IMP DH, tiazofurin also decreased activities of the guanylate metabolic enzymes, guanine phosphoribosyltransferase and GMP reductase, and the pyrimidine salvage enzymes, deoxycytidine and thymidine kinases with t1/2 of 2.6, 4.7, 6.0, 3.4, and 6.5 h, respectively. In cycloheximide-treated rats, where much of protein biosynthesis was blocked, the t1/2(8) of these five enzymes in bone marrow were shorter, 1.6, 4.3, 3.0, 0.6, and 0.8 h, respectively. Thus, the impact of tiazofurin in the bone marrow entails a decrease in the activity of the target enzyme, IMP DH, and also of other enzymes in purine and pyrimidine biosynthesis as a result of the enzyme half-lives shortened by this drug. These novel observations should assist in achieving better protection and recovery of bone marrow during and after chemotherapy.
Cancer Res 1993 Dec 15
PMID:Sequential impact of tiazofurin and ribavirin on the enzymic program of the bone marrow. 790 99


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