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

Bacillus subtilis mutants defective in purine metabolism have been isolated by selecting for resistance to purine analogs. Mutants resistant to 2-fluoroadenine were found to be defective in adenine phosphoribosyltransferase (apt) activity and slightly impaired in adenine uptake. By making use of apt mutants and mutants defective in adenosine phosphorylase activity, it was shown that adenine deamination is an essential step in the conversion of both adenine and adenosine to guanine nucleotides. Mutants resistant to 8-azaguanine, pbuG mutants, appeared to be defective in hypoxanthine and guanine transport and normal in hypoxanthine-guanine phosphoribosyltransferase activity. Purine auxotrophic pbuG mutants grew in a concentration-dependent way on hypoxanthine, while normal growth was observed on inosine as the purine source. Inosine was taken up by a different transport system and utilized after conversion to hypoxanthine. Two mutants resistant to 8-azaxanthine were isolated: one was defective in xanthine phosphoribosyltransferase (xpt) activity and xanthine transport, and another had reduced GMP synthetase activity. The results obtained with the various mutants provide evidence for the existence of specific purine base transport systems. The genetic lesions causing the mutant phenotypes, apt, pbuG, and xpt, have been located on the B. subtilis linkage map at 243, 55, and 198 degrees, respectively.
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PMID:Genetic and physiological characterization of Bacillus subtilis mutants resistant to purine analogs. 311 Jan 31

Lesch-Nyhan syndrome involves disorders of both purine and dopamine metabolism. Neonatal lesioning of dopaminergic neurons with 6-hydroxydopamine (6-OHDA) has been proposed as a rodent model of the dopamine deficiency in this childhood disorder. In the present studies, the functional interaction between purines and dopamine was examined in adult rats which received 6-OHDA lesions either as neonates or as adults. Even though dopamine levels were decreased by at least 92%, both neonatal- and adult-6-OHDA-lesioned rats had normal hypoxanthine-guanine phosphoribosyltransferase function and purine nucleotide levels (adenosine, ADP, ATP and AMP), indicating that hypoxanthine-guanine phosphoribosyltransferase is not localized only to dopaminergic neurons in striatum. However, the 6-OHDA-lesioned animals were supersensitive to the locomotor activating effects of the adenosine antagonist, theophylline, with the response being greater in adult-6-OHDA-lesioned rats. This effect was presynaptic to dopaminergic neurons as indicated by alpha-methyltyrosine blockade of the theophylline response and its reinstatement by L-dopa. The presynaptic nature of this action of theophylline was supported further by a lack of interaction between theophylline and the direct acting D1- and D2-dopamine agonists, SKF-38393 and LY-171555, respectively. After systemic administration of SKF-38393 or L-dopa, central microinjection of the adenosine agonists, 2-chloroadenosine or 5'-N-ethylcarboxamide adenosine, were effective in preventing self mutilation induced by these dopamine agonists in neonatally lesioned rats. Relative potencies of the adenosine agonists for A1 and A2-adenosine receptors suggested involvement of an A2-adenosine receptor in this action.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Assessment of purine-dopamine interactions in 6-hydroxydopamine-lesioned rats: evidence for pre- and postsynaptic influences by adenosine. 312 93

The pathways of adenine nucleotide catabolism were investigated in cultured beating cardiomyocytes. The activity of the enzymes involved in AMP degradation was assayed in cell extracts. Fluxes of label from ATP to the various purine derivatives were measured in intact cells. Under physiological conditions, cells degraded AMP through deamination to IMP. IMP was rapidly degraded to inosine, hypoxanthine, xanthine and uric acid, which were effluxed from the cells. This is in accord with the fact that the activity of AMP deaminase (EC 3.5.4.6) was 7-fold that of AMP 5'-Nucleotidase (EC 3.1.3.5). Mild ATP-degradation, induced by inhibition of glycolysis by iodoacetate, caused no alterations in the degradation pathways (more than 85% through deamination to IMP). However, fast ATP-degradation (83% of adenine nucleotides/10 min), induced by simultaneous inhibition of glycolysis and electron transport (by antimycin A), caused increased dephosphorylation of AMP to adenosine (50% of total AMP-degradation). The cardiomyocyte extracts were found to contain a significant activity of purine nucleoside phosphorylase (EC 2.4.2.1). Despite the presence of hypoxanthine-guanine phosphoribosyltransferase (EC 2.4.2.8), salvage of hypoxanthine to IMP, both at physiological as well as at conditions associated with ATP degradation, was slow. The salvage of adenosine appeared to be efficient at physiological conditions, but not at fast rates of ATP degradation.
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PMID:Pathways of adenine nucleotide catabolism in primary rat cardiomyocyte cultures. 325 63

Spontaneous and ethyl methanesulfate induced mutants of Saccharomyces cerevisiae, with partial and complete deficiency of adenine phosphoribosyltransferase (APRT, EC 2.4.2.7), were isolated by selection for resistance to 8-azaadenine. Matings between totally deficient mutants and tester strain resulted in diploid heterozygotes that were sensitive to azaadenine. Upon sporulation and tetrad analysis, azaadenine resistance (and APRT deficiency) segregated as expected for a single Mendelian gene. Hypoxanthine-guanine phosphoribosyltransferase (EC 2.4.2.8) activity in the mutants was similar to that in the wild-type cells. There was no detectable activity of adenine aminohydrolase (EC 3.5.4.2) in the wild-type or mutant cells.
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PMID:Mutants of Saccharomyces cerevisiae deficient in adenine phosphoribosyltransferase. 330 56

WI-L2 B lymphoblasts deficient in hypoxanthine-guanine phosphoribosyltransferase (HGPRT) excreted amounts of hypoxanthine two to three times larger than CEM T lymphoblasts deficient in HGPRT, despite similar growth rates. ATP consumption occurred at a higher rate in WI-L2 cells than in CEM cells when cultivated in a glucose-free buffer, because of higher RNA synthesis in WI-L2 cells. The introduction of actinomycin D and azaserine resulted in lower hypoxanthine excretion in WI-L2 cells than in CEM cells, not in parallel with changes of the adenylate pool size. When the energy charge was high, de novo purine synthesis was a major determinant for purine excretion. The adenylate pool ratio (AMP/ATP) change caused by the introduction of oligomycin was greater during ATP depletion and recovery in WI-L2 cells than in CEM cells. WI-L2 cells were observed to have AMP deaminase activity three to four times higher than CEM cells. The major component of AMP deaminase in these cells was liver type. The higher rate of RNA synthesis caused greater changes of (AMP/ATP) and required higher AMP deaminase activity for recovery. When the energy charge was low, AMP deaminase was a major determinant for purine excretion.
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PMID:Major determinants of purine excretion from human lymphoblasts. 343 82

A screening method using high-performance liquid chromatography (HPLC) for the simultaneous detection of deficiencies of adenine phosphoribosyltransferase (APRT) and hypoxanthine phosphoribosyltransferase (HPRT) activities in human erythrocytes is described. Both enzyme reactions of APRT and HPRT in lysates treated with a charcoal-dextran were simultaneously carried out in the same reaction tube and the enzyme activities were determined by measuring the increases in absorbance at 260 nm of adenosine and inosine converted from adenosine-5'-monophosphate and inosine-5'-monophosphate with alkaline phosphatase. Adenosine and inosine were separated from adenine and hypoxanthine by a reversed-phase column. The method could detect 1% of normal APRT activity and 0.3% of normal HPRT activity. The within-run coefficients of variation for APRT and HPRT activities were 3.2 and 3.4%, respectively.
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PMID:Screening for adenine and hypoxanthine phosphoribosyltransferase deficiencies in human erythrocytes by high-performance liquid chromatography. 343 62

Studies with purified enzymes have shown that 2'-deoxycoformycin (dCF) is a potent and selective inhibitor of adenosine deaminase (ADA). Specificity of dCF's effects on adenosine metabolism in intact human skin fibroblasts was investigated by examining the isotopic flux from exogenous [14C] adenosine to metabolic products in hypoxanthine phosphoribosyltransferase deficient (HPRT-) cells which cannot recycle hypoxanthine. Apparent ADA activity (as estimated by isotopic flux to inosine and hypoxanthine) was profoundly inhibited by dCF (with at least 50% inhibition at 10(-8) M and 95% inhibition at 10(-5) M dCF). The degree of inhibition was similar at various exogenous adenosine concentrations ranging from 1 to 400 microM. Some inhibition of isotopic flux to adenine nucleotides (an ADA independent process in HPRT- cells) could be demonstrated, but only in media containing high concentrations of adenosine. Even at 400 microM adenosine, the highest concentration employed, isotopic flux to adenine nucleotides was unaffected by concentrations of dCF below 10(-6) M, and only 30% inhibition was achieved with 10(-5) M dCF. Inhibition of adenosine phosphorylation to AMP appears to be the most likely explanation for dCF inhibition of isotopic flux from [14C] adenosine to adenine nucleotides, probably due to substrate inhibition of adenosine kinase by high levels of intracellular adenosine produced when ADA is inhibited by dCF. No evidence for dCF inhibition of either adenosine transport or phosphorylations within the adenine nucleotide pool (from AMP to ADP or from ADP to ATP) was found. Thus, at physiological levels of exogenous adenosine (0.03 to 2.6 microM), dCF appears to be a potent and highly specific inhibitor of ADA in human skin fibroblasts.
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PMID:Specificity of 2'-deoxycoformycin inhibition of adenosine metabolism in intact human skin fibroblasts. 348 39

Cells with and without hypoxanthine-guanine phosphoribosyltransferase (HGPRT) activity were used to examine the transfer of purine metabolites through the medium and via cell contacts. HGPRT- Chinese hamster and human fibroblasts were able to incorporate 3H-labeled purine metabolite(s) from medium in which mouse HGPRT+ B82 cells had been grown for 24 h with [3H]hypoxanthine, but mouse A9 fibroblasts that were deficient in HGPRT, adenine phosphoribosyltransferase (APRT), and methylthioadenosine phosphorylase (MTAP) were unable to incorporate these metabolites. This suggests that in recipient cells incorporation is due to [3H]MTA, which has been shown previously to be the major 3H-labeled purine metabolite to accumulate in B82 medium, being cleaved by MTAP to [3H]adenine, which is phosphoribosylated by APRT to [3H]AMP. Incorporation by recipient cells of metabolites from the medium is referred to as contact-independent metabolite transfer (CIMT). In autoradiograms of B82/A9 cocultures that were labeled with [3H]hypoxanthine, grains were found over A9 that were not in contact with B82, although A9 did not act as recipients of CIMT. This is termed proximity-dependent metabolite transfer (PDMT). Both CIMT and PDMT interfered with the assessment of nucleotide exchange between HGPRT+ and HGPRT- cells through cell contacts, which is referred to as contact-dependent metabolite transfer (CDMT). These problems were unique to HGPRT+ mouse L cells. However, HGPRT- mouse L cells, A9, could be used as potential recipients. A9 were positive recipients of CDMT with only one of five cell lines tested, which suggested that these cells were selective communicators. CDMT could not be studied with [3H]guanine because the nuclei of HGPRT- cells became labeled.
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PMID:Transfer of purine metabolites between cells through the medium and via cell contacts in cocultures of HGPRT+ and HGPRT- cells. 367 80

Mutant promastigotes of Leishmania donovani deficient in adenine phosphoribosyltransferase (APRTase) have been isolated in medium containing 4-aminopyrazolopyrimidine. The generation of APRTase-deficient mutants occurred in two discrete steps. In the first step, clones were isolated with 50% of wildtype levels of APRTase activity. These cells were reselected and colonies totally deficient in APRTase were isolated. Partially and totally APRTase-deficient cells exhibited intermediate and complete resistance to cytotoxic adenine analogs, respectively. Nevertheless, wildtype and mutant cells could salvage adenine and utilize adenine as a purine source equally efficiently, suggesting that the adenine deaminase-HGPRTase pathway plays an important role in promastigote adenine metabolism. Kinetic and thermal inactivation studies of purified APRTase and isoelectric focusing of crude extracts from wildtype and partially APRTase-deficient cells suggested that the latter cells possessed wildtype APRTase activity at half the amount found in wildtype parental cells. These data suggest that Leishmania donovani possess two copies of the APRTase structural gene and that these organisms might be diploid for the APRTase locus.
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PMID:Adenine phosphoribosyltransferase-deficient Leishmania donovani. 376 43

Simple methods for the detection of hypoxanthine-guanine phosphoribosyltransferase and/or adenine phosphoribosyltransferase deficiencies using dried filter paper blood spots were studied. Enzyme activities in the eluate from dried filter paper blood spots stored for 4 weeks at room conditions were shown to be quite stable. Autoradiographs prepared from dried filter paper blood spots and DE-81 papers soaked with enzyme reaction mixtures containing 14C-hypoxanthine and/or 14C-adenine showed sharp radioactive spots in normal subjects. No activity was evident in the cases of the Lesch-Nyhan syndrome and/or adenine phosphoribosyltransferase deficiency. The methods seem to be suitable for screening.
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PMID:Simple screening methods for hypoxanthine-guanine phosphoribosyltransferase and adenine phosphoribosyltransferase deficiencies using dried blood spots on filter paper. 376 88


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