Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.4.2.7 (adenine phosphoribosyltransferase)
 692 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

6-Methylpurine, an analog of adenine, inhibits the growth of Neurospora crassa. From kinetic studies it was found that 6-methylpurine is converted to its nucleotide form by adenine phosphoribosyltransferase (EC 2.4.2.7), and inhibits the de novo purine biosynthesis. Adenine relieves the growth inhibition caused by 6-methylpurine, whereas hypoxanthine is not very effective. Studies dealing with hypoxanthine utilization in the presence of 6-methylpurine indicated a severely reduced uptake of hypoxanthine and a general slowdown in its further metabolism. Two mutants (Mepr-3 and Mepr-10) which are resistant to 6-methylpurine were characterized. Studies of purine base uptake and the in vivo and in vitro conversion to nucleotides indicated that Mepr-10 may be an adenine phosphoribosyltransferase-defective mutant, whereas Mepr-3 may be a mutant with altered feedback response to 6-methylpurine. Both mutants showed a severely lowered hypoxanthine phosphoribosyltransferase activity, but because 6-methylpurine did not have any effect on the conversion of hypoxanthine to IMP in the wild type, it was concluded that 6-methylpurine resistance in these mutants cannot be due to lowered hypoxanthine phosphoribosyltransferase activity, but rather that the lowering of enzyme activity may be a secondary effect.
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PMID:Nature of 6-methylpurine inhibition and characterization of two 6-methylpurine-resistant mutants of Neurospora crassa. 15 98

Adenine aminohydrolase (EC 3.5.4.2) from four species of Leishmania and from Crithidia fasciculata was examined for specific activities, affinity for substrate (adenine), and stability to heat. All were found to be strongly and non-competitively inhibited by both coformycin and deoxycoformycin, two tight-binding inhibitors of adenosine deaminase (adenosine aminohydrolase, EC 3.5.4.4). Deoxycoformycin is the more potent inhibitor of the two. Neither inhibitor was active against the purine phosphoribosyltransferases. When deoxycoformycin was added to the defined growth medium containing hypoxanthine as the purine source, the growth of C. fasciculata was unaffected, but when adenine was the purine source for the organism, severe inhibition resulted. This implies that hypoxanthine is the obligatory base for nucleotide synthesis and that the adenine phosphoribosyltransferase (AMP:pyrophosphate phosphoribosyltransferase, EC 2.4.2.7) is, in some manner,idenied access to exogenous substrate.
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PMID:Adenine aminohydrolase: occurrence and possible significance in trypanosomid flagellates. 29 Oct 31

The metabolic and growth inhibitory effects of adenosine toward the human lymphoblast line WI-L2 were potentiated by the adenosine deaminase inhibitors erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA) and coformycin. EHNA, 5 micron, or coformycin, 3.5 micron, at concentrations that inhibited adenosine deaminase activity more than 90% had little effect on cell growth or the metabolic parameters studied. Adenosine, 50 micron, plus EHNA, 5 micron, arrested cell growth in both parent and adenosine kinase-deficient lymphoblasts, implicating the nucleoside as the mediator of the cytostatic effect. Adenosine, 50 micron, in combination with the adenosine deaminase inhibitors reduced 14CO2 generation from [1-14C]glucose by 38%, depleted 5-phosphoribosyl-1-pyrophosphate by more than 90%, and reduced pyrimidine ribonucleotide concentrations. Uridine, 10 or 100 micron, reversed adenosine plus EHNA growth inhibition in WI-L2 but not in adenosine kinase mutants. Adenine, 500 micron, which may be converted to the same intracellular nucleotides as adenosine, reduced the growth rate by 50% in both parent and adenine phosphoribosyltransferase-deficient lymphoblasts. Although adenine also depleted cells of 5-phosphoribosyl-1-pyrophosphate and reduced pyrimidine ribonucleotide by 50%, the mechanisms of adenine and adenosine toxicity differ. In contrast to the ability of uridine to reverse adenosine cytostasis, growth inhibition by adenine was not reversed by uridine, indicating that pyrimidine ribonucleotide depletion is not the primary mechanisms of adenine toxicity.
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PMID:Cytotoxic and metabolic effects of adenosine and adenine on human lymphoblasts. 66 33

Adenine uptake in cultured Chinese hamster fibroblasts showed biphasic saturation kinetics. The transport system was highly specific for adenine and was competitively inhibited by adenosine. Utilizing mutant clones of Chinese hamster fibroblasts that have either reduced or negligible adenine phosphoribosyltransferase (APRT) activity, we found that (1) adenine was not accumulated against a concentration gradient in the absence of APRT activity and (2) after rapid initial uptake equal to that of the parent the rates of adenine accumulation found for the mutants correlated strongly with their residual APRT activities. Furthermore, using either artificially depressed phosphoribosylpyrophosphate pool size and APRT activities or the mutants with decreased APRT activity, we found that adenine transport was independent of phosphorylation by APRT. These studies suggest that adenine is transported as the free base by facilitated diffusion and is subsequently phosphorylated by APRT.
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PMID:Role of adenine phosphoribosyltransferase in adenine uptake in wild-type and APRT- mutants of CHO. 74 95

We studied the clinical and biochemical manifestations of complete adenine phosphoribosyltransferase deficiency in the kindred of a male homozygous child excreting stones of 2,8-dihydroxyade-nine. Abnormal amounts of adenine, 8-hydroxyade-nine and 2,8-dihydroxyadenine (25 per cent of total purine metabolites) appeared in the urine of the propositus and his clinically normal brother, but not in heterozygotes or a control. Adenine phosphoribosyl-transferase activity in erythrocytes was less than 1 per cent of normal in both homozygotes and varied from 20 to 57 per cent of normal in six heterozygotes. Heterozygotes exhibited neither hyperuricemia nor gout. Treatment of the propositus with allopurinol and a low purine diet stopped stone formation. In addition, excretion of 2,8-dihydroxyadenine decreased. An autosomal recessive mode of inheritance with variable expression in the phenotype is indicated. Homozygotes may be detected by their raised urinary adenine levels or absence of detectable erythrocyte adenine phosphoribosyltransferase activity (or both).
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PMID:Complete deficiency of adenine phosphoribosyltransferase. Report of a family. 86 83

Adenine and adenosine metabolism has been studied in intact human erythrocytes in vitro using high performance liquid chromatography, isotopic labeling and electrophoresis. Their metabolism to nucleotides was controlled by phosphoribose diphosphate synthesis which was phosphate dependent. Adenosine formed hypoxanthine or IMP depending upon Pi concentration, but adenosine kinase and deaminase activities were not affected by P levels. Free [14C]adenine and [14C]hypoxanthine were found in cellular extracts. Rapid interconversions occurred to give a distribution for ATP : ADP : AMP of 10 : 1 : 0.1. Marked decomposition of ATP to ADP and AMP occurred during incubations in plasma and Earle's media in air on nitrogen, but ATP levels remained stable in phosphate buffers and in the presence of oxygen. At physiological Pi (1 mM) adenosine kinase activity grossly exceeded adenine phosphoribosyltransferase activity. The latter was approximately 7 fold that of hypoxanthine phosphoribosyltransferase activity. These differences decreased with increasing Pi levels. No significant increase in corresponding nucleotides was obtained by incubation with high levels (0.5 mM) of adenine, guanine or guanosine at physiological Ii, ATP increased by 10% independently of the substrate employed and significant amounts of IMP and GTP were formed adenosine and guanosine, respectively. The existence of a bound intracellular pool of ATP is suggested.
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PMID:Studies on adenine and adenosine metabolism by intact human erythrocytes using high performance liquid chromatography. 94 98

The characteristics of adenine, guanine, hypoxanthine, xanthine, and uracil uptake in Escherichia coli B show that each base is transported by a specific system. The data support the concept that the transport of guanine, hypoxanthine, xanthine, and uracil function without direct involvement of the respective purine or pyrimidine phosphoribosyltransferase enzymes. Uracil phosphoribosyltransferase is not demonstrable in E. coli B, and large differences are observed in the inhibitory effects of heterologous purines on the uptake of guanine, hypoxanthine, and xanthine as compared to the corresponding inhibitory effects reported for the soluble purine phosphoribosyltransferase enzymes of E. coli B. Additional evidence is provided by the low Km values determined for the transport of adenine, guanine, hypoxanthine, and xanthine relative to the corresponding Km values for the phosphoribosyltransferase enzymes. Data are presented indicating that adenine may be transported without participation of adenine phosphoribosyltransferase. The stimulatory effect of glucose, the inhibitory effect of KCN, and the high intracellular to extracellular concentration gradients of the bases produced in the presence of glucose provide evidence that the transport processes are energy-dependent. The Km values for transport of the purines and uracil range from 10(-7) M to 5 X 10(-7) M. Characteristics of adenine and uracil uptake are similar in E. coli B, E. coli K-12, and a showdomycin-resistant mutant of E. coli B. Adenosine and deoxyadenosine are transported in E. coli B by independent transport systems. Adenine or hypoxanthine does not share the adenosine or deoxyadenosine transport systems as evidence by the mutual lack of competition of free bases and nucleosides on transport. The transport systems for deoxyadenosine and adenosine are defective in the mutant.
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PMID:Transport of purines and deoxyadenosine in Escherichia coli. 110 20

The enzymes that catalyse the salvage of purines in Entamoeba histolytica trophozoites have been surveyed. Adenine deaminase (EC 3.5.4.2), adenosine deaminase (EC 3.5.4.4), guanine deaminase (EC 3.5.4.3), adenine phosphoribosyltransferase (PRTase) (EC 2.4.2.7), xanthine PRTase (EC 2.4.2.22) and hypoxanthine PRTase (EC 2.4.2.8) were all detected in cell homogenates but only at low activities, whereas AMP deaminase (EC 3.5.4.6) and guanine PRTase (EC 2.4.2.8) were not found. Phosphorylases (EC 2.4.2.1) active in both anabolic and catabolic directions were present and all nucleosides tested were phosphorylated by kinases (EC 2.7.1.15, EC 2.7.1.20, EC 2.7.1.73). 3'-Nucleotidase (EC 3.1.3.6) and 5'-nucleotidase (EC 3.1.3.5) were found, the former being mainly particulate. Nucleotide interconversion enzymes (adenylosuccinate lyase, EC 4.3.2.2; adenylosuccinate synthetase, EC 6.3.4.4; IMP dehydrogenase, EC 1.2.1.14; GMP synthetase, EC 6.3.5.2 and GMP reductase, EC 1.6.6.8) were not detected. The results suggest that in E. histolytica the main route of nucleotide synthesis is from the individual bases through the actions of phosphorylases and kinases.
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PMID:Purine-metabolising enzymes in Entamoeba histolytica. 287 91

1. A simple method for diagnosing adenine phosphoribosyltransferase (APRT) deficiency using urine is described. 2. T.l.c. of 1 microliter urine from a child with APRT deficiency was performed and adenine was easily detected by its brilliant blue phosphorescence at liquid nitrogen temperature. 3. Four physicochemical characteristics of adenine were recorded: RF value, and the colour, decay time and pH sensitivity of phosphorescence. 4. Adenine was not detected in the urine of 116 subjects used as controls. These included healthy individuals and patients with inherited metabolic disorders, diseases of purine metabolism and of the kidney and urinary tract. Some of them were taking a variety of drugs including purine derivatives. 5. The test correctly diagnosed three cases of APRT deficiency out of 10 urine samples tested blind.
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PMID:Adenine phosphoribosyltransferase deficiency: a simple diagnostic test. 340 38

Exogenous adenine strongly inhibited mitogen-stimulated transformation, cytoplasmic immunoglobulin production, and natural killer activity of human mononuclear leukocytes at the high concentration of 1.0 mM. These inhibitions by adenine were not due to cytotoxicity, because the viability of cultured cells was not affected by adenine up to 1.0 mM. As the magnitude of inhibition by adenine of these in vitro immunological functions was similar in normal and adenine phosphoribosyltransferase-deficient cells, its inhibition was not mediated by corresponding nucleotides. Adenine at the concentration of 0.1 mM caused 50% inhibition of cytoplasmic immunoglobulin production without alternating cell proliferation or viability. This suggests that an appropriate concentration of adenine may inhibit the differentiation of B cells to plasma cells rather than affecting cell proliferation. Understanding the mechanisms of adenine inhibition may lead to new approaches for the regulation of immune responses.
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PMID:Inhibition by adenine of in vitro immunological functions of normal and adenine phosphoribosyltransferase-deficient human lymphocytes. 383 54


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