The Experts below are selected from a list of 33 Experts worldwide ranked by ideXlab platform
Mitsuo Itakura - One of the best experts on this subject based on the ideXlab platform.
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Increased rate of purine biosynthesis in rat liver after bilateral adrenalectomy
2016Co-Authors: Mitsuo Itakura, Noriaki Maeda, Kamejiro YamashitaAbstract:MASHITA. Increased rate of purine biosynthesis in rat liver after bilateral adrenalectorny. Am. J. Physiol. 251 (Endocrinol. Me-tab. 14): E373-E378,1986.-In bilaterally adrenalectomized rat liver the increased rate of de novo purine synthesis was shown by the increased [ 14C]glycine incorporation into hepatic acid-soluble purines with unchanged rapidly miscible glycine pool size and its turnover rate and by the increased rate of chasing of radiolabeled purines. At 24 h after adrenalectomy, the rate of de novo purine synthesis increased by 70%, Sphosphoribo-syl- 1-pyrophosphate (PRPP) content increased by 200%, the specific activity of Amidophosphoribosyltransferase (EC 2.4.2. 14; ATase) did not change, ATP and GTP showed a 33 and 24 % decrease, and AMP and ADP showed a 245 and 38% increase. Combined, the metabolic pool size data reflected an unchanged total inhibitory potential on ATase. Replacemen
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feedback inhibition of Amidophosphoribosyltransferase regulates the rate of cell growth via purine nucleotide dna and protein syntheses
Journal of Biological Chemistry, 2001Co-Authors: Takashi Yamaoka, Makiko Yano, Maki Kondo, Hidemi Sasaki, Satoshi Hino, Rumi Katashima, Maki Moritani, Mitsuo ItakuraAbstract:Next Section Abstract To clarify the contributions of Amidophosphoribosyltransferase (ATase) and its feedback regulation to the rates of purine de novo synthesis, DNA synthesis, protein synthesis, and cell growth, mutated human ATase (mhATase) resistant to feedback inhibition by purine ribonucleotides was engineered by site-directed mutagenesis and expressed in CHO ade−A cells (an ATase-deficient cell line of Chinese hamster ovary fibroblasts) and in transgenic mice (mhATase-Tg mice). In Chinese hamster ovary transfectants with mhATase, the following parameters were examined: ATase activity and its subunit structure, the metabolic rates of de novo and salvage pathways, DNA and protein synthesis rates, and the rate of cell growth. In mhATase-Tg mice, ATase activity in the liver and spleen, the metabolic rate of the de novopathway in the liver, serum uric acid concentration, urinary excretion of purine derivatives, and T lymphocyte proliferation by phytohemagglutinin were examined. We concluded the following. 1) ATase and its feedback inhibition regulate not only the rate of purinede novo synthesis but also DNA and protein synthesis rates and the rate of cell growth in cultured fibroblasts. 2) Suppression of the de novo pathway by the salvage pathway is mainly due to the feedback inhibition of ATase by purine ribonucleotides produced via the salvage pathway, whereas the suppression of the salvage pathway by the de novo pathway is due to consumption of 5-phosphoribosyl 1-pyrophosphate by the de novo pathway. 3) The feedback inhibition of ATase is more important for the regulation of the de novo pathway than that of 5-phosphoribosyl 1-pyrophosphate synthetase. 4) ATase superactivity leads to hyperuricemia and an increased bromodeoxyuridine incorporation in T lymphocytes stimulated by phytohemagglutinin.
Denise V Clark - One of the best experts on this subject based on the ideXlab platform.
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the prat purine synthesis gene duplication in drosophila melanogaster and drosophila virilis is associated with a retrotransposition event and diversification of expression patterns
Journal of Molecular Evolution, 2003Co-Authors: Nicolas Malmanche, Dennis Drapeau, Patrick Cafferty, Denise V ClarkAbstract:Abstract The Drosophila melanogaster Prat gene encodes Amidophosphoribosyltransferase (PRAT; EC 2.4.2.14), which performs the first step in de novo purine nucleotide synthesis. Prat mutations have a recessive lethal phenotype that is found for other genes encoding enzymes in this pathway. The D. melanogaster genome project has revealed a second gene, CG10078 or Prat2, encoding a protein with 76% amino acid sequence identity with Prat. The two genes map to different arms of chromosome 3 and have different intron/exon organizations, as we confirmed by cDNA sequence analysis of Prat2. With the goal to determine the functional significance of this gene duplication, we isolated and sequenced two PRAT-encoding genes from Drosophila virilis. We find that the two D. virilis genes are orthologous to the two D. melanogaster genes in terms of intron/exon organization, amino acid coding sequence, and 5′ noncoding sequence. The absence of introns in both DmelPrat and DvirPrat genes suggests that Prat originated from a retrotransposition of Prat2 and that the gene duplication has been preserved in the two species since their divergence approximately 40 million years ago. Analysis of mRNA expression in development shows that maternal expression, detected in adult ovaries and embryos prior to the onset of zygotic transcription, is present for Prat but not Prat2 in both species. Taken together, these findings support the notion that two PRAT-encoding genes have evolved distinct functions in both Drosophila species.
Nicolas Malmanche - One of the best experts on this subject based on the ideXlab platform.
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the prat purine synthesis gene duplication in drosophila melanogaster and drosophila virilis is associated with a retrotransposition event and diversification of expression patterns
Journal of Molecular Evolution, 2003Co-Authors: Nicolas Malmanche, Dennis Drapeau, Patrick Cafferty, Denise V ClarkAbstract:Abstract The Drosophila melanogaster Prat gene encodes Amidophosphoribosyltransferase (PRAT; EC 2.4.2.14), which performs the first step in de novo purine nucleotide synthesis. Prat mutations have a recessive lethal phenotype that is found for other genes encoding enzymes in this pathway. The D. melanogaster genome project has revealed a second gene, CG10078 or Prat2, encoding a protein with 76% amino acid sequence identity with Prat. The two genes map to different arms of chromosome 3 and have different intron/exon organizations, as we confirmed by cDNA sequence analysis of Prat2. With the goal to determine the functional significance of this gene duplication, we isolated and sequenced two PRAT-encoding genes from Drosophila virilis. We find that the two D. virilis genes are orthologous to the two D. melanogaster genes in terms of intron/exon organization, amino acid coding sequence, and 5′ noncoding sequence. The absence of introns in both DmelPrat and DvirPrat genes suggests that Prat originated from a retrotransposition of Prat2 and that the gene duplication has been preserved in the two species since their divergence approximately 40 million years ago. Analysis of mRNA expression in development shows that maternal expression, detected in adult ovaries and embryos prior to the onset of zygotic transcription, is present for Prat but not Prat2 in both species. Taken together, these findings support the notion that two PRAT-encoding genes have evolved distinct functions in both Drosophila species.
Ronald R Breaker - One of the best experts on this subject based on the ideXlab platform.
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a rare bacterial rna motif is implicated in the regulation of the purf gene whose encoded enzyme synthesizes phosphoribosylamine
RNA, 2020Co-Authors: Sarah N Malkowski, Ruben M Atilho, Etienne B Greenlee, Christina E Weinberg, Ronald R BreakerAbstract:The Fibro-purF motif is a putative structured noncoding RNA domain that was discovered previously in species of Fibrobacter by using comparative sequence analysis methods. An updated bioinformatics search yielded a total of only 30 unique-sequence representatives, exclusively found upstream of the purF gene that codes for the enzyme Amidophosphoribosyltransferase. This enzyme synthesizes the compound 5-phospho-D-ribosylamine (PRA), which is the first committed step in purine biosynthesis. The consensus model for Fibro-purF motif RNAs includes a predicted three-stem junction that carries numerous conserved nucleotide positions within the regions joining the stems. This architecture appears to be of sufficient size and complexity for the formation of the ligand-binding aptamer portion of a riboswitch. In this study, we conducted biochemical analyses of a representative Fibro-purF motif RNA to confirm that the RNA generally folds according to the predicted consensus model. However, due to the instability of PRA, binding of this ligand candidate by the RNA could not be directly assessed. Genetic analyses were used to demonstrate that Fibro-purF motif RNAs regulate gene expression in accordance with predicted PRA concentrations. These findings indicate that Fibro-purF motif RNAs are genetic regulation elements that likely suppress PRA biosynthesis when sufficient levels of this purine precursor are present.
Takashi Yamaoka - One of the best experts on this subject based on the ideXlab platform.
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feedback inhibition of Amidophosphoribosyltransferase regulates the rate of cell growth via purine nucleotide dna and protein syntheses
Journal of Biological Chemistry, 2001Co-Authors: Takashi Yamaoka, Makiko Yano, Maki Kondo, Hidemi Sasaki, Satoshi Hino, Rumi Katashima, Maki Moritani, Mitsuo ItakuraAbstract:Next Section Abstract To clarify the contributions of Amidophosphoribosyltransferase (ATase) and its feedback regulation to the rates of purine de novo synthesis, DNA synthesis, protein synthesis, and cell growth, mutated human ATase (mhATase) resistant to feedback inhibition by purine ribonucleotides was engineered by site-directed mutagenesis and expressed in CHO ade−A cells (an ATase-deficient cell line of Chinese hamster ovary fibroblasts) and in transgenic mice (mhATase-Tg mice). In Chinese hamster ovary transfectants with mhATase, the following parameters were examined: ATase activity and its subunit structure, the metabolic rates of de novo and salvage pathways, DNA and protein synthesis rates, and the rate of cell growth. In mhATase-Tg mice, ATase activity in the liver and spleen, the metabolic rate of the de novopathway in the liver, serum uric acid concentration, urinary excretion of purine derivatives, and T lymphocyte proliferation by phytohemagglutinin were examined. We concluded the following. 1) ATase and its feedback inhibition regulate not only the rate of purinede novo synthesis but also DNA and protein synthesis rates and the rate of cell growth in cultured fibroblasts. 2) Suppression of the de novo pathway by the salvage pathway is mainly due to the feedback inhibition of ATase by purine ribonucleotides produced via the salvage pathway, whereas the suppression of the salvage pathway by the de novo pathway is due to consumption of 5-phosphoribosyl 1-pyrophosphate by the de novo pathway. 3) The feedback inhibition of ATase is more important for the regulation of the de novo pathway than that of 5-phosphoribosyl 1-pyrophosphate synthetase. 4) ATase superactivity leads to hyperuricemia and an increased bromodeoxyuridine incorporation in T lymphocytes stimulated by phytohemagglutinin.