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Showing 1 to 20 of 21 for “"Purine biosynthesis"”.
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A Comparison of Functionally Divergent Forms of the Purine Biosynthesis Enzyme PurE.
Purines are the basic building block for essential biomolecules such as DNA, RNA, NADH, CoA, and several essential vitamin cofactors. Most organisms have the ability to synthesize purines through the de novo purine biosynthesis pathway.
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Mechanistic studies on de novo purine biosynthesis : probing for intermediates of AIR synthetase, FGAR amidotransferase and AIR carboxylase
Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 1994.
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Channeling in purine biosynthesis : efforts to detect interactions between PurF and PurD and characterization of the FGAR-AT complex
Purine biosynthesis has been used as a paradigm for the study of metabolism of unstable molecules. Both phosphoribosylamine (PRA) and N5-carboxyaminoimidazole ribonucleotide (N5-CAIR) have estimated half-lives in vivo of seconds. In order to avoid metabolite decomposition, one strategy cells could …
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Screening for purine transporters in S. aureus
… pathogenesis depends on its ability to acquire purines to cause disease. In this study, I screened a library of individual mutants under purine import-dependent conditions by inhibiting the purine biosynthesis using the pharmacological agents methotrexate and 6-mercaptopurine and supplementing …
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Metabolomics of Mammalian and Cellular Models of Aging
… consistent with increases in healthspan.</p> <p>Purines are molecules essential for many cell processes, including RNA and DNA synthesis, regulation of enzyme activity, protein synthesis and function, energy metabolism and transfer, essential coenzyme function, and cell signaling. Purines are …
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Characterization of Vancomycin Resistance in Staphylococcus Aureus
… First, a potential link between up-regulated purine biosynthesis and increased vancomycin resistance due to a thickened cell wall was examined. Despite exploration of multiple mechanisms to increase purine levels within the cell, increased purine synthesis did not provide S. aureus with any …
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Glutamine Antagonism and Its Utlity [sic] as a Therapeutic Modality in Cancer
… inhibit glutamine-derived nitrogen labeling in purines but unexpectedly does not limit the contribution of glutamine-derived carbon labeling of tricarboxylic acid (TCA) cycle metabolites. Additionally, I found that DON and JHU-083 can limit the levels of purines but not the levels of most TCA …
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Stimulation of adenylosuccinate synthetase by thyroid hormones
The effect of thyroid hormones on purine biosynthesis was studied in vitro. With 100,000 x g supernatant fraction of rat liver homogenate, the results suggested that thyroid hormones stimulated total purine synthesis from labeled glycine-1-¹⁴C. Further studies indicated that these hormones …
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Nutrient and Stress-Induced Mitochondrial Hyperfusion Regulates Cell Death Pathways
… reprogramming that upregulated nucleotide biosynthesis pathways, independent of mTORC1. Additionally, we found the loss of fumarate hydratase prevented amino acid induced mitochondrial hyperfusion, which suggested that amino acid metabolism via the TCA cycle mediates the mitochondrial …
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GCN2 eIF2 Kinase Promotes Prostate Cancer by Maintaining Amino Acid Homeostasis
… and reduced proliferation in PCa. We identified purine biosynthesis as a key metabolic pathway dependent on GCN2. Inhibition of GCN2 and the accompanying depletion of AAs decreases purine levels in PCa cells, ultimately resulting in reduced ribosome biogenesis leading to the activation of a …
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Synthesis of novel 5-substituted pyrrolo[2,3-d]pyrimidine antifolates as selective and potent anti-tumor agents
… of GARFTase dependent salvage pathway for purine biosynthesis inside the tumor. Based on this premise, five 5-substituted pyrrolo[2,3-<em>d</em>]pyrimidines have been designed, synthesized and characterized. Among them four are novel compounds and one is a previously reported compound. The …
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Understanding the intrinsic antibiotic resistance in Lysobacter enzymogenes, a ubiquitous environmental bacterium
… as well as related to cell-wall recycling and purine biosynthesis. Third, we demonstrated that the post-transcriptional regulator CsrA not only conferred MDR, but also contributed to biocontrol activity in LeC3. Furthermore, two putative small regulatory RNAs (sRNAs), referred to as csrB and …
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Studies in the Folate Metabolism of Rats
… It was concluded that methotrexate inhibits purine biosynthesis by interfering with the steps involving formylfolate. This inhibitory action of methotrexate is in addition to the inhibition of dihydrofolate reductase. In view of this, the effects of 6-mercaptopurine, a classical purine …
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The proton-coupled folate transporter: biology and therapeutic applications to cancer
… and survival required for nucleotide biosynthesis and amino acid metabolism. In cancer therapy, inhibition of folate-dependent metabolic pathways has been achieved through the use of antifolates. Unfortunately, the efficacy of many clinically approved antifolates is limited by a lack …
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Target regulation and prioritization by the small RNA SgrS in Escherichia coli
… GTP cyclohydrolase I and a repressor of purine biosynthesis, respectively. SgrS represses translation of each of the four target mRNAs via distinct mechanisms. SgrS binding sites overlapping the Shine-Dalgarno sequences of adiY and folE mRNAs suggest that SgrS pairing with these targets …
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Enzymology And Medicinal Chemistry Of N5-Carboxyaminoimidazole Ribonucleotide Synthetase : A Novel Antibacterial Target
… synthetase), a key enzyme in microbial de novo purine biosynthesis, catalyzes the conversion of aminoimidazole ribonucleotide (AIR) to N5-CAIR. To date, this enzyme has been observed only in microorganisms, and thus, it represents an ideal target for antimicrobial drug development. Here we …
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Design and Synthesis of Pyrimidine Based Fused Heterocyclics in the Potential Treatment of Cancer and Opportunistic Infection
… folate cofactor for DNA, RNA, and methionine biosynthesis. Hence, selectively inhibiting pjDHFR is an important strategy for effective treatment of infection by the pathogen. Structure-based design, using pjDHFR homology model and through the identification of amino acid differences between …
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Monitoring lactococcal phages during milk fermentation
… of the purR gene, a core gene encoding a purine biosynthesis repressor. Interestingly, this approach resulted not only in differentiation of the subspecies but also in differentiation of the biovariant diacetylactis. Subsequent sequencing of the soft-core epsD gene of these isolates …
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Target Based Design and Synthesis of Fused Pyrimidines in the Potential Treatment of Cancer and Opportunistic Infection
… targets to inhibit <em>de novo</em> purine biosynthesis. Synthetic efforts for the development of pyrrolo[3,2-<em>d</em>]pyrimidines with different linkers and aryl substitutions have been discussed.</p>
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