• Title/Summary/Keyword: nucleotide metabolism

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The Association between Gut Microbiota and Its Metabolites in Gestational Diabetes Mellitus

  • Hua Lin;Changxi Liao;Rujing Zhang
    • Journal of Microbiology and Biotechnology
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    • v.34 no.10
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    • pp.1995-2004
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    • 2024
  • Gut microbial metabolites have been demonstrated to play a role in diabetes mellitus and gestational diabetes mellitus (GDM). This study aimed to investigate gut microbiome, fecal metabolomics, and their association in pregnant women with and without GDM. The metabolome indicated that the top 2 differential metabolic pathways between control (Con) and GDM groups were phenylalanine metabolism and nucleotide metabolism. The increased Phenylalanylglycine, m-coumaric acid, and Phenylacetic acid were among the top differential metabolites between Con and GDM groups and involved in phenylalanine metabolism. Uracil and hypoxanthine were top differential metabolites in Con vs. GDM and involved in nucleotide metabolism. The proficiently altered gut microbiota at the class level was c_unclassified_ Firmicutes. Association analysis between gut microbiota and fecal metabolites indicated that the increased gut symbiont Clostridium belonged to Firmicutes and was linked to the dysregulation of phenylalanine metabolism in GDM. This study may provide the mechanism underlying how Clostridium-phenylalanine metabolism association contributes to GDM pathogenesis and also be a novel therapeutic strategy to treat GDM.

Improving Mycoplasma ovipneumoniae culture medium by a comparative transcriptome method

  • Wang, Xiaohui;Zhang, Wenguang;Hao, Yongqing
    • Journal of Veterinary Science
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    • v.21 no.2
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    • pp.30.1-30.11
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    • 2020
  • Mycoplasma ovipneumoniae (Mo) is difficult to culture, resulting in many difficulties in related research and application. Since nucleotide metabolism is a basic metabolism affects growth, this study conducted a "point-to-point" comparison of the corresponding growth phases between the Mo NM151 strain and the Mycoplasma mycoides subsp. capri (Mmc) PG3 strain. The results showed that the largest difference in nucleotide metabolism was found in the stationary phase. Nucleotide synthesis in PG3 was mostly de novo, while nucleotide synthesis in NM151 was primarily based on salvage synthesis. Compared with PG3, the missing reactions of NM151 referred to the synthesis of deoxythymine monophosphate. We proposed and validated a culture medium with added serine to fill this gap and prolong the stationary phase of NM151. This solved the problem of the fast death of Mo, which is significant for related research and application.

Construction and Expression of Mutant cDNAs Responsible for Genetic Polymorphism in Aldehyde Oxidase in Donryu Strain Rats

  • Adachi, Mayuko;Itoh, Kunio;Masubuchi, Akiko;Watanabe, Nobuaki;Tanaka, Yorihisa
    • BMB Reports
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    • v.40 no.6
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    • pp.1021-1027
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    • 2007
  • We demonstrated the genetic polymorphism of aldehyde oxidase (AO) in Donryu strain rats: the ultrarapid metabolizer (UM) with nucleotide mutation of (377G, 2604C) coding for amino acid substitution of (110Gly, 852Val), extensive metabolizer (EM) with (377G/A, 2604C/T) coding for (110Gly/Ser, 852Val/Ala), and poor metabolizer (PM) with (377A, 2604T) coding for (110Ser, 852Ala), respectively. The results suggested that 377G > A and/or 2604C > T should be responsible for the genetic polymorphism. In this study, we constructed an E. coli expression system of four types of AO cDNA including Mut-1 with (377G, 2604T) and Mut-2 with (377A, 2604C) as well as naturally existing nucleotide sequences of UM and PM in order to clarify which one is responsible for the polymorphism. Mut-1 and Mut-2 showed almost the same high and low activity as that of the UM and PM groups, respectively. Thus, the expression study of mutant AO cDNA directly revealed that the nucleotide substitution of 377G > A, but not that of 2604C > T, will play a critical role in the genetic polymorphism of AO in Donryu strain rats. The reason amino acid substitution will cause genetic polymorphism in AO activity was discussed.

Physio-biochemical changes correlated with cadmium adaptation and detoxification mechanism in klebsiella aerogenes (Klebsiella aerogenes의 카드뮴 적응 및 해독기작에 관련된 생리생화학적인 변화)

  • 이기성;송인극;박영식;윤성녀;최영길
    • Korean Journal of Microbiology
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    • v.28 no.3
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    • pp.249-257
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    • 1990
  • In the course of operating the accommodative and detoxifying mechanism against cadmium, its physio-biochemical changes were observed in Klebsiella aerogenes ATCC 10031. Changes of enzyme activity concerned phosphate metabolism, changes of phospholipid composition and in view of energy metabolism the changes of the nucleotide pool were examined. Activities of both alkaline and acid phosphatase were derepressed 4-10 folds under cadmium added cultures. Moreover, production of phospholipid such as lysophosphatidyl choline (LPC), phosphatidyl serine (PS) and phosphatidyl ethanolamone (PE) was increased and uridylate nucleotide pool was increased under Cd-surplus culture. These results i.e. overproduction of phosphatase catalyzing phosphate residue, increase of the production of PE and PS which have a close affinity with cadmium, and indrease of uridylate nucleotide pool used as a carrier of polysaccharide synthesis like bacterial capsule exhibited cellular responses for active defence against Cd-pressure. It was postulated that these phenomena should play another assistant roles in Cd-detoxifing mechanism.

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카드뮴이 카드뮴 내성 효모세포내의 효소 활성에 미치는 영향

  • 유대식;박은규;박정문
    • Microbiology and Biotechnology Letters
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    • v.24 no.3
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    • pp.268-273
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    • 1996
  • An extremely cadmium tolerant yeast, Hansenula anomala B-7 used to determine the modification of the intracellular enzyme activities by cadmium ion. The activities of alcohol dehydrogenase, phosphofructokinase, and cytidine deaminase were decreased up to 90%, 40%, and 86% compa- red with the control by 1 mM cadmium nitrate respectively, but the activities of malate dehydrogenase, 6- phosphogluconate dehydrogenase, cytochrome c oxidase, and alkaline phosphatase were increased up to 440%, 136%, 260% and 155% compared with the control by 1 mM cadmium nitrate respectively. These results show that the activities of the enzymes participating in Embden-Mayerhof pathway (e.g. anaerobic metabolism) were reduced by cadmium, but those involved in hexose monophosphate pathway and tricarboxylic acid cycle (e.g. aerobic metabolism) were stimulated in contrast. It has been suggested that the diminished activity of cytidine deaminase in pyrimidine nucleotide dissimilation occured due to the inhibited nucleotide dissimilation by cadmium ion; the enhanced activity of cytochrome c oxidase was specifically required in order to oxidize a raised amount of NADH and NADPH due to the increased aerobic metabolism.

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Role of MicroRNAs in the Warburg Effect and Mitochondrial Metabolism in Cancer

  • Jin, Li-Hui;Wei, Chen
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.17
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    • pp.7015-7019
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    • 2014
  • Metabolism lies at the heart of cell biology. The metabolism of cancer cells is significantly different from that of their normal counterparts during tumorigenesis and progression. Elevated glucose metabolism is one of the hallmarks of cancer cells, even under aerobic conditions. The Warburg effect not only allows cancer cells to meet their high energy demands and supply biological materials for anabolic processes including nucleotide and lipid synthesis, but it also minimizes reactive oxygen species production in mitochondria, thereby providing a growth advantage for tumors. Indeed, the mitochondria also play a more essential role in tumor development. As information about the numorous microRNAs has emerged, the importance of metabolic phenotypes mediated by microRNAs in cancer is being increasingly emphasized. However, the consequences of dysregulation of Warburg effect and mitochondrial metabolism modulated by microRNAs in tumor initiation and progression are still largely unclear.

Cancer Metabolism: Fueling More than Just Growth

  • Lee, Namgyu;Kim, Dohoon
    • Molecules and Cells
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    • v.39 no.12
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    • pp.847-854
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    • 2016
  • The early landmark discoveries in cancer metabolism research have uncovered metabolic processes that support rapid proliferation, such as aerobic glycolysis (Warburg effect), glutaminolysis, and increased nucleotide biosynthesis. However, there are limitations to the effectiveness of specifically targeting the metabolic processes which support rapid proliferation. First, as other normal proliferative tissues also share similar metabolic features, they may also be affected by such treatments. Secondly, targeting proliferative metabolism may only target the highly proliferating "bulk tumor" cells and not the slowergrowing, clinically relevant cancer stem cell subpopulations which may be required for an effective cure. An emerging body of research indicates that altered metabolism plays key roles in supporting proliferation-independent functions of cancer such as cell survival within the ischemic and acidic tumor microenvironment, immune system evasion, and maintenance of the cancer stem cell state. As these aspects of cancer cell metabolism are critical for tumor maintenance yet are less likely to be relevant in normal cells, they represent attractive targets for cancer therapy.

Deregulation of Aspartokinase by Single Nucleotide Exchange Leads to Global Flux Rearrangement in the Central Metabolism of Corynebacterium glutamicum

  • Kim Hyung-Min;Heinzle Elmar;Wittmann Christoph
    • Journal of Microbiology and Biotechnology
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    • v.16 no.8
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    • pp.1174-1179
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    • 2006
  • The wild-type Corynebacterium glutamicum ATIC 13032 and Corynebacterium glutamicum ATTC 13032 lysC S301Y, exhibiting a deregulated aspartokinase, were compared concerning growth, lysine production, and intracellular carbon fluxes. Both strains differ by only one single nucleotide over the whole genome. In comparison to the wild-type, the mutant showed significant production of lysine with a molar yield of 0.087 mol (mol glucose$^{-1}$) whereas the biomass yield was reduced. The deregulation of aspartokinase further led to a global rearrangement of carbon flux throughout the whole central metabolism. This involved an increased flux through the pentose phosphate pathway (PPP) and an increased flux through anaplerosis. Because of this, the mutant revealed an enhanced supply of NADPH and oxaloacetate required for lysine biosynthesis. Additionally, the lumped flux through phosphoenolpyruvate carboxykinase and malic enzyme, withdrawing oxaloacetate back to the glycolysis and therefore detrimental for lysine production, was increased. The reason for this might be a contribution of malic enzyme to NADPH supply in the mutant in the mutant. The observed complex changes are remarkable, because they are due to the minimum genetic modification possible, the exchange of only one single nucleotide.

Characterisation of multiple substrate-specific (d)ITP/(d)XTPase and modelling of deaminated purine nucleotide metabolism

  • Davies, Oluwafemi;Mendes, Pedro;Smallbone, Kieran;Malys, Naglis
    • BMB Reports
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    • v.45 no.4
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    • pp.259-264
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    • 2012
  • Accumulation of modified nucleotides is defective to various cellular processes, especially those involving DNA and RNA. To be viable, organisms possess a number of (deoxy)nucleotide phosphohydrolases, which hydrolyze these nucleotides removing them from the active NTP and dNTP pools. Deamination of purine bases can result in accumulation of such nucleotides as ITP, dITP, XTP and dXTP. E. coli RdgB has been characterised as a deoxyribonucleoside triphosphate pyrophosphohydrolase that can act on these nucleotides. S. cerevisiae homologue encoded by YJR069C was purified and its (d)NTPase activity was assayed using fifteen nucleotide substrates. ITP, dITP, and XTP were identified as major substrates and kinetic parameters measured. Inhibition by ATP, dATP and GTP were established. On the basis of experimental and published data, modelling and simulation of ITP, dITP, XTP and dXTP metabolism was performed. (d)ITP/(d)XTPase is a new example of enzyme with multiple substrate-specificity demonstrating that multispecificity is not a rare phenomenon