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Metabolites 53건

  1. [해외논문]   Perturbations of Lipid Metabolism Indexed by Lipidomic Biomarkers  

    Lamaziere, Antonin (INSERM U1057, Faculte de Medicine, “P. et M. Curie” 27 rue Chaligny, Paris 75012, France) , Wolf, Claude (Email: antonin.lamaziere@upmc.fr ) , Quinn, Peter J. (INSERM U1057, Faculte de Medicine, “P. et M. Curie” 27 rue Chaligny, Paris 75012, France)
    Metabolites v.2 no.4 ,pp. 1 - 18 , 2012 ,

    초록

    The lipidome of the liver and the secreted circulating lipoproteins can now be interrogated conveniently by automated mass spectrometric methods. Multivariate analysis of the liver and serum lipid composition in various animal modes or in human patients has pointed to specific molecular species markers. The perturbations of lipid metabolism can be categorized on the basis of three basic pathological mechanisms: (1) an accelerated rate of de novo lipogenesis; (2) perturbation of the peroxisome pathway of ether-lipid and very-long-chain fatty acid biosynthesis; (3) a change in the rate of interconversion of essential omega-3 and -6 polyunsaturated fatty acids. This review provides examples to illustrate the practicalities of lipidomic studies in biomedicine.

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  2. [해외논문]   Mass Spectrometry Based Lipidomics: An Overview of Technological Platforms  

    Kö (Core Facility for Mass Spectrometry, Medical University of Graz, Stiftingtalstrasse 24, 8010 Graz, Austria) , feler, Harald C. (Email: martin.troetzmueller@medunigraz.at ) , Fauland, Alexander (Institute of Analytical Chemistry and Food Chemistry, Graz University of Technology, Stremayrgasse 9/II, 8010 Graz, Austria) , Rechberger, Gerald N. (Email: alexander.fauland@tugraz.at ) , Trö (Department for Molecular Biosciences, University of Graz, Humboldtstrasse 50/II, 8010 Graz, Austria) , tzmü (Email: gerald.rechberger@uni-graz.at ) , ller, Martin (Core Facility for Mass Spectrometry, Medical University of Graz, Stiftingtalstrasse 24, 8010 Graz, Austria)
    Metabolites v.2 no.4 ,pp. 19 - 38 , 2012 ,

    초록

    One decade after the genomic and the proteomic life science revolution, new 'omics' fields are emerging. The metabolome encompasses the entity of small molecules—Most often end products of a catalytic process regulated by genes and proteins—with the lipidome being its fat soluble subdivision. Within recent years, lipids are more and more regarded not only as energy storage compounds but also as interactive players in various cellular regulation cycles and thus attain rising interest in the bio-medical community. The field of lipidomics is, on one hand, fuelled by analytical technology advances, particularly mass spectrometry and chromatography, but on the other hand new biological questions also drive analytical technology developments. Compared to fairly standardized genomic or proteomic high-throughput protocols, the high degree of molecular heterogeneity adds a special analytical challenge to lipidomic analysis. In this review, we will take a closer look at various mass spectrometric platforms for lipidomic analysis. We will focus on the advantages and limitations of various experimental setups like 'shotgun lipidomics', liquid chromatography—Mass spectrometry (LC-MS) and matrix assisted laser desorption ionization-time of flight (MALDI-TOF) based approaches. We will also examine available software packages for data analysis, which nowadays is in fact the rate limiting step for most 'omics' workflows.

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  3. [해외논문]   Comparative Chemistry of Aspergillus oryzae (RIB40) and A. flavus (NRRL 3357)  

    Rank, Christian (Department of Systems Biology, Center for Microbial Biotechnology, Technical University of Denmark, Søltofts Plads B221, DK-2800 Kgs. Lyngby, Denmark) , Klejnstrup, Marie Louise (Email: christian.rank@gmail.com (C.R.)) , Petersen, Lene Maj (marlk@bio.dtu.dk (M.L.K.)) , Kildgaard, Sara (lmape@bio.dtu.dk (L.M.P.)) , Frisvad, Jens Christian (sarakildgaard@hotmail.com (S.K.)) , Gotfredsen, Charlotte Held (jcf@bio.dtu.dk (J.C.F.) ) , Larsen, Thomas Ostenfeld (Department of Systems Biology, Center for Microbial Biotechnology, Technical University of Denmark, Søltofts Plads B221, DK-2800 Kgs. Lyngby, Denmark)
    Metabolites v.2 no.4 ,pp. 39 - 56 , 2012 ,

    초록

    Aspergillus oryzae and A. flavus are important species in industrial biotechnology and food safety and have been some of the first aspergilli to be fully genome sequenced. Bioinformatic analysis has revealed 99.5% gene homology between the two species pointing towards a large coherence in the secondary metabolite production. In this study we report on the first comparison of secondary metabolite production between the full genome sequenced strains of A. oryzae (RIB40) and A. flavus (NRRL 3357). Surprisingly, the overall chemical profiles of the two strains were mostly very different across 15 growth conditions. Contrary to previous studies we found the aflatrem precursor 13-desoxypaxilline to be a major metabolite from A. oryzae under certain growth conditions. For the first time, we additionally report A. oryzae to produce parasiticolide A and two new analogues hereof, along with four new alkaloids related to the A. flavus metabolites ditryptophenalines and miyakamides. Generally the secondary metabolite capability of A. oryzae presents several novel end products likely to result from the domestication process from A. flavus .

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  4. [해외논문]   Quantification of Signaling Lipids by Nano-Electrospray Ionization Tandem Mass Spectrometry (Nano-ESI MS/MS)  

    Haag, Mathias (Heidelberg University Biochemistry Center, University of Heidelberg, Heidelberg, Germany) , Schmidt, Angelika (Email: mathias.haag@bzh.uni-heidelberg.de (M.H.)) , Sachsenheimer, Timo (timo.sachsenheimer@bzh.uni-heidelberg.de (T.S.) ) , Brü (Tumorimmunology Program, Division of Immunogenetics (D030), German Cancer Research Center (DKFZ), Heidelberg, Germany) , gger, Britta (Email: a.schmidt@dkfz.de )
    Metabolites v.2 no.4 ,pp. 57 - 76 , 2012 ,

    초록

    Lipids, such as phosphoinositides (PIPs) and diacylglycerol (DAG), are important signaling intermediates involved in cellular processes such as T cell receptor (TCR)-mediated signal transduction. Here we report identification and quantification of PIP, PIP 2 and DAG from crude lipid extracts. Capitalizing on the different extraction properties of PIPs and DAGs allowed us to efficiently recover both lipid classes from one sample. Rapid analysis of endogenous signaling molecules was performed by nano-electrospray ionization tandem mass spectrometry (nano-ESI MS/MS), employing lipid class-specific neutral loss and multiple precursor ion scanning for their identification and quantification. Profiling of DAG, PIP and PIP 2 molecular species in primary human T cells before and after TCR stimulation resulted in a two-fold increase in DAG levels with a shift towards 1-stearoyl-2-arachidonoyl-DAG in stimulated cells. PIP 2 levels were slightly reduced, while PIP levels remained unchanged.

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  5. [해외논문]   The Effect of LC-MS Data Preprocessing Methods on the Selection of Plasma Biomarkers in Fed vs. Fasted Rats  

    Gü (Department of Human Nutrition, Faculty of Life Sciences, University of Copenhagen, Rolighedsvej 30, 1958, Frederiksberg C, Denmark) , rdeniz, Gö (Email: mkri@life.ku.dk (M.K.)) , zde (ldra@life.ku.dk (L.O.D.) ) , Kristensen, Mette (Department of Human Nutrition, Faculty of Life Sciences, University of Copenhagen, Rolighedsvej 30, 1958, Frederiksberg C, Denmark) , Skov, Thomas (Email: mkri@life.ku.dk (M.K.)) , Dragsted, Lars O. (ldra@life.ku.dk (L.O.D.) )
    Metabolites v.2 no.4 ,pp. 77 - 99 , 2012 ,

    초록

    The metabolic composition of plasma is affected by time passed since the last meal and by individual variation in metabolite clearance rates. Rat plasma in fed and fasted states was analyzed with liquid chromatography quadrupole-time-of-flight mass spectrometry (LC-QTOF) for an untargeted investigation of these metabolite patterns. The dataset was used to investigate the effect of data preprocessing on biomarker selection using three different softwares, MarkerLynx TM , MZmine, XCMS along with a customized preprocessing method that performs binning of m/z channels followed by summation through retention time. Direct comparison of selected features representing the fed or fasted state showed large differences between the softwares. Many false positive markers were obtained from custom data preprocessing compared with dedicated softwares while MarkerLynx TM provided better coverage of markers. However, marker selection was more reliable with the gap filling (or peak finding) algorithms present in MZmine and XCMS. Further identification of the putative markers revealed that many of the differences between the markers selected were due to variations in features representing adducts or daughter ions of the same metabolites or of compounds from the same chemical subclasses, e.g., lyso-phosphatidylcholines (LPCs) and lyso-phosphatidylethanolamines (LPEs). We conclude that despite considerable differences in the performance of the preprocessing tools we could extract the same biological information by any of them. Carnitine, branched-chain amino acids, LPCs and LPEs were identified by all methods as markers of the fed state whereas acetylcarnitine was abundant during fasting in rats.

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  6. [해외논문]   Genetics of Polyketide Metabolism in Aspergillus nidulans  

    Klejnstrup, Marie L. (Department of Systems Biology, Center for Microbial Biotechnology, Technical University of Denmark, Søltofts Plads B221, DK-2800 Kgs. Lyngby, Denmark) , Frandsen, Rasmus J. N. (Email: marlk@bio.dtu.dk (M.L.K.)) , Holm, Dorte K. (tol@bio.dtu.dk (T.O.L) ) , Nielsen, Morten T. (Department of Systems Biology, Center for Microbial Biotechnology, Technical University of Denmark, Søltofts Plads B223, DK-2800 Kgs. Lyngby, Denmark) , Mortensen, Uffe H. (Email: rasf@bio.dtu.dk (R.J.N.F.)) , Larsen, Thomas O. (dmkp@bio.dtu.dk (D.K.H.)) , Nielsen, Jakob B. (motni@bio.dtu.dk (M.T.N.))
    Metabolites v.2 no.4 ,pp. 100 - 133 , 2012 ,

    초록

    Secondary metabolites are small molecules that show large structural diversity and a broad range of bioactivities. Some metabolites are attractive as drugs or pigments while others act as harmful mycotoxins. Filamentous fungi have the capacity to produce a wide array of secondary metabolites including polyketides. The majority of genes required for production of these metabolites are mostly organized in gene clusters, which often are silent or barely expressed under laboratory conditions, making discovery and analysis difficult. Fortunately, the genome sequences of several filamentous fungi are publicly available, greatly facilitating the establishment of links between genes and metabolites. This review covers the attempts being made to trigger the activation of polyketide metabolism in the fungal model organism Aspergillus nidulans . Moreover, it will provide an overview of the pathways where ten polyketide synthase genes have been coupled to polyketide products. Therefore, the proposed biosynthesis of the following metabolites will be presented; naphthopyrone, sterigmatocystin, aspyridones, emericellamides, asperthecin, asperfuranone, monodictyphenone/emodin, orsellinic acid, and the austinols.

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  7. [해외논문]   Lipidomics of Glycosphingolipids  

    Farwanah, Hany , Kolter, Thomas
    Metabolites v.2 no.4 ,pp. 134 - 164 , 2012 ,

    초록

    Glycosphingolipids (GSLs) contain one or more sugars that are attached to a sphingolipid moiety, usually to a ceramide, but in rare cases also to a sphingoid base. A large structural heterogeneity results from differences in number, identity, linkage, and anomeric configuration of the carbohydrate residues, and also from structural differences within the hydrophobic part. GSLs form complex cell-type specific patterns, which change with the species, the cellular differentiation state, viral transformation, ontogenesis, and oncogenesis. Although GSL structures can be assigned to only a few series with a common carbohydrate core, their structural variety and the complex pattern are challenges for their elucidation and quantification by mass spectrometric techniques. We present a general overview of the application of lipidomics for GSL determination. This includes analytical procedures and instrumentation together with recent correlations of GSL molecular species with human diseases. Difficulties such as the structural complexity and the lack of standard substances for complex GSLs are discussed.

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  8. [해외논문]   Investigation of Phenolic Acids in Suspension Cultures of Vitis vinifera Stimulated with Indanoyl-Isoleucine, N -Linolenoyl-L-Glutamine, Malonyl Coenzyme A and Insect Saliva  

    Riedel, Heidi (Department of Food Technology and Food Chemistry, Methods of Food Biotechnology, Technische Universität Berlin, Königin- Luise-Str. 22, 14195 Berlin, Germany) , Akumo, Divine N. (Email: neminn@gmail.com (N.M.M.T.S.)) , Saw, Nay Min Min Thaw (iryna.m.smetanska@tu-berlin.de (I.S.) ) , Smetanska, Iryna (Laboratory of Bioprocess Engineering, Department of Biotechnology, Technische Universität Berlin, Ackerstr. 71-76, D-13355 Berlin, Germany) , Neubauer, Peter (Email: akumo2@yahoo.com (D.N.A.))
    Metabolites v.2 no.4 ,pp. 165 - 177 , 2012 ,

    초록

    Vitis vinifera c.v. Muscat de Frontignan (grape) contains various high valuable bioactive phenolic compounds with pharmaceutical properties and industrial interest which are not fully exploited. The focus of this investigation consists in testing the effects of various biological elicitors on a non-morphogenic callus suspension culture of V. vinifera. The investigated elicitors: Indanoyl-isoleucine (IN), N -linolenoyl-L-glutamine (LG), insect saliva (IS) and malonyl coenzyme A (MCoA) were aimed at mimicking the influence of environmental pathogens on plants in their natural habitats and at provoking exogenous induction of the phenylpropanoid pathway. The elicitors' indanoyl-isoleucine (IN), N -linolenoyl-L-glutamine (LG) and insect saliva (IS), as well as malonyl coenzyme A (MCoA), were independently inoculated to stimulate the synthesis of phenylpropanoids. All of the enhancers positively increased the concentration of phenolic compounds in grape cells. The highest concentration of phenolic acids was detected after 2 h for MCoA, after 48 h for IN and after 24 h for LG and IS respectively. At the maximum production time, treated grape cells had a 3.5-fold (MCoA), 1.6-fold (IN) and 1.5-fold (IS) higher phenolic acid content compared to the corresponding control samples. The HPLC results of grape cells showed two major resveratrol derivatives: 3- O -Glucosyl-resveratrol and 4-(3,5-dihydroxyphenyl)-phenol. Their influences of the different elicitors, time of harvest and biomass concentration ( p

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  9. [해외논문]   Intracellular Metabolite Pool Changes in Response to Nutrient Depletion Induced Metabolic Switching in Streptomyces coelicolor  

    Wentzel, Alexander (Department of Biotechnology, SINTEF Materials and Chemistry, Sem Sælandsvei 2a, N-7465 Trondheim, Norway) , Sletta, Havard (Emails: havard.sletta@sintef.no (H.S.)) , Consortium, Stream (trond.e.ellingsen@sintef.no (T.E.E.) ) , Ellingsen, Trond E. (Department of Biotechnology, SINTEF Materials and Chemistry, Sem Sælandsvei 2a, N-7465 Trondheim, Norway) , Bruheim, Per (Emails: havard.sletta@sintef.no (H.S.))
    Metabolites v.2 no.4 ,pp. 178 - 194 , 2012 ,

    초록

    A metabolite profiling study of the antibiotic producing bacterium Streptomyces coelicolor A3(2) has been performed. The aim of this study was to monitor intracellular metabolite pool changes occurring as strains of S. coelicolor react to nutrient depletion with metabolic re-modeling, so-called metabolic switching, and transition from growth to secondary metabolite production phase. Two different culture media were applied, providing depletion of the key nutrients phosphate and L-glutamate, respectively, as the triggers for metabolic switching. Targeted GC-MS and LC-MS methods were employed to quantify important primary metabolite groups like amino acids, organic acids, sugar phosphates and other phosphorylated metabolites, and nucleotides in time-course samples withdrawn from fully-controlled batch fermentations. A general decline, starting already in the early growth phase, was observed for nucleotide pools and phosphorylated metabolite pools for both the phosphate and glutamate limited cultures. The change in amino acid and organic acid pools were more scattered, especially in the phosphate limited situation while a general decrease in amino acid and non-amino organic acid pools was observed in the L-glutamate limited situation. A phoP deletion mutant showed basically the same metabolite pool changes as the wild-type strain M145 when cultivated on phosphate limited medium. This implies that the inactivation of the phoP gene has only little effect on the detected metabolite levels in the cell. The energy charge was found to be relatively constant during growth, transition and secondary metabolite production phase. The results of this study and the employed targeted metabolite profiling methodology are directly relevant for the evaluation of precursor metabolite and energy supply for both natural and heterologous production of secondary metabolites in S. coelicolor .

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  10. [해외논문]   Shotgun Lipidomics by Sequential Precursor Ion Fragmentation on a Hybrid Quadrupole Time-of-Flight Mass Spectrometer  

    Simons, Brigitte (AB SCIEX, 71 Four Valley Dr. Concord, ON L4K4V8, Canada) , Kauhanen, Dimple (Emails: brigitte.simons@absciex.com (B.S.)) , Sylvä (eva.duchoslav@absciex.com (E.D.) ) , nne, Tuulia (Zora Biosciences, Biologinkuja 1, Espoo, FI-2150, Finland) , Tarasov, Kirill (Emails: dimple.kauhanen@zora.fi (D.K.)) , Duchoslav, Eva (tuulia.sylvanne@zora.fi (T.S.)) , Ekroos, Kim (kirill.tarasov@zora.fi (K.T.) )
    Metabolites v.2 no.4 ,pp. 195 - 213 , 2012 ,

    초록

    Shotgun lipidomics has evolved into a myriad of multi-dimensional strategies for molecular lipid characterization, including bioinformatics tools for mass spectrum interpretation and quantitative measurements to study systems-lipidomics in complex biological extracts. Taking advantage of spectral mass accuracy, scan speed and sensitivity of improved quadrupole linked time-of-flight mass analyzers, we developed a bias-free global lipid profiling acquisition technique of sequential precursor ion fragmentation called MS/MS ALL . This generic information-independent tandem mass spectrometry (MS) technique consists of a Q1 stepped mass isolation window through a set mass range in small increments, fragmenting and recording all product ions and neutral losses. Through the accurate MS and MS/MS information, the molecular lipid species are resolved, including distinction of isobaric and isomeric species, and composed into more precise lipidomic outputs. The method demonstrates good reproducibility and at least 3 orders of dynamic quantification range for isomeric ceramides in human plasma. More than 400 molecular lipids in human plasma were uncovered and quantified in less than 12 min, including acquisitions in both positive and negative polarity modes. We anticipate that the performance of sequential precursor ion fragmentation both in quality and throughput will lead to the uncovering of new avenues throughout the biomedical research community, enhance biomarker discovery and provide novel information target discovery programs as it will prospectively shed new insight into affected metabolic and signaling pathways.

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