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Keywords = isotope-assisted metabolomics

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24 pages, 3197 KiB  
Article
Integrated Physiological, Transcriptomic and Metabolomic Analyses of the Response of Rice to Aniline Toxicity
by Jingjing Wang, Ruixin Wang, Lei Liu, Wenrui Zhang, Zhonghuan Yin, Rui Guo, Dan Wang and Changhong Guo
Int. J. Mol. Sci. 2025, 26(2), 582; https://doi.org/10.3390/ijms26020582 - 11 Jan 2025
Viewed by 965
Abstract
The accumulation of aniline in the natural environment poses a potential threat to crops, and thus, investigating the effects of aniline on plants holds practical implications for agricultural engineering and its affiliated industries. This study combined physiological, transcriptomic, and metabolomic methods to investigate [...] Read more.
The accumulation of aniline in the natural environment poses a potential threat to crops, and thus, investigating the effects of aniline on plants holds practical implications for agricultural engineering and its affiliated industries. This study combined physiological, transcriptomic, and metabolomic methods to investigate the growth status and molecular-level response mechanisms of rice under stress from varying concentrations of aniline. At a concentration of 1 mg/L, aniline exhibited a slight growth-promoting effect on rice. However, higher concentrations of aniline significantly inhibited rice growth and even caused notable damage to the rice seedlings. Physiological data indicated that under aniline stress, the membrane of rice underwent oxidative damage. Furthermore, when the concentration of aniline was excessively high, the cells suffered severe damage, resulting in the inhibition of antioxidant enzyme synthesis and activity. Transcriptomic and metabolomic analyses indicated that the phenylpropanoid biosynthesis pathway became quite active under aniline stress, with alterations in various enzymes and metabolites related to lignin synthesis. In addition to the phenylpropanoid biosynthesis pathway, amino acid metabolism, lipid metabolism, and purine metabolism were also critical pathways related to rice’s response to aniline stress. Significant changes occurred in the expression levels of multiple genes (e.g., PRX, C4H, GST, and ilvH, among others) associated with functions such as antioxidant activity, membrane remodeling, signal transduction, and nitrogen supply. Similarly, notable alterations were observed in the accumulation of various metabolites (for instance, glutamic acid, phosphatidic acid, phosphatidylglycerol, and asparagine, etc.) related to these functions. Our research findings have unveiled the potential of compounds such as phenylpropanoids and amino acids in assisting rice to cope with aniline stress. A more in-depth and detailed exploration of the specific mechanisms by which these substances function in the process of plant resistance to aniline stress (for instance, utilizing carbon-14 isotope tracing to monitor the metabolic pathway of aniline within plants) will facilitate the cultivation of plant varieties that are resistant to aniline. This will undoubtedly benefit activities such as ensuring food production and quality in aniline-contaminated environments, as well as utilizing plants for the remediation of aniline-polluted environments. Full article
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15 pages, 2743 KiB  
Article
Stable Isotope-Assisted Untargeted Metabolomics Identifies ALDH1A1-Driven Erythronate Accumulation in Lung Cancer Cells
by Jie Zhang, Mark A. Keibler, Wentao Dong, Jenny Ghelfi, Thekla Cordes, Tamara Kanashova, Arnaud Pailot, Carole L. Linster, Gunnar Dittmar, Christian M. Metallo, Tim Lautenschlaeger, Karsten Hiller and Gregory Stephanopoulos
Biomedicines 2023, 11(10), 2842; https://doi.org/10.3390/biomedicines11102842 - 19 Oct 2023
Cited by 1 | Viewed by 2566
Abstract
Using an untargeted stable isotope-assisted metabolomics approach, we identify erythronate as a metabolite that accumulates in several human cancer cell lines. Erythronate has been reported to be a detoxification product derived from off-target glycolytic metabolism. We use chemical inhibitors and genetic silencing to [...] Read more.
Using an untargeted stable isotope-assisted metabolomics approach, we identify erythronate as a metabolite that accumulates in several human cancer cell lines. Erythronate has been reported to be a detoxification product derived from off-target glycolytic metabolism. We use chemical inhibitors and genetic silencing to define the pentose phosphate pathway intermediate erythrose 4-phosphate (E4P) as the starting substrate for erythronate production. However, following enzyme assay-coupled protein fractionation and subsequent proteomics analysis, we identify aldehyde dehydrogenase 1A1 (ALDH1A1) as the predominant contributor to erythrose oxidation to erythronate in cell extracts. Through modulating ALDH1A1 expression in cancer cell lines, we provide additional support. We hence describe a possible alternative route to erythronate production involving the dephosphorylation of E4P to form erythrose, followed by its oxidation by ALDH1A1. Finally, we measure increased erythronate concentrations in tumors relative to adjacent normal tissues from lung cancer patients. These findings suggest the accumulation of erythronate to be an example of metabolic reprogramming in cancer cells, raising the possibility that elevated levels of erythronate may serve as a biomarker of certain types of cancer. Full article
(This article belongs to the Special Issue The Biology of Non-small Cell Lung Cancer)
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21 pages, 4597 KiB  
Article
Light-Induced Changes in Secondary Metabolite Production of Trichoderma atroviride
by Kristina Missbach, Daniel Flatschacher, Christoph Bueschl, Jonathan Matthew Samson, Stefan Leibetseder, Martina Marchetti-Deschmann, Susanne Zeilinger and Rainer Schuhmacher
J. Fungi 2023, 9(8), 785; https://doi.org/10.3390/jof9080785 - 26 Jul 2023
Cited by 8 | Viewed by 2440
Abstract
Many studies aim at maximizing fungal secondary metabolite production but the influence of light during cultivation has often been neglected. Here, we combined an untargeted isotope-assisted liquid chromatography–high-resolution mass spectrometry-based metabolomics approach with standardized cultivation of Trichoderma atroviride under three defined light regimes [...] Read more.
Many studies aim at maximizing fungal secondary metabolite production but the influence of light during cultivation has often been neglected. Here, we combined an untargeted isotope-assisted liquid chromatography–high-resolution mass spectrometry-based metabolomics approach with standardized cultivation of Trichoderma atroviride under three defined light regimes (darkness (PD), reduced light (RL) exposure, and 12/12 h light/dark cycle (LD)) to systematically determine the effect of light on secondary metabolite production. Comparative analyses revealed a similar metabolite profile upon cultivation in PD and RL, whereas LD treatment had an inhibiting effect on both the number and abundance of metabolites. Additionally, the spatial distribution of the detected metabolites for PD and RL was analyzed. From the more than 500 detected metabolites, only 25 were exclusively produced upon fungal growth in darkness and 85 were significantly more abundant in darkness. The majority were detected under both cultivation conditions and annotation revealed a cluster of substances whose production followed the pattern observed for the well-known T. atroviride metabolite 6-pentyl-alpha-pyrone. We conclude that cultivation of T. atroviride under RL can be used to maximize secondary metabolite production. Full article
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29 pages, 2666 KiB  
Review
Isotope-Assisted Metabolic Flux Analysis: A Powerful Technique to Gain New Insights into the Human Metabolome in Health and Disease
by Bilal Moiz, Andrew Li, Surya Padmanabhan, Ganesh Sriram and Alisa Morss Clyne
Metabolites 2022, 12(11), 1066; https://doi.org/10.3390/metabo12111066 - 4 Nov 2022
Cited by 11 | Viewed by 3697
Abstract
Cell metabolism represents the coordinated changes in genes, proteins, and metabolites that occur in health and disease. The metabolic fluxome, which includes both intracellular and extracellular metabolic reaction rates (fluxes), therefore provides a powerful, integrated description of cellular phenotype. However, intracellular fluxes cannot [...] Read more.
Cell metabolism represents the coordinated changes in genes, proteins, and metabolites that occur in health and disease. The metabolic fluxome, which includes both intracellular and extracellular metabolic reaction rates (fluxes), therefore provides a powerful, integrated description of cellular phenotype. However, intracellular fluxes cannot be directly measured. Instead, flux quantification requires sophisticated mathematical and computational analysis of data from isotope labeling experiments. In this review, we describe isotope-assisted metabolic flux analysis (iMFA), a rigorous computational approach to fluxome quantification that integrates metabolic network models and experimental data to generate quantitative metabolic flux maps. We highlight practical considerations for implementing iMFA in mammalian models, as well as iMFA applications in in vitro and in vivo studies of physiology and disease. Finally, we identify promising new frontiers in iMFA which may enable us to fully unlock the potential of iMFA in biomedical research. Full article
(This article belongs to the Special Issue Frontiers in Metabolic Flux Analysis on Human Disease)
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22 pages, 3703 KiB  
Article
Gramiketides, Novel Polyketide Derivatives of Fusarium graminearum, Are Produced during the Infection of Wheat
by Bernhard Seidl, Katrin Rehak, Christoph Bueschl, Alexandra Parich, Raveevatoo Buathong, Bernhard Wolf, Maria Doppler, Rudolf Mitterbauer, Gerhard Adam, Netnapis Khewkhom, Gerlinde Wiesenberger and Rainer Schuhmacher
J. Fungi 2022, 8(10), 1030; https://doi.org/10.3390/jof8101030 - 28 Sep 2022
Cited by 4 | Viewed by 2761
Abstract
The plant pathogen Fusarium graminearum is a proficient producer of mycotoxins and other in part still unknown secondary metabolites, some of which might act as virulence factors on wheat. The PKS15 gene is expressed only in planta, so far hampering the identification [...] Read more.
The plant pathogen Fusarium graminearum is a proficient producer of mycotoxins and other in part still unknown secondary metabolites, some of which might act as virulence factors on wheat. The PKS15 gene is expressed only in planta, so far hampering the identification of an associated metabolite. Here we combined the activation of silent gene clusters by chromatin manipulation (kmt6) with blocking the metabolic flow into the competing biosynthesis of the two major mycotoxins deoxynivalenol and zearalenone. Using an untargeted metabolomics approach, two closely related metabolites were found in triple mutants (kmt6 tri5 pks4,13) deficient in production of the major mycotoxins deoxynivalenol and zearalenone, but not in strains with an additional deletion in PKS15 (kmt6 tri5 pks4,13 pks15). Characterization of the metabolites, by LC-HRMS/MS in combination with a stable isotope-assisted tracer approach, revealed that they are likely hybrid polyketides comprising a polyketide part consisting of malonate-derived acetate units and a structurally deviating part. We propose the names gramiketide A and B for the two metabolites. In a biological experiment, both gramiketides were formed during infection of wheat ears with wild-type but not with pks15 mutants. The formation of the two gramiketides during infection correlated with that of the well-known virulence factor deoxynivalenol, suggesting that they might play a role in virulence. Full article
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15 pages, 1645 KiB  
Article
A Micro-Scale Analytical Method for Determining Glycogen Turnover by NMR and FTMS
by Timothy L. Scott, Juan Zhu, Teresa A. Cassel, Sara Vicente-Muñoz, Penghui Lin, Richard M. Higashi, Andrew N. Lane and Teresa W.-M. Fan
Metabolites 2022, 12(8), 760; https://doi.org/10.3390/metabo12080760 - 18 Aug 2022
Cited by 2 | Viewed by 2467
Abstract
Glycogen is a readily deployed intracellular energy storage macromolecule composed of branched chains of glucose anchored to the protein glycogenin. Although glycogen primarily occurs in the liver and muscle, it is found in most tissues, and its metabolism has been shown to be [...] Read more.
Glycogen is a readily deployed intracellular energy storage macromolecule composed of branched chains of glucose anchored to the protein glycogenin. Although glycogen primarily occurs in the liver and muscle, it is found in most tissues, and its metabolism has been shown to be important in cancers and immune cells. Robust analysis of glycogen turnover requires stable isotope tracing plus a reliable means of quantifying total and labeled glycogen derived from precursors such as 13C6-glucose. Current methods for analyzing glycogen are time- and sample-consuming, at best semi-quantitative, and unable to measure stable isotope enrichment. Here we describe a microscale method for quantifying both intact and acid-hydrolyzed glycogen by ultra-high-resolution Fourier transform mass spectrometric (UHR-FTMS) and/or NMR analysis in stable isotope resolved metabolomics (SIRM) studies. Polar metabolites, including intact glycogen and their 13C positional isotopomer distributions, are first measured in crude biological extracts by high resolution NMR, followed by rapid and efficient acid hydrolysis to glucose under N2 in a focused beam microwave reactor, with subsequent analysis by UHR-FTMS and/or NMR. We optimized the microwave digestion time, temperature, and oxygen purging in terms of recovery versus degradation and found 10 min at 110–115 °C to give >90% recovery. The method was applied to track the fate of 13C6-glucose in primary human lung BEAS-2B cells, human macrophages, murine liver and patient-derived tumor xenograft (PDTX) in vivo, and the fate of 2H7-glucose in ex vivo lung organotypic tissue cultures of a lung cancer patient. We measured the incorporation of 13C6-glucose into glycogen and its metabolic intermediates, UDP-Glucose and glucose-1-phosphate, to demonstrate the utility of the method in tracing glycogen turnover in cells and tissues. The method offers a quantitative, sensitive, and convenient means to analyze glycogen turnover in mg amounts of complex biological materials. Full article
(This article belongs to the Section Cell Metabolism)
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12 pages, 2180 KiB  
Article
Exploring the Characteristic Aroma of Beef from Japanese Black Cattle (Japanese Wagyu) via Sensory Evaluation and Gas Chromatography-Olfactometry
by Shuji Ueda, Minoru Yamanoue, Yasuhito Sirai and Eiji Iwamoto
Metabolites 2021, 11(1), 56; https://doi.org/10.3390/metabo11010056 - 15 Jan 2021
Cited by 27 | Viewed by 5557
Abstract
Beef from Japanese Black cattle (Japanese Wagyu) is renowned for its flavor characteristics. To clarify the key metabolites contributing to this rich and sweet aroma of beef, an omics analysis combined with GC-olfactometry (GC-O) and metabolomics analysis with gas chromatography–mass spectrometry (GC-MS) were [...] Read more.
Beef from Japanese Black cattle (Japanese Wagyu) is renowned for its flavor characteristics. To clarify the key metabolites contributing to this rich and sweet aroma of beef, an omics analysis combined with GC-olfactometry (GC-O) and metabolomics analysis with gas chromatography–mass spectrometry (GC-MS) were applied. GC-O analysis identified 39 odor-active odorants from the volatile fraction of boiled beef distilled by solvent-assisted flavor evaporation. Eight odorants predicted to contribute to Wagyu beef aroma were compared between Japanese Black cattle and Holstein cattle using a stable isotope dilution assay with GC–tandem quadrupole mass spectrometry. By correlating the sensory evaluation values of retronasal aroma, γ-hexalactone, γ-decalactone, and γ-undecalactone showed a high correlation with the Wagyu beef aroma. Metabolomics data revealed a high correlation between the amounts of odorants and multiple metabolites, such as glutamine, decanoic acid, lactic acid, and phosphoric acid. These results provide useful information for assessing the aroma and quality of beef. Full article
(This article belongs to the Special Issue Metabolomic Applications in Animal Science Volume 2)
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16 pages, 2741 KiB  
Article
Enhanced Metabolome Coverage and Evaluation of Matrix Effects by the Use of Experimental-Condition-Matched 13C-Labeled Biological Samples in Isotope-Assisted LC-HRMS Metabolomics
by Asja Ćeranić, Christoph Bueschl, Maria Doppler, Alexandra Parich, Kangkang Xu, Marc Lemmens, Hermann Buerstmayr and Rainer Schuhmacher
Metabolites 2020, 10(11), 434; https://doi.org/10.3390/metabo10110434 - 27 Oct 2020
Cited by 10 | Viewed by 2693
Abstract
Stable isotope-assisted approaches can improve untargeted liquid chromatography-high resolution mass spectrometry (LC-HRMS) metabolomics studies. Here, we demonstrate at the example of chemically stressed wheat that metabolome-wide internal standardization by globally 13C-labeled metabolite extract (GLMe-IS) of experimental-condition-matched biological samples can help to improve [...] Read more.
Stable isotope-assisted approaches can improve untargeted liquid chromatography-high resolution mass spectrometry (LC-HRMS) metabolomics studies. Here, we demonstrate at the example of chemically stressed wheat that metabolome-wide internal standardization by globally 13C-labeled metabolite extract (GLMe-IS) of experimental-condition-matched biological samples can help to improve the detection of treatment-relevant metabolites and can aid in the post-acquisition assessment of putative matrix effects in samples obtained upon different treatments. For this, native extracts of toxin- and mock-treated (control) wheat ears were standardized by the addition of uniformly 13C-labeled wheat ear extracts that were cultivated under similar experimental conditions (toxin-treatment and control) and measured with LC-HRMS. The results show that 996 wheat-derived metabolites were detected with the non-condition-matched 13C-labeled metabolite extract, while another 68 were only covered by the experimental-condition-matched GLMe-IS. Additional testing is performed with the assumption that GLMe-IS enables compensation for matrix effects. Although on average no severe matrix differences between both experimental conditions were found, individual metabolites may be affected as is demonstrated by wrong decisions with respect to the classification of significantly altered metabolites. When GLMe-IS was applied to compensate for matrix effects, 272 metabolites showed significantly altered levels between treated and control samples, 42 of which would not have been classified as such without GLMe-IS. Full article
(This article belongs to the Special Issue Stable Isotope Guided Metabolomics)
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18 pages, 2469 KiB  
Article
Postprandial Metabolic Effects of Fiber Mixes Revealed by in vivo Stable Isotope Labeling in Humans
by Lisa Schlicker, Hanny M. Boers, Christian-Alexander Dudek, Gang Zhao, Arnab Barua, Jean-Pierre Trezzi, Michael Meyer-Hermann, Doris M. Jacobs and Karsten Hiller
Metabolites 2019, 9(5), 91; https://doi.org/10.3390/metabo9050091 - 7 May 2019
Cited by 4 | Viewed by 5331
Abstract
Food supplementation with a fiber mix of guar gum and chickpea flour represents a promising approach to reduce the risk of type 2 diabetes mellitus (T2DM) by attenuating postprandial glycemia. To investigate the effects on postprandial metabolic fluxes of glucose-derived metabolites in response [...] Read more.
Food supplementation with a fiber mix of guar gum and chickpea flour represents a promising approach to reduce the risk of type 2 diabetes mellitus (T2DM) by attenuating postprandial glycemia. To investigate the effects on postprandial metabolic fluxes of glucose-derived metabolites in response to this fiber mix, a randomized, cross-over study was designed. Twelve healthy, male subjects consumed three different flatbreads either supplemented with 2% guar gum or 4% guar gum and 15% chickpea flour or without supplementation (control). The flatbreads were enriched with ~2% of 13C-labeled wheat flour. Blood was collected at 16 intervals over a period of 360 min after bread intake and plasma samples were analyzed by GC-MS based metabolite profiling combined with stable isotope-assisted metabolomics. Although metabolite levels of the downstream metabolites of glucose, specifically lactate and alanine, were not altered in response to the fiber mix, supplementation of 4% guar gum was shown to significantly delay and reduce the exogenous formation of these metabolites. Metabolic modeling and computation of appearance rates revealed that the effects induced by the fiber mix were strongest for glucose and attenuated downstream of glucose. Further investigations to explore the potential of fiber mix supplementation to counteract the development of metabolic diseases are warranted. Full article
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20 pages, 2462 KiB  
Article
Stable Isotope-Assisted Evaluation of Different Extraction Solvents for Untargeted Metabolomics of Plants
by Maria Doppler, Bernhard Kluger, Christoph Bueschl, Christina Schneider, Rudolf Krska, Sylvie Delcambre, Karsten Hiller, Marc Lemmens and Rainer Schuhmacher
Int. J. Mol. Sci. 2016, 17(7), 1017; https://doi.org/10.3390/ijms17071017 - 28 Jun 2016
Cited by 89 | Viewed by 9374
Abstract
The evaluation of extraction protocols for untargeted metabolomics approaches is still difficult. We have applied a novel stable isotope-assisted workflow for untargeted LC-HRMS-based plant metabolomics , which allows for the first time every detected feature to be considered for method evaluation. The efficiency [...] Read more.
The evaluation of extraction protocols for untargeted metabolomics approaches is still difficult. We have applied a novel stable isotope-assisted workflow for untargeted LC-HRMS-based plant metabolomics , which allows for the first time every detected feature to be considered for method evaluation. The efficiency and complementarity of commonly used extraction solvents, namely 1 + 3 (v/v) mixtures of water and selected organic solvents (methanol, acetonitrile or methanol/acetonitrile 1 + 1 (v/v)), with and without the addition of 0.1% (v/v) formic acid were compared. Four different wheat organs were sampled, extracted and analysed by LC-HRMS. Data evaluation was performed with the in-house-developed MetExtract II software and R. With all tested solvents a total of 871 metabolites were extracted in ear, 785 in stem, 733 in leaf and 517 in root samples, respectively. Between 48% (stem) and 57% (ear) of the metabolites detected in a particular organ were found with all extraction mixtures, and 127 of 996 metabolites were consistently shared between all extraction agent/organ combinations. In aqueous methanol, acidification with formic acid led to pronounced pH dependency regarding the precision of metabolite abundance and the number of detectable metabolites, whereas extracts of acetonitrile-containing mixtures were less affected. Moreover, methanol and acetonitrile have been found to be complementary with respect to extraction efficiency. Interestingly, the beneficial properties of both solvents can be combined by the use of a water-methanol-acetonitrile mixture for global metabolite extraction instead of aqueous methanol or aqueous acetonitrile alone. Full article
(This article belongs to the Special Issue Metabolomics in the Plant Sciences)
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18 pages, 438 KiB  
Article
Novel Strategy for Non-Targeted Isotope-Assisted Metabolomics by Means of Metabolic Turnover and Multivariate Analysis
by Yasumune Nakayama, Yoshihiro Tamada, Hiroshi Tsugawa, Takeshi Bamba and Eiichiro Fukusaki
Metabolites 2014, 4(3), 722-739; https://doi.org/10.3390/metabo4030722 - 25 Aug 2014
Cited by 6 | Viewed by 8845
Abstract
Isotope-labeling is a useful technique for understanding cellular metabolism. Recent advances in metabolomics have extended the capability of isotope-assisted studies to reveal global metabolism. For instance, isotope-assisted metabolomics technology has enabled the mapping of a global metabolic network, estimation of flux at branch [...] Read more.
Isotope-labeling is a useful technique for understanding cellular metabolism. Recent advances in metabolomics have extended the capability of isotope-assisted studies to reveal global metabolism. For instance, isotope-assisted metabolomics technology has enabled the mapping of a global metabolic network, estimation of flux at branch points of metabolic pathways, and assignment of elemental formulas to unknown metabolites. Furthermore, some data processing tools have been developed to apply these techniques to a non-targeted approach, which plays an important role in revealing unknown or unexpected metabolism. However, data collection and integration strategies for non-targeted isotope-assisted metabolomics have not been established. Therefore, a systematic approach is proposed to elucidate metabolic dynamics without targeting pathways by means of time-resolved isotope tracking, i.e., “metabolic turnover analysis”, as well as multivariate analysis. We applied this approach to study the metabolic dynamics in amino acid perturbation of Saccharomyces cerevisiae. In metabolic turnover analysis, 69 peaks including 35 unidentified peaks were investigated. Multivariate analysis of metabolic turnover successfully detected a pathway known to be inhibited by amino acid perturbation. In addition, our strategy enabled identification of unknown peaks putatively related to the perturbation. Full article
(This article belongs to the Special Issue Metabolomics and Biotechnology)
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24 pages, 579 KiB  
Review
Application of Stable Isotope-Assisted Metabolomics for Cell Metabolism Studies
by Le You, Baichen Zhang and Yinjie J. Tang
Metabolites 2014, 4(2), 142-165; https://doi.org/10.3390/metabo4020142 - 31 Mar 2014
Cited by 40 | Viewed by 13765
Abstract
The applications of stable isotopes in metabolomics have facilitated the study of cell metabolisms. Stable isotope-assisted metabolomics requires: (1) properly designed tracer experiments; (2) stringent sampling and quenching protocols to minimize isotopic alternations; (3) efficient metabolite separations; (4) high resolution mass spectrometry to [...] Read more.
The applications of stable isotopes in metabolomics have facilitated the study of cell metabolisms. Stable isotope-assisted metabolomics requires: (1) properly designed tracer experiments; (2) stringent sampling and quenching protocols to minimize isotopic alternations; (3) efficient metabolite separations; (4) high resolution mass spectrometry to resolve overlapping peaks and background noises; and (5) data analysis methods and databases to decipher isotopic clusters over a broad m/z range (mass-to-charge ratio). This paper overviews mass spectrometry based techniques for precise determination of metabolites and their isotopologues. It also discusses applications of isotopic approaches to track substrate utilization, identify unknown metabolites and their chemical formulas, measure metabolite concentrations, determine putative metabolic pathways, and investigate microbial community populations and their carbon assimilation patterns. In addition, 13C-metabolite fingerprinting and metabolic models can be integrated to quantify carbon fluxes (enzyme reaction rates). The fluxome, in combination with other “omics” analyses, may give systems-level insights into regulatory mechanisms underlying gene functions. More importantly, 13C-tracer experiments significantly improve the potential of low-resolution gas chromatography-mass spectrometry (GC-MS) for broad-scope metabolism studies. We foresee the isotope-assisted metabolomics to be an indispensable tool in industrial biotechnology, environmental microbiology, and medical research. Full article
(This article belongs to the Special Issue Cell and Tissue Metabolomics)
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