{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T04:37:37Z","timestamp":1792643857776,"version":"4.5.0"},"reference-count":93,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T00:00:00Z","timestamp":1792540800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T00:00:00Z","timestamp":1792540800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["406455\/2022\u20108"],"award-info":[{"award-number":["406455\/2022\u20108"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["KO 2329\/7\u20102"],"award-info":[{"award-number":["KO 2329\/7\u20102"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004189","name":"Max-Planck-Gesellschaft","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004189","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["nph.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["New Phytologist"],"abstract":"<jats:title>Summary<\/jats:title>\n                  <jats:p>\n                    Carbon fluxes throughout metabolic networks can be investigated experimentally through\n                    <jats:sup>13<\/jats:sup>\n                    C\u2010isotope labelling experiments (\n                    <jats:sup>13<\/jats:sup>\n                    C\u2010ILE) and\n                    <jats:sup>13<\/jats:sup>\n                    C\u2010metabolic flux analysis (\n                    <jats:sup>13<\/jats:sup>\n                    C\u2010MFA).\n                    <jats:sup>13<\/jats:sup>\n                    C\u2010ILE involves the application of isotopically labelled substrates to a biological system to detect label distribution throughout the metabolic network, while\n                    <jats:sup>13<\/jats:sup>\n                    C\u2010MFA is a computational approach that quantitatively estimates fluxes by fitting isotope\u2010labelling data to metabolic network models.\n                    <jats:sup>13<\/jats:sup>\n                    C\u2010MFA can encompass more metabolic reactions and provide subcellular flux estimates that remain difficult to validate directly using current\n                    <jats:sup>13<\/jats:sup>\n                    C\u2010ILE approaches. Overcoming major bottlenecks of\n                    <jats:sup>13<\/jats:sup>\n                    C\u2010ILE is thus needed to improve and validate\n                    <jats:sup>13<\/jats:sup>\n                    C\u2010MFA. Mass spectrometry (MS)\u2010based\n                    <jats:sup>13<\/jats:sup>\n                    C\u2010ILE has been carried out mostly at isotopologue rather than isotopomer level. Isotopologues differ in their isotopic composition, while isotopomers have the same isotopic composition but at different positions within the molecule. Thus,\n                    <jats:sup>13<\/jats:sup>\n                    C\u2010isotopomer approaches discriminate which atoms of a metabolite have received\n                    <jats:sup>13<\/jats:sup>\n                    C, enabling better comprehension of the regulation of metabolic pathways. Here, we highlight the major challenges to improve MS\u2010based positional\n                    <jats:sup>13<\/jats:sup>\n                    C analysis and discuss the advantages of this approach over MS\u2010based methods with low or no carbon\u2010positional resolution. We further demonstrate how positional\n                    <jats:sup>13<\/jats:sup>\n                    C analysis has been used to estimate enzyme activity\n                    <jats:italic>in vivo<\/jats:italic>\n                    and to study plant metabolism.\n                  <\/jats:p>","DOI":"10.1111\/nph.71696","type":"journal-article","created":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T03:39:16Z","timestamp":1792640356000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["From isotopologues to isotopomers: advances in mass spectrometry\u2010based positional\n                    <scp>\n                      <sup>13<\/sup>\n                      C\n                    <\/scp>\n                    analysis in plants"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8643-7320","authenticated-orcid":false,"given":"Val\u00e9ria F.","family":"Lima","sequence":"first","affiliation":[{"name":"LabPlant, Departamento de Bioqu\u00edmica e Biologia Molecular Universidade Federal do Cear\u00e1  Fortaleza CE 60451\u2010970 Brazil"},{"name":"National Institute of Science and Technology on Plant Physiology Under Stress Conditions  Vi\u00e7osa MG 36570\u2010900 Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-6012-5975","authenticated-orcid":false,"given":"J\u00f4natas G.S.B.","family":"Oliveira","sequence":"additional","affiliation":[{"name":"LabPlant, Departamento de Bioqu\u00edmica e Biologia Molecular Universidade Federal do Cear\u00e1  Fortaleza CE 60451\u2010970 Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3249-0441","authenticated-orcid":false,"given":"Luisa","family":"Wittemeier","sequence":"additional","affiliation":[{"name":"Max\u2010Planck Institute of Molecular Plant Physiology  Am M\u00fchlenberg 1 14476 Potsdam Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9675-4883","authenticated-orcid":false,"given":"Joachim","family":"Kopka","sequence":"additional","affiliation":[{"name":"Max\u2010Planck Institute of Molecular Plant Physiology  Am M\u00fchlenberg 1 14476 Potsdam Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1842-420X","authenticated-orcid":false,"given":"Danilo M.","family":"Daloso","sequence":"additional","affiliation":[{"name":"LabPlant, Departamento de Bioqu\u00edmica e Biologia Molecular Universidade Federal do Cear\u00e1  Fortaleza CE 60451\u2010970 Brazil"},{"name":"National Institute of Science and Technology on Plant Physiology Under Stress Conditions  Vi\u00e7osa MG 36570\u2010900 Brazil"},{"name":"ForCE Metabolomics  Fortaleza CE 60451\u2010970 Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,21]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1111\/nph.14719","article-title":"Direct assessment of the metabolic origin of carbon atoms in glutamate from illuminated leaves using 13C\u2010NMR","volume":"216","author":"Abadie C","year":"2017","journal-title":"New Phytologist"},{"key":"e_1_2_13_3_1","doi-asserted-by":"crossref","first-page":"1843","DOI":"10.1111\/nph.15500","article-title":"In vivo phosphoenolpyruvate carboxylase activity is controlled by CO2 and O2 mole fractions and represents a major flux at high photorespiration rates","volume":"221","author":"Abadie C","year":"2019","journal-title":"New Phytologist"},{"key":"e_1_2_13_4_1","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1038\/s41592-021-01197-1","article-title":"Mass spectrometry\u2010based metabolomics: a guide for annotation, quantification and best reporting practices","volume":"18","author":"Alseekh S","year":"2021","journal-title":"Nature Methods"},{"key":"e_1_2_13_5_1","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1016\/j.cmet.2015.08.021","article-title":"Integrated, step\u2010wise, mass\u2010isotopomeric flux analysis of the TCA cycle","volume":"22","author":"Alves TC","year":"2015","journal-title":"Cell Metabolism"},{"key":"e_1_2_13_6_1","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.1016\/j.copbio.2013.02.003","article-title":"13C metabolic flux analysis: optimal design of isotopic labeling experiments","volume":"24","author":"Antoniewicz MR","year":"2013","journal-title":"Current Opinion in Biotechnology"},{"key":"e_1_2_13_7_1","doi-asserted-by":"crossref","first-page":"7554","DOI":"10.1021\/ac0708893","article-title":"Accurate assessment of amino acid mass isotopomer distributions for metabolic flux analysis","volume":"79","author":"Antoniewicz MR","year":"2007","journal-title":"Analytical Chemistry"},{"key":"e_1_2_13_8_1","doi-asserted-by":"crossref","first-page":"2246","DOI":"10.1074\/mcp.M114.038190","article-title":"Dissecting the subcellular compartmentation of proteins and metabolites in Arabidopsis leaves using non\u2010aqueous fractionation","volume":"13","author":"Arrivault S","year":"2014","journal-title":"Molecular & Cellular Proteomics"},{"key":"e_1_2_13_9_1","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.plantsci.2016.05.011","article-title":"Can stable isotope mass spectrometry replace radiolabelled approaches in metabolic studies?","volume":"249","author":"Batista Silva W","year":"2016","journal-title":"Plant Science"},{"key":"e_1_2_13_10_1","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1006\/abio.1993.1363","article-title":"Determination of the 13C\u2010labeling pattern of glucose by gas chromatography\u2010mass spectrometry","volume":"212","author":"Beylot M","year":"1993","journal-title":"Analytical Biochemistry"},{"key":"e_1_2_13_11_1","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/S0021-9673(03)00356-X","article-title":"Comprehensive chemical derivatization for gas chromatography\u2013mass spectrometry\u2010based multi\u2010targeted profiling of the major phytohormones","volume":"993","author":"Birkemeyer C","year":"2003","journal-title":"Journal of Chromatography A"},{"key":"e_1_2_13_12_1","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.tibtech.2004.12.001","article-title":"Metabolome analysis: the potential of in vivo labeling with stable isotopes for metabolite profiling","volume":"23","author":"Birkemeyer C","year":"2005","journal-title":"Trends in Biotechnology"},{"key":"e_1_2_13_13_1","doi-asserted-by":"crossref","first-page":"1830","DOI":"10.1016\/j.cmet.2023.07.013","article-title":"Comprehensive isotopomer analysis of glutamate and aspartate in small tissue samples","volume":"35","author":"Cai F","year":"2023","journal-title":"Cell Metabolism"},{"key":"e_1_2_13_14_1","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1104\/pp.113.234468","article-title":"A diel flux balance model captures interactions between light and dark metabolism during day\u2013night cycles in C3 and Crassulacean acid metabolism leaves","volume":"165","author":"Cheung CYM","year":"2014","journal-title":"Plant Physiology"},{"key":"e_1_2_13_15_1","doi-asserted-by":"crossref","first-page":"4628","DOI":"10.1021\/ac300611n","article-title":"Measuring complete isotopomer distribution of aspartate using gas chromatography\/tandem mass spectrometry","volume":"84","author":"Choi J","year":"2012","journal-title":"Analytical Chemistry"},{"key":"e_1_2_13_16_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1146\/annurev-arplant-050718-100221","article-title":"Modeling plant metabolism: from network reconstruction to mechanistic models","volume":"71","author":"Clark TJ","year":"2020","journal-title":"Annual Review of Plant Biology"},{"key":"e_1_2_13_17_1","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.ymben.2011.12.005","article-title":"Selection of tracers for 13C\u2010metabolic flux analysis using elementary metabolite units (EMU) basis vector methodology","volume":"14","author":"Crown SB","year":"2012","journal-title":"Metabolic Engineering"},{"key":"e_1_2_13_18_1","doi-asserted-by":"crossref","first-page":"E1392","DOI":"10.1073\/pnas.1424840112","article-title":"Thioredoxin, a master regulator of the tricarboxylic acid cycle in plant mitochondria","volume":"112","author":"Daloso DM","year":"2015","journal-title":"Proceedings of the National Academy of Sciences, USA"},{"key":"e_1_2_13_19_1","doi-asserted-by":"crossref","DOI":"10.3389\/fpls.2022.885051","article-title":"Validation of carbon isotopologue distribution measurements by GC\u2010MS and application to 13C\u2010metabolic flux analysis of the tricarboxylic acid cycle in Brassica napus leaves","volume":"13","author":"Dellero Y","year":"2023","journal-title":"Frontiers in Plant Science"},{"key":"e_1_2_13_20_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.jplph.2023.154162","article-title":"U\u201013C\u2010glucose incorporation into source leaves of Brassica napus highlights light\u2010dependent regulations of metabolic fluxes within central carbon metabolism","volume":"292","author":"Dellero Y","year":"2024","journal-title":"Journal of Plant Physiology"},{"key":"e_1_2_13_21_1","doi-asserted-by":"crossref","DOI":"10.3390\/metabo13040466","article-title":"Evaluation of GC\/MS\u2010based 13C\u2010positional approaches for TMS derivatives of organic and amino acids and application to plant 13C\u2010labeled experiments","volume":"13","author":"Dellero Y","year":"2023","journal-title":"Metabolites"},{"key":"e_1_2_13_22_1","unstructured":"DobsonG.2023.Utilisation of metabolic resources inArabidopsis thalianasuspension culture. PhD thesis University of Oxford Oxford England."},{"key":"e_1_2_13_23_1","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1038\/s41592-019-0344-8","article-title":"SIRIUS 4: a rapid tool for turning tandem mass spectra into metabolite structure information","volume":"16","author":"D\u00fchrkop K","year":"2019","journal-title":"Nature Methods"},{"key":"e_1_2_13_24_1","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1038\/nrm1451","article-title":"Metabolite profiling: from diagnostics to systems biology","volume":"5","author":"Fernie AR","year":"2004","journal-title":"Nature Reviews Molecular Cell Biology"},{"key":"e_1_2_13_25_1","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.1038\/81137","article-title":"Metabolite profiling for plant functional genomics","volume":"18","author":"Fiehn O","year":"2000","journal-title":"Nature Biotechnology"},{"key":"e_1_2_13_26_1","doi-asserted-by":"crossref","first-page":"2369","DOI":"10.1093\/pcp\/pcz123","article-title":"The lack of mitochondrial thioredoxin TRXo1 affects in vivo alternative oxidase activity and carbon metabolism under different light conditions","volume":"60","author":"Florez\u2010Sarasa I","year":"2019","journal-title":"Plant and Cell Physiology"},{"key":"e_1_2_13_27_1","doi-asserted-by":"crossref","first-page":"5987","DOI":"10.1093\/jxb\/erab098","article-title":"Thioredoxin\u2010mediated regulation of (photo)respiration and central metabolism","volume":"72","author":"Fonseca\u2010Pereira P","year":"2021","journal-title":"Journal of Experimental Botany"},{"key":"e_1_2_13_28_1","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1038\/s41477-022-01294-9","article-title":"Integrated flux and pool size analysis in plant central metabolism reveals unique roles of glycine and serine during photorespiration","volume":"9","author":"Fu X","year":"2023","journal-title":"Nature Plants"},{"key":"e_1_2_13_29_1","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1111\/tpj.14472","article-title":"Resolving subcellular plant metabolism","volume":"100","author":"F\u00fcrtauer L","year":"2019","journal-title":"The Plant Journal"},{"key":"e_1_2_13_30_1","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1093\/jxb\/erh006","article-title":"An approach to the genetics of nitrogen use efficiency in maize","volume":"55","author":"Gallais A","year":"2004","journal-title":"Journal of Experimental Botany"},{"key":"e_1_2_13_31_1","doi-asserted-by":"crossref","first-page":"1877","DOI":"10.1038\/s41477-025-02091-w","article-title":"Metabolic flux analysis in leaf metabolism quantifies the link between photorespiration and one carbon metabolism","volume":"11","author":"Gashu K","year":"2025","journal-title":"Nature Plants"},{"key":"e_1_2_13_32_1","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.tplants.2016.12.008","article-title":"The unprecedented versatility of the plants thioredoxin system","volume":"22","author":"Geigenberger P","year":"2017","journal-title":"Trends in Plant Science"},{"key":"e_1_2_13_33_1","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1111\/j.1365-313X.2011.04682.x","article-title":"Elemental formula annotation of polar and lipophilic metabolites using 13C, 15N and 34S isotope labelling, in combination with high\u2010resolution mass spectrometry","volume":"68","author":"Giavalisco P","year":"2011","journal-title":"The Plant Journal"},{"key":"e_1_2_13_34_1","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.ymben.2015.08.006","article-title":"13C metabolic flux analysis at a genome\u2010scale","volume":"32","author":"Gopalakrishnan S","year":"2015","journal-title":"Metabolic Engineering"},{"key":"e_1_2_13_35_1","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.ymben.2018.03.008","article-title":"Elucidation of photoautotrophic carbon flux topology in Synechocystis PCC 6803 using genome\u2010scale carbon mapping models","volume":"47","author":"Gopalakrishnan S","year":"2018","journal-title":"Metabolic Engineering"},{"key":"e_1_2_13_36_1","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1002\/jlcr.2580330304","article-title":"Stereoselective synthesis of stable isotope labeled L\u2010\u03b1\u2010amino acids: the enzymatic preparation of 13C\u2010labeled L\u2010glutamic acids","volume":"33","author":"Goux WJ","year":"1993","journal-title":"Journal of Labelled Compounds and Radiopharmaceuticals"},{"key":"e_1_2_13_37_1","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1007\/s00122-006-0429-5","article-title":"The genetics of nitrogen use in hexaploid wheat: N utilisation, development and yield","volume":"114","author":"Habash DZ","year":"2007","journal-title":"Theoretical and Applied Genetics"},{"key":"e_1_2_13_38_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.trac.2023.117225","article-title":"Scaling\u2010up metabolomics: current state and perspectives","volume":"167","author":"Hajjar G","year":"2023","journal-title":"TrAC Trends in Analytical Chemistry"},{"key":"e_1_2_13_39_1","doi-asserted-by":"crossref","first-page":"1803","DOI":"10.1038\/nprot.2014.115","article-title":"Flux profiling of photosynthetic carbon metabolism in intact plants","volume":"9","author":"Heise R","year":"2014","journal-title":"Nature Protocols"},{"key":"e_1_2_13_40_1","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1104\/pp.18.01357","article-title":"Genome\u2010scale fluxome of Synechococcus elongatus UTEX 2973 using transient 13C\u2010labeling data","volume":"179","author":"Hendry JI","year":"2019","journal-title":"Plant Physiology"},{"key":"e_1_2_13_41_1","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1080\/10256019808234070","article-title":"Enzymatic synthesis of [1\u201013C]\u2010 and [1\u201014C]\u2010L\u2010phenylalanine","volume":"34","author":"Jemielity J","year":"1998","journal-title":"Isotopes in Environmental and Health Studies"},{"key":"e_1_2_13_42_1","doi-asserted-by":"crossref","first-page":"1911","DOI":"10.1111\/nph.19734","article-title":"Isotopically nonstationary metabolic flux analysis of plants: recent progress and future opportunities","volume":"242","author":"Koley S","year":"2024","journal-title":"New Phytologist"},{"key":"e_1_2_13_43_1","doi-asserted-by":"crossref","first-page":"7653","DOI":"10.1093\/jxb\/erab389","article-title":"Whither metabolic flux analysis in plants?","volume":"72","author":"Kruger NJ","year":"2021","journal-title":"Journal of Experimental Botany"},{"key":"e_1_2_13_44_1","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1007\/BF00390260","article-title":"Dark fixation of CO2 during gluconeogenesis by the cotyledons of Cucurbita pepo L","volume":"140","author":"Leegood RC","year":"1978","journal-title":"Planta"},{"key":"e_1_2_13_45_1","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1007\/978-1-4939-7819-9_4","volume-title":"Plant metabolomics","author":"Lima VF","year":"2018"},{"key":"e_1_2_13_46_1","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.1111\/tpj.15484","article-title":"Establishment of a GC\u2010MS\u2010based 13C\u2010positional isotopomer approach suitable for investigating metabolic fluxes in plant primary metabolism","volume":"108","author":"Lima VF","year":"2021","journal-title":"The Plant Journal"},{"key":"e_1_2_13_47_1","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1038\/nprot.2006.59","article-title":"Gas chromatography mass spectrometry\u2013based metabolite profiling in plants","volume":"1","author":"Lisec J","year":"2006","journal-title":"Nature Protocols"},{"key":"e_1_2_13_48_1","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1038\/nature10011","article-title":"Controllability of complex networks","volume":"473","author":"Liu YY","year":"2011","journal-title":"Nature"},{"key":"e_1_2_13_49_1","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.jchromb.2007.10.022","article-title":"LC\u2010MS\u2010based metabonomics analysis","volume":"866","author":"Lu X","year":"2008","journal-title":"Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences"},{"key":"e_1_2_13_50_1","doi-asserted-by":"crossref","first-page":"16967","DOI":"10.1073\/pnas.1319485111","article-title":"Isotopically nonstationary 13 C flux analysis of changes in Arabidopsis thaliana leaf metabolism due to high light acclimation","volume":"111","author":"Ma F","year":"2014","journal-title":"Proceedings of the National Academy of Sciences, USA"},{"key":"e_1_2_13_51_1","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/S0922-338X(97)87337-0","article-title":"Production of L\u2010[3\u201013C] serine from [13C] formaldehyde and glycine using an enzyme system combined with tetrahydrofolate regeneration","volume":"83","author":"Maeda H","year":"1997","journal-title":"Journal of Fermentation and Bioengineering"},{"key":"e_1_2_13_52_1","doi-asserted-by":"crossref","DOI":"10.1093\/plphys\/kiaf406","article-title":"Genome\u2010scale metabolic models in plant stress physiology: implications for future climate resilience","volume":"199","author":"Mangaravite \u00c9","year":"2025","journal-title":"Plant Physiology"},{"key":"e_1_2_13_53_1","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1007\/978-1-4939-1170-7_16","volume-title":"Metabolic flux analysis: methods and protocols. Methods in molecular biology, vol. 1191","author":"Matsuoka Y","year":"2014"},{"key":"e_1_2_13_54_1","doi-asserted-by":"crossref","first-page":"1362","DOI":"10.1021\/acs.analchem.5b03887","article-title":"MID max: LC\u2010MS\/MS method for measuring the precursor and product mass isotopomer distributions of metabolic intermediates and cofactors for metabolic flux analysis applications","volume":"88","author":"McCloskey D","year":"2016","journal-title":"Analytical Chemistry"},{"key":"e_1_2_13_55_1","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1007\/s40626-019-00139-9","article-title":"Metabolomics for understanding stomatal movements","volume":"31","author":"Medeiros DB","year":"2019","journal-title":"Theoretical and Experimental Plant Physiology"},{"key":"e_1_2_13_56_1","doi-asserted-by":"crossref","DOI":"10.1007\/s11306-024-02167-2","article-title":"Navigating common pitfalls in metabolite identification and metabolomics bioinformatics","volume":"20","author":"Novoa\u2010Del\u2010Toro EM","year":"2024","journal-title":"Metabolomics: Official Journal of the Metabolomic Society"},{"key":"e_1_2_13_57_1","doi-asserted-by":"crossref","first-page":"A0073","DOI":"10.5702\/massspectrometry.A0073","article-title":"Fragmentation of dicarboxylic and tricarboxylic acids in the Krebs cycle using GC\u2010EI\u2010MS and GC\u2010EI\u2010MS\/MS","volume":"8","author":"Okahashi N","year":"2019","journal-title":"Mass Spectrometry"},{"key":"e_1_2_13_58_1","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1016\/S0968-0004(03)00064-1","article-title":"Metabolic pathways in the post\u2010genome era","volume":"28","author":"Papin JA","year":"2003","journal-title":"Trends in Biochemical Sciences"},{"key":"e_1_2_13_59_1","doi-asserted-by":"crossref","DOI":"10.1002\/cppb.20100","article-title":"Mass spectrometry\u2010based untargeted plant metabolomics","volume":"4","author":"Perez de Souza L","year":"2019","journal-title":"Current Protocols in Plant Biology"},{"key":"e_1_2_13_60_1","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1038\/s41592-021-01116-4","article-title":"Ultra\u2010high\u2010performance liquid chromatography high\u2010resolution mass spectrometry variants for metabolomics research","volume":"18","author":"Perez de Souza L","year":"2021","journal-title":"Nature Methods"},{"key":"e_1_2_13_61_1","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.plaphy.2022.10.022","article-title":"Thioredoxins regulate the metabolic fluxes throughout the tricarboxylic acid cycle and associated pathways in a light\u2010independent manner","volume":"193","author":"Porto NP","year":"2022","journal-title":"Plant Physiology and Biochemistry"},{"key":"e_1_2_13_62_1","doi-asserted-by":"crossref","DOI":"10.1093\/plphys\/kiaf020","article-title":"Dynamic photosynthetic labeling and carbon\u2010positional mass spectrometry monitor in vivo RUBISCO carbon assimilation rates","volume":"197","author":"Rajarathinam Y","year":"2025","journal-title":"Plant Physiology"},{"key":"e_1_2_13_63_1","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1111\/j.1365-313X.2005.02649.x","article-title":"Measuring multiple fluxes through plant metabolic networks","volume":"45","author":"Ratcliffe RG","year":"2006","journal-title":"The Plant Journal"},{"key":"e_1_2_13_64_1","doi-asserted-by":"crossref","DOI":"10.1186\/s13321-016-0115-9","article-title":"MetFrag relaunched: incorporating strategies beyond in silico fragmentation","volume":"8","author":"Ruttkies C","year":"2016","journal-title":"Journal of Cheminformatics"},{"key":"e_1_2_13_65_1","doi-asserted-by":"crossref","DOI":"10.3390\/ijms19092506","article-title":"The sugar\u2010signaling hub: overview of regulators and interaction with the hormonal and metabolic network","volume":"19","author":"Sakr S","year":"2018","journal-title":"International Journal of Molecular Sciences"},{"key":"e_1_2_13_66_1","doi-asserted-by":"crossref","first-page":"5961","DOI":"10.1093\/jxb\/erx388","article-title":"Metabolite profiling at the cellular and subcellular level reveals metabolites associated with salinity tolerance in sugar beet","volume":"68","author":"Sazzad Hossain M","year":"2017","journal-title":"Journal of Experimental Botany"},{"key":"e_1_2_13_67_1","doi-asserted-by":"crossref","first-page":"1332","DOI":"10.1016\/j.febslet.2005.01.029","article-title":"GC\u2010MS libraries for the rapid identification of metabolites in complex biological samples","volume":"579","author":"Schauer N","year":"2005","journal-title":"FEBS Letters"},{"key":"e_1_2_13_68_1","doi-asserted-by":"crossref","first-page":"3832","DOI":"10.1038\/s41467-021-23953-9","article-title":"Ion identity molecular networking for mass spectrometry\u2010based metabolomics in the GNPS environment","volume":"12","author":"Schmid R","year":"2021","journal-title":"Nature Communications"},{"key":"e_1_2_13_69_1","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1038\/s41589-020-00724-z","article-title":"A community resource for paired genomic and metabolomic data mining","volume":"17","author":"Schorn MA","year":"2021","journal-title":"Nature Chemical Biology"},{"key":"e_1_2_13_70_1","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1038\/73786","article-title":"A general definition of metabolic pathways useful for systematic organization and analysis of complex metabolic networks","volume":"18","author":"Schuster S","year":"2000","journal-title":"Nature Biotechnology"},{"key":"e_1_2_13_71_1","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.pbi.2004.03.016","article-title":"Understanding flux in plant metabolic networks","volume":"7","author":"Schwender J","year":"2004","journal-title":"Current Opinion in Plant Biology"},{"key":"e_1_2_13_72_1","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1111\/nph.12283","article-title":"Concurrent overactivation of the cytosolic glutamine synthetase and the GABA shunt in the ABA\u2010deficient sitiens mutant of tomato leads to resistance against Botrytis cinerea","volume":"199","author":"Seifi HS","year":"2013","journal-title":"New Phytologist"},{"key":"e_1_2_13_73_1","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1104\/pp.114.254474","article-title":"Phosphoenolpyruvate carboxylase in Arabidopsis leaves plays a crucial role in carbon and nitrogen metabolism","volume":"167","author":"Shi J","year":"2015","journal-title":"Plant Physiology"},{"key":"e_1_2_13_74_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.mec.2020.e00123","article-title":"Metabolic flux analysis of secondary metabolism in plants","volume":"10","author":"Shih M","year":"2020","journal-title":"Metabolic Engineering Communications"},{"key":"e_1_2_13_75_1","doi-asserted-by":"crossref","first-page":"3872","DOI":"10.1093\/jxb\/eraf125","article-title":"The mitochondrial thioredoxin system regulates the TCA cycle\u2010derived metabolic fluxes toward the GS\/GOGAT cycle in illuminated leaves","volume":"76","author":"Souza PVL","year":"2025","journal-title":"Journal of Experimental Botany"},{"key":"e_1_2_13_76_1","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1016\/j.tplants.2013.11.003","article-title":"Why measure enzyme activities in the era of systems biology?","volume":"19","author":"Stitt M","year":"2014","journal-title":"Trends in Plant Science"},{"key":"e_1_2_13_77_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1333\/s00897072045a","article-title":"Isotopomers and isotopologues: the history behind the confusion","volume":"12","author":"Stoll S","year":"2007","journal-title":"Chemical Educator"},{"key":"e_1_2_13_78_1","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1007\/s11306-013-0569-y","article-title":"Annotating unknown components from GC\/EI\u2010MS\u2010based metabolite profiling experiments using GC\/APCI(+)\u2010QTOFMS","volume":"10","author":"Strehmel N","year":"2014","journal-title":"Metabolomics"},{"key":"e_1_2_13_79_1","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1111\/j.1469-8137.2005.01513.x","article-title":"Regulation of metabolic networks: understanding metabolic complexity in the systems biology era","volume":"168","author":"Sweetlove LJ","year":"2005","journal-title":"New Phytologist"},{"key":"e_1_2_13_80_1","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1146\/annurev-arplant-050312-120233","article-title":"The spatial organization of metabolism within the plant cell","volume":"64","author":"Sweetlove LJ","year":"2013","journal-title":"Annual Review of Plant Biology"},{"key":"e_1_2_13_81_1","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1111\/tpj.13464","article-title":"Engineering central metabolism \u2013 a grand challenge for plant biologists","volume":"90","author":"Sweetlove LJ","year":"2017","journal-title":"The Plant Journal"},{"key":"e_1_2_13_82_1","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1038\/s41477-025-01965-3","article-title":"Non\u2010canonical plant metabolism","volume":"11","author":"Sweetlove LJ","year":"2025","journal-title":"Nature Plants"},{"key":"e_1_2_13_83_1","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1105\/tpc.112.106989","article-title":"Metabolic fluxes in an illuminated Arabidopsis rosette","volume":"25","author":"Szecowka M","year":"2013","journal-title":"Plant Cell"},{"key":"e_1_2_13_84_1","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.tibtech.2012.10.011","article-title":"Network analysis: tackling complex data to study plant metabolism","volume":"31","author":"Toubiana D","year":"2013","journal-title":"Trends in Biotechnology"},{"key":"e_1_2_13_85_1","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1046\/j.1432-1033.2003.03469.x","article-title":"Regulation of pyruvate dehydrogenase complex activity in plant cells","volume":"270","author":"Tovar\u2010M\u00e9ndez A","year":"2003","journal-title":"European Journal of Biochemistry"},{"key":"e_1_2_13_86_1","doi-asserted-by":"crossref","first-page":"7946","DOI":"10.1021\/acs.analchem.6b00770","article-title":"Hydrogen rearrangement rules: computational MS\/MS fragmentation and structure elucidation using MS\u2010FINDER software","volume":"88","author":"Tsugawa H","year":"2016","journal-title":"Analytical Chemistry"},{"key":"e_1_2_13_87_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.plaphy.2025.109905","article-title":"Flux in the field: genome\u2010scale modelling reveals changes in soybean (Glycine max) seed reserve metabolism under drought stress","volume":"224","author":"Vinson CC","year":"2025","journal-title":"Plant Physiology and Biochemistry"},{"key":"e_1_2_13_88_1","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1006\/mben.2001.0187","article-title":"13C metabolic flux analysis","volume":"3","author":"Wiechert W","year":"2001","journal-title":"Metabolic Engineering"},{"key":"e_1_2_13_89_1","doi-asserted-by":"crossref","first-page":"7136","DOI":"10.1093\/jxb\/erab316","article-title":"Carbon flux around leaf\u2010cytosolic glyceraldehyde\u20103\u2010phosphate dehydrogenase introduces a 13C signal in plant glucose","volume":"72","author":"Wieloch T","year":"2021","journal-title":"Journal of Experimental Botany"},{"key":"e_1_2_13_90_1","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1111\/nph.70412","article-title":"Positional 13C enrichment analysis of aspartate determines PEPC activity in vivo","volume":"248","author":"Wittemeier L","year":"2025","journal-title":"New Phytologist"},{"key":"e_1_2_13_91_1","doi-asserted-by":"crossref","first-page":"1333","DOI":"10.1093\/bioinformatics\/btu015","article-title":"INCA: a computational platform for isotopically non\u2010stationary metabolic flux analysis","volume":"30","author":"Young JD","year":"2014","journal-title":"Bioinformatics"},{"key":"e_1_2_13_92_1","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1002\/bit.21632","article-title":"An elementary metabolite unit (EMU) based method of isotopically nonstationary flux analysis","volume":"99","author":"Young JD","year":"2008","journal-title":"Biotechnology and Bioengineering"},{"key":"e_1_2_13_93_1","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1038\/nprot.2009.58","article-title":"13C\u2010based metabolic flux analysis","volume":"4","author":"Zamboni N","year":"2009","journal-title":"Nature Protocols"},{"key":"e_1_2_13_94_1","doi-asserted-by":"crossref","first-page":"1104","DOI":"10.1016\/j.molp.2021.03.023","article-title":"Two mitochondrial phosphatases, PP2c63 and Sal2, are required for posttranslational regulation of the TCA cycle in Arabidopsis","volume":"14","author":"Zhang Y","year":"2021","journal-title":"Molecular Plant"}],"container-title":["New Phytologist"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/nph.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/nph.71696","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/nph.onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/nph.71696","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/nph.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/nph.71696","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T03:39:29Z","timestamp":1792640369000},"score":1,"resource":{"primary":{"URL":"https:\/\/nph.onlinelibrary.wiley.com\/doi\/10.1111\/nph.71696"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,21]]},"references-count":93,"alternative-id":["10.1111\/nph.71696"],"URL":"https:\/\/doi.org\/10.1111\/nph.71696","archive":["Portico"],"relation":{},"ISSN":["0028-646X","1469-8137"],"issn-type":[{"value":"0028-646X","type":"print"},{"value":"1469-8137","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,21]]},"assertion":[{"value":"2026-05-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-04","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-21","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"nph.71696"}}