#METABOLOMICS WORKBENCH smvanliempd_20250402_085356 DATATRACK_ID:5813 STUDY_ID:ST003869 ANALYSIS_ID:AN006358 PROJECT_ID:PR002425 VERSION 1 CREATED_ON April 16, 2025, 11:12 pm #PROJECT PR:PROJECT_TITLE Measuring TCA cycle metabolites in cells after labeling via 13C5-glutamine with PR:PROJECT_TITLE high resolution LCMS. PR:PROJECT_SUMMARY Measuring TCA cycle metabolites in cells after labeling via 13C5-glutamine with PR:PROJECT_SUMMARY high resolution LCMS. Cell treatments consisted of Linc and DLST knock down and PR:PROJECT_SUMMARY controls. PR:INSTITUTE CIC bioGUNE - Centro de Investigación Cooperativa en Biociencias PR:LAST_NAME van Liempd PR:FIRST_NAME Sebastiaan PR:ADDRESS Parque Tecnológico de Vizcaya Ed. 800, Derio, Bizkaia, 48160, Spain PR:EMAIL smvanliempd@cicbiogune.es PR:PHONE 944061317 #STUDY ST:STUDY_TITLE A long non-coding RNA (lncRNA}-mediated metabolic rewiring of cell senescence ST:STUDY_SUMMARY Despite not proliferating, senescent cells remain metabolically active to ST:STUDY_SUMMARY maintain the senescence program. However, the mechanisms behind this metabolic ST:STUDY_SUMMARY reprogramming are not well understood. We identify sin-lncRNA, a previously ST:STUDY_SUMMARY uncharacterized long noncoding RNA (lncRNA), a key player in this response. ST:STUDY_SUMMARY While strongly activated in senescence by C/EBPβ, sin-lncRNA loss reinforces ST:STUDY_SUMMARY the senescence program by altering oxidative phosphorylation and rewiring ST:STUDY_SUMMARY mitochondrial metabolism. By interacting with dihydrolipoamide ST:STUDY_SUMMARY S-succinyltransferase (DLST), it facilitates its mitochondrial localization. ST:STUDY_SUMMARY DLST is an enzyme of the TCA cycle that regulates the conversion of ST:STUDY_SUMMARY -ketoglutarate to succinyl-CoA. Results of metabolomic experiment show that ST:STUDY_SUMMARY the TCA is strongly affected upon DLST knockdown as seen by reduction in ST:STUDY_SUMMARY intermediate metabolites. However, sin-lncRNA does not affect any of the ST:STUDY_SUMMARY metabolites detected. Alternatively, we have observed that a compensatory ST:STUDY_SUMMARY mechanism includes the upregulation of the GABA shunt pathway. Moreover, ST:STUDY_SUMMARY depletion of sin-lncRNA causes DLST nuclear translocation, leading to ST:STUDY_SUMMARY transcriptional changes in OXPHOS genes. While not expressed in highly ST:STUDY_SUMMARY proliferative cancer cells it is strongly induced upon cisplatin-induced ST:STUDY_SUMMARY senescence. Depletion of sin-lncRNA in ovarian cancer cells, reduces oxygen ST:STUDY_SUMMARY consumption and increases extracellular acidification, sensitizing cells to ST:STUDY_SUMMARY cisplatin treatment. Altogether, these results indicate that sin-lncRNA is ST:STUDY_SUMMARY specifically induced in senescence to maintain metabolic homeostasis, unveiling ST:STUDY_SUMMARY an RNA-dependent metabolic rewiring specific to senescent cells. ST:INSTITUTE CIC bioGUNE - Centro de Investigación Cooperativa en Biociencias ST:LAST_NAME van Liempd ST:FIRST_NAME Sebastiaan ST:ADDRESS Parque Tecnológico de Vizcaya Ed. 800, Derio, Bizkaia, 48160, Spain ST:EMAIL smvanliempd@cicbiogune.es ST:PHONE 944061317 #SUBJECT SU:SUBJECT_TYPE Cultured cells SU:SUBJECT_SPECIES Homo sapiens SU:TAXONOMY_ID 9606 SU:CELL_STRAIN_DETAILS IMR90 ER:RAS fibroblasts #SUBJECT_SAMPLE_FACTORS: SUBJECT(optional)[tab]SAMPLE[tab]FACTORS(NAME:VALUE pairs separated by |)[tab]Raw file names and additional sample data SUBJECT_SAMPLE_FACTORS - 20230524_TCA_CELLS_UNAV_Marta_007a Precursor:- | Knock.down:- | Sample source:Curve RAW_FILE_NAME(Raw file name)=20230524_TCA_CELLS_UNAV_Marta_007a.mzXML; Sample.ID=Curve01 SUBJECT_SAMPLE_FACTORS - 20230524_TCA_CELLS_UNAV_Marta_008a Precursor:- | Knock.down:- | Sample source:Curve RAW_FILE_NAME(Raw file name)=20230524_TCA_CELLS_UNAV_Marta_008a.mzXML; Sample.ID=Curve02 SUBJECT_SAMPLE_FACTORS - 20230524_TCA_CELLS_UNAV_Marta_009a Precursor:- | Knock.down:- | Sample source:Curve RAW_FILE_NAME(Raw file name)=20230524_TCA_CELLS_UNAV_Marta_009a.mzXML; Sample.ID=Curve03 SUBJECT_SAMPLE_FACTORS - 20230524_TCA_CELLS_UNAV_Marta_010a Precursor:- | Knock.down:- | Sample source:Curve RAW_FILE_NAME(Raw file name)=20230524_TCA_CELLS_UNAV_Marta_010a.mzXML; Sample.ID=Curve04 SUBJECT_SAMPLE_FACTORS - 20230524_TCA_CELLS_UNAV_Marta_011a Precursor:- | Knock.down:- | Sample source:Curve RAW_FILE_NAME(Raw file name)=20230524_TCA_CELLS_UNAV_Marta_011a.mzXML; Sample.ID=Curve05 SUBJECT_SAMPLE_FACTORS - 20230524_TCA_CELLS_UNAV_Marta_012a Precursor:- | Knock.down:- | Sample source:Curve RAW_FILE_NAME(Raw file name)=20230524_TCA_CELLS_UNAV_Marta_012a.mzXML; Sample.ID=Curve06 SUBJECT_SAMPLE_FACTORS - 20230524_TCA_CELLS_UNAV_Marta_013a Precursor:- | Knock.down:- | Sample source:Curve RAW_FILE_NAME(Raw file name)=20230524_TCA_CELLS_UNAV_Marta_013a.mzXML; Sample.ID=Curve07 SUBJECT_SAMPLE_FACTORS - 20230524_TCA_CELLS_UNAV_Marta_014a Precursor:- | Knock.down:- | Sample source:Curve RAW_FILE_NAME(Raw file name)=20230524_TCA_CELLS_UNAV_Marta_014a.mzXML; Sample.ID=Curve08 SUBJECT_SAMPLE_FACTORS - 20230524_TCA_CELLS_UNAV_Marta_015a Precursor:- | Knock.down:- | Sample source:Curve RAW_FILE_NAME(Raw file name)=20230524_TCA_CELLS_UNAV_Marta_015a.mzXML; Sample.ID=Curve09 SUBJECT_SAMPLE_FACTORS - 20230524_TCA_CELLS_UNAV_Marta_016a Precursor:- | Knock.down:- | Sample source:Curve RAW_FILE_NAME(Raw file name)=20230524_TCA_CELLS_UNAV_Marta_016a.mzXML; Sample.ID=Curve10 SUBJECT_SAMPLE_FACTORS - 20230524_TCA_CELLS_UNAV_Marta_017a Precursor:- | Knock.down:- | Sample source:Curve RAW_FILE_NAME(Raw file name)=20230524_TCA_CELLS_UNAV_Marta_017a.mzXML; Sample.ID=Curve11 SUBJECT_SAMPLE_FACTORS - 20230524_TCA_CELLS_UNAV_Marta_018a Precursor:- | Knock.down:- | Sample source:Curve RAW_FILE_NAME(Raw file name)=20230524_TCA_CELLS_UNAV_Marta_018a.mzXML; Sample.ID=Curve12 SUBJECT_SAMPLE_FACTORS - 20230524_TCA_CELLS_UNAV_Marta_019a Precursor:- | Knock.down:- | Sample source:Curve RAW_FILE_NAME(Raw file name)=20230524_TCA_CELLS_UNAV_Marta_019a.mzXML; Sample.ID=Curve13 SUBJECT_SAMPLE_FACTORS - 20230524_TCA_CELLS_UNAV_Marta_020a Precursor:- | Knock.down:- | Sample source:Blank RAW_FILE_NAME(Raw file name)=20230524_TCA_CELLS_UNAV_Marta_020a.mzXML; Sample.ID=Blank1 SUBJECT_SAMPLE_FACTORS - 20230524_TCA_CELLS_UNAV_Marta_021a Precursor:- | Knock.down:- | Sample source:Blank RAW_FILE_NAME(Raw file name)=20230524_TCA_CELLS_UNAV_Marta_021a.mzXML; Sample.ID=Blank2 SUBJECT_SAMPLE_FACTORS - 20230524_TCA_CELLS_UNAV_Marta_022a Precursor:- | Knock.down:- | Sample source:Blank RAW_FILE_NAME(Raw file name)=20230524_TCA_CELLS_UNAV_Marta_022a.mzXML; Sample.ID=Blank3 SUBJECT_SAMPLE_FACTORS - 20230524_TCA_CELLS_UNAV_Marta_023a Precursor:- | Knock.down:- | Sample source:QC_INIT RAW_FILE_NAME(Raw file name)=20230524_TCA_CELLS_UNAV_Marta_023a.mzXML; Sample.ID=QC_INIT1 SUBJECT_SAMPLE_FACTORS - 20230524_TCA_CELLS_UNAV_Marta_024a Precursor:- | Knock.down:- | Sample source:QC_INIT RAW_FILE_NAME(Raw file name)=20230524_TCA_CELLS_UNAV_Marta_024a.mzXML; Sample.ID=QC_INIT2 SUBJECT_SAMPLE_FACTORS - 20230524_TCA_CELLS_UNAV_Marta_025a Precursor:- | Knock.down:- | Sample source:QC_INIT RAW_FILE_NAME(Raw file name)=20230524_TCA_CELLS_UNAV_Marta_025a.mzXML; Sample.ID=QC_INIT3 SUBJECT_SAMPLE_FACTORS - 20230524_TCA_CELLS_UNAV_Marta_026a Precursor:- | Knock.down:- | Sample source:QC_INIT RAW_FILE_NAME(Raw file name)=20230524_TCA_CELLS_UNAV_Marta_026a.mzXML; Sample.ID=QC_INIT4 SUBJECT_SAMPLE_FACTORS - 20230524_TCA_CELLS_UNAV_Marta_027a Precursor:- | Knock.down:- | Sample source:QC RAW_FILE_NAME(Raw file name)=20230524_TCA_CELLS_UNAV_Marta_027a.mzXML; Sample.ID=QC01 SUBJECT_SAMPLE_FACTORS - 20230524_TCA_CELLS_UNAV_Marta_028a Precursor:- | Knock.down:- | Sample source:QC RAW_FILE_NAME(Raw file name)=20230524_TCA_CELLS_UNAV_Marta_028a.mzXML; Sample.ID=QC02 SUBJECT_SAMPLE_FACTORS - 20230524_TCA_CELLS_UNAV_Marta_029a Precursor:- | Knock.down:- | Sample source:QC RAW_FILE_NAME(Raw file name)=20230524_TCA_CELLS_UNAV_Marta_029a.mzXML; Sample.ID=QC03 SUBJECT_SAMPLE_FACTORS - 20230524_TCA_CELLS_UNAV_Marta_030a Precursor:- | Knock.down:- | Sample source:QC RAW_FILE_NAME(Raw file name)=20230524_TCA_CELLS_UNAV_Marta_030a.mzXML; Sample.ID=QC04 SUBJECT_SAMPLE_FACTORS - 20230524_TCA_CELLS_UNAV_Marta_031a Precursor:- | Knock.down:- | Sample source:QC RAW_FILE_NAME(Raw file name)=20230524_TCA_CELLS_UNAV_Marta_031a.mzXML; Sample.ID=QC05 SUBJECT_SAMPLE_FACTORS - 20230524_TCA_CELLS_UNAV_Marta_032a Precursor:- | Knock.down:- | Sample source:Curve RAW_FILE_NAME(Raw file name)=20230524_TCA_CELLS_UNAV_Marta_032a.mzXML; Sample.ID=Curve01 SUBJECT_SAMPLE_FACTORS - 20230524_TCA_CELLS_UNAV_Marta_033a Precursor:- | Knock.down:- | Sample source:Curve RAW_FILE_NAME(Raw file name)=20230524_TCA_CELLS_UNAV_Marta_033a.mzXML; Sample.ID=Curve02 SUBJECT_SAMPLE_FACTORS - 20230524_TCA_CELLS_UNAV_Marta_034a Precursor:- | Knock.down:- | Sample source:Curve RAW_FILE_NAME(Raw file name)=20230524_TCA_CELLS_UNAV_Marta_034a.mzXML; Sample.ID=Curve03 SUBJECT_SAMPLE_FACTORS - 20230524_TCA_CELLS_UNAV_Marta_035a Precursor:- | Knock.down:- | Sample source:Curve RAW_FILE_NAME(Raw file name)=20230524_TCA_CELLS_UNAV_Marta_035a.mzXML; Sample.ID=Curve04 SUBJECT_SAMPLE_FACTORS - 20230524_TCA_CELLS_UNAV_Marta_036a Precursor:- | Knock.down:- | Sample source:Curve RAW_FILE_NAME(Raw file name)=20230524_TCA_CELLS_UNAV_Marta_036a.mzXML; Sample.ID=Curve05 SUBJECT_SAMPLE_FACTORS - 20230524_TCA_CELLS_UNAV_Marta_037a Precursor:- | Knock.down:- | Sample source:Curve RAW_FILE_NAME(Raw file name)=20230524_TCA_CELLS_UNAV_Marta_037a.mzXML; Sample.ID=Curve06 SUBJECT_SAMPLE_FACTORS - 20230524_TCA_CELLS_UNAV_Marta_038a Precursor:- | Knock.down:- | Sample source:Curve RAW_FILE_NAME(Raw file name)=20230524_TCA_CELLS_UNAV_Marta_038a.mzXML; Sample.ID=Curve07 SUBJECT_SAMPLE_FACTORS - 20230524_TCA_CELLS_UNAV_Marta_039a Precursor:- | Knock.down:- | Sample source:Curve RAW_FILE_NAME(Raw file name)=20230524_TCA_CELLS_UNAV_Marta_039a.mzXML; Sample.ID=Curve08 SUBJECT_SAMPLE_FACTORS - 20230524_TCA_CELLS_UNAV_Marta_040a Precursor:- | Knock.down:- | Sample source:Curve RAW_FILE_NAME(Raw file name)=20230524_TCA_CELLS_UNAV_Marta_040a.mzXML; Sample.ID=Curve09 SUBJECT_SAMPLE_FACTORS - 20230524_TCA_CELLS_UNAV_Marta_041a Precursor:- | Knock.down:- | Sample source:Curve RAW_FILE_NAME(Raw file name)=20230524_TCA_CELLS_UNAV_Marta_041a.mzXML; Sample.ID=Curve10 SUBJECT_SAMPLE_FACTORS - 20230524_TCA_CELLS_UNAV_Marta_042a Precursor:- | Knock.down:- | Sample source:Curve RAW_FILE_NAME(Raw file name)=20230524_TCA_CELLS_UNAV_Marta_042a.mzXML; Sample.ID=Curve11 SUBJECT_SAMPLE_FACTORS - 20230524_TCA_CELLS_UNAV_Marta_043a Precursor:- | Knock.down:- | Sample source:Curve RAW_FILE_NAME(Raw file name)=20230524_TCA_CELLS_UNAV_Marta_043a.mzXML; Sample.ID=Curve12 SUBJECT_SAMPLE_FACTORS - 20230524_TCA_CELLS_UNAV_Marta_044a Precursor:- | Knock.down:- | Sample source:Curve RAW_FILE_NAME(Raw file name)=20230524_TCA_CELLS_UNAV_Marta_044a.mzXML; Sample.ID=Curve13 SUBJECT_SAMPLE_FACTORS - 20230524_TCA_CELLS_UNAV_Marta_045a Precursor:13C5-Glutamine | Knock.down:CTL | Sample source:Fibroblasts RAW_FILE_NAME(Raw file name)=20230524_TCA_CELLS_UNAV_Marta_045a.mzXML; Sample.ID=CTL_1 SUBJECT_SAMPLE_FACTORS - 20230524_TCA_CELLS_UNAV_Marta_046a Precursor:13C5-Glutamine | Knock.down:CTL | Sample source:Fibroblasts RAW_FILE_NAME(Raw file name)=20230524_TCA_CELLS_UNAV_Marta_046a.mzXML; Sample.ID=CTL_2 SUBJECT_SAMPLE_FACTORS - 20230524_TCA_CELLS_UNAV_Marta_047a Precursor:13C5-Glutamine | Knock.down:CTL | Sample source:Fibroblasts RAW_FILE_NAME(Raw file name)=20230524_TCA_CELLS_UNAV_Marta_047a.mzXML; Sample.ID=CTL_3 SUBJECT_SAMPLE_FACTORS - 20230524_TCA_CELLS_UNAV_Marta_048a Precursor:13C5-Glutamine | Knock.down:CTL | Sample source:Fibroblasts RAW_FILE_NAME(Raw file name)=20230524_TCA_CELLS_UNAV_Marta_048a.mzXML; Sample.ID=CTL_4 SUBJECT_SAMPLE_FACTORS - 20230524_TCA_CELLS_UNAV_Marta_049a Precursor:13C5-Glutamine | Knock.down:CTL | Sample source:Fibroblasts RAW_FILE_NAME(Raw file name)=20230524_TCA_CELLS_UNAV_Marta_049a.mzXML; Sample.ID=CTL_5 SUBJECT_SAMPLE_FACTORS - 20230524_TCA_CELLS_UNAV_Marta_050a Precursor:Unlabelled | Knock.down:CTL | Sample source:Fibroblasts RAW_FILE_NAME(Raw file name)=20230524_TCA_CELLS_UNAV_Marta_050a.mzXML; Sample.ID=Unlabelled_1 SUBJECT_SAMPLE_FACTORS - 20230524_TCA_CELLS_UNAV_Marta_051a Precursor:Unlabelled | Knock.down:CTL | Sample source:Fibroblasts RAW_FILE_NAME(Raw file name)=20230524_TCA_CELLS_UNAV_Marta_051a.mzXML; Sample.ID=Unlabelled_2 SUBJECT_SAMPLE_FACTORS - 20230524_TCA_CELLS_UNAV_Marta_052a Precursor:Unlabelled | Knock.down:CTL | Sample source:Fibroblasts RAW_FILE_NAME(Raw file name)=20230524_TCA_CELLS_UNAV_Marta_052a.mzXML; Sample.ID=Unlabelled_3 SUBJECT_SAMPLE_FACTORS - 20230524_TCA_CELLS_UNAV_Marta_053a Precursor:Unlabelled | Knock.down:CTL | Sample source:Fibroblasts RAW_FILE_NAME(Raw file name)=20230524_TCA_CELLS_UNAV_Marta_053a.mzXML; Sample.ID=Unlabelled_4 SUBJECT_SAMPLE_FACTORS - 20230524_TCA_CELLS_UNAV_Marta_054a Precursor:Unlabelled | Knock.down:CTL | Sample source:Fibroblasts RAW_FILE_NAME(Raw file name)=20230524_TCA_CELLS_UNAV_Marta_054a.mzXML; Sample.ID=Unlabelled_5 SUBJECT_SAMPLE_FACTORS - 20230524_TCA_CELLS_UNAV_Marta_055a Precursor:13C5-Glutamine | Knock.down:Linc KD | Sample source:Fibroblasts RAW_FILE_NAME(Raw file name)=20230524_TCA_CELLS_UNAV_Marta_055a.mzXML; Sample.ID=Linc KD_1 SUBJECT_SAMPLE_FACTORS - 20230524_TCA_CELLS_UNAV_Marta_056a Precursor:13C5-Glutamine | Knock.down:Linc KD | Sample source:Fibroblasts RAW_FILE_NAME(Raw file name)=20230524_TCA_CELLS_UNAV_Marta_056a.mzXML; Sample.ID=Linc KD_2 SUBJECT_SAMPLE_FACTORS - 20230524_TCA_CELLS_UNAV_Marta_057a Precursor:13C5-Glutamine | Knock.down:Linc KD | Sample source:Fibroblasts RAW_FILE_NAME(Raw file name)=20230524_TCA_CELLS_UNAV_Marta_057a.mzXML; Sample.ID=Linc KD_3 SUBJECT_SAMPLE_FACTORS - 20230524_TCA_CELLS_UNAV_Marta_058a Precursor:13C5-Glutamine | Knock.down:Linc KD | Sample source:Fibroblasts RAW_FILE_NAME(Raw file name)=20230524_TCA_CELLS_UNAV_Marta_058a.mzXML; Sample.ID=Linc KD_4 SUBJECT_SAMPLE_FACTORS - 20230524_TCA_CELLS_UNAV_Marta_059a Precursor:13C5-Glutamine | Knock.down:Linc KD | Sample source:Fibroblasts RAW_FILE_NAME(Raw file name)=20230524_TCA_CELLS_UNAV_Marta_059a.mzXML; Sample.ID=Linc KD_5 SUBJECT_SAMPLE_FACTORS - 20230524_TCA_CELLS_UNAV_Marta_060a Precursor:13C5-Glutamine | Knock.down:DLST KD | Sample source:Fibroblasts RAW_FILE_NAME(Raw file name)=20230524_TCA_CELLS_UNAV_Marta_060a.mzXML; Sample.ID=DLST KD_1 SUBJECT_SAMPLE_FACTORS - 20230524_TCA_CELLS_UNAV_Marta_061a Precursor:13C5-Glutamine | Knock.down:DLST KD | Sample source:Fibroblasts RAW_FILE_NAME(Raw file name)=20230524_TCA_CELLS_UNAV_Marta_061a.mzXML; Sample.ID=DLST KD_2 SUBJECT_SAMPLE_FACTORS - 20230524_TCA_CELLS_UNAV_Marta_062a Precursor:13C5-Glutamine | Knock.down:DLST KD | Sample source:Fibroblasts RAW_FILE_NAME(Raw file name)=20230524_TCA_CELLS_UNAV_Marta_062a.mzXML; Sample.ID=DLST KD_3 SUBJECT_SAMPLE_FACTORS - 20230524_TCA_CELLS_UNAV_Marta_063a Precursor:13C5-Glutamine | Knock.down:DLST KD | Sample source:Fibroblasts RAW_FILE_NAME(Raw file name)=20230524_TCA_CELLS_UNAV_Marta_063a.mzXML; Sample.ID=DLST KD_4 SUBJECT_SAMPLE_FACTORS - 20230524_TCA_CELLS_UNAV_Marta_064a Precursor:13C5-Glutamine | Knock.down:DLST KD | Sample source:Fibroblasts RAW_FILE_NAME(Raw file name)=20230524_TCA_CELLS_UNAV_Marta_064a.mzXML; Sample.ID=DLST KD_5 SUBJECT_SAMPLE_FACTORS - 20230524_TCA_CELLS_UNAV_Marta_065a Precursor:13C5-Glutamine | Knock.down:CTL | Sample source:Fibroblasts RAW_FILE_NAME(Raw file name)=20230524_TCA_CELLS_UNAV_Marta_065a.mzXML; Sample.ID=CTL_1 SUBJECT_SAMPLE_FACTORS - 20230524_TCA_CELLS_UNAV_Marta_066a Precursor:13C5-Glutamine | Knock.down:CTL | Sample source:Fibroblasts RAW_FILE_NAME(Raw file name)=20230524_TCA_CELLS_UNAV_Marta_066a.mzXML; Sample.ID=CTL_2 SUBJECT_SAMPLE_FACTORS - 20230524_TCA_CELLS_UNAV_Marta_067a Precursor:13C5-Glutamine | Knock.down:CTL | Sample source:Fibroblasts RAW_FILE_NAME(Raw file name)=20230524_TCA_CELLS_UNAV_Marta_067a.mzXML; Sample.ID=CTL_3 SUBJECT_SAMPLE_FACTORS - 20230524_TCA_CELLS_UNAV_Marta_068a Precursor:13C5-Glutamine | Knock.down:CTL | Sample source:Fibroblasts RAW_FILE_NAME(Raw file name)=20230524_TCA_CELLS_UNAV_Marta_068a.mzXML; Sample.ID=CTL_4 SUBJECT_SAMPLE_FACTORS - 20230524_TCA_CELLS_UNAV_Marta_069a Precursor:13C5-Glutamine | Knock.down:CTL | Sample source:Fibroblasts RAW_FILE_NAME(Raw file name)=20230524_TCA_CELLS_UNAV_Marta_069a.mzXML; Sample.ID=CTL_5 SUBJECT_SAMPLE_FACTORS - 20230524_TCA_CELLS_UNAV_Marta_070a Precursor:Unlabelled | Knock.down:CTL | Sample source:Fibroblasts RAW_FILE_NAME(Raw file name)=20230524_TCA_CELLS_UNAV_Marta_070a.mzXML; Sample.ID=Unlabelled_1 SUBJECT_SAMPLE_FACTORS - 20230524_TCA_CELLS_UNAV_Marta_071a Precursor:Unlabelled | Knock.down:CTL | Sample source:Fibroblasts RAW_FILE_NAME(Raw file name)=20230524_TCA_CELLS_UNAV_Marta_071a.mzXML; Sample.ID=Unlabelled_2 SUBJECT_SAMPLE_FACTORS - 20230524_TCA_CELLS_UNAV_Marta_072a Precursor:Unlabelled | Knock.down:CTL | Sample source:Fibroblasts RAW_FILE_NAME(Raw file name)=20230524_TCA_CELLS_UNAV_Marta_072a.mzXML; Sample.ID=Unlabelled_3 SUBJECT_SAMPLE_FACTORS - 20230524_TCA_CELLS_UNAV_Marta_073a Precursor:Unlabelled | Knock.down:CTL | Sample source:Fibroblasts RAW_FILE_NAME(Raw file name)=20230524_TCA_CELLS_UNAV_Marta_073a.mzXML; Sample.ID=Unlabelled_4 SUBJECT_SAMPLE_FACTORS - 20230524_TCA_CELLS_UNAV_Marta_074a Precursor:Unlabelled | Knock.down:CTL | Sample source:Fibroblasts RAW_FILE_NAME(Raw file name)=20230524_TCA_CELLS_UNAV_Marta_074a.mzXML; Sample.ID=Unlabelled_5 SUBJECT_SAMPLE_FACTORS - 20230524_TCA_CELLS_UNAV_Marta_075a Precursor:13C5-Glutamine | Knock.down:Linc KD | Sample source:Fibroblasts RAW_FILE_NAME(Raw file name)=20230524_TCA_CELLS_UNAV_Marta_075a.mzXML; Sample.ID=Linc KD_1 SUBJECT_SAMPLE_FACTORS - 20230524_TCA_CELLS_UNAV_Marta_076a Precursor:13C5-Glutamine | Knock.down:Linc KD | Sample source:Fibroblasts RAW_FILE_NAME(Raw file name)=20230524_TCA_CELLS_UNAV_Marta_076a.mzXML; Sample.ID=Linc KD_2 SUBJECT_SAMPLE_FACTORS - 20230524_TCA_CELLS_UNAV_Marta_077a Precursor:13C5-Glutamine | Knock.down:Linc KD | Sample source:Fibroblasts RAW_FILE_NAME(Raw file name)=20230524_TCA_CELLS_UNAV_Marta_077a.mzXML; Sample.ID=Linc KD_3 SUBJECT_SAMPLE_FACTORS - 20230524_TCA_CELLS_UNAV_Marta_078a Precursor:13C5-Glutamine | Knock.down:Linc KD | Sample source:Fibroblasts RAW_FILE_NAME(Raw file name)=20230524_TCA_CELLS_UNAV_Marta_078a.mzXML; Sample.ID=Linc KD_4 SUBJECT_SAMPLE_FACTORS - 20230524_TCA_CELLS_UNAV_Marta_079a Precursor:13C5-Glutamine | Knock.down:Linc KD | Sample source:Fibroblasts RAW_FILE_NAME(Raw file name)=20230524_TCA_CELLS_UNAV_Marta_079a.mzXML; Sample.ID=Linc KD_5 SUBJECT_SAMPLE_FACTORS - 20230524_TCA_CELLS_UNAV_Marta_080a Precursor:13C5-Glutamine | Knock.down:DLST KD | Sample source:Fibroblasts RAW_FILE_NAME(Raw file name)=20230524_TCA_CELLS_UNAV_Marta_080a.mzXML; Sample.ID=DLST KD_1 SUBJECT_SAMPLE_FACTORS - 20230524_TCA_CELLS_UNAV_Marta_081a Precursor:13C5-Glutamine | Knock.down:DLST KD | Sample source:Fibroblasts RAW_FILE_NAME(Raw file name)=20230524_TCA_CELLS_UNAV_Marta_081a.mzXML; Sample.ID=DLST KD_2 SUBJECT_SAMPLE_FACTORS - 20230524_TCA_CELLS_UNAV_Marta_082a Precursor:13C5-Glutamine | Knock.down:DLST KD | Sample source:Fibroblasts RAW_FILE_NAME(Raw file name)=20230524_TCA_CELLS_UNAV_Marta_082a.mzXML; Sample.ID=DLST KD_3 SUBJECT_SAMPLE_FACTORS - 20230524_TCA_CELLS_UNAV_Marta_083a Precursor:13C5-Glutamine | Knock.down:DLST KD | Sample source:Fibroblasts RAW_FILE_NAME(Raw file name)=20230524_TCA_CELLS_UNAV_Marta_083a.mzXML; Sample.ID=DLST KD_4 SUBJECT_SAMPLE_FACTORS - 20230524_TCA_CELLS_UNAV_Marta_084a Precursor:13C5-Glutamine | Knock.down:DLST KD | Sample source:Fibroblasts RAW_FILE_NAME(Raw file name)=20230524_TCA_CELLS_UNAV_Marta_084a.mzXML; Sample.ID=DLST KD_5 #COLLECTION CO:COLLECTION_SUMMARY CELLS: IMR90-ER:RAS fibroblasts were cultured in DMEM medium (GIBCO), CO:COLLECTION_SUMMARY supplemented with 10% fetal bovine serum (GIBCO) and 1x penicillin/streptomycin CO:COLLECTION_SUMMARY (GIBCO). Cells were maintained at 37 °C in the presence of 5% CO2. For the CO:COLLECTION_SUMMARY metabolic analysis, cells were transfected in 6- well plates in triplicates with CO:COLLECTION_SUMMARY siRNA control, siRNA against DLST or siRNA against sin-lncRNA using RNAiMax CO:COLLECTION_SUMMARY (Invitrogen). 24h later, they were treated with 500nM 4-OHT to induce senescence CO:COLLECTION_SUMMARY for 6 days. After that cells were washed and sent on dry ice for analysis. CO:COLLECTION_SUMMARY INCUBATIONS: The samples indicated with the "Precursor" parameter 13C5-Glutamine CO:COLLECTION_SUMMARY were incubated with 4mM uniformly 13C-labelled glutamine and the ones indicated CO:COLLECTION_SUMMARY with Glutamine were incubated with 4mM non-labelled glutamine. CURVE: Curve CO:COLLECTION_SUMMARY samples as defined in the study design were serial dilutions of the pooled CO:COLLECTION_SUMMARY analytes (alpha ketoglutarate, Citrate, Glutamate, Glutamine, Isocitrate, CO:COLLECTION_SUMMARY Malate) in water/MeOH (75/25 %v/v). The following concentrations in µM were CO:COLLECTION_SUMMARY used: 100, 50, 25, 10, 5, 2.5, 1, 0.5, 0.25, 0.1, 0.05, 0.025 and 0 (blank). CO:COLLECTION_SUMMARY Curve_12 has the highest concentration and Curve_00 is the blank. CO:SAMPLE_TYPE Fibroblasts CO:STORAGE_CONDITIONS -80℃ CO:COLLECTION_TUBE_TEMP 20 #TREATMENT TR:TREATMENT_SUMMARY Cells were incubated either with non-labeled and 13C5-labeled glutamate. TR:TREATMENT_SUMMARY Knockdowns were performed with siRNA for the various genes. #SAMPLEPREP SP:SAMPLEPREP_SUMMARY Cells from three wells (1E6 cells/well) were pooled to obtain one LCMS sample. SP:SAMPLEPREP_SUMMARY Therefore, cells were extracted with 200 μL icecold extraction liquid per well. SP:SAMPLEPREP_SUMMARY The volume from one well was transferred to the next and finally the resulting SP:SAMPLEPREP_SUMMARY 600 μL volume was passed over the three wells two times. The extraction liquid SP:SAMPLEPREP_SUMMARY consisted of a mixture of ice-cold methanol/water (50/50 %v/v). Subsequently 400 SP:SAMPLEPREP_SUMMARY μL of the cell homogenate plus 400μL of chloroform was transferred to a new SP:SAMPLEPREP_SUMMARY aliquot and shaken at 1400 rpm for 60 minutes at 4 °C. Next the aliquots were SP:SAMPLEPREP_SUMMARY centrifuged for 30 minutes at 14000 rpm at 4 °C. 250μL of the aqueous phase SP:SAMPLEPREP_SUMMARY was transferred to a fresh aliquot. The chilled supernatants were evaporated SP:SAMPLEPREP_SUMMARY with a speedvac in approximately 2h. The resulting pellets were resuspended in SP:SAMPLEPREP_SUMMARY 150 μL water/MeOH (75/25 %v/v). #CHROMATOGRAPHY CH:CHROMATOGRAPHY_SUMMARY Samples were measured with a UPLC system (Acquity, Waters Inc., Manchester, UK) CH:CHROMATOGRAPHY_SUMMARY coupled to a Time-of-Flight mass spectrometer (ToF MS, SYNAPT G2S, Waters Inc.). CH:CHROMATOGRAPHY_SUMMARY A 2.1 x 100 mm, 1.7 μm Phenyl-Hexyl column (Waters Inc.), thermostated at 40 CH:CHROMATOGRAPHY_SUMMARY °C, was used to separate the analytes before entering the MS. Mobile phase CH:CHROMATOGRAPHY_SUMMARY solvent A (aqueous phase) consisted of 99.5% water and 0.5% FA while solvent B CH:CHROMATOGRAPHY_SUMMARY (organic phase) consisted of 99.5% MeCN and 0.5% FA. In order to obtain a good CH:CHROMATOGRAPHY_SUMMARY separation of the analytes the following gradient was used: from 98% A to 0% A CH:CHROMATOGRAPHY_SUMMARY in 2 minutes in a curved gradient (Curve 8, as defined by Waters), constant at CH:CHROMATOGRAPHY_SUMMARY 0% A for 1 minutes, back to 98% A in 0.2 minutes in a linear gradient (Curve 6, CH:CHROMATOGRAPHY_SUMMARY as defined by Waters). The flow rate was 0.250 mL/min and the injection volume CH:CHROMATOGRAPHY_SUMMARY was 3 μL. After every 6 injections sample was injected. The gradient curves are CH:CHROMATOGRAPHY_SUMMARY defined by Waters as: The convex curve set conforms to the following: C(t) = Cf CH:CHROMATOGRAPHY_SUMMARY – [ (Cf – Ci) * (X^N) ] Where X = (Tf – t) / (Tf – Ti), and where the CH:CHROMATOGRAPHY_SUMMARY notation X^N indicates the quantity X raised to the Nth power, where Curve 2 N = CH:CHROMATOGRAPHY_SUMMARY 8 Curve 3 N = 5 Curve 4 N = 3 Curve 5 N = 2 The concave curve set (including CH:CHROMATOGRAPHY_SUMMARY linear) conforms to the following: C(t) = Ci + [ (Cf – Ci) * (X^N) ] Where X = CH:CHROMATOGRAPHY_SUMMARY (t – Ti) / (Tf – Ti), and where the notation X^N indicates the quantity X CH:CHROMATOGRAPHY_SUMMARY raised to the Nth power, where Curve 6 N = 1 Curve 7 N = 2 Curve 8 N = 3 Curve 9 CH:CHROMATOGRAPHY_SUMMARY N = 5 Curve 10 N = 8. CH:CHROMATOGRAPHY_TYPE Reversed phase CH:INSTRUMENT_NAME Waters Acquity I-Class CH:COLUMN_NAME Waters ACQUITY UPLC BEH Phenyl (100 x 2.1mm,1.7um) CH:SOLVENT_A 100% Water; 0.5% formic acid CH:SOLVENT_B 100% Acetonitrile; 0.5% formic acid CH:FLOW_GRADIENT from 98% A to 0% A in 2 minutes in a curved gradient (Curve 8, as defined by CH:FLOW_GRADIENT Waters), constant at 0% A for 1 minutes, back to 98% A in 0.2 minutes in a CH:FLOW_GRADIENT linear gradient (Curve 6, as defined by Waters) CH:FLOW_RATE 0.25 mL/min CH:COLUMN_TEMPERATURE 40 #ANALYSIS AN:ANALYSIS_TYPE MS #MS MS:INSTRUMENT_NAME Waters Synapt G2 S QTOF MS:INSTRUMENT_TYPE QTOF MS:MS_TYPE ESI MS:ION_MODE NEGATIVE MS:MS_COMMENTS mass corrected with Leu-Enk lock mass processed in TargetLynx. Data is reported MS:MS_COMMENTS as Integrated peak area of the extracted ion current for the specific m/z within MS:MS_COMMENTS a 0.01Da window in "single ion counts". MS:ION_SOURCE_TEMPERATURE 450 MS:ION_SPRAY_VOLTAGE 500V MS:IONIZATION ESI MS:MASS_ACCURACY 3ppm MS:SOURCE_TEMPERATURE 120 #MS_METABOLITE_DATA MS_METABOLITE_DATA:UNITS Integrated peak area MS_METABOLITE_DATA_START Samples 20230524_TCA_CELLS_UNAV_Marta_007a 20230524_TCA_CELLS_UNAV_Marta_008a 20230524_TCA_CELLS_UNAV_Marta_009a 20230524_TCA_CELLS_UNAV_Marta_010a 20230524_TCA_CELLS_UNAV_Marta_011a 20230524_TCA_CELLS_UNAV_Marta_012a 20230524_TCA_CELLS_UNAV_Marta_013a 20230524_TCA_CELLS_UNAV_Marta_014a 20230524_TCA_CELLS_UNAV_Marta_015a 20230524_TCA_CELLS_UNAV_Marta_016a 20230524_TCA_CELLS_UNAV_Marta_017a 20230524_TCA_CELLS_UNAV_Marta_018a 20230524_TCA_CELLS_UNAV_Marta_019a 20230524_TCA_CELLS_UNAV_Marta_020a 20230524_TCA_CELLS_UNAV_Marta_021a 20230524_TCA_CELLS_UNAV_Marta_022a 20230524_TCA_CELLS_UNAV_Marta_023a 20230524_TCA_CELLS_UNAV_Marta_024a 20230524_TCA_CELLS_UNAV_Marta_025a 20230524_TCA_CELLS_UNAV_Marta_026a 20230524_TCA_CELLS_UNAV_Marta_027a 20230524_TCA_CELLS_UNAV_Marta_028a 20230524_TCA_CELLS_UNAV_Marta_029a 20230524_TCA_CELLS_UNAV_Marta_030a 20230524_TCA_CELLS_UNAV_Marta_031a 20230524_TCA_CELLS_UNAV_Marta_032a 20230524_TCA_CELLS_UNAV_Marta_033a 20230524_TCA_CELLS_UNAV_Marta_034a 20230524_TCA_CELLS_UNAV_Marta_035a 20230524_TCA_CELLS_UNAV_Marta_036a 20230524_TCA_CELLS_UNAV_Marta_037a 20230524_TCA_CELLS_UNAV_Marta_038a 20230524_TCA_CELLS_UNAV_Marta_039a 20230524_TCA_CELLS_UNAV_Marta_040a 20230524_TCA_CELLS_UNAV_Marta_041a 20230524_TCA_CELLS_UNAV_Marta_042a 20230524_TCA_CELLS_UNAV_Marta_043a 20230524_TCA_CELLS_UNAV_Marta_044a 20230524_TCA_CELLS_UNAV_Marta_045a 20230524_TCA_CELLS_UNAV_Marta_046a 20230524_TCA_CELLS_UNAV_Marta_047a 20230524_TCA_CELLS_UNAV_Marta_048a 20230524_TCA_CELLS_UNAV_Marta_049a 20230524_TCA_CELLS_UNAV_Marta_050a 20230524_TCA_CELLS_UNAV_Marta_051a 20230524_TCA_CELLS_UNAV_Marta_052a 20230524_TCA_CELLS_UNAV_Marta_053a 20230524_TCA_CELLS_UNAV_Marta_054a 20230524_TCA_CELLS_UNAV_Marta_055a 20230524_TCA_CELLS_UNAV_Marta_056a 20230524_TCA_CELLS_UNAV_Marta_057a 20230524_TCA_CELLS_UNAV_Marta_058a 20230524_TCA_CELLS_UNAV_Marta_059a 20230524_TCA_CELLS_UNAV_Marta_060a 20230524_TCA_CELLS_UNAV_Marta_061a 20230524_TCA_CELLS_UNAV_Marta_062a 20230524_TCA_CELLS_UNAV_Marta_063a 20230524_TCA_CELLS_UNAV_Marta_064a 20230524_TCA_CELLS_UNAV_Marta_065a 20230524_TCA_CELLS_UNAV_Marta_066a 20230524_TCA_CELLS_UNAV_Marta_067a 20230524_TCA_CELLS_UNAV_Marta_068a 20230524_TCA_CELLS_UNAV_Marta_069a 20230524_TCA_CELLS_UNAV_Marta_070a 20230524_TCA_CELLS_UNAV_Marta_071a 20230524_TCA_CELLS_UNAV_Marta_072a 20230524_TCA_CELLS_UNAV_Marta_073a 20230524_TCA_CELLS_UNAV_Marta_074a 20230524_TCA_CELLS_UNAV_Marta_075a 20230524_TCA_CELLS_UNAV_Marta_076a 20230524_TCA_CELLS_UNAV_Marta_077a 20230524_TCA_CELLS_UNAV_Marta_078a 20230524_TCA_CELLS_UNAV_Marta_079a 20230524_TCA_CELLS_UNAV_Marta_080a 20230524_TCA_CELLS_UNAV_Marta_081a 20230524_TCA_CELLS_UNAV_Marta_082a 20230524_TCA_CELLS_UNAV_Marta_083a 20230524_TCA_CELLS_UNAV_Marta_084a Factors Precursor:- | Knock.down:- | Sample source:Curve Precursor:- | Knock.down:- | Sample source:Curve Precursor:- | Knock.down:- | Sample source:Curve Precursor:- | Knock.down:- | Sample source:Curve Precursor:- | Knock.down:- | Sample source:Curve Precursor:- | Knock.down:- | Sample source:Curve Precursor:- | Knock.down:- | Sample source:Curve Precursor:- | Knock.down:- | Sample source:Curve Precursor:- | Knock.down:- | Sample source:Curve Precursor:- | Knock.down:- | Sample source:Curve Precursor:- | Knock.down:- | Sample source:Curve Precursor:- | Knock.down:- | Sample source:Curve Precursor:- | Knock.down:- | Sample source:Curve Precursor:- | Knock.down:- | Sample source:Blank Precursor:- | Knock.down:- | Sample source:Blank Precursor:- | Knock.down:- | Sample source:Blank Precursor:- | Knock.down:- | Sample source:QC_INIT Precursor:- | Knock.down:- | Sample source:QC_INIT Precursor:- | Knock.down:- | Sample source:QC_INIT Precursor:- | Knock.down:- | Sample source:QC_INIT Precursor:- | Knock.down:- | Sample source:QC Precursor:- | Knock.down:- | Sample source:QC Precursor:- | Knock.down:- | Sample source:QC Precursor:- | Knock.down:- | Sample source:QC Precursor:- | Knock.down:- | Sample source:QC Precursor:- | Knock.down:- | Sample source:Curve Precursor:- | Knock.down:- | Sample source:Curve Precursor:- | Knock.down:- | Sample source:Curve Precursor:- | Knock.down:- | Sample source:Curve Precursor:- | Knock.down:- | Sample source:Curve Precursor:- | Knock.down:- | Sample source:Curve Precursor:- | Knock.down:- | Sample source:Curve Precursor:- | Knock.down:- | Sample source:Curve Precursor:- | Knock.down:- | Sample source:Curve Precursor:- | Knock.down:- | Sample source:Curve Precursor:- | Knock.down:- | Sample source:Curve Precursor:- | Knock.down:- | Sample source:Curve Precursor:- | Knock.down:- | Sample source:Curve Precursor:13C5-Glutamine | Knock.down:CTL | Sample source:Fibroblasts Precursor:13C5-Glutamine | Knock.down:CTL | Sample source:Fibroblasts Precursor:13C5-Glutamine | Knock.down:CTL | Sample source:Fibroblasts Precursor:13C5-Glutamine | Knock.down:CTL | Sample source:Fibroblasts Precursor:13C5-Glutamine | Knock.down:CTL | Sample source:Fibroblasts Precursor:Unlabelled | Knock.down:CTL | Sample source:Fibroblasts Precursor:Unlabelled | Knock.down:CTL | Sample source:Fibroblasts Precursor:Unlabelled | Knock.down:CTL | Sample source:Fibroblasts Precursor:Unlabelled | Knock.down:CTL | Sample source:Fibroblasts Precursor:Unlabelled | Knock.down:CTL | Sample source:Fibroblasts Precursor:13C5-Glutamine | Knock.down:Linc KD | Sample source:Fibroblasts Precursor:13C5-Glutamine | Knock.down:Linc KD | Sample source:Fibroblasts Precursor:13C5-Glutamine | Knock.down:Linc KD | Sample source:Fibroblasts Precursor:13C5-Glutamine | Knock.down:Linc KD | Sample source:Fibroblasts Precursor:13C5-Glutamine | Knock.down:Linc KD | Sample source:Fibroblasts Precursor:13C5-Glutamine | Knock.down:DLST KD | Sample source:Fibroblasts Precursor:13C5-Glutamine | Knock.down:DLST KD | Sample source:Fibroblasts Precursor:13C5-Glutamine | Knock.down:DLST KD | Sample source:Fibroblasts Precursor:13C5-Glutamine | Knock.down:DLST KD | Sample source:Fibroblasts Precursor:13C5-Glutamine | Knock.down:DLST KD | Sample source:Fibroblasts Precursor:13C5-Glutamine | Knock.down:CTL | Sample source:Fibroblasts Precursor:13C5-Glutamine | Knock.down:CTL | Sample source:Fibroblasts Precursor:13C5-Glutamine | Knock.down:CTL | Sample source:Fibroblasts Precursor:13C5-Glutamine | Knock.down:CTL | Sample source:Fibroblasts Precursor:13C5-Glutamine | Knock.down:CTL | Sample source:Fibroblasts Precursor:Unlabelled | Knock.down:CTL | Sample source:Fibroblasts Precursor:Unlabelled | Knock.down:CTL | Sample source:Fibroblasts Precursor:Unlabelled | Knock.down:CTL | Sample source:Fibroblasts Precursor:Unlabelled | Knock.down:CTL | Sample source:Fibroblasts Precursor:Unlabelled | Knock.down:CTL | Sample source:Fibroblasts Precursor:13C5-Glutamine | Knock.down:Linc KD | Sample source:Fibroblasts Precursor:13C5-Glutamine | Knock.down:Linc KD | Sample source:Fibroblasts Precursor:13C5-Glutamine | Knock.down:Linc KD | Sample source:Fibroblasts Precursor:13C5-Glutamine | Knock.down:Linc KD | Sample source:Fibroblasts Precursor:13C5-Glutamine | Knock.down:Linc KD | Sample source:Fibroblasts Precursor:13C5-Glutamine | Knock.down:DLST KD | Sample source:Fibroblasts Precursor:13C5-Glutamine | Knock.down:DLST KD | Sample source:Fibroblasts Precursor:13C5-Glutamine | Knock.down:DLST KD | Sample source:Fibroblasts Precursor:13C5-Glutamine | Knock.down:DLST KD | Sample source:Fibroblasts Precursor:13C5-Glutamine | Knock.down:DLST KD | Sample source:Fibroblasts AKG 19.6 28.737 31.554 12.741 7.105 28.191 6.488 97.391 226.455 382.385 1165.078 2424.6 4304.841 15.068 4.114 10.853 35.959 12.296 24.921 19.344 25.907 27.355 51.859 28.323 59.344 25.197 4.628 39.079 39.873 43.316 31.309 78.775 117.552 179.281 396.454 982.282 2119.909 3728.516 48.895 0 0 0 35.465 78.1 53.997 67.018 91.741 100.168 0 0 0 0 0 0 0 0 0 0 42.546 0 0 0 47.283 49.82 69.642 93.021 74.342 102.567 0 0 0 0 0 0 0 0 0 0 AKG_13C5 4.028 2.211 6.203 1.558 7.269 5.343 14.8 8.014 4.388 0 4.036 8.214 0 7.234 7.511 6.995 18.271 19.141 16.033 8.54 15.859 10.99 14.711 9.188 21.96 0 4.181 1.36 5.629 2.515 1.587 1.773 0 2.208 6.654 11.94 4.31 4.789 46.656 24.109 29.023 15.089 41.083 0 0 0 0 0 40.8 38.808 13.449 13.354 36.076 24.673 36.094 39.002 41.617 55.081 52.034 20.019 31.11 25.823 41.024 0 0 0 0 0 34.812 26.768 13.84 18.301 21.145 26.258 16.416 39.391 38.304 46.803 Citrate 21.792 58.955 63.388 131.432 273.833 651.353 1237.75 3269.769 6484.881 12406.748 34885.176 70098.375 130194.367 5.997 12.488 0 3138.267 3252.592 3381.719 318.027 1604.8 1255.658 2609.057 1872.482 2670.295 3.299 53.749 92.272 157.843 358.75 741.959 1425.752 3589.524 6916.728 12691.95 32397.16 63451.711 110541.664 3634.77 2046.925 2901.578 2303.49 3322.719 7421.202 6499.691 7344.536 6576.554 7647.635 2640.708 2325.603 3036.359 2901.569 3012.155 1186.525 1830.297 2260.47 1762.111 2301.887 3545.784 1927.525 2834.372 2302.174 3594.611 5081.491 6485.049 7192.321 7132.573 8693.202 2554.291 2426.41 3101.098 3047.935 1343.6 1445.375 856.798 2280.216 1855.63 2188.49 Citrate_13C1 3.252 3.65 4.619 9.794 22.944 45.8 102.788 250.295 466.177 914.689 2396.118 4803.248 8812.465 5.676 12.957 1.189 277.759 263.626 279.55 29.287 146.884 114.785 226.174 154.502 229.999 1.054 1.087 5.449 10.886 32.086 62.367 107.345 254.45 492.34 895.428 2259.822 4311.373 7334.979 398.353 214.394 287.665 234.332 340.502 547.948 486.39 499.105 445.527 532.167 246.374 202.905 285.638 258.872 270.756 94.587 147.055 183.966 131.44 181.246 355.378 193.516 298.673 245.971 377.138 369.922 469.174 503.845 506.084 614.187 257.035 215.279 262.669 285.465 130.253 105.367 86.291 156.276 153.108 168.66 Citrate_13C2 2.053 0 1.307 1.12 6.633 11.122 20.367 57.023 133.601 210.655 580.079 1191.772 2053.245 4.685 2.198 4.932 191.162 209.281 232.686 22.434 108.95 80.459 172.489 115.132 163.274 2.597 1.556 1.46 2.802 8.717 19.434 26.296 56.718 108.758 229.895 559.979 1016.712 1711.361 596.07 321.059 421.1 357.816 492.176 120.813 119.889 130.982 127.79 129.226 291.229 218.927 279.419 311.581 294.652 69.911 99.24 125.968 102.427 120.945 566.575 332.523 430.419 360.31 566.749 87.539 120.315 127.219 133.674 144.186 290.191 253.642 271.524 324.089 138.78 74.568 54.771 128.191 106.461 124.711 Citrate_13C3 1.076 0 1.349 0 2.195 1.476 2.097 1.984 8.456 12.779 37.001 65.023 132.779 1.776 1.613 0 164.552 162.48 181.295 16.721 84.881 68.733 124.897 91.688 130.458 0 1.692 1.229 1.751 1.549 0 4.138 1.898 9.032 10.51 36.328 61.65 122.245 436.732 256.9 338.784 312.932 412.228 0 0 0 0 0 274.796 242.644 246.339 345.939 346.506 58.559 116.433 134.738 109.268 138.378 408.727 247.363 332.041 317.832 467.975 0 0 0 0 0 278.66 232.611 252.249 367.541 151.421 74.349 60.321 140.001 124.693 121.759 Citrate_13C4 0 0 1.428 2.922 0 2.624 1.053 4.699 1.155 1.649 7.849 1.882 8.506 0 2.271 3.263 829.765 881.226 925.368 91.003 462.248 338.682 747.346 506.446 728.88 0 3.024 2.065 1.233 2.214 1.077 3.693 1.517 1.73 2.489 2.214 8.914 8.181 2844.903 1764.121 2297.387 1852.197 2440.428 0 0 0 0 0 1490.777 1380.27 1325.847 1812.303 1719.672 241.583 486.291 542.865 447.94 558.54 2806.12 1578.738 2187.045 1818.098 2720.303 0 0 0 0 0 1504.205 1514.305 1413.959 1804.274 836.343 303.46 249.683 537.598 510.125 550.201 Citrate_13C5 4.27 1.21 2.353 1.328 2.963 2.88 0 1.051 1.688 0 0 1.033 6.728 1.408 1.719 2.902 196.449 253.897 256.841 14.075 94.206 95.108 211.194 139.017 184.053 4.275 3.556 1.815 0 0 1.276 1.326 2.014 1.789 4.159 1.831 1.181 1.167 357.778 284.42 413.651 393.533 495.035 0 0 0 0 0 373.568 322.357 231.281 602.698 547.394 151.198 295.225 334.645 260.582 232.83 399.995 277.102 382.149 388.589 568.256 0 0 0 0 0 406.923 314.238 277.777 637.819 244.53 188.127 101.374 291.915 272.238 295.867 Citrate_13C6 1.088 2.101 3.269 3.729 2.862 0 0 0 1.713 2.506 1.421 1.897 0 1.088 1.602 0 18.353 15.868 21.306 4.486 11.915 5.578 18.778 12.908 22.318 1.196 4.703 0 1.943 3.566 0 1.713 0 3.61 1.802 1.3 4.046 0 66.804 26.138 53.933 49.167 42.299 0 0 0 0 0 42.101 24.387 36.413 33.399 18.737 11.07 0 8.645 12.012 11.908 51.96 28.815 18.716 53.079 55.608 0 0 0 0 0 32.792 36.097 24.321 29.233 17.284 6.307 0 16.934 5.824 11.18 Glutamate 1.104 7.661 10.913 31.396 70.063 132.614 273.922 732.28 1323.22 2447.746 5998.073 11098.808 19676.186 4.23 1.743 1.317 19917.748 19768.984 19890.322 4497.55 13432.062 11305.174 16252.133 12968.632 16135.06 2.752 10.545 12.458 25.19 53.322 104.65 217.262 601.491 1142.479 2196.139 5174.323 9643.315 16960.723 6232.268 8662.045 8534.56 7487.531 8657.231 36809.715 38383.504 40350.77 38524.84 40298.574 10772.154 10964.459 10464.525 11604.621 12347.764 9291.916 13423.942 14486.274 12507.001 14977.419 6603.743 8731.056 9289.586 7407.002 9130.336 32594.803 38240.672 40327.621 40467.066 42521.766 10305.561 10748.745 10601.58 11642.91 8285.737 10969.669 8823.302 14298.993 13078.581 14020.096 Glutamate_13C1 2.006 3.926 2.041 2.3 1.285 10.68 21.457 47.531 88.017 176.59 364.219 686.041 1127.839 4.609 4.837 1.678 1276.136 1301.495 1322.27 311.232 879.095 737.053 1115.281 846.549 1159.531 1.421 3.697 3.162 3.368 4.523 10.607 15.847 32.949 82.073 135.052 317.45 582.549 1031.288 510.484 756.314 711.654 614.53 714.34 2257.951 2220.301 2335.001 2269.499 2384.322 826.054 813.385 816.665 796.823 848.499 599.626 871.063 916.661 777.813 960.324 544.358 725.754 772.786 655.575 754.954 1821.348 2281.219 2364.167 2334.689 2464.663 805.778 816.907 776.464 861.752 602.064 684.465 585.277 907.339 864.965 901.592 Glutamate_13C2 3.157 1.746 2.522 1.627 1.963 5.118 7.039 6.798 17.504 27.72 68.584 116.179 208.151 0 0 1.541 392.356 361.961 383.773 86.746 268.904 236.212 338.309 247.45 320.464 2.842 2.335 0 1.426 2.232 2.67 3.53 3.103 20.35 24.499 60.213 96.787 159.753 276.721 391.834 392.436 307.897 356 349.482 358.278 367.081 336.202 356 380.638 354.495 357.977 327.854 348.387 199.246 315.627 323.864 290.236 327.803 286.925 376.968 356.815 348.485 380.038 296.428 378.942 362.036 387.225 382.754 393.767 314.811 393.774 342.268 256.526 240.857 204.995 325.146 285.276 323.781 Glutamate_13C3 2.646 1.006 6.72 3.067 2.976 1.925 1.319 0 8.123 4.793 4.721 0 0 1.484 1.989 3.897 1275.573 1260.11 1300.551 321.49 905.708 769.9 1135.384 871.67 1108.533 3.383 3.246 1.124 1.064 1.133 0 3.331 2.792 2.962 2.03 4.722 6.959 7.394 1444.593 2117.306 1971.615 1739.117 1938.844 0 0 0 0 0 1789.948 1717.142 1896.841 1884.019 1816.637 671.308 1001.503 1042.498 932.406 1131.352 1593.093 2066.414 2041.777 1739.986 2039.502 0 0 0 0 0 1875.435 1821.717 1992.247 1848.271 1302.25 732.3 672.273 1025.838 1026.389 1123.721 Glutamate_13C4 0 1.124 1.145 1.7 5.342 2.026 1.058 4.037 7.625 4.94 3.669 5.884 6.014 2.267 2.425 2.586 248.99 360.535 336.658 90.34 271.152 238.505 275.353 278.686 260.789 2.165 3.144 0 4.214 3.02 2.051 3.09 1.047 0 1.77 1.953 4.646 4.167 139.39 206.025 189.402 147.712 175.905 0 0 0 0 0 339.674 366.297 317.898 362.478 406.037 194.618 346.554 294.697 324.445 318.363 146.135 264.241 197.492 214.417 137.691 0 0 0 0 0 234.499 333.022 374.487 343.756 314.029 242.243 234.217 282.389 357.326 363.889 Glutamate_13C5 1.25 2.078 2.164 1.943 1.706 1.165 0 2.319 1.353 0 5.141 2.922 4.406 4.61 7.763 4.267 17193.965 17192.205 17602.998 3683.584 12275.802 9975.252 15334.705 12078.865 14989.006 4.3 4.387 2.782 2.483 2.649 0 2.912 1.027 3.496 1.849 1.234 1.827 4.562 13602.464 21209.404 21130.648 18876.637 20009.4 0 0 0 0 0 22797.617 25078.828 21886.225 25150.666 26278.213 14967.662 21903.359 23585.242 21800.178 26926.547 14486.723 21028.459 22333.135 18076.816 21166.711 0 0 0 0 0 22345.842 24005.33 22270.639 25446.975 18267.326 17467.521 15080.268 23701.992 23325.604 23360.141 Glutamine 2.445 8.959 15.456 39.669 92.589 178.947 331.258 779.749 1559.131 2731.697 5477.879 8881.475 13456.39 3.961 3.772 0 5596.794 5618.14 5656.061 2110.653 5330.819 4461.133 5586.723 4907.86 5421.64 1.491 11.207 17.311 29.743 73.519 142.206 284.952 699.862 1299.282 2298.943 4800.056 7501.217 11415.633 294.51 294.469 285.947 255.791 259.672 21810.266 19600.313 20716.063 18408.578 19723.305 309.339 341.159 362.775 345.871 407.285 327.391 433.675 376.578 421.548 479.663 259.527 292.441 285.685 256.115 282.149 20857.848 19560.783 20618.945 19507.119 20393.941 310.658 352.876 349.905 334.373 386.076 338.864 337.858 372.18 447.794 497.056 Glutamine_13C1 0 0 4.807 4.213 9.822 17.63 19.796 44.785 70.703 105.443 242.424 336.298 388.463 2.386 2.714 2.367 195.194 214.713 179.233 80.002 206.334 171.531 224.567 153.845 244.22 3.115 4.088 1.501 1.978 6.367 7.682 17.208 29.732 76.126 104.824 203.317 286.921 395.677 10.026 29.901 8.765 10.092 11.811 1011.195 788.815 916.773 648.909 579.787 15.412 10.34 4.569 9.798 26.579 10.012 15.754 15.868 20.849 31.549 25.941 16.024 21.093 23.588 23.851 587.342 769.261 861.639 551.017 618.378 10.009 12.296 19.873 17.803 14.354 31.944 14.573 43.906 27.445 21.39 Glutamine_13C2 1.452 4.055 0 2.086 3.113 1.832 3.166 8.018 7.826 14.896 44.294 64.013 93.162 0 0 2.734 39.481 61.023 38.159 14.455 38.882 27.497 53.897 38.615 38.45 1.591 0 4.47 0 2.55 3.128 2.8 8.08 12.521 17.567 24.533 48.612 56.267 90.541 35.624 26.698 26.188 36.595 133.649 105.11 120.325 72.931 84.432 43.89 16.013 15.683 39.072 37.424 0 0 0 0 0 68.796 22.093 28.939 25.482 62.598 137.64 86.731 103.399 124.598 133.617 43.854 35.732 25.734 33.121 10.49 0 0 0 0 0 Glutamine_13C3 2.345 2.485 0 1.74 1.112 2.162 1.237 3.216 3.594 4.579 3.071 5.501 6.042 5.469 1.014 2.136 41.786 22.559 20.31 10.344 22.454 14.079 27.788 13.13 18.895 4.68 0 8.094 3.843 0 2.306 1.129 1.508 3.536 1.748 2.152 5.275 3.99 42.892 31.541 17.827 25.665 21.957 0 0 0 0 0 35.725 18.651 29.711 34.178 26.142 27.626 21.291 25.229 25.643 32.9 15.837 18.828 22.512 23.912 45.559 0 0 0 0 0 10.867 19.462 21.975 20.554 26.634 28.572 21.431 25.136 32.824 27.593 Glutamine_13C4 3.591 2.149 1.46 3.482 1.19 1.37 0 1.258 2.649 3.993 5.158 2.609 1.444 1.26 3.883 1.387 609.301 620.267 574.935 223.073 538.258 472.778 564.05 546.114 567.154 0 3.349 1.53 1.521 3.319 0 1.869 1.453 3.305 1.941 4.476 1.663 3.355 445.252 457.641 463.47 467.45 436.103 0 0 0 0 0 514.448 501.628 541.802 647.591 736.068 776.47 849.088 845.41 922.709 1061.517 379.842 536.341 487.019 533.757 514.558 0 0 0 0 0 508.389 576.172 534.426 630.178 755.753 724.809 761.394 812.065 993.129 1017.312 Glutamine_13C5 1.821 1.145 1.307 1.475 1.298 1.953 1.361 4.594 3.144 1.645 1.461 3.578 2.69 1.209 0 1.405 17273.766 17574.74 17117.588 6311.088 16205.43 13432.25 17017.693 15615.51 17605.336 3.24 0 7.831 4.051 1.809 0 1.384 3.532 0 2.215 0 2.028 3.346 14410.228 16839.285 16769.168 15958.18 15933.838 0 0 0 0 0 14960.359 17717.49 17545.602 20438.594 23161.215 21452.154 26507.869 25025.379 28022.076 32379.391 13570.556 16477.348 17341.535 16206.907 17651.699 0 0 0 0 0 15297.813 17985.105 16758.84 20225.236 22132.814 19644.473 20843.828 24249.215 29286.021 29592.508 Isocitrate 20.611 29.631 28.197 108.138 187.242 406.41 683.139 1744.896 3247.417 6083.033 16143.004 34683.973 68148.617 0 0 0 103.399 118.55 119.753 9.866 77.321 59.097 93.851 80.38 81.139 2.766 30.242 42.178 63.973 181.993 404.277 702.951 1726.373 3235.604 5844.776 15518.312 31590.854 59283.707 136.226 71.048 83.433 68.916 90.637 222.323 94.028 184.927 112.654 115.064 83.727 70.724 92.9 118.551 81.113 29.414 0 24.263 18.561 44.609 146.815 67.525 80.845 91.222 90.218 140.333 85.282 170.595 134.293 138.808 87.026 75.694 115.294 102.778 51.137 30.15 0 35.8 28.359 31.166 Isocitrate_13C2 4.624 1.313 1.332 2.106 8.078 5.468 12.361 35.836 53.594 110.48 279.485 585.992 1129.42 5.263 5.604 2.23 4.28 7.026 5.917 3.167 3.218 5.196 8.236 5.617 10.087 1.542 4.128 2.243 3.077 2.008 9.092 19.721 27.767 65.402 102.964 250.973 500.062 943.155 20.399 14.36 10.159 8.644 11.484 0 0 0 0 0 11.16 0 5.747 11.972 0 0 0 0 0 0 20.313 12.802 8.118 8.887 7.369 0 0 0 0 0 12.625 0 9.179 14.11 0 0 0 0 0 0 Isocitrate_13C3 2.898 1.519 0 2.689 1.897 1.036 3.624 4.078 1.111 6.412 15.096 31.988 72.474 0 1.04 1.21 10.627 4.308 7.455 0 4.053 3.241 1.419 3.428 6.148 6.542 1.809 1.295 1.402 1.054 0 1.656 3.486 5.502 5.667 16.993 42.146 64.554 21.327 7.762 12.977 10.501 13.152 0 0 0 0 0 13.309 9.13 0 11.943 0 0 0 0 0 0 18.122 11.276 12.602 12.568 14.276 0 0 0 0 0 9.866 9.683 0 6.883 0 0 0 0 0 0 Isocitrate_13C4 4.025 1.062 1.138 0 2.547 2.661 0 1.968 1.367 0 3.67 0 1.416 2.593 2.003 1.958 30.813 31.389 29.086 4.755 16.283 12.1 25.245 22.061 20.633 2.864 1.067 0 1.432 1.87 1.273 0 1.903 3.16 5.124 6.983 5.507 1.907 107.806 52.585 57.726 61.961 58.932 0 0 0 0 0 47.779 43.193 37.665 67.942 44.161 0 0 0 0 7.639 91.353 57.261 59.432 55.303 60.302 0 0 0 0 0 47.29 41.925 50.144 64.972 27.202 0 0 0 0 7.773 Isocitrate_13C5 1.362 2.797 1.827 1.244 2.002 3.185 1.172 1.585 1.283 2.184 2.097 4.037 1.245 8.324 2.512 5.086 9.409 7.975 3.333 3.341 4.947 2.763 3.09 5.988 8.512 2.536 0 1.481 1.709 0 2.751 0 2.516 2.504 1.738 2.536 3.367 1.569 8.174 9.749 18.319 15.451 10.409 0 0 0 0 0 10.79 7.368 10.73 20.52 11.612 0 0 0 0 0 12.949 7.292 6.606 14.815 12.187 0 0 0 0 0 9.117 9.928 5.058 12.619 7.662 0 0 0 0 0 Malate 2.96 2.802 8.701 8.974 26.426 53.433 97.371 256.742 484.596 949.311 2421.729 4789.461 8169.663 5.315 3.268 6.989 391.782 383.752 370.35 43.953 186.035 147.522 303.101 213.983 307.645 3.291 8.037 9.348 10.919 22.913 47.767 87.15 250.27 450.75 856.038 2202.717 4346.444 7133.956 465.979 324.421 358.863 285.137 409.859 591.997 622.659 607.769 703.218 677.261 384.222 387.807 452.232 394.707 427.914 119.517 178.863 176.554 140.732 168.66 444.172 310.299 358.399 292.901 460.093 420.358 678.292 628.855 749.583 740.101 412.644 392.984 456.088 396.747 205.85 137.381 104.347 176.307 151.683 154.256 Malate_13C1 3.205 2.133 3.329 5.029 2.229 3.49 6.909 14.358 22.283 49.202 122.561 226.597 371.769 4.916 1.597 2.662 30.675 30.641 31.465 3.624 20.175 14.763 23.07 19.882 29.419 0 1.067 1.632 2.258 1.283 3.384 4.382 17.047 25.442 50.675 126.1 208.592 339.883 46.714 27.665 30.425 21.812 35.451 41.888 37.919 38.509 42.888 46.433 35.933 35.287 35.6 29.719 29.178 9.672 19.878 17.569 12.953 18.009 41.788 22.326 30.676 26.792 40.862 35.607 49.057 42.561 43.446 37.17 30.937 38.575 40.343 31.947 20.71 10.168 9.504 22.047 12.159 15.587 Malate_13C2 1.773 7.906 2.748 2.418 1.755 2.864 4.299 4.484 9.344 13.414 31.07 67.532 102.765 0 0 2.462 17.185 1.701 10.219 8.802 12.597 16.542 20.675 22.763 26.653 2.658 1.399 0 1.037 4.698 1.167 3.051 2.255 6.787 10.274 32.706 60.071 95.376 80.986 37.511 33.721 38.74 24.904 0 0 0 0 0 25.859 26.588 30.477 41.98 31.088 0 0 0 0 0 48.645 17.096 40.801 23.85 34.339 0 0 0 0 0 25.773 31.279 10.964 30.85 29.493 0 0 0 0 0 Malate_13C3 1.272 2.428 2.328 2.542 1.038 3.303 2.331 1.04 4.423 0 3.696 4.302 5.248 2.587 1.186 1.389 28.858 24.623 23.083 3.163 11.717 14.073 23.267 14.915 12.727 2.85 1.612 3.793 4.579 2.355 2.432 1.299 2.207 2.48 0 1.178 2.855 5.795 31.968 25.41 34.255 25.855 34.488 0 0 0 0 0 52.609 33.859 38.995 48.77 68.698 9.034 18.925 16.856 13.495 18.474 49.77 27.554 34.39 33.676 50.437 0 0 0 0 0 40.307 35.645 43.378 54.807 30.471 7.889 7.223 25.254 13.918 23.777 Malate_13C4 3.241 0 4.477 3.619 1.323 5.037 5.498 1.266 0 2.627 4.035 1.281 5.252 3.765 2.353 3.599 173.959 162.44 166.016 20.642 73.505 65.65 135.903 97.423 135.83 1.944 1.333 1.253 0 1.124 1.811 1.498 1.514 1.928 1.104 1.014 9.143 2.127 406.097 238.948 298.982 241.41 335.07 0 0 0 0 0 341.69 304.512 305.146 329.857 338.372 50.153 69.669 68.852 60.778 83.815 363.858 242.86 298.967 251.968 372.597 0 0 0 0 0 320.993 307.975 326.96 317.654 170.32 61.652 40.865 63.628 50.806 76.539 MS_METABOLITE_DATA_END #METABOLITES METABOLITES_START metabolite_name HMDB PubChem KEGG Glutamine HMDB0000641 5961 C00064 Glutamine_13C1 - - - Glutamine_13C2 - - - Glutamine_13C3 - - - Glutamine_13C4 - - - Glutamine_13C5 - - - Glutamate HMDB0000148 33032 C00025 Glutamate_13C1 - - - Glutamate_13C2 - - - Glutamate_13C3 - - - Glutamate_13C4 - - - Glutamate_13C5 - - - Malate HMDB0000156 222656 C00149 Malate_13C1 - - - Malate_13C2 - - - Malate_13C3 - - - Malate_13C4 - - - Citrate HMDB0000094 311 C00158 Citrate_13C1 - - - Citrate_13C2 - - - Citrate_13C3 - - - Citrate_13C4 - - - Citrate_13C5 - - - Citrate_13C6 - - - AKG HMDB0000208 51 C00026 AKG_13C5 - - - Isocitrate HMDB0000193 1198 C00311 Isocitrate_13C2 - - - Isocitrate_13C3 - - - Isocitrate_13C4 - - - Isocitrate_13C5 - - - METABOLITES_END #END