#METABOLOMICS WORKBENCH Madjihounoum_20221203_061829 DATATRACK_ID:3623 STUDY_ID:ST002435 ANALYSIS_ID:AN003968 PROJECT_ID:PR001567 VERSION 1 CREATED_ON January 11, 2023, 1:34 pm #PROJECT PR:PROJECT_TITLE Multiomics study of CHCHD10S59L-related disease reveals energy metabolism PR:PROJECT_TITLE downregulation: OXPHOS and β-oxidation deficiencies associated with lipids PR:PROJECT_TITLE alterations PR:PROJECT_SUMMARY Mutations in the coiled-coil-helix-coiled-coil-helix domain containing 10 PR:PROJECT_SUMMARY (CHCHD10) gene have been associated with a large clinical spectrum including PR:PROJECT_SUMMARY myopathy, cardiomyopathy and amyotrophic lateral sclerosis (ALS). Herein, we PR:PROJECT_SUMMARY analyzed the metabolic changes induced by the p.S59L CHCHD10 mutation to PR:PROJECT_SUMMARY identify new therapeutic opportunities. Using metabolomic, lipidomic and PR:PROJECT_SUMMARY proteomic analysis we observed a strong alteration of metabolism in plasma and PR:PROJECT_SUMMARY heart of Chchd10S59L/+ mice compared to their wild type littermates at PR:PROJECT_SUMMARY pre-symptomatic and symptomatic stages. In plasma, levels of phospholipids were PR:PROJECT_SUMMARY decreased while those of carnitine derivatives and most of amino acids were PR:PROJECT_SUMMARY increased. The cardiac tissue from Chchd10S59L/+ mice showed a decreased PR:PROJECT_SUMMARY Oxidative Phosphorylation (OXPHOS) and β-oxidation proteins levels as well as PR:PROJECT_SUMMARY tricarboxylic acid cycle (TCA) intermediates and carnitine pathway metabolism. PR:PROJECT_SUMMARY In parallel, lipidomics analysis reveals a drastic change in the lipidome, PR:PROJECT_SUMMARY including triglyceride, cardiolipin and phospholipids. Consistent with this PR:PROJECT_SUMMARY energetic deficiency in cardiac tissue, we show that L-acetylcarnitine PR:PROJECT_SUMMARY supplementation improves the mitochondrial network length in IPS-derived PR:PROJECT_SUMMARY cardiomyocytes from a patient carrying the CHCHD10S59L/+ mutation. These data PR:PROJECT_SUMMARY indicate that a bioenergetic intermediate such as L-acetylcarnitine may restore PR:PROJECT_SUMMARY mitochondrial function in CHCHD10-related disease, due to the reduction in PR:PROJECT_SUMMARY energy deficit that could be compensated by carnitine metabolic pathways. PR:INSTITUTE INSERM PR:LAST_NAME Madji Hounoum PR:FIRST_NAME Blandine PR:ADDRESS 151 Route Saint Antoine de Genistière 06204 Nice PR:EMAIL madjihounoum@yahoo.fr PR:PHONE +33 (0)4 89 06 43 01 #STUDY ST:STUDY_TITLE Metabolomics analysis of plasma from CHCHD10S59L/+ KI mice ST:STUDY_SUMMARY Mutations in the coiled-coil-helix-coiled-coil-helix domain containing 10 ST:STUDY_SUMMARY (CHCHD10) gene have been associated with a large clinical spectrum including ST:STUDY_SUMMARY myopathy, cardiomyopathy and amyotrophic lateral sclerosis (ALS). Herein, we ST:STUDY_SUMMARY analyzed the metabolic changes induced by the p.S59L CHCHD10 mutation to ST:STUDY_SUMMARY identify new therapeutic opportunities. Using metabolomic, lipidomic and ST:STUDY_SUMMARY proteomic analysis we observed a strong alteration of metabolism in plasma and ST:STUDY_SUMMARY heart of Chchd10S59L/+ mice compared to their wild type littermates at ST:STUDY_SUMMARY pre-symptomatic and symptomatic stages. In plasma, levels of phospholipids were ST:STUDY_SUMMARY decreased while those of carnitine derivatives and most of amino acids were ST:STUDY_SUMMARY increased. The cardiac tissue from Chchd10S59L/+ mice showed a decreased ST:STUDY_SUMMARY Oxidative Phosphorylation (OXPHOS) and β-oxidation proteins levels as well as ST:STUDY_SUMMARY tricarboxylic acid cycle (TCA) intermediates and carnitine pathway metabolism. ST:STUDY_SUMMARY In parallel, lipidomics analysis reveals a drastic change in the lipidome, ST:STUDY_SUMMARY including triglyceride, cardiolipin and phospholipids. Consistent with this ST:STUDY_SUMMARY energetic deficiency in cardiac tissue, we show that L-acetylcarnitine ST:STUDY_SUMMARY supplementation improves the mitochondrial network length in IPS-derived ST:STUDY_SUMMARY cardiomyocytes from a patient carrying the CHCHD10S59L/+ mutation. These data ST:STUDY_SUMMARY indicate that a bioenergetic intermediate such as L-acetylcarnitine may restore ST:STUDY_SUMMARY mitochondrial function in CHCHD10-related disease, due to the reduction in ST:STUDY_SUMMARY energy deficit that could be compensated by carnitine metabolic pathways. ST:INSTITUTE INSERM ST:LAST_NAME Madji Hounoum ST:FIRST_NAME Blandine ST:ADDRESS 151 Route Saint Antoine de Genistière 06204 Nice ST:EMAIL madjihounoum@yahoo.fr ST:PHONE +33 (0)4 89 06 43 01 #SUBJECT SU:SUBJECT_TYPE Mammal SU:SUBJECT_SPECIES Mus musculus SU:TAXONOMY_ID 10090 #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 - Plasma_2014 Genotype:Wild-type | Gender:female | Stage:Pre-symptomatic RAW_FILE_NAME=C18_Neg_Plasma_2014.mzXML SUBJECT_SAMPLE_FACTORS - Plasma_2015 Genotype:Wild-type | Gender:female | Stage:Pre-symptomatic RAW_FILE_NAME=C18_Neg_Plasma_2015.mzXML SUBJECT_SAMPLE_FACTORS - Plasma_2024 Genotype:Wild-type | Gender:female | Stage:Pre-symptomatic RAW_FILE_NAME=C18_Neg_Plasma_2024.mzXML SUBJECT_SAMPLE_FACTORS - Plasma_2027 Genotype:Wild-type | Gender:female | Stage:Pre-symptomatic RAW_FILE_NAME=C18_Neg_Plasma_2027.mzXML SUBJECT_SAMPLE_FACTORS - Plasma_2012 Genotype:CHCHD10S59L/+ | Gender:female | Stage:Pre-symptomatic RAW_FILE_NAME=C18_Neg_Plasma_2012.mzXML SUBJECT_SAMPLE_FACTORS - Plasma_2016 Genotype:CHCHD10S59L/+ | Gender:female | Stage:Pre-symptomatic RAW_FILE_NAME=C18_Neg_Plasma_2016.mzXML SUBJECT_SAMPLE_FACTORS - Plasma_2017 Genotype:CHCHD10S59L/+ | Gender:female | Stage:Pre-symptomatic RAW_FILE_NAME=C18_Neg_Plasma_2017.mzXML SUBJECT_SAMPLE_FACTORS - Plasma_2025 Genotype:CHCHD10S59L/+ | Gender:female | Stage:Pre-symptomatic RAW_FILE_NAME=C18_Neg_Plasma_2025.mzXML SUBJECT_SAMPLE_FACTORS - Plasma_2800 Genotype:Wild-type | Gender:Male | Stage:Pre-symptomatic RAW_FILE_NAME=C18_Neg_Plasma_2800.mzXML SUBJECT_SAMPLE_FACTORS - Plasma_2801 Genotype:CHCHD10S59L/+ | Gender:Male | Stage:Pre-symptomatic RAW_FILE_NAME=C18_Neg_Plasma_2801.mzXML SUBJECT_SAMPLE_FACTORS - Plasma_2772 Genotype:Wild-type | Gender:female | Stage:Symptomatic RAW_FILE_NAME=C18_Neg_Plasma_2772.mzXML SUBJECT_SAMPLE_FACTORS - Plasma_2773 Genotype:Wild-type | Gender:female | Stage:Symptomatic RAW_FILE_NAME=C18_Neg_Plasma_2773.mzXML SUBJECT_SAMPLE_FACTORS - Plasma_2768 Genotype:CHCHD10S59L/+ | Gender:female | Stage:Symptomatic RAW_FILE_NAME=C18_Neg_Plasma_2768.mzXML SUBJECT_SAMPLE_FACTORS - Plasma_2769 Genotype:CHCHD10S59L/+ | Gender:female | Stage:Symptomatic RAW_FILE_NAME=C18_Neg_Plasma_2769.mzXML SUBJECT_SAMPLE_FACTORS - Plasma_2008 Genotype:Wild-type | Gender:Male | Stage:Symptomatic RAW_FILE_NAME=C18_Neg_Plasma_2008.mzXML SUBJECT_SAMPLE_FACTORS - Plasma_2018 Genotype:Wild-type | Gender:Male | Stage:Symptomatic RAW_FILE_NAME=C18_Neg_Plasma_2018.mzXML SUBJECT_SAMPLE_FACTORS - Plasma_2019 Genotype:Wild-type | Gender:Male | Stage:Symptomatic RAW_FILE_NAME=C18_Neg_Plasma_2019.mzXML SUBJECT_SAMPLE_FACTORS - Plasma_2020 Genotype:Wild-type | Gender:Male | Stage:Symptomatic RAW_FILE_NAME=C18_Neg_Plasma_2020.mzXML SUBJECT_SAMPLE_FACTORS - Plasma_2007 Genotype:CHCHD10S59L/+ | Gender:Male | Stage:Symptomatic RAW_FILE_NAME=C18_Neg_Plasma_2007.mzXML SUBJECT_SAMPLE_FACTORS - Plasma_2009 Genotype:CHCHD10S59L/+ | Gender:Male | Stage:Symptomatic RAW_FILE_NAME=C18_Neg_Plasma_2009.mzXML SUBJECT_SAMPLE_FACTORS - Plasma_2010 Genotype:CHCHD10S59L/+ | Gender:Male | Stage:Symptomatic RAW_FILE_NAME=C18_Neg_Plasma_2010.mzXML SUBJECT_SAMPLE_FACTORS - Plasma_2021 Genotype:CHCHD10S59L/+ | Gender:Male | Stage:Symptomatic RAW_FILE_NAME=C18_Neg_Plasma_2021.mzXML SUBJECT_SAMPLE_FACTORS - Plasma_1674 Genotype:Wild-type | Gender:female | Stage:Symptomatic RAW_FILE_NAME=C18_Neg_Plasma_1674.mzXML SUBJECT_SAMPLE_FACTORS - Plasma_1675 Genotype:CHCHD10S59L/+ | Gender:female | Stage:Symptomatic RAW_FILE_NAME=C18_Neg_Plasma_1675.mzXML SUBJECT_SAMPLE_FACTORS - Plasma_QC1 Genotype:QC | Gender:QC | Stage:QC RAW_FILE_NAME=C18_Neg_Plasma_QC1.mzXML SUBJECT_SAMPLE_FACTORS - Plasma_QC2 Genotype:QC | Gender:QC | Stage:QC RAW_FILE_NAME=C18_Neg_Plasma_QC2.mzXML SUBJECT_SAMPLE_FACTORS - Plasma_QC3 Genotype:QC | Gender:QC | Stage:QC RAW_FILE_NAME=C18_Neg_Plasma_QC3.mzXML SUBJECT_SAMPLE_FACTORS - Plasma_QC4 Genotype:QC | Gender:QC | Stage:QC RAW_FILE_NAME=C18_Neg_Plasma_QC4.mzXML #COLLECTION CO:COLLECTION_SUMMARY Blood was taken by cardiac puncture from mice at pre-symptomatic (16 to 20 weeks CO:COLLECTION_SUMMARY of ages, n=5 mice per group) and symptomatic (40 to 48 weeks of ages, n=7 mice CO:COLLECTION_SUMMARY per group) stages, and transferred to EDTA coated tubes (Sarstedt). Then, blood CO:COLLECTION_SUMMARY was centrifuged at 500 rpm for 10 min at 4°C, plasma was collected and CO:COLLECTION_SUMMARY immediately frozen in microtubes (Eppendorf) and stored at −80°C until CO:COLLECTION_SUMMARY further analyses CO:SAMPLE_TYPE Blood (plasma) CO:STORAGE_CONDITIONS -80℃ #TREATMENT TR:TREATMENT_SUMMARY Then, blood was centrifuged at 500 rpm for 10 min at 4°C, plasma was collected TR:TREATMENT_SUMMARY and immediately frozen in microtubes (Eppendorf) and stored at −80°C until TR:TREATMENT_SUMMARY further analyses #SAMPLEPREP SP:SAMPLEPREP_SUMMARY 20 µL were precipitated with methanol and centrifuged at 16 000 x g for 10 mins SP:SAMPLEPREP_SUMMARY at 4°C, and the supernatant was dried SP:PROCESSING_STORAGE_CONDITIONS 4℃ SP:EXTRACT_STORAGE -80℃ #CHROMATOGRAPHY CH:CHROMATOGRAPHY_TYPE Reversed phase CH:INSTRUMENT_NAME Thermo Dionex Ultimate 3000 CH:COLUMN_NAME Phenomenex Kinetex XB-C18 (150 x 2.1mm,1.7um) CH:SOLVENT_A Water CH:SOLVENT_B ACN CH:FLOW_GRADIENT 20 minutes CH:FLOW_RATE 0.4 mL/min CH:COLUMN_TEMPERATURE 55°C #ANALYSIS AN:ANALYSIS_TYPE MS #MS MS:INSTRUMENT_NAME Thermo Q Exactive Plus Orbitrap MS:INSTRUMENT_TYPE Orbitrap MS:MS_TYPE ESI MS:ION_MODE NEGATIVE MS:MS_COMMENTS The full-scan acquisition ranged from 58 to 870 m/z, the instrument operated at MS:MS_COMMENTS 70,000 resolution (m/z = 200).A targeted analysis was applied on the samples, MS:MS_COMMENTS based on a library of standard compounds (Mass Spectroscopy Metabolite Library MS:MS_COMMENTS (MSML®) of standards, IROA Technologies™). The following criteria were MS:MS_COMMENTS followed to identify the metabolites: (1) retention time of the detected MS:MS_COMMENTS metabolite within ± 20 s of the standard reference, (2) exact measured of MS:MS_COMMENTS molecular mass of the metabolite within a range of 10 ppm around the known MS:MS_COMMENTS molecular mass of the reference compound, and (3) correspondence between MS:MS_COMMENTS isotopic ratios of the metabolite and the standard reference. The signal value MS:MS_COMMENTS was calculated using Xcalibur® software (Thermo Fisher Scientific, San Jose, MS:MS_COMMENTS CA) by integrating the chromatographic peak area corresponding to the selected MS:MS_COMMENTS metabolite. #MS_METABOLITE_DATA MS_METABOLITE_DATA:UNITS Relative units MS_METABOLITE_DATA_START Samples Plasma_2014 Plasma_2015 Plasma_2800 Plasma_2801 Plasma_2020 Plasma_2769 Plasma_2007 Plasma_2009 Plasma_1674 Plasma_2773 Plasma_2012 Plasma_2016 Plasma_1675 Plasma_2772 Plasma_2010 Plasma_2018 Plasma_2025 Plasma_2008 Plasma_2021 Plasma_2019 Plasma_2017 Plasma_2024 Plasma_2027 Plasma_2768 Plasma_QC1 Plasma_QC2 Plasma_QC3 Plasma_QC4 Factors Genotype:Wild-type | Gender:female | Stage:Pre-symptomatic Genotype:Wild-type | Gender:female | Stage:Pre-symptomatic Genotype:Wild-type | Gender:Male | Stage:Pre-symptomatic Genotype:CHCHD10S59L/+ | Gender:Male | Stage:Pre-symptomatic Genotype:Wild-type | Gender:Male | Stage:Symptomatic Genotype:CHCHD10S59L/+ | Gender:female | Stage:Symptomatic Genotype:CHCHD10S59L/+ | Gender:Male | Stage:Symptomatic Genotype:CHCHD10S59L/+ | Gender:Male | Stage:Symptomatic Genotype:Wild-type | Gender:female | Stage:Symptomatic Genotype:Wild-type | Gender:female | Stage:Symptomatic Genotype:CHCHD10S59L/+ | Gender:female | Stage:Pre-symptomatic Genotype:CHCHD10S59L/+ | Gender:female | Stage:Pre-symptomatic Genotype:CHCHD10S59L/+ | Gender:female | Stage:Symptomatic Genotype:Wild-type | Gender:female | Stage:Symptomatic Genotype:CHCHD10S59L/+ | Gender:Male | Stage:Symptomatic Genotype:Wild-type | Gender:Male | Stage:Symptomatic Genotype:CHCHD10S59L/+ | Gender:female | Stage:Pre-symptomatic Genotype:Wild-type | Gender:Male | Stage:Symptomatic Genotype:CHCHD10S59L/+ | Gender:Male | Stage:Symptomatic Genotype:Wild-type | Gender:Male | Stage:Symptomatic Genotype:CHCHD10S59L/+ | Gender:female | Stage:Pre-symptomatic Genotype:Wild-type | Gender:female | Stage:Pre-symptomatic Genotype:Wild-type | Gender:female | Stage:Pre-symptomatic Genotype:CHCHD10S59L/+ | Gender:female | Stage:Symptomatic Genotype:QC | Gender:QC | Stage:QC Genotype:QC | Gender:QC | Stage:QC Genotype:QC | Gender:QC | Stage:QC Genotype:QC | Gender:QC | Stage:QC OROTIC_ACID 181E+05 217E+05 289E+04 915E+05 358E+05 000E+00 105E+06 471E+05 100E+04 467E+03 765E+05 499E+05 262E+06 503E+04 161E+06 898E+05 411E+03 434E+03 688E+05 744E+03 851E+05 144E+05 275E+05 240E+03 500E-05 131E-04 216E-05 147E-04 N-ACETYLNEURAMINATE 101E+06 121E+06 399E+05 977E+05 817E+05 000E+00 115E+06 180E+05 975E+05 132E+06 575E+05 656E+05 208E+06 196E+06 125E+06 801E+05 114E+06 364E+05 181E+06 780E+05 942E+05 104E+06 792E+05 107E+06 157E-04 154E-04 136E-04 408E-05 L-ASPARAGINE 123E+06 364E+06 170E+06 174E+06 129E+06 000E+00 303E+06 223E+06 125E+06 129E+06 206E+06 234E+06 118E+06 751E+05 209E+06 142E+06 375E+06 139E+06 162E+06 206E+06 397E+06 167E+06 238E+06 229E+06 466E-04 457E-04 486E-04 147E-04 N-ACETYL-L-ASPARTIC_ACID 321E+06 597E+06 197E+06 264E+06 199E+06 000E+00 202E+06 220E+06 125E+07 160E+06 252E+06 505E+06 568E+07 324E+06 465E+06 241E+06 450E+06 175E+06 123E+06 249E+06 473E+06 327E+06 438E+06 329E+06 951E-04 749E-04 791E-04 828E-04 CREATININE 182E+05 144E+05 119E+05 162E+05 262E+05 265E+03 422E+05 411E+05 491E+05 288E+05 247E+05 255E+05 111E+06 138E+05 348E+05 197E+05 294E+05 611E+05 348E+05 173E+05 169E+05 207E+05 290E+05 123E+05 658E-05 466E-05 817E-05 644E-05 CITRAMALATE 782E+06 970E+06 178E+06 657E+06 312E+06 000E+00 181E+06 662E+06 832E+06 913E+05 472E+06 108E+07 225E+07 238E+06 108E+07 549E+06 951E+06 984E+05 136E+06 233E+06 121E+07 241E+06 807E+06 384E+06 128E-03 126E-03 133E-03 776E-04 3-UREIDOPROPIONATE 399E+04 000E+00 194E+05 250E+04 100E+05 000E+00 106E+06 801E+05 207E+06 679E+05 131E+06 474E+04 955E+05 346E+04 685E+05 877E+04 126E+06 308E+05 412E+05 000E+00 998E+05 105E+05 393E+05 390E+04 890E-05 790E-05 858E-05 657E-05 MALONATE 228E+05 283E+05 134E+06 289E+06 186E+06 000E+00 807E+05 785E+05 179E+06 448E+05 555E+05 951E+05 371E+05 684E+05 269E+06 222E+06 155E+06 109E+06 933E+05 314E+06 267E+06 472E+06 106E+06 193E+06 261E-04 225E-04 248E-04 243E-04 ALPHA-AMINOADIPATE 143E+06 678E+06 216E+06 173E+06 182E+06 000E+00 227E+06 238E+06 213E+06 125E+06 221E+06 158E+06 145E+06 257E+06 177E+06 169E+06 400E+06 116E+06 213E+06 242E+06 382E+06 139E+06 227E+06 187E+06 532E-04 439E-04 541E-04 492E-04 L-ARABITOL 212E+05 983E+05 254E+05 130E+05 181E+05 410E+03 500E+05 451E+05 262E+05 562E+05 240E+05 737E+05 712E+05 163E+05 253E+05 228E+05 437E+05 315E+05 299E+05 297E+05 699E+05 213E+05 632E+05 294E+05 816E-05 698E-05 803E-05 861E-05 LINOLEATE 925E+06 170E+06 411E+06 264E+07 294E+07 892E+05 307E+07 261E+07 841E+07 787E+07 624E+07 653E+06 107E+08 739E+06 298E+07 372E+07 233E+07 263E+07 407E+07 376E+07 146E+07 107E+08 404E+07 237E+07 565E-03 569E-03 606E-03 601E-03 CYTIDINE_2',3'-CYCLIC_MONO-PHOS-PHAT 503E+05 682E+05 560E+04 194E+05 115E+05 231E+03 302E+05 761E+05 308E+05 121E+04 265E+05 640E+05 278E+05 340E+04 755E+05 571E+04 690E+05 235E+04 151E+05 409E+04 764E+05 778E+04 749E+05 877E+04 907E-05 764E-05 797E-05 758E-05 PALMITATE 102E+07 280E+06 296E+06 129E+07 117E+07 927E+05 118E+07 129E+07 244E+07 183E+07 148E+07 716E+06 139E+07 512E+06 136E+07 168E+07 928E+06 119E+07 150E+07 136E+07 766E+06 174E+07 130E+07 120E+07 209E-03 175E-03 192E-03 187E-03 STEARATE 976E+06 392E+06 223E+06 950E+06 925E+06 130E+06 934E+06 995E+06 118E+07 110E+07 971E+06 922E+06 695E+06 396E+06 112E+07 108E+07 869E+06 893E+06 112E+07 102E+07 748E+06 108E+07 103E+07 103E+07 147E-03 152E-03 160E-03 157E-03 L-HISTIDINE 331E+06 606E+06 118E+06 485E+05 129E+06 000E+00 311E+06 196E+06 406E+05 688E+05 357E+06 274E+06 734E+06 115E+06 566E+06 302E+05 605E+06 944E+05 366E+06 394E+06 724E+06 449E+06 499E+06 445E+06 807E-04 679E-04 773E-04 774E-04 2-HYDROXY-4-(METHYLTHIO)BUTYRIC_ACI 298E+06 116E+06 894E+05 282E+06 272E+06 217E+04 353E+06 323E+06 180E+06 260E+06 313E+06 410E+06 896E+05 665E+05 520E+06 264E+06 482E+06 389E+06 232E+06 276E+06 546E+06 165E+06 324E+06 186E+06 460E-04 454E-04 483E-04 525E-04 3-(2-HYDROXYPHENYL)PROPANOATE 582E+06 863E+05 766E+05 332E+05 331E+05 000E+00 543E+05 824E+05 177E+06 643E+05 103E+06 118E+07 662E+05 207E+05 470E+05 387E+05 898E+05 122E+06 352E+06 321E+05 177E+07 253E+06 176E+05 116E+06 932E-05 965E-05 104E-04 106E-04 GLUCOSE_6-PHOSPHATE 380E+06 191E+07 858E+06 297E+06 331E+06 407E+03 149E+06 298E+06 426E+06 284E+06 232E+06 398E+06 579E+06 631E+07 447E+06 309E+06 267E+06 318E+06 283E+07 330E+06 279E+06 545E+06 180E+06 162E+07 126E-03 131E-03 139E-03 125E-03 L-TRYPTOPHAN 565E+07 399E+07 743E+06 314E+07 240E+07 000E+00 674E+07 833E+07 129E+08 568E+07 757E+07 616E+07 114E+08 201E+07 836E+07 321E+07 677E+07 183E+07 415E+07 185E+07 881E+07 476E+07 101E+08 678E+07 101E-02 942E-03 101E-02 105E-02 L-PHENYLALANINE 335E+07 292E+07 937E+06 321E+07 251E+07 237E+03 406E+07 538E+07 573E+07 232E+07 373E+07 523E+07 515E+07 121E+07 575E+07 326E+07 628E+07 222E+07 267E+07 333E+07 703E+07 294E+07 501E+07 336E+07 677E-03 630E-03 675E-03 651E-03 L-TYROSINE 102E+07 101E+07 446E+06 110E+07 827E+06 266E+03 203E+07 196E+07 281E+07 906E+06 121E+07 128E+07 273E+07 411E+06 224E+07 116E+07 257E+07 883E+06 125E+07 136E+07 250E+07 742E+06 170E+07 134E+07 241E-03 221E-03 252E-03 235E-03 3-HYDROXYBENZOATE 162E+07 108E+07 104E+06 608E+06 630E+06 000E+00 116E+07 136E+07 269E+06 471E+06 847E+06 234E+07 743E+05 105E+06 135E+07 684E+06 170E+07 432E+06 406E+06 206E+06 165E+07 125E+07 212E+07 416E+06 147E-03 140E-03 146E-03 153E-03 N-ACETYLGLYCINE 231E+06 465E+06 358E+06 207E+06 319E+06 377E+04 292E+06 251E+06 519E+06 194E+06 199E+06 344E+06 553E+06 455E+06 246E+06 325E+06 181E+06 142E+06 232E+06 369E+06 225E+06 228E+06 306E+06 219E+06 468E-04 456E-04 421E-04 444E-04 L-GLUTAMIC_ACID 970E+06 176E+07 921E+06 732E+06 827E+06 000E+00 865E+06 101E+07 764E+06 845E+06 701E+06 588E+06 146E+07 256E+07 793E+06 722E+06 823E+06 658E+06 187E+07 810E+06 656E+06 947E+06 625E+06 123E+07 221E-03 202E-03 214E-03 202E-03 3-DEHYDROSHIKIMATE 140E+06 122E+06 555E+05 176E+06 148E+06 000E+00 194E+06 243E+06 346E+06 222E+06 202E+06 120E+06 115E+06 113E+06 227E+06 177E+06 174E+06 968E+05 129E+06 948E+05 150E+06 141E+06 170E+06 172E+06 316E-04 298E-04 315E-04 314E-04 CHOLATE 105E+06 207E+05 193E+05 716E+06 402E+06 000E+00 705E+06 254E+07 286E+07 153E+07 115E+07 240E+06 930E+06 121E+06 431E+07 459E+06 419E+06 352E+06 282E+07 294E+06 439E+06 276E+07 853E+06 612E+06 175E-03 174E-03 181E-03 181E-03 ELAIDIC_ACID 121E+07 189E+06 431E+06 282E+07 272E+07 828E+05 269E+07 269E+07 778E+07 598E+07 458E+07 513E+06 961E+07 721E+06 330E+07 312E+07 172E+07 259E+07 350E+07 258E+07 105E+07 416E+07 251E+07 281E+07 523E-03 528E-03 524E-03 531E-03 LACTATE 298E-01 339E-01 112E-01 308E-01 252E-01 000E+00 295E-01 370E-01 418E-01 288E-01 307E-01 397E-01 311E-01 185E-01 384E-01 248E-01 327E-01 214E-01 179E-01 173E-01 314E-01 202E-01 357E-01 249E-01 266E-01 293E-01 278E-01 279E-01 MANNITOL 420E+06 876E+06 465E+06 563E+06 520E+06 000E+00 541E+06 896E+06 125E+07 151E+07 121E+07 615E+06 880E+06 733E+06 547E+06 608E+06 712E+06 552E+06 342E+06 355E+06 530E+06 294E+06 962E+06 683E+06 142E-03 136E-03 134E-03 137E-03 L-ASPARTATE 143E+08 384E+08 262E+08 920E+07 154E+08 000E+00 109E+08 913E+07 613E+06 778E+07 146E+08 226E+08 221E+06 290E+08 561E+07 138E+08 122E+08 140E+08 164E+08 180E+08 140E+08 123E+08 165E+08 163E+08 339E-02 315E-02 322E-02 313E-02 BENZYL_ALCOHOL 303E+06 236E+05 000E+00 457E+05 935E+05 000E+00 198E+06 170E+06 116E+06 305E+06 122E+06 200E+06 104E+05 818E+04 145E+06 272E+06 124E+07 803E+05 299E+06 118E+06 987E+06 504E+05 908E+06 139E+05 409E-04 383E-04 414E-04 407E-04 GUANOSINE_5'-MONOPHOSPHATE 616E+06 488E+06 232E+06 153E+06 793E+06 000E+00 554E+06 103E+07 510E+05 179E+05 251E+06 193E+06 109E+05 374E+06 293E+06 597E+06 208E+06 999E+05 895E+06 359E+06 100E+06 995E+06 114E+06 104E+07 795E-04 740E-04 758E-04 797E-04 ADENOSINE_5'-MONOPHOSPHATE 233E+07 203E+07 110E+07 764E+06 452E+07 000E+00 361E+07 551E+07 413E+06 668E+05 898E+06 104E+07 743E+05 648E+06 145E+07 286E+07 110E+07 100E+07 342E+07 274E+07 511E+06 311E+07 622E+06 201E+07 338E-03 324E-03 327E-03 326E-03 ALLANTOIN 147E+07 649E+06 735E+06 154E+07 136E+07 000E+00 244E+07 215E+07 216E+07 325E+07 264E+07 163E+07 241E+07 106E+07 245E+07 136E+07 227E+07 174E+07 315E+07 153E+07 214E+07 123E+07 198E+07 130E+07 356E-03 332E-03 333E-03 331E-03 L-SERINE 336E+06 745E+06 599E+06 550E+06 400E+06 000E+00 101E+07 618E+06 486E+06 350E+06 513E+06 508E+06 940E+06 462E+06 572E+06 443E+06 769E+06 441E+06 808E+06 541E+06 804E+06 453E+06 580E+06 704E+06 128E-03 125E-03 131E-03 121E-03 URIDINE-5-MONOPHOSPHATE 462E+06 302E+06 185E+06 164E+06 635E+06 000E+00 550E+06 931E+06 656E+05 000E+00 157E+06 101E+06 677E+05 288E+06 269E+06 500E+06 156E+06 122E+06 179E+07 358E+06 538E+05 645E+06 541E+05 612E+06 656E-04 644E-04 642E-04 691E-04 THYMIDINE 366E+06 159E+06 928E+05 428E+06 374E+06 216E+03 458E+06 584E+06 980E+06 675E+06 747E+06 486E+06 785E+06 119E+06 581E+06 381E+06 524E+06 327E+06 120E+06 320E+06 454E+06 274E+06 664E+06 278E+06 749E-04 733E-04 773E-04 772E-04 N-ACETYL-L-METHIONINE 213E+06 259E+06 341E+05 213E+06 135E+06 305E+03 317E+06 504E+06 605E+06 185E+06 280E+06 403E+06 104E+07 735E+05 637E+06 185E+06 590E+06 120E+06 896E+05 121E+06 724E+06 231E+06 332E+06 196E+06 533E-04 497E-04 511E-04 532E-04 RIBOSE_5-PHOSPHATE 270E+06 588E+06 911E+06 529E+06 692E+06 000E+00 405E+06 580E+06 210E+06 491E+06 203E+06 356E+06 696E+06 335E+07 683E+06 802E+06 364E+06 130E+07 120E+07 272E+06 370E+06 112E+07 280E+06 206E+07 174E-03 167E-03 171E-03 165E-03 MALATE 699E+07 963E+07 743E+06 214E+07 802E+06 000E+00 180E+07 345E+07 259E+07 682E+06 183E+07 106E+08 708E+07 147E+07 903E+07 116E+07 474E+07 365E+06 241E+07 564E+06 885E+07 130E+07 527E+07 202E+07 488E-03 481E-03 508E-03 514E-03 GLUCURONIC_ACID 108E+07 173E+07 448E+07 229E+07 270E+07 268E+04 253E+07 181E+07 519E+06 140E+07 208E+07 796E+06 589E+06 520E+07 167E+07 365E+07 239E+07 205E+07 367E+07 696E+07 236E+07 862E+07 134E+07 610E+07 655E-03 617E-03 636E-03 618E-03 N-ACETYL-L-GLUTAMIC_ACID 312E+06 137E+07 828E+05 254E+06 138E+06 254E+03 171E+06 302E+06 408E+06 576E+05 203E+06 193E+07 753E+06 118E+06 421E+06 188E+06 925E+06 737E+05 388E+06 138E+06 129E+07 129E+06 371E+06 216E+06 734E-04 698E-04 735E-04 739E-04 FUMARATE 637E+06 102E+07 150E+06 396E+06 219E+06 812E+03 448E+06 817E+06 727E+06 207E+06 434E+06 948E+06 148E+07 299E+06 146E+07 306E+06 934E+06 123E+06 627E+06 138E+06 115E+07 247E+06 664E+06 386E+06 105E-03 100E-03 102E-03 102E-03 3-SULFINO-L-ALANINE 332E+07 163E+07 164E+07 322E+07 354E+07 000E+00 265E+07 300E+07 270E+07 313E+07 196E+07 212E+07 510E+06 216E+07 261E+07 276E+07 277E+07 455E+07 655E+07 315E+07 252E+07 475E+07 197E+07 207E+07 497E-03 508E-03 515E-03 532E-03 CREATINE 521E+06 425E+06 451E+06 431E+06 585E+06 000E+00 116E+07 787E+06 751E+06 600E+06 567E+06 446E+06 188E+07 411E+06 563E+06 525E+06 732E+06 128E+07 115E+07 665E+06 508E+06 613E+06 571E+06 335E+06 144E-03 136E-03 141E-03 138E-03 GLUCONIC_ACID 640E+07 211E+08 154E+08 883E+07 106E+08 000E+00 988E+07 983E+07 223E+07 346E+07 759E+07 678E+07 249E+07 999E+07 876E+07 114E+08 135E+08 638E+07 168E+08 220E+08 140E+08 720E+07 927E+07 851E+07 226E-02 216E-02 224E-02 220E-02 CITRULLINE 439E+06 462E+06 624E+06 547E+06 570E+06 345E+03 934E+06 779E+06 547E+06 496E+06 765E+06 556E+06 169E+07 675E+06 813E+06 602E+06 101E+07 477E+06 104E+07 806E+06 113E+07 536E+06 586E+06 106E+07 155E-03 154E-03 159E-03 149E-03 XANTHINE 914E+05 254E+07 502E+06 228E+07 143E+07 000E+00 907E+06 237E+07 730E+07 237E+07 344E+07 271E+05 303E+05 189E+07 308E+07 175E+07 132E+07 828E+06 526E+06 655E+06 496E+06 873E+06 647E+07 851E+04 321E-03 309E-03 325E-03 321E-03 N6-(DELTA2-ISOPENTENYL)-ADENINE 502E+06 784E+06 168E+06 321E+06 303E+06 108E+06 514E+06 988E+06 720E+06 351E+06 500E+06 957E+06 422E+06 163E+06 117E+07 287E+06 845E+06 230E+06 295E+06 263E+06 111E+07 215E+06 820E+06 291E+06 911E-04 911E-04 918E-04 892E-04 TAURINE 923E+07 209E+08 151E+08 136E+08 129E+08 502E+03 234E+08 222E+08 186E+08 204E+08 178E+08 111E+08 302E+08 150E+08 132E+08 120E+08 144E+08 132E+08 671E+08 142E+08 176E+08 193E+08 925E+07 166E+08 374E-02 359E-02 370E-02 354E-02 PANTOTHENIC_ACID 253E+07 307E+07 480E+06 167E+07 117E+07 000E+00 134E+07 239E+07 439E+07 125E+07 212E+07 505E+07 559E+07 937E+06 280E+07 124E+07 385E+07 723E+06 110E+07 975E+06 429E+07 213E+07 434E+07 162E+07 402E-03 389E-03 409E-03 409E-03 TRANS-ACONITATE 807E+06 112E+07 322E+06 557E+06 481E+06 000E+00 375E+06 731E+06 331E+06 146E+06 389E+06 945E+06 131E+07 104E+07 138E+07 611E+06 868E+06 279E+06 248E+06 626E+06 109E+07 704E+06 773E+06 114E+07 117E-03 119E-03 121E-03 120E-03 CITRATE 892E+08 103E+09 538E+08 737E+08 603E+08 000E+00 397E+08 733E+08 273E+08 216E+08 515E+08 984E+08 961E+08 900E+08 123E+09 645E+08 886E+08 407E+08 310E+08 652E+08 113E+09 674E+08 856E+08 992E+08 141E-01 134E-01 137E-01 140E-01 DEOXYCHOLATE 383E+06 119E+06 000E+00 185E+06 350E+06 000E+00 331E+06 891E+06 262E+07 124E+07 958E+06 320E+06 531E+06 636E+05 108E+07 280E+06 567E+06 285E+06 379E+06 334E+06 895E+06 337E+06 123E+07 207E+06 871E-04 896E-04 868E-04 902E-04 URIDINE 478E+07 828E+07 332E+06 140E+07 138E+07 000E+00 326E+07 646E+07 318E+07 210E+07 260E+07 725E+07 234E+07 529E+06 493E+07 574E+06 415E+07 709E+06 863E+06 421E+06 439E+07 148E+07 944E+07 671E+06 547E-03 527E-03 544E-03 554E-03 INOSINE_5'-MONOPHOSPHATE 205E+07 126E+07 497E+06 168E+06 316E+06 000E+00 135E+07 242E+07 699E+05 413E+05 109E+06 319E+06 000E+00 404E+06 185E+06 275E+06 147E+06 534E+06 463E+07 447E+06 491E+05 119E+07 252E+06 558E+06 135E-03 129E-03 135E-03 134E-03 HOMOSERINE 137E+07 395E+07 186E+07 217E+07 181E+07 000E+00 455E+07 334E+07 184E+07 175E+07 256E+07 263E+07 366E+07 174E+07 276E+07 207E+07 485E+07 185E+07 423E+07 272E+07 508E+07 159E+07 256E+07 394E+07 603E-03 582E-03 597E-03 576E-03 ALPHA-GLUCOSE 345E+08 290E+08 664E+08 551E+08 617E+08 000E+00 726E+08 528E+08 366E+08 564E+08 632E+08 315E+08 388E+08 425E+08 443E+08 625E+08 540E+08 567E+08 611E+08 635E+08 542E+08 395E+08 320E+08 458E+08 103E-01 995E-02 990E-02 982E-02 3-HYDROXYPHENYLACETATE 792E+07 269E+07 335E+06 374E+07 209E+07 000E+00 619E+07 640E+07 146E+07 348E+07 653E+07 895E+07 000E+00 482E+06 571E+07 333E+07 811E+07 412E+07 354E+07 316E+07 852E+07 585E+07 983E+07 254E+07 822E-03 802E-03 809E-03 838E-03 GLYCERATE 416E+06 514E+06 631E+06 556E+06 506E+06 000E+00 597E+06 462E+06 620E+06 499E+06 539E+06 632E+06 487E+06 536E+06 689E+06 444E+06 688E+06 723E+06 122E+07 636E+06 714E+06 515E+06 560E+06 418E+06 103E-03 991E-04 100E-03 102E-03 HIPPURATE 451E+07 158E+07 308E+07 216E+08 160E+08 000E+00 184E+08 409E+08 118E+09 535E+08 479E+08 679E+06 247E+08 750E+07 376E+08 215E+08 231E+08 154E+08 114E+08 123E+08 139E+08 105E+08 191E+08 815E+07 406E-02 392E-02 405E-02 408E-02 5-OXO-L-PROLINE 634E+07 581E+07 875E+07 179E+08 132E+08 000E+00 115E+08 959E+07 278E+08 643E+07 100E+08 443E+07 594E+08 843E+07 131E+08 148E+08 964E+07 626E+07 622E+07 167E+08 870E+07 168E+08 711E+07 163E+08 226E-02 220E-02 229E-02 226E-02 CETOGLUTARATE 802E+06 105E+07 274E+06 133E+07 635E+06 000E+00 181E+07 303E+07 228E+07 544E+06 212E+07 477E+07 105E+08 640E+06 564E+07 124E+07 471E+07 365E+06 283E+06 330E+06 545E+07 616E+06 234E+07 136E+07 367E-03 359E-03 368E-03 364E-03 SUBERIC_ACID 535E+08 539E+08 549E+08 536E+08 524E+08 553E+08 530E+08 528E+08 517E+08 528E+08 535E+08 533E+08 553E+08 550E+08 526E+08 543E+08 529E+08 529E+08 535E+08 539E+08 514E+08 505E+08 536E+08 539E+08 991E-02 955E-02 957E-02 955E-02 SUCCINATE 215E+08 684E+08 248E+07 740E+07 449E+07 211E+04 698E+07 275E+08 105E+08 146E+07 722E+07 476E+08 146E+08 276E+07 332E+08 360E+07 292E+08 192E+07 426E+07 244E+07 458E+08 331E+07 413E+08 326E+07 315E-02 306E-02 319E-02 314E-02 4-METHYL-2-OXO-PENTANOIC_ACID 531E+07 124E+07 100E+07 685E+07 439E+07 111E+05 760E+07 112E+08 188E+08 909E+07 107E+08 395E+07 855E+07 104E+07 125E+08 730E+07 752E+07 619E+07 483E+07 413E+07 797E+07 512E+07 625E+07 346E+07 113E-02 111E-02 115E-02 115E-02 INDOXYL_SULFATE 238E+08 136E+08 352E+06 652E+07 786E+07 000E+00 245E+08 339E+08 558E+08 558E+08 404E+08 343E+08 170E+08 239E+07 229E+08 107E+08 571E+08 557E+07 144E+08 582E+07 718E+08 766E+07 379E+08 294E+08 417E-02 405E-02 412E-02 420E-02 N-ACETYL-L-PHENYLALANINE 720E+06 453E+06 194E+06 693E+06 532E+06 127E+05 975E+06 130E+07 160E+07 560E+06 954E+06 139E+07 189E+07 239E+06 177E+07 677E+06 172E+07 560E+06 252E+06 577E+06 241E+07 562E+06 840E+06 545E+06 157E-03 151E-03 154E-03 154E-03 3-HYDROXYBUTANOIC_ACID 694E+07 105E+08 263E+07 827E+07 677E+07 000E+00 769E+07 122E+08 111E+08 532E+07 577E+07 999E+07 416E+07 263E+07 129E+08 737E+07 960E+07 399E+07 420E+07 640E+07 119E+08 448E+07 827E+07 518E+07 124E-02 124E-02 126E-02 128E-02 FORMYL-L-METHIONYL_PEPTIDE 329E+06 187E+06 851E+05 381E+06 261E+06 198E+03 301E+06 357E+06 228E+06 212E+06 246E+06 487E+06 190E+06 105E+06 405E+06 256E+06 596E+06 403E+06 239E+06 301E+06 530E+06 202E+06 358E+06 291E+06 517E-04 509E-04 521E-04 510E-04 4-ACETAMIDOBUTANOATE 805E+07 172E+07 108E+06 704E+06 490E+06 252E+04 427E+07 166E+08 210E+07 751E+06 396E+07 820E+06 101E+07 144E+06 964E+07 916E+06 655E+07 412E+06 687E+06 421E+06 125E+08 354E+06 203E+07 476E+06 519E-03 513E-03 530E-03 516E-03 4-METHYL-2-OXOVALERIC_ACID 500E+07 137E+07 133E+07 575E+07 426E+07 993E+04 730E+07 102E+08 191E+08 865E+07 933E+07 342E+07 106E+08 119E+07 106E+08 578E+07 669E+07 533E+07 495E+07 385E+07 775E+07 596E+07 517E+07 267E+07 109E-02 107E-02 110E-02 110E-02 N-ACETYL-TRYPTOPHAN 552E+06 256E+06 165E+06 543E+06 443E+06 000E+00 955E+06 124E+07 148E+07 946E+06 102E+07 585E+06 219E+07 380E+06 146E+07 565E+06 880E+06 326E+06 322E+06 340E+06 120E+07 585E+06 685E+06 602E+06 130E-03 130E-03 131E-03 132E-03 MS_METABOLITE_DATA_END #METABOLITES METABOLITES_START metabolite_name RT (min) OROTIC_ACID 1.5494308 N-ACETYLNEURAMINATE 0.95982426 L-ASPARAGINE 0.83376608 N-ACETYL-L-ASPARTIC_ACID 1.3221222 CREATININE 0.82930775 CITRAMALATE 1.3221222 3-UREIDOPROPIONATE 1.139387 MALONATE 1.1794995 ALPHA-AMINOADIPATE 0.86050777 L-ARABITOL 0.8471369 LINOLEATE 14.183729 CYTIDINE_2',3'-CYCLIC_MONO-PHOS-PHAT 1.6621581 PALMITATE 14.428865 STEARATE 15.073351 L-HISTIDINE 0.82930775 2-HYDROXY-4-(METHYLTHIO)BUTYRIC_ACI 8.1026959 3-(2-HYDROXYPHENYL)PROPANOATE 8.65239399999999 GLUCOSE_6-PHOSPHATE 0.95982426 L-TRYPTOPHAN 5.2666198 L-PHENYLALANINE 3.3781045 L-TYROSINE 1.4736622 3-HYDROXYBENZOATE 5.9529968 N-ACETYLGLYCINE 1.175041 L-GLUTAMIC_ACID 0.8471369 3-DEHYDROSHIKIMATE 1.9251204 CHOLATE 12.1647079999999 ELAIDIC_ACID 14.593775 LACTATE 1.2374412 MANNITOL 0.83822207 L-ASPARTATE 0.86050777 BENZYL_ALCOHOL 9.7657399 GUANOSINE_5'-MONOPHOSPHATE 1.7869539 ADENOSINE_5'-MONOPHOSPHATE 1.4558327 ALLANTOIN 0.86050777 L-SERINE 0.83376608 URIDINE-5-MONOPHOSPHATE 1.5984581 THYMIDINE 5.1418239 N-ACETYL-L-METHIONINE 6.4610951 RIBOSE_5-PHOSPHATE 0.9642807 MALATE 1.0413325 GLUCURONIC_ACID 0.86050777 N-ACETYL-L-GLUTAMIC_ACID 1.7735831 FUMARATE 1.5939997 3-SULFINO-L-ALANINE 1.1661287 CREATINE 0.83376608 GLUCONIC_ACID 0.86050777 CITRULLINE 0.83822207 XANTHINE 1.6220455 N6-(DELTA2-ISOPENTENYL)-ADENINE 9.0040878 TAURINE 0.83822207 PANTOTHENIC_ACID 5.6543783 TRANS-ACONITATE 2.7853231 CITRATE 1.4023493 DEOXYCHOLATE 12.806516 URIDINE 1.8582663 INOSINE_5'-MONOPHOSPHATE 2.139058 HOMOSERINE 0.83822207 ALPHA-GLUCOSE 0.83822207 3-HYDROXYPHENYLACETATE 9.5817172 GLYCERATE 0.91844716 HIPPURATE 7.1118184 5-OXO-L-PROLINE 1.617589 CETOGLUTARATE 1.5583434 SUBERIC_ACID 8.9091545 SUCCINATE 1.6577015 4-METHYL-2-OXO-PENTANOIC_ACID 8.8155585 INDOXYL_SULFATE 8.1561813 N-ACETYL-L-PHENYLALANINE 8.8423003 3-HYDROXYBUTANOIC_ACID 2.3217958 FORMYL-L-METHIONYL_PEPTIDE 5.6989489 4-ACETAMIDOBUTANOATE 4.4554442 4-METHYL-2-OXOVALERIC_ACID 9.09322749999999 N-ACETYL-TRYPTOPHAN 8.83338539999999 METABOLITES_END #END