#METABOLOMICS WORKBENCH Madjihounoum_20221203_055157 DATATRACK_ID:3622 STUDY_ID:ST002434 ANALYSIS_ID:AN003966 PROJECT_ID:PR001567 VERSION 1 CREATED_ON January 10, 2023, 8:43 am #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:DEPARTMENT C3M PR:LABORATORY RICCI 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 heart 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 #FACTORS #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 - Heart_1 Genotype:Wild-type | Gender:Male | Stage:Symptomatic RAW_FILE_NAME=HILIC_POS_Heart_1.mzXML SUBJECT_SAMPLE_FACTORS - Heart_2 Genotype:Wild-type | Gender:Male | Stage:Symptomatic RAW_FILE_NAME=HILIC_POS_Heart_2.mzXML SUBJECT_SAMPLE_FACTORS - Heart_3 Genotype:Wild-type | Gender:Male | Stage:Symptomatic RAW_FILE_NAME=HILIC_POS_Heart_3.mzXML SUBJECT_SAMPLE_FACTORS - Heart_4 Genotype:Wild-type | Gender:Male | Stage:Symptomatic RAW_FILE_NAME=HILIC_POS_Heart_4.mzXML SUBJECT_SAMPLE_FACTORS - Heart_5 Genotype:Wild-type | Gender:Male | Stage:Symptomatic RAW_FILE_NAME=HILIC_POS_Heart_5.mzXML SUBJECT_SAMPLE_FACTORS - Heart_6 Genotype:Wild-type | Gender:Male | Stage:Symptomatic RAW_FILE_NAME=HILIC_POS_Heart_6.mzXML SUBJECT_SAMPLE_FACTORS - Heart_7 Genotype:CHCHD10S59L/+ | Gender:Male | Stage:Symptomatic RAW_FILE_NAME=HILIC_POS_Heart_7.mzXML SUBJECT_SAMPLE_FACTORS - Heart_8 Genotype:CHCHD10S59L/+ | Gender:Male | Stage:Symptomatic RAW_FILE_NAME=HILIC_POS_Heart_8.mzXML SUBJECT_SAMPLE_FACTORS - Heart_9 Genotype:CHCHD10S59L/+ | Gender:Male | Stage:Symptomatic RAW_FILE_NAME=HILIC_POS_Heart_9.mzXML SUBJECT_SAMPLE_FACTORS - Heart_10 Genotype:CHCHD10S59L/+ | Gender:Male | Stage:Symptomatic RAW_FILE_NAME=HILIC_POS_Heart_10.mzXML SUBJECT_SAMPLE_FACTORS - Heart_11 Genotype:CHCHD10S59L/+ | Gender:Male | Stage:Symptomatic RAW_FILE_NAME=HILIC_POS_Heart_11.mzXML SUBJECT_SAMPLE_FACTORS - Heart_12 Genotype:CHCHD10S59L/+ | Gender:Male | Stage:Symptomatic RAW_FILE_NAME=HILIC_POS_Heart_12.mzXML SUBJECT_SAMPLE_FACTORS - Heart_13 Genotype:Wild-type | Gender:female | Stage:Symptomatic RAW_FILE_NAME=HILIC_POS_Heart_13.mzXML SUBJECT_SAMPLE_FACTORS - Heart_14 Genotype:Wild-type | Gender:female | Stage:Symptomatic RAW_FILE_NAME=HILIC_POS_Heart_14.mzXML SUBJECT_SAMPLE_FACTORS - Heart_15 Genotype:Wild-type | Gender:Male | Stage:Symptomatic RAW_FILE_NAME=HILIC_POS_Heart_15.mzXML SUBJECT_SAMPLE_FACTORS - Heart_16 Genotype:CHCHD10S59L/+ | Gender:female | Stage:Symptomatic RAW_FILE_NAME=HILIC_POS_Heart_16.mzXML SUBJECT_SAMPLE_FACTORS - Heart_17 Genotype:CHCHD10S59L/+ | Gender:female | Stage:Symptomatic RAW_FILE_NAME=HILIC_POS_Heart_17.mzXML SUBJECT_SAMPLE_FACTORS - Heart_18 Genotype:CHCHD10S59L/+ | Gender:Male | Stage:Symptomatic RAW_FILE_NAME=HILIC_POS_Heart_18.mzXML SUBJECT_SAMPLE_FACTORS - Heart_19 Genotype:Wild-type | Gender:female | Stage:Symptomatic RAW_FILE_NAME=HILIC_POS_Heart_19.mzXML SUBJECT_SAMPLE_FACTORS - Heart_20 Genotype:Wild-type | Gender:female | Stage:Symptomatic RAW_FILE_NAME=HILIC_POS_Heart_20.mzXML SUBJECT_SAMPLE_FACTORS - Heart_21 Genotype:Wild-type | Gender:Male | Stage:Symptomatic RAW_FILE_NAME=HILIC_POS_Heart_21.mzXML SUBJECT_SAMPLE_FACTORS - Heart_22 Genotype:CHCHD10S59L/+ | Gender:female | Stage:Symptomatic RAW_FILE_NAME=HILIC_POS_Heart_22.mzXML SUBJECT_SAMPLE_FACTORS - Heart_23 Genotype:CHCHD10S59L/+ | Gender:female | Stage:Symptomatic RAW_FILE_NAME=HILIC_POS_Heart_23.mzXML SUBJECT_SAMPLE_FACTORS - Heart_24 Genotype:CHCHD10S59L/+ | Gender:Male | Stage:Symptomatic RAW_FILE_NAME=HILIC_POS_Heart_24.mzXML SUBJECT_SAMPLE_FACTORS - Heart_QC1 Genotype:QC | Gender:QC | Stage:QC RAW_FILE_NAME=HILIC_POS_Heart_QC1.mzXML SUBJECT_SAMPLE_FACTORS - Heart_QC2 Genotype:QC | Gender:QC | Stage:QC RAW_FILE_NAME=HILIC_POS_Heart_QC2.mzXML SUBJECT_SAMPLE_FACTORS - Heart_QC3 Genotype:QC | Gender:QC | Stage:QC RAW_FILE_NAME=HILIC_POS_Heart_QC3.mzXML SUBJECT_SAMPLE_FACTORS - Heart_QC4 Genotype:QC | Gender:QC | Stage:QC RAW_FILE_NAME=HILIC_POS_Heart_QC4.mzXML SUBJECT_SAMPLE_FACTORS - Heart_QC5 Genotype:QC | Gender:QC | Stage:QC RAW_FILE_NAME=HILIC_POS_Heart_QC5.mzXML #COLLECTION CO:COLLECTION_SUMMARY Cardiac tissue samples were immediately flash frozen in liquid nitrogen and CO:COLLECTION_SUMMARY stored at -80 °C until further analyses CO:SAMPLE_TYPE Cardiac tissue CO:STORAGE_CONDITIONS -80℃ #TREATMENT TR:TREATMENT_SUMMARY NA #SAMPLEPREP SP:SAMPLEPREP_SUMMARY Tissues were ground to powder by using liquid nitrogen cooled mortar and pestle. SP:SAMPLEPREP_SUMMARY 11.1 mg of powder tissue were extracted with 1 mL cold acetonitrile/water (1:1, SP:SAMPLEPREP_SUMMARY v/v). The suspension was vortexed, incubated at 4°C for 1 h, centrifuged at 16 SP:SAMPLEPREP_SUMMARY 000 x g for 10 mins at 4°C and then 450 µL of the supernatant was dried. For SP:SAMPLEPREP_SUMMARY plasma metabolites extraction, 20 µL were precipitated with methanol and SP:SAMPLEPREP_SUMMARY centrifuged at 16 000 x g for 10 mins at 4°C, and the supernatant was dried. SP:SAMPLEPREP_SUMMARY All dried metabolites extract from tissues were reconstituted in 100 µL of SP:SAMPLEPREP_SUMMARY either methanol/water (1: 9, v/v) or ACN/water (9: 1, v/v) depending on the SP:SAMPLEPREP_SUMMARY LC-column used and 10 µL was injected into LC-HRMS system 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 C18 (150 x 2.1mm, 2.6 um) CH:SOLVENT_A Water CH:SOLVENT_B ACN CH:FLOW_GRADIENT 20 minutes CH:FLOW_RATE 0.4 mL/min #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 During the full-scan acquisition, which ranged from 58 to 870 m/z, the MS:MS_COMMENTS instrument operated at 70,000 resolution (m/z = 200).A targeted analysis was MS:MS_COMMENTS applied on the samples, based on a library of standard compounds (Mass MS:MS_COMMENTS Spectroscopy Metabolite Library (MSML®) of standards, IROA Technologies™). MS:MS_COMMENTS The following criteria were followed to identify the metabolites: (1) retention MS:MS_COMMENTS time of the detected metabolite within ± 20 s of the standard reference, (2) MS:MS_COMMENTS exact measured of molecular mass of the metabolite within a range of 10 ppm MS:MS_COMMENTS around the known molecular mass of the reference compound, and (3) MS:MS_COMMENTS correspondence between isotopic ratios of the metabolite and the standard MS:MS_COMMENTS reference. The signal value was calculated using Xcalibur® software (Thermo MS:MS_COMMENTS Fisher Scientific, San Jose, CA) by integrating the chromatographic peak area MS:MS_COMMENTS corresponding to the selected metabolite. #MS_METABOLITE_DATA MS_METABOLITE_DATA:UNITS relative units MS_METABOLITE_DATA_START Samples Heart_1 Heart_10 Heart_11 Heart_12 Heart_13 Heart_14 Heart_15 Heart_16 Heart_17 Heart_18 Heart_19 Heart_2 Heart_20 Heart_21 Heart_22 Heart_23 Heart_24 Heart_3 Heart_4 Heart_5 Heart_6 Heart_7 Heart_8 Heart_9 Heart_QC1 Heart_QC2 Heart_QC3 Heart_QC4 Heart_QC5 Factors Genotype:Wild-type | Gender:Male | Stage:Symptomatic Genotype:CHCHD10S59L/+ | Gender:Male | 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:Wild-type | Gender:Male | Stage:Symptomatic Genotype:CHCHD10S59L/+ | Gender:female | Stage:Symptomatic Genotype:CHCHD10S59L/+ | Gender:female | Stage:Symptomatic Genotype:CHCHD10S59L/+ | Gender:Male | Stage:Symptomatic Genotype:Wild-type | Gender:female | Stage:Symptomatic Genotype:Wild-type | Gender:Male | Stage:Symptomatic Genotype:Wild-type | Gender:female | Stage:Symptomatic Genotype:Wild-type | Gender:Male | Stage:Symptomatic Genotype:CHCHD10S59L/+ | Gender:female | Stage:Symptomatic Genotype:CHCHD10S59L/+ | Gender:female | Stage:Symptomatic Genotype:CHCHD10S59L/+ | Gender:Male | Stage:Symptomatic Genotype:Wild-type | Gender:Male | Stage:Symptomatic Genotype:Wild-type | Gender:Male | Stage:Symptomatic Genotype:Wild-type | Gender:Male | Stage:Symptomatic Genotype:Wild-type | Gender:Male | Stage:Symptomatic Genotype:CHCHD10S59L/+ | Gender:Male | Stage:Symptomatic Genotype:CHCHD10S59L/+ | Gender:Male | Stage:Symptomatic Genotype:CHCHD10S59L/+ | Gender:Male | 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 Genotype:QC | Gender:QC | Stage:QC TAURINE 112E+09 190E+07 828E+08 104E+09 119E+09 105E+09 101E+09 957E+08 117E+09 948E+08 808E+08 127E+09 106E+09 101E+09 898E+08 103E+09 102E+09 985E+08 109E+09 110E+09 933E+08 900E+08 113E+09 929E+08 100E+09 102E+09 954E+08 924E+08 888E+08 LACTATE 914E+08 289E+07 722E+08 889E+08 150E+09 873E+08 688E+08 815E+08 121E+09 989E+08 615E+08 132E+09 972E+08 107E+09 581E+08 776E+08 918E+08 947E+08 999E+08 105E+09 941E+08 759E+08 137E+09 564E+08 914E+08 864E+08 829E+08 793E+08 777E+08 INOSINE 736E+07 287E+05 105E+08 272E+08 165E+08 102E+08 800E+07 199E+08 406E+08 156E+08 386E+07 176E+08 131E+08 910E+07 170E+08 304E+08 247E+08 753E+07 585E+07 874E+07 108E+08 168E+08 299E+08 158E+08 228E+08 219E+08 206E+08 179E+08 179E+08 GLUCOSE-6-PHOSPHATE 183E+08 384E+05 110E+08 169E+08 686E+07 126E+08 112E+08 144E+08 705E+07 122E+08 116E+08 942E+07 113E+08 800E+07 110E+08 123E+08 851E+07 558E+07 163E+08 145E+08 109E+08 151E+08 116E+08 137E+08 230E+07 102E+08 119E+08 108E+08 109E+08 ADENOSINE_5-MONOPHOSPHATE 284E+08 152E+05 727E+07 509E+07 263E+08 236E+08 143E+08 653E+07 785E+07 817E+07 146E+08 288E+08 197E+08 205E+08 489E+07 743E+07 758E+07 201E+08 181E+08 235E+08 150E+08 814E+07 108E+08 621E+07 146E+08 142E+08 123E+08 101E+08 105E+08 ISOCITRIC_ACID 772E+07 129E+05 417E+07 542E+07 173E+08 146E+08 158E+08 776E+07 142E+08 779E+07 650E+07 187E+08 154E+08 126E+08 450E+07 163E+08 903E+07 166E+08 926E+07 118E+08 113E+08 453E+07 832E+07 101E+08 866E+07 865E+07 818E+07 791E+07 809E+07 L-GLUTAMIC_ACID 756E+07 199E+06 851E+07 112E+08 115E+08 776E+07 544E+07 880E+07 108E+08 104E+08 720E+07 116E+08 868E+07 778E+07 635E+07 731E+07 908E+07 794E+07 979E+07 970E+07 750E+07 825E+07 104E+08 482E+07 810E+07 830E+07 743E+07 687E+07 673E+07 INOSINE_5-PHOSPHATE 251E+07 325E+05 778E+07 824E+07 254E+08 792E+07 215E+08 906E+07 623E+07 343E+07 297E+07 753E+07 864E+07 162E+08 935E+07 316E+07 677E+07 169E+08 374E+07 639E+07 165E+08 680E+07 481E+07 160E+08 883E+07 911E+07 782E+07 663E+07 660E+07 MALATE 772E+07 131E+06 281E+07 406E+07 650E+07 766E+07 357E+07 352E+07 462E+07 231E+07 457E+07 653E+07 636E+07 654E+07 298E+07 645E+07 240E+07 186E+07 567E+07 619E+07 600E+07 212E+07 419E+07 274E+07 400E+07 415E+07 372E+07 347E+07 353E+07 L-ASPARTATE 226E+07 533E+05 405E+07 426E+07 426E+07 501E+07 163E+07 593E+07 970E+07 593E+07 496E+07 561E+07 329E+07 320E+07 361E+07 704E+07 530E+07 214E+07 373E+07 324E+07 182E+07 484E+07 689E+07 525E+07 432E+07 441E+07 387E+07 354E+07 353E+07 RIBOSE_5-PHOSPHATE 219E+07 126E+05 365E+07 370E+07 295E+07 257E+07 336E+07 272E+07 259E+07 222E+07 160E+07 269E+07 185E+07 308E+07 317E+07 178E+07 211E+07 398E+07 210E+07 221E+07 408E+07 265E+07 435E+07 470E+07 314E+07 304E+07 287E+07 250E+07 254E+07 AZELAIC_ACID 369E+07 801E+06 231E+07 150E+07 335E+07 350E+07 364E+07 192E+07 115E+08 292E+07 210E+07 212E+07 206E+07 104E+07 164E+07 234E+07 272E+07 161E+07 257E+07 286E+07 276E+07 230E+07 267E+07 171E+07 230E+07 238E+07 234E+07 241E+07 241E+07 URIDINE 122E+07 365E+04 133E+07 321E+07 201E+07 175E+07 122E+07 281E+07 655E+07 243E+07 984E+06 261E+07 138E+07 151E+07 211E+07 681E+07 349E+07 130E+07 152E+07 150E+07 143E+07 177E+07 473E+07 220E+07 233E+07 241E+07 213E+07 193E+07 189E+07 3-SULFINO-L-ALANINE 245E+07 109E+05 994E+06 513E+06 341E+07 400E+07 424E+07 105E+07 698E+06 119E+07 321E+07 364E+07 251E+07 256E+07 879E+06 615E+06 772E+06 297E+07 580E+07 871E+07 293E+07 247E+07 759E+06 642E+06 232E+07 217E+07 202E+07 178E+07 179E+07 XANTHINE 139E+07 440E+04 172E+07 109E+07 482E+07 290E+07 201E+07 276E+07 857E+06 194E+07 134E+07 298E+07 228E+07 261E+07 204E+07 134E+04 109E+07 276E+07 175E+07 215E+07 250E+07 255E+07 138E+07 262E+07 199E+07 201E+07 185E+07 162E+07 173E+07 CREATINE 223E+07 338E+05 110E+07 143E+07 237E+07 223E+07 179E+07 137E+07 172E+07 141E+07 122E+07 221E+07 206E+07 233E+07 120E+07 163E+07 135E+07 159E+07 205E+07 187E+07 175E+07 143E+07 183E+07 139E+07 168E+07 169E+07 157E+07 148E+07 152E+07 GLUCOSE 173E+07 739E+05 145E+07 836E+06 184E+07 739E+06 120E+07 119E+07 113E+07 153E+07 154E+07 187E+07 149E+07 186E+07 214E+07 213E+07 134E+07 376E+07 146E+07 284E+07 236E+07 152E+07 112E+07 285E+07 174E+07 177E+07 167E+07 150E+07 151E+07 FUMARATE 307E+07 466E+04 719E+06 962E+06 288E+07 223E+07 943E+06 121E+07 213E+07 145E+07 137E+07 331E+07 282E+07 282E+07 778E+06 217E+07 170E+07 920E+06 216E+07 232E+07 174E+07 137E+07 311E+07 992E+06 167E+07 165E+07 151E+07 141E+07 143E+07 URIDINE-5-PHOSPHATE 281E+07 359E+04 196E+07 168E+07 237E+07 127E+07 116E+07 244E+07 313E+07 241E+07 130E+07 329E+07 153E+07 184E+07 203E+07 268E+07 256E+07 171E+07 154E+07 216E+07 136E+07 230E+07 280E+07 406E+07 188E+07 191E+07 166E+07 140E+07 143E+07 PANTOTHENIC_ACID 126E+07 410E+04 382E+06 711E+06 403E+07 357E+07 162E+07 144E+07 197E+07 787E+06 178E+07 189E+07 334E+07 125E+07 181E+07 354E+07 112E+07 113E+07 132E+07 149E+07 116E+07 573E+06 104E+07 121E+07 147E+07 145E+07 139E+07 131E+07 131E+07 GUANOSINE_5-PHOSPHATE 188E+07 432E+04 142E+07 102E+07 263E+07 156E+07 150E+07 146E+07 148E+07 162E+07 924E+06 239E+07 154E+07 189E+07 143E+07 130E+07 131E+07 275E+07 101E+07 175E+07 176E+07 203E+07 178E+07 281E+07 149E+07 153E+07 135E+07 111E+07 112E+07 5-OXO-L-PROLINE 121E+07 114E+06 824E+06 107E+07 192E+07 960E+06 755E+06 110E+07 175E+07 125E+07 740E+06 142E+07 835E+06 108E+07 704E+06 136E+07 144E+07 926E+06 935E+06 107E+07 770E+06 896E+06 142E+07 112E+07 122E+07 122E+07 113E+07 104E+07 107E+07 SUCCINATE 257E+07 214E+05 101E+07 442E+06 143E+07 883E+06 736E+06 103E+07 791E+06 228E+07 112E+07 222E+07 121E+07 108E+07 601E+06 410E+06 190E+07 129E+07 165E+07 177E+07 875E+06 204E+07 223E+07 278E+07 124E+07 126E+07 113E+07 101E+07 106E+07 SUBERIC_ACID 857E+06 338E+06 575E+06 481E+06 945E+06 633E+06 560E+06 570E+06 174E+07 615E+06 548E+06 438E+06 471E+06 354E+06 508E+06 465E+06 659E+06 558E+06 849E+06 641E+06 577E+06 476E+06 515E+06 471E+06 637E+06 724E+06 650E+06 693E+06 646E+06 GLUCONIC_ACID 456E+06 157E+05 711E+06 851E+06 860E+06 426E+06 303E+06 839E+06 158E+07 113E+07 419E+06 779E+06 457E+06 465E+06 740E+06 922E+06 112E+07 565E+06 395E+06 625E+06 440E+06 805E+06 145E+07 935E+06 639E+06 690E+06 627E+06 593E+06 560E+06 N-ACETYL-ASPARTIC_ACID 383E+06 401E+05 236E+06 235E+06 981E+06 565E+06 291E+06 408E+06 109E+07 366E+06 112E+07 167E+07 803E+06 796E+06 372E+06 487E+06 491E+06 649E+06 108E+07 140E+07 696E+06 238E+06 380E+06 369E+06 583E+06 619E+06 565E+06 503E+06 503E+06 2-HYDROXYBUTYRIC_ACID 286E+06 000E+00 308E+06 385E+06 492E+06 223E+06 206E+06 278E+06 462E+06 384E+06 143E+06 418E+06 295E+06 290E+06 236E+06 287E+07 335E+06 302E+06 204E+06 272E+06 260E+06 629E+06 573E+06 268E+07 478E+06 486E+06 456E+06 422E+06 432E+06 L-SERINE 183E+06 365E+05 636E+06 671E+06 204E+06 227E+06 151E+06 634E+06 753E+06 750E+06 172E+06 238E+06 155E+06 292E+06 477E+06 442E+06 511E+06 274E+06 201E+06 161E+06 169E+06 395E+06 517E+06 367E+06 416E+06 414E+06 383E+06 353E+06 359E+06 N-Acetyl-4-O-acetylneuraminic_acid 370E+06 000E+00 278E+06 489E+06 550E+06 407E+06 262E+06 381E+06 696E+06 438E+06 253E+06 550E+06 402E+06 381E+06 341E+06 506E+06 507E+06 313E+06 427E+06 455E+06 364E+06 341E+06 670E+06 518E+06 428E+06 419E+06 401E+06 338E+06 339E+06 HOMOSERINE 155E+06 108E+05 479E+06 381E+06 217E+06 133E+06 109E+06 458E+06 633E+06 442E+06 117E+06 270E+06 123E+06 153E+06 500E+06 444E+06 511E+06 260E+06 158E+06 155E+06 127E+06 291E+06 367E+06 342E+06 282E+06 278E+06 263E+06 258E+06 246E+06 ETHANOLAMINE_PHOSPHATE 219E+06 381E+04 331E+06 211E+06 215E+06 216E+06 204E+06 368E+06 243E+06 214E+06 318E+06 524E+06 217E+06 235E+06 258E+06 229E+06 475E+06 222E+06 179E+06 207E+06 253E+06 232E+06 193E+06 529E+06 280E+06 275E+06 254E+06 244E+06 240E+06 ALLANTOIN 232E+06 239E+04 342E+06 292E+06 309E+06 248E+06 198E+06 247E+06 263E+06 297E+06 190E+06 321E+06 181E+06 202E+06 282E+06 308E+06 269E+06 317E+06 203E+06 219E+06 202E+06 307E+06 341E+06 333E+06 270E+06 275E+06 245E+06 221E+06 220E+06 L-HISTIDINE 277E+06 303E+04 189E+06 266E+06 335E+06 217E+06 128E+06 242E+06 407E+06 277E+06 978E+05 341E+06 244E+06 300E+06 222E+06 405E+06 276E+06 214E+06 192E+06 162E+06 196E+06 160E+06 327E+06 225E+06 239E+06 255E+06 238E+06 209E+06 216E+06 L-PHENYLALANINE 196E+06 147E+04 300E+06 347E+06 349E+06 136E+06 776E+05 293E+06 530E+06 270E+06 842E+05 361E+06 116E+06 194E+06 407E+06 435E+06 354E+06 292E+06 152E+06 198E+06 143E+06 262E+06 384E+06 417E+06 343E+06 341E+06 254E+06 166E+06 164E+06 L-TYROSINE 192E+06 223E+04 364E+06 367E+06 367E+06 118E+06 883E+05 259E+06 363E+06 271E+06 797E+05 357E+06 839E+05 197E+06 218E+06 192E+06 298E+06 278E+06 166E+06 145E+06 117E+06 199E+06 354E+06 216E+06 283E+06 279E+06 210E+06 170E+06 163E+06 3-METHYGLUTARIC_ACID 175E+06 641E+05 135E+06 848E+05 222E+06 104E+06 789E+05 108E+06 150E+06 121E+06 912E+05 770E+05 640E+05 756E+05 100E+06 828E+05 741E+05 131E+06 153E+06 919E+05 926E+05 936E+05 846E+05 838E+05 170E+06 187E+06 165E+06 157E+06 161E+06 L-ASPARAGINE 778E+05 313E+04 298E+06 276E+06 800E+05 106E+06 738E+05 260E+06 238E+06 261E+06 659E+05 102E+06 741E+05 145E+06 167E+06 199E+06 189E+06 926E+05 965E+05 858E+05 733E+05 203E+06 216E+06 203E+06 169E+06 168E+06 159E+06 142E+06 153E+06 3-UREIDOPROPIONATE 778E+05 313E+04 298E+06 276E+06 800E+05 106E+06 738E+05 260E+06 238E+06 261E+06 659E+05 102E+06 741E+05 145E+06 167E+06 199E+06 189E+06 926E+05 965E+05 858E+05 733E+05 203E+06 216E+06 203E+06 169E+06 168E+06 159E+06 142E+06 153E+06 L-ARGININE 181E+06 105E+03 132E+06 103E+06 240E+06 143E+06 119E+06 180E+06 169E+06 228E+06 116E+06 236E+06 168E+06 217E+06 159E+06 129E+06 982E+05 328E+06 136E+06 157E+06 239E+06 161E+06 220E+06 140E+06 171E+06 181E+06 164E+06 139E+06 151E+06 HIPPURATE 123E+06 000E+00 374E+06 215E+06 382E+06 178E+06 677E+05 352E+06 277E+06 263E+06 180E+06 144E+06 201E+06 480E+05 523E+06 555E+05 369E+06 287E+06 610E+05 162E+06 551E+05 396E+05 868E+05 398E+05 166E+06 165E+06 165E+06 153E+06 150E+06 (2-AMINOETHYL)PHOSPHONATE 521E+05 649E+03 000E+00 855E+05 423E+05 911E+05 128E+06 631E+05 314E+05 657E+04 198E+05 990E+05 916E+05 239E+05 928E+05 636E+05 148E+06 123E+06 100E+06 138E+06 108E+06 942E+05 154E+06 951E+05 908E+05 644E+05 366E+05 240E+05 144E+06 PHOSPHOCREATINE 136E+06 000E+00 339E+06 333E+06 144E+06 711E+05 898E+05 354E+06 310E+06 393E+06 124E+06 230E+06 123E+06 151E+06 320E+06 412E+06 616E+06 131E+06 182E+06 164E+06 885E+05 462E+06 465E+06 315E+06 173E+06 183E+06 160E+06 138E+06 137E+06 LINOLEATE 898E+05 173E+04 693E+05 117E+06 342E+06 281E+06 220E+06 755E+05 104E+06 828E+05 158E+06 233E+06 143E+06 185E+06 709E+05 208E+06 128E+06 245E+06 377E+06 228E+06 266E+06 144E+06 117E+06 161E+06 112E+06 112E+06 118E+06 124E+06 121E+06 PALMITATE 767E+05 999E+04 742E+05 113E+06 182E+06 240E+06 167E+06 756E+05 803E+05 691E+05 258E+06 168E+06 115E+06 121E+06 659E+05 202E+06 110E+06 153E+06 326E+06 240E+06 157E+06 102E+06 814E+05 945E+05 998E+05 101E+06 116E+06 110E+06 109E+06 GLYCERATE 827E+05 111E+05 126E+06 895E+05 154E+06 121E+06 926E+05 115E+06 153E+06 159E+06 820E+05 143E+06 114E+06 111E+06 131E+06 105E+06 943E+05 137E+06 122E+06 116E+06 243E+06 999E+05 981E+05 992E+05 118E+06 124E+06 117E+06 102E+06 105E+06 L-TRYPTOPHAN 932E+05 000E+00 139E+06 232E+06 364E+06 121E+06 241E+05 116E+06 293E+06 160E+06 579E+05 137E+06 725E+05 139E+06 111E+06 173E+06 168E+06 266E+06 885E+05 788E+05 807E+05 158E+06 319E+06 150E+06 150E+06 149E+06 124E+06 979E+05 964E+05 4-METHYL-2-OXO-VALERIC_ACID 398E+05 458E+04 270E+06 737E+05 202E+06 318E+05 735E+04 143E+06 183E+06 117E+06 115E+05 105E+06 427E+05 570E+05 133E+06 163E+06 221E+06 164E+06 191E+04 119E+05 252E+05 105E+06 642E+05 978E+05 702E+05 625E+05 590E+05 522E+05 719E+05 TRANS-ACONITATE 435E+05 589E+02 340E+05 927E+05 112E+06 164E+06 143E+06 793E+05 133E+06 781E+05 426E+05 201E+06 108E+06 884E+05 328E+05 218E+06 660E+05 182E+06 107E+06 990E+05 117E+06 457E+05 658E+05 698E+05 860E+05 862E+05 791E+05 706E+05 700E+05 CITRULLINE 755E+05 132E+04 973E+05 748E+05 103E+06 840E+05 640E+05 923E+05 947E+05 102E+06 567E+05 971E+05 689E+05 951E+05 106E+06 553E+05 751E+05 912E+05 628E+05 698E+05 755E+05 423E+05 787E+05 407E+05 783E+05 799E+05 701E+05 722E+05 664E+05 4-METHYL-2-OXO-PENTANOIC_ACID 429E+05 668E+04 173E+06 641E+05 147E+06 512E+05 155E+05 127E+06 133E+06 132E+06 617E+04 103E+06 504E+05 513E+05 125E+06 106E+06 162E+06 181E+06 179E+04 777E+04 173E+05 106E+06 521E+05 672E+05 770E+05 676E+05 672E+05 573E+05 617E+05 10-HYDROXYDECANOATE 463E+05 230E+05 546E+05 579E+05 755E+05 613E+05 474E+05 680E+05 782E+05 560E+05 596E+05 505E+05 553E+05 536E+05 512E+05 752E+05 576E+05 597E+05 732E+05 481E+05 438E+05 362E+05 495E+05 441E+05 479E+05 445E+05 522E+05 610E+05 602E+05 FERULATE 849E+05 427E+05 774E+05 555E+05 630E+05 172E+06 165E+05 118E+06 625E+05 354E+05 786E+05 476E+05 139E+06 309E+05 461E+05 385E+05 683E+05 388E+05 210E+05 290E+05 448E+05 233E+06 661E+05 875E+05 523E+05 565E+05 552E+05 592E+05 573E+05 L-METHIONINE 410E+05 000E+00 115E+06 145E+06 707E+05 349E+05 791E+04 119E+06 220E+06 110E+06 798E+04 909E+05 305E+05 396E+05 811E+05 116E+06 127E+06 527E+05 139E+04 111E+04 127E+05 471E+05 118E+06 676E+05 742E+05 704E+05 635E+05 546E+05 541E+05 CREATININE 739E+05 000E+00 399E+05 579E+05 839E+05 767E+05 673E+05 475E+05 627E+05 482E+05 423E+05 749E+05 749E+05 782E+05 390E+05 498E+05 451E+05 519E+05 761E+05 646E+05 591E+05 517E+05 641E+05 468E+05 610E+05 617E+05 632E+05 526E+05 537E+05 CITRAMALATE 605E+05 000E+00 229E+05 245E+05 107E+06 501E+05 518E+05 247E+05 619E+05 385E+05 632E+05 681E+05 481E+05 743E+05 260E+05 650E+05 644E+05 618E+05 131E+06 192E+06 573E+05 910E+05 593E+05 512E+05 622E+05 620E+05 575E+05 544E+05 525E+05 STEARATE 177E+05 463E+04 416E+05 122E+06 476E+05 832E+05 488E+05 493E+05 538E+05 361E+05 716E+05 471E+05 653E+05 634E+05 521E+05 114E+06 103E+06 373E+05 625E+05 447E+05 461E+05 539E+05 606E+05 307E+05 433E+05 428E+05 489E+05 514E+05 525E+05 MANNITOL 469E+05 411E+04 574E+05 521E+05 825E+05 441E+05 377E+05 460E+05 491E+05 550E+05 517E+05 485E+05 530E+05 498E+05 837E+05 516E+05 494E+05 506E+05 562E+05 647E+05 862E+05 512E+05 474E+05 638E+05 609E+05 630E+05 606E+05 529E+05 495E+05 THYMIDINE 317E+05 000E+00 352E+05 640E+05 905E+05 462E+05 342E+05 685E+05 113E+06 412E+05 362E+05 111E+06 495E+05 675E+05 428E+05 954E+05 106E+06 455E+05 370E+05 328E+05 412E+05 653E+05 786E+05 704E+05 525E+05 547E+05 495E+05 479E+05 488E+05 CARNOSINE 153E+05 249E+04 555E+05 143E+06 199E+05 124E+05 734E+04 767E+05 157E+06 831E+05 112E+04 156E+05 344E+04 133E+05 846E+05 105E+06 923E+05 307E+04 113E+05 111E+05 118E+05 505E+05 154E+06 883E+05 519E+05 574E+05 481E+05 420E+05 460E+05 L-ARABITOL 253E+05 375E+03 300E+05 363E+05 188E+05 188E+05 123E+05 209E+05 400E+05 284E+05 373E+05 227E+05 290E+05 196E+05 189E+06 473E+05 516E+05 265E+05 175E+05 196E+05 279E+05 424E+05 472E+05 440E+05 354E+05 410E+05 366E+05 298E+05 325E+05 N6-(DELTA2-ISOPENTENYL)-ADENINE 239E+05 128E+03 418E+05 499E+05 553E+05 234E+05 132E+05 406E+05 681E+05 542E+05 199E+05 368E+05 168E+05 176E+05 285E+05 248E+05 611E+05 228E+05 202E+05 298E+05 177E+05 352E+05 498E+05 156E+05 295E+05 280E+05 306E+05 301E+05 307E+05 HYDROXYDODECANOIC_ACID 257E+05 216E+05 244E+05 277E+05 293E+05 333E+05 332E+05 289E+05 306E+05 262E+05 289E+05 273E+05 309E+05 296E+05 286E+05 288E+05 259E+05 271E+05 249E+05 303E+05 252E+05 213E+05 253E+05 264E+05 252E+05 257E+05 272E+05 313E+05 277E+05 URACIL 166E+05 000E+00 182E+05 434E+05 294E+05 236E+05 158E+05 400E+05 892E+05 351E+05 121E+05 352E+05 185E+05 212E+05 285E+05 910E+05 495E+05 194E+05 209E+05 207E+05 194E+05 282E+05 661E+05 330E+05 324E+05 330E+05 273E+05 271E+05 265E+05 MALONATE 338E+05 106E+04 211E+05 147E+05 372E+05 506E+05 381E+05 230E+05 336E+05 201E+05 392E+05 409E+05 367E+05 204E+05 144E+05 260E+05 207E+05 257E+05 514E+05 534E+05 208E+05 221E+05 123E+05 101E+05 275E+05 298E+05 238E+05 237E+05 239E+05 3-(4-HYDROXYPHENYL)LACTATE 216E+05 448E+04 991E+04 815E+04 252E+05 268E+05 213E+05 109E+05 342E+05 127E+05 127E+05 109E+05 117E+05 684E+04 709E+04 857E+04 134E+05 105E+05 455E+05 278E+05 221E+05 105E+05 103E+05 768E+04 168E+05 176E+05 168E+05 174E+05 165E+05 L-CYSTEIC_ACID 160E+05 110E+03 190E+05 902E+04 136E+05 461E+05 388E+05 203E+05 413E+04 217E+05 562E+05 314E+05 744E+04 448E+04 130E+05 000E+00 665E+04 331E+05 490E+05 708E+05 346E+05 339E+05 326E+05 209E+04 176E+05 206E+05 229E+05 190E+05 160E+05 FORMYL-METHIONYL_PEPTIDE 917E+04 000E+00 113E+05 178E+05 138E+05 916E+04 220E+04 174E+05 282E+05 182E+05 147E+04 160E+05 917E+04 122E+05 151E+05 288E+05 206E+05 137E+05 000E+00 000E+00 309E+04 109E+05 242E+05 170E+05 107E+05 116E+05 114E+05 107E+05 107E+05 ETHYLMALONIC_ACID 184E+05 187E+04 706E+04 717E+04 244E+05 162E+05 105E+05 787E+04 147E+05 862E+04 981E+04 237E+05 213E+05 169E+05 780E+04 145E+05 958E+04 110E+05 165E+05 142E+05 146E+05 807E+04 103E+05 100E+05 135E+05 127E+05 124E+05 101E+05 106E+05 N-ACETYL-TRYPTOPHAN 728E+04 113E+03 174E+05 139E+05 251E+05 954E+04 298E+04 124E+05 157E+05 155E+05 781E+04 968E+04 505E+04 185E+05 282E+05 139E+05 202E+05 235E+05 543E+04 638E+04 782E+04 135E+05 216E+05 133E+05 109E+05 107E+05 104E+05 917E+04 103E+05 L-LYSINE 161E+05 000E+00 194E+05 147E+05 235E+05 121E+05 876E+04 148E+05 204E+05 152E+05 712E+04 259E+05 131E+05 137E+05 949E+04 112E+05 105E+05 223E+05 110E+05 154E+05 146E+05 123E+05 239E+05 133E+05 210E+05 185E+05 153E+05 893E+04 101E+05 MS_METABOLITE_DATA_END #METABOLITES METABOLITES_START metabolite_name RT(min) TAURINE 0.78947596 LACTATE 1.2206197 INOSINE 3.0749393 GLUCOSE-6-PHOSPHATE 0.93935298 ADENOSINE_5-MONOPHOSPHATE 1.38692 ISOCITRIC_ACID 1.4136616 L-GLUTAMIC_ACID 0.81176115 INOSINE_5-PHOSPHATE 1.9615971 MALATE 1.021076 L-ASPARTATE 0.79393215 RIBOSE_5-PHOSPHATE 0.9616383 AZELAIC_ACID 9.7352481 URIDINE 1.8655597 3-SULFINO-L-ALANINE 1.1252614 XANTHINE 1.631445 CREATINE 0.8295885 GLUCOSE 0.7805614 FUMARATE 1.5847095 URIDINE-5-PHOSPHATE 1.5044822 PANTOTHENIC_ACID 5.6229924 GUANOSINE_5-PHOSPHATE 1.6893868 5-OXO-L-PROLINE 1.6047035 SUCCINATE 1.6492721 SUBERIC_ACID 8.9013871 GLUCONIC_ACID 0.84295935 N-ACETYL-ASPARTIC_ACID 1.3142176 2-HYDROXYBUTYRIC_ACID 2.2589307 L-SERINE 0.76273223 N-Acetyl-4-O-acetylneuraminic_acid 0.95272398 HOMOSERINE 0.80284683 ETHANOLAMINE_PHOSPHATE 0.77164655 ALLANTOIN 0.84741768 L-HISTIDINE 0.74044886 L-PHENYLALANINE 3.4737582 L-TYROSINE 1.5000242 3-METHYGLUTARIC_ACID 5.6967297 L-ASPARAGINE 0.76273223 3-UREIDOPROPIONATE 0.76273223 L-ARGININE 0.74044886 HIPPURATE 7.0086324 (2-AMINOETHYL)PHOSPHONATE 0.82067393 PHOSPHOCREATINE 0.9112802 LINOLEATE 14.171243 PALMITATE 14.419606 GLYCERATE 0.90682162 L-TRYPTOPHAN 5.3660421 4-METHYL-2-OXO-VALERIC_ACID 8.6275518 TRANS-ACONITATE NF CITRULLINE 0.84741768 4-METHYL-2-OXO-PENTANOIC_ACID 8.5096411 10-HYDROXYDECANOATE 11.503684 FERULATE 9.6309291 L-METHIONINE 1.1564615 CREATININE 0.8295885 CITRAMALATE 1.8231742 STEARATE 15.036166 MANNITOL 0.83850283 THYMIDINE 5.1265026 CARNOSINE 0.74490486 L-ARABITOL 0.83850283 N6-(DELTA2-ISOPENTENYL)-ADENINE 8.9816141 HYDROXYDODECANOIC_ACID 11.548253 URACIL 1.8655597 MALONATE 1.1653759 3-(4-HYDROXYPHENYL)LACTATE 7.5232659 L-CYSTEIC_ACID 0.86225091 FORMYL-METHIONYL_PEPTIDE 5.6229924 ETHYLMALONIC_ACID 4.0875729 N-ACETYL-TRYPTOPHAN 8.8147477 L-LYSINE 0.7003343 METABOLITES_END #END