#METABOLOMICS WORKBENCH amuir_20190103_160816 DATATRACK_ID:1594 STUDY_ID:ST001119 ANALYSIS_ID:AN001830 PROJECT_ID:PR000750 VERSION 1 CREATED_ON January 14, 2019, 11:14 am #PROJECT PR:PROJECT_TITLE Quantification of microenvironmental metabolites in murine cancers reveals PR:PROJECT_TITLE determinants of tumor nutrient availability PR:PROJECT_SUMMARY Cancer cell metabolism is heavily influenced by microenvironmental factors, PR:PROJECT_SUMMARY including nutrient availability. Therefore, knowledge of microenvironmental PR:PROJECT_SUMMARY nutrient levels is essential to understand tumor metabolism. To measure the PR:PROJECT_SUMMARY extracellular nutrient levels available to tumors, we developed a quantitative PR:PROJECT_SUMMARY metabolomics method to measure the absolute concentrations of >118 metabolites PR:PROJECT_SUMMARY in plasma and tumor interstitial fluid, the extracellular fluid that perfuses PR:PROJECT_SUMMARY tumors. Comparison of nutrient levels in tumor interstitial fluid and plasma PR:PROJECT_SUMMARY revealed that the nutrients available to tumors differ from those present in PR:PROJECT_SUMMARY circulation. Further, by comparing interstitial fluid nutrient levels between PR:PROJECT_SUMMARY autochthonous and transplant models of murine pancreatic and lung PR:PROJECT_SUMMARY adenocarcinoma, we found that tumor type, anatomical location and animal diet PR:PROJECT_SUMMARY affect local nutrient availability. These data provide a comprehensive PR:PROJECT_SUMMARY characterization of the nutrients present in the tumor microenvironment of PR:PROJECT_SUMMARY widely used models of lung and pancreatic cancer and identify factors that PR:PROJECT_SUMMARY influence metabolite levels in tumors. PR:INSTITUTE University of Chicago PR:LAST_NAME Muir PR:FIRST_NAME Alexander PR:ADDRESS 929 E 57th St. GCIS W 306, Chicago, Illinois, 60637, USA PR:EMAIL muir.alexander@gmail.com PR:PHONE 5104950975 #STUDY ST:STUDY_TITLE Quantification of microenvironmental metabolites in murine cancers reveals ST:STUDY_TITLE determinants of tumor nutrient availability ST:STUDY_SUMMARY Cancer cell metabolism is heavily influenced by microenvironmental factors, ST:STUDY_SUMMARY including nutrient availability. Therefore, knowledge of microenvironmental ST:STUDY_SUMMARY nutrient levels is essential to understand tumor metabolism. To measure the ST:STUDY_SUMMARY extracellular nutrient levels available to tumors, we developed a quantitative ST:STUDY_SUMMARY metabolomics method to measure the absolute concentrations of >118 metabolites ST:STUDY_SUMMARY in plasma and tumor interstitial fluid, the extracellular fluid that perfuses ST:STUDY_SUMMARY tumors. Comparison of nutrient levels in tumor interstitial fluid and plasma ST:STUDY_SUMMARY revealed that the nutrients available to tumors differ from those present in ST:STUDY_SUMMARY circulation. Further, by comparing interstitial fluid nutrient levels between ST:STUDY_SUMMARY autochthonous and transplant models of murine pancreatic and lung ST:STUDY_SUMMARY adenocarcinoma, we found that tumor type, anatomical location and animal diet ST:STUDY_SUMMARY affect local nutrient availability. These data provide a comprehensive ST:STUDY_SUMMARY characterization of the nutrients present in the tumor microenvironment of ST:STUDY_SUMMARY widely used models of lung and pancreatic cancer and identify factors that ST:STUDY_SUMMARY influence metabolite levels in tumors. ST:INSTITUTE University of Chicago ST:LAST_NAME Muir ST:FIRST_NAME Alexander ST:ADDRESS 929 E 57th St. W GCIS 306, Chicago, Illinois, 60637, USA ST:EMAIL muir.alexander@gmail.com ST:PHONE 5104950975 #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]Additional sample data SUBJECT_SAMPLE_FACTORS - 1234 KP 1 TIF Sample Type:lung_subcutaneous Run number=2 SUBJECT_SAMPLE_FACTORS - 1234 KP 2 TIF Sample Type:lung_subcutaneous Run number=2 SUBJECT_SAMPLE_FACTORS - 1234 KP 3 TIF Sample Type:lung_subcutaneous Run number=2 SUBJECT_SAMPLE_FACTORS - 1234 KP 4 TIF Sample Type:lung_subcutaneous Run number=2 SUBJECT_SAMPLE_FACTORS - 1234 KP 5 TIF Sample Type:lung_subcutaneous Run number=2 SUBJECT_SAMPLE_FACTORS - 1234 KP 6 TIF Sample Type:lung_subcutaneous Run number=2 SUBJECT_SAMPLE_FACTORS - 1234 KPK 1 TIF Sample Type:Keap1_mutant_lung_subcutaneous Run number=2 SUBJECT_SAMPLE_FACTORS - 1234 KPK 3 TIF Sample Type:Keap1_mutant_lung_subcutaneous Run number=2 SUBJECT_SAMPLE_FACTORS - 1234 KPK 4 TIF Sample Type:Keap1_mutant_lung_subcutaneous Run number=2 SUBJECT_SAMPLE_FACTORS - 1234 KPK 5 TIF Sample Type:Keap1_mutant_lung_subcutaneous Run number=2 SUBJECT_SAMPLE_FACTORS - 1234 KPK 6 TIF Sample Type:Keap1_mutant_lung_subcutaneous Run number=2 SUBJECT_SAMPLE_FACTORS - 1233 KP 3 TIF Sample Type:lung_subcutaneous Run number=2 SUBJECT_SAMPLE_FACTORS - 1233 KP 4 TIF Sample Type:lung_subcutaneous Run number=2 SUBJECT_SAMPLE_FACTORS - 1233 KP 5 TIF Sample Type:lung_subcutaneous Run number=2 SUBJECT_SAMPLE_FACTORS - 1233 KP 6 TIF Sample Type:lung_subcutaneous Run number=2 SUBJECT_SAMPLE_FACTORS - 1233 KPK 1 TIF Sample Type:Keap1_mutant_lung_subcutaneous Run number=2 SUBJECT_SAMPLE_FACTORS - 1233 KPK 5 TIF Sample Type:Keap1_mutant_lung_subcutaneous Run number=2 SUBJECT_SAMPLE_FACTORS - 1233 KPK 6 TIF Sample Type:Keap1_mutant_lung_subcutaneous Run number=2 SUBJECT_SAMPLE_FACTORS - 1339 TIF Sample Type:pancreatic ductal adenocarcinoma Run number=2 SUBJECT_SAMPLE_FACTORS - 5197 TIF Sample Type:pancreatic ductal adenocarcinoma Run number=2 SUBJECT_SAMPLE_FACTORS - AL1 TIF Sample Type:pancreatic ductal adenocarcinoma Run number=2 SUBJECT_SAMPLE_FACTORS - 268 TIF Sample Type:pancreatic ductal adenocarcinoma Run number=2 SUBJECT_SAMPLE_FACTORS - 142 TIF Sample Type:pancreatic ductal adenocarcinoma Run number=2 SUBJECT_SAMPLE_FACTORS - 172 TIF Sample Type:pancreatic ductal adenocarcinoma Run number=2 SUBJECT_SAMPLE_FACTORS - TBt0 plasma 705 Sample Type:pancreatic ductal adenocarcinoma plasma Run number=2 SUBJECT_SAMPLE_FACTORS - TBt0 plasma 708 Sample Type:pancreatic ductal adenocarcinoma plasma Run number=2 SUBJECT_SAMPLE_FACTORS - TBt0 plasma 707 Sample Type:pancreatic ductal adenocarcinoma plasma Run number=2 SUBJECT_SAMPLE_FACTORS - TBt0 plasma 712 Sample Type:pancreatic ductal adenocarcinoma plasma Run number=2 SUBJECT_SAMPLE_FACTORS - TBt0 plasma 711 Sample Type:pancreatic ductal adenocarcinoma plasma Run number=2 SUBJECT_SAMPLE_FACTORS - TBt0 plasma 710 Sample Type:pancreatic ductal adenocarcinoma plasma Run number=2 SUBJECT_SAMPLE_FACTORS - 922 TIF Sample Type:pancreatic ductal adenocarcinoma Run number=1 SUBJECT_SAMPLE_FACTORS - 58 TIF Sample Type:pancreatic ductal adenocarcinoma Run number=1 SUBJECT_SAMPLE_FACTORS - 5197 TIF repeat Sample Type:pancreatic ductal adenocarcinoma Run number=1 SUBJECT_SAMPLE_FACTORS - 172 TIF repeat Sample Type:pancreatic ductal adenocarcinoma Run number=1 SUBJECT_SAMPLE_FACTORS - 142 TIF repeat Sample Type:pancreatic ductal adenocarcinoma Run number=1 SUBJECT_SAMPLE_FACTORS - 1339 TIF repeat Sample Type:pancreatic ductal adenocarcinoma Run number=1 SUBJECT_SAMPLE_FACTORS - 268 TIF repeat Sample Type:pancreatic ductal adenocarcinoma Run number=1 SUBJECT_SAMPLE_FACTORS - AL1 TIF repeat Sample Type:pancreatic ductal adenocarcinoma Run number=1 SUBJECT_SAMPLE_FACTORS - X1 TIF Sample Type:pancreatic ductal adenocarcinoma subcutaneous Run number=1 SUBJECT_SAMPLE_FACTORS - X2 TIF Sample Type:pancreatic ductal adenocarcinoma subcutaneous Run number=1 SUBJECT_SAMPLE_FACTORS - X3 TIF Sample Type:pancreatic ductal adenocarcinoma subcutaneous Run number=1 SUBJECT_SAMPLE_FACTORS - X4 TIF Sample Type:pancreatic ductal adenocarcinoma subcutaneous Run number=1 SUBJECT_SAMPLE_FACTORS - X5 TIF Sample Type:pancreatic ductal adenocarcinoma subcutaneous Run number=1 SUBJECT_SAMPLE_FACTORS - 922_Plasma Sample Type:pancreatic ductal adenocarcinoma plasma cardiac puncture Run number=1 SUBJECT_SAMPLE_FACTORS - 58_Plasma Sample Type:pancreatic ductal adenocarcinoma plasma cardiac puncture Run number=1 SUBJECT_SAMPLE_FACTORS - 5197_Plasma Sample Type:pancreatic ductal adenocarcinoma plasma cardiac puncture Run number=1 SUBJECT_SAMPLE_FACTORS - 172_Plasma Sample Type:pancreatic ductal adenocarcinoma plasma cardiac puncture Run number=1 SUBJECT_SAMPLE_FACTORS - 142_Plasma Sample Type:pancreatic ductal adenocarcinoma plasma cardiac puncture Run number=1 SUBJECT_SAMPLE_FACTORS - 268_Plasma Sample Type:pancreatic ductal adenocarcinoma plasma cardiac puncture Run number=1 SUBJECT_SAMPLE_FACTORS - AL1_Plasma Sample Type:pancreatic ductal adenocarcinoma plasma cardiac puncture Run number=1 SUBJECT_SAMPLE_FACTORS - X2_Plasma Sample Type:pancreatic ductal adenocarcinoma plasma cardiac puncture Run number=1 SUBJECT_SAMPLE_FACTORS - X3_Plasma Sample Type:pancreatic ductal adenocarcinoma plasma cardiac puncture Run number=1 SUBJECT_SAMPLE_FACTORS - X4_Plasma Sample Type:pancreatic ductal adenocarcinoma plasma cardiac puncture Run number=1 SUBJECT_SAMPLE_FACTORS - 3731_Plasma Sample Type:pancreatic ductal adenocarcinoma plasma cardiac puncture Run number=1 SUBJECT_SAMPLE_FACTORS - 4198_Plasma Sample Type:pancreatic ductal adenocarcinoma plasma cardiac puncture Run number=1 SUBJECT_SAMPLE_FACTORS - 4300_Plasma Sample Type:pancreatic ductal adenocarcinoma plasma cardiac puncture Run number=1 SUBJECT_SAMPLE_FACTORS - A0_Plasma Sample Type:pancreatic ductal adenocarcinoma plasma cardiac puncture Run number=1 SUBJECT_SAMPLE_FACTORS - A1_Plasma Sample Type:pancreatic ductal adenocarcinoma plasma cardiac puncture Run number=1 SUBJECT_SAMPLE_FACTORS - B0_Plasma Sample Type:pancreatic ductal adenocarcinoma plasma cardiac puncture Run number=1 SUBJECT_SAMPLE_FACTORS - B1_Plasma Sample Type:pancreatic ductal adenocarcinoma plasma cardiac puncture Run number=1 SUBJECT_SAMPLE_FACTORS - B2_Plasma Sample Type:pancreatic ductal adenocarcinoma plasma cardiac puncture Run number=1 #COLLECTION CO:COLLECTION_SUMMARY Isolation of tumor interstitial fluid (TIF) TIF was isolated from tumors using a CO:COLLECTION_SUMMARY previously described centrifugal method (Eil et al., 2016; Haslene-Hox et al., CO:COLLECTION_SUMMARY 2011; Ho et al., 2015; Wiig et al., 2003). Briefly, tumor bearing animals were CO:COLLECTION_SUMMARY euthanized by cervical dislocation and tumors were rapidly dissected from the CO:COLLECTION_SUMMARY animals. Dissections took <1 min. to complete. Blood was collected from the same CO:COLLECTION_SUMMARY animal via cardiac puncture, and was immediately placed in EDTA-tubes (Sarstedt, CO:COLLECTION_SUMMARY North Rhine-Westphalia, Germany) and centrifuged at 845 x g for 10 minutes at CO:COLLECTION_SUMMARY 4°C to separate plasma. Plasma was frozen in liquid nitrogen and stored at CO:COLLECTION_SUMMARY -80°C until further analysis. Tumors were then weighed and briefly rinsed in CO:COLLECTION_SUMMARY room temperature saline (150mM NaCl) and blotted on filter paper (VWR, Radnor, CO:COLLECTION_SUMMARY PA, 28298-020). The entire process of preparing the tumor prior to isolation of CO:COLLECTION_SUMMARY TIF took ~2 min. The tumors were then put onto 20µm nylon filters (Spectrum CO:COLLECTION_SUMMARY Labs, Waltham, MA, 148134) affixed atop 50mL conical tubes, and centrifuged for CO:COLLECTION_SUMMARY 10 min. at 4°C at 106 x g. TIF was then collected from the conical tube, frozen CO:COLLECTION_SUMMARY in liquid nitrogen and stored at -80°C until further analysis. CO:SAMPLE_TYPE Interstitial Fluid #TREATMENT TR:TREATMENT_SUMMARY N/A #SAMPLEPREP SP:SAMPLEPREP_SUMMARY Quantification of metabolite levels in TIF and plasma In order to quantitate SP:SAMPLEPREP_SUMMARY metabolites in TIF and plasma samples, we first constructed a library of 149 SP:SAMPLEPREP_SUMMARY chemical standards of plasma polar metabolites (see Supplementary File 1 for SP:SAMPLEPREP_SUMMARY suppliers for each chemical standard). These compounds were selected to SP:SAMPLEPREP_SUMMARY encompass a number of metabolic processes and have previously been included in SP:SAMPLEPREP_SUMMARY efforts to profile plasma polar metabolites by LC/MS (Cantor et al., 2017; Evans SP:SAMPLEPREP_SUMMARY et al., 2009; Lawton et al., 2008; Mazzone et al., 2016). We pooled these SP:SAMPLEPREP_SUMMARY metabolites into 7 separate chemical standard pools (Supplementary File 1). To SP:SAMPLEPREP_SUMMARY do this, each metabolite in a given pool was weighed and then mixed (6 cycles of SP:SAMPLEPREP_SUMMARY 1 min. mixing at 25 Hz followed by 3 min. resting) using a Mixer Mill MM301 SP:SAMPLEPREP_SUMMARY (Retsch, Düsseldorf, Germany), and mixed metabolite powder stocks were stored SP:SAMPLEPREP_SUMMARY at -20°C prior to resuspension and analysis. Stock solutions of the mixed SP:SAMPLEPREP_SUMMARY standards pools containing ~5mM, ~1mM, ~300µM, ~100µM, ~30µM, ~10µM, ~3µM SP:SAMPLEPREP_SUMMARY and ~1µM of each metabolite were made in HPLC grade water and were stored at SP:SAMPLEPREP_SUMMARY -80°C (see Supplementary File 1 for the concentration of each metabolite in the SP:SAMPLEPREP_SUMMARY external standard pools). We refer to these stock solutions as “external SP:SAMPLEPREP_SUMMARY standard pools” throughout. External standard pools were used to confirm the SP:SAMPLEPREP_SUMMARY retention time and m/z for each analyte and provide standards to quantitate SP:SAMPLEPREP_SUMMARY concentrations of stable isotope labeled internal standards used in downstream SP:SAMPLEPREP_SUMMARY analysis, as well as to quantitate metabolite concentrations in TIF and plasma SP:SAMPLEPREP_SUMMARY samples directly where internal standards were not available (see below for SP:SAMPLEPREP_SUMMARY details). To extract polar metabolites from plasma, TIF or the external standard SP:SAMPLEPREP_SUMMARY pools, 5µL of TIF, plasma or external sample pools was mixed with 45uL of SP:SAMPLEPREP_SUMMARY acetonitrile:methanol:formic acid (75:25:0.1) extraction buffer including the SP:SAMPLEPREP_SUMMARY following isotopically labeled internal standards: 13C labeled yeast extract SP:SAMPLEPREP_SUMMARY (Cambridge Isotope Laboratory, Andover, MA, ISO1), 13C3 lactate (Sigma Aldrich, SP:SAMPLEPREP_SUMMARY Darmstadt, Germany, 485926), 13C3 glycerol (Cambridge Isotope Laboratory, SP:SAMPLEPREP_SUMMARY Andover, MA, CLM-1510), 13C6 15N2 cystine (Cambridge Isotope Laboratory, SP:SAMPLEPREP_SUMMARY Andover, MA, CNLM-4244), 2H9 choline (Cambridge Isotope Laboratory, Andover, MA, SP:SAMPLEPREP_SUMMARY DLM-549), 13C4 3-hydroxybutyrate (Cambridge Isotope Laboratory, Andover, MA, SP:SAMPLEPREP_SUMMARY CLM-3853), 13C6 glucose (Cambridge Isotope Laboratory, Andover, MA, CLM-1396), SP:SAMPLEPREP_SUMMARY 13C2 15N taurine (Cambridge Isotope Laboratory, Andover, MA, CNLM-10253), 2H3 SP:SAMPLEPREP_SUMMARY creatinine (Cambridge Isotope Laboratory, Andover, MA, DLM-3653), 8-13C adenine SP:SAMPLEPREP_SUMMARY (Cambridge Isotope Laboratory, Andover, MA, CLM-1654), 13C5 hypoxanthine SP:SAMPLEPREP_SUMMARY (Cambridge Isotope Laboratory, Andover, MA, CLM-8042), 8-13C guanine (Cambridge SP:SAMPLEPREP_SUMMARY Isotope Laboratory, Andover, MA, CLM-1019), 13C3 serine (Cambridge Isotope SP:SAMPLEPREP_SUMMARY Laboratory, Andover, MA, CLM-1574) and 13C2 glycine (Cambridge Isotope SP:SAMPLEPREP_SUMMARY Laboratory, Andover, MA, CLM-1017). All solvents used in the extraction buffer SP:SAMPLEPREP_SUMMARY were HPLC grade. Samples were then vortexed for 10 min. at 4°C and insoluble SP:SAMPLEPREP_SUMMARY material was sedimented by centrifugation at 15kg for 10 min. at 4°C. 20µL of SP:SAMPLEPREP_SUMMARY the soluble polar metabolite extract was taken for LC/MS analysis. #CHROMATOGRAPHY CH:CHROMATOGRAPHY_TYPE HILIC CH:INSTRUMENT_NAME Thermo Dionex Ultimate 3000 CH:COLUMN_NAME SeQuant ZIC- pHILIC (150 x 2.1mm, 5um) #ANALYSIS AN:ANALYSIS_TYPE MS #MS MS:INSTRUMENT_NAME Thermo Q Exactive Orbitrap MS:INSTRUMENT_TYPE Orbitrap MS:MS_TYPE ESI MS:ION_MODE POSITIVE MS:MS_COMMENTS LC/MS analysis was performed using a QExactive orbitrap mass spectrometer using MS:MS_COMMENTS an Ion Max source and heated electrospray ionization (HESI) probe coupled to a MS:MS_COMMENTS Dionex Ultimate 3000 UPLC system (Thermo Fisher Scientific, Waltham, MA). MS:MS_COMMENTS External mass calibration was performed every 7 days. 2μL of each sample was MS:MS_COMMENTS injected onto a ZIC-pHILIC 2.1 × 150 mm analytical column equipped with a 2.1 MS:MS_COMMENTS × 20 mm guard column (both 5 μm particle size, EMD Millipore). The autosampler MS:MS_COMMENTS and column oven were held at 4°C and 25°C, respectively. Buffer A was 20 mM MS:MS_COMMENTS ammonium carbonate, 0.1% ammonium hydroxide; buffer B was acetonitrile. The MS:MS_COMMENTS chromatographic gradient was run at a flow rate of 0.150 mL/min as follows: 0-20 MS:MS_COMMENTS min: linear gradient from 80% to 20% B; 20-20.5 min: linear gradient from 20% to MS:MS_COMMENTS 80% B; 20.5-28min: hold at 80% B. The mass spectrometer was operated in full MS:MS_COMMENTS scan, polarity-switching mode with the spray voltage set to 3.0 kV, the heated MS:MS_COMMENTS capillary held at 275°C, and the HESI probe held at 350°C. The sheath gas flow MS:MS_COMMENTS rate was set to 40 units, the auxiliary gas flow was set to 15 units, and the MS:MS_COMMENTS sweep gas flow was set to 1 unit. The MS data acquisition was performed in a MS:MS_COMMENTS range of 70-1000 m/z, with the resolution set to 70,000, the AGC target at 1e6, MS:MS_COMMENTS and the maximum injection time at 20 msec. Metabolite identification and MS:MS_COMMENTS quantification was performed with XCalibur 2.2 software (Thermo Fisher MS:MS_COMMENTS Scientific, Waltham, MA) using a 5ppm mass accuracy and a 0.5 min. retention MS:MS_COMMENTS time window. For metabolite identification, external standard pools were used MS:MS_COMMENTS for assignment of metabolites to peaks at given m/z and retention time, and to MS:MS_COMMENTS determine the limit of detection for each metabolite (see Supplementary File 1 MS:MS_COMMENTS for the m/z, retention time and limit of detection for each metabolite MS:MS_COMMENTS analyzed). Metabolite quantification was performed by two separate methods. MS:MS_COMMENTS Where internal standards were available, first, comparison of the peak areas of MS:MS_COMMENTS the stable isotope labeled internal standards with the external standard pools MS:MS_COMMENTS allowed for quantification of the concentration of labeled internal standards in MS:MS_COMMENTS the extraction buffer. Subsequently, we compared the peak area of a given MS:MS_COMMENTS metabolite in the TIF and plasma samples with the peak area of the internal MS:MS_COMMENTS standard to quantitate the concentration of that metabolite in the TIF or plasma MS:MS_COMMENTS sample. 70 metabolites were quantitated using this internal standard method (see MS:MS_COMMENTS Supplementary File 1 for the metabolites quantitated with internal standards). MS:MS_COMMENTS For metabolites without internal standards, the peak area of each analyte was MS:MS_COMMENTS normalized to the peak area of a labeled amino acid internal standard that MS:MS_COMMENTS eluted at roughly the same retention time to account for differences in recovery MS:MS_COMMENTS between samples (see Supplementary File 1 for the labeled amino acid paired to MS:MS_COMMENTS each metabolite analyzed without an internal standard). From the normalized peak MS:MS_COMMENTS areas of metabolites in the external standard pools, we generated a standard MS:MS_COMMENTS curve describing the relationship between metabolite concentration and MS:MS_COMMENTS normalized peak area. The standard curves were linear with fits typically at or MS:MS_COMMENTS above r2=0.95. Metabolites which did not meet these criteria were excluded from MS:MS_COMMENTS further analysis. These equations were then used to convert normalized peak MS:MS_COMMENTS areas of analytes in the TIF or plasma samples into analyte concentration in the MS:MS_COMMENTS samples. 74 metabolites were quantitated using this method. The relationship MS:MS_COMMENTS between metabolite concentration and normalized peak area is matrix dependent, MS:MS_COMMENTS and the external standards are prepared in water, which is a different matrix MS:MS_COMMENTS than either TIF or plasma. Therefore, we consider metabolite measurements using MS:MS_COMMENTS this external standard method semi-quantitative. #MS_METABOLITE_DATA MS_METABOLITE_DATA:UNITS micromoles/L MS_METABOLITE_DATA_START Samples 1234 KP 1 TIF 1234 KP 2 TIF 1234 KP 3 TIF 1234 KP 4 TIF 1234 KP 5 TIF 1234 KP 6 TIF 1234 KPK 1 TIF 1234 KPK 3 TIF 1234 KPK 4 TIF 1234 KPK 5 TIF 1234 KPK 6 TIF 1233 KP 3 TIF 1233 KP 4 TIF 1233 KP 5 TIF 1233 KP 6 TIF 1233 KPK 1 TIF 1233 KPK 5 TIF 1233 KPK 6 TIF 1339 TIF 5197 TIF AL1 TIF 268 TIF 142 TIF 172 TIF TBt0 plasma 705 TBt0 plasma 708 TBt0 plasma 707 TBt0 plasma 712 TBt0 plasma 711 TBt0 plasma 710 922 TIF 58 TIF 5197 TIF 172 TIF 142 TIF 1339 TIF 268 TIF AL1 TIF X1 TIF X2 TIF X3 TIF X4 TIF X5 TIF 922_Plasma 58_Plasma 5197_Plasma 172_Plasma 142_Plasma 268_Plasma AL1_Plasma X2_Plasma X3_Plasma X4_Plasma 3731_Plasma 4198_Plasma 4300_Plasma A0_Plasma A1_Plasma B0_Plasma B1_Plasma B2_Plasma Factors Sample Type:lung_subcutaneous Sample Type:lung_subcutaneous Sample Type:lung_subcutaneous Sample Type:lung_subcutaneous Sample Type:lung_subcutaneous Sample Type:lung_subcutaneous Sample Type:Keap1_mutant_lung_subcutaneous Sample Type:Keap1_mutant_lung_subcutaneous Sample Type:Keap1_mutant_lung_subcutaneous Sample Type:Keap1_mutant_lung_subcutaneous Sample Type:Keap1_mutant_lung_subcutaneous Sample Type:lung_subcutaneous Sample Type:lung_subcutaneous Sample Type:lung_subcutaneous Sample Type:lung_subcutaneous Sample Type:Keap1_mutant_lung_subcutaneous Sample Type:Keap1_mutant_lung_subcutaneous Sample Type:Keap1_mutant_lung_subcutaneous Sample Type:pancreatic ductal adenocarcinoma Sample Type:pancreatic ductal adenocarcinoma Sample Type:pancreatic ductal adenocarcinoma Sample Type:pancreatic ductal adenocarcinoma Sample Type:pancreatic ductal adenocarcinoma Sample Type:pancreatic ductal adenocarcinoma Sample Type:pancreatic ductal adenocarcinoma plasma Sample Type:pancreatic ductal adenocarcinoma plasma Sample Type:pancreatic ductal adenocarcinoma plasma Sample Type:pancreatic ductal adenocarcinoma plasma Sample Type:pancreatic ductal adenocarcinoma plasma Sample Type:pancreatic ductal adenocarcinoma plasma Sample Type:pancreatic ductal adenocarcinoma Sample Type:pancreatic ductal adenocarcinoma Sample Type:pancreatic ductal adenocarcinoma Sample Type:pancreatic ductal adenocarcinoma Sample Type:pancreatic ductal adenocarcinoma Sample Type:pancreatic ductal adenocarcinoma Sample Type:pancreatic ductal adenocarcinoma Sample Type:pancreatic ductal adenocarcinoma Sample Type:pancreatic ductal adenocarcinoma subcutaneous Sample Type:pancreatic ductal adenocarcinoma subcutaneous Sample Type:pancreatic ductal adenocarcinoma subcutaneous Sample Type:pancreatic ductal adenocarcinoma subcutaneous Sample Type:pancreatic ductal adenocarcinoma subcutaneous Sample Type:pancreatic ductal adenocarcinoma plasma cardiac puncture Sample Type:pancreatic ductal adenocarcinoma plasma cardiac puncture Sample Type:pancreatic ductal adenocarcinoma plasma cardiac puncture Sample Type:pancreatic ductal adenocarcinoma plasma cardiac puncture Sample Type:pancreatic ductal adenocarcinoma plasma cardiac puncture Sample Type:pancreatic ductal adenocarcinoma plasma cardiac puncture Sample Type:pancreatic ductal adenocarcinoma plasma cardiac puncture Sample Type:pancreatic ductal adenocarcinoma plasma cardiac puncture Sample Type:pancreatic ductal adenocarcinoma plasma cardiac puncture Sample Type:pancreatic ductal adenocarcinoma plasma cardiac puncture Sample Type:pancreatic ductal adenocarcinoma plasma cardiac puncture Sample Type:pancreatic ductal adenocarcinoma plasma cardiac puncture Sample Type:pancreatic ductal adenocarcinoma plasma cardiac puncture Sample Type:pancreatic ductal adenocarcinoma plasma cardiac puncture Sample Type:pancreatic ductal adenocarcinoma plasma cardiac puncture Sample Type:pancreatic ductal adenocarcinoma plasma cardiac puncture Sample Type:pancreatic ductal adenocarcinoma plasma cardiac puncture Sample Type:pancreatic ductal adenocarcinoma plasma cardiac puncture Acetylaspartate 9.751861895 7.021337708 16.7216308 13.39933697 20.46051983 20.58710635 5.730935817 3.755816887 7.058453787 5.407029982 7.106410577 4.324080225 13.6414673 6.061312628 25.83011905 15.24034266 6.77530761 26.1075299 2.267303198 4.197245096 3.328432353 2.011616495 4.665241571 1.575962273 5.599191083 6.006358137 2.263095207 0 2.283677147 2.26492556 11.52267069 8.222925637 13.47982491 9.615096937 12.50258678 11.19489459 10.61550885 12.50361247 20.24546376 30.1521033 19.94335915 16.06237684 13.00130155 3.502905209 3.990012138 2.282339864 35.42491242 5.086937935 12.9348141 29.3147682 11.82229843 65.67658469 9.892226982 5.523559125 4.486934629 9.958624556 7.285671077 10.36457574 5.654956631 42.56408533 8.557090379 CAR(2:0) 47.58272154 40.00224584 67.02071823 44.27766196 39.4059959 47.77278905 35.65324926 28.77545713 32.32242496 28.12745796 28.28099478 37.20709062 40.20094651 38.92004051 45.02665815 40.39896808 37.35258656 34.92171839 24.79848863 35.87338005 19.46929235 48.14478531 40.15297688 38.24637035 16.8442554 29.03982086 19.16891322 27.10598083 21.16555804 20.03503003 22.0181879 3.346856998 21.54965137 20.4206514 23.64049653 17.54466773 31.27585464 16.0059407 18.7868043 26.12827924 17.51154057 13.79072532 5.027876425 24.1777533 19.8495084 27.54087749 23.59332315 25.69606799 48.99299209 23.73271525 17.55908368 33.56383327 23.69291334 30.27348003 29.16722212 18.51246012 28.35155829 24.2295022 15.92825379 19.37985746 20.33859392 Acetylglutamate 1.882111487 1.525316233 2.532518328 6.614551808 1.52608617 11.55983409 2.031571991 1.300237834 1.882150698 2.285742004 1.886010955 2.015528252 2.941847091 2.565170808 6.829351983 2.284395672 1.335747368 4.617324757 0.452126422 0.695448649 0.725667016 0.502943092 0.810866688 1.012328208 1.037225852 1.362377977 0.934803663 0.75505456 0.717451808 0.969949493 4.505135245 0.267860709 0.798123513 1.153719015 1.161046907 0.637523493 0.643898507 0.915394696 1.470007894 2.118213164 2.751080723 1.744611061 1.239596356 1.412495486 0.635069439 0.401616716 1.022443513 0.954589631 0.577512136 1.475114816 0.771778036 1.3375786 1.958983429 2.058027279 1.504148699 1.029173497 0.634732867 1.201543042 1.190223222 2.226827066 1.994941989 N-acetylglutamic acid 1.519218676 1.181296551 0 7.882240534 0 18.78473414 1.792121341 1.402236059 0.981458424 1.003168987 0 0 1.756097471 1.512057277 4.229389432 2.034299969 1.090649666 3.774665265 0.41606243 0 0.60976178 0.581050515 1.52518796 0.954426652 0.65256841 1.016586802 1.101539272 1.46109576 1.724961862 1.249195207 2.161724949 0.002837799 0.422578909 0.463088438 0.768867168 0.183669004 0.257499602 0.340974656 0.088365227 0.118860298 0.190150658 0.140105721 0.072077508 1.00916635 0.333396227 0.712315613 0.705364663 1.100239573 0.497720573 0.666675362 0.211683925 0.462561 0.452692689 0.849918749 0.437501137 0.332551997 0.31084606 0.517743797 0.515089493 0.485019895 0.697534103 Alanine 1477.601504 1460.898583 2369.249825 1555.371674 1490.224779 1818.157489 993.0499739 951.2824143 967.8472364 938.9218088 1022.094635 1156.803814 1105.190297 1300.290429 1567.666943 1219.856481 951.2973447 1216.345536 852.436384 1190.114307 1313.230191 893.4094236 1616.217892 1584.490204 742.945932 776.4629301 627.3814586 716.1694013 711.9608054 630.1156167 1217.552669 333.1641184 1091.463322 1457.96729 1423.766564 778.7132058 637.0859691 1247.0075 1026.167512 1465.426648 1156.489676 923.0624977 1253.169352 708.4766732 793.7125724 462.8607379 580.1783001 933.1493426 411.6127221 1273.681078 540.6679642 713.7316541 790.1442387 1538.567224 668.4429368 1059.25792 616.9596605 756.0284423 1068.926156 1378.809399 954.1500306 Aminoadipic acid 38.78291671 30.28767625 38.47576318 32.95914517 26.19602202 30.29578916 29.37060641 17.59106573 37.96546499 21.47492896 19.37518293 24.0182348 25.97852025 29.08466685 34.36680169 30.59652263 26.8409361 26.86028712 14.98124992 23.87874511 13.54881365 12.23891126 14.36803381 14.43616659 7.83190105 8.26417656 7.219752822 10.51584199 11.31821406 10.23103186 21.03602492 2.372827583 21.87563987 14.22168578 12.96535381 13.8123145 10.73599606 12.59609031 24.36095547 36.07168165 29.31277506 20.81251001 17.24838656 7.797344978 3.747853352 9.201854309 3.664447861 5.135224522 5.865123968 6.399646869 16.37339733 21.2260077 21.60532308 7.482913764 8.8810436 3.985332434 9.268693365 10.68495647 13.46536338 44.7356106 30.04010486 Arginine 19.06443411 7.252390551 6.125749985 5.282286638 8.170987948 6.171955202 101.4784558 29.38947115 77.02418165 20.24870282 48.17201974 11.05382304 8.295794126 9.922700046 14.34747305 5.637237704 20.07442278 23.06018101 2.190709526 2.909511147 0.928995594 1.112859723 0.739840598 1.185018136 114.0448206 114.7557333 81.755335 104.3835086 109.9064345 90.67583942 3.050101311 3.350659073 5.185003645 0.874305399 1.061648904 2.059540072 1.598560239 1.004387528 130.2980503 191.4482151 56.28577019 140.1698806 1.43866332 148.7824863 144.5451687 144.517793 50.85454898 52.29013489 57.15668733 79.11539179 123.697469 136.0309152 234.1710539 144.7357197 125.953668 162.9087998 107.8200086 200.3116279 145.992975 163.1760116 112.894061 Asparagine 130.6023695 128.6055513 181.8300545 130.3646657 109.6060401 154.7586808 127.9660813 109.3935195 103.1102939 104.2134536 102.1661084 86.25744176 90.2958124 120.4907367 127.0327742 133.4814398 118.722869 121.4782269 62.36418623 86.17447917 84.90750856 47.67983718 92.70471409 92.19929284 51.62294869 61.15502976 60.6851774 55.59359117 53.7847186 47.7073223 145.5120829 64.24938341 137.9661836 108.5594509 123.0992345 98.7378968 62.86656817 125.7886126 155.3118461 255.3262587 167.6502276 130.0165531 218.5777994 74.18726372 142.3474674 37.82441429 42.2568508 83.41490528 44.19802612 135.3175861 57.38987869 59.63398264 83.41781995 179.1725278 87.92150719 116.167942 45.51020237 71.94668689 93.64352087 143.2840866 109.5140808 Dimethylarginine 0.50184422 0.484193878 0.607475153 0.965283517 0.274823788 1.427311703 0.454451342 0.502612031 0.405635147 0.453793461 0.623417744 0.308808749 0.479047793 0.435241079 0.517138911 0.497362074 0.405603238 0.695033186 0.280336028 0.512846563 0.292586777 0.283825004 0.443363277 0.302983109 1.355417639 -0.000666914 0.656116519 0.656486361 0.278725023 0.45542938 5.505386745 3.94007549 5.666549758 4.77754041 5.273541988 4.715470792 4.6593386 4.790779014 5.565877314 5.979835471 5.749938624 5.093097685 4.862274545 1.915217302 1.817696274 1.85348304 10.209842 1.545203169 1.662848682 1.98287254 1.269608666 3.47043412 2.044521372 3.782773725 2.75150259 1.935884919 1.300018891 5.09607671 1.115862164 2.345147915 1.38914783 Beta-Alanine 51.41106715 57.49258009 94.32987802 69.34500578 53.76593872 71.52203259 36.16165803 33.33101517 40.85079669 36.06779923 35.26051699 36.58262075 71.69272286 54.76014444 94.70487346 63.12339549 37.3133332 78.67668272 27.21063465 21.21239336 28.62585444 21.43167052 42.77032819 40.89964314 -0.049315336 -0.049315336 -0.049315336 -0.049315336 -0.049315336 -0.049315336 37.54394962 1.328655954 1.328655954 25.2219133 1.328655954 26.59191032 19.22639932 1.328655954 1.328655954 1.328655954 21.81048154 1.328655954 28.62500001 -0.130474814 -0.130474814 -0.130474814 22.89080349 -0.130474814 -0.130474814 -0.130474814 -0.130474814 -0.130474814 -0.130474814 4.145774946 -0.130474814 -0.130474814 -0.130474814 -0.130474814 -0.130474814 -0.130474814 -0.130474814 Betaine 105.8216713 106.5444625 139.2434886 98.05087576 78.91105725 144.4425046 142.837959 121.5133355 133.2316566 102.7125708 103.8617454 128.8865699 151.4595732 177.4042422 231.0706168 120.396259 147.3887679 194.1324607 117.1697257 128.8785965 121.1769909 128.6920818 279.5684288 215.2861109 117.0327177 66.08383779 98.50971702 72.59467054 52.27119038 74.64580817 162.4913724 55.69394241 95.16325049 162.4617328 220.9887103 85.13871375 92.09299539 86.66454149 93.26725956 131.8540869 75.10066681 60.53873668 68.8347376 66.076949 186.2103327 65.51566165 102.477164 126.4220546 70.0502468 94.9780758 57.47795237 101.2937135 76.23207407 70.19025794 66.37184191 78.68878979 72.5690108 67.38041091 54.30607409 24.20912529 26.11786012 Biotin 0.002826218 0.019753934 -0.000824309 0.015145274 -9.32E-05 -0.001653613 0.007191076 0.004036532 0.003617461 0.007225587 0.013895741 0.001332775 -0.011751626 -0.004414166 0.003151779 -0.000547012 0.023476234 0.003612425 0.010931476 0.033029667 0.007095792 0.014067541 0.00062006 0.012773544 0.023763812 0.032284701 0.027832355 0.043838329 0.020163368 0.034783184 0.664968184 0.610949694 0.682848498 0.682566563 0.667372641 0.622178806 0.638155324 0.629795871 0.62123506 0.625204916 0.692303974 0.623997653 0.648880318 0.023870791 0.039106424 0.04246356 0.030860955 0.025219527 0.050969276 0.056774827 0.044696088 0.064108592 0.071458659 0.030833754 0.047588737 0.052620076 0.04462642 0.082671014 0.028605568 0.043904928 0.027508195 Carnitine 85.15883348 54.30166331 79.28129017 59.58076014 48.7163566 87.16970841 57.6129778 51.03526704 63.2382696 44.29376124 72.93184293 68.60965342 59.04032046 81.17964063 84.10486538 91.01131244 67.40704501 68.88634161 44.6075399 55.3321503 33.19664999 38.01201009 51.58083234 51.38141487 19.25803535 28.44586723 21.44644204 18.45199432 24.5034454 18.95080445 58.75844782 11.45710437 49.757781 45.14952763 45.31129414 39.81098454 37.96884786 31.20456177 52.57942788 77.69218126 56.80636423 36.73480021 38.47962428 36.29192385 23.7563983 26.17243122 22.77850859 23.94599507 29.25516324 36.33089428 28.75609372 52.63446928 37.14821463 44.87380165 38.15303557 30.71177417 29.45874469 33.1969182 20.82278726 33.88445556 30.87187372 Carnosine 3.441964292 2.827131542 2.822444167 1.16069137 1.317825862 2.043373614 7.086377991 1.532661543 2.207236585 6.635751057 3.731310509 3.459888652 3.222129714 2.284849498 5.038806319 3.280610634 1.964702399 8.4915149 0.549212985 1.348792449 1.110208004 2.436559017 1.586830126 0.773938972 0.587717101 1.036455273 0.696866563 0.43130803 0.777905993 0.673492892 0.343077235 -0.486542317 0.711616547 0.494998459 1.409000351 -0.082173463 2.276165753 0.496247377 8.079209334 13.91643325 6.190643052 7.548600202 2.396574571 1.196928799 0.871015773 0.065977203 0 1.466280018 0.858014711 3.877259655 0 0 0.925243521 0.499699484 0 0 0 0 0.931492582 0 0.463623788 CDP-choline 6.035761066 6.008376357 0.999903055 5.828454682 7.359997355 4.336828988 4.311640743 3.6078098 2.832820732 3.357023489 4.518454223 4.067249923 5.105713997 2.636193023 8.979487511 6.509615436 3.5668513 8.245812651 2.029120327 2.209274745 1.437348675 1.199059874 3.476820899 2.848524629 0 0 0.200356434 0 0 0 17.56446371 16.76181117 17.36041761 17.62134742 17.35814069 17.0452149 16.93815389 17.15892185 16.81991405 16.89981142 16.7608756 16.92439707 16.77011376 0 0 0 0 0 0.053905426 0.390710152 0 0 0.039992624 0 0.06331146 0.036789873 0 0 0 0.460478023 0 Choline 278.1276076 184.1214408 518.2658537 235.1523465 310.4324551 269.0818933 142.0342924 118.4704366 188.5093176 108.3322592 100.1442733 139.9611507 103.3714055 179.4973683 165.2393386 133.6150625 114.0569952 167.7272463 187.6935607 140.1607098 160.3591924 163.7488327 238.6695896 231.221329 15.67710122 16.38137171 15.79968273 12.37270813 13.37496963 14.62944991 275.1857024 36.29661944 169.1373042 270.5205826 249.2162086 233.7193365 195.4204874 201.6048741 199.5058573 258.8710374 140.2670984 110.8017822 143.9440531 38.9625066 31.37936562 19.87124123 33.42313739 35.14006702 43.68352655 52.14609709 194.325077 25.88177189 31.93497547 32.75012211 46.10703464 43.4751766 32.01636463 45.84034936 25.36060064 30.34552173 22.14719172 Citrulline 88.15390748 92.65472947 117.5041674 103.5488256 72.47766498 88.35252069 70.7973772 76.76301086 66.65549717 72.62592506 79.65429988 72.24442963 78.04071942 92.41364609 87.82976 77.54820934 75.60332559 78.62293249 49.2893677 89.49997628 69.26348931 44.13371129 72.85960328 118.2886202 70.70284109 95.1251049 67.21368806 66.50959119 67.76534176 63.6335111 68.32345369 23.49573758 89.17375422 118.7336027 70.99230729 49.75405387 44.47320851 70.54090156 92.67026061 113.7511 91.80319292 70.15543614 57.02214981 92.4292023 111.6055237 90.27563399 81.74070755 103.2841851 88.94934436 150.4394309 37.50909313 69.8332313 77.17728258 173.2026534 94.47160686 121.651458 46.87104607 58.02065231 69.43715311 88.13716106 67.32597942 CMP 1.338209928 2.521155128 0 0.490199002 1.183620002 0.556348636 7.830706737 6.77711581 6.299187371 1.520728764 14.43031801 1.199179694 5.197963417 1.175228105 37.5950458 34.28826023 19.87044747 20.50475065 8.463278603 15.57675842 25.53299538 16.65609972 32.77498276 29.54606189 0 0 0 0 0 0 6.902465103 4.12569389 9.515423664 17.73421709 16.04646981 6.45000631 10.94671379 15.25915372 4.847329524 6.887906104 4.444411198 4.269949734 4.942203664 0 0 0 0 0 0.807769258 1.657977188 0 0 0 0 0.136250432 0.186697075 0 0 0 1.447585334 0 Coenzyme A 1.316336383 0 2.267949549 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0.354600147 -0.113280318 0.775533691 2.856121073 0.592667181 0.063761245 0.993622578 0.782861887 0.519913722 1.136898584 0.188288892 -0.041281659 -0.113280318 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Creatinine 13.1745421 13.75912517 21.56811931 49.85866471 12.15248051 93.46462137 15.4455037 11.16119744 11.2105553 13.64420111 16.54513025 11.58989042 15.23309483 14.1006176 28.95243119 17.18848407 10.77619446 30.80361365 8.814539218 11.84623593 6.340353716 9.458987013 22.06748411 13.2136703 10.67540078 10.71574372 7.391182477 6.423975374 6.909439666 7.220915017 17.49920532 8.950329163 19.09762533 20.81494172 33.03964768 13.61085128 13.25018966 11.17464414 20.55010956 30.60788373 21.44222865 17.76596359 19.47300209 12.12282909 13.38792652 8.720610554 6.456523997 27.62710305 12.54704929 12.36902623 12.98972868 16.41262497 21.22169504 18.17340443 11.57455632 20.86104219 8.571142582 10.81913216 9.816527489 19.46740717 8.573853244 Cystathionine 4.538569411 4.034288323 4.712624814 4.573419624 2.951074844 6.78713672 3.433548285 4.16627188 4.455808702 2.450274333 4.424410975 3.839904247 5.415368209 5.529650387 7.918934279 7.412083117 8.359213718 15.07488496 2.617458122 3.307833181 6.503108543 4.305443926 4.519825572 4.196697773 0 3.198245394 2.289846055 0.532144116 0.84592271 0 6.125622451 0.7293341 2.702297546 4.069510982 4.36682535 2.089797234 3.338231744 5.375365208 23.49327878 73.87447751 37.44111575 17.85928666 1.760640526 0.905059864 0.38209038 0.645454786 0.620447866 0.23011855 0.772704788 0.409644896 1.248097543 3.716095807 0.376575442 1.308883106 0.437740333 0.896451456 2.838999842 15.87384908 6.040684358 Cystine 37.94173718 35.30691239 14.2898507 22.27409382 7.732735125 32.89821882 29.19593872 69.33885732 20.99186682 86.05692177 35.02167951 127.7525135 47.84135534 39.48013983 30.5017593 45.85147465 35.00368883 78.74238455 26.68796841 40.37149014 21.81686634 18.58310629 18.29601149 13.67064425 6.895769852 13.62902938 6.815938953 49.84165137 52.81559703 17.15535149 67.67039586 54.28939985 110.5816766 16.05272458 32.36616798 47.4052264 32.87421016 46.92109548 70.87278098 117.759362 148.1701441 119.6655369 57.19110164 150.3679462 153.3738799 79.11850665 137.2282013 63.75149901 80.02623838 80.96965056 135.3288814 133.2988241 86.34924958 29.94784796 52.29083553 56.37094368 85.85677445 122.0882013 114.4542796 60.80388529 Cytidine 37.63311987 30.03189353 31.87806512 37.75119894 30.0675825 36.47209646 14.30046996 14.36771687 24.39033516 23.36637673 9.517092046 37.5094648 42.76255287 35.6797185 23.94808828 14.33990987 16.39279849 17.57877722 13.98421484 17.12172294 14.7775512 17.07502208 10.23165184 10.46243171 1.945984614 2.481369641 2.66710961 1.870995589 1.865627177 1.503851265 10.15401663 2.929974081 12.65724563 10.25596965 9.349068426 13.63135143 13.43400853 11.8987848 39.2193697 53.08822192 28.6986748 26.01798948 11.36388071 3.174193882 3.958208713 3.674271532 1.659113067 1.078644452 3.299364011 4.213786396 4.447621458 8.311290375 7.19133489 2.759856862 4.995576101 3.578084933 5.680560268 5.837120897 6.0003723 4.218696068 2.617132554 dATP 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 3.011352768 3.011352768 3.011352768 3.011352768 3.011352768 3.011352768 3.011352768 3.011352768 3.011352768 3.011352768 3.011352768 3.011352768 3.011352768 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Deoxycytidine 0.853099268 1.284801928 1.183928781 0.983413555 0.87430753 0.800891013 1.127354741 0.512748535 0.938207089 0.611388813 0.671749661 0.955220432 1.102082557 1.185322881 0.731008233 0.866949174 0.753384211 1.190440325 0.584670065 0.971368118 0.3908791 0.393408738 0.291483232 0.425893391 0.581149044 0.721712092 0.791950014 0.477319044 0.384433019 0.499222904 1.433527202 0.361173223 1.907917575 1.198146015 0.909012461 1.272945891 0.823414568 0.957872088 22.868958 23.31127 12.81877848 11.40113949 2.727404354 1.561254614 1.266998139 0.938189448 0.56259691 1.058439328 0.902228866 1.369934945 0.432616629 0.724455977 1.101694633 1.940419435 0.940382157 0.91162523 0.834400526 0.835973603 0.702879339 0.595281388 0.493082133 Fructose-1,6-biphosphate 0 0 0 0 1.226574311 0 0 0 0 0 0 0 0 0 1.185614713 0 0 0 0 0 0.321648 1.247791476 1.60110371 6.157210323 0 0 0 0 0 0 17.29834172 10.06193421 10.06193421 15.51483819 10.06193421 10.06193421 12.10703811 10.06193421 10.06193421 10.06193421 10.06193421 10.06193421 10.06193421 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Gamma-Aminobutyric acid 2.013118039 1.770186738 6.425485914 3.529812792 3.142877262 2.868387809 1.638731485 2.008580587 0.938474791 1.799772841 2.795760265 4.273683042 3.716155137 4.531999537 7.488694504 4.135593444 1.970285065 5.504931335 5.436477521 7.193343989 8.289150879 7.001299725 10.76044652 186.0965855 0.742906075 0 1.522316794 1.010640724 0.550260871 1.141865604 6.652106813 5.50356224 4.242785157 197.1168779 11.04727932 4.506221419 6.714642213 9.085439952 2.768251636 3.541075805 5.697324352 2.665479605 4.007759077 3.970210822 2.006143185 1.728271492 4.86279363 2.012781984 1.107855348 4.129917807 5.178436724 3.693588056 2.916572856 3.362607562 3.141606621 3.425984208 1.656070662 2.551467241 0.298358281 2.77541761 2.129513387 5-Glutamyl-alanine -0.525695409 -0.45166984 -0.525695409 -0.503615426 -0.525695409 -0.525695409 0.132473851 -0.148761311 -0.357058667 -0.362610532 -0.362126555 -0.378912727 -0.280953366 -0.456292801 -0.417975943 -0.407052546 -0.399731135 -0.475856069 -0.331136739 -0.156416616 -0.408100057 -0.479063136 -0.525695409 -0.525695409 1.302236098 1.995595629 1.751810768 1.937247264 1.27549288 1.693747226 0.420095623 0.261206035 2.400885591 0.136158569 0.500932534 0.919356638 0.554601376 2.926376057 0.89562773 0.575384724 2.147336763 3.178004279 5.186940339 6.43981342 7.901081915 4.552914698 3.389907936 5.82911251 3.983992675 3.847538799 4.197218475 Glutamine 972.5883865 703.1706526 889.0079336 829.7847891 564.5008501 797.0189361 546.2790731 442.3207927 392.4115878 296.1872784 391.2607226 528.7025021 539.2130967 532.458155 730.0829158 817.8146614 743.0496461 490.3127242 581.008811 926.1649414 784.8094588 446.0349612 1311.406138 765.4587152 393.9924159 398.9354315 395.4523431 390.4028605 392.0439082 357.5931549 784.0826622 233.3219326 933.8126417 849.3976736 1329.218605 606.9140814 434.4065702 808.9145226 768.8470321 971.3683624 753.7321554 495.369478 713.4155156 809.8507141 1298.730111 767.6734611 534.2129188 1343.523627 647.3864408 1379.737511 470.1843747 722.492578 629.2090152 1083.324672 697.7422529 1261.756602 552.0578182 656.5093089 804.9568229 941.6643572 695.1514906 Glycerol 3-phosphate 451.1669671 238.5619406 469.0861864 457.7669683 445.5059604 389.1599174 197.7799118 153.8539251 220.3357871 140.2999356 118.2054693 113.1614116 170.8037761 143.2246924 212.3050519 181.0370495 134.4998006 251.1674001 345.2785808 240.6622101 296.4632932 223.9823022 568.0381467 323.2155789 13.85871505 37.81483367 14.28856431 10.45570571 9.653807527 13.63026465 286.3023728 14.4481998 123.5469248 132.9197606 181.3759457 151.6832038 106.3713113 132.9103574 117.0101735 197.7714875 90.79289616 75.9494617 68.5764343 22.7653752 16.91100591 14.97065133 46.9303746 10.40167224 54.66196543 87.67849344 57.0307774 80.33664256 63.48508109 12.27139549 35.92644136 53.1364818 53.55359847 96.93179056 39.88885993 317.2656914 78.9333863 sn-glycero-3-phosphocholine 361.5241969 251.0442138 476.3100323 344.4115462 367.6316625 366.2395001 146.8568362 116.6471671 170.592237 153.8575367 108.1773958 170.3187316 170.8090621 160.1293845 254.654638 166.7003486 137.6597993 127.1975536 150.3777687 105.3295294 112.2005252 92.57124349 126.7616526 84.79643954 6.948753593 6.020266232 6.867021607 6.092281712 7.597251158 5.086645784 230.2179151 18.75558541 114.8256936 103.7453913 157.9856233 176.986813 101.9348765 125.5546425 66.89630958 71.49903035 49.85498091 49.37618614 76.30411867 8.128286683 5.637131226 4.154650591 4.818315701 3.546041858 10.98278084 25.46957801 7.203235041 10.08315745 15.75453027 4.121936137 6.020066452 4.744299932 14.25804872 15.8674457 11.35870577 19.8431176 14.11260737 Glycine 1597.644625 1307.318298 2109.974779 1341.047411 1035.608962 1147.664062 1915.719788 1894.097045 1693.007967 1408.092803 1361.36481 1018.215048 1125.242111 1361.15435 1069.79665 1398.843179 1178.178836 1305.392003 741.478841 822.391701 835.1464523 623.3814228 826.0655957 909.3124823 332.670969 334.0867261 244.282862 246.8422236 269.2299565 210.843083 3654.407745 380.9727713 1765.399654 3055.328675 1294.395092 1302.6817 1401.582863 953.7357037 2063.585161 2150.184251 1073.824448 1532.705479 1627.02392 176.407012 186.2071863 99.15614885 7.137721035 133.5106406 162.8059049 219.5244238 105.6222519 257.3557455 128.4848134 268.2230894 126.5085115 211.2231425 268.1262773 354.0019808 107.768253 88.86545329 57.01404177 GSH 76.35501583 22.20193976 247.1752914 224.7496191 187.7047034 127.6273142 76.71932007 35.91098487 5.614785785 53.56714245 0 11.4480288 54.59300936 15.29517712 86.88190215 61.75790433 45.6712068 58.25019345 6.080725071 1.536873154 6.143024232 6.367377276 2.654864486 2.515118649 0 0.230280134 0.319220431 0.454754343 0 0.338034361 16.00081873 13.28723783 5.399861844 80.80292002 20.85541332 15.18859599 10.40424877 6.788231689 4.09920963 1.534889162 1.19505117 2.001563119 0.998097684 8.79292417 14.51735116 11.80538201 0.537318984 1.734522624 GSSG 0 339.5223029 0 1212.93349 883.2805172 0 358.6935225 417.5824841 399.4298429 330.3637903 0 261.5240667 227.679971 215.0173828 0 511.5458757 639.4341066 480.1552623 81.69349102 100.3502391 110.1008177 124.3524153 202.7331511 165.0258268 0 7.438720064 9.19670733 5.015135886 4.429173096 5.444671781 249.8316793 13.66575183 172.7351654 186.8782407 267.4863419 106.9609375 163.9368771 139.3405807 124.3080235 123.1859995 104.2556291 69.17855209 72.86034213 19.75657937 18.70963051 6.189706282 20.81624744 50.07105517 16.67622574 20.02423278 68.08971308 23.10921462 22.28594406 5.962273949 30.28630338 11.00132184 72.91131008 0 Guanidoacetic acid 23.31201215 18.27750237 17.79128574 52.97770605 9.27617659 119.1246809 29.60040406 25.19102601 42.65822703 15.65336963 18.13901698 16.38052515 29.96654948 21.96828486 43.02067324 26.11397959 20.85091325 49.8320225 23.53828048 67.15232604 45.61970259 10.43838111 23.22110464 20.59061189 18.44480775 11.80619208 11.66187734 7.277729542 7.75604302 6.762888687 6.918951124 -1.079572776 13.22277225 3.1652342 2.627179936 2.360039287 0.774672292 5.981709328 1.985828831 5.69381556 2.82043926 1.481603918 4.140765373 1.662312157 1.525405535 1.519100556 -0.026621321 0.315471084 -0.026621321 2.243299661 2.565766114 14.3569214 2.515430428 3.035318894 0.296770226 0.33899441 -0.026621321 3.281658619 1.441976161 -0.026621321 0.603842402 Histidine 119.6497846 121.9991162 143.5378222 102.3231195 90.91878004 133.6682622 108.3838917 98.69415251 96.98039008 96.67261933 137.4672216 106.0073333 91.41982004 118.1444982 100.5765661 122.5117227 109.9487175 110.6022391 80.48739016 113.0918616 96.12959519 56.0979598 108.6414619 109.7682192 56.01112632 59.69507967 54.43875415 58.5681665 56.81852188 58.85796942 113.1118626 53.71614592 117.402517 101.1790941 111.1628579 67.16625974 53.11253679 97.76874338 90.62192087 128.8712903 109.686923 78.71790274 128.4751656 89.52071444 196.1084447 65.93637607 56.32203177 111.6207067 67.09027788 137.4162277 46.39641161 65.62792824 81.65413415 165.4880694 71.95810372 135.8051747 47.25390045 64.67260734 91.30160606 118.7548313 68.46742296 Hypotaurine 107.533609 85.47705295 159.569016 107.4732254 104.406889 147.5402869 109.3322404 110.9349539 92.93932967 69.61007058 67.31030363 71.23689809 81.51714475 114.0179057 95.48796775 136.7054002 127.6745673 144.3963545 51.64744692 43.8102611 45.39609873 60.40497752 82.47010066 87.29538581 9.229709671 20.604782 11.89975294 8.445396321 17.62322429 9.29858719 80.87045708 28.32135185 50.15811648 80.87880025 69.90304314 50.01792581 50.23236715 50.63243788 105.5598436 250.9890847 137.5434301 72.6089305 94.53866059 3.586415568 6.590410216 2.362795035 6.698450734 3.917310625 19.21954218 22.61702832 7.93418267 13.33323459 6.537496671 12.53383822 3.046063489 9.738402356 1.225722363 1.89925923 4.08355237 29.37479425 16.7114672 Hypoxanthine 253.5546437 165.2998647 432.8895146 289.3180835 308.6176983 256.2796559 97.31358622 94.64587788 93.66710116 138.0506621 41.82066408 121.5002105 143.5540393 134.9874222 152.6295554 65.70896615 52.0997691 101.897669 86.90160087 29.51588293 63.12156483 72.15877689 132.3037348 125.8835919 0.011779247 0 0.011826065 0.007306475 0.053811593 0.021976931 151.9956139 9.778256066 50.02264466 123.8730027 143.4465338 102.1848238 116.7517955 111.0613541 37.95212303 69.26156648 24.01151017 35.67489569 0.099741089 2.823030135 0.282926654 1.929718012 4.370124633 0.635697354 6.748881782 13.77886582 64.75041845 111.7574758 44.24182852 8.631403508 13.15066094 40.7463715 75.80551067 45.25864819 52.1972603 2.084067607 IMP 0 0 0 0 0 0 7.191508953 0.314074016 1.04895294 0 28.58274478 0 0 0 24.91826551 33.7707332 21.15148835 39.77458561 0.767656594 4.482957565 5.360545565 4.884007816 10.57415915 10.53370144 41.86206391 7.745633058 2.115325531 0.467599934 4.448735745 1.396133017 6.529061442 2.830056728 4.501508662 9.176809154 8.542276461 2.72527825 6.335634222 6.27495074 5.238569234 20.14552685 11.17292458 12.67687614 6.039527059 0 0.116798023 0.385089934 0 9.209929926 58.99976798 69.62234306 8.824024759 0 2.081891947 0 0 0 0.757759764 0 0.325202978 276.6045928 2.246430613 Indolelactic acid 0.156034328 0.421725686 0.815104251 0.952203915 -0.128698655 1.067425774 0.414359676 1.02290419 0.144108589 0.906798614 2.011036547 -0.104310644 0.11079298 0.379545017 1.680869557 0.259138854 0.103451143 1.128531476 -0.523487523 0.021558943 -0.161411539 -0.484167297 -0.264853631 -0.436691927 1.023781274 1.222639071 0.47828177 0.327442943 0.375447884 0.417530597 1.633477386 1.326470765 2.226204626 1.724001143 1.928480722 1.513465584 1.575433581 1.828065391 2.218983655 2.472428865 2.718043728 2.574440629 2.454490356 0.93889176 1.357429351 1.449779103 0.99518086 0.694197053 1.232227956 1.869945583 1.337638716 2.187689523 3.00345909 6.807358889 2.985314868 2.844792481 1.397498273 1.429029056 1.330340215 1.965794755 1.732477146 Inosine 105.1910189 152.5092446 211.0302015 193.9803195 187.7580148 121.1433033 59.95073528 77.03194625 42.18865129 99.31193387 22.74675792 88.16210678 118.4562367 91.19304012 106.9849757 47.23356538 45.37775781 52.00579292 33.59859268 7.895194223 49.27767459 68.50519727 63.24851461 86.17680235 -0.003173838 -0.003173838 -0.003173838 -0.003173838 -0.003173838 -0.003173838 29.63516291 17.44057406 10.33485865 55.26366412 46.58801575 28.36763237 43.68047089 42.05833521 9.15892792 16.28000901 5.097237249 10.20344295 0.950846225 0.366951008 1.319824098 0.537714676 1.185121162 0.364729595 2.270045053 10.06313132 9.041903857 24.98762587 8.607401104 -0.010011816 4.174546461 2.708226067 17.36105456 26.48500165 11.09718425 8.775430737 0.424636399 Isoleucine 134.863772 147.3537253 152.2714954 142.7903899 103.8575977 168.8374713 139.8661015 123.7741839 126.4271329 123.8518796 150.4858745 117.1923661 125.9066697 166.6561548 138.1862657 152.0346247 162.5385456 163.8632484 77.7225922 154.1487669 62.32264859 87.0136555 87.23424179 75.19635937 138.929323 105.7044312 105.0553902 106.6772903 100.125008 123.1944995 197.7884815 86.3236437 190.8226013 91.75809591 111.8992045 108.171802 119.1710512 93.60257315 169.7844191 230.3848107 223.1488834 178.28145 141.6528604 175.7054221 219.7133733 186.578505 72.84809657 126.2201681 165.8338379 108.7184003 83.24933604 118.8087913 187.4341645 199.1284564 270.1900822 220.6659024 82.14972097 169.6689417 110.8099005 165.0478069 132.0122423 Kynurenine 6.155597634 3.811621223 11.6945735 2.782104892 2.338945764 1.342118791 0.416685415 1.2879735 1.020558914 0.609101699 1.014380695 0.202507999 0.143960121 0.313572326 0.244622653 0.772589024 1.118814475 1.021736956 0.107669353 0.357855283 0.11053981 0.140965834 0.144577322 0.242077124 0.457501668 0.571750468 0.456071476 0.267649795 0.244244759 0.396427687 1.656073394 0.401061833 1.903226022 0.738481821 1.700162085 0.309510556 0.430828414 0.313450179 0.973459184 4.68188314 3.306711088 1.357761851 2.769043504 1.065596498 3.88465192 1.10091544 0.568389211 0.921790526 0.915420258 1.177829505 1.978909946 4.12064235 2.34069313 1.846236165 2.131414443 2.469992161 1.564934304 1.903584438 4.937418079 6.642756714 Leucine 228.7536872 291.5908553 326.1115558 254.4496712 208.2222054 306.8658019 278.8653536 213.4584304 226.8208626 246.4946744 312.7331973 231.0586306 230.2336621 307.5752414 273.6847362 277.6353932 309.2434877 282.1260425 143.7693627 257.1858014 149.2834372 165.7941858 174.0198507 137.5285209 189.1946224 149.6462983 135.9214187 147.7529021 134.9437228 179.8195382 425.6760694 178.4957891 418.3528804 204.5466634 249.7506282 223.0939183 246.9000325 251.9722227 380.8532492 514.5082653 428.2358624 378.8890448 294.3806017 343.369986 414.0009496 321.5550413 147.0656153 243.2640945 367.2376452 290.6586192 148.1018394 242.6766434 319.4010187 471.6491343 486.841628 490.9759159 109.8542339 306.9307053 176.9662312 284.3154074 206.6259806 Lysine 336.7476436 373.4507605 447.699808 343.2662008 238.9679585 462.2103239 422.9879499 339.0433851 369.1448422 363.2920244 478.4627321 341.7297048 295.7832567 411.4224993 376.5285292 346.6999601 344.9348372 416.5989491 202.4909692 406.8306757 191.030301 156.4315651 272.0818153 263.8638685 343.1471107 278.6266956 297.3171938 276.1464085 272.3213036 225.2874073 214.4739795 58.31174269 213.7011866 132.8342225 134.2582077 104.7919594 73.36850157 101.4417944 193.2864365 294.2086097 243.2330463 231.9321787 179.3576738 237.1528906 231.5399951 165.361522 97.66944399 196.3375602 138.4788462 192.226739 143.600556 168.293683 310.8326515 351.8792311 230.8212375 311.9274514 235.2034758 316.3929688 284.2789413 443.2896772 315.5994574 Methionine 117.054317 145.5435738 195.7619163 136.7222219 97.18687387 165.8832291 132.2144971 105.0641983 116.9033652 116.9317177 132.2211278 92.22754562 102.7745448 140.6480481 181.4898834 128.4594583 118.1075897 140.9552993 64.88211492 111.1251295 74.01577065 44.00128256 148.6860595 106.8716473 94.56854513 71.27759085 85.47675993 85.23186383 84.51657241 81.3457359 94.31384027 43.47957405 83.14522692 79.46405289 106.6768621 54.96198359 35.39498235 62.50833488 75.62151517 120.6844842 115.1376658 94.54178042 79.96089188 87.83882995 146.7118644 59.13265704 62.77949287 139.0622688 42.93613449 92.98444899 59.73040588 87.90669253 122.0982864 147.5053725 90.27502559 123.6445014 75.51434408 98.01782195 146.9090273 325.809578 455.1953466 Methionine sulfoxide 6.787343373 9.739246569 12.11354472 10.48975667 6.90971041 13.80898009 8.191513628 6.349706258 7.76681457 8.749978075 10.43045666 6.359766586 7.828247874 10.89259314 13.60515991 8.922974649 7.716759408 19.66927001 4.027527813 5.10108952 3.193812232 1.838568211 5.550223854 3.920063372 4.920815931 2.01503233 3.054042664 2.51696313 3.353419189 3.254698071 5.134343051 1.947598945 3.781596738 3.031837796 3.842289143 2.886088598 1.209666974 2.315511325 8.439589037 11.14015283 6.481905431 5.940022939 4.693335725 5.757185465 7.980407884 3.660587643 1.745539158 4.660412864 1.450954567 3.655107625 4.682072579 4.461595254 7.226430017 4.894257727 4.925993847 5.833015792 1.845960611 1.695900572 3.148661558 8.571783398 7.623994779 N6-acetyllysine 0.758220021 0.610604972 1.386550127 0.622180065 0.445713084 1.064188101 0.747268242 0.69901814 0.67705839 0.662231531 1.097568202 0.75712288 0.568531191 0.814380563 1.106301016 0.810819899 0.649674119 0.70181287 0.352706724 1.074900321 0.435532055 0.45883182 0.668778233 0.328743127 0.867362864 0.765124137 0.679007571 0.582482544 0.536761804 0.617382345 0.952095171 0.220412005 1.000094242 0.398113889 0.57621903 0.4070129 0.502326928 0.491780432 0.523641799 0.659551935 0.558505521 0.553202602 0.427598667 1.22487548 0.755698121 0.951750388 0.349599685 0.836084647 0.9749566 0.874503835 0.377777807 0.688930875 0.908437019 1.4229805 1.083189894 0.779989878 0.654877974 0.757895991 0.503311559 0.507661925 0.426678874 Niacinamide 112.0665072 89.63141893 162.3112639 120.1893711 112.0158052 97.58947518 57.20864602 61.67372706 57.67219478 58.31546289 48.14552143 48.93324062 65.32411852 59.69744873 85.41074745 65.00591297 56.36818349 64.67974393 36.70425104 34.08820153 38.30974609 41.63818423 52.67911749 48.40651776 3.812695824 6.325389921 4.829003205 6.196686455 6.734397522 5.944341467 64.29105115 6.055187327 33.22178175 52.5012404 51.00453769 35.50249074 36.70867473 36.4277499 30.02088007 43.79426365 23.33226024 21.23870915 29.14155053 4.073568304 4.331500444 3.28458815 7.782685753 4.720341397 10.06777394 15.09998214 6.59228691 10.44953089 10.00546509 3.534625687 5.943409288 6.14541664 4.557446688 8.00007106 5.779016563 22.81782738 9.921084753 Ornithine 193.7184289 237.0036739 284.3595606 214.5779982 150.0441607 266.6714338 166.4757247 177.7329585 169.7813833 198.2695167 241.7934452 148.4158064 173.5642261 221.9268544 221.7927384 222.259314 207.8116232 272.3312436 146.6329922 267.0165361 133.2623753 88.83577409 144.4759292 153.7463257 60.94966462 51.76115646 40.85417706 74.10355245 54.65885474 46.6621775 485.3623248 171.0940171 479.770226 280.1978373 254.3174214 267.5814603 160.0699949 258.5378676 376.2018453 590.8775011 475.1524037 327.5174507 418.9204445 207.8711488 294.292895 134.4637396 73.31173615 243.4562352 150.023078 294.320136 94.59077572 99.00922509 293.4380915 326.8784271 295.2465345 230.6258737 82.0439921 153.8174026 130.8346527 209.6924322 166.712498 Pantothenic acid 1.989301708 1.614112183 1.983728809 3.044519479 1.374562402 4.502303415 1.46073583 1.567444459 1.506391025 1.409075918 1.861651255 1.540073363 1.91054638 2.086382741 2.533794195 2.091895823 2.014630543 2.749482701 1.568558005 5.572986674 4.253171433 2.990341194 3.2081381 4.200140822 2.577716408 2.163877231 1.679260722 1.135568546 1.029939836 1.003269988 2.349184994 0.701228667 5.802799396 4.517140923 3.590454508 1.740565942 3.200278933 4.985019991 3.951888231 5.630622761 5.032194094 3.771294746 4.90966967 2.006745183 4.319178464 3.90686808 3.132183326 2.400226596 3.660834986 7.879141398 3.698619971 6.237344561 6.064875786 8.0202205 4.60801893 5.50072275 5.235089132 5.794750189 7.208012216 7.514648639 6.289676046 Alpha-N-Phenylacetylglutamine -0.001678739 -0.001678739 -0.001678739 -0.000214761 -0.001678739 0.003099494 -0.001678739 -0.001678739 -0.001678739 -0.001678739 -0.001678739 -0.001678739 -0.001678739 -0.001678739 -0.001678739 -0.001678739 -0.001678739 0.000221168 -0.001678739 -0.001678739 0.00793224 -0.001678739 0.00599036 -0.000260313 -0.001678739 0.000786125 -0.001678739 0.000896899 -0.000445113 -0.000788419 -0.398273795 -0.398273795 -0.398273795 -0.391254445 -0.39006785 -0.398273795 -0.394085808 -0.375126524 -0.398273795 -0.398273795 -0.393003755 -0.396872229 -0.398273795 -0.009919343 -0.009351108 0.000178678 -0.011928701 0.020548773 -0.007708294 0.042300631 -0.011928701 -0.001546716 -0.009040212 -0.011928701 -0.011928701 -0.005153444 -0.011928701 -0.011928701 -0.001224937 -0.011928701 -0.011928701 Phenylalanine 128.6613119 149.4007125 177.6367622 138.3741212 108.1781402 166.4478492 160.4252081 121.366132 120.8981706 124.6838318 150.8873511 111.8294893 108.8682472 144.8572962 135.3683298 142.6022398 144.4956703 153.8906978 69.81689283 114.1660122 107.5425574 69.8109355 90.34148894 128.9243881 79.44563292 69.69965872 64.44209972 54.24094669 62.08015463 73.67462416 84.56265235 48.10004661 94.19625274 105.5964831 72.94867373 56.25108088 54.18360388 92.03817783 107.2662209 142.8815404 121.329407 108.9621622 143.9188503 81.75457299 138.4335034 73.69082894 79.94772155 77.92340629 78.11671289 137.1633258 51.77359322 77.27940424 120.70646 206.5298493 103.6837289 124.3845629 46.03938691 97.03557439 95.23088761 107.3167516 75.11722829 Choline phosphate 284.2566962 256.8067574 637.4198314 321.8478285 376.7852427 472.1997096 256.7320597 348.6438406 294.4397475 339.8369801 255.3543012 378.0797604 350.3485287 469.6298122 472.6270338 260.6063922 191.6764749 252.456973 143.9278958 110.3805169 165.74581 195.9384199 321.8471783 302.2334733 3.548108986 2.809154925 2.995762199 1.972938099 3.068947143 2.47739216 234.7140093 29.63041873 113.7256768 281.4285485 366.312881 164.187747 222.3093833 210.5585184 176.5982324 134.5159948 91.7209461 81.113568 164.6122992 7.131623989 6.077927509 6.102685594 6.922606132 5.251281086 13.58727443 27.09143043 8.850867931 10.37086005 13.13279766 5.274595695 13.55833121 9.594021448 9.813953795 18.8986913 7.361680214 21.52954983 12.98605497 Phosphocreatine 981.4011539 1016.979762 1321.814197 1148.343152 1574.094718 1431.104491 371.617806 269.3296696 520.6100236 286.7571899 316.2176318 654.0467949 708.8492216 853.5623371 1289.654842 949.7282558 634.2836019 596.5234938 964.0111115 508.200497 1298.405664 1020.136618 1352.246258 1800.079949 90.44154742 106.0574571 36.49284962 46.69953476 60.21048511 69.77212209 251.2666118 133.2665172 253.6643799 801.5490996 561.2137432 424.2982234 471.9572549 546.6539231 243.0288414 190.0797247 160.4517505 150.1386643 184.9605661 27.06987946 31.20775191 23.17918997 116.2839595 53.1354595 267.7950031 82.10388906 34.78313766 48.27265368 58.63992294 19.83992785 33.64270016 78.69640818 85.16730516 167.8996241 32.93040548 230.7496507 63.92965265 Phosphoserine -0.008548841 1.11883681 -0.008548841 0.37815326 -0.008548841 -0.008548841 -0.008548841 0.656584341 -0.008548841 -0.008548841 -0.008548841 -0.008548841 -0.008548841 -0.008548841 -0.008548841 -0.008548841 -0.008548841 -0.008548841 -0.008548841 -0.008548841 0.258691388 -0.008548841 -0.008548841 0.392429317 -0.008548841 -0.008548841 -0.008548841 -0.008548841 -0.008548841 -0.008548841 3.715889705 3.715889705 3.715889705 3.715889705 3.715889705 3.715889705 3.715889705 3.715889705 3.715889705 3.715889705 3.715889705 3.715889705 3.715889705 -0.02285815 -0.02285815 -0.02285815 -0.02285815 -0.02285815 -0.02285815 -0.02285815 -0.02285815 -0.02285815 -0.02285815 -0.02285815 -0.02285815 -0.02285815 -0.02285815 -0.02285815 -0.02285815 -0.02285815 -0.02285815 Picolinic acid -0.590489989 -0.327442455 -0.493377795 -0.341923573 -0.413041518 -0.490402978 -0.218675654 -0.413034458 -0.283769043 -0.236710444 0.520476084 -0.43342704 -0.325832556 -0.312288855 -0.076794331 -0.460953751 -0.419558616 -0.032003157 -0.479486928 -0.238146965 -0.36867107 -0.453632783 -0.587160549 -0.472154605 0.277903156 -0.248678974 -0.307221971 -0.334557303 -0.163087252 -0.167754698 6.583315818 6.241751246 6.373719379 6.421366285 6.330477377 6.208765142 6.13452452 6.152565506 6.337327554 6.498674583 6.242199355 6.305780483 6.463714344 0.30436742 1.009229714 0.088818509 0.135019938 0.27448682 0.313035566 0.269212797 0.275808265 0.38603686 0.572805353 0.756448016 0.757680752 0.856284558 0.205836969 0.366419136 0.288306163 0.392666848 0.452011344 Pipecolic acid 8.583815568 7.640104085 10.81948452 11.59420743 7.756266871 17.63774073 5.466283814 7.107623046 5.193265278 6.666682664 11.33182036 6.635643214 7.512970032 6.950049423 12.17112943 9.423856826 7.179141484 9.683002916 3.034728813 4.65994788 3.395189351 7.413252815 11.48794574 5.023815067 4.681119019 7.498020199 6.625804328 4.492690811 4.225088284 3.75295403 7.313926963 1.670441138 4.74427552 4.921631198 9.088392837 3.064132207 7.461424909 3.467706734 3.138497645 3.548711089 3.872701379 2.84043679 1.810547839 6.869497857 5.299949536 3.950556604 3.192939281 11.53027109 8.286948954 4.955766641 1.602290335 3.017136173 3.694656424 8.825892434 8.523324699 6.817706217 2.181676175 1.984804614 2.514934218 2.692456105 2.146922665 Proline 266.5239638 308.2964552 411.567101 274.1028181 242.4539956 340.4679006 299.223591 245.912827 253.3866508 267.8845668 266.9660167 228.3904164 273.4839114 345.4691975 396.7502669 302.987817 273.3566866 347.9826388 121.6916453 214.075082 178.22464 112.2193201 211.1058706 217.1574705 157.4068587 119.7759445 123.3042094 142.1716291 141.8216484 144.4390932 164.1948186 52.40197569 138.5810528 141.8417266 136.5282047 80.3069351 70.69820844 123.5994995 198.9465514 307.1195944 193.2232981 150.9300484 160.2605315 93.65616699 154.2578286 55.18030176 60.61231091 116.2364309 51.40498577 142.6635065 44.87821911 61.37416666 107.0490977 221.6639938 86.88396981 135.9019042 50.13971875 78.57867685 71.78793852 78.58757903 68.62677079 Riboflavin 0.034503499 0.04842611 0.01414877 0.467498637 0 1.014028887 0.043643953 0.062845049 0.022842989 0.04194044 0.060333036 0.010296233 0.077007883 0.054478214 0.200022143 0.06246339 0.024916549 0.230967157 0.058717439 0.085660012 0.035506842 0.078526562 0.034954978 0.012139857 0.08459396 0.084894592 0.127715861 0.068008695 0.088885361 0.081604464 4.340569435 4.2434226 4.373712675 4.33072777 4.328341661 4.30368378 4.320613652 4.284696595 4.295544931 4.283466125 4.292381444 4.299322251 4.279363326 0.014898705 0.076000881 0.009589814 0.030668254 0.044160196 0.06659038 0.057287682 0.004050552 0.021101069 0.063356717 0.078991075 0.044565461 0.05381473 -0.004006828 0.019183691 -0.006906214 0.05191747 -0.007799117 S-Adenosylhomocysteine 3.583782806 0.869553366 0 1.004861211 0 0 1.077548041 0.7485091 0.791600793 0.67497425 0 0 1.413015934 1.863201722 2.286179697 0 0 0.761743795 0.12413621 0.112955588 0.259382037 0.269499405 0.332828687 0.436598298 0 0.048496684 0.019358544 0.016308217 0 0.008579892 0.344328449 0.084944617 0.274810833 0.570718116 0.582569305 0.243644492 0.41700712 0.434352586 0.241566201 0.616483767 0.426676595 0.413476892 0.404587359 0.220124996 0.105502923 0.095518798 0.017459875 0.054448456 0.098747623 0.331659994 0.159320559 0.250896506 0.245117967 0.123073418 0.309700496 0.157798246 0.090884554 0.185366344 0.467851151 7.834766854 3.035896252 Sarcosine 5.557564403 4.58291939 10.15569717 7.087410807 5.012748031 11.9003362 6.715823237 5.714432895 7.441930892 7.824391571 5.485626579 4.398467687 5.087012626 5.262705534 9.266582665 2.468347444 6.322690967 10.23564262 2.941861898 4.580024098 2.143853827 9.164166243 29.9817123 10.22390582 1.351641377 0.125754322 1.483341258 -0.028600131 0.476223118 0.27875888 9.775485263 6.503980937 6.208278344 8.492828018 14.2015747 5.803591025 7.147133419 5.728718743 5.943395753 9.242077449 6.857903728 5.866034924 5.501540548 8.892252711 20.87122092 10.46736518 7.821558113 15.24776336 28.51815107 12.85205363 22.45148498 100.4061045 29.99954463 14.49350334 21.42234245 22.20603624 23.27712703 56.3260466 14.37964886 86.13489437 30.79249228 Serine 284.269857 240.605888 384.2346875 263.1826591 260.2826565 264.5709966 245.150711 165.9306138 189.7484884 162.4878012 175.932713 154.1522615 207.6834357 210.950993 254.6512539 274.576189 228.6788125 252.0019657 110.7186016 165.4417714 155.437434 110.905907 193.4518392 185.8968323 148.0409321 110.7716528 127.3053632 116.8190099 102.236631 241.0471597 81.08411136 217.8588563 228.0955073 264.9486995 145.5806661 140.8813335 208.2527232 698.6851015 964.1825177 437.8722224 335.6428746 301.2841902 41.27668897 82.81703564 21.79368771 0.525083921 38.07520272 8.895559398 59.31847129 13.56720369 26.49537058 44.41674393 133.3377095 28.88352554 49.83624008 15.51345779 24.68757031 44.02282386 10.46606427 16.19052285 Threonine 473.5658506 482.3380044 823.0219406 468.2215552 409.3366875 623.1605947 485.178049 397.3203263 383.5798868 426.5774375 364.9767576 322.1682753 328.7840601 313.6190436 406.1454896 318.8054223 360.5316652 387.8223083 170.903391 269.6594154 289.1961822 160.3268337 244.2215432 313.2529903 150.3288619 136.6337149 136.4907919 144.571767 160.1081506 138.9652243 281.7317917 120.1329307 254.8995572 314.2985156 263.6147688 210.8410539 145.0304937 292.9168006 281.1035336 623.9367689 384.7728182 282.2737509 250.2343932 194.6773678 425.0311758 122.0813718 134.290239 225.0649977 144.3386855 405.8822712 171.0979794 207.8959602 257.7569279 406.7639732 245.0017689 472.5180374 178.3209202 197.9022748 384.4331258 918.5475331 596.6892846 Urocanic acid 6.259538541 7.501467436 13.65764529 6.407319322 12.68019438 2.68158562 12.98347283 2.378937288 7.364431701 5.774468557 8.012391677 3.455160538 12.73645268 4.909892356 16.11915579 10.26844625 6.58651885 26.60757462 0.026320195 0.467955206 0.519438633 0.444774103 0.198417601 0.340305841 0.343464982 1.714997834 0.080522585 0.268356131 0.532648027 0.199537167 0.205595961 1.114004106 0.649203375 0.423393402 0.221636685 0.035538047 0.458764581 0.774151322 102.6817076 180.2085189 77.94050095 50.33134526 12.28948046 0.06097079 3.942896278 0.457462653 0.424151583 0.529826125 0.208563581 2.233367356 0.243066444 0.175492098 0.855966131 0.876587999 0.443685957 0.469983894 0.057080554 0.825516956 0.228520315 0.75293565 0.788587298 Tryptophan 75.04515625 94.39496052 98.53405508 71.96525504 61.86779893 93.46379484 104.0345215 95.05544353 96.78747151 73.86435199 89.79149934 56.35403145 50.12116417 85.02573534 64.88560552 75.32927468 112.9084364 70.1082882 27.37882981 92.93670432 25.7874562 22.69715597 30.13224264 26.99178632 117.5928856 96.03837862 77.49492694 60.7809487 65.02632156 72.3344985 37.27371774 9.71391517 71.34529685 20.97763717 22.29288117 24.14678102 18.42597769 22.13730643 63.03584394 122.3116899 100.8656439 84.87108319 101.6813215 70.44210276 86.54312477 98.10378201 27.91903709 27.92682089 51.32861279 60.00859653 69.05304448 99.28200855 134.8076633 66.94244518 76.35089825 67.12594675 69.47738756 89.63768318 81.89705754 149.8867235 150.5304214 Tyrosine 128.0339293 145.9327732 179.0763892 139.3211608 109.792736 144.0743689 157.0035698 108.3606246 115.2677666 109.5206896 131.5564068 85.87932492 95.74826609 133.2312053 100.8318852 118.4331081 122.5282747 116.6971907 43.69432878 124.2565386 56.46780857 50.67255534 42.31075743 76.43867043 106.4229195 71.05836038 85.54249317 94.7141943 89.80925383 95.61698706 73.12987674 25.26457095 110.4829076 67.23845132 36.13267111 37.30368883 43.67961177 48.56849486 92.8014588 171.7722659 134.7900076 117.0485286 134.9150991 61.73101605 71.72604626 83.44113059 42.17898329 33.13945965 53.72577696 68.97602096 69.01394086 103.4496355 138.3369918 154.3675249 70.61498956 63.30234224 64.57649912 96.18098823 106.4840921 225.1733167 159.7464192 UMP 0 0.337332859 0 0 0 0 27.50466485 12.38022507 11.47585179 0.45851065 66.08148283 0 1.984118499 0 116.7882445 151.4704593 118.3212038 109.4666167 18.73565552 61.68561075 60.65801178 23.25945882 112.1310604 91.00032747 0 7.368014723 0 0 0 0 31.95609776 15.20438513 43.88811266 62.8219434 55.15182682 22.84755185 27.09970558 51.45445801 13.51916774 22.79165708 15.71554891 15.62022003 17.74219796 0 0 0 0 0.3505977 2.980727687 5.565294544 0 0 2.026817921 0 0 1.164548749 0 0 0 6.808515269 0.436907159 Valine 291.4467907 347.3905533 408.7003144 323.1411213 254.6800968 362.1116608 339.0499884 263.8538972 285.4389057 294.2843469 362.9016187 284.3058598 295.971067 387.1364301 334.5607292 320.623101 348.6584851 338.7952937 186.9189725 313.0425685 173.34293 200.5003849 180.6849343 183.7575883 289.4454957 217.7360866 213.8219496 246.5932117 237.5401755 267.0238977 222.1207334 81.93089722 202.072117 121.4842003 121.6710913 135.2341643 128.8361239 120.9377939 199.4900309 306.2743089 241.0910669 192.6737281 181.1156986 228.291584 308.6472921 187.1607097 98.98984211 151.4776661 212.209549 191.7934219 103.3819152 154.9230195 196.1221708 359.9372267 319.0010312 333.7692003 77.96735988 156.5335932 140.3153512 207.2701714 184.3594575 MS_METABOLITE_DATA_END #METABOLITES METABOLITES_START metabolite_name Acetylaspartate CAR(2:0) Acetylglutamate N-acetylglutamic acid Alanine Aminoadipic acid Arginine Asparagine Dimethylarginine Beta-Alanine Betaine Biotin Carnitine Carnosine CDP-choline Choline Citrulline CMP Coenzyme A Creatinine Cystathionine Cystine Cytidine dATP Deoxycytidine Fructose-1,6-biphosphate Gamma-Aminobutyric acid 5-Glutamyl-alanine Glutamine Glycerol 3-phosphate sn-glycero-3-phosphocholine Glycine GSH GSSG Guanidoacetic acid Histidine Hypotaurine Hypoxanthine IMP Indolelactic acid Inosine Isoleucine Kynurenine Leucine Lysine Methionine Methionine sulfoxide N6-acetyllysine Niacinamide Ornithine Pantothenic acid Alpha-N-Phenylacetylglutamine Phenylalanine Choline phosphate Phosphocreatine Phosphoserine Picolinic acid Pipecolic acid Proline Riboflavin S-Adenosylhomocysteine Sarcosine Serine Threonine Urocanic acid Tryptophan Tyrosine UMP Valine METABOLITES_END #END