#METABOLOMICS WORKBENCH stringek_20161208_071018 DATATRACK_ID:797 STUDY_ID:ST000605 ANALYSIS_ID:AN000926 PROJECT_ID:PR000442 VERSION 1 CREATED_ON May 25, 2017, 1:20 pm #PROJECT PR:PROJECT_TITLE Whole blood and serum 1D-1H-NMR metabolomics PR:PROJECT_TYPE Cross-center Quantitative NMR Urine Metabolomics Study PR:PROJECT_SUMMARY Serum is a common sample of convenience for metabolomics studies. Its processing PR:PROJECT_SUMMARY time can be lengthy and may result in the loss of metabolites including those of PR:PROJECT_SUMMARY red blood cells (RBC). Unlike serum, whole blood (WB) can be quickly processed, PR:PROJECT_SUMMARY minimizing the influence of hemolysis without excluding RBC metabolites. To PR:PROJECT_SUMMARY determine differences between serum and WB metabolomes, both sample types, PR:PROJECT_SUMMARY collected from healthy volunteers, were assayed by 1H-NMR spectroscopy. A total PR:PROJECT_SUMMARY of 34 and 51 aqueous metabolites were quantified from serum and WB, PR:PROJECT_SUMMARY respectively. Free hemoglobin (Hgb) levels in serum were measured and the PR:PROJECT_SUMMARY correlation between Hgb and serum metabolites was determined. All metabolites PR:PROJECT_SUMMARY detected in serum were detected at higher concentrations in WB with the PR:PROJECT_SUMMARY exception of acetoacetate and propylene glycol. The 18 unique metabolites of WB PR:PROJECT_SUMMARY included adenosine, AMP, ADP and ATP, which are associated with RBC metabolism. PR:PROJECT_SUMMARY The use of serum results in the underrepresentation of a number of metabolic PR:PROJECT_SUMMARY pathways including branched chain amino acid degradation and glycolysis and PR:PROJECT_SUMMARY gluconeogenesis. The range of free Hgb in serum was 0.03-0.010 g/dL and 8 PR:PROJECT_SUMMARY metabolites were associated (p < 0.05) with free Hgb. The range of free Hgb in PR:PROJECT_SUMMARY serum samples from 18 sepsis patients was 0.02-0.46 g/dL. WB and serum have PR:PROJECT_SUMMARY unique aqueous metabolite profiles but the use of serum may introduce potential PR:PROJECT_SUMMARY pathway bias. Use of WB for metabolomics may be particularly important for PR:PROJECT_SUMMARY studies in diseases like sepsis in which RBC metabolism is altered and PR:PROJECT_SUMMARY mechanical and sepsis-induced hemolysis contributes to variance in the PR:PROJECT_SUMMARY metabolome. This study has been published: Shock 2015;44:200-208. PR:INSTITUTE University of Michigan, University of Mississippi PR:DEPARTMENT Clinical Pharmacy, Center for Bioinformatics and Computational Medicine, PR:DEPARTMENT Emergency Medicine (UMich); Emergency Medicine (UMISS) PR:LABORATORY NMR Metabolomics Laboratory, University of Michigan PR:LAST_NAME Stringer PR:FIRST_NAME Kathleen PR:ADDRESS College of Pharmacy, University of Michigan, 428 Church Street, Ann Arbor, MI PR:ADDRESS 48109 PR:EMAIL stringek@umich.edu PR:PHONE NA PR:FUNDING_SOURCE NIH (GM069438, GM113041); Upjohn Award, College of Pharmacy #STUDY ST:STUDY_TITLE Whole blood reveals more metabolic detail of the human metabolome than serum as ST:STUDY_TITLE measured by 1H-NMR spectroscopy: Implications for sepsis metabolomics ST:STUDY_TYPE Single timepoint; healthy controls ST:STUDY_SUMMARY Healthy volunteers ST:INSTITUTE University of Michigan ST:DEPARTMENT Clinical Pharmacy ST:LABORATORY The NMR Metabolomics Laboratory (Stringer) ST:LAST_NAME Stringer ST:FIRST_NAME Kathleen ST:ADDRESS University of Michigan, 2900 Huron Parkway, Ann Arbor, MI 48105 ST:EMAIL stringek@umich.edu ST:PHONE NA ST:TOTAL_SUBJECTS 19 whole blood; 20 serum #SUBJECT SU:SUBJECT_TYPE Human SU:SUBJECT_SPECIES Homo sapiens SU:TAXONOMY_ID 9606 SU:AGE_OR_AGE_RANGE Healthy - Mean (±SD): 54.9±8.2 years | Sepsis - Mean (+SD): 54.7±17.3 years SU:WEIGHT_OR_WEIGHT_RANGE Healthy - Mean (+SD): 74.4±1.71 kg; BMI < 30 SU:HEIGHT_OR_HEIGHT_RANGE Healthy - Mean (±SD): 171.8±10.3cm SU:GENDER Healthy - males and females | Sepsis - males and females SU:HUMAN_RACE Healthy - Caucasian (C) and African American (AA) | Sepsis - Caucasian (C) and SU:HUMAN_RACE African American (AA) SU:HUMAN_MEDICATIONS Healthy - None SU:HUMAN_PRESCRIPTION_OTC Healthy - None SU:HUMAN_SMOKING_STATUS Healthy - Non smokers SU:HUMAN_ALCOHOL_DRUG_USE Healthy - None SU:HUMAN_INCLUSION_CRITERIA Healthy - non-smoking, non-obese with no known medical conditions that require SU:HUMAN_INCLUSION_CRITERIA chronic drug therapy | Sepsis - admitted to emergency department or intensive SU:HUMAN_INCLUSION_CRITERIA care unit. Clinical indices for severe sepsis or septic shock were met: SU:HUMAN_INCLUSION_CRITERIA confirmed or suspected infection, two or more criteria of systemic inflammatory SU:HUMAN_INCLUSION_CRITERIA response criteria, and hypoperfusion evidenced by either a systolic blood SU:HUMAN_INCLUSION_CRITERIA pressure of <90mmHg after 20 min of fluid resuscitation or a blood lactate level SU:HUMAN_INCLUSION_CRITERIA of at least 36 mg/dL. #SUBJECT_SAMPLE_FACTORS: SUBJECT(optional)[tab]SAMPLE[tab]FACTORS(NAME:VALUE pairs separated by |)[tab]Additional sample data SUBJECT_SAMPLE_FACTORS - CCMB01S Sample Type:Serum | Gender:M | Race:C Initial volume (serum)=620; NMR pH (serum)=6.85 SUBJECT_SAMPLE_FACTORS - CCMB02S Sample Type:Serum | Gender:F | Race:C Initial volume (serum)=550; NMR pH (serum)=6.53 SUBJECT_SAMPLE_FACTORS - CCMB03S Sample Type:Serum | Gender:M | Race:C Initial volume (serum)=415; NMR pH (serum)=6.66 SUBJECT_SAMPLE_FACTORS - CCMB04S Sample Type:Serum | Gender:M | Race:C Initial volume (serum)=500; NMR pH (serum)=6.63 SUBJECT_SAMPLE_FACTORS - CCMB05S Sample Type:Serum | Gender:M | Race:C Initial volume (serum)=550; NMR pH (serum)=7.11 SUBJECT_SAMPLE_FACTORS - CCMB06S Sample Type:Serum | Gender:F | Race:C Initial volume (serum)=500; NMR pH (serum)=6.37 SUBJECT_SAMPLE_FACTORS - CCMB07S Sample Type:Serum | Gender:F | Race:C Initial volume (serum)=655; NMR pH (serum)=6.97 SUBJECT_SAMPLE_FACTORS - CCMB08S Sample Type:Serum | Gender:F | Race:AA Initial volume (serum)=620; NMR pH (serum)=6.45 SUBJECT_SAMPLE_FACTORS - CCMB09S Sample Type:Serum | Gender:F | Race:C Initial volume (serum)=185; NMR pH (serum)=6.87 SUBJECT_SAMPLE_FACTORS - CCMB10S Sample Type:Serum | Gender:F | Race:C Initial volume (serum)=490; NMR pH (serum)=7.45 SUBJECT_SAMPLE_FACTORS - CCMB11S Sample Type:Serum | Gender:F | Race:C Initial volume (serum)=465; NMR pH (serum)=6.35 SUBJECT_SAMPLE_FACTORS - CCMB12S Sample Type:Serum | Gender:M | Race:C Initial volume (serum)=545; NMR pH (serum)=6.82 SUBJECT_SAMPLE_FACTORS - CCMB13S Sample Type:Serum | Gender:F | Race:AA Initial volume (serum)=680; NMR pH (serum)=6.7 SUBJECT_SAMPLE_FACTORS - CCMB14S Sample Type:Serum | Gender:M | Race:C Initial volume (serum)=600; NMR pH (serum)=6.39 SUBJECT_SAMPLE_FACTORS - CCMB15S Sample Type:Serum | Gender:M | Race:C Initial volume (serum)=200; NMR pH (serum)=6.07 SUBJECT_SAMPLE_FACTORS - CCMB16S Sample Type:Serum | Gender:F | Race:C Initial volume (serum)=400; NMR pH (serum)=6.74 SUBJECT_SAMPLE_FACTORS - CCMB17S Sample Type:Serum | Gender:M | Race:C Initial volume (serum)=450; NMR pH (serum)=6.65 SUBJECT_SAMPLE_FACTORS - CCMB18S Sample Type:Serum | Gender:M | Race:C Initial volume (serum)=630; NMR pH (serum)=6.3 SUBJECT_SAMPLE_FACTORS - CCMB19S Sample Type:Serum | Gender:M | Race:C Initial volume (serum)=430; NMR pH (serum)=7.89 SUBJECT_SAMPLE_FACTORS - CCMB20S Sample Type:Serum | Gender:F | Race:C Initial volume (serum)=650; NMR pH (serum)=7.93 SUBJECT_SAMPLE_FACTORS - CCMB01WB Sample Type:Whole Blood | Gender:M | Race:C Initial volume (serum)=650; NMR pH (serum)=7.38 SUBJECT_SAMPLE_FACTORS - CCMB02WB Sample Type:Whole Blood | Gender:F | Race:C Initial volume (serum)=820; NMR pH (serum)=7.32 SUBJECT_SAMPLE_FACTORS - CCMB03WB Sample Type:Whole Blood | Gender:M | Race:C Initial volume (serum)=740; NMR pH (serum)=7.22 SUBJECT_SAMPLE_FACTORS - CCMB04WB Sample Type:Whole Blood | Gender:M | Race:C Initial volume (serum)=660; NMR pH (serum)=7.42 SUBJECT_SAMPLE_FACTORS - CCMB05WB Sample Type:Whole Blood | Gender:M | Race:C Initial volume (serum)=680; NMR pH (serum)=7.39 SUBJECT_SAMPLE_FACTORS - CCMB06WB Sample Type:Whole Blood | Gender:F | Race:C Initial volume (serum)=712; NMR pH (serum)=7.38 SUBJECT_SAMPLE_FACTORS - CCMB07WB Sample Type:Whole Blood | Gender:F | Race:C Initial volume (serum)=700; NMR pH (serum)=7.33 SUBJECT_SAMPLE_FACTORS - CCMB08WB Sample Type:Whole Blood | Gender:F | Race:AA Initial volume (serum)=910; NMR pH (serum)=7.43 SUBJECT_SAMPLE_FACTORS - CCMB09WB Sample Type:Whole Blood | Gender:F | Race:C Initial volume (serum)=728; NMR pH (serum)=7.28 SUBJECT_SAMPLE_FACTORS - CCMB10WB Sample Type:Whole Blood | Gender:F | Race:C Initial volume (serum)=720; NMR pH (serum)=7.48 SUBJECT_SAMPLE_FACTORS - CCMB11WB Sample Type:Whole Blood | Gender:F | Race:C Initial volume (serum)=680; NMR pH (serum)=7.35 SUBJECT_SAMPLE_FACTORS - CCMB12WB Sample Type:Whole Blood | Gender:M | Race:C Initial volume (serum)=720; NMR pH (serum)=7.19 SUBJECT_SAMPLE_FACTORS - CCMB13WB Sample Type:Whole Blood | Gender:F | Race:AA Initial volume (serum)=810; NMR pH (serum)=7.43 SUBJECT_SAMPLE_FACTORS - CCMB14WB Sample Type:Whole Blood | Gender:M | Race:C Initial volume (serum)=800; NMR pH (serum)=7.38 SUBJECT_SAMPLE_FACTORS - CCMB15WB Sample Type:Whole Blood | Gender:M | Race:C Initial volume (serum)=800; NMR pH (serum)=7.39 SUBJECT_SAMPLE_FACTORS - CCMB16WB Sample Type:Whole Blood | Gender:F | Race:C Initial volume (serum)=830; NMR pH (serum)=7.47 SUBJECT_SAMPLE_FACTORS - CCMB17WB Sample Type:Whole Blood | Gender:M | Race:C Initial volume (serum)=790; NMR pH (serum)=7.49 SUBJECT_SAMPLE_FACTORS - CCMB18WB Sample Type:Whole Blood | Gender:M | Race:C Initial volume (serum)=1000; NMR pH (serum)=7.47 SUBJECT_SAMPLE_FACTORS - CCMB19WB Sample Type:Whole Blood | Gender:M | Race:C Initial volume (serum)=880; NMR pH (serum)=7.43 SUBJECT_SAMPLE_FACTORS - CCMB20WB Sample Type:Whole Blood | Gender:F | Race:C Initial volume (serum)=880; NMR pH (serum)=7.38 #COLLECTION CO:COLLECTION_SUMMARY Healthy - Direct venipuncture collection of WB and Serum from healthy controls | CO:COLLECTION_SUMMARY Sepsis - Indwelling arterial or venous catheter CO:COLLECTION_PROTOCOL_COMMENTS Healthy - Fasting (12h) blood samples (serum and whole blood) were collected CO:COLLECTION_PROTOCOL_COMMENTS between 8:30-9:30am by single direct venipuncture. | Sepsis - Serum generated CO:COLLECTION_PROTOCOL_COMMENTS via indwelling catheters as part of clinical trial (NCT 00372502) CO:SAMPLE_TYPE Healthy - Blood: Whole Blood and Serum | Sepsis - Blood serum CO:COLLECTION_METHOD Healthy - Direct venipuncture | Sepsis - indwelling catheters CO:COLLECTION_LOCATION Healthy - Michigan Clinical Research Unit | Sepsis - University of Mississippi CO:COLLECTION_FREQUENCY Healthy - 1 | Sepsis - 1 CO:COLLECTION_TIME Healthy - Fasting, between 0830-0930 | Sepsis - N/A CO:STORAGE_CONDITIONS Healthy - Serum: Initial RT then -80°C following processing (within 2h) Whole CO:STORAGE_CONDITIONS blood: Initial 0°C then -80°C following processing (within 10mins) | Sepsis - CO:STORAGE_CONDITIONS Initial RT then -80°C following processing (within 2h) CO:STORAGE_VIALS Healthy - SST: Becton-Dickinson vacutainer Serum Separator tubes. WB: CO:STORAGE_VIALS Becton-Dickinson vacutainer Sodium Heparin tubes | Sepsis - SST: CO:STORAGE_VIALS Becton-Dickinson vacutainer Serum Separator tubes CO:COLLECTION_TUBE_TEMP Healthy - RT | Sepsis - RT CO:ADDITIVES Healthy - Serum: none. Whole blood: Sodium Heparin | Sepsis - none CO:BLOOD_SERUM_OR_PLASMA Healthy - Whole blood and Serum | Sepsis - Serum #TREATMENT TR:TREATMENT_SUMMARY No treatment #SAMPLEPREP SP:SAMPLEPREP_SUMMARY Methanol:cholorform extraction, filtration SP:SAMPLEPREP_PROTOCOL_COMMENTS Lipid fractions saved, stored at -20°C SP:PROCESSING_METHOD Methanol:Chloroform Extraction, filtration SP:PROCESSING_STORAGE_CONDITIONS 0-4°C SP:EXTRACTION_METHOD Methanol:chloroform extraction SP:EXTRACT_ENRICHMENT Ultra-filtration to remove residual protein SP:EXTRACT_CLEANUP N/A SP:EXTRACT_STORAGE -80°C SP:SAMPLE_RESUSPENSION 500 uL Deuterium Oxide (D2O) SP:SAMPLE_SPIKING DSS-IS2 (Chenomx, Inc) #CHROMATOGRAPHY CH:CHROMATOGRAPHY_TYPE - CH:INSTRUMENT_NAME - CH:COLUMN_NAME - #ANALYSIS AN:ANALYSIS_TYPE NMR #NMR NM:INSTRUMENT_NAME Agilent 500/54 Premium Shielded VNMRS system NM:INSTRUMENT_TYPE FT-NMR NM:NMR_EXPERIMENT_TYPE 1D-1H NM:STANDARD_CONCENTRATION 10% (~0.5mM) NM:SPECTROMETER_FREQUENCY 500 MHz NM:NMR_PROBE ONE-Probe NM:NMR_SOLVENT D2O NM:NMR_TUBE_SIZE 5mm NM:SHIMMING_METHOD Auto shim (gradient shimming), manual when necessary. NM:PULSE_SEQUENCE 1D-NOESY NM:WATER_SUPPRESSION saturation at 80 Hz induced field strength NM:PULSE_WIDTH 5.5ms NM:OFFSET_FREQUENCY around -178Hz NM:CHEMICAL_SHIFT_REF_CPD DSS-d6 (whole blood), Formate (serum) NM:TEMPERATURE 25°C NM:BASELINE_CORRECTION_METHOD manual NM:CHEMICAL_SHIFT_REF_STD DSS-d6 (whole blood), Formate (serum) NM:BINNED_INCREMENT N/A NM:BINNED_DATA_PROTOCOL_FILE N/A NM:BINNED_DATA_EXCLUDED_RANGE N/A #NMR_METABOLITE_DATA NMR_METABOLITE_DATA:UNITS uM NMR_METABOLITE_DATA_START Samples CCMB01S CCMB02S CCMB03S CCMB04S CCMB05S CCMB06S CCMB07S CCMB08S CCMB09S CCMB10S CCMB11S CCMB12S CCMB13S CCMB14S CCMB15S CCMB16S CCMB17S CCMB18S CCMB19S CCMB20S CCMB01WB CCMB02WB CCMB03WB CCMB04WB CCMB05WB CCMB06WB CCMB07WB CCMB08WB CCMB09WB CCMB10WB CCMB11WB CCMB12WB CCMB13WB CCMB14WB CCMB15WB CCMB16WB CCMB17WB CCMB18WB CCMB19WB CCMB20WB Factors Sample Type:Serum | Gender:M | Race:C Sample Type:Serum | Gender:F | Race:C Sample Type:Serum | Gender:M | Race:C Sample Type:Serum | Gender:M | Race:C Sample Type:Serum | Gender:M | Race:C Sample Type:Serum | Gender:F | Race:C Sample Type:Serum | Gender:F | Race:C Sample Type:Serum | Gender:F | Race:AA Sample Type:Serum | Gender:F | Race:C Sample Type:Serum | Gender:F | Race:C Sample Type:Serum | Gender:F | Race:C Sample Type:Serum | Gender:M | Race:C Sample Type:Serum | Gender:F | Race:AA Sample Type:Serum | Gender:M | Race:C Sample Type:Serum | Gender:M | Race:C Sample Type:Serum | Gender:F | Race:C Sample Type:Serum | Gender:M | Race:C Sample Type:Serum | Gender:M | Race:C Sample Type:Serum | Gender:M | Race:C Sample Type:Serum | Gender:F | Race:C Sample Type:Whole Blood | Gender:M | Race:C Sample Type:Whole Blood | Gender:F | Race:C Sample Type:Whole Blood | Gender:M | Race:C Sample Type:Whole Blood | Gender:M | Race:C Sample Type:Whole Blood | Gender:M | Race:C Sample Type:Whole Blood | Gender:F | Race:C Sample Type:Whole Blood | Gender:F | Race:C Sample Type:Whole Blood | Gender:F | Race:AA Sample Type:Whole Blood | Gender:F | Race:C Sample Type:Whole Blood | Gender:F | Race:C Sample Type:Whole Blood | Gender:F | Race:C Sample Type:Whole Blood | Gender:M | Race:C Sample Type:Whole Blood | Gender:F | Race:AA Sample Type:Whole Blood | Gender:M | Race:C Sample Type:Whole Blood | Gender:M | Race:C Sample Type:Whole Blood | Gender:F | Race:C Sample Type:Whole Blood | Gender:M | Race:C Sample Type:Whole Blood | Gender:M | Race:C Sample Type:Whole Blood | Gender:M | Race:C Sample Type:Whole Blood | Gender:F | Race:C 2-Hydroxybutyrate 37.8 25 22.8 12.1 17.8 11.7 17.9 26.7 16.7 18.5 23.1 18.4 25 29.9 17.3 20.7 87 11 10.6 25.5 9 10.8 5.9 3.8 7.2 9.3 15.3 21.8 11.1 9.2 29.2 15.8 12.4 24.4 6.3 23.6 64.6 4.7 5.2 2-Oxoisocaproate 12 8.5 10.2 10.8 8.1 8.1 8.1 11.2 10.4 10 11.5 7.2 8.5 16.8 10.8 9 24 10.3 10.8 3-Hydroxybutyrate 254.2 31.5 44.5 15.5 21.4 14.7 35.6 54.5 16.1 22.4 54.2 27.9 31.5 22.5 72.9 24.9 145.8 31.7 121.8 264.3 18.2 24.3 19.3 15.1 11.3 14.6 24.7 71.4 19.3 19.7 57 29.4 19.7 31.3 44 37.6 126.7 23.8 68.1 3-Hydroxyisobutyrate 12.8 10.5 8.7 10.6 6.3 7.8 6.1 7.4 8.1 4.2 13 4.2 10.5 11.6 11.2 8 28.7 3.8 10.9 3-Methyl-2-oxovalerate 10.9 11.6 11.2 11.2 11.6 10.2 10.2 11.7 10.5 8.4 8.5 8.2 11.6 16 10 11.9 22.6 10.5 12.1 Acetate 66.3 108.8 129.6 61.5 85.7 45.1 53.6 68.9 59.5 82.7 75.2 59.8 108.8 101.1 72 57.2 998.5 90.7 108.8 41.8 46.7 43.4 33.9 30 30.7 34 34.9 101.2 41.6 43.8 43.1 37.6 66.9 85.2 55.3 60.8 685.2 51 44.6 Acetoacetate 23.8 5 5.4 4 3.8 5.9 5.5 6.9 11.6 7.4 7.3 3.5 4.9 10 11 8.2 10.3 5.4 6.7 16.2 Adenosine 5 9.5 10.1 3 5.4 6.2 3.8 5.1 8.8 5.2 10 3.6 9.5 9.2 23.7 4.9 16.4 6 19.1 ADP 85.2 68.5 99.4 70.9 72.5 68.5 60.8 67.5 85.2 75.9 60.7 68.8 68.5 93.8 81.9 84.9 110.2 91.2 111.6 Alanine 167.9 255.6 325.9 234 271.1 229.3 291.7 223.2 254.9 207.2 255.8 217.8 255.6 444.9 336.3 289.6 377.7 275.1 445.5 142.1 225.6 207.7 194 209.1 172 207.2 183.5 216.9 254.6 152.4 244.1 144.3 224 390.3 139.6 281.2 323.6 154.7 238.7 AMP 53 32.4 45.6 25.8 26.8 27.3 26.3 28.9 58.4 70.4 36.4 77.2 32.4 75.6 81.5 44.3 96.9 96.1 123.9 Arginine 46 69.8 68.4 51.9 59.1 60.6 59.7 54 32 27 40.5 54.1 69.8 62.2 67.2 49.3 22.6 36.8 18.5 41 68.9 40 56.9 26.3 32.7 26 44.4 88.6 55.5 39.4 57.4 60.1 64.9 83.9 69.1 88.1 66.5 43.3 49.4 Asparagine 24.7 81.1 92.1 62.4 109.1 79.1 68 65.7 69.7 80.2 71.5 67.3 81.1 78.7 63 84.3 121.8 73.2 93.4 Aspartate 23.8 86.7 107.5 66.4 117.5 45.2 42.3 25.6 69 109.7 31.5 85.8 86.7 34.4 15.9 90.2 134.7 60 157.5 ATP 184.3 310.9 297.3 295.2 417.9 212.7 408.8 271.8 249.8 209.3 222.5 181.6 310.9 222.9 280.5 249.5 242 147 146.5 Betaine 9.8 45 32.1 39.2 42.4 19 41.5 18 45.5 29.7 103.6 28.8 45 14.7 25.1 41 39.5 59.2 17.4 15.2 16.2 17.6 14.9 25 20.2 6.3 24.8 21.2 16.6 25.6 31 12.6 22.3 40.2 26.5 23.9 16.1 24.9 18.1 Carnitine 19.9 21.5 19.5 30.1 19.9 13 18.9 20.9 19.2 10.2 18.8 16 21.5 30.1 24.3 23.1 21.9 22.7 21.4 15.7 19.2 19.3 10.6 18.4 15.3 11.2 14.6 22.6 20.8 13.8 17.5 19.2 25.4 30.1 20 27.4 12.4 14.8 16.1 Choline 8.1 13.9 15 11 28.7 9.2 13.6 9.5 11.7 9.9 15.2 6 13.9 14.8 20.2 12.4 14.5 13 14.8 3.9 5.9 6.7 4 3.1 4.8 2.1 4.3 7.7 5.3 5.1 6.3 3.8 9.1 9.9 8.7 8.7 4.6 6.1 5.1 Citrate 38.4 21.6 47.3 30.1 31.2 26.1 44.9 31.8 26.8 33 20.1 22.7 21.6 22.7 29.9 34.6 35.8 25.6 64.5 29.1 23 16.7 25 24.2 32.3 21.3 25.9 32 31.8 23.8 35.9 27 36.2 30.8 30.7 26.4 38.5 47.4 80.8 Creatine 190.4 176.7 216.3 49.9 155.4 143.9 120.3 159.9 82.6 116.6 212.1 164 176.7 167.2 188.8 95.6 221.1 194.5 248.6 24.4 19.3 27.9 9.8 7.8 28.1 19.2 13.3 23.8 11 21.1 57.9 33.2 18.1 22.9 19.1 14.7 47.5 10.4 16.1 Creatine phosphate 8.2 13.2 27.7 15.6 21.4 16.2 19.1 10.3 9.1 11.4 23.5 19.8 13.2 22.6 35.9 24.8 35.5 23.4 21.7 13.1 6.1 3.5 13.3 12.5 6 8.2 7.8 11.2 15.8 10.7 20.3 12.5 11.5 19 14.2 13.2 13.9 10.3 8.2 Creatinine 30.1 33.9 51.8 38.8 18.7 23.4 26.5 41 24.8 29.1 15.1 31.6 33.9 29.6 32 24.3 28.4 34.6 25.3 20.3 32.1 39.2 35.3 33.7 26.5 26.5 21.6 47.6 27.2 14 24.1 22.4 29.7 32.3 21.8 35 42.2 32.5 24.5 Ethanol 26.1 18.1 32.9 22.7 34.3 17.8 54.9 17 34.1 29.7 23.1 51.8 18.1 20.1 48.1 71.1 50 24.6 37 37.5 25.9 100.6 54.2 21.8 77.3 18.5 25.7 52.5 33.3 55 74.3 17.9 29.9 41 46.8 28.9 29.9 165.6 92.1 Formate 26.7 45.7 57.5 31.5 55.3 25.8 22.9 31.9 23.3 36.9 30.5 21.3 45.7 47.5 22.9 34.3 22.6 33.9 41.8 Glucose 1978.1 2341.3 2839.5 2219.6 2147.2 1977.8 3020.9 2209.3 1837 1887.3 2103.3 2224.2 2341.3 3313.6 3416.2 2498 2683.9 2492.2 3015 1980.6 2169 2502.4 1709.7 2039.4 1766.8 2100.4 2253 2438.2 2121.1 1634.8 2369.3 1877.6 2247.6 3471.9 2127.3 2699.2 2277.1 1725 1855.6 Glutamate 65.8 157.8 153.6 106.8 132.9 128.4 149.7 133.6 153 136.6 121.6 126.7 157.8 174.4 253 158.2 166.7 145.6 194.5 43.1 67.9 67 27.2 48.3 22 40.3 33.4 33.9 59.3 30.6 52.3 42.4 77.4 105.5 29 67 100.3 42.5 47.2 Glutamine 230.3 309.6 319.7 302.5 351.3 255.1 304.3 309.4 229.8 240.4 181.4 199.7 309.6 258.3 472.8 264.6 322.4 356.8 457.9 219.6 247.9 266.5 212 246.7 239.6 244.4 201.3 317.9 280.3 213.4 245.2 245 294.7 306.2 290.6 310.6 342.8 274.8 284.6 Glutathione 250 460.1 497.6 406.2 437.1 317.4 376.1 259.3 289 273.8 240.1 283.5 460.1 246.6 471.7 324.9 315.1 381.3 446.5 Glycerol 43.9 60.2 70.8 38.7 57.8 50.8 66 37.8 40.5 39.3 45.8 40.4 60.2 47.4 46.6 57.5 41.7 13.2 89.5 481.3 140.9 146.1 103.2 26.1 35.7 47 45.9 627.7 60.3 49.6 347.4 58.2 48.7 414 172 130.1 34.2 68.4 203.2 Glycine 234.9 287.1 290.8 221.5 320.2 159.2 281.2 199.8 184.8 254.7 145.3 204.9 287.1 230.1 495.4 246.9 271.6 381.8 497 120.1 232.1 161.6 116.9 149.1 121.9 84.7 140.3 128.6 293 154.3 62.1 90.7 116 147.3 172.3 138.5 156.1 128.5 163.7 Histidine 32.3 54.7 64.7 50.4 63 58.5 55.7 47 54.2 38.6 57.9 58.8 54.7 63.5 55.6 55.4 72.7 60.7 66.7 IMP 12.8 23.5 30.4 15 40.5 8.2 30.1 15.1 29.4 89.6 36.7 37.1 23.5 99 28.9 29.7 107.3 54.7 30.7 Isoleucine 50.9 38.1 45.4 35.6 39 27.7 36.1 26.4 37.8 40.9 39 37.7 38.1 60.9 55.1 42.6 131.1 39.7 46.4 39.3 33.5 29.8 21.7 20 24.4 20.8 17.2 23 26.5 18.3 34.8 21.1 36.5 34.4 13.6 34 94.8 21.5 24.4 Lactate 858.5 3021.9 1711.1 705.4 1096 588.3 2178.4 739.2 1849.9 1087.9 680 1253.4 3021.9 1295.2 1032.3 1648.1 1350.8 1018.5 1142 1052.4 1005.4 2684 1067.7 684.4 657.1 722.6 1533.8 922.6 1982.6 762.3 664.1 941.8 1216.8 1724.1 591.6 1692.8 1331.3 812.6 761.8 Leucine 81.8 75.3 77.8 77.3 85.2 56.6 74.1 59 74.8 70.4 84.7 52.9 75.3 118.5 90.4 78.6 210.9 92.5 79.8 49.2 40 39.5 29.6 37.9 29.5 30 34.2 32.6 47.1 29 40.6 32.4 47.7 62.6 23.5 52.2 110.7 37.8 35.9 Lysine 67.9 85.5 104.2 107.4 115 75.3 89.6 76.1 71.9 90.4 87.7 60.9 85.5 107.6 135.8 83 189.3 110 121.7 64.1 78.2 106.6 67.2 91.9 88.5 80.9 70.8 89.2 70.5 72 104.1 98.9 98.9 123.7 89.3 112.9 164.7 100.6 59.3 Malonate 12.8 17.4 24.1 15.9 21.8 15.3 7.9 20.1 16.1 17.8 13.6 11.1 17.4 9.6 22.5 16.2 25.1 51.1 21.3 Methionine 18.4 24.6 28.3 27.2 27.1 21 24.3 20.6 20 22.8 21.6 16.5 24.6 22.1 29.3 26.6 57.2 20 26.2 12.2 19.6 17.1 17.5 23.1 18.4 11.2 14.1 23 13.1 14.2 20.8 14.8 25.4 8.9 13.9 23.4 44.1 9.9 10.1 O-Acetylcarnitine 8.5 10.9 8.1 7.2 10.9 4.8 11.5 8.8 6.2 6.4 7.1 7.8 10.9 11.7 14.7 7.9 14.8 13.1 12.3 Ornithine 66.4 45.8 50.3 81.9 77.4 38.4 57.2 55.3 44 67.6 50.4 45.5 45.8 64.5 66.1 58.8 128.6 59.4 133.1 60.8 33.4 48.5 27 20.3 41.8 11 19.7 20.4 27.3 24.9 20.2 22.1 38.9 40.4 26.2 38.9 38.5 34.3 54.1 Phenylalanine 32.1 48.6 54.9 51.4 50.5 39.7 41.9 50.4 33.8 39.1 35.9 36.3 48.6 45.4 18.7 42.7 59 45.1 39.7 24.7 38.6 43.3 25.8 33.1 30 31.2 24.8 40.1 28.6 35.3 45.2 26.7 34.3 39.9 22.4 41.3 48.4 23.7 26.9 Proline 99.5 133 141.4 132.7 131.5 72.7 166.8 104.4 95.5 80.3 63.5 81.9 133 137.2 75.4 103.1 294.9 121 195.2 50.2 66 90.8 55.1 49.2 59.9 43.8 52.9 39.9 88.6 33.6 47.6 54.5 72 111.2 34.1 69.7 125.5 73.5 85.9 Propylene glycol 9.7 15.3 15.7 24.1 27.8 19 17.7 10.5 11.8 16.4 22.4 37.6 18.4 22.5 28.5 20.2 27.1 69.3 37.4 26.9 Pyruvate 6.8 9.9 9 1.5 6.5 3.3 3.9 2.2 35 31.1 23.4 38.3 9.9 55 36.1 25.5 41.6 27.6 47 Sarcosine 2 2.9 3 2.2 2.1 1.9 1.6 2.7 2.5 2 1.7 1.8 2.9 2 3.1 2.1 15.6 1.2 2.4 Serine 85.7 113.7 152.2 135.9 151.7 85.9 151.7 79.7 77.7 72.1 131.8 72.8 113.7 104.3 157 115.3 130.7 146.8 161.7 92.1 108.1 65.3 60.4 72.8 62.4 49.9 34.2 129.9 74.1 59 49.3 50.2 80 62.5 103.8 88.6 85.9 37.2 79.6 Succinate 4.9 8.3 9.6 5.7 8.7 5.8 7.2 4.7 7.1 7 1.7 7.1 8.3 7.1 10.5 6 5.5 5.9 6.5 Taurine 86.9 171.5 144.2 154.9 220.9 145.1 193.8 150.6 143.3 169.2 170.1 200.1 171.5 161.8 271.4 169.3 211 146.3 243.6 79.7 80 107.2 90.6 70.1 78.7 65.8 64.3 139.3 51.7 85.4 70.6 68.7 136.5 131.3 137.3 143.6 106.3 73.7 70 Threonine 65.2 103.5 116.9 85.9 129.5 54.1 89 75.8 63.3 40 39 68.5 103.5 46.6 80.6 71.1 187.9 59.2 134.6 60.7 123.9 91.7 98.4 133.7 133.3 76.5 72.3 144.2 80.2 79.9 68.2 95.3 91.3 97 108 112.8 203.9 97.6 55.3 Trimethylamine N-oxide 28 27.7 33.6 33.3 34.6 11 50.6 20.3 22.7 38 40.3 20.9 27.7 51.8 41.1 33 33.2 54.2 39.1 Tryptophan 26.4 24.1 36.8 24.9 27.5 28.1 21.4 30 18.6 19.4 16.4 25.2 24.1 40.8 31.4 32.8 65.5 29.8 26.5 18.5 26.2 26.3 17 30.5 16.5 21.6 20.7 20.8 24.1 23.8 17.6 31.4 26.6 47.8 17.9 44.1 65 15.5 11.4 Tyrosine 26.8 45.3 53.5 53.2 55.2 35.8 45.6 38.1 47.3 40.8 38.1 37.1 45.3 60 51.7 39.7 107.6 42.6 45.4 24 43 38.7 26.7 37 37.8 32.6 26.6 50.3 35.1 26.5 45.5 26.5 38 65.6 35.4 41.4 87.9 23.7 27.7 Valine 122.6 143.4 148.6 122.2 132.8 87.6 129.3 85.9 114.3 111.3 155.9 111.7 143.4 167 150 133.3 275.8 141.5 126.5 121.2 122.8 129.1 92.9 109.4 93.5 79.5 85.1 97.3 103.1 84 148.4 91.2 118.6 172.1 85.8 137.1 212.4 85.6 61.8 NMR_METABOLITE_DATA_END #METABOLITES METABOLITES_START metabolite_name KEGG ID 2-Hydroxybutyrate C05984 2-Oxoisocaproate C00233 3-Hydroxybutyrate C01089 3-Hydroxyisobutyrate C06001 3-Methyl-2-oxovalerate C03465 Acetate C00033 Acetoacetate C00164 Adenosine C00212 ADP C00008 Alanine C00041 AMP C00020 Arginine C00062 Asparagine C00152 Aspartate C00049 ATP C00002 Betaine C00719 Carnitine C00318 Choline C00114 Citrate C00158 Creatine C00300 Creatine phosphate C02305 Creatinine C00791 Ethanol C00469 Formate C00058 Glucose C00031 Glutamate C00217 Glutamine C00064 Glutathione C00051 Glycerol C00116 Glycine C00037 Histidine C00135 IMP C00130 Isoleucine C00407 Lactate C00186 Leucine C00123 Lysine C00047 Malonate C00383 Methionine C00073 O-Acetylcarnitine C02571 Ornithine C00077 Phenylalanine C00079 Proline C00148 Propylene glycol C00583 Pyruvate C00022 Sarcosine C00213 Serine C00065 Succinate C00042 Taurine C00245 Threonine C00188 Trimethylamine N-oxide C01104 Tryptophan C00078 Tyrosine C00082 Valine C00183 METABOLITES_END #END