#METABOLOMICS WORKBENCH montewillis_20170324_120951 DATATRACK_ID:867 STUDY_ID:ST000576 ANALYSIS_ID:AN000886 PROJECT_ID:PR000424 VERSION 1 CREATED_ON April 3, 2017, 9:53 am #PROJECT PR:PROJECT_TITLE Effects of the Kinase Inhibitor Sorafenib on Heart, Muscle, Liver, and Serum PR:PROJECT_TITLE Metabolism In Vivo using Non-targeted Metabolomics Analysis Mice PR:PROJECT_TYPE GC-MS non targeted analysis PR:PROJECT_SUMMARY Non targeted metabolomic analysis on samples from rats expressing human amylin. PR:INSTITUTE University of North Carolina PR:DEPARTMENT McAllister heart Institute, Department of Internal medicine PR:LABORATORY Multiple Centers PR:LAST_NAME Willis PR:FIRST_NAME Monte PR:ADDRESS 111 Mason Farm road, Chapel Hill, North Carolina, 27599-7126, USA PR:EMAIL monte_willis@med.unc.edu PR:PHONE 919-360-7599 PR:FUNDING_SOURCE NIH, Fondation Leducq #STUDY ST:STUDY_TITLE Effects of the Kinase Inhibitor Sorafenib on Heart Metabolism In Vivo using ST:STUDY_TITLE Non-targeted Metabolomics Analysis tissue). ST:STUDY_SUMMARY The human kinome consists of ~500 kinases, including 150 proposed as therapeutic ST:STUDY_SUMMARY targets. progression, cell death, differentiation, and survival. It is not ST:STUDY_SUMMARY surprising, then, that new tyrosine kinase inhibitors (TKIs) developed to treat ST:STUDY_SUMMARY cancer also exhibit cardiotoxicity, including sorafenib. We hypothesized that ST:STUDY_SUMMARY sorafenib cardiotoxicity is related to its deleterious effects on specific ST:STUDY_SUMMARY cardiac metabolic pathways given the critical role of TKs in cardiac metabolism. ST:STUDY_SUMMARY FVB/N mice (10/group) were challenged with sorafenib or vehicle control daily ST:STUDY_SUMMARY for two weeks. Echocardiographic assessment of the heart identified systolic ST:STUDY_SUMMARY dysfunction consistent with cardiotoxicity compared to vehicle treated controls. ST:STUDY_SUMMARY Cardiac, skeletal muscle, liver, and serum were flash frozen and prepped for ST:STUDY_SUMMARY non-targeted GC-MS metabolomics analysis. Compared to vehicle treated controls, ST:STUDY_SUMMARY sorafenib-treated hearts exhibited significant alterations in 11 metabolites, ST:STUDY_SUMMARY including markedly altered taurine/hypotaurine metabolism by pathway enrichment ST:STUDY_SUMMARY analysis (25-fold enrichment). These studies identify sorafenib-induced ST:STUDY_SUMMARY alterations in cardiac alanine and taurine/hypotaurine metabolic. Interventions ST:STUDY_SUMMARY to rescue or prevent sorafenib-related cardiotoxicity warrant consideration of ST:STUDY_SUMMARY therapies targeting the taurine/hypotaurine deficiency identified in the current ST:STUDY_SUMMARY study. ST:INSTITUTE University of North Carolina ST:DEPARTMENT McAllister heart Institute, Department of Internal medicine ST:LABORATORY Multiple Centers ST:LAST_NAME Willis ST:FIRST_NAME Monte ST:ADDRESS 111 Mason Farm road, Chapel Hill, North Carolina, 27599-7126, USA ST:EMAIL monte_willis@med.unc.edu ST:PHONE 919-360-7599 ST:STUDY_COMMENTS Heart, Liver, Skeletal Muscle (Gastrocnemius), Serum #SUBJECT SU:SUBJECT_TYPE Animal 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 - PBS Ctl 1 Vehicle (PBS) Control Treatment:Vehicle (PBS) Control Treatment FVB Strain Mus musculus=FVB Strain Mus musculus SUBJECT_SAMPLE_FACTORS - PBS Ctl 2 Vehicle (PBS) Control Treatment:Vehicle (PBS) Control Treatment FVB Strain Mus musculus=FVB Strain Mus musculus SUBJECT_SAMPLE_FACTORS - PBS Ctl 3 Vehicle (PBS) Control Treatment:Vehicle (PBS) Control Treatment FVB Strain Mus musculus=FVB Strain Mus musculus SUBJECT_SAMPLE_FACTORS - PBS Ctl 4 Vehicle (PBS) Control Treatment:Vehicle (PBS) Control Treatment FVB Strain Mus musculus=FVB Strain Mus musculus SUBJECT_SAMPLE_FACTORS - PBS Ctl 5 Vehicle (PBS) Control Treatment:Vehicle (PBS) Control Treatment FVB Strain Mus musculus=FVB Strain Mus musculus SUBJECT_SAMPLE_FACTORS - PBS Ctl 6 Vehicle (PBS) Control Treatment:Vehicle (PBS) Control Treatment FVB Strain Mus musculus=FVB Strain Mus musculus SUBJECT_SAMPLE_FACTORS - PBS Ctl 7 Vehicle (PBS) Control Treatment:Vehicle (PBS) Control Treatment FVB Strain Mus musculus=FVB Strain Mus musculus SUBJECT_SAMPLE_FACTORS - PBS Ctl 8 Vehicle (PBS) Control Treatment:Vehicle (PBS) Control Treatment FVB Strain Mus musculus=FVB Strain Mus musculus SUBJECT_SAMPLE_FACTORS - PBS Ctl 9 Vehicle (PBS) Control Treatment:Vehicle (PBS) Control Treatment FVB Strain Mus musculus=FVB Strain Mus musculus SUBJECT_SAMPLE_FACTORS - PBS Ctl 10 Vehicle (PBS) Control Treatment:Vehicle (PBS) Control Treatment FVB Strain Mus musculus=FVB Strain Mus musculus SUBJECT_SAMPLE_FACTORS - 30mg/kg Sor 1 Vehicle (PBS) Control Treatment:30 mg/kg Sorafenib Treatment FVB Strain Mus musculus=FVB Strain Mus musculus SUBJECT_SAMPLE_FACTORS - 30mg/kg Sor 2 Vehicle (PBS) Control Treatment:30 mg/kg Sorafenib Treatment FVB Strain Mus musculus=FVB Strain Mus musculus SUBJECT_SAMPLE_FACTORS - 30mg/kg Sor 3 Vehicle (PBS) Control Treatment:30 mg/kg Sorafenib Treatment FVB Strain Mus musculus=FVB Strain Mus musculus SUBJECT_SAMPLE_FACTORS - 30mg/kg Sor 4 Vehicle (PBS) Control Treatment:30 mg/kg Sorafenib Treatment FVB Strain Mus musculus=FVB Strain Mus musculus SUBJECT_SAMPLE_FACTORS - 30mg/kg Sor 5 Vehicle (PBS) Control Treatment:30 mg/kg Sorafenib Treatment FVB Strain Mus musculus=FVB Strain Mus musculus SUBJECT_SAMPLE_FACTORS - 30mg/kg Sor 6 Vehicle (PBS) Control Treatment:30 mg/kg Sorafenib Treatment FVB Strain Mus musculus=FVB Strain Mus musculus SUBJECT_SAMPLE_FACTORS - 30mg/kg Sor 7 Vehicle (PBS) Control Treatment:30 mg/kg Sorafenib Treatment FVB Strain Mus musculus=FVB Strain Mus musculus SUBJECT_SAMPLE_FACTORS - 30mg/kg Sor 8 Vehicle (PBS) Control Treatment:30 mg/kg Sorafenib Treatment FVB Strain Mus musculus=FVB Strain Mus musculus SUBJECT_SAMPLE_FACTORS - 30mg/kg Sor 9 Vehicle (PBS) Control Treatment:30 mg/kg Sorafenib Treatment FVB Strain Mus musculus=FVB Strain Mus musculus SUBJECT_SAMPLE_FACTORS - 30mg/kg Sor 10 Vehicle (PBS) Control Treatment:30 mg/kg Sorafenib Treatment FVB Strain Mus musculus=FVB Strain Mus musculus #COLLECTION CO:COLLECTION_SUMMARY Cardiac tissue was harvested and flash frozen in a liquid nitrogen cooled CO:COLLECTION_SUMMARY biopress #TREATMENT TR:TREATMENT_SUMMARY Fraction of cardiac tissue weighed (25äóñ50 mg wet weight), then the finely TR:TREATMENT_SUMMARY cut up tissue quickly added to fresh pre-made buffer (50 % acetyl-nitrile, 50 % TR:TREATMENT_SUMMARY water, 0.3% formic acid) at a standard concentration of 25 mg/475 microlieters TR:TREATMENT_SUMMARY (mcl) buffer then fully homogenized on ice for 20 seconds and placed on dry TR:TREATMENT_SUMMARY ice/stored at - 80C #SAMPLEPREP SP:SAMPLEPREP_SUMMARY The samples were crash deprotonized by methanol precipitation and spiked with SP:SAMPLEPREP_SUMMARY D27-deuterated myristic acid (D27-C14:0) as an internal standard for SP:SAMPLEPREP_SUMMARY retention-time locking and dried. The trimethylsilyl-D27-C14:0 standard SP:SAMPLEPREP_SUMMARY retention time (RT) was set at 16.727 min. Reactive carbonyls were stabilized at SP:SAMPLEPREP_SUMMARY 50C with methoxyamine hydrochloride in dry pyridine. Metabolites were made SP:SAMPLEPREP_SUMMARY volatile with TMS groups using N-methyl-N-(trimethylsilyl) trifluoroacetamide or SP:SAMPLEPREP_SUMMARY MSTFA with catalytic trimethylchlorosilane at 50C. #CHROMATOGRAPHY CH:CHROMATOGRAPHY_SUMMARY GC/MS methods follow previous studies using a 6890 N GC connected to a 5975 CH:CHROMATOGRAPHY_SUMMARY Inert single quadrupole MS (Agilent Technologies, Santa Clara, CA) (Bonikos et CH:CHROMATOGRAPHY_SUMMARY al. 1975; Fiehn 2008; Kind et al. 2009). The two wall-coated, open-tubular GC CH:CHROMATOGRAPHY_SUMMARY columns connected in series are both from J&W/Agilent (part 122äóñ5512), CH:CHROMATOGRAPHY_SUMMARY DB5-MS, 15 meters in length, 0.25 mm in diameter, with an 0.25-l m luminal film. CH:CHROMATOGRAPHY_SUMMARY Positive ions generated with conventional electron-ionization at 70 eV are CH:CHROMATOGRAPHY_SUMMARY scanned broadly from 600 to 50 m/z in the detector throughout the 45 min cycle CH:CHROMATOGRAPHY_SUMMARY time. CH:CHROMATOGRAPHY_TYPE GC CH:INSTRUMENT_NAME Agilent 6890N CH:COLUMN_NAME Agilent DB5-MS (15m × 0.25mm, 0.25um) #ANALYSIS AN:ANALYSIS_TYPE MS #MS MS:MS_COMMENTS - MS:INSTRUMENT_NAME Agilent 5975 MS:INSTRUMENT_TYPE Single quadrupole MS:MS_TYPE EI MS:ION_MODE POSITIVE #MS_METABOLITE_DATA MS_METABOLITE_DATA:UNITS Peak values (Log transformed) MS_METABOLITE_DATA_START Samples PBS Ctl 1 PBS Ctl 2 PBS Ctl 3 PBS Ctl 4 PBS Ctl 5 PBS Ctl 6 PBS Ctl 7 PBS Ctl 8 PBS Ctl 9 PBS Ctl 10 30mg/kg Sor 1 30mg/kg Sor 2 30mg/kg Sor 3 30mg/kg Sor 4 30mg/kg Sor 5 30mg/kg Sor 6 30mg/kg Sor 7 30mg/kg Sor 8 30mg/kg Sor 9 30mg/kg Sor 10 Factors Vehicle (PBS) Control Treatment:Vehicle (PBS) Control Treatment Vehicle (PBS) Control Treatment:Vehicle (PBS) Control Treatment Vehicle (PBS) Control Treatment:Vehicle (PBS) Control Treatment Vehicle (PBS) Control Treatment:Vehicle (PBS) Control Treatment Vehicle (PBS) Control Treatment:Vehicle (PBS) Control Treatment Vehicle (PBS) Control Treatment:Vehicle (PBS) Control Treatment Vehicle (PBS) Control Treatment:Vehicle (PBS) Control Treatment Vehicle (PBS) Control Treatment:Vehicle (PBS) Control Treatment Vehicle (PBS) Control Treatment:Vehicle (PBS) Control Treatment Vehicle (PBS) Control Treatment:Vehicle (PBS) Control Treatment Vehicle (PBS) Control Treatment:30 mg/kg Sorafenib Treatment Vehicle (PBS) Control Treatment:30 mg/kg Sorafenib Treatment Vehicle (PBS) Control Treatment:30 mg/kg Sorafenib Treatment Vehicle (PBS) Control Treatment:30 mg/kg Sorafenib Treatment Vehicle (PBS) Control Treatment:30 mg/kg Sorafenib Treatment Vehicle (PBS) Control Treatment:30 mg/kg Sorafenib Treatment Vehicle (PBS) Control Treatment:30 mg/kg Sorafenib Treatment Vehicle (PBS) Control Treatment:30 mg/kg Sorafenib Treatment Vehicle (PBS) Control Treatment:30 mg/kg Sorafenib Treatment Vehicle (PBS) Control Treatment:30 mg/kg Sorafenib Treatment 1,5-Anhydroglucitol 18.26 18.57 18.67 18.89 18.33 18.14 19.49 18.62 18.39 18.02 18.5 15.44 18.55 18.04 16.77 18.55 19.18 19.29 16.83 19 2-Aminoadipic acid 21.69 22.01 22.3 21.43 21.42 21.64 21.9 22.03 20.8 20.48 22.11 19.02 22.26 21.07 21.31 21.84 22.29 22.29 19.16 22.34 2-Hydroxypyridine 18.08 18.72 18.67 18.24 17.73 18.13 18.23 19.1 18.03 18.67 17.98 15.75 18.53 17.34 17.46 18.04 18.16 18.19 17.53 18.81 5'-Deoxy-5'-(methylthio) adenosine 14.55 13.16 14.45 13.42 13.55 13.98 15.11 15.65 15.54 14.55 14.29 12.9 15.19 14.67 14.98 15.3 6-Hydroxynicotinic acid 17.93 15.71 17.3 17.63 17.77 17.98 18.68 17.72 18.95 18.13 16.72 15.57 17.06 14.41 17.98 16.63 17.68 18.7 17.55 16.86 Adenine 18.59 18.98 19.38 18.56 18.48 18.71 19.21 18.94 17.38 17.95 18.98 16.19 19.11 17.8 18.09 18.68 19.37 19.66 16.53 19.44 Adenosine-5-monophosphate 24.3 23.8 24.58 23.17 24.27 23.97 23.72 23.34 22.71 22.38 22.27 19.62 23.43 20.98 22.62 23.06 24.49 23.56 20.74 23.45 Adenosine/Inosine 20.85 19.99 21.33 17.62 20.07 19.08 17.86 18.8 20.21 16.97 19.9 17.29 19.44 16.99 19.61 17.34 20.21 19.58 17.85 17.68 Alanine 21.37 21.62 22.14 21.48 21.32 21.67 22 21.64 21.07 20.1 22.27 18.68 21.62 21.03 20.74 21.75 21.83 21.95 19.57 21.63 alpha-Monopalmitin 23.55 23.7 24.14 23.27 23.44 23.45 23.91 24.5 23.83 23.44 24.01 21.74 24.11 22.96 22.95 23.63 24.11 24.28 22.4 24.43 alpha-Monostearin 26.22 26.62 26.72 26.02 26.2 26.21 26.54 26.02 26.56 26.26 26.82 24.81 26.73 25.87 25.82 26.39 26.87 26.7 25.44 27.09 alpha-Tocopherol 16.15 15.63 16.26 15.69 15.9 16.32 16.47 14.58 12.74 12 16.47 15.75 16.2 15.72 16.21 16.49 16.9 11.89 14.64 Arachidic acid/ 1-Heneicosanol 18.01 17.71 18.19 18.01 16.63 17.38 18.06 17.58 16.38 15.45 17.47 13.48 17.58 17.45 17.19 17.44 18.4 18.56 13.87 18.16 Arachidonic acid (also Eicosapentaenoic acid) 19.84 18.28 19.18 19.18 19.19 19.16 19.03 18.66 20.1 19.06 18.42 16.86 19.44 15.35 18.75 17.77 19.12 19.83 18.74 18.7 Aspartic acid 20.88 22.1 22.54 20.53 21.35 21.69 22.37 22.22 22.27 20.62 21.95 18.69 22.53 21.23 22.36 22.61 23.41 22.36 21.66 22.66 Benzoic acid 19.61 20.52 20.12 19.73 19.46 19.59 19.66 19.89 19.02 18.33 19.72 17.44 19.97 19.6 18.93 19.8 19.7 19.85 16.98 20.06 beta-Hydroxybutyric acid 19.58 20.23 20.49 19.26 19.6 19.92 18.93 19.63 19.27 18.03 19.46 16.27 19.14 17.76 20.19 20.54 19.08 19.23 18.56 20.54 beta-Monopalmitin 17.95 16.51 17.64 17.3 17.48 17.73 17.88 18.03 18.06 17.64 17.21 14.42 17.53 16.76 16.64 17.13 18.11 18.46 15.55 18.12 beta-Monostearin 20.81 20.66 21.25 20.47 20.64 20.53 21.13 21.52 21.06 20.64 20.96 18.23 21.17 20.05 20.04 20.64 21.51 21.44 19.17 21.52 beta-Sitosterol 17.11 18 17.95 15.35 16.3 17.75 18.21 16.21 15.24 17.41 12.2 14.74 16.04 17.51 18.15 17.93 17.41 C10 hydrocarbon 17.51 17.83 17.88 17.62 17.47 17.64 17.76 17.56 17.72 17.79 16.86 18.53 17.58 17.41 17.68 18.73 18.71 16.35 18.43 C11 hydrocarbon 15.83 16.76 15.68 15.84 17.52 17.6 15.58 17.44 15.03 15.83 15.64 15.5 15.34 15.56 17.35 17.86 16.11 16.16 15.55 15.54 C12 hydrocarbon 16.25 16.38 16.8 16.33 16.21 16.31 16.28 16.6 15.94 15.22 16.58 14.15 16.32 16.12 16.38 16.15 16.61 16.42 13.6 16.97 C13 hydrocarbon 18.36 18.87 18.86 18.11 18.31 18.27 18.33 18.26 17.33 17.12 18.37 16.36 18.35 18.28 17.88 18.48 18.71 18.85 15.85 18.78 C15 hydrocarbon 18.32 18.08 18.82 17.87 18.09 18.04 17.96 18.13 17.19 16.79 18.21 16.23 18.11 18.24 17.53 18.22 18.37 18.57 15.73 18.33 C17 hydrocarbon 16.77 17.96 16.97 17.13 17.32 17.48 17.27 17.04 16.63 16.07 17.89 15.76 17.21 17.07 16.83 16.6 16.76 17 15.06 16.89 C21 Hydrocarbon 17.11 17.24 17.54 16.39 17.07 17.02 16.78 16.55 15.62 15.11 16.78 14.26 16.67 16.95 16.21 16.64 17.2 17.26 13.88 17.3 Campesterol 20.34 20.14 21.07 19.68 19.76 20.11 20.55 20.32 19.69 18.93 20.55 16.73 20.88 18.59 19.19 20.48 20.82 20.53 18.09 20.66 Cholesterol 25.3 25.37 26.08 25.13 25 25.29 25.69 25.62 25.02 24.54 25.53 22.89 25.8 23.78 24.78 25.31 25.92 26.08 23.87 25.97 Citric acid/isocitric acid 21.76 21.58 21.95 22.36 21.73 22.38 22.22 21.97 20.66 21.07 21.83 18.06 21.21 21.74 20.88 22.46 22.01 22.74 20.1 22.89 Creatinine 22.26 23.08 23.42 22.21 21.86 22.11 23.1 22.94 19.75 21.54 23.26 20.81 23.84 22.53 22.88 22.8 23.86 23.94 21.66 23.81 Dehydroalanine (possibly from cysteine) 17.91 17.66 18.08 17.48 17.78 17.78 17.78 17.27 17.64 15.25 17.65 13.79 16.6 14.63 16.42 16.9 17.91 17.8 11 16.37 Dehydroascorbic acid (possibly alpha-ketoglutarate) 20.23 20.27 20.93 19.9 19.95 20.28 20.39 20.48 19.11 19.46 20.48 17.96 20.64 19.27 20 20.17 20.74 21.04 18.4 20.79 deuterated Myristic Acid (RTL std) 22.92 23.23 23.63 22.64 22.59 22.75 23.26 23.36 22.4 21.99 23.21 20.81 23.54 22.2 22.33 22.96 23.51 23.58 20.97 23.58 Disaccharide 16.34 15.93 16.93 16.56 15.83 16.61 15.92 16.43 16.4 17.23 16.11 14.5 15.49 16.39 16.8 16.89 13.1 16.26 Docosahexaenoic acid 22.11 20.56 21.16 21.61 21.69 21.56 21.69 21.35 22.27 21.18 20.64 19.47 21.77 18.8 21.19 19.95 21.74 22.34 21.03 21.22 Ethanolamine 16.59 15.97 15.93 16.49 16.25 16.39 16.18 17 18.39 17.79 15.98 14.53 15.22 14.35 13.91 15.15 15.68 15.69 14.41 15.38 Fructose or similar ketohexose 16.27 14.24 15.96 15.62 14.78 15.06 16.64 16.07 14.49 13.23 17.42 13.91 14.43 14.5 14.74 17.06 17.39 15.91 Fumaric acid 20.9 21.28 20.97 20.17 20.31 21.06 20.7 19.4 17.96 16.63 20.67 15.66 19.31 17.87 18.93 20.77 20.86 20.31 14.68 17.96 Glucose and other aldohexoses 24.55 25.03 23.92 24.49 22.2 24.51 25.64 24.87 23.69 23.9 24.8 21.93 24.86 23.62 22.61 24.49 25.98 25.45 21.46 25.43 Glucose-6-phosphate or similar 18.79 18.75 17.24 19.51 17.41 18.31 20.26 19.68 19.74 18.48 19.85 16.54 19.01 16.83 19.24 16.72 19.57 19.48 17.39 19.36 Glutamic acid 23.39 24.83 24.38 23.51 23.42 24.38 24.86 24.94 23.6 22.93 24.55 21.51 23.98 23.42 23.58 24.75 25.11 25.17 22.52 24.83 Glutamine 19 23.75 23.03 18.78 19.74 20.99 20.59 22.16 17.55 16.12 23.99 21.9 23.64 21.8 18.54 22.91 22.62 23.23 22.23 23.79 Glycerol 1-phosphate 22.49 22.14 22.52 21.72 22.31 22.25 22.39 22.07 22.23 21.2 21.97 19.78 21.77 20.61 21.81 21.15 22.63 22.66 20.07 21.71 Glycine 19.26 21.53 20.8 18.95 19.49 19.88 20.45 20.33 20.81 18.21 19.98 17.69 19.69 19.15 18.65 20.5 20.81 20.34 17.66 20.36 Heptadecanoic acid/Octadecanol 18.67 17.95 18.49 18 18.12 17.88 18.77 18.3 18.03 17.45 18.14 15.42 18.07 17.52 17.54 17.83 18.87 19.03 15.69 18.4 Hexitols 15.22 14.99 17.1 15.11 15.36 14.06 16.66 15.6 15.95 14.38 18.22 16 14.48 14.53 14.85 18.23 16.5 15.69 Homoserine 16.62 16.49 16.95 16.17 16.22 16.27 16.8 16.78 15.65 15.46 16.48 14.24 16.37 16.39 15.8 16.23 16.88 16.96 14.4 16.72 Hypotaurine 20.18 20.82 20.24 19.93 20.06 20.3 20.55 19.8 18.27 18.58 18.8 15.89 18.19 17.55 18.29 18.98 19.28 19.39 16.54 18.75 Hypoxanthine 15.47 14.8 16 13.38 14.89 14.46 13.18 12.68 14.62 14.95 12.51 14.05 14.16 14.64 14.85 13.68 11.19 Inosine/Adenosine 18.49 17.22 19.16 15.14 18.61 17.69 15.77 13.75 18.43 16.73 15.18 16.64 14.81 16.36 17.43 16.19 15.33 Isoleucine/Leucine 16.76 17.19 14.72 14.66 16.03 15.63 16.55 14.55 16.28 16.72 15.53 14.82 16.77 16.66 17.02 12.28 17.2 Lactic acid 25.3 25.26 26.13 24.35 24.93 24.74 24.94 24.92 24.68 23.53 25.83 21.97 25.36 23.77 25.18 24.57 25.96 25.44 23.25 24.96 Linoleic acid 20.46 19.73 21.53 20.13 20.47 20.61 20.67 20.39 20.98 20.07 20 17.32 20.68 17.95 19.81 19.31 20.57 21.37 19.6 20.6 Lysine 21.5 21.91 22.09 20.9 20.92 21.59 21.62 22.53 20.32 19.45 22.3 20.17 21.52 21.02 19.93 22.09 22.13 22.09 19.1 22.37 Malic acid 22.78 23.56 23.23 22.56 22.67 22.54 22.66 22.94 21.9 21.48 23.59 19.82 23.18 22.15 22.9 23.1 23.63 23.11 20.85 23.3 Methionine 15.2 17.4 16.94 14.71 14.91 15.58 17.54 17.11 15.56 14.77 16.91 13.35 16.72 15.11 15.49 16.26 17.89 17.77 15.5 17.42 MSTFA artifact 18.74 19.7 19.43 19.05 18.76 19.16 18.64 19.46 18.7 18.95 18.42 15.87 18.07 17.97 17.36 18.3 18.49 18.1 15.39 18.54 Myoinositol 23.21 23.74 23.76 23.02 22.88 23.46 23.5 22.93 22.65 22.24 22.99 20.99 23.52 22.14 22.73 23.5 23.48 23.88 21.31 23.72 Myoinositol-2-phosphate 18.75 16.4 17.72 18.51 18.58 18.38 18.72 17.26 18.82 17.55 16.14 14.25 16.56 14.05 17.07 15.42 17.79 18.02 12.34 16.91 Myristic acid or Pentadecanol 19.42 19.08 19.86 18.74 18.88 18.76 19.47 19.06 18.37 17.87 18.92 16.62 19.07 18.65 18.85 18.88 19.7 19.95 16.53 19.01 Nicotinamide 17.52 17.65 18.02 16.93 17.19 17.53 17.11 17.26 16.57 16.25 18.32 15.91 18.77 15.77 16.96 16.88 18.24 17.75 17.13 O-Methylphosphate 17.16 15.78 16.66 18.01 16.83 17.32 18.39 18.78 17.76 17.78 16.52 16.29 17.81 17.16 16.93 17.11 18.1 16.61 18.57 O-Phosphocolamine 21.2 21.28 20.8 21.11 21.09 21.54 20.87 20.8 21.08 20.04 18.7 16.08 17.03 17.34 16.76 19.43 18.58 17.92 14.73 17.75 Oleic acid 19 18.48 20.24 18.64 18.8 19.15 18.74 19.23 18.09 19.2 18.2 16.6 19.48 15.65 18.65 17.63 17.95 19.7 18.59 19.34 Palmitic acid 23.67 23.78 24.27 23.21 23.89 23.64 23.72 23.97 23.84 23.28 23.98 21.6 23.96 23.47 23 23.61 23.93 24 22.27 24.09 Pantothenic acid 19.75 19.62 20.02 19.33 19.23 19.58 20.12 20.03 18.73 19.24 19.63 15.85 19.36 18.19 18.83 19.68 20.2 20.43 17.3 20.46 Pentadecanoic acid/Hexadecanol 17.74 18.3 17.66 17.77 16.42 17.8 17.99 16.71 16.91 17.56 16.37 16.15 17.93 19.11 18.63 15.21 18.42 Pentitols 16.12 14.84 17.17 16.7 16.94 17.61 18.2 17.48 17.81 16.58 17.43 17.59 15.8 15.62 16.06 16.93 18.5 15.51 17.99 Phenol 20.36 20.54 19.99 18.38 17.28 17.08 17.55 17.89 16.49 16.73 21.05 20.45 20.76 19.21 17.82 17.73 17.99 18.02 18.04 Phenylalanine 15.21 18.42 18.45 16.39 16.11 17.09 18.25 18.67 17.75 16.76 18.11 15.72 18.34 16.98 17.02 17.88 19.1 19.09 16.6 18.59 Phosphoric acid 26.66 26.93 27.01 26.14 26.66 26.6 26.45 26.36 25.91 25.45 26.92 24.55 26.7 25.85 26.17 26.57 26.9 26.69 24.66 26.43 Prunetin or similar isoflavone 12.98 13.23 14.1 12.52 13.16 12.99 13.7 14.3 13.97 13.12 13.4 13.77 12.18 11.58 13 13.81 13.83 14.66 Pyrophosphate 19.73 18.38 20.87 21.15 19.27 20.4 22.44 22.13 18.36 19.47 18.75 13.52 19.81 20.22 18.75 21.67 21.13 22.31 15.46 22.24 Pyruvic acid 15.98 16.69 16.18 16.07 16.24 16.33 15.54 15.8 15.92 14.42 15.83 15.86 15.82 15.56 14.78 16.13 15.76 13.62 16.31 Serine 19.41 21.67 21.27 18.74 19.71 20.41 21.05 21.33 17.11 18.17 21.66 14.48 21.33 19.94 19.73 21.49 21.82 22.32 17.97 22.2 Siloxanes 15.72 15.54 16.01 14.54 15.16 15.11 15.58 15.71 14.79 13.72 14.69 15.21 14.74 15.22 13.6 14.37 13.45 16.18 Spermidine 17.13 18.86 18.72 17 17.64 16.52 17.19 18.37 16.45 17.27 19.11 17.56 17.79 16.89 18.86 18.89 18.61 18.52 Squalene 19.95 19.51 19.71 19.62 19.27 19.63 19.87 19.64 18.8 17.98 19.72 15.19 19.39 17.94 19.07 19.41 20.23 20.55 17.56 20.22 Stearamide 17.97 13.3 16.68 17.24 18.34 16.49 16.75 17.2 18.93 19.11 15.2 13.17 15.97 16.37 15.46 15.4 17.7 16.78 15.93 Stearic acid 24.91 24.5 24.91 24.39 24.71 24.6 24.98 24.73 24.58 24.02 24.65 22.49 24.66 24.23 24.07 24.37 25.13 25.16 23 24.77 Succinic acid 22.71 22.38 23.32 22.14 22.51 22.58 22.44 22.1 22.49 20.9 22.51 18.96 21.9 21.11 22.45 22.2 22.64 22.58 20.74 22.48 Taurine 26.44 25.02 25.23 26.59 26.33 26.04 26.5 25.95 24.54 24.97 25.2 23.97 24.17 25.31 26.07 25.22 25.53 26.08 24.53 22.74 Threonine 19.62 20.98 21.1 18.79 18.97 19.56 20.75 20.92 18.59 17.5 20.46 20.61 19.74 19.05 20.46 21.64 21.3 17.47 21.39 Tyrosine 18.12 17.86 19.23 17.59 16.64 17.85 18.95 19.68 16.45 15.48 18.03 15.15 18.29 17.04 16.05 17.92 19.51 19.06 16.09 19.03 Urea 23.83 23.82 21.73 23.37 23.05 23.51 24.56 24.13 23.16 22.25 24.02 20.58 23.86 22.85 23.08 23.42 24.75 24.06 21.24 23.51 Valine 17.51 18.93 19.08 17.55 16.56 18.11 18.45 19 17.06 14.92 18.24 18.39 17.87 15.79 18.68 18.95 18.97 13.74 19.19 MS_METABOLITE_DATA_END #METABOLITES METABOLITES_START metabolite_name 1,5-Anhydroglucitol 2-Aminoadipic acid 2-Hydroxypyridine 5'-Deoxy-5'-(methylthio) adenosine 6-Hydroxynicotinic acid Adenine Adenosine-5-monophosphate Adenosine/Inosine Alanine alpha-Monopalmitin alpha-Monostearin alpha-Tocopherol Arachidic acid/ 1-Heneicosanol Arachidonic acid (also Eicosapentaenoic acid) Aspartic acid Benzoic acid beta-Hydroxybutyric acid beta-Monopalmitin beta-Monostearin beta-Sitosterol C10 hydrocarbon C11 hydrocarbon C12 hydrocarbon C13 hydrocarbon C15 hydrocarbon C17 hydrocarbon C21 Hydrocarbon Campesterol Cholesterol Citric acid/isocitric acid Creatinine Dehydroalanine (possibly from cysteine) Dehydroascorbic acid (possibly alpha-ketoglutarate) deuterated Myristic Acid (RTL std) Disaccharide Docosahexaenoic acid Ethanolamine Fructose or similar ketohexose Fumaric acid Glucose and other aldohexoses Glucose-6-phosphate or similar Glutamic acid Glutamine Glycerol 1-phosphate Glycine Heptadecanoic acid/Octadecanol Hexitols Homoserine Hypotaurine Hypoxanthine Inosine/Adenosine Isoleucine/Leucine Lactic acid Linoleic acid Lysine Malic acid Methionine MSTFA artifact Myoinositol Myoinositol-2-phosphate Myristic acid or Pentadecanol Nicotinamide O-Methylphosphate O-Phosphocolamine Oleic acid Palmitic acid Pantothenic acid Pentadecanoic acid/Hexadecanol Pentitols Phenol Phenylalanine Phosphoric acid Prunetin or similar isoflavone Pyrophosphate Pyruvic acid Serine Siloxanes Spermidine Squalene Stearamide Stearic acid Succinic acid Taurine Threonine Tyrosine Urea Valine METABOLITES_END #END