#METABOLOMICS WORKBENCH nemkovt_20220112_091932 DATATRACK_ID:3033 STUDY_ID:ST002058 ANALYSIS_ID:AN003350 PROJECT_ID:PR001303
VERSION             	1
CREATED_ON             	January 12, 2022, 12:50 pm
#PROJECT
PR:PROJECT_TITLE                 	Unchecked oxidative stress is an insurmountable barrier for tumour cells that
PR:PROJECT_TITLE                 	disseminate to skeletal muscle
PR:PROJECT_SUMMARY               	Skeletal muscle has been recognized as an inhospitable site for disseminated
PR:PROJECT_SUMMARY               	tumour cells (DTCs) for decades, yet its antimetastatic nature has eluded a
PR:PROJECT_SUMMARY               	thorough mechanistic description. Here, we show that DTCs traffic to and persist
PR:PROJECT_SUMMARY               	within skeletal muscle, raising the question as to how this tissue suppresses
PR:PROJECT_SUMMARY               	colonization. We employed mouse and organotypic culture models along with
PR:PROJECT_SUMMARY               	metabolomic profiling and ultimately find that oxidative stress is a principal
PR:PROJECT_SUMMARY               	suppressor of DTC proliferation in skeletal muscle. DTCs bypassed this oxidative
PR:PROJECT_SUMMARY               	constraint upon colonization of more fertile sites, but were unable to in
PR:PROJECT_SUMMARY               	muscle. Functional studies demonstrated that disrupting redox homeostasis via
PR:PROJECT_SUMMARY               	chemogenetic induction of reactive oxygen species slowed proliferation in lung.
PR:PROJECT_SUMMARY               	Conversely, enhancing antioxidant potential of tumour cells via ectopic
PR:PROJECT_SUMMARY               	expression of catalase allowed robust colonization of skeletal muscle. These
PR:PROJECT_SUMMARY               	findings reveal a profound metabolic bottleneck imposed on DTCs and sustained by
PR:PROJECT_SUMMARY               	skeletal muscle. Understanding this biology could reveal novel DTC
PR:PROJECT_SUMMARY               	vulnerabilities.
PR:INSTITUTE                     	University of Colorado Anschutz Medical Campus
PR:LAST_NAME                     	Nemkov
PR:FIRST_NAME                    	Travis
PR:ADDRESS                       	12801 E 17th Avenue, RC-1 South, Rm 9403G, Aurora, CO, 80045, USA
PR:EMAIL                         	travis.nemkov@cuanschutz.edu
PR:PHONE                         	303-724-3253
#STUDY
ST:STUDY_TITLE                   	Muscle/Lung/Tumor metabolomics
ST:STUDY_SUMMARY                 	Skeletal muscle (SkM, tibialis anterior and upper arm) and lung samples analyzed
ST:STUDY_SUMMARY                 	by LC-MS metabolomics. These tissue types are analyzed as healthy control,
ST:STUDY_SUMMARY                 	Mcherry+ tumor, or adjacent tissue.
ST:INSTITUTE                     	University of Colorado Anschutz Medical Campus
ST:LAST_NAME                     	Nemkov
ST:FIRST_NAME                    	Travis
ST:ADDRESS                       	12801 East 17th Ave. Research 1 South Rm 9121 Aurora CO 80045
ST:EMAIL                         	travis.nemkov@cuanschutz.edu
ST:PHONE                         	303-724-3253
#SUBJECT
SU:SUBJECT_TYPE                  	Mammal
SU:SUBJECT_SPECIES               	Mus musculus
SU:TAXONOMY_ID                   	10090
#SUBJECT_SAMPLE_FACTORS:         	SUBJECT(optional)[tab]SAMPLE[tab]FACTORS(NAME:VALUE pairs separated by |)[tab]Raw file names and additional sample data
SUBJECT_SAMPLE_FACTORS           	4T1-1	4T1-1_R7-	Tissue:Tibialis_anterior | Treatment:Tumor	RAW_FILE_NAME=4T1-1_R7-.raw
SUBJECT_SAMPLE_FACTORS           	4T1-15	4T1-15_R11-	Tissue:Tibialis_anterior | Treatment:Tumor	RAW_FILE_NAME=4T1-15_R11-.raw
SUBJECT_SAMPLE_FACTORS           	4T1-19	4T1-19_R15-	Tissue:Upper_Arm_SkM | Treatment:Tumor	RAW_FILE_NAME=4T1-19_R15-.raw
SUBJECT_SAMPLE_FACTORS           	4T1-27	4T1-27_R18-	Tissue:Upper_Arm_SkM | Treatment:Tumor	RAW_FILE_NAME=4T1-27_R18-.raw
SUBJECT_SAMPLE_FACTORS           	CTL-1	CTL-1_R23-	Tissue:Tibialis_anterior | Treatment:Control	RAW_FILE_NAME=CTL-1_R23-.raw
SUBJECT_SAMPLE_FACTORS           	CTL-5	CTL-5_R2-	Tissue:Tibialis_anterior | Treatment:Control	RAW_FILE_NAME=CTL-5_R2-.raw
SUBJECT_SAMPLE_FACTORS           	CTL-9	CTL-9_R1-	Tissue:Tibialis_anterior | Treatment:Control	RAW_FILE_NAME=CTL-9_R1-.raw
SUBJECT_SAMPLE_FACTORS           	CTL-3	CTL-3_R6-	Tissue:Upper_Arm_SkM | Treatment:Control	RAW_FILE_NAME=CTL-3_R6-.raw
SUBJECT_SAMPLE_FACTORS           	CTL-7	CTL-7_R3-	Tissue:Upper_Arm_SkM | Treatment:Control	RAW_FILE_NAME=CTL-7_R3-.raw
SUBJECT_SAMPLE_FACTORS           	CTL-11	CTL-11_R21-	Tissue:Upper_Arm_SkM | Treatment:Control	RAW_FILE_NAME=CTL-11_R21-.raw
SUBJECT_SAMPLE_FACTORS           	4T1-17	4T1-17_R4-	Tissue:Lung | Treatment:Tumor	RAW_FILE_NAME=4T1-17_R4-.raw
SUBJECT_SAMPLE_FACTORS           	4T1-21	4T1-21_R22-	Tissue:Lung | Treatment:Tumor	RAW_FILE_NAME=4T1-21_R22-.raw
SUBJECT_SAMPLE_FACTORS           	4T1-25	4T1-25_R16-	Tissue:Lung | Treatment:Tumor	RAW_FILE_NAME=4T1-25_R16-.raw
SUBJECT_SAMPLE_FACTORS           	CTL-4	CTL-4_R20-	Tissue:Lung | Treatment:Control	RAW_FILE_NAME=CTL-4_R20-.raw
SUBJECT_SAMPLE_FACTORS           	CTL-8	CTL-8_R13-	Tissue:Lung | Treatment:Control	RAW_FILE_NAME=CTL-8_R13-.raw
SUBJECT_SAMPLE_FACTORS           	CTL-12	CTL-12_R14-	Tissue:Lung | Treatment:Control	RAW_FILE_NAME=CTL-12_R14-.raw
SUBJECT_SAMPLE_FACTORS           	4T1-1	4T1-1_R7+	Tissue:Tibialis_anterior | Treatment:Tumor	RAW_FILE_NAME=4T1-1_R7+.raw
SUBJECT_SAMPLE_FACTORS           	4T1-15	4T1-15_R11+	Tissue:Tibialis_anterior | Treatment:Tumor	RAW_FILE_NAME=4T1-15_R11+.raw
SUBJECT_SAMPLE_FACTORS           	4T1-19	4T1-19_R15+	Tissue:Upper_Arm_SkM | Treatment:Tumor	RAW_FILE_NAME=4T1-19_R15+.raw
SUBJECT_SAMPLE_FACTORS           	4T1-27	4T1-27_R18+	Tissue:Upper_Arm_SkM | Treatment:Tumor	RAW_FILE_NAME=4T1-27_R18+.raw
SUBJECT_SAMPLE_FACTORS           	CTL-1	CTL-1_R23+	Tissue:Tibialis_anterior | Treatment:Control	RAW_FILE_NAME=CTL-1_R23+.raw
SUBJECT_SAMPLE_FACTORS           	CTL-5	CTL-5_R2+	Tissue:Tibialis_anterior | Treatment:Control	RAW_FILE_NAME=CTL-5_R2+.raw
SUBJECT_SAMPLE_FACTORS           	CTL-9	CTL-9_R1+	Tissue:Tibialis_anterior | Treatment:Control	RAW_FILE_NAME=CTL-9_R1+.raw
SUBJECT_SAMPLE_FACTORS           	CTL-3	CTL-3_R6+	Tissue:Upper_Arm_SkM | Treatment:Control	RAW_FILE_NAME=CTL-3_R6+.raw
SUBJECT_SAMPLE_FACTORS           	CTL-7	CTL-7_R3+	Tissue:Upper_Arm_SkM | Treatment:Control	RAW_FILE_NAME=CTL-7_R3+.raw
SUBJECT_SAMPLE_FACTORS           	CTL-11	CTL-11_R21+	Tissue:Upper_Arm_SkM | Treatment:Control	RAW_FILE_NAME=CTL-11_R21+.raw
SUBJECT_SAMPLE_FACTORS           	4T1-17	4T1-17_R4+	Tissue:Lung | Treatment:Tumor	RAW_FILE_NAME=4T1-17_R4+.raw
SUBJECT_SAMPLE_FACTORS           	4T1-21	4T1-21_R22+	Tissue:Lung | Treatment:Tumor	RAW_FILE_NAME=4T1-21_R22+.raw
SUBJECT_SAMPLE_FACTORS           	4T1-25	4T1-25_R16+	Tissue:Lung | Treatment:Tumor	RAW_FILE_NAME=4T1-25_R16+.raw
SUBJECT_SAMPLE_FACTORS           	CTL-4	CTL-4_R20+	Tissue:Lung | Treatment:Control	RAW_FILE_NAME=CTL-4_R20+.raw
SUBJECT_SAMPLE_FACTORS           	CTL-8	CTL-8_R13+	Tissue:Lung | Treatment:Control	RAW_FILE_NAME=CTL-8_R13+.raw
SUBJECT_SAMPLE_FACTORS           	CTL-12	CTL-12_R14+	Tissue:Lung | Treatment:Control	RAW_FILE_NAME=CTL-12_R14+.raw
#COLLECTION
CO:COLLECTION_SUMMARY            	Lung and skeletal muscle (TA and bulk muscles from the upper arm) were collected
CO:COLLECTION_SUMMARY            	upon necropsy and imaged for mCherry+ 4T1-SkM lesions (Zeiss AxioZoom). Once a
CO:COLLECTION_SUMMARY            	mCherry+ lesion was identified, the region was excised, leaving as little tissue
CO:COLLECTION_SUMMARY            	margins as possible. The sample was weighed and then flash frozen using LN2.
CO:COLLECTION_SUMMARY            	Healthy lung and skeletal muscle samples were collected through the same
CO:COLLECTION_SUMMARY            	process, without the mCherry imaging step. 4T1-parental and 4T1-SkM cells were
CO:COLLECTION_SUMMARY            	plated in 6-well plates at an initial density of 50,000 cells/well and collected
CO:COLLECTION_SUMMARY            	48h later (final density ~275,000 cells/well). Wells were washed twice with 1x
CO:COLLECTION_SUMMARY            	PBS and cells were scraped into 1.5 mL microcentrifuge tubes and spun at 16,000
CO:COLLECTION_SUMMARY            	x g for 3 minutes. Samples were then flash frozen and stored at -80°C until
CO:COLLECTION_SUMMARY            	ready to process.
CO:SAMPLE_TYPE                   	Lung
#TREATMENT
TR:TREATMENT_SUMMARY             	Lung and skeletal muscle (TA and bulk muscles from the upper arm) were collected
TR:TREATMENT_SUMMARY             	upon necropsy and imaged for mCherry+ 4T1-SkM lesions (Zeiss AxioZoom). Once a
TR:TREATMENT_SUMMARY             	mCherry+ lesion was identified, the region was excised, leaving as little tissue
TR:TREATMENT_SUMMARY             	margins as possible. The sample was weighed and then flash frozen using LN2.
TR:TREATMENT_SUMMARY             	Healthy lung and skeletal muscle samples were collected through the same
TR:TREATMENT_SUMMARY             	process, without the mCherry imaging step. 4T1-parental and 4T1-SkM cells were
TR:TREATMENT_SUMMARY             	plated in 6-well plates at an initial density of 50,000 cells/well and collected
TR:TREATMENT_SUMMARY             	48h later (final density ~275,000 cells/well). Wells were washed twice with 1x
TR:TREATMENT_SUMMARY             	PBS and cells were scraped into 1.5 mL microcentrifuge tubes and spun at 16,000
TR:TREATMENT_SUMMARY             	x g for 3 minutes. Samples were then flash frozen and stored at -80°C until
TR:TREATMENT_SUMMARY             	ready to process.
#SAMPLEPREP
SP:SAMPLEPREP_SUMMARY            	Prior to LC-MS analysis, tissue samples were weighed and resuspended in
SP:SAMPLEPREP_SUMMARY            	pre-chilled (-20°C) methanol:acetonitrile:water (5:3:2, v:v) to a final
SP:SAMPLEPREP_SUMMARY            	concentration of 30 mg/ml, cell samples were placed on ice and re-suspended with
SP:SAMPLEPREP_SUMMARY            	methanol:acetonitrile:water (5:3:2, v:v) at a concentration of 2x106 cells/mL,
SP:SAMPLEPREP_SUMMARY            	and media samples were extracted with the same solution at a dilution of 1:25
SP:SAMPLEPREP_SUMMARY            	(v/v). Suspensions were vortexed continuously for 30 min at 4°C. Insoluble
SP:SAMPLEPREP_SUMMARY            	material was removed by centrifugation at 18,000 g for 10 min at 4°C and
SP:SAMPLEPREP_SUMMARY            	supernatants were isolated for metabolomics analysis by UHPLC-MS. Analyses were
SP:SAMPLEPREP_SUMMARY            	performed as previously published85,86. Injection volumes for tissue, cell, and
SP:SAMPLEPREP_SUMMARY            	media extracts were 2 L, 10 L, and 10L, respectively. The analytical
SP:SAMPLEPREP_SUMMARY            	platform employs a Vanquish UHPLC system (ThermoFisher) coupled online to a Q
SP:SAMPLEPREP_SUMMARY            	Exactive mass spectrometer (ThermoFisher). Samples were resolved over a Kinetex
SP:SAMPLEPREP_SUMMARY            	C18 column, 2.1 x 150 mm, 1.7 m particle size (Phenomenex, Torrance, CA)
SP:SAMPLEPREP_SUMMARY            	equipped with a guard column (SecurityGuardTM Ultracartridge – UHPLC C18 for
SP:SAMPLEPREP_SUMMARY            	2.1 mm ID Columns – AJO-8782 – Phenomenex, Torrance, CA) using an aqueous
SP:SAMPLEPREP_SUMMARY            	phase (A) of water and 0.1% formic acid and a mobile phase (B) of acetonitrile
SP:SAMPLEPREP_SUMMARY            	and 0.1% formic acid for positive ion polarity mode, and an aqueous phase (A) of
SP:SAMPLEPREP_SUMMARY            	water:acetonitrile (95:5) with 1 mM ammonium acetate, and a mobile phase (B) of
SP:SAMPLEPREP_SUMMARY            	acetonitrile:water (95:5) with 1 mM ammonium acetate for negative ion polarity
SP:SAMPLEPREP_SUMMARY            	mode. Samples were eluted from the column using either an isocratic elution of
SP:SAMPLEPREP_SUMMARY            	5% B flowed at 250 L/min and 25°C or a gradient from 5% to 95% B over 1 min,
SP:SAMPLEPREP_SUMMARY            	followed by an isocratic hold at 95% B for 2 min, flowed at 400 L/min and
SP:SAMPLEPREP_SUMMARY            	45°C. The Q Exactive mass spectrometer (ThermoFisher) was operated
SP:SAMPLEPREP_SUMMARY            	independently in positive or negative ion mode, scanning in Full MS mode (2
SP:SAMPLEPREP_SUMMARY            	scans) from 60 to 900 m/z at 70,000 resolution, with 4 kV spray voltage, 45
SP:SAMPLEPREP_SUMMARY            	sheath gas, 15 auxiliary gas. Calibration was performed prior to analysis using
SP:SAMPLEPREP_SUMMARY            	the PierceTM Positive and Negative Ion Calibration Solutions (ThermoFisher).
SP:SAMPLEPREP_SUMMARY            	Acquired data was then converted from raw to mzXML file format using Mass Matrix
SP:SAMPLEPREP_SUMMARY            	(Cleveland, OH). Samples were analyzed in randomized order with a technical
SP:SAMPLEPREP_SUMMARY            	mixture injected periodically through analysis to qualify instrument
SP:SAMPLEPREP_SUMMARY            	performance. Metabolite assignments, isotopologue distributions, and correction
SP:SAMPLEPREP_SUMMARY            	for expected natural abundances of deuterium, 13C, and 15N isotopes were
SP:SAMPLEPREP_SUMMARY            	performed using MAVEN (Princeton, NJ)92.
#CHROMATOGRAPHY
CH:CHROMATOGRAPHY_TYPE           	Reversed phase
CH:INSTRUMENT_NAME               	QExactive
CH:COLUMN_NAME                   	Kinetex C18 2.1x100
#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                   	The Q Exactive mass spectrometer (ThermoFisher) was operated independently in
MS:MS_COMMENTS                   	positive or negative ion mode, scanning in Full MS mode (2 scans) from 60 to
MS:MS_COMMENTS                   	900 m/z at 70,000 resolution, with 4 kV spray voltage, 45 sheath gas, 15
MS:MS_COMMENTS                   	auxiliary gas. Calibration was performed prior to analysis using the PierceTM
MS:MS_COMMENTS                   	Positive and Negative Ion Calibration Solutions (ThermoFisher). Acquired data
MS:MS_COMMENTS                   	was then converted from raw to mzXML file format using Mass Matrix (Cleveland,
MS:MS_COMMENTS                   	OH). Samples were analyzed in randomized order with a technical mixture injected
MS:MS_COMMENTS                   	periodically through analysis to qualify instrument performance. Metabolite
MS:MS_COMMENTS                   	assignments, isotopologue distributions, and correction for expected natural
MS:MS_COMMENTS                   	abundances of deuterium, 13C, and 15N isotopes were performed using MAVEN
MS:MS_COMMENTS                   	(Princeton, NJ)
#MS_METABOLITE_DATA
MS_METABOLITE_DATA:UNITS	AU
MS_METABOLITE_DATA_START
Samples	4T1-1_R7+	4T1-15_R11+	4T1-19_R15+	4T1-27_R18+	CTL-1_R23+	CTL-5_R2+	CTL-9_R1+	CTL-3_R6+	CTL-7_R3+	CTL-11_R21+	4T1-17_R4+	4T1-21_R22+	4T1-25_R16+	CTL-4_R20+	CTL-8_R13+	CTL-12_R14+
Factors	Tissue:Tibialis_anterior | Treatment:Tumor	Tissue:Tibialis_anterior | Treatment:Tumor	Tissue:Upper_Arm_SkM | Treatment:Tumor	Tissue:Upper_Arm_SkM | Treatment:Tumor	Tissue:Tibialis_anterior | Treatment:Control	Tissue:Tibialis_anterior | Treatment:Control	Tissue:Tibialis_anterior | Treatment:Control	Tissue:Upper_Arm_SkM | Treatment:Control	Tissue:Upper_Arm_SkM | Treatment:Control	Tissue:Upper_Arm_SkM | Treatment:Control	Tissue:Lung | Treatment:Tumor	Tissue:Lung | Treatment:Tumor	Tissue:Lung | Treatment:Tumor	Tissue:Lung | Treatment:Control	Tissue:Lung | Treatment:Control	Tissue:Lung | Treatment:Control
L-alanine	2.93E+07	3.17E+07	2.69E+07	3.99E+07	2.89E+07	5.00E+07	4.47E+07	3.32E+07	2.81E+07	3.76E+07	7.50E+06	7.69E+06	6.57E+06	4.33E+06	6.26E+06	4.29E+06
L-arginine	3.95E+06	3.18E+06	4.07E+06	3.61E+06	2.64E+06	4.29E+06	4.96E+06	4.50E+06	4.73E+06	4.16E+06	2.67E+06	1.38E+06	9.80E+05	1.94E+06	3.78E+06	2.39E+06
L-asparagine	2.01E+06	1.94E+06	2.38E+06	2.31E+06	1.18E+06	1.52E+06	1.60E+06	1.47E+06	1.61E+06	1.64E+06	9.56E+05	1.38E+06	8.93E+05	5.74E+05	8.78E+05	6.34E+05
L-aspartate	2.95E+06	2.87E+06	3.73E+06	4.67E+06	1.71E+06	2.39E+06	3.49E+06	2.65E+06	1.90E+06	2.80E+06	7.04E+06	6.82E+06	5.03E+06	7.03E+06	5.24E+06	4.92E+06
L-cysteine	1.37E+05	3.36E+05	6.96E+05	5.66E+05	1.41E+05	1.03E+05	7.18E+04	1.02E+05	1.30E+04	1.98E+05	5.90E+05	5.81E+05	4.81E+05	1.70E+05	2.28E+05	5.19E+04
L-glutamate	4.58E+07	2.97E+07	4.17E+07	4.68E+07	4.70E+07	3.69E+07	3.58E+07	3.39E+07	2.68E+07	2.66E+07	3.87E+07	5.71E+07	4.19E+07	4.18E+07	2.97E+07	2.86E+07
L-glutamine	5.44E+07	6.21E+07	7.13E+07	7.17E+07	8.25E+07	1.07E+08	8.53E+07	1.02E+08	9.04E+07	9.00E+07	1.94E+07	1.15E+07	1.06E+07	1.24E+07	1.12E+07	6.65E+06
glycine	5.99E+06	7.25E+06	6.07E+06	6.06E+06	5.62E+06	6.29E+06	5.67E+06	8.70E+06	7.45E+06	9.92E+06	1.04E+07	7.58E+06	5.84E+06	6.05E+06	7.49E+06	7.18E+06
L-histidine	1.46E+07	1.17E+07	7.64E+06	1.01E+07	1.58E+07	1.60E+07	1.51E+07	1.59E+07	1.46E+07	1.56E+07	2.86E+06	2.34E+06	1.99E+06	1.57E+06	2.45E+06	1.30E+06
L-leucine	1.63E+07	1.78E+07	2.17E+07	1.52E+07	1.27E+07	1.70E+07	1.46E+07	9.60E+06	1.20E+07	1.12E+07	9.67E+06	1.37E+07	1.32E+07	9.96E+06	1.33E+07	9.57E+06
L-lysine	1.89E+07	1.26E+07	1.50E+07	1.45E+07	1.73E+07	2.12E+07	2.80E+07	2.25E+07	2.41E+07	2.64E+07	7.40E+06	5.04E+06	5.73E+06	4.64E+06	8.76E+06	5.27E+06
L-methionine	1.94E+07	1.61E+07	1.41E+07	1.72E+07	9.57E+06	1.58E+07	2.20E+07	1.32E+07	1.20E+07	1.75E+07	1.10E+07	1.07E+07	1.01E+07	4.76E+06	9.74E+06	6.14E+06
L-phenylalanine	8.80E+06	8.24E+06	1.05E+07	9.14E+06	5.15E+06	8.16E+06	1.01E+07	4.58E+06	6.05E+06	4.35E+06	4.81E+06	6.61E+06	5.94E+06	3.09E+06	5.13E+06	3.16E+06
L-proline	4.83E+07	4.30E+07	5.13E+07	4.35E+07	1.60E+07	2.22E+07	2.76E+07	2.01E+07	2.18E+07	2.17E+07	1.48E+07	2.09E+07	2.44E+07	8.78E+06	1.82E+07	1.28E+07
L-serine	2.47E+06	2.61E+06	3.03E+06	2.78E+06	2.78E+06	3.09E+06	2.56E+06	3.44E+06	2.64E+06	3.18E+06	1.35E+06	1.83E+06	1.25E+06	9.44E+05	1.55E+06	1.10E+06
L-threonine	7.40E+06	9.81E+06	7.13E+06	1.06E+07	7.21E+06	9.68E+06	7.63E+06	6.36E+06	8.58E+06	7.51E+06	3.63E+06	3.86E+06	3.97E+06	2.10E+06	3.48E+06	2.06E+06
L-tryptophan	2.66E+07	2.03E+07	2.37E+07	1.88E+07	8.52E+06	9.61E+06	1.40E+07	5.64E+06	9.68E+06	8.01E+06	2.34E+07	1.24E+07	1.21E+07	1.02E+07	1.65E+07	8.19E+06
L-tyrosine	1.37E+07	1.02E+07	1.17E+07	9.44E+06	4.68E+06	9.42E+06	1.11E+07	6.49E+06	6.36E+06	8.56E+06	9.08E+06	8.78E+06	6.19E+06	2.94E+06	5.83E+06	4.06E+06
L-valine	3.91E+07	3.25E+07	4.55E+07	3.65E+07	2.39E+07	3.89E+07	3.26E+07	2.87E+07	3.61E+07	2.70E+07	2.42E+07	2.54E+07	1.93E+07	1.71E+07	2.22E+07	1.69E+07
L-cystine	7.99E+03	0.00E+00	3.27E+03	0.00E+00	2.18E+04	0.00E+00	0.00E+00	0.00E+00	0.00E+00	0.00E+00	6.31E+03	0.00E+00	6.01E+03	1.80E+04	1.43E+04	1.33E+04
AMP	5.12E+06	5.45E+06	1.45E+06	4.14E+06	3.14E+06	1.56E+06	4.21E+06	2.50E+06	1.35E+06	4.62E+06	2.54E+07	2.51E+07	1.83E+07	3.22E+07	1.17E+07	1.86E+07
dAMP	0.00E+00	0.00E+00	1.44E+04	0.00E+00	3.89E+03	0.00E+00	0.00E+00	0.00E+00	6.87E+03	1.98E+03	6.71E+03	7.06E+04	3.45E+04	1.75E+04	9.29E+03	6.81E+03
Adenosine	3.15E+06	1.54E+06	2.85E+06	2.42E+06	5.04E+05	6.18E+05	2.64E+05	6.73E+05	2.45E+05	3.01E+05	2.44E+07	8.05E+06	6.42E+06	2.36E+07	1.12E+07	6.61E+06
Adenine	8.17E+05	3.65E+05	2.61E+05	4.79E+05	2.03E+05	2.21E+05	2.73E+05	2.65E+05	2.55E+05	2.21E+05	1.66E+06	1.08E+06	6.77E+05	1.52E+06	8.65E+05	6.94E+05
GMP	1.14E+06	4.85E+05	1.10E+06	8.30E+05	8.32E+05	8.50E+05	1.11E+06	8.78E+05	7.71E+05	8.66E+05	4.11E+06	4.06E+06	2.69E+06	3.85E+06	2.58E+06	3.35E+06
Guanosine	6.22E+05	2.93E+05	8.86E+05	1.19E+06	5.77E+04	1.11E+05	8.21E+04	6.94E+04	5.84E+04	3.91E+04	8.36E+05	8.97E+05	1.09E+06	8.23E+05	1.02E+06	9.18E+05
Guanine	2.72E+05	1.51E+05	3.92E+05	6.20E+05	1.03E+05	1.19E+05	1.58E+05	6.93E+04	1.13E+05	9.11E+04	4.91E+05	5.98E+05	5.57E+05	5.27E+05	5.87E+05	4.88E+05
CMP	1.91E+05	1.06E+05	2.48E+05	3.54E+05	1.55E+05	1.84E+05	1.90E+05	1.15E+05	4.26E+04	1.34E+05	6.21E+05	9.43E+05	8.30E+05	6.61E+05	4.05E+05	4.93E+05
Cytidine	1.13E+06	8.82E+05	1.98E+06	1.12E+06	6.88E+05	5.78E+05	7.22E+05	4.29E+05	3.35E+05	3.98E+05	1.13E+06	1.26E+06	1.47E+06	1.34E+06	1.86E+06	1.47E+06
Cytosine	8.17E+05	5.27E+05	1.13E+06	6.05E+05	4.49E+05	3.97E+05	4.05E+05	2.62E+05	1.80E+05	1.83E+05	6.66E+05	8.45E+05	8.69E+05	8.14E+05	1.08E+06	1.14E+06
Thymidine	1.48E+04	4.99E+03	9.02E+03	4.64E+03	4.13E+03	8.44E+03	6.69E+03	4.06E+03	6.31E+03	5.19E+03	1.25E+04	0.00E+00	0.00E+00	0.00E+00	7.89E+03	0.00E+00
Thymine	2.99E+04	3.00E+04	2.64E+04	3.78E+04	2.15E+04	2.22E+04	3.49E+04	1.93E+04	1.94E+04	1.99E+04	1.48E+04	4.93E+04	2.48E+04	1.17E+04	1.15E+04	1.43E+04
UMP	8.04E+05	2.96E+05	9.66E+05	1.06E+06	1.34E+06	1.07E+06	1.17E+06	8.29E+05	8.43E+05	1.18E+06	1.50E+06	2.59E+06	1.55E+06	1.60E+06	1.05E+06	1.18E+06
Uracil	5.25E+05	3.33E+05	1.19E+06	1.13E+06	2.67E+05	3.45E+05	1.70E+05	2.04E+05	1.80E+05	1.59E+05	4.38E+05	1.34E+06	8.24E+05	4.12E+05	4.09E+05	4.23E+05
IMP	5.74E+07	3.03E+07	4.73E+07	4.47E+07	5.49E+07	6.20E+07	4.68E+07	6.22E+07	5.77E+07	6.49E+07	3.46E+06	4.77E+06	3.98E+06	1.14E+06	1.10E+06	8.50E+05
Inosine	1.13E+07	6.73E+06	1.76E+07	1.66E+07	3.79E+06	4.68E+06	3.17E+06	4.83E+06	4.04E+06	3.14E+06	2.08E+06	4.80E+06	5.69E+06	2.34E+06	4.02E+06	5.01E+06
Hypoxanthine	4.88E+07	3.21E+07	8.46E+07	8.83E+07	2.33E+07	2.89E+07	2.43E+07	2.91E+07	2.63E+07	2.32E+07	2.45E+07	4.75E+07	4.10E+07	2.64E+07	4.85E+07	5.04E+07
Xanthosine	2.13E+03	0.00E+00	1.49E+04	8.06E+03	0.00E+00	2.23E+03	2.10E+03	0.00E+00	0.00E+00	0.00E+00	5.56E+03	1.94E+04	1.90E+04	4.32E+03	9.03E+03	8.16E+03
Xanthine	1.43E+06	8.89E+05	3.65E+06	2.49E+06	1.01E+06	1.39E+06	1.48E+06	1.06E+06	9.21E+05	1.03E+06	1.93E+06	3.75E+06	2.75E+06	1.76E+06	2.37E+06	2.90E+06
Urate	4.42E+05	2.97E+05	9.64E+05	3.60E+05	3.54E+05	5.49E+05	3.66E+05	2.59E+05	2.84E+05	2.77E+05	2.09E+06	2.20E+06	2.01E+06	1.36E+06	1.15E+06	1.29E+06
5-Hydroxyisourate	1.33E+06	2.60E+06	3.08E+06	3.63E+06	4.27E+06	2.76E+06	2.39E+06	2.86E+06	3.85E+06	3.47E+06	1.59E+06	9.57E+05	6.76E+05	8.54E+04	4.70E+05	2.58E+04
(S)(+)-Allantoin	3.95E+05	3.23E+05	4.28E+05	3.23E+05	4.07E+05	2.97E+05	3.59E+05	4.33E+05	3.27E+05	3.05E+05	3.48E+05	2.25E+05	2.82E+05	2.76E+05	3.99E+05	2.12E+05
Allantoate	4.08E+04	2.30E+04	6.82E+04	3.24E+04	0.00E+00	3.07E+04	2.84E+04	1.29E+04	2.30E+04	1.81E+04	1.35E+05	2.65E+05	4.08E+05	6.89E+04	1.72E+05	7.78E+04
3',5'-Cyclic IMP	1.61E+04	1.07E+04	1.91E+04	1.49E+04	2.00E+04	1.71E+04	6.66E+03	1.06E+04	3.67E+03	1.93E+04	0.00E+00	0.00E+00	0.00E+00	0.00E+00	2.26E+03	0.00E+00
Adenylyl sulfate	1.40E+05	1.14E+05	1.31E+05	1.32E+05	1.48E+05	1.25E+05	1.24E+05	1.35E+05	1.45E+05	1.59E+05	2.14E+04	3.84E+04	4.12E+04	2.23E+03	9.92E+03	0.00E+00
Pyridoxal	5.37E+04	1.64E+04	3.56E+04	7.57E+04	3.09E+03	1.68E+04	2.95E+03	1.83E+04	2.97E+03	8.18E+03	3.18E+04	1.96E+04	9.53E+03	2.42E+04	2.82E+04	1.04E+04
Nicotinamide	8.90E+07	5.58E+07	4.60E+07	6.27E+07	8.70E+07	7.81E+07	1.02E+08	6.62E+07	5.85E+07	5.97E+07	2.35E+07	2.42E+07	1.97E+07	1.83E+07	1.48E+07	2.10E+07
Nicotinate ribonucleotide	3.55E+03	1.45E+05	0.00E+00	4.38E+03	0.00E+00	0.00E+00	6.23E+03	2.74E+04	2.81E+04	0.00E+00	5.01E+03	0.00E+00	0.00E+00	0.00E+00	0.00E+00	0.00E+00
NADPH	3.26E+04	4.45E+04	6.61E+04	0.00E+00	5.75E+04	2.22E+04	4.46E+04	3.04E+04	0.00E+00	2.18E+04	0.00E+00	0.00E+00	0.00E+00	0.00E+00	0.00E+00	0.00E+00
NADH	1.84E+04	1.17E+04	0.00E+00	0.00E+00	1.38E+03	4.77E+03	2.42E+03	7.77E+03	4.35E+03	2.30E+03	0.00E+00	0.00E+00	0.00E+00	0.00E+00	0.00E+00	0.00E+00
Glutathione	6.16E+07	3.65E+07	4.60E+07	4.92E+07	5.42E+07	7.02E+07	5.18E+07	6.61E+07	5.91E+07	5.12E+07	6.81E+07	8.95E+07	4.82E+07	3.61E+07	2.14E+07	3.64E+07
Glutathione disulfide	8.22E+05	6.91E+05	8.36E+05	6.46E+05	4.18E+05	8.07E+05	4.68E+05	4.88E+05	5.25E+05	2.71E+05	3.27E+06	1.76E+06	1.62E+06	3.18E+06	2.52E+06	3.28E+06
5-Oxoproline	3.48E+07	3.45E+07	3.98E+07	4.42E+07	4.89E+07	4.38E+07	5.06E+07	6.02E+07	5.23E+07	5.22E+07	1.67E+07	1.52E+07	1.33E+07	1.28E+07	1.10E+07	7.76E+06
S-Glutathionyl-L-cysteine	4.74E+04	8.00E+04	1.77E+05	3.57E+04	0.00E+00	2.64E+04	4.58E+04	0.00E+00	0.00E+00	1.24E+04	2.94E+05	2.67E+05	2.51E+05	3.75E+05	5.49E+05	4.03E+05
Cys-Gly	4.47E+05	2.59E+05	2.73E+05	3.34E+05	3.94E+05	4.56E+05	3.70E+05	4.84E+05	4.18E+05	3.66E+05	4.85E+05	6.68E+05	3.12E+05	2.94E+05	1.92E+05	2.56E+05
Ascorbate	6.03E+05	4.94E+05	7.84E+05	6.39E+05	5.05E+05	5.61E+05	4.00E+05	5.98E+05	5.37E+05	4.32E+05	3.82E+06	2.16E+06	9.82E+05	1.72E+06	5.17E+05	8.02E+05
Dehydroascorbate	2.06E+04	1.35E+04	3.59E+04	3.13E+04	3.14E+04	3.01E+04	2.34E+04	2.13E+04	1.42E+04	1.98E+04	6.00E+04	4.84E+04	2.60E+04	4.62E+04	3.64E+04	4.44E+04
gamma-L-Glutamyl-D-alanine	8.47E+04	6.71E+04	9.12E+04	5.67E+04	1.03E+05	1.03E+05	9.22E+04	5.54E+04	8.53E+04	6.39E+04	2.57E+05	7.58E+04	7.26E+04	1.13E+05	2.05E+05	1.36E+05
gamma-Glutamyl-gamma-aminobutyrate	1.09E+05	7.57E+04	1.02E+05	1.00E+05	1.40E+05	1.41E+05	1.21E+05	1.35E+05	8.41E+04	8.40E+04	4.06E+04	9.89E+04	3.67E+04	3.04E+04	3.73E+04	2.09E+04
gamma-L-Glutamylputrescine	1.35E+05	1.08E+05	1.36E+05	9.64E+04	1.24E+05	1.33E+05	1.14E+05	1.04E+05	7.57E+04	4.23E+04	1.69E+04	2.15E+04	4.02E+04	3.18E+03	2.30E+03	0.00E+00
(5-L-Glutamyl)-L-glutamine	5.77E+04	9.79E+04	1.00E+05	0.00E+00	3.50E+04	2.43E+04	1.72E+04	7.99E+03	4.28E+03	7.80E+03	3.69E+05	1.72E+05	1.37E+05	2.23E+05	2.62E+05	1.40E+05
L-Homocysteine	9.67E+04	4.05E+04	5.24E+04	3.40E+04	5.09E+04	4.72E+04	3.75E+04	4.17E+04	3.01E+04	6.85E+04	5.14E+04	5.32E+04	2.39E+04	3.23E+04	2.71E+04	1.93E+04
Phosphoserine	8.94E+04	3.43E+04	7.27E+04	4.44E+04	3.96E+04	1.97E+04	4.52E+04	4.01E+04	1.60E+04	1.04E+04	1.84E+05	3.05E+05	2.25E+05	1.87E+05	1.84E+05	1.05E+05
S-Adenosyl-L-homocysteine	1.17E+05	9.39E+04	2.35E+05	2.04E+05	1.68E+05	1.97E+05	1.36E+05	1.37E+05	1.31E+05	1.32E+05	3.69E+05	3.95E+05	3.17E+05	2.66E+05	2.82E+05	4.00E+05
S-Adenosyl-L-methionine	2.14E+05	1.82E+05	1.64E+05	2.09E+05	2.65E+05	2.29E+05	1.94E+05	1.91E+05	1.75E+05	2.38E+05	2.12E+05	2.95E+05	2.14E+05	2.10E+05	1.76E+05	1.75E+05
Ornithine	9.31E+05	1.05E+06	1.04E+06	6.98E+05	7.14E+05	1.23E+06	1.53E+06	7.09E+05	1.04E+06	1.26E+06	7.73E+05	1.32E+06	1.74E+06	2.88E+05	8.46E+05	4.34E+05
L-Citrulline	7.76E+06	8.18E+06	4.88E+06	7.06E+06	9.53E+06	1.01E+07	8.04E+06	8.32E+06	8.45E+06	9.20E+06	2.06E+06	1.85E+06	1.82E+06	1.58E+06	2.15E+06	1.08E+06
Argininosuccinate	3.28E+04	2.33E+04	6.58E+04	7.85E+04	2.74E+04	3.48E+04	2.02E+04	3.68E+04	1.78E+04	3.51E+04	2.60E+04	3.32E+04	2.22E+04	9.48E+03	2.75E+04	1.48E+04
5-Methylthioadenosine	4.53E+05	4.16E+05	2.38E+05	2.91E+05	2.25E+05	2.25E+05	2.51E+05	2.67E+05	2.47E+05	2.04E+05	1.02E+06	9.91E+05	6.55E+05	6.18E+05	5.04E+05	5.47E+05
Putrescine	1.59E+05	1.07E+05	5.69E+04	1.25E+05	6.51E+04	5.57E+04	5.66E+04	4.40E+04	5.02E+04	5.56E+04	2.01E+05	3.16E+05	1.81E+05	8.87E+04	7.23E+04	9.95E+04
Spermidine	9.38E+05	1.23E+06	8.60E+05	1.24E+06	5.50E+05	5.21E+05	5.61E+05	6.96E+05	6.90E+05	5.81E+05	1.38E+06	2.66E+06	2.95E+06	1.78E+06	2.87E+06	2.76E+06
Spermine	1.26E+05	9.78E+04	2.31E+04	2.84E+04	2.41E+04	3.07E+04	2.37E+04	3.05E+04	3.74E+04	3.70E+04	6.49E+04	7.67E+04	9.02E+04	8.30E+04	1.19E+05	1.02E+05
N1-Acetylspermidine	1.27E+05	1.06E+05	1.72E+05	1.95E+05	1.62E+04	1.59E+04	1.79E+04	3.63E+04	4.23E+04	1.76E+04	3.19E+05	6.83E+05	3.19E+05	1.74E+05	1.97E+05	1.38E+05
Atherospermidine	4.02E+03	6.84E+03	0.00E+00	0.00E+00	0.00E+00	0.00E+00	0.00E+00	0.00E+00	0.00E+00	0.00E+00	2.39E+04	1.82E+04	1.92E+04	3.32E+04	7.72E+03	2.58E+04
Asymmetric dimethyl arginine	3.19E+05	1.86E+05	3.25E+05	2.81E+05	2.17E+05	2.61E+05	3.07E+05	3.19E+05	2.19E+05	2.29E+05	1.31E+05	3.45E+05	2.46E+05	1.35E+05	1.56E+05	1.43E+05
Carnosine	1.72E+07	1.74E+07	3.65E+06	7.53E+06	1.94E+07	1.61E+07	1.60E+07	1.64E+07	1.47E+07	1.63E+07	7.89E+04	8.74E+04	1.49E+05	6.55E+04	8.42E+04	4.78E+04
Phosphocreatine	4.05E+05	2.80E+06	2.84E+04	2.59E+04	2.59E+04	6.98E+04	1.99E+04	7.85E+05	5.84E+05	1.82E+04	6.00E+05	2.75E+05	4.25E+05	3.01E+05	2.58E+05	2.47E+05
Guanidinoacetate	6.87E+05	6.29E+05	5.40E+05	8.06E+05	5.83E+05	7.50E+05	5.92E+05	4.76E+05	2.66E+05	4.12E+05	5.19E+05	6.49E+05	4.17E+05	3.03E+05	3.15E+05	2.22E+05
trans-4-Hydroxy-L-proline	4.40E+06	3.50E+06	1.92E+06	2.90E+06	8.71E+06	7.71E+06	6.86E+06	8.80E+06	6.42E+06	7.18E+06	1.13E+06	1.86E+06	1.35E+06	9.39E+05	8.81E+05	7.22E+05
5-6-Dihydrouracil	5.94E+05	5.90E+05	4.97E+05	7.84E+05	8.06E+05	9.13E+05	6.79E+05	8.03E+05	8.21E+05	7.75E+05	5.24E+04	4.68E+04	3.47E+04	2.72E+04	5.53E+04	3.26E+04
Taurine	1.72E+08	1.84E+08	1.54E+08	1.76E+08	1.71E+08	1.88E+08	1.59E+08	1.89E+08	1.70E+08	1.85E+08	5.40E+07	5.13E+07	5.52E+07	4.93E+07	4.24E+07	3.80E+07
Hypotaurine	1.01E+06	1.53E+06	1.48E+06	2.04E+06	1.64E+06	1.76E+06	1.41E+06	1.97E+06	1.57E+06	1.51E+06	1.06E+06	8.44E+05	6.58E+05	7.24E+05	7.71E+05	6.60E+05
L-Methionine S-oxide	2.26E+05	1.37E+05	2.10E+05	1.42E+05	1.34E+05	1.78E+05	3.01E+05	1.27E+05	1.62E+05	1.62E+05	3.07E+05	3.29E+05	1.62E+05	2.61E+05	4.06E+05	3.83E+05
Kynurenine	2.38E+04	1.92E+04	5.98E+04	1.86E+04	1.41E+04	1.18E+04	1.87E+04	1.03E+04	1.17E+04	9.96E+03	3.13E+04	2.66E+04	2.54E+04	2.55E+04	3.53E+04	2.41E+04
N-formyl kynurenine	1.15E+04	1.72E+04	5.92E+03	1.24E+04	1.57E+04	1.44E+04	2.65E+04	5.48E+03	1.27E+04	7.83E+03	9.26E+03	1.27E+04	1.58E+04	1.10E+04	1.22E+04	3.18E+03
g-Oxalo-crotonate	4.87E+05	4.76E+05	1.02E+06	8.15E+05	2.76E+05	2.85E+05	2.51E+05	2.20E+05	1.95E+05	1.88E+05	7.11E+05	1.12E+06	1.17E+06	7.03E+05	1.17E+06	1.21E+06
2-Aminomuconate	2.94E+04	2.27E+04	2.82E+04	2.69E+04	1.34E+04	1.46E+04	9.24E+03	4.91E+04	3.40E+04	2.01E+04	4.35E+04	3.65E+04	2.33E+04	3.35E+04	1.22E+04	1.86E+04
L-Adrenaline	6.99E+03	6.00E+03	1.67E+04	1.68E+04	4.66E+03	9.90E+03	1.70E+04	1.61E+04	1.68E+04	2.63E+04	8.94E+03	9.26E+03	6.39E+03	7.95E+03	4.99E+03	8.61E+03
Serotonin	2.96E+04	2.39E+04	4.37E+04	1.67E+04	1.81E+04	2.11E+04	2.18E+04	1.31E+04	1.02E+04	9.45E+03	1.01E+05	2.82E+04	3.40E+04	6.31E+05	5.01E+05	5.70E+05
Ectoine	1.60E+05	1.82E+05	1.47E+05	7.39E+04	1.28E+05	1.49E+05	2.09E+05	3.09E+05	2.09E+05	2.27E+05	1.61E+05	1.17E+05	2.36E+05	3.21E+05	4.80E+05	4.57E+05
3D-(3-5/4)-Trihydroxycyclohexane-1-2-dione	4.13E+03	4.03E+03	2.69E+03	0.00E+00	3.05E+03	2.52E+03	0.00E+00	0.00E+00	0.00E+00	1.67E+03	3.05E+04	1.73E+04	4.87E+04	6.35E+04	6.20E+04	7.28E+04
sn-glycero-3-Phosphoethanolamine	2.77E+05	1.93E+05	2.41E+05	5.16E+05	1.21E+05	9.54E+04	1.06E+05	1.11E+05	1.16E+05	7.76E+04	1.30E+06	1.11E+06	8.16E+05	1.06E+06	9.80E+05	8.13E+05
Diethanolamine	2.76E+04	4.73E+04	1.60E+04	4.17E+04	9.29E+03	2.21E+04	1.62E+04	1.83E+04	1.77E+04	1.74E+04	1.35E+04	1.33E+04	1.81E+04	1.35E+04	1.98E+04	1.09E+04
Triethanolamine	3.45E+05	2.15E+05	1.58E+06	2.76E+05	5.46E+04	2.85E+04	2.35E+04	3.57E+04	1.38E+04	1.28E+04	1.51E+04	7.17E+04	4.00E+04	8.78E+03	1.27E+04	1.85E+04
N-Methylethanolamine phosphate	1.31E+05	1.41E+05	1.44E+05	1.66E+05	1.72E+05	1.64E+05	1.75E+05	1.71E+05	1.75E+05	1.79E+05	1.48E+05	1.24E+05	1.36E+05	1.12E+05	1.17E+05	1.13E+05
CDP-choline	2.72E+04	3.68E+04	6.62E+04	7.80E+04	1.69E+04	7.59E+03	1.36E+04	3.32E+04	1.13E+04	1.29E+04	3.13E+04	1.77E+05	5.63E+04	3.37E+04	2.38E+04	4.14E+04
L-Carnitine	9.60E+07	1.11E+08	7.93E+07	9.70E+07	1.68E+08	1.64E+08	1.49E+08	1.10E+08	9.91E+07	1.10E+08	7.01E+07	4.38E+07	4.38E+07	6.48E+07	6.27E+07	4.72E+07
Acetylcarnitine	2.00E+08	9.90E+07	1.20E+08	9.89E+07	1.42E+08	1.79E+08	1.38E+08	1.22E+08	1.01E+08	9.81E+07	7.81E+07	5.54E+07	3.84E+07	5.76E+07	4.51E+07	5.81E+07
Propenoylcarnitine	2.81E+04	1.16E+04	1.13E+04	5.20E+03	1.98E+04	2.02E+04	1.86E+04	2.67E+04	2.30E+04	1.08E+04	1.33E+04	1.05E+04	1.47E+04	1.04E+04	1.47E+04	1.14E+04
Propionylcarnitine	7.34E+05	7.51E+05	4.80E+05	5.48E+05	2.65E+05	4.18E+05	3.76E+05	3.59E+05	3.60E+05	4.39E+05	4.57E+05	2.68E+05	2.25E+05	2.57E+05	2.12E+05	2.07E+05
Butyrylcarnitine	5.46E+06	6.36E+06	5.18E+06	5.42E+06	3.81E+06	4.47E+06	7.49E+06	5.23E+06	5.82E+06	4.82E+06	1.01E+07	3.90E+06	2.77E+06	5.14E+06	4.34E+06	3.80E+06
Tiglylcarnitine	6.56E+04	1.61E+05	6.18E+04	1.24E+05	5.26E+04	1.68E+05	1.89E+05	5.51E+04	1.58E+05	1.65E+05	3.96E+04	2.50E+04	3.12E+04	1.81E+04	2.99E+04	1.44E+04
Isovalerylcarnitine	9.43E+05	1.21E+06	7.22E+05	1.17E+06	3.63E+05	8.26E+05	1.24E+06	2.75E+05	7.46E+05	1.09E+06	1.11E+06	6.42E+05	6.66E+05	4.36E+05	9.79E+05	6.39E+05
Malonylcarnitine	5.82E+05	4.42E+05	4.74E+05	4.17E+05	6.46E+05	7.81E+05	6.93E+05	3.60E+05	3.60E+05	4.04E+05	1.33E+05	8.44E+04	1.38E+05	7.71E+04	8.70E+04	7.87E+04
Hexenoylcarnitine	3.57E+04	4.14E+04	2.00E+04	5.84E+04	4.43E+04	5.41E+04	5.39E+04	4.05E+04	6.15E+04	3.26E+04	3.92E+04	3.97E+04	4.33E+04	2.96E+04	4.52E+04	4.47E+04
Hexanoylcarnitine	1.30E+06	1.11E+06	1.46E+06	1.83E+06	1.16E+06	9.71E+05	1.91E+06	1.20E+06	1.42E+06	1.52E+06	7.81E+05	3.25E+05	2.40E+05	3.51E+05	3.02E+05	2.84E+05
Methylmalonylcarnitine	7.12E+05	3.05E+05	5.40E+05	6.08E+05	6.71E+05	1.03E+06	1.04E+06	8.25E+05	9.57E+05	6.06E+05	1.06E+05	9.63E+04	1.83E+05	8.59E+04	1.06E+05	8.21E+04
Hydroxyisovaleroyl carnitine	2.70E+05	1.97E+05	1.24E+05	1.41E+05	2.34E+05	2.41E+05	2.63E+05	2.37E+05	2.49E+05	1.71E+05	9.88E+04	6.35E+04	7.20E+04	7.27E+04	9.85E+04	5.72E+04
Octenoylcarnitine	4.54E+04	3.28E+04	3.52E+04	5.19E+04	5.89E+04	3.04E+04	6.13E+04	3.51E+04	3.10E+04	4.39E+04	2.30E+04	1.70E+04	1.87E+04	1.56E+04	1.44E+04	1.80E+04
Octanoylcarnitine	4.79E+05	4.51E+05	5.45E+05	2.22E+05	4.03E+05	2.89E+05	7.26E+05	3.52E+05	3.46E+05	5.61E+05	1.34E+05	3.19E+04	3.75E+04	5.29E+04	4.24E+04	3.62E+04
Methylglutarylcarnitine	1.55E+04	1.75E+04	2.15E+04	1.74E+04	1.87E+04	1.70E+04	1.63E+04	2.22E+04	1.30E+04	6.25E+03	1.40E+04	2.11E+04	8.97E+03	2.16E+04	1.17E+04	2.08E+04
Pimelylcarnitine	1.26E+04	2.10E+04	5.46E+03	1.72E+04	2.02E+04	1.63E+04	6.04E+03	1.09E+04	1.82E+04	7.52E+03	1.00E+04	6.95E+03	2.87E+04	9.44E+03	2.55E+04	1.97E+04
Hydroxyoctanoyl carnitine	1.53E+05	1.14E+05	1.56E+05	2.54E+05	2.93E+05	1.76E+05	3.45E+05	1.87E+05	1.95E+05	2.30E+05	1.70E+05	1.15E+05	5.75E+04	1.02E+05	8.58E+04	9.51E+04
Decanoylcarnitine	7.07E+04	2.22E+04	6.39E+04	5.87E+04	6.86E+04	3.21E+04	1.02E+05	6.98E+04	4.40E+04	7.70E+04	1.35E+04	5.52E+03	1.06E+04	1.12E+04	5.24E+03	4.30E+03
Hydroxynonanoyl carnitine	4.10E+04	3.89E+04	2.15E+04	2.52E+04	2.48E+04	2.89E+04	2.52E+04	2.33E+04	2.64E+04	1.77E+04	3.09E+04	3.16E+04	3.85E+04	2.11E+04	2.51E+04	4.10E+04
Hydroxydecanoyl carnitine	1.46E+05	6.77E+04	2.88E+05	5.18E+05	5.07E+05	2.45E+05	7.07E+05	2.49E+05	1.49E+05	3.52E+05	1.58E+05	9.76E+04	6.99E+04	9.31E+04	6.81E+04	1.20E+05
Dodecenoylcarnitine	6.81E+04	2.48E+04	2.51E+04	1.41E+04	2.57E+04	2.14E+04	2.95E+04	2.00E+04	1.91E+04	1.59E+04	1.83E+04	2.03E+04	1.25E+04	2.56E+04	1.04E+04	2.19E+04
Hydroxyundecanoyl carnitine	5.59E+03	3.48E+03	4.25E+03	5.37E+03	8.71E+03	6.12E+03	5.04E+03	3.77E+03	3.58E+03	3.40E+03	6.60E+03	3.50E+03	5.65E+03	8.71E+03	8.60E+03	8.44E+03
Hydroxydodecanoyl carnitine	2.39E+04	9.83E+03	6.13E+04	1.15E+05	1.53E+05	6.12E+04	1.57E+05	1.14E+05	4.43E+04	9.40E+04	4.00E+04	2.87E+04	1.31E+04	3.07E+04	1.67E+04	1.63E+04
Tetradecenoylcarnitine	6.84E+04	1.57E+05	2.73E+04	4.49E+04	3.30E+04	1.15E+04	3.52E+04	1.42E+04	1.18E+04	2.03E+04	1.98E+03	5.02E+02	3.45E+03	6.26E+03	3.23E+03	1.70E+03
Tetradecanoylcarnitine	9.87E+05	7.78E+05	3.23E+05	6.03E+05	1.23E+05	1.43E+05	1.52E+05	2.61E+05	2.69E+05	2.94E+04	4.95E+05	2.06E+05	6.53E+05	4.13E+05	8.28E+04	4.83E+05
Dodecanedioylcarnitine	8.17E+03	4.56E+03	9.96E+03	7.83E+03	3.31E+03	3.87E+03	9.04E+03	4.71E+03	9.82E+03	1.13E+04	3.46E+03	7.76E+03	3.99E+03	9.20E+03	5.47E+03	1.41E+04
Hexadecenoyl carnitine	9.33E+05	1.88E+05	3.45E+05	5.73E+05	4.64E+04	9.50E+04	4.72E+05	5.14E+05	6.93E+05	2.10E+04	7.17E+05	7.23E+04	3.76E+05	4.02E+05	2.37E+04	4.06E+05
Hydroxyhexadecenoylcarnitine	3.18E+03	1.55E+04	0.00E+00	5.47E+03	0.00E+00	0.00E+00	9.20E+02	7.71E+02	0.00E+00	0.00E+00	0.00E+00	0.00E+00	7.35E+03	0.00E+00	4.70E+03	1.54E+03
Heptadecanoyl carnitine	1.21E+04	4.04E+03	1.34E+04	2.14E+04	1.25E+04	2.16E+04	6.11E+03	3.30E+03	3.19E+03	7.62E+03	1.68E+04	1.64E+04	1.05E+04	6.64E+03	1.03E+04	8.03E+03
Hydroxyhexadecanoyl carnitine	1.54E+05	1.27E+05	9.54E+04	6.26E+04	1.11E+05	1.10E+05	3.33E+05	7.88E+04	3.57E+04	1.56E+05	8.64E+04	6.30E+04	6.05E+04	5.76E+04	4.70E+04	9.39E+04
Alpha-linolenyl carnitine	5.97E+04	6.17E+04	8.13E+04	2.11E+04	8.34E+04	1.79E+04	6.13E+04	8.02E+04	5.61E+04	8.22E+04	6.49E+04	3.05E+03	8.07E+04	4.53E+04	8.16E+02	1.19E+04
Linoelaidyl carnitine	4.79E+05	7.29E+04	2.05E+05	1.99E+05	1.00E+04	4.75E+04	3.39E+05	3.90E+05	3.65E+05	1.35E+04	5.51E+05	2.47E+04	8.17E+04	3.24E+05	3.98E+03	4.80E+04
Elaidic carnitine	6.25E+05	1.20E+06	3.02E+04	1.17E+05	6.63E+03	9.79E+03	2.12E+04	2.30E+04	3.88E+04	2.65E+03	4.99E+04	1.49E+04	7.92E+05	4.02E+04	5.87E+04	1.01E+06
Hydroxyoctadecenoylcarnitine	1.87E+05	6.37E+04	3.44E+05	1.35E+05	1.36E+05	2.26E+05	1.33E+05	7.51E+05	4.67E+05	4.58E+04	4.41E+05	1.39E+05	6.79E+04	4.66E+05	3.41E+04	1.11E+05
Cervonyl carnitine	9.47E+04	2.53E+04	3.57E+04	3.93E+04	5.54E+03	9.68E+03	3.79E+04	8.18E+04	4.04E+04	0.00E+00	4.75E+04	8.21E+03	3.16E+04	3.92E+04	1.52E+03	1.26E+04
Docosapentaenoyl carnitine	9.40E+03	1.03E+03	5.09E+03	4.65E+03	5.88E+02	6.37E+02	4.41E+03	1.31E+04	1.16E+04	0.00E+00	5.96E+03	1.15E+03	9.25E+02	1.38E+04	0.00E+00	3.08E+02
Hexadecadienoylcarnitine	1.26E+05	2.95E+05	1.78E+05	2.11E+05	1.39E+05	9.23E+04	4.74E+04	3.89E+04	5.49E+04	6.10E+04	3.05E+03	1.94E+03	0.00E+00	1.95E+03	0.00E+00	0.00E+00
3-4-Dihydroxy-L-phenylalanine	0.00E+00	3.52E+03	2.71E+03	1.56E+03	3.20E+03	3.21E+03	1.34E+03	1.65E+03	3.00E+03	0.00E+00	6.61E+03	4.86E+03	3.51E+03	2.16E+04	2.70E+04	2.37E+04
Tyramine	4.68E+04	4.67E+04	3.12E+04	3.94E+04	5.69E+04	4.51E+04	3.87E+04	3.54E+04	4.50E+04	3.13E+04	3.43E+04	3.64E+04	3.75E+04	3.23E+04	3.33E+04	5.36E+04
4-Hydroxyphenylacetylglutamic acid	0.00E+00	0.00E+00	4.72E+03	5.36E+03	0.00E+00	0.00E+00	0.00E+00	0.00E+00	0.00E+00	0.00E+00	4.66E+04	4.09E+04	3.32E+04	3.53E+04	4.13E+04	4.50E+04
4-Coumarate	1.78E+06	1.21E+06	1.43E+06	1.20E+06	6.59E+05	1.12E+06	1.42E+06	8.48E+05	8.26E+05	9.97E+05	1.01E+06	1.15E+06	8.12E+05	4.28E+05	7.86E+05	5.18E+05
3alpha-12alpha-Dihydroxy-5beta-cholanate	1.56E+03	4.75E+02	4.85E+02	5.49E+02	6.40E+02	1.75E+03	6.42E+02	3.93E+02	0.00E+00	0.00E+00	7.72E+02	3.81E+02	3.29E+02	5.27E+02	7.75E+02	0.00E+00
Leukotriene C4	0.00E+00	4.14E+03	2.52E+03	5.60E+03	0.00E+00	0.00E+00	2.26E+03	0.00E+00	2.94E+03	3.85E+03	3.46E+03	6.24E+03	5.78E+03	9.94E+03	8.13E+03	4.40E+04
Testosterone	6.26E+03	3.96E+02	0.00E+00	1.70E+03	4.63E+02	0.00E+00	1.92E+03	3.86E+02	4.74E+02	3.11E+02	1.46E+03	1.49E+03	2.44E+02	5.23E+02	3.99E+02	1.47E+03
Mevalonate	3.10E+05	3.45E+05	4.37E+05	4.53E+05	5.21E+05	5.93E+05	5.68E+05	7.02E+05	5.87E+05	5.89E+05	1.26E+05	5.61E+04	7.07E+04	8.19E+04	7.31E+04	3.82E+04
Sphingosine	5.81E+04	4.51E+04	3.31E+05	1.25E+05	6.16E+05	5.46E+05	4.86E+04	6.87E+04	5.06E+04	5.18E+05	1.07E+05	8.36E+05	6.50E+04	1.26E+05	3.26E+05	8.25E+04
Biliverdin	5.19E+02	1.30E+03	4.37E+02	0.00E+00	0.00E+00	0.00E+00	0.00E+00	0.00E+00	3.56E+02	0.00E+00	2.13E+03	5.10E+02	2.97E+03	2.86E+03	4.39E+03	2.24E+03
trimethylamineoxide	9.59E+03	0.00E+00	0.00E+00	0.00E+00	0.00E+00	0.00E+00	1.05E+04	0.00E+00	8.92E+04	7.06E+05	3.10E+03	3.12E+03	0.00E+00	0.00E+00	2.49E+03	0.00E+00
4-Imidazolone-5-propanoate	5.09E+04	1.70E+04	1.69E+04	3.52E+03	3.18E+03	3.40E+04	1.99E+04	1.96E+04	6.12E+03	4.41E+03	3.95E+04	3.55E+04	3.48E+04	4.17E+04	3.09E+04	2.00E+04
N-Acetylmethionine	5.52E+04	3.34E+04	1.67E+05	1.51E+05	1.11E+05	9.51E+04	9.16E+04	5.15E+04	5.89E+04	4.61E+04	8.81E+04	2.08E+05	1.19E+05	7.13E+04	1.45E+05	1.33E+05
N-Acetyl-D-phenylalanine	3.61E+04	3.63E+04	3.21E+04	2.79E+04	1.44E+04	2.41E+04	4.30E+04	3.83E+03	1.03E+04	9.24E+03	5.35E+04	1.48E+04	6.41E+03	1.93E+04	4.78E+04	1.42E+04
N-Acetyl-L-aspartate	1.02E+05	1.15E+05	1.58E+05	1.23E+05	7.71E+04	6.10E+04	8.49E+04	2.11E+05	1.72E+05	9.30E+04	2.17E+05	1.74E+05	1.65E+05	1.25E+05	6.60E+04	9.12E+04
N-Acetyl-L-glutamate	8.94E+03	5.54E+03	3.05E+04	1.14E+04	2.38E+04	1.72E+04	2.29E+04	2.14E+04	1.71E+04	1.16E+04	2.49E+04	2.07E+04	2.14E+04	1.19E+04	9.95E+03	4.04E+04
N-Acetyl-L-histidine	9.19E+06	7.42E+06	2.23E+06	4.41E+06	1.01E+07	9.51E+06	9.24E+06	1.02E+07	8.51E+06	9.21E+06	8.82E+05	6.98E+05	6.34E+05	9.38E+05	7.91E+05	9.14E+05
MS_METABOLITE_DATA_END
#METABOLITES
METABOLITES_START
metabolite_name	CmpdID	parent	medRt
L-alanine	C00041	90.055664	0.656
L-arginine	C00062	175.119019	0.633
L-asparagine	C00152	133.060974	0.645
L-aspartate	C00049	134.044937	0.651
L-cysteine	C00097	122.027374	0.699
L-glutamate	C00025	148.060501	0.66
L-glutamine	C00064	147.076477	0.652
glycine	C00037	76.040161	0.651
L-histidine	C00135	156.076859	0.628
L-leucine	C00123	132.102051	0.97
L-lysine	C00047	147.112854	0.614
L-methionine	C00073	150.058472	0.734
L-phenylalanine	C00079	166.08638	1.451
L-proline	C00148	116.07103	0.701
L-serine	C00065	106.050369	0.661
L-threonine	C00188	120.065834	0.695
L-tryptophan	C00078	205.097244	1.745
L-tyrosine	C00082	182.081268	0.735
L-valine	C00183	118.086647	0.714
L-cystine	C00491	241.030792	0.588
AMP	C00020	348.070312	0.696
dAMP	C00360	332.076385	0.723
Adenosine	C00212	268.103882	0.74
Adenine	C00147	136.061981	0.729
GMP	C00144	364.064911	0.708
Guanosine	C00387	284.098816	0.717
Guanine	C00242	152.056931	0.716
CMP	C00055	324.059082	0.671
Cytidine	C00475	244.092834	0.696
Cytosine	C00380	112.05101	0.696
Thymidine	C00214	243.098999	1.765
Thymine	C00178	127.050507	1.285
UMP	C00105	325.042999	0.695
Uracil	C00106	113.034958	0.754
IMP	C00130	349.05426	0.704
Inosine	C00294	269.087921	0.719
Hypoxanthine	C00262	137.045883	0.719
Xanthosine	C01762	285.082977	1.053
Xanthine	C00385	153.04071	0.723
Urate	C00366	169.035721	0.732
5-Hydroxyisourate	C11821	185.031631	0.649
(S)(+)-Allantoin	C02350	159.051376	0.691
Allantoate	C00499	177.06105	0.606
3',5'-Cyclic IMP	C00943	331.04422	0.709
Adenylyl sulfate	C00224	428.027069	0.735
Pyridoxal	C00250	168.065582	0.765
Nicotinamide	C00153	123.055565	0.804
Nicotinate ribonucleotide	C01185	337.057037	0.661
NADPH	C00005	746.094299	0.661
NADH	C00004	666.131348	1.679
Glutathione	C00051	308.090851	0.715
Glutathione disulfide	C00127	613.158997	0.713
5-Oxoproline	C01879	130.050064	0.661
S-Glutathionyl-L-cysteine	C05526	427.095062	0.659
Cys-Gly	C01419	179.048569	0.715
Ascorbate	C00072	177.039581	0.738
Dehydroascorbate	C05422	175.023651	0.831
gamma-L-Glutamyl-D-alanine	C03738	219.097488	0.705
gamma-Glutamyl-gamma-aminobutyrate	C15767	233.113266	0.718
gamma-L-Glutamylputrescine	C15699	218.150101	0.608
(5-L-Glutamyl)-L-glutamine	C05283	276.118866	0.674
L-Homocysteine	C00155	136.042755	0.71
Phosphoserine	C02532	186.016373	0.657
S-Adenosyl-L-homocysteine	C00021	385.128845	0.718
S-Adenosyl-L-methionine	C00019	399.14447	0.633
Ornithine	C01602	133.097321	0.622
L-Citrulline	C00327	176.103012	0.658
Argininosuccinate	C03406	291.129761	0.65
5-Methylthioadenosine	C00170	298.096741	1.732
Putrescine	C00134	89.108139	0.598
Spermidine	C00315	146.165253	0.568
Spermine	C00750	203.22316	0.568
N1-Acetylspermidine	C00612	188.175797	0.6
Atherospermidine	C09347	306.075409	0.72
Asymmetric dimethyl arginine	C03626	203.150375	0.655
Carnosine	C00386	227.113892	0.614
Phosphocreatine	C02305	212.04303	0.727
Guanidinoacetate	C00581	118.061516	0.66
trans-4-Hydroxy-L-proline	C01157	132.06572	0.681
5-6-Dihydrouracil	C00429	115.050644	0.683
Taurine	C00245	126.022171	0.658
Hypotaurine	C00519	110.027557	0.654
L-Methionine S-oxide	C02989	166.053101	0.72
Kynurenine	C00328	209.092209	1.408
N-formyl kynurenine	C02700	237.088776	0.636
g-Oxalo-crotonate	C03453	159.027863	0.813
2-Aminomuconate	C02220	158.044861	0.746
L-Adrenaline	C00788	184.096848	1.695
Serotonin	C00780	177.102325	1.154
Ectoine	C06231	143.08168	0.695
3D-(3-5/4)-Trihydroxycyclohexane-1-2-dione	C04287	161.044525	0.725
sn-glycero-3-Phosphoethanolamine	C01233	216.063156	0.655
Diethanolamine	C06772	106.086823	0.691
Triethanolamine	C06771	150.11261	0.668
N-Methylethanolamine phosphate	C01210	156.042191	0.617
CDP-choline	C00307	489.114319	0.656
L-Carnitine	C00318	162.112442	0.662
Acetylcarnitine	HMDB0000201	204.123062	0.718
Propenoylcarnitine	HMDB0013124	216.123123	0.932
Propionylcarnitine	HMDB0000824	218.138748	1.064
Butyrylcarnitine	HMDB0002013	232.154358	1.741
Tiglylcarnitine	HMDB02366	244.154419	1.776
Isovalerylcarnitine	HMDB0000688	246.169983	1.775
Malonylcarnitine	HMDB0062592	248.112808	0.712
Hexenoylcarnitine	HMDB0013161	258.170044	1.835
Hexanoylcarnitine	HMDB0000705	260.185669	1.815
Methylmalonylcarnitine	HMDB0013133	262.128479	0.723
Hydroxyisovaleroyl carnitine	HMDB0062555	262.164948	1.109
Octenoylcarnitine	HMDB0013324	286.201172	1.89
Octanoylcarnitine	HMDB0000791	288.216827	1.903
Methylglutarylcarnitine	HMDB0000552	290.159698	1.824
Pimelylcarnitine	HMDB0013328	304.175537	1.806
Hydroxyoctanoyl carnitine	HMDB0061634	304.211823	1.807
Decanoylcarnitine	HMDB0000651	316.248169	2.02
Hydroxynonanoyl carnitine	HMDB0061635	318.227478	1.813
Hydroxydecanoyl carnitine	HMDB0061636	332.24292	1.887
Dodecenoylcarnitine	HMDB0013326	342.263763	1.867
Hydroxyundecanoyl carnitine	HMDB0061637	346.258789	1.906
Hydroxydodecanoyl carnitine	HMDB0061638	360.274323	2.027
Tetradecenoylcarnitine	HMDB0062588	370.295074	3.768
Tetradecanoylcarnitine	HMDB0005066	372.31073	1.888
Dodecanedioylcarnitine	HMDB0013327	374.253815	1.89
Hexadecenoyl carnitine	HMDB0006317	398.326721	1.993
Hydroxyhexadecenoylcarnitine	HMDB0013333	414.321289	3.673
Heptadecanoyl carnitine	HMDB0006210	414.357666	1.962
Hydroxyhexadecanoyl carnitine	HMDB0061642	416.336945	2.79
Alpha-linolenyl carnitine	HMDB0006319	422.325867	2.862
Linoelaidyl carnitine	HMDB0006461	424.341797	2.131
Elaidic carnitine	HMDB06464	426.357574	3.517
Hydroxyoctadecenoylcarnitine	HMDB0013339	442.35257	1.969
Cervonyl carnitine	HMDB0006510	472.342224	1.953
Docosapentaenoyl carnitine	HMDB0006321	474.357849	2.122
Hexadecadienoylcarnitine	HMDB0013334	396.310791	3.793
3-4-Dihydroxy-L-phenylalanine	C00355	198.076172	1.715
Tyramine	C00483	138.091461	1.795
4-Hydroxyphenylacetylglutamic acid	C05595	282.09668	0.647
4-Coumarate	C00811	165.054764	0.735
3alpha-12alpha-Dihydroxy-5beta-cholanate	C04483	393.297394	3.718
Leukotriene C4	C02166	626.310913	1.848
Testosterone	C00535	289.216217	2.112
Mevalonate	C00418	149.08165	0.649
Sphingosine	C00319	300.289612	1.86
Biliverdin	C00500	583.255249	2.085
trimethylamineoxide	C01104	76.076256	0.63
4-Imidazolone-5-propanoate	C03680	157.060974	0.593
N-Acetylmethionine	C02712	192.068863	1.781
N-Acetyl-D-phenylalanine	C05620	208.096985	1.849
N-Acetyl-L-aspartate	C01042	176.055496	0.744
N-Acetyl-L-glutamate	C00624	190.071411	1.901
N-Acetyl-L-histidine	C02997	198.087814	0.639
METABOLITES_END
#END