#METABOLOMICS WORKBENCH nmatulionis_20211021_161130 DATATRACK_ID:2898 STUDY_ID:ST001954 ANALYSIS_ID:AN003179 PROJECT_ID:PR001241
VERSION             	1
CREATED_ON             	October 25, 2021, 12:42 pm
#PROJECT
PR:PROJECT_TITLE                 	A pathogenic role for histone H3 copper reductase activity in a yeast model of
PR:PROJECT_TITLE                 	Friedreich’s Ataxia
PR:PROJECT_SUMMARY               	Disruptions to iron-sulfur (Fe-S) clusters, essential cofactors for a broad
PR:PROJECT_SUMMARY               	range of proteins, cause widespread cellular defects resulting in human disease.
PR:PROJECT_SUMMARY               	An underappreciated source of damage to Fe-S clusters are cuprous (Cu1+) ions.
PR:PROJECT_SUMMARY               	Since histone H3 enzymatically produces Cu1+ to support copper-dependent
PR:PROJECT_SUMMARY               	functions, we asked whether this activity could become detrimental to Fe-S
PR:PROJECT_SUMMARY               	clusters. Here, we report that histone H3-mediated Cu1+ toxicity is a major
PR:PROJECT_SUMMARY               	determinant of cellular functional pool of Fe-S clusters. Inadequate Fe-S
PR:PROJECT_SUMMARY               	cluster supply, either due to diminished assembly as occurs in Friedreich’s
PR:PROJECT_SUMMARY               	Ataxia or defective distribution, causes severe metabolic and growth defects in
PR:PROJECT_SUMMARY               	S. cerevisiae. Decreasing Cu1+ abundance, through attenuation of histone cupric
PR:PROJECT_SUMMARY               	reductase activity or depletion of total cellular copper, restored Fe-S
PR:PROJECT_SUMMARY               	cluster-dependent metabolism and growth. Our findings reveal a novel interplay
PR:PROJECT_SUMMARY               	between chromatin and mitochondria in Fe-S cluster homeostasis, and a potential
PR:PROJECT_SUMMARY               	pathogenic role for histone enzyme activity and Cu1+ in diseases with Fe-S
PR:PROJECT_SUMMARY               	cluster dysfunction.
PR:INSTITUTE                     	University of California, Los Angeles
PR:DEPARTMENT                    	Biomedical Sciences
PR:LAST_NAME                     	Matulionis
PR:FIRST_NAME                    	Nedas
PR:ADDRESS                       	615 Charles E Young Dr S, BSRB 354-05
PR:EMAIL                         	nmatulionis@mednet.ucla.edu
PR:PHONE                         	3302346450
#STUDY
ST:STUDY_TITLE                   	A pathogenic role for histone H3 copper reductase activity in a yeast model of
ST:STUDY_TITLE                   	Friedreich’s Ataxia
ST:STUDY_SUMMARY                 	Disruptions to iron-sulfur (Fe-S) clusters, essential cofactors for a broad
ST:STUDY_SUMMARY                 	range of proteins, cause widespread cellular defects resulting in human disease.
ST:STUDY_SUMMARY                 	An underappreciated source of damage to Fe-S clusters are cuprous (Cu1+) ions.
ST:STUDY_SUMMARY                 	Since histone H3 enzymatically produces Cu1+ to support copper-dependent
ST:STUDY_SUMMARY                 	functions, we asked whether this activity could become detrimental to Fe-S
ST:STUDY_SUMMARY                 	clusters. Here, we report that histone H3-mediated Cu1+ toxicity is a major
ST:STUDY_SUMMARY                 	determinant of cellular functional pool of Fe-S clusters. Inadequate Fe-S
ST:STUDY_SUMMARY                 	cluster supply, either due to diminished assembly as occurs in Friedreich’s
ST:STUDY_SUMMARY                 	Ataxia or defective distribution, causes severe metabolic and growth defects in
ST:STUDY_SUMMARY                 	S. cerevisiae. Decreasing Cu1+ abundance, through attenuation of histone cupric
ST:STUDY_SUMMARY                 	reductase activity or depletion of total cellular copper, restored Fe-S
ST:STUDY_SUMMARY                 	cluster-dependent metabolism and growth. Our findings reveal a novel interplay
ST:STUDY_SUMMARY                 	between chromatin and mitochondria in Fe-S cluster homeostasis, and a potential
ST:STUDY_SUMMARY                 	pathogenic role for histone enzyme activity and Cu1+ in diseases with Fe-S
ST:STUDY_SUMMARY                 	cluster dysfunction.
ST:INSTITUTE                     	University of California, Los Angeles
ST:LAST_NAME                     	Matulionis
ST:FIRST_NAME                    	Nedas
ST:ADDRESS                       	615 Charles E Young Dr S, BSRB 354-05
ST:EMAIL                         	nmatulionis@mednet.ucla.edu
ST:PHONE                         	3302346450
#SUBJECT
SU:SUBJECT_TYPE                  	Yeast
SU:SUBJECT_SPECIES               	Saccharomyces cerevisiae
SU:TAXONOMY_ID                   	4932
#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           	cell culture	cells-yeast-WT-01	Strain:wild type	RAW_FILE_NAME=cells-yeast-WT-01
SUBJECT_SAMPLE_FACTORS           	cell culture	cells-yeast-H3-A110C-01	Strain:H3A110C	RAW_FILE_NAME=cells-yeast-H3-A110C-01
SUBJECT_SAMPLE_FACTORS           	cell culture	cells-yeast-H3-H113N-01	Strain:H3H113N	RAW_FILE_NAME=cells-yeast-H3-H113N-01
SUBJECT_SAMPLE_FACTORS           	cell culture	cells-yeast-H3-dSGH1-01	Strain:dGsh1	RAW_FILE_NAME=cells-yeast-H3-dSGH1-01
SUBJECT_SAMPLE_FACTORS           	cell culture	cells-yeast-WT-02	Strain:wild type	RAW_FILE_NAME=cells-yeast-WT-02
SUBJECT_SAMPLE_FACTORS           	cell culture	cells-yeast-H3-A110C-02	Strain:H3A110C	RAW_FILE_NAME=cells-yeast-H3-A110C-02
SUBJECT_SAMPLE_FACTORS           	cell culture	cells-yeast-H3-H113N-02	Strain:H3H113N	RAW_FILE_NAME=cells-yeast-H3-H113N-02
SUBJECT_SAMPLE_FACTORS           	cell culture	cells-yeast-H3-dSGH1-02	Strain:dGsh1	RAW_FILE_NAME=cells-yeast-H3-dSGH1-02
SUBJECT_SAMPLE_FACTORS           	cell culture	cells-yeast-WT-03	Strain:wild type	RAW_FILE_NAME=cells-yeast-WT-03
SUBJECT_SAMPLE_FACTORS           	cell culture	cells-yeast-H3-A110C-03	Strain:H3A110C	RAW_FILE_NAME=cells-yeast-H3-A110C-03
SUBJECT_SAMPLE_FACTORS           	cell culture	cells-yeast-H3-H113N-03	Strain:H3H113N	RAW_FILE_NAME=cells-yeast-H3-H113N-03
SUBJECT_SAMPLE_FACTORS           	cell culture	cells-yeast-H3-dSGH1-03	Strain:dGsh1	RAW_FILE_NAME=cells-yeast-H3-dSGH1-03
SUBJECT_SAMPLE_FACTORS           	cell culture	cells-yeast-WT-04	Strain:wild type	RAW_FILE_NAME=cells-yeast-WT-04
SUBJECT_SAMPLE_FACTORS           	cell culture	cells-yeast-H3-A110C-04	Strain:H3A110C	RAW_FILE_NAME=cells-yeast-H3-A110C-04
SUBJECT_SAMPLE_FACTORS           	cell culture	cells-yeast-H3-H113N-04	Strain:H3H113N	RAW_FILE_NAME=cells-yeast-H3-H113N-04
SUBJECT_SAMPLE_FACTORS           	cell culture	cells-yeast-H3-dSGH1-04	Strain:dGsh1	RAW_FILE_NAME=cells-yeast-H3-dSGH1-04
SUBJECT_SAMPLE_FACTORS           	cell culture	cells-yeast-WT-05	Strain:wild type	RAW_FILE_NAME=cells-yeast-WT-05
SUBJECT_SAMPLE_FACTORS           	cell culture	cells-yeast-H3-A110C-05	Strain:H3A110C	RAW_FILE_NAME=cells-yeast-H3-A110C-05
SUBJECT_SAMPLE_FACTORS           	cell culture	cells-yeast-H3-H113N-05	Strain:H3H113N	RAW_FILE_NAME=cells-yeast-H3-H113N-05
SUBJECT_SAMPLE_FACTORS           	cell culture	cells-yeast-H3-dSGH1-05	Strain:dGsh1	RAW_FILE_NAME=cells-yeast-H3-dSGH1-05
#COLLECTION
CO:COLLECTION_SUMMARY            	Please refer to Treatment and Sample Prep sections.
CO:SAMPLE_TYPE                   	Yeast cells
#TREATMENT
TR:TREATMENT_SUMMARY             	Yeast strains with wild type or mutant histone H3 were cultured in yeast
TR:TREATMENT_SUMMARY             	Synthetic Complete Medium before collection and extraction. As a control and for
TR:TREATMENT_SUMMARY             	comparison, a strain with GSH1 deleted is included. GSH1 encodes for gamma
TR:TREATMENT_SUMMARY             	glutamylcysteine synthetase, which catalyzes the first step in glutathione
TR:TREATMENT_SUMMARY             	biosynthesis.
#SAMPLEPREP
SP:SAMPLEPREP_SUMMARY            	To extract metabolites, we washed the cells with ice-cold 150 mM ammonium
SP:SAMPLEPREP_SUMMARY            	acetate, pH 7.3, and then added 500 uL 80% methanol and incubated for 20 minutes
SP:SAMPLEPREP_SUMMARY            	at -80°C. Cells were then scraped off the plate, vortexed and centrifuged for
SP:SAMPLEPREP_SUMMARY            	10 minutes at maximum speed. We dried 400 uL of the supernatant under vacuum and
SP:SAMPLEPREP_SUMMARY            	stored the dried metabolites at -80°C. Dried metabolites were reconstituted in
SP:SAMPLEPREP_SUMMARY            	100 µL of a 50% acetonitrile(ACN) 50% dH20 solution. Samples were vortexed and
SP:SAMPLEPREP_SUMMARY            	spun down for 10 min at 17,000g. 70 µL of the supernatant was then transferred
SP:SAMPLEPREP_SUMMARY            	to HPLC glass vials.
#CHROMATOGRAPHY
CH:CHROMATOGRAPHY_SUMMARY        	Samples were run on a Vanquish (Thermo Scientific) UHPLC system with mobile
CH:CHROMATOGRAPHY_SUMMARY        	phase A (20 mM ammonium carbonate, pH 9.7) and mobile phase B (100%
CH:CHROMATOGRAPHY_SUMMARY        	Acetonitrile) at a flow rate of 150 µL/min on a SeQuant ZIC-pHILIC Polymeric
CH:CHROMATOGRAPHY_SUMMARY        	column (2.1 × 150 mm 5 μm, EMD Millipore) at 35°C. Separation was achieved
CH:CHROMATOGRAPHY_SUMMARY        	with a linear gradient from 20% A to 80% A in 20 min followed by a linear
CH:CHROMATOGRAPHY_SUMMARY        	gradient from 80% A to 20% A from 20 min to 20.5 min. 20% A was then held from
CH:CHROMATOGRAPHY_SUMMARY        	20.5 min to 28 min.
CH:CHROMATOGRAPHY_TYPE           	HILIC
CH:INSTRUMENT_NAME               	Thermo Vanquish Horizon
CH:COLUMN_NAME                   	SeQuant ZIC-HILIC (150 x 2.1mm, 5um)
CH:FLOW_GRADIENT                 	100% Acetonitrile
CH:FLOW_RATE                     	150 µL/min
CH:COLUMN_TEMPERATURE            	35°C
CH:SOLVENT_A                     	20 mM Ammonium carbonate, pH 9.7
CH:SOLVENT_B                     	100% Acetonitrile
CH:INTERNAL_STANDARD             	10 nM Trifluoromethanesulfonate (extraction buffer)
#ANALYSIS
AN:ANALYSIS_TYPE                 	MS
AN:LABORATORY_NAME               	UCLA
AN:OPERATOR_NAME                 	Nedas Matulionis
#MS
MS:INSTRUMENT_NAME               	Thermo Q Exactive Orbitrap
MS:INSTRUMENT_TYPE               	Orbitrap
MS:MS_TYPE                       	ESI
MS:ION_MODE                      	UNSPECIFIED
MS:MS_COMMENTS                   	The UHPLC was coupled to a Q-Exactive (Thermo Scientific) mass analyzer running
MS:MS_COMMENTS                   	in polarity switching mode with spray-voltage=3.2kV, sheath-gas=40, aux-gas=15,
MS:MS_COMMENTS                   	sweep-gas=1, aux-gas-temp=350°C, and capillary-temp=275°C. For both polarities
MS:MS_COMMENTS                   	mass scan settings were kept at full-scan-range=(70-1000),
MS:MS_COMMENTS                   	ms1-resolution=70,000, max-injection-time=250ms, and AGC-target=1E6. MS2 data
MS:MS_COMMENTS                   	was also collected from the top three most abundant singly-charged ions in each
MS:MS_COMMENTS                   	scan with normalized-collision-energy=35. Each of the resulting “.RAW” files
MS:MS_COMMENTS                   	was then centroided and converted into two “.mzXML” files (one for positive
MS:MS_COMMENTS                   	scans and one for negative scans) using msconvert from ProteoWizard. These
MS:MS_COMMENTS                   	“.mzXML” files were imported into the MZmine 2 software package. Ion
MS:MS_COMMENTS                   	chromatograms were generated from MS1 spectra via the built-in Automated Data
MS:MS_COMMENTS                   	Analysis Pipeline (ADAP) chromatogram module and peaks were detected via the
MS:MS_COMMENTS                   	ADAP wavelets algorithm. Peaks were aligned across all samples via the Random
MS:MS_COMMENTS                   	sample consensus aligner module, gap-filled, and assigned identities using an
MS:MS_COMMENTS                   	exact mass MS1(+/-15ppm) and retention time RT (+/-0.5min) search of our
MS:MS_COMMENTS                   	in-house MS1-RT database. Peak boundaries and identifications were then further
MS:MS_COMMENTS                   	refined by manual curation. Peaks were quantified by area under the curve
MS:MS_COMMENTS                   	integration and exported as CSV files. If stable isotope tracing was used in the
MS:MS_COMMENTS                   	experiment, the peak areas were additionally processed via the R package AccuCor
MS:MS_COMMENTS                   	to correct for natural isotope abundance. Peak areas for each sample were
MS:MS_COMMENTS                   	normalized by the measured area of the internal standard
MS:MS_COMMENTS                   	trifluoromethanesulfonate (present in the extraction buffer) and by the number
MS:MS_COMMENTS                   	of cells present in the extracted well.
#MS_METABOLITE_DATA
MS_METABOLITE_DATA:UNITS	Peak Area
MS_METABOLITE_DATA_START
Samples	cells-yeast-H3-A110C-01	cells-yeast-H3-A110C-02	cells-yeast-H3-A110C-03	cells-yeast-H3-A110C-04	cells-yeast-H3-A110C-05	cells-yeast-H3-H113N-01	cells-yeast-H3-H113N-02	cells-yeast-H3-H113N-03	cells-yeast-H3-H113N-04	cells-yeast-H3-H113N-05	cells-yeast-H3-dSGH1-01	cells-yeast-H3-dSGH1-02	cells-yeast-H3-dSGH1-03	cells-yeast-H3-dSGH1-04	cells-yeast-H3-dSGH1-05	cells-yeast-WT-01	cells-yeast-WT-02	cells-yeast-WT-03	cells-yeast-WT-04	cells-yeast-WT-05
Factors	Strain:H3A110C	Strain:H3A110C	Strain:H3A110C	Strain:H3A110C	Strain:H3A110C	Strain:H3H113N	Strain:H3H113N	Strain:H3H113N	Strain:H3H113N	Strain:H3H113N	Strain:dGsh1	Strain:dGsh1	Strain:dGsh1	Strain:dGsh1	Strain:dGsh1	Strain:wild type	Strain:wild type	Strain:wild type	Strain:wild type	Strain:wild type
glycine	1.70E+07	1.57E+07	2.07E+07	1.72E+07	2.34E+07	9168753.594	1.02E+07	1.08E+07	1.52E+07	1.47E+07	1.95E+07	1.67E+07	1.78E+07	2.24E+07	3.10E+07	1.67E+07	1.37E+07	1.72E+07	2.00E+07	2.08E+07
alanine	3.37E+08	2.78E+08	3.47E+08	2.86E+08	3.10E+08	4.41E+08	4.77E+08	5.27E+08	5.90E+08	5.15E+08	5.42E+08	8.20E+08	6.30E+08	9.46E+08	1.00E+09	3.10E+08	2.74E+08	3.25E+08	3.28E+08	3.04E+08
choline	8.30E+07	1.24E+08	1.55E+08	7.68E+07	6.25E+07	6.77E+07	8.02E+07	7.67E+07	1.17E+08	4.95E+07	2.40E+08	3.07E+08	2.12E+08	3.00E+08	2.82E+08	7.71E+07	8.91E+07	1.19E+08	3.62E+07	3.32E+07
serine	1.94E+08	2.17E+08	2.14E+08	2.16E+08	2.38E+08	1.38E+08	1.66E+08	1.52E+08	2.18E+08	2.08E+08	1.88E+08	2.28E+08	1.84E+08	2.53E+08	2.94E+08	1.92E+08	1.89E+08	1.82E+08	2.36E+08	2.40E+08
creatinine	461138.5027	120586.8742	431188.8348	215172.129	201301.5588	436931.9447	177332.5271	155538.4022	532479.4642	682773.6305	149467.9284	405557.3995	218638.1903	507630.0336	424106.4812	619691.2848	617981.9907	391534.2596	544504.1731	299347.2832
proline	4.84E+09	4.43E+09	5.31E+09	4.25E+09	4.93E+09	3.59E+09	3.73E+09	4.17E+09	4.45E+09	3.89E+09	3.68E+09	3.19E+09	3.37E+09	2.87E+09	3.08E+09	4.69E+09	4.17E+09	4.95E+09	4.16E+09	4.28E+09
betaine	3.30E+07	2.32E+07	2.30E+07	2.99E+07	3.87E+07	2.81E+07	4.04E+07	3.26E+07	4.11E+07	3.40E+07	4.19E+07	3.01E+07	2.09E+07	1.90E+07	2.08E+07	1.32E+07	2.43E+07	2.86E+07	3.45E+07	3.46E+07
valine	6.86E+08	5.61E+08	6.86E+08	4.97E+08	6.21E+08	7.45E+08	7.51E+08	7.07E+08	1.25E+09	7.40E+08	6.36E+08	1.37E+09	9.18E+08	1.47E+09	1.45E+09	7.29E+08	4.89E+08	5.24E+08	4.79E+08	5.11E+08
threonine	2.44E+09	2.63E+09	2.71E+09	2.57E+09	3.17E+09	1.35E+09	1.49E+09	1.44E+09	1.92E+09	1.80E+09	2.49E+09	2.26E+09	2.20E+09	2.47E+09	2.65E+09	2.40E+09	2.43E+09	2.43E+09	2.81E+09	2.91E+09
nicotinamide	2.34E+07	2.27E+07	6341071.203	4.59E+07	5.58E+07	7779284.468	3.45E+07	3260227.723	5.34E+07	4.08E+07	1.63E+07	4.17E+07	2.05E+07	7.65E+07	6.69E+07	3.77E+07	5.26E+07	4705328.205	3.88E+07	5.88E+07
creatine	559899.7636	0	1274473.761	880626.2696	0	0	0	0	0	2832243.773	0	0	0	984125.7527	451255.4896	4647397.537	3675965.134	2971765.091	3412243.129	322201.3536
leucine / isoleucine	1.57E+09	1.59E+09	2.09E+09	1.60E+09	2.17E+09	1.17E+09	1.32E+09	1.43E+09	1.94E+09	1.68E+09	2.46E+09	2.68E+09	2.49E+09	2.76E+09	3.22E+09	1.53E+09	1.42E+09	1.71E+09	1.53E+09	1.79E+09
asparagine	3.24E+08	3.09E+08	3.86E+08	3.22E+08	3.67E+08	2.04E+08	2.38E+08	2.42E+08	3.82E+08	2.91E+08	3.24E+08	3.52E+08	2.73E+08	3.61E+08	4.14E+08	3.16E+08	2.75E+08	3.20E+08	3.31E+08	3.68E+08
ornithine	9.21E+07	9.76E+07	9.93E+07	8.15E+07	1.14E+08	2.18E+08	2.62E+08	3.05E+08	3.10E+08	2.34E+08	1.50E+08	9.10E+07	9.04E+07	8.91E+07	1.05E+08	9.49E+07	9.48E+07	8.56E+07	9.75E+07	9.58E+07
gamma-butyrobetaine	8288090.151	3725186.918	3663195.291	3783588.737	4233009.49	2.41E+07	2.18E+07	7498876.691	1.54E+07	1.06E+07	1.68E+07	1.09E+07	7598683.371	4901361.289	4138448.364	3023981.976	3310083.495	2889112.78	4510286.283	4192325.911
lysine	5.11E+09	4.70E+09	4.79E+09	4.85E+09	5.83E+09	5.27E+09	5.91E+09	5.92E+09	7.43E+09	5.77E+09	3.68E+09	3.51E+09	2.80E+09	3.92E+09	3.98E+09	5.22E+09	4.50E+09	4.46E+09	4.93E+09	5.09E+09
methionine	2.10E+09	1.98E+09	2.28E+09	1.52E+09	1.86E+09	1.63E+09	1.55E+09	1.55E+09	1.86E+09	1.40E+09	2.08E+09	2.02E+09	1.67E+09	1.38E+09	1.55E+09	2.09E+09	1.74E+09	1.94E+09	1.55E+09	1.58E+09
carnitine	1.39E+07	4861133.508	4701486.462	4382978.729	5717055.799	1.96E+07	1.67E+07	5988238.482	1.06E+07	6560094.141	3.14E+07	1.80E+07	1.25E+07	8196815.754	7219685.269	4295233.169	4508251.431	4060381.157	5852201.082	5172957.449
methioninesulfoxide	1.38E+08	1.81E+08	1.95E+08	2.04E+08	2.20E+08	8.81E+07	8.98E+07	9.91E+07	1.66E+08	1.53E+08	1.92E+08	2.14E+08	2.02E+08	2.40E+08	3.40E+08	1.59E+08	1.66E+08	1.58E+08	1.74E+08	2.02E+08
phenylalanine	1.31E+09	1.59E+09	2.08E+09	1.35E+09	1.88E+09	1.56E+09	1.82E+09	2.12E+09	2.56E+09	2.00E+09	3.39E+09	4.39E+09	3.67E+09	4.19E+09	4.67E+09	1.27E+09	1.29E+09	1.61E+09	1.28E+09	1.46E+09
arginine	5.06E+09	4.90E+09	4.87E+09	4.81E+09	5.86E+09	4.05E+09	4.96E+09	4.68E+09	6.03E+09	4.75E+09	2.43E+09	3.18E+09	2.52E+09	3.63E+09	3.72E+09	5.03E+09	4.40E+09	4.47E+09	4.69E+09	4.90E+09
citrulline	4.71E+08	4.83E+08	4.94E+08	4.80E+08	4.58E+08	1.33E+09	1.11E+09	1.32E+09	1.27E+09	9.48E+08	6.49E+08	3.27E+08	3.49E+08	2.74E+08	2.61E+08	4.50E+08	5.06E+08	4.58E+08	4.85E+08	4.40E+08
phosphocholine	1.42E+07	1.93E+07	4.83E+07	1.41E+07	3.51E+07	1.25E+07	1.98E+07	1.49E+07	2.65E+07	1.36E+07	3.35E+07	7.47E+07	8.09E+07	2.01E+08	1.63E+08	1.49E+07	1.64E+07	2.60E+07	1.46E+07	1.44E+07
N-trimethyllysine	6.62E+07	5.39E+07	7.09E+07	6.66E+07	7.69E+07	6.55E+07	8.74E+07	7.81E+07	1.27E+08	7.76E+07	5.28E+07	5.16E+07	4.17E+07	7.06E+07	2.57E+07	6.10E+07	6.02E+07	6.81E+07	7.03E+07	7.24E+07
acetyl-carnitine	7893108.325	4301822.766	3982920.889	5041806.009	6152201.377	3.25E+07	3.05E+07	1.05E+07	2.13E+07	1.77E+07	1.22E+07	9097663.097	9754915.746	5820794.69	4793387.808	3003217.223	3821299.336	2364803.55	5714319.348	4707116.418
kynurenine	1.77E+07	3.03E+07	3.39E+07	1.77E+07	2.10E+07	9.75E+07	1.43E+08	1.40E+08	1.68E+08	1.10E+08	1.76E+07	2.01E+07	1.50E+07	1.43E+07	9337722.626	1.55E+07	1.81E+07	2.57E+07	1.66E+07	1.74E+07
cystathionine	3.08E+08	2.75E+08	3.37E+08	2.83E+08	3.56E+08	1.11E+08	1.56E+08	1.29E+08	2.32E+08	1.37E+08	7.34E+08	8.56E+08	4.85E+08	7.99E+08	7.08E+08	3.00E+08	2.72E+08	3.03E+08	3.04E+08	3.00E+08
glycerophosphocholine	1.66E+08	1.89E+08	3.26E+08	1.24E+08	2.51E+08	3.77E+08	4.94E+08	5.56E+08	4.23E+08	3.33E+08	2.69E+08	8.61E+08	1.24E+09	1.75E+09	1.40E+09	1.64E+08	1.67E+08	4.28E+08	1.83E+08	1.32E+08
adenosine	1.24E+08	1.25E+08	8.04E+07	6.77E+07	7.19E+07	6.58E+07	7.49E+07	5.52E+07	4.14E+07	3.77E+07	1.48E+08	1.28E+08	9.77E+07	7.91E+07	9.95E+07	1.28E+08	1.28E+08	1.27E+08	8.13E+07	7.38E+07
5'-methylthioadenosine	8.64E+07	4.52E+07	3.17E+07	4.58E+07	5.87E+07	3.97E+07	4.40E+07	2.82E+07	4.67E+07	3.18E+07	3.86E+07	9.87E+07	5.80E+07	1.43E+08	1.52E+08	8.64E+07	4.53E+07	2.22E+07	7.74E+07	7.05E+07
S-adenosyl-methionine	1.40E+07	1.61E+07	2.00E+07	1.71E+07	2.00E+07	2.45E+07	2.54E+07	2.41E+07	2.99E+07	2.10E+07	6.84E+07	1.61E+08	1.34E+08	3.80E+08	4.60E+08	1.29E+07	1.51E+07	1.50E+07	1.43E+07	1.56E+07
CDP-choline	1287212.002	2824223.292	5055453.354	790956.4987	2516997.187	591772.3073	1557177.637	5033015.857	0	0	2435350.968	1068623.447	3170707.125	2539640.943	1313590.221	984377.7383	989250.7035	1551912.886	1521436.674	434056.4214
NAD+	1.43E+08	1.50E+08	1.41E+08	1.40E+08	2.10E+08	8.07E+07	9.95E+07	7.83E+07	1.09E+08	1.04E+08	1.82E+08	1.69E+08	1.55E+08	2.04E+08	1.89E+08	1.53E+08	1.47E+08	1.22E+08	1.14E+08	1.60E+08
NADP+	1152928.037	1329795.563	1414357.97	697690.517	1691170.378	1169932.602	1157950.499	566963.7106	1113643.168	733428.0991	5695100.428	6327634.569	4575494.077	6411258.436	5731836.128	1709981.023	1612593.811	1062233.227	693242.7119	931927.7239
riboflavin	408776.3594	666002.8828	363686.5781	474604.7511	388097.6406	1011647.906	1075591.469	719931.125	1533605.492	675249.0279	911474.0391	1454313.609	1440814.701	1875520.901	1255317.693	801663.8669	837577.9177	427270.6914	401705.8055	295217.8476
caffeine	7811.226563	8406.632813	14493.27148	17635.06836	1968.789063	18042.37695	37346.48633	7868.117188	30911.23633	0	5454.09375	3570.005859	12843.77344	10624.97852	34009.51434	16952.44727	6440.173828	13468.32106	0	0
pyruvate	1.36E+08	1.45E+08	1.81E+08	1.53E+08	1.63E+08	7.23E+07	7.00E+07	8.24E+07	1.34E+08	8.12E+07	8.05E+07	6.57E+07	6.64E+07	8.92E+07	7.23E+07	1.27E+08	1.41E+08	1.69E+08	1.28E+08	1.42E+08
lactate	1.61E+08	7.16E+07	8.56E+07	1.67E+08	2.13E+08	1.48E+08	9.09E+07	7.68E+07	2.52E+08	1.82E+08	8.10E+07	1.40E+08	6.97E+07	2.86E+08	3.03E+08	1.52E+08	6.67E+07	4.84E+07	1.49E+08	1.85E+08
phosphate	4885763.757	6632116.173	9549451.8	8638117.352	1.07E+07	4270729.121	4499606.826	4163558.298	1.24E+07	8998486.024	6830496.246	7813372.028	7507004.526	8156445.275	1.20E+07	6138112.794	7077692.719	6546852.479	5324778.517	7746901.455
gamma-amino-butyrate	2.54E+08	2.38E+08	2.65E+08	2.37E+08	2.89E+08	2.08E+08	2.61E+08	2.46E+08	3.38E+08	2.76E+08	2.36E+08	2.53E+08	2.20E+08	2.32E+08	2.41E+08	2.56E+08	2.36E+08	2.52E+08	2.65E+08	2.63E+08
fumarate	9.12E+07	7.46E+07	8.26E+07	8.02E+07	7.41E+07	4.00E+07	5.10E+07	5.32E+07	6.10E+07	4.10E+07	7.40E+07	8.89E+07	5.03E+07	9.52E+07	7.60E+07	8.79E+07	6.64E+07	7.64E+07	6.61E+07	5.18E+07
succinate	1.81E+09	1.02E+09	1.30E+09	1.49E+09	2.06E+09	1.23E+09	8.61E+08	9.43E+08	1.74E+09	1.40E+09	3.55E+08	1.57E+08	1.24E+08	1.40E+08	1.24E+08	1.63E+09	1.01E+09	1.28E+09	1.67E+09	1.67E+09
picolinic acid	4136232.118	4077490.54	4015513.406	1607709.389	3827070.788	9307711.276	6639073.767	2697733.778	9969290.685	4231424.406	5230626.604	8839967.153	5504136.327	3910627.242	6854732.46	4125316.295	2807598.342	2624032.087	2077006.682	2995243.564
aspartate	4.29E+09	4.30E+09	4.63E+09	4.26E+09	5.46E+09	2.59E+09	3.22E+09	3.09E+09	4.45E+09	3.52E+09	2.70E+09	2.90E+09	1.81E+09	2.51E+09	2.88E+09	4.50E+09	4.01E+09	4.26E+09	4.48E+09	4.60E+09
malate	9.96E+08	8.76E+08	9.05E+08	9.45E+08	8.38E+08	4.79E+08	6.25E+08	6.18E+08	7.42E+08	5.03E+08	8.29E+08	1.06E+09	6.43E+08	1.21E+09	9.99E+08	9.59E+08	7.88E+08	8.54E+08	8.18E+08	6.54E+08
phosphorylethanolamine	2986151.689	2565849.927	2392714.301	2898547.083	3978079.486	1588248.554	2112636.898	1210734.677	2634557.207	2368892.191	3074838.797	1442515.178	950073.6209	1125983.015	976829.3033	3702042.43	2820154.879	2392415.902	3290518.996	3059490.388
alpha-ketoglutarate	5.89E+07	7.54E+07	9.75E+07	1.08E+08	1.06E+08	8.49E+07	9.60E+07	8.81E+07	1.26E+08	1.02E+08	6.12E+07	5.31E+07	7.38E+07	1.12E+08	1.41E+08	9.41E+07	7.42E+07	7.09E+07	1.13E+08	1.06E+08
glutamine	3.52E+09	3.25E+09	3.43E+09	3.39E+09	4.12E+09	3.92E+09	4.92E+09	5.08E+09	5.96E+09	5.50E+09	2.67E+09	3.14E+09	3.29E+09	3.71E+09	4.20E+09	3.45E+09	3.00E+09	3.21E+09	3.76E+09	3.63E+09
glutamate	1.26E+10	1.17E+10	1.31E+10	1.18E+10	1.43E+10	1.05E+10	1.28E+10	1.21E+10	1.64E+10	1.37E+10	1.15E+10	1.25E+10	1.07E+10	1.10E+10	1.16E+10	1.26E+10	1.15E+10	1.24E+10	1.29E+10	1.30E+10
hydroxyglutarate	7.45E+07	4.83E+07	4.26E+07	6.80E+07	5.81E+07	1.32E+08	1.62E+08	1.18E+08	2.21E+08	1.49E+08	7.71E+07	1.27E+08	8.65E+07	1.50E+08	9.69E+07	5.74E+07	4.85E+07	4.55E+07	7.80E+07	5.40E+07
trifluoromethanesulfonate*	2.91E+07	3.25E+07	3.10E+07	2.70E+07	2.91E+07	3.25E+07	3.33E+07	2.74E+07	9.33E+07	2.72E+07	3.43E+07	3.37E+07	4.84E+07	3.00E+07	5.34E+07	2.84E+07	3.20E+07	2.74E+07	4.08E+07	2.53E+07
xylulose	2.07E+07	2.11E+07	2.68E+07	1.49E+07	2.13E+07	1.42E+07	1.62E+07	1.84E+07	2.10E+07	1.34E+07	2.51E+07	2.71E+07	2.00E+07	1.38E+07	1.85E+07	2.06E+07	1.75E+07	2.19E+07	1.48E+07	1.66E+07
histidine	2.70E+09	2.92E+09	2.99E+09	2.83E+09	3.30E+09	2.65E+09	3.20E+09	3.35E+09	4.36E+09	3.43E+09	3.02E+09	3.74E+09	2.93E+09	4.00E+09	4.14E+09	2.63E+09	2.51E+09	2.55E+09	2.74E+09	2.94E+09
orotate	1.48E+08	7.03E+07	1.17E+08	3.04E+07	5.72E+07	2.78E+08	1.45E+08	8.90E+07	1.71E+08	3.46E+07	1.33E+08	1.65E+08	6.70E+07	1.97E+07	1.26E+07	1.64E+08	8.54E+07	1.44E+08	3.37E+07	4.40E+07
dihydroorotate	2.53E+07	1.33E+07	2.76E+07	1.31E+07	0	6.05E+07	2.21E+07	1.75E+07	1.05E+08	27156.85449	1.77E+07	1.86E+07	9077054.063	4860831.984	0	2.86E+07	1.28E+07	1.79E+07	2302641.626	86453.00977
quinolinic acid	1.34E+07	2.42E+07	1.72E+07	2.26E+07	1.91E+07	2.80E+07	3.66E+07	2.72E+07	7.29E+07	3.91E+07	9710212.828	1.00E+07	5791543.002	6924215.42	5756244.986	1.19E+07	1.42E+07	1.34E+07	2.08E+07	1.65E+07
phosphoenolpyruvate	8739088.119	1.09E+07	1.34E+07	7661889.573	5821011.413	1.87E+07	3.53E+07	3.22E+07	1.06E+07	1.03E+07	4462706.078	6456855.241	8393266.804	3049570.351	1849171.48	1.03E+07	6328668.466	9866851.789	8561552.988	6831724.541
dihydroxyacetone-phosphate	3.09E+07	3.61E+07	1.60E+08	7.82E+07	4.20E+07	1.99E+07	1.22E+07	4.65E+07	6.87E+07	4.04E+07	5.93E+07	2.66E+07	3.01E+07	6.28E+07	4.42E+07	2.49E+07	2.08E+07	1.00E+08	2.58E+07	4.60E+07
glycerol-3-phosphate	2.17E+07	1.48E+07	1.24E+07	2.84E+07	2.35E+07	1.62E+07	1.20E+07	1.47E+07	2.09E+07	1.71E+07	1.24E+07	2.10E+07	1.76E+07	3.26E+07	2.86E+07	2.17E+07	1.48E+07	1.24E+07	2.43E+07	2.29E+07
cis-aconitate	7.52E+07	7.68E+07	7.99E+07	9.94E+07	4.14E+07	8.55E+07	9.30E+07	1.10E+08	9.64E+07	6.64E+07	2.48E+08	3.27E+08	3.38E+08	2.48E+08	1.38E+08	7.58E+07	9.81E+07	1.03E+08	9.46E+07	7.96E+07
carbamoyl-aspartate	6536742.948	3491248.638	9166185.874	7280224.755	9823179.863	1.15E+07	7953111.974	8577779.087	2.63E+07	1.07E+07	2757573.513	4108209.9	1985793.072	4621011.613	4210884.545	6449811.581	3822677.697	6125394.871	8292340.702	7637905.122
glucose	1.32E+08	1.42E+08	4.16E+08	2.86E+08	5.74E+08	1.36E+08	1.29E+08	8.53E+07	5.36E+08	4.16E+08	4.20E+08	5.70E+08	5.54E+08	7.22E+08	1.19E+09	1.40E+08	1.77E+08	2.05E+08	9.35E+07	4.01E+08
tyrosine	3.02E+08	3.45E+08	4.82E+08	3.40E+08	5.31E+08	5.25E+08	6.32E+08	7.39E+08	9.72E+08	8.03E+08	1.27E+09	2.44E+09	2.22E+09	2.85E+09	3.12E+09	2.99E+08	3.02E+08	3.61E+08	3.20E+08	4.27E+08
sorbitol	3.09E+08	2.83E+08	3.04E+08	2.89E+08	3.50E+08	4.69E+08	5.59E+08	5.90E+08	8.34E+08	6.17E+08	3.02E+08	3.45E+08	2.58E+08	3.67E+08	3.89E+08	2.87E+08	2.37E+08	2.85E+08	3.09E+08	3.08E+08
phosphoserine	534061.8487	783178.822	806049.8223	608593.2248	1209440.536	290173.1892	483507.6704	543183.4203	554817.681	386857.6488	456387.7761	776810.4913	955819.1735	839012.26	826082.3005	516645.3041	717220.1673	700710.1526	645409.9043	717662.4212
phosphoglycerate	2.35E+07	3.04E+07	4.12E+07	4.82E+07	5.91E+07	2.97E+07	5.12E+07	5.31E+07	6.76E+07	5.80E+07	3.00E+07	3.94E+07	4.01E+07	5.07E+07	5.56E+07	2.50E+07	3.06E+07	3.00E+07	2.94E+07	4.18E+07
N-acetylglutamate	8.40E+08	6.58E+08	7.07E+08	8.27E+08	9.60E+08	4.94E+08	6.16E+08	6.34E+08	8.73E+08	8.20E+08	1.27E+09	6.37E+08	6.83E+08	4.50E+08	5.49E+08	7.73E+08	6.70E+08	6.92E+08	9.09E+08	9.16E+08
citrate / isocitrate	6.68E+08	5.25E+08	9.30E+08	6.81E+08	7.51E+08	4.82E+08	6.05E+08	5.45E+08	7.47E+08	5.05E+08	2.10E+09	3.00E+09	3.05E+09	3.90E+09	3.02E+09	5.65E+08	7.81E+08	7.81E+08	6.68E+08	7.12E+08
erythrose-4-phosphate	881985.9944	1866243.064	973501.5924	4186343.256	1753776.389	639706.5382	328890.5175	203764.2267	1046802.703	1248656.138	3680809.851	4595250.487	3154125.446	4543365.564	3867899.938	1009023.8	2037059.064	1574753.437	653648.4452	2504444.291
lauric acid	4.00E+08	1.62E+08	2.68E+08	1.18E+08	1.55E+08	1.97E+08	1.37E+08	1.70E+08	2.31E+08	1.06E+08	1.44E+08	8.51E+07	9.63E+07	5.17E+07	6.18E+07	3.97E+08	1.43E+08	2.03E+08	1.11E+08	1.12E+08
tryptophan	1.38E+08	2.40E+08	4.49E+08	1.52E+08	2.47E+08	1.22E+08	1.70E+08	2.32E+08	2.42E+08	1.70E+08	5.17E+08	1.06E+09	9.36E+08	7.54E+08	8.51E+08	1.39E+08	2.21E+08	3.69E+08	1.21E+08	1.80E+08
myristic acid	2.40E+08	1.85E+08	2.25E+08	1.59E+08	1.79E+08	1.39E+08	1.75E+08	1.70E+08	1.83E+08	1.34E+08	1.85E+08	1.35E+08	1.88E+08	1.12E+08	1.14E+08	2.59E+08	1.90E+08	2.09E+08	1.79E+08	1.58E+08
phosphoribosylamine	102129.7244	592466.4421	956522.3707	485522.9647	441168.9979	138986.0059	407930.5531	315774.7746	762779.5101	331836.6723	511687.5154	1877206.669	1794350.248	554672.089	754540.586	302583.5187	716397.1648	600264.1529	70433.36445	410782.6811
rib/ribul/xylul-ose-phosphate	7083090.969	7367541.813	2.64E+07	1.52E+07	1.45E+07	4932387.024	5000818.438	7818756.18	2.38E+07	1.21E+07	1.40E+07	1.03E+07	1.21E+07	1.37E+07	1.64E+07	6855685.859	6143681.133	1.80E+07	7241720.387	1.32E+07
S-(2-Succinyl)-L-cysteine	487274.3852	868639.4837	436943.2351	654594.8435	585355.8917	354154.4623	976835.9247	515433.4733	978511.2552	873022.7333	513777.3371	1577713.421	812206.9291	1285989.404	339455.9441	643786.825	768821.8033	382130.3394	914430.7563	730117.2134
cytidine	1.20E+07	1.47E+07	1.24E+07	8903087.505	1.01E+07	2.70E+07	3.38E+07	3.74E+07	3.41E+07	2.30E+07	1.61E+07	2.30E+07	2.30E+07	9973636.493	7881813.634	1.21E+07	1.16E+07	1.38E+07	1.03E+07	8360636.319
palmitic acid	3.10E+09	3.27E+09	3.40E+09	3.34E+09	3.47E+09	2.41E+09	3.04E+09	3.04E+09	3.58E+09	3.71E+09	3.07E+09	3.19E+09	3.29E+09	3.49E+09	3.58E+09	3.34E+09	3.07E+09	3.36E+09	3.66E+09	3.44E+09
fructose-1-phosphate	1.93E+07	3.66E+07	3.98E+07	6.99E+07	4.03E+07	1.60E+07	1.44E+07	1.70E+07	3.15E+07	3.39E+07	6.61E+07	9.00E+07	7.12E+07	8.27E+07	9.87E+07	2.35E+07	3.72E+07	4.33E+07	1.13E+07	5.01E+07
inosine	3.06E+08	3.99E+08	3.19E+08	3.09E+08	3.42E+08	4.66E+08	7.81E+08	9.41E+08	1.03E+09	7.47E+08	2.68E+08	5.14E+08	3.77E+08	4.71E+08	5.28E+08	2.56E+08	2.74E+08	2.72E+08	2.97E+08	2.56E+08
6-phosphogluconic acid	9097898.984	2.45E+07	3.87E+07	1.76E+07	1.85E+07	7736418.905	1.24E+07	4499604.013	2.58E+07	1.15E+07	4.25E+07	6.27E+07	4.54E+07	3.86E+07	2.89E+07	9625207.248	3.27E+07	2.32E+07	6642747.068	1.25E+07
saccharopine	7.41E+07	6.77E+07	7.77E+07	7.00E+07	9.02E+07	5.58E+07	7.73E+07	6.49E+07	9.36E+07	5.98E+07	7.08E+07	8.11E+07	7.14E+07	7.49E+07	6.49E+07	8.31E+07	7.15E+07	7.51E+07	7.29E+07	7.02E+07
oleic acid	3.44E+08	2.64E+08	4.72E+08	1.69E+08	1.98E+08	7.53E+08	1.01E+09	1.14E+09	1.02E+09	4.77E+08	2.09E+08	2.04E+08	5.13E+08	9.82E+07	1.32E+08	3.72E+08	2.73E+08	4.67E+08	2.27E+08	1.34E+08
guanosine	8593444.53	2.12E+07	1.40E+07	1.31E+07	7575919.384	1.62E+07	2.82E+07	4.23E+07	3.28E+07	1.52E+07	8023406.392	1.20E+07	1.13E+07	1.19E+07	8797391.673	8909700.842	1.28E+07	1.32E+07	1.04E+07	5515257.012
stearic acid	9.80E+08	1.02E+09	8.43E+08	7.73E+08	8.20E+08	7.53E+08	8.47E+08	7.93E+08	8.26E+08	8.54E+08	7.63E+08	9.13E+08	7.67E+08	8.16E+08	9.03E+08	9.10E+08	1.02E+09	8.11E+08	8.76E+08	9.04E+08
GAR	209078.7121	283946.3302	271819.8339	243215.8331	227485.2475	271487.9901	202585.0347	256892.3132	197835.5487	298883.6252	258699.2307	174233.2288	243515.9205	228532.7497	294102.7889	201382.5813	177099.6599	309121.6334	271323.6894	327420.893
sedoheptulose-7-phosphate	2805419.634	4555312.633	7862542.056	6096219.933	4616288.862	2608014.298	3659574.929	2950047.28	7408489.737	3948349.993	6401131.644	7943740.62	6953774.857	7059493.737	8372192.631	3086543.631	4707465.035	5971144.108	2258909.231	4502121.265
argininosuccinate	4.54E+07	4.76E+07	7.24E+07	3.23E+07	5.72E+07	1.25E+07	2.22E+07	1.90E+07	2.44E+07	1.50E+07	1.77E+07	1.29E+07	8736611.032	7499141.862	6547468.467	4.33E+07	3.80E+07	4.39E+07	2.18E+07	2.49E+07
phosphatidylethanolamine	2.50E+07	2.42E+07	2.22E+07	2.44E+07	2.69E+07	1.18E+07	1.38E+07	1.11E+07	1.62E+07	1.27E+07	1.40E+07	1.15E+07	1.00E+07	1.01E+07	9314000.236	2.80E+07	2.51E+07	2.15E+07	2.24E+07	2.25E+07
N-acetylglucosamine-phosphate	2521360.357	3604760.562	4940960.09	3581099.361	3998357.576	1627092.438	3265285.813	4357459.578	4256345.531	3000132.156	2769989.585	4593836.594	4818684.125	3218440.594	4026729.719	3160847.678	3561903.476	5136044.994	3801741.143	3325509.782
GSH	2.66E+09	2.80E+09	2.88E+09	2.95E+09	3.23E+09	2.47E+09	3.24E+09	3.08E+09	4.40E+09	3.28E+09	3616416.156	4674542.037	7482199.5	1.35E+07	1.18E+07	2.75E+09	2.72E+09	2.75E+09	2.97E+09	2.92E+09
arachidic acid	6380577.476	5271103.693	3978872.315	3459836.6	3159472.343	4870981.124	5451846.952	4634356.572	3791056.118	2766203.506	3669156.479	4407833.113	3387248.527	3735163.354	3926961.629	4637413.166	6065855.174	2944868.391	3652436.184	4331815.752
FGAR	4743244.661	2444700.591	2806448.702	1903227.185	3074202.074	0	192371.1014	517541.4237	0	0	3252472.116	185235.9415	520760.8089	0	0	1868165.913	2121170.517	4669334.379	1158310.336	388497.2887
dTMP	9305635.532	5978375.567	4711141.691	4242108.906	5207154.108	4553924.063	5465752.928	6326892.639	2500067.868	2543315.518	1.02E+07	6579592.672	7415787.281	6164435.092	5318989.942	9491065.428	6460041.094	5987803.895	1.07E+07	5518913.577
CMP	8569331.957	6721726.539	5161230.693	4506232.892	5346911.024	5405852.568	6148077.552	2475890.702	3776205.641	2786833.432	6617675.684	7010605.743	4765042.533	7156894.819	5164580.075	9362576.76	8543705.17	5830927.899	1.03E+07	5396522.087
UMP	1.50E+08	1.02E+08	8.19E+07	7.61E+07	9.36E+07	6.45E+07	7.40E+07	4.18E+07	4.21E+07	2.94E+07	6.93E+07	5.87E+07	3.64E+07	4.53E+07	3.56E+07	1.46E+08	1.17E+08	1.05E+08	1.65E+08	9.11E+07
fructose-1;6-bisphosphate	3938762.076	1.33E+07	9.82E+07	1.16E+07	1.19E+07	4252497.88	8098678.379	1.51E+07	1.65E+07	7448963.783	3.39E+07	1.58E+08	2.24E+08	6.46E+07	7.37E+07	4537893.921	1.40E+07	5.15E+07	4065530.055	6821640.137
AMP	5.33E+08	4.70E+08	3.08E+08	3.97E+08	3.74E+08	1.90E+08	2.23E+08	1.16E+08	1.40E+08	1.28E+08	5.51E+08	5.55E+08	4.12E+08	5.68E+08	4.74E+08	5.38E+08	5.89E+08	4.16E+08	4.43E+08	4.03E+08
IMP	3429042.607	3742031.607	2916704.951	8688956.644	6613640.939	1186549.291	2663449.714	3084701.482	6508573.678	3374491.533	1632887.111	1390542.939	1517562.808	1887323.09	2394712.252	3277493.786	4406081.955	2159014.569	7337524.747	2810472.454
GMP	2.26E+07	2.41E+07	1.78E+07	1.54E+07	1.72E+07	1.04E+07	1.33E+07	7149586.961	7959645.766	5692333.912	3.48E+07	3.44E+07	2.88E+07	2.72E+07	2.59E+07	2.55E+07	3.08E+07	2.24E+07	2.31E+07	1.43E+07
FAICAR	7922336.264	4696415.188	3704769.36	3862336.844	3336339.873	6319833.952	5268551.042	4313209.808	4172169.5	3345118.188	5844817.431	4057336.389	3531307.936	2590037.625	3554353.563	1.09E+07	4592364.836	4115447.483	3307017.906	3084366.082
S-adenosyl-homocysteine	2.28E+07	2.10E+07	2.10E+07	1.59E+07	1.94E+07	6297094.628	8784978.1	6042277.409	7671120.418	4943353.794	1.36E+07	1.20E+07	8747569.761	1.22E+07	1.02E+07	2.15E+07	2.05E+07	1.85E+07	1.91E+07	1.52E+07
CDP	9649143.88	1.20E+07	7792705.597	9750221.163	1.34E+07	8498882.481	7795998.858	3965203.054	6511175.173	6167087.069	1.81E+07	3.05E+07	1.67E+07	4.23E+07	3.72E+07	1.06E+07	1.44E+07	8385376.143	7132323.179	9460697.567
UDP	9.51E+07	1.11E+08	9.15E+07	1.03E+08	1.33E+08	6.18E+07	6.19E+07	3.87E+07	5.09E+07	4.93E+07	1.13E+08	1.57E+08	9.89E+07	1.68E+08	1.38E+08	1.06E+08	1.22E+08	8.82E+07	7.76E+07	9.88E+07
S-(1;2-Dicarboxyethyl)glutathione	1621214.782	1.05E+07	1232117.467	1500875.796	8613288.212	352871.0873	9469492.529	734288.3413	4281489.807	3806669.864	14774.28314	0	0	0	0	8503720.818	1.21E+07	840617.2066	4436128.284	4575678.392
ADP	5.05E+07	7.18E+07	7.43E+07	6.00E+07	1.11E+08	4.54E+07	4.21E+07	3.30E+07	3.57E+07	3.50E+07	6.76E+07	7.42E+07	6.59E+07	1.07E+08	8.64E+07	6.04E+07	7.31E+07	6.76E+07	4.75E+07	6.18E+07
GDP	6697093.697	8531597.742	4012337.866	5528470.219	6652902.146	4212358.049	3766090.245	2744686.423	2918882.384	2888829.914	1.01E+07	1.03E+07	7794515.257	1.32E+07	1.26E+07	7565755.021	8789786.301	4604407.951	4331894.162	4805119.268
CDP-ethanolamine	4525419.238	4679582.352	6368743.357	3538909.765	5996289.612	2006806.877	3912894.78	2856932.891	3943959.9	2254987.372	4440081.954	2365265.665	2340254.627	1845723.044	1262443.642	4418530.092	4814745.192	4056754.011	3398951.773	2469938.672
dCTP	177593.5185	311092.6072	290465.2862	219637.8502	34414.12347	591687.2652	557328.5008	449669.1385	609030.4887	422359.8095	510676.1212	727789.1304	441161.471	777895.3259	474849.5604	217204.9673	336708.1526	199991.0835	172809.7668	124257.9453
dTTP	968266.4261	1372861.088	1943765.247	1506139.426	2443031.559	1928290.999	2137832.046	1659816.041	3359982.039	2300661.567	2055754.34	2646541.298	2428179.539	6009633.943	3925979.897	1118801.176	1365745.935	1161705.677	903493.2976	1563554.266
CTP	1821174.279	2815267.132	3201829.503	2977271.236	4434788.832	3576682.128	2619154.496	1687990.597	4544555.177	2331233.294	3737252.476	6126976.034	4233901.882	9323180.455	7104660.035	2401625.888	3962290.857	2119740.501	1690720.299	2692276.417
UTP	1.49E+07	2.39E+07	3.02E+07	2.41E+07	3.80E+07	1.65E+07	1.89E+07	1.25E+07	2.65E+07	1.55E+07	1.68E+07	2.13E+07	1.68E+07	2.83E+07	1.78E+07	1.75E+07	2.69E+07	1.75E+07	1.52E+07	2.19E+07
dATP	60008.97234	232179.6423	303295.892	169258.283	165585.5969	441672.392	543640.7027	209845.4868	668411.3967	524935.0231	248074.2898	486218.1474	684527.8497	949472.5357	1064492.673	0	353573.2511	79693.24679	0	0
ATP	1.31E+07	2.05E+07	3.73E+07	2.05E+07	3.32E+07	1.62E+07	1.96E+07	1.58E+07	2.46E+07	1.58E+07	1.32E+07	1.36E+07	1.46E+07	2.21E+07	1.57E+07	1.68E+07	2.43E+07	1.98E+07	1.26E+07	1.78E+07
GTP	1957740.477	3254049.596	2258103.82	2286756.784	2571460.224	2254845.061	1821048.314	1314440.36	2653146.905	1068526.338	3748464.188	3453876.308	3215316.948	3838546.085	2926806.234	2603290.712	4085439.298	1680608.994	1563856.227	1900121.578
UDP-N-acetylglucosamine	1.66E+08	1.65E+08	1.76E+08	1.52E+08	2.09E+08	2.03E+08	1.82E+08	1.49E+08	1.99E+08	1.77E+08	2.03E+08	1.76E+08	1.45E+08	2.22E+08	1.67E+08	2.04E+08	1.70E+08	1.38E+08	1.16E+08	1.68E+08
GSSG	1.48E+08	8.75E+07	1.03E+08	5.02E+07	4.99E+07	1.27E+08	1.65E+08	1.19E+08	1.21E+08	7.26E+07	63544.9549	65709.13867	96626.96534	65971.62045	31893.45898	1.10E+08	7.60E+07	9.15E+07	4.35E+07	4.77E+07
NADH	5.16E+07	6.15E+07	2.76E+08	7.57E+07	7.19E+07	1.52E+07	1.87E+07	1.09E+07	6038463.756	3.18E+07	5.45E+07	2.91E+07	1.97E+07	3.41E+07	1.81E+07	8.56E+07	8.61E+07	1.08E+08	5.50E+07	8.03E+07
NADPH	264603.1271	161021.3316	300382.7748	0	0	0	0	0	0	0	2826915.725	1164053.02	266038.0345	0	41502.25462	401836.4448	431078.6546	95535.06461	0	0
CoA	4011312.301	4220660.938	1969187.303	2446406.195	2596525.98	1405872.275	1646612.634	1192307.9	744127.9897	1235799.61	1571587.339	322264.3374	674885.4453	1836003.235	1065778.209	5411939.027	4392871.524	2745321.502	2542904.142	3647331.546
acetyl-CoA	1405681.303	725932.8469	933752.4788	4904306.618	3254527.615	1089517.47	237269.7466	619180.8697	1635787.072	2550325.741	1984979.052	1892270.815	1255025.39	9093970.777	6191792.569	1072994.98	1187060.473	1123560.113	3568708.788	4723286.081
glyceraldehyde-3-phosphate	165036.0938	424145.8125	861097.6719	2312794.516	1109739.203	283628.2676	334286.8969	415539.8594	3182219.344	1653044.594	282732.9063	204325.6484	201702.9063	794658.3125	183081.9336	156764.8828	131843.2969	545398.3438	970948.6328	1921758.266
cystine	0	0	0	0	0	0	0	0	0	0	6.70E+07	6.17E+07	6.47E+07	9.42E+07	1.25E+08	0	0	0	0	0
SAICAR	0	0	0	0	0	0	0	0	0	0	82437.10951	0	0	0	0	0	38740.71331	112546.813	0	0
fructose	2366779.668	1658905.763	1463418.625	2411142.615	3932680.137	2306882.75	1198326.656	1183127.938	2444613.688	2837058.637	1558382.743	1791802.719	1335677.656	2206109.073	2195726.284	1310351.781	1037927.75	1208696.313	2470746.266	2750219.204
MS_METABOLITE_DATA_END
#METABOLITES
METABOLITES_START
metabolite_name	PubChem ID	formula	polarity	pos m/z	neg m/z	RT, min
glucose	5793	C6H12O6	neg	181.071	179.056	7.34
malate	525	C4H6O5	neg	135.029	133.014	9.56
succinate	1110	C4H6O4	neg	119.034	117.019	8.92
aspartate	5960	C4H7NO4	neg	134.045	132.03	8.5
glutamine	5961	C5H10N2O3	neg	147.076	145.062	7.64
histidine	6274	C6H9N3O2	neg	156.077	154.062	7.49
glutamate	33032	C5H9NO4	neg	148.06	146.046	8.25
tyrosine	6057	C9H11NO3	neg	182.081	180.067	6.25
tryptophan	6305	C11H12N2O2	neg	205.097	203.083	5.36
sedoheptulose-7-phosphate	22833559	C7H15O10P	neg	291.048	289.033	9.67
ATP	5957	C10H16N5O13P3	neg	508.003	505.988	10.05
ADP	6022	C10H15N5O10P2	neg	428.037	426.022	8.97
AMP	6083	C10H14N5O7P	neg	348.07	346.056	7.8
GTP	135398633	C10H16N5O14P3	neg	523.998	521.983	12.11
GMP	135398631	C10H14N5O8P	neg	364.065	362.051	10
UTP	6133	C9H15N2O15P3	neg	484.976	482.961	11.06
UDP	6031	C9H14N2O12P2	neg	405.009	402.995	10
UMP	6030	C9H13N2O9P	neg	325.043	323.029	8.82
CTP	6176	C9H16N3O14P3	neg	483.992	481.977	11.5
CDP	6132	C9H15N3O11P2	neg	404.025	402.011	10.37
glycerol-3-phosphate	754	C3H9O6P	neg	173.021	171.006	8.66
alpha-ketoglutarate	51	C5H6O5	neg	147.029	145.014	9.18
cis-aconitate	643757	C6H6O6	neg	175.024	173.009	11.01
glycine	750	C2H5NO2	pos	76.039	74.025	8.12
alanine	5950	C3H7NO2	pos	90.055	88.04	7.37
proline	614	C5H9NO2	pos	116.071	114.056	5.96
serine	5951	C3H7NO3	pos	106.05	104.035	8.07
threonine	6288	C4H9NO3	pos	120.066	118.051	7.06
lysine	5962	C6H14N2O2	pos	147.113	145.098	12.09
arginine	6322	C6H14N4O2	pos	175.119	173.104	12.57
phenylalanine	6140	C9H11NO2	pos	166.086	164.072	4.25
creatinine	588	C4H7N3O	pos	114.066	112.052	3.94
S-adenosyl-methionine	34756	C15H23N6O5S	pos	399.145	NULL	8.37
methionine	6137	C5H11NO2S	pos	150.058	148.044	5.29
valine	6287	C5H11NO2	pos	118.086	116.072	5.7
acetyl-carnitine	7045767	C9H17NO4	pos	204.123	NULL	4.72
asparagine	6267	C4H8N2O3	pos	133.061	131.046	7.82
phosphoglycerate	439183	C3H7O7P	neg	187	184.986	10.16
phosphoenolpyruvate	1005	C3H5O6P	neg	168.99	166.975	10.66
sorbitol	5780	C6H14O6	neg	183.086	181.072	6.77
citrulline	9750	C6H13N3O3	pos	176.103	174.088	8.37
argininosuccinate	439998	C10H18N4O6	neg	291.13	289.115	9.78
oleic acid	445639	C18H34O2	neg	283.263	281.249	1.46
palmitic acid	985	C16H32O2	neg	257.248	255.233	1.51
stearic acid	5281	C18H36O2	neg	285.279	283.264	1.51
fumarate	444972	C4H4O4	neg	117.018	115.004	9.56
pyruvate	1060	C3H4O3	neg	89.023	87.009	3.76
lactate	612	C3H6O3	neg	91.039	89.024	4.73
choline	305	C5H14NO+	pos	104.107	NULL	9.16
guanosine	135398635	C10H13N5O5	neg	284.099	282.084	6.04
cytidine	6175	C9H13N3O5	neg	244.093	242.078	5.88
S-adenosyl-homocysteine	439155	C14H20N6O5S	neg	385.129	383.114	6.56
IMP	135398640	C10H13N4O8P	neg	349.054	347.04	9.13
6-phosphogluconic acid	91493	C6H13O10P	neg	277.032	275.017	10.95
erythrose-4-phosphate	122357	C4H9O7P	neg	201.016	199.001	10.1
fructose-1;6-bisphosphate	10267	C6H14O12P2	neg	341.003	338.989	11.33
CDP-ethanolamine	123727	C11H20N4O11P2	neg	447.068	445.053	9.5
UDP-N-acetylglucosamine	445675	C17H27N3O17P2	neg	608.089	606.074	8.88
NADH	439153	C21H29N7O14P2	neg	666.132	664.118	7.54
NAD+	5892	C21H27N7O14P2	pos	664.116	NULL	7.77
CMP	6131	C9H14N3O8P	neg	324.059	322.045	9.34
carnitine	288	C7H15NO3	pos	162.112	NULL	6.32
CDP-choline	13804	C14H26N4O11P2	pos	489.115	NULL	8.58
lauric acid	3893	C12H24O2	neg	201.185	199.17	1.6
myristic acid	11005	C14H28O2	neg	229.216	227.202	1.56
arachidic acid	10467	C20H40O2	neg	313.31	311.296	1.46
ornithine	6262	C5H12N2O2	pos	133.097	131.083	11.14
GSH	124886	C10H17N3O6S	neg	308.091	306.077	8.14
GSSG	65359	C20H32N6O12S2	neg	613.159	611.145	10.58
phosphoserine	68841	C3H8NO6P	neg	186.016	184.002	9.83
5'-methylthioadenosine	439176	C11H15N5O3S	pos	298.097	296.082	2.27
cystathionine	834	C7H14N2O4S	pos	223.075	221.06	9.21
dihydroxyacetone-phosphate	668	C3H7O6P	neg	171.005	168.991	8.92
glyceraldehyde-3-phosphate	729	C3H7O6P	neg	171.005	168.991	9.61
NADP+	5886	C21H29N7O17P3	pos	744.083	NULL	10.08
NADPH	5884	C21H30N7O17P3	neg	746.098	744.084	10.43
creatine	586	C4H9N3O2	pos	132.077	130.062	7.37
saccharopine	160556	C11H20N2O6	neg	277.139	275.125	8.92
phosphorylethanolamine	1015	C2H8NO4P	neg	142.026	140.012	9.13
glycerophosphocholine	657272	C8H20NO6P	pos	258.11	NULL	7.11
carbamoyl-aspartate	279	C5H8N2O5	neg	177.051	175.036	10.05
gamma-amino-butyrate	119	C4H9NO2	neg	104.071	102.056	8.25
citrate / isocitrate	311	C6H8O7	neg	193.034	191.02	11.13
N-acetylglucosamine-phosphate	439219	C8H16NO9P	neg	302.064	300.049	8.55
adenosine	60961	C10H13N5O4	pos	268.104	266.089	3.34
inosine	135398641	C10H12N4O5	neg	269.088	267.073	5
fructose	2723872	C6H12O6	neg	181.071	179.056	6.51
xylulose	5289590	C5H10O5	neg	151.06	149.046	5.1
fructose-1-phosphate	65246	C6H13O9P	neg	261.037	259.022	9.38
hydroxyglutarate	43	C5H8O5	neg	149.044	147.03	8.97
rib/ribul/xylul-ose-phosphate	439190	C5H11O8P	neg	231.026	229.012	9.23
phosphocholine	1014	C5H15NO4P	pos	184.074	NULL	8.22
kynurenine	846	C10H12N2O3	pos	209.092	207.078	4.72
acetyl-CoA	444493	C23H38N7O17P3S	neg	810.133	808.119	6.88
dihydroorotate	5461056	C5H6N2O4	neg	NULL	157.025	5.78
orotate	1492348	C5H4N2O4	neg	157.024	155.01	5.41
leucine / isoleucine	6106	C6H13NO2	pos	132.102	130.087	4.71
phosphate	1004	H3O4P	neg	98.984	96.97	7.04
nicotinamide	936	C6H6N2O	pos	123.055	121.041	2.53
methioninesulfoxide	158980	C5H11NO3S	pos	166.053	164.039	6.48
CoA	87642	C21H36N7O16P3S	neg	768.122	766.108	7.85
cystine	595	C6H12N2O4S2	neg	241.031	239.017	8.82
riboflavin	493570	C17H20N4O6	pos	377.146	375.131	3.26
GDP	135398619	C10H15N5O11P2	neg	444.032	442.017	11.01
dTTP	64968	C10H17N2O14P3	neg	482.997	480.982	9.73
dATP	15993	C10H16N5O12P3	neg	492.008	489.994	9.5
phosphoribosylamine	150	C5H12NO7P	neg	230.042	228.028	9.18
dCTP	65091	C9H16N3O13P3	neg	467.997	465.982	10.84
phosphatidylethanolamine	5327011	C9H18NO8P	neg	300.084	298.07	8.88
N-acetylglutamate	70914	C7H11NO5	neg	190.071	188.056	8.09
betaine	247	C5H11NO2	pos	118.086	116.072	4.92
dTMP	9700	C10H15N2O8P	neg	323.064	321.049	7.09
N-trimethyllysine	440121	C9H21N2O2	pos	189.16	189.16	10.69
gamma-butyrobetaine	725	C7H16NO2	pos	146.118	144.103	6.32
caffeine	2519	C8H10N4O2	pos	195.088	193.073	2.05
picolinic acid	1018	C6H5NO2	neg	124.039	122.025	3.71
quinolinic acid	1066	C7H5NO4	neg	168.029	166.015	8.7
S-(1;2-Dicarboxyethyl)glutathione	329770102	C14H21N3O10S	neg	424.102	422.087	11.6
S-(2-Succinyl)-L-cysteine	NULL	C7H11NO6S	neg	238.038	236.023	10.55
FAICAR	166760	C10H15N4O9P	neg	367.065	365.05	7.17
SAICAR	160666	C13H19N4O12P	neg	455.081	453.066	11.99
FGAR	130805	C8H15N2O9P	neg	315.059	313.044	8.82
GAR	160913	C7H15N2O8P	neg	287.064	285.049	6.83
trifluoromethanesulfonate*	2758875	CF3O3SH	neg	150.967	148.953	1.88
METABOLITES_END
#END