#METABOLOMICS WORKBENCH msekiya_20250728_212836 DATATRACK_ID:6225 STUDY_ID:ST004082 ANALYSIS_ID:AN006760 PROJECT_ID:PR002563
VERSION             	1
CREATED_ON             	July 30, 2025, 7:45 am
#PROJECT
PR:PROJECT_TITLE                 	IMR90 cells treated with exosomes with or without CtBP2
PR:PROJECT_SUMMARY               	We prepared two types of MEF (mouse embryonic fibroblast) cells: one is cells
PR:PROJECT_SUMMARY               	with wild-type CtBP2-HA knock-in and the other is cells with CtBP2 mutant-HA
PR:PROJECT_SUMMARY               	knock-in. The latter does not secrete CtBP2 in exosomes. We isolated exosomes
PR:PROJECT_SUMMARY               	from these cells and treated IMR90 fibroblasts (WT and Mut, respectively).
PR:INSTITUTE                     	University of Tsukuba
PR:LAST_NAME                     	Sekiya
PR:FIRST_NAME                    	Motohiro
PR:ADDRESS                       	1-1-1 Tennodai, Tsukuba, Ibaraki, 3058575, Japan
PR:EMAIL                         	msekiya@md.tsukuba.ac.jp
PR:PHONE                         	+81-29-853-3053
#STUDY
ST:STUDY_TITLE                   	The secreted metabolite sensor CtBP2 links metabolism to healthy lifespan
ST:STUDY_SUMMARY                 	While metabolic homeostasis is coordinated by metabolite-sensing molecules
ST:STUDY_SUMMARY                 	within a cell, their roles in horizontal regulation across cells remain
ST:STUDY_SUMMARY                 	underexplored. Here, we describe a system regulated by a metabolite sensor
ST:STUDY_SUMMARY                 	CtBP2. CtBP2 is secreted via exosomes in response to reductive metabolism, which
ST:STUDY_SUMMARY                 	is suppressed by oxidative stress. A series of pro-longevity agents induce CtBP2
ST:STUDY_SUMMARY                 	secretion, and administration of exosomal CtBP2 extends lifespan of aged mice.
ST:STUDY_SUMMARY                 	Consistently, serum CtBP2 concentrations are higher in human subjects from
ST:STUDY_SUMMARY                 	families with a history of longevity and exhibit an age-dependent decline.
ST:STUDY_SUMMARY                 	Healthspan is also improved by exosomal CtBP2, as exemplified by protection
ST:STUDY_SUMMARY                 	against frailty in mice and negative associations between serum CtBP2 levels and
ST:STUDY_SUMMARY                 	cardiovascular diseases in humans. These health benefits could be attributed to
ST:STUDY_SUMMARY                 	the proper channeling of reducing equivalents into a chain of activation of
ST:STUDY_SUMMARY                 	CYB5R3 and AMPK. Our findings illustrate a previously uncharacterized metabolic
ST:STUDY_SUMMARY                 	system that provides insights into the regulation of human health and holds
ST:STUDY_SUMMARY                 	promise for future clinical applications.
ST:INSTITUTE                     	University of Tsukuba
ST:LAST_NAME                     	Sekiya
ST:FIRST_NAME                    	Motohiro
ST:ADDRESS                       	1-1-1 Tennodai, Tsukuba, Ibaraki, 3058575, Japan
ST:EMAIL                         	msekiya@md.tsukuba.ac.jp
ST:PHONE                         	+81298533053
#SUBJECT
SU:SUBJECT_TYPE                  	Cultured cells
SU:SUBJECT_SPECIES               	Homo sapiens
SU:TAXONOMY_ID                   	9606
#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           	-	WT-1	Group:WT | Sample source:IMR90 fibroblasts	RAW_FILE_NAME(Raw data(positive))=TSUUY09101_C_20240802_004_d1.mzML; RAW_FILE_NAME(Raw data(negative))=TSUUY09101_A_20240802_004_d2.mzML
SUBJECT_SAMPLE_FACTORS           	-	WT-2	Group:WT | Sample source:IMR90 fibroblasts	RAW_FILE_NAME(Raw data(positive))=TSUUY09101_C_20240802_005_d1.mzML; RAW_FILE_NAME(Raw data(negative))=TSUUY09101_A_20240802_005_d2.mzML
SUBJECT_SAMPLE_FACTORS           	-	WT-3	Group:WT | Sample source:IMR90 fibroblasts	RAW_FILE_NAME(Raw data(positive))=TSUUY09101_C_20240802_006_d1.mzML; RAW_FILE_NAME(Raw data(negative))=TSUUY09101_A_20240802_006_d2.mzML
SUBJECT_SAMPLE_FACTORS           	-	Mut-1	Group:Mut | Sample source:IMR90 fibroblasts	RAW_FILE_NAME(Raw data(positive))=TSUUY09101_C_20240802_007_d1.mzML; RAW_FILE_NAME(Raw data(negative))=TSUUY09101_A_20240802_007_d2.mzML
SUBJECT_SAMPLE_FACTORS           	-	Mut-2	Group:Mut | Sample source:IMR90 fibroblasts	RAW_FILE_NAME(Raw data(positive))=TSUUY09101_C_20240802_008_d1.mzML; RAW_FILE_NAME(Raw data(negative))=TSUUY09101_A_20240802_008_d2.mzML
SUBJECT_SAMPLE_FACTORS           	-	Mut-3	Group:Mut | Sample source:IMR90 fibroblasts	RAW_FILE_NAME(Raw data(positive))=TSUUY09101_C_20240802_009_d1.mzML; RAW_FILE_NAME(Raw data(negative))=TSUUY09101_A_20240802_009_d2.mzML
#COLLECTION
CO:COLLECTION_SUMMARY            	We identified an anti-aging effect of CtBP2 in exosomes. To investigate the
CO:COLLECTION_SUMMARY            	mechanistic insights behind this, we decided to treat IMR90 fibroblasts with
CO:COLLECTION_SUMMARY            	exosomes with or without CtBP2. Since we revealed that CtBP2 mutant lacking the
CO:COLLECTION_SUMMARY            	metabolite sensing pocket cannot be secreted via exosomes, we prepared two types
CO:COLLECTION_SUMMARY            	of MEF cells: one is cells with wild-type CtBP2-HA knock-in and the other is
CO:COLLECTION_SUMMARY            	cells with the CtBP2 mutant-HA knock-in. We isolated exosomes from these cells
CO:COLLECTION_SUMMARY            	and treated IMR90 fibroblasts for 1.5 days. Exosomes from MEF cells with
CO:COLLECTION_SUMMARY            	wild-type CtBP2-HA knock-in contain CtBP2, and exosomes from those with mutant
CO:COLLECTION_SUMMARY            	CtBP2-HA knock-in does not. WT and Mut denote metabolites extracted from IMR90
CO:COLLECTION_SUMMARY            	cells treated with exosomes with and without CtBP2, respectively.
CO:SAMPLE_TYPE                   	Fibroblast cells
#TREATMENT
TR:TREATMENT_SUMMARY             	IMR90 fibroblast cells were treated with exosomes with or without CtBP2, for 1.5
TR:TREATMENT_SUMMARY             	days in DMEM 10% exosome-free fetal bovine serum.
#SAMPLEPREP
SP:SAMPLEPREP_SUMMARY            	Culture medium was aspirated from the dish, and the cells were washed twice with
SP:SAMPLEPREP_SUMMARY            	5% mannitol solution (10 mL and 2 mL for the first and second wash,
SP:SAMPLEPREP_SUMMARY            	respectively). The cells were then treated with 800 µL of methanol and
SP:SAMPLEPREP_SUMMARY            	incubated at room temperature for 30 sec to suppress enzyme activity. Next, 550
SP:SAMPLEPREP_SUMMARY            	µL of Milli-Q water containing internal standards (H3304-1002, Human Metabolome
SP:SAMPLEPREP_SUMMARY            	Technologies, Inc. (HMT), Tsuruoka, Yamagata, Japan) was added to the cell
SP:SAMPLEPREP_SUMMARY            	extract, followed by further incubation at room temperature for 30 sec. The cell
SP:SAMPLEPREP_SUMMARY            	extract was then centrifuged at 2,300 ×g, 4ºC for 5 min, after which 700 µL
SP:SAMPLEPREP_SUMMARY            	of the supernatant was centrifugally filtered through a Millipore 5-kDa cutoff
SP:SAMPLEPREP_SUMMARY            	filter (UltrafreeMC-PLHCC, HMT) at 9,100 ×g, 4ºC for 120 min to remove
SP:SAMPLEPREP_SUMMARY            	macromolecules. Subsequently, the filtrate was evaporated to dryness under
SP:SAMPLEPREP_SUMMARY            	vacuum and reconstituted in 50 µL of Milli-Q water for metabolome analysis at
SP:SAMPLEPREP_SUMMARY            	HMT.
#CHROMATOGRAPHY
CH:CHROMATOGRAPHY_TYPE           	CE
CH:INSTRUMENT_NAME               	Agilent 7100 CE
CH:COLUMN_NAME                   	Fused silica capillary (80 cm x 50 um)
CH:SOLVENT_A                     	Anion Buffer Solution (p/n:I3302-1023)
CH:SOLVENT_B                     	N/A
CH:FLOW_GRADIENT                 	N/A
CH:FLOW_RATE                     	N/A
CH:COLUMN_TEMPERATURE            	N/A
#ANALYSIS
AN:ANALYSIS_TYPE                 	MS
#MS
MS:INSTRUMENT_NAME               	Thermo Q Exactive Plus Orbitrap
MS:INSTRUMENT_TYPE               	Orbitrap
MS:MS_TYPE                       	ESI
MS:ION_MODE                      	NEGATIVE
MS:MS_COMMENTS                   	CE-HRMS(omega) Negative (Anion) mode
#MS_METABOLITE_DATA
MS_METABOLITE_DATA:UNITS	arbitrary unit
MS_METABOLITE_DATA_START
Samples	WT-1	WT-2	WT-3	Mut-1	Mut-2	Mut-3									
Factors	Group:WT | Sample source:IMR90 fibroblasts	Group:WT | Sample source:IMR90 fibroblasts	Group:WT | Sample source:IMR90 fibroblasts	Group:Mut | Sample source:IMR90 fibroblasts	Group:Mut | Sample source:IMR90 fibroblasts	Group:Mut | Sample source:IMR90 fibroblasts
Glyoxylic acid	8.8E-04	N.D.	N.D.	1.0E-03	5.5E-04	1.1E-03									
Propionic acid	N.D.	N.D.	N.D.	N.D.	N.D.	N.D.									
Glycolic acid	4.4E-03	5.6E-03	5.2E-03	N.D.	5.5E-03	4.5E-03									
Pyruvic acid	1.3E-02	1.1E-02	N.D.	N.D.	N.D.	1.1E-02									
Isobutyric acid"	N.D.	3.8E-03	N.D.	2.6E-03	3.6E-03	3.0E-03									
Oxamic acid	N.D.	N.D.	N.D.	N.D.	4.2E-04	N.D.									
Lactic acid	4.3E+00	5.0E+00	4.4E+00	3.4E+00	3.4E+00	3.2E+00									
Phenol	2.2E-02	2.3E-02	2.4E-02	2.0E-02	2.3E-02	2.3E-02									
2-Hydroxypyridine	1.2E-03	3.1E-03	3.2E-03	1.2E-03	2.7E-03	1.7E-03									
Valeric acid"	4.7E-03	7.3E-03	6.0E-03	5.6E-03	6.2E-03	5.3E-03									
N-Formylglycine	7.3E-04	2.9E-04	9.6E-04	4.3E-04	2.1E-03	4.3E-04									
2-Hydroxybutyric acid	N.D.	N.D.	N.D.	N.D.	N.D.	N.D.									
3-Hydroxybutyric acid	1.8E-02	1.7E-02	1.5E-02	1.5E-02	1.4E-02	1.3E-02									
Glyceric acid	3.5E-03	4.8E-03	5.1E-03	3.2E-03	4.5E-03	3.6E-03									
Fumaric acid	9.0E-02	9.6E-02	8.9E-02	7.0E-02	8.5E-02	7.0E-02									
Maleic acid	N.D.	7.2E-04	N.D.	N.D.	N.D.	N.D.									
4-Oxovaleric acid	3.0E-03	4.0E-03	3.7E-03	2.7E-03	4.3E-03	2.7E-03									
2-Oxoisovaleric acid	1.1E-02	3.3E-02	2.5E-02	1.0E-02	1.6E-02	9.4E-03									
4-Methylpentanoic acid"	7.6E-03	8.0E-03	7.5E-03	7.2E-03	9.0E-03	7.3E-03									
N-Acetylglycine	2.2E-03	1.9E-03	2.1E-03	1.9E-03	2.3E-03	1.9E-03									
Succinic acid	3.9E-02	5.4E-02	5.6E-02	3.4E-02	3.9E-02	4.0E-02									
2-Hydroxyisovaleric acid-1"	9.7E-03	9.7E-03	9.3E-03	7.8E-03	8.6E-03	7.8E-03									
2-Hydroxyisovaleric acid-2"	2.7E-03	2.6E-03	2.5E-03	1.9E-03	1.7E-03	1.6E-03									
5-Hydroxypentanoic acid"	2.8E-04	3.8E-04	3.6E-04	N.D.	8.7E-04	2.5E-04									
2-Ethylhydracrylic acid-2	1.0E-03	1.1E-03	8.5E-04	9.6E-04	1.0E-03	9.5E-04									
Benzoic acid	3.4E-03	3.8E-03	3.1E-03	3.0E-03	4.6E-03	2.4E-03									
Isethionic acid	1.6E-03	1.9E-03	2.0E-03	2.1E-03	6.9E-03	1.3E-03									
5-Oxoproline	8.4E-01	9.1E-01	9.6E-01	6.9E-01	6.9E-01	6.9E-01									
Citraconic acid	5.8E-03	6.7E-03	N.D.	5.0E-03	N.D.	N.D.									
4-Oxohexanoic acid"	2.7E-03	2.4E-03	2.6E-03	N.D.	2.8E-03	2.6E-03									
2-Oxohexanoic acid"	1.4E-01	2.2E-01	1.7E-01	1.0E-01	1.2E-01	9.4E-02									
Heptanoic acid	N.D.	4.8E-03	4.9E-03	N.D.	6.2E-03	4.8E-03									
N-Acetyl- -alanine"	3.3E-02	3.1E-02	3.0E-02	2.8E-02	2.9E-02	2.7E-02									
Methylsuccinic acid"	3.1E-03	4.1E-03	3.8E-03	3.6E-03	4.2E-03	4.4E-03									
2-Hydroxy-3-methylvaleric acid"	1.3E-03	1.3E-03	1.3E-03	1.0E-03	1.3E-03	8.2E-04									
3-Hydroxyhexanoic acid"	4.7E-04	3.8E-04	N.D.	3.8E-04	1.8E-04	1.9E-04									
Iminodiacetic acid	1.6E-03	1.9E-03	3.5E-03	1.3E-03	2.1E-03	1.8E-03									
Malic acid	2.0E+00	1.8E+00	1.8E+00	1.9E+00	1.9E+00	1.8E+00									
Threonic acid	1.1E-01	1.1E-01	1.0E-01	1.2E-01	1.1E-01	1.1E-01									
m-Toluic acid"	1.9E-02	1.8E-02	1.9E-02	2.2E-02	2.2E-02	2.1E-02									
4-Hydroxyphenylacetaldehyde	9.4E-03	9.2E-03	9.3E-03	5.7E-03	8.2E-03	6.9E-03									
o-Hydroxybenzoic acid	6.2E-04	2.3E-04	5.5E-04	5.4E-04	1.0E-03	4.0E-04									
p-Hydroxybenzoic acid"	N.D.	4.6E-04	3.3E-04	N.D.	3.7E-04	N.D.									
6-Hydroxynicotinic acid	N.D.	7.9E-04	N.D.	N.D.	1.7E-03	N.D.									
Ethanolamine phosphate	8.5E-02	9.1E-02	1.0E-01	7.6E-02	1.4E-01	1.6E-01									
5-Hydroxymethyluracil	2.9E-03	2.6E-03	2.6E-03	N.D.	1.3E-03	1.5E-03									
Octanoic acid-2	5.5E-03	6.3E-03	5.1E-03	4.7E-03	9.5E-03	4.8E-03									
Octanoic acid-1"	2.7E-03	N.D.	N.D.	2.8E-03	3.2E-03	N.D.									
N-Propionylalanine-1"	3.6E-04	6.7E-04	5.1E-04	4.2E-04	1.2E-03	3.7E-04									
Isobutyrylglycine"	1.2E-03	1.8E-03	2.1E-03	1.9E-03	3.8E-03	1.5E-03									
2-Oxoglutaric acid	9.6E-02	1.5E-01	1.1E-01	8.8E-02	9.4E-02	8.3E-02									
2-Methylglutaric acid"	N.D.	N.D.	N.D.	N.D.	5.0E-03	N.D.									
3-Ureidoisobutyric acid	N.D.	N.D.	N.D.	N.D.	N.D.	N.D.									
2-Hydroxyglutaric acid	7.0E-02	6.7E-02	6.4E-02	6.2E-02	5.7E-02	5.6E-02									
Citramalic acid	1.7E-03	3.0E-03	3.8E-03	1.7E-03	N.D.	N.D.									
Mevalonic acid	8.7E-04	1.1E-03	1.1E-03	1.0E-03	5.5E-03	5.9E-04									
Pantoic acid	3.5E-04	1.1E-03	1.0E-03	1.1E-03	8.5E-04	2.2E-04									
Tartaric acid	N.D.	1.5E-03	1.5E-03	1.9E-03	1.8E-03	1.5E-03									
2-Deoxyribonic acid-2	1.1E-03	4.4E-03	2.0E-03	1.3E-03	N.D.	2.1E-03									
2-Deoxyribonic acid-1	N.D.	2.5E-04	3.9E-04	N.D.	1.6E-04	N.D.									
3-Phenylpropionic acid	3.9E-03	5.4E-03	5.2E-03	3.5E-03	6.0E-03	3.5E-03									
2-(Hydroxymethyl)benzoic acid"	1.4E-03	1.2E-03	1.2E-03	1.7E-03	2.2E-03	1.4E-03									
Cysteinesulfinic acid	2.6E-02	2.6E-02	2.6E-02	2.3E-02	2.7E-02	2.6E-02									
Phosphoglycolic acid	4.8E-04	N.D.	4.4E-04	5.2E-04	N.D.	5.4E-04									
Orotic acid	8.9E-04	1.1E-03	9.0E-04	4.0E-04	4.1E-04	3.4E-04									
Dihydroorotic acid	7.5E-04	8.5E-04	7.2E-04	N.D.	4.2E-04	3.5E-04									
Succinylacetone	N.D.	2.5E-04	N.D.	N.D.	5.5E-04	N.D.									
Pelargonic acid	2.1E-02	2.1E-02	1.8E-02	2.0E-02	3.6E-02	1.7E-02									
2-Methylbutyrylglycine-1"	1.1E-03	1.2E-03	1.2E-03	1.1E-03	1.2E-03	1.1E-03									
2-Methylbutyrylglycine-2	N.D.	2.9E-04	1.2E-04	N.D.	2.3E-04	1.2E-04									
3-Methyladipic acid"	6.8E-04	7.9E-04	N.D.	3.7E-04	1.3E-03	N.D.									
3-Hydroxyoctanoic acid-2"	4.9E-04	5.4E-04	5.1E-04	4.1E-04	3.4E-04	4.4E-04									
3-Hydroxyoctanoic acid-1"	5.6E-04	4.9E-04	6.7E-04	N.D.	9.1E-04	N.D.									
Indole-3-carboxylic acid	5.7E-04	1.4E-04	2.3E-04	3.1E-04	2.3E-04	N.D.									
N-Acetylthreonine	1.3E-02	1.2E-02	1.2E-02	1.3E-02	1.3E-02	1.3E-02									
3-Hydroxy-3-methylglutaric acid	2.7E-02	2.7E-02	2.4E-02	2.6E-02	2.4E-02	2.3E-02									
2-Hydroxyadipic acid	1.8E-03	1.8E-03	N.D.	N.D.	N.D.	N.D.									
N-Acetylcysteine	4.5E-03	5.9E-03	4.4E-03	3.7E-03	3.3E-03	2.8E-03									
Phenylpyruvic acid	6.8E-04	N.D.	N.D.	6.9E-04	3.6E-04	5.1E-04									
N-Formylanthranilic acid	4.6E-04	2.2E-04	4.5E-04	2.1E-04	2.0E-04	N.D.									
Phthalic acid	2.0E-03	1.6E-03	N.D.	1.4E-03	4.6E-03	1.2E-03									
Terephthalic acid	2.2E-03	2.0E-03	N.D.	2.2E-03	2.1E-03	2.0E-03									
Arabinonic acid	8.3E-04	1.3E-03	1.3E-03	9.5E-04	1.1E-03	7.3E-04									
p-Methoxyphenylacetic acid"	3.9E-04	1.7E-04	2.1E-04	N.D.	1.3E-04	N.D.									
N-Acetyltaurine	2.2E-02	2.0E-02	1.9E-02	2.6E-02	2.3E-02	2.5E-02									
Phosphoenolpyruvic acid	2.0E-02	1.9E-02	1.7E-02	1.7E-02	1.8E-02	1.4E-02									
Uric acid	8.6E-03	9.9E-03	8.6E-03	7.2E-03	7.6E-03	6.9E-03									
Cysteic acid	9.5E-04	7.9E-04	9.5E-04	1.2E-03	1.2E-03	1.2E-03									
Glyceraldehyde 3-phosphate	7.5E-04	2.2E-03	1.0E-03	2.7E-04	7.0E-04	2.0E-04									
Dihydroxyacetone phosphate	3.5E-02	1.4E-01	1.2E-01	3.3E-02	7.1E-02	3.5E-02									
Glycerol 2-phosphate	6.3E-03	2.1E-04	4.5E-04	4.1E-03	1.5E-03	4.8E-03									
Glycerol 3-phosphate	1.9E-01	1.6E-01	1.6E-01	1.8E-01	1.7E-01	1.8E-01									
Decanoic acid	1.4E-02	1.4E-02	1.4E-02	1.2E-02	2.9E-02	1.2E-02									
N-Hexanoylglycine"	9.5E-04	8.7E-04	9.8E-04	6.6E-04	1.1E-03	8.4E-04									
Phenol sulphate	1.3E-03	1.1E-03	9.3E-04	1.5E-03	1.7E-03	1.3E-03									
p-Phenolsulfonic acid	6.6E-04	8.2E-04	8.2E-04	6.7E-04	9.7E-04	5.5E-04									
cis-Aconitic acid	1.9E-01	1.8E-01	1.8E-01	1.8E-01	1.6E-01	1.7E-01									
N-Acetylasparagine	2.7E-03	3.2E-03	2.8E-03	2.5E-03	2.6E-03	3.1E-03									
Suberic acid	1.9E-03	1.7E-03	2.8E-03	1.0E-03	3.5E-03	1.2E-03									
N-Acetylaspartic acid	3.6E-02	3.7E-02	3.3E-02	4.4E-02	4.3E-02	3.8E-02									
Glucurone	1.9E-01	1.5E-01	1.7E-01	1.3E-01	2.2E-01	1.7E-01									
"1,2,3-Propanetricarboxylic acid"	N.D.	2.0E-04	N.D.	N.D.	N.D.	N.D.									
N-Carbamoylaspartic acid	1.1E-02	1.1E-02	1.1E-02	4.6E-03	4.4E-03	4.7E-03									
N-Formylmethionine	3.7E-03	3.5E-03	3.1E-03	3.0E-03	3.4E-03	2.9E-03									
Hippuric acid	N.D.	8.9E-05	5.6E-04	N.D.	N.D.	N.D.									
Caffeic acid"	N.D.	1.3E-04	N.D.	N.D.	3.3E-04	4.4E-04									
Hydroxyphenyllactic acid"	1.0E-02	1.1E-02	1.1E-02	8.9E-03	7.3E-03	7.7E-03									
Homocysteic acid	6.4E-04	5.4E-04	6.1E-04	7.5E-04	6.8E-04	4.7E-04									
3-Methoxy-4-hydroxyphenylethyleneglycol	5.9E-03	5.1E-03	6.9E-03	3.3E-03	5.3E-03	4.6E-03									
O-Phosphoserine	9.5E-03	8.9E-03	1.0E-02	1.3E-02	1.1E-02	1.2E-02									
2-Phosphoglyceric acid	7.0E-03	7.4E-03	7.3E-03	5.4E-03	6.1E-03	6.9E-03									
3-Phosphoglyceric acid	4.1E-02	4.0E-02	4.0E-02	3.4E-02	3.6E-02	3.6E-02									
Undecanoic acid	2.6E-03	2.1E-03	2.3E-03	2.2E-03	3.8E-03	2.2E-03									
p-Cresol sulfate	6.0E-03	8.2E-03	7.5E-03	5.3E-03	6.1E-03	5.7E-03									
N-Acetylglutamine	3.3E-03	2.8E-03	3.2E-03	3.2E-03	3.3E-03	3.2E-03									
Azelaic acid	3.9E-03	5.2E-03	7.7E-03	2.2E-03	6.3E-03	2.6E-03									
3-Hydroxydecanoic acid"	5.7E-04	5.3E-04	6.4E-04	4.4E-04	8.9E-04	4.9E-04									
Indole-3-glyoxylic acid	2.3E-04	N.D.	2.4E-04	N.D.	N.D.	N.D.									
N-Acetylglutamic acid	1.6E-02	1.7E-02	1.6E-02	1.7E-02	1.7E-02	1.5E-02									
"2,4-Dichlorobenzoic acid"	N.D.	N.D.	2.4E-04	N.D.	3.8E-04	N.D.									
N-Acetylmethionine	3.4E-02	2.9E-02	2.9E-02	2.4E-02	2.3E-02	2.4E-02									
Citric acid	2.7E+00	2.6E+00	2.4E+00	2.4E+00	2.4E+00	2.3E+00									
Isocitric acid	1.8E-01	1.7E-01	1.7E-01	1.7E-01	1.6E-01	1.6E-01									
Quinic acid	4.7E-04	1.4E-03	1.9E-03	3.1E-04	9.5E-04	1.2E-03									
Phenaceturic acid"	2.3E-03	2.5E-03	1.9E-03	2.0E-03	2.1E-03	1.5E-03									
Glucuronic acid"	3.7E-03	4.2E-03	4.2E-03	2.5E-03	3.4E-03	2.4E-03									
Gluconic acid	1.2E-01	1.1E-01	1.0E-01	9.6E-02	9.6E-02	9.0E-02									
Lauric acid	7.1E-02	5.9E-02	6.0E-02	6.3E-02	7.0E-02	6.1E-02									
Capryloylglycine	N.D.	1.6E-03	1.8E-03	1.7E-04	6.0E-04	4.7E-04									
p-Sulfobenzoic acid	N.D.	N.D.	1.8E-04	N.D.	4.2E-04	N.D.									
Sebacic acid	2.6E-04	8.5E-04	1.3E-03	3.3E-04	1.3E-03	N.D.									
5-Methoxyindoleacetic acid"	6.7E-04	5.4E-04	4.2E-04	N.D.	N.D.	N.D.									
Phenylpropionylglycine"	N.D.	N.D.	N.D.	2.2E-04	1.2E-04	2.2E-04									
p-Hydroxyphenylacetylglycine	N.D.	3.7E-04	3.1E-04	N.D.	3.4E-04	N.D.									
Glucaric acid	2.7E-03	2.9E-03	2.4E-03	2.2E-03	2.6E-03	2.1E-03									
Mucic acid	5.5E-03	6.6E-03	5.7E-03	4.9E-03	5.0E-03	3.9E-03									
Phosphocreatine	1.4E+00	1.3E+00	1.3E+00	1.3E+00	1.3E+00	1.3E+00									
3-Indoxylsulfuric acid	5.3E-04	7.5E-04	4.2E-04	3.4E-04	2.7E-04	3.9E-04									
Deoxyxylulose 5-phosphate	N.D.	N.D.	N.D.	1.4E-04	N.D.	2.0E-04									
2-Deoxyribose 1-phosphate	N.D.	4.9E-04	5.8E-04	N.D.	2.3E-04	1.7E-04									
Tridecanoic acid	3.2E-03	2.4E-03	2.5E-03	3.1E-03	2.6E-03	2.8E-03									
Undecanedioic acid	7.3E-04	6.8E-04	1.1E-03	N.D.	1.1E-03	6.8E-04									
O-Succinylhomoserine	1.4E-02	1.3E-02	1.3E-02	1.4E-02	1.2E-02	1.3E-02									
Pantothenic acid	4.2E-01	3.8E-01	3.8E-01	3.7E-01	3.7E-01	3.7E-01									
N-Acetyltyrosine	N.D.	1.5E-03	1.9E-03	3.4E-04	1.5E-03	N.D.									
Myristoleic acid	3.8E-03	3.0E-03	3.2E-03	2.9E-03	2.8E-03	2.8E-03									
Myristic acid	3.7E-02	2.5E-02	3.1E-02	3.4E-02	2.3E-02	2.7E-02									
Ribose 5-phosphate	7.8E-04	2.1E-02	1.2E-02	7.7E-04	1.4E-03	6.8E-04									
Ribulose 5-phosphate	1.1E-02	3.8E-02	3.7E-02	9.5E-03	1.7E-02	9.9E-03									
Dodecanedioic acid	5.2E-04	N.D.	3.1E-04	N.D.	3.2E-04	1.6E-04									
N-Lactoylphenylalanine	1.6E-02	1.5E-02	1.4E-02	1.1E-02	9.2E-03	9.9E-03									
7-Amino-4-hydroxy-2-naphthalenesulfonic acid	2.5E-04	2.5E-04	N.D.	2.0E-04	N.D.	N.D.									
Dimethylallylpyrophosphate	2.2E-04	N.D.	2.4E-04	N.D.	N.D.	N.D.									
-Glu-Taurine	5.6E-03	5.1E-03	5.1E-03	5.2E-03	5.3E-03	5.8E-03									
myo-Inositol 1-phosphate"	4.0E-02	3.3E-02	2.7E-02	4.1E-02	2.7E-02	2.2E-02									
Fructose 6-phosphate	1.6E-02	2.1E-02	2.1E-02	1.9E-02	2.2E-02	2.1E-02									
myo-Inositol 2-phosphate	2.1E-02	2.0E-02	1.8E-02	2.0E-02	1.9E-02	1.9E-02									
Glucose 1-phosphate	5.7E-02	5.6E-02	5.7E-02	5.4E-02	5.2E-02	5.0E-02									
Glucose 6-phosphate	8.2E-02	1.0E-01	1.1E-01	1.0E-01	1.0E-01	1.0E-01									
Sulfotyrosine	8.3E-03	7.2E-03	7.1E-03	6.9E-03	7.2E-03	7.2E-03									
Sorbitol 6-phosphate	2.1E-02	5.9E-03	8.0E-03	1.9E-02	9.9E-03	1.8E-02									
N2-Phenylacetylglutamine	N.D.	3.0E-04	5.3E-04	N.D.	N.D.	N.D.									
"2,3-Diphosphoglyceric acid"	2.5E-01	2.5E-01	2.5E-01	2.0E-01	2.0E-01	2.1E-01									
6-Phosphogluconic acid	3.6E-02	3.6E-02	3.6E-02	3.2E-02	3.2E-02	3.3E-02									
Xanthosine	2.9E-04	3.7E-04	3.0E-04	1.9E-04	2.4E-04	1.9E-04									
Orotidine	1.0E-03	8.9E-04	8.2E-04	3.9E-04	5.1E-04	4.7E-04									
Sedoheptulose 7-phosphate	4.3E-02	4.1E-02	4.5E-02	2.8E-02	3.0E-02	3.1E-02									
N-Acetylmuramic acid	2.2E-04	N.D.	N.D.	N.D.	N.D.	N.D.									
Retinoic acid	2.5E-03	7.2E-04	8.7E-04	7.8E-04	8.0E-04	7.1E-04									
N-Acetylgalactosamine 4-sulfate	2.1E-04	4.9E-04	4.0E-04	2.4E-04	2.6E-04	2.0E-04									
N-Acetylglucosamine 6-phosphate	8.3E-03	8.5E-03	9.3E-03	8.5E-03	9.0E-03	8.3E-03									
N-Acetylglucosamine 1-phosphate	3.6E-02	3.6E-02	3.7E-02	3.3E-02	3.2E-02	3.1E-02									
N-Acetylaspartylglutamic acid	1.9E-03	2.2E-03	1.5E-03	2.6E-03	2.5E-03	2.6E-03									
dCMP	N.D.	N.D.	N.D.	N.D.	N.D.	N.D.									
5-Diphosphomevalonic acid	N.D.	N.D.	N.D.	1.8E-04	N.D.	N.D.									
dUMP	2.3E-03	2.2E-03	2.2E-03	2.1E-03	2.2E-03	2.0E-03									
N-Acetylneuraminic acid	6.1E-02	5.9E-02	6.0E-02	5.1E-02	5.0E-02	4.9E-02									
"Ribulose 1,5-diphosphate"	8.7E-03	7.4E-03	7.4E-03	6.7E-03	5.7E-03	6.7E-03									
Geranyl diphosphate	2.1E-04	N.D.	N.D.	N.D.	N.D.	N.D.									
dTMP	4.0E-04	3.5E-04	5.0E-04	N.D.	2.9E-04	3.6E-04									
CMP	1.4E-02	1.3E-02	1.4E-02	1.7E-02	1.4E-02	1.7E-02									
3'-CMP	2.9E-03	2.9E-03	3.0E-03	3.1E-03	2.9E-03	2.9E-03									
3'-UMP	7.6E-04	4.8E-04	4.0E-04	7.3E-04	3.9E-04	4.9E-04									
UMP	2.7E-01	3.9E-02	1.0E-01	3.9E-01	1.8E-01	3.8E-01									
N-Glycolylneuraminic acid	1.6E-02	1.6E-02	1.6E-02	1.5E-02	1.5E-02	1.5E-02									
cAMP	3.3E-03	2.8E-03	2.9E-03	2.5E-03	2.8E-03	2.7E-03									
Phytic acid_divalent	6.3E-02	4.8E-02	5.5E-02	5.2E-02	4.9E-02	5.5E-02									
5-Aminoimidazole-4-carboxamide ribotide	1.8E-03	1.9E-03	2.0E-03	1.1E-03	1.0E-03	1.1E-03									
Ascorbate 2-glucoside	6.1E-04	N.D.	3.1E-04	5.0E-04	N.D.	4.9E-04									
"Fructose 1,6-diphosphate"	8.0E-01	8.3E-01	8.6E-01	7.1E-01	7.1E-01	7.3E-01									
3'-AMP	1.3E-03	1.1E-03	1.1E-03	1.1E-03	1.2E-03	9.0E-04									
AMP	9.2E-02	7.5E-02	7.7E-02	9.3E-02	7.8E-02	8.8E-02									
IMP	4.8E-03	4.1E-03	4.3E-03	3.5E-03	3.4E-03	2.9E-03									
Maltobionic acid	3.4E-04	N.D.	4.5E-04	N.D.	4.1E-04	1.9E-04									
GMP	2.8E-02	2.2E-02	2.3E-02	2.4E-02	2.1E-02	2.1E-02									
XMP	3.3E-04	3.5E-04	4.2E-04	N.D.	N.D.	N.D.									
NADPH_divalent	9.7E-02	1.5E-01	1.1E-01	7.8E-02	1.0E-01	7.8E-02									
Farnesyl pyrophosphate	7.5E-04	5.8E-04	8.6E-04	7.7E-04	6.0E-04	6.8E-04									
CoA_divalent	5.1E-02	3.2E-02	2.2E-02	3.8E-02	3.9E-02	2.4E-02									
dCDP	7.0E-04	2.3E-04	2.1E-04	7.2E-04	4.0E-04	7.7E-04									
PRPP	1.5E-02	8.8E-03	1.0E-02	1.3E-02	7.2E-03	1.3E-02									
FAD_divalent	1.5E-02	1.5E-02	1.6E-02	1.5E-02	1.4E-02	1.4E-02									
dTDP	1.8E-03	4.7E-04	7.9E-04	1.3E-03	7.4E-04	1.3E-03									
CDP	8.2E-02	2.6E-02	2.6E-02	7.8E-02	4.7E-02	7.8E-02									
UDP	2.1E-01	7.9E-02	7.4E-02	2.0E-01	1.4E-01	2.1E-01									
dADP	9.7E-04	5.1E-04	3.6E-04	2.3E-04	3.2E-04	5.6E-04									
"P1, P4-Di(adenosine-5') tetraphosphate_divalent"	4.8E-03	3.4E-03	4.6E-03	3.9E-03	4.1E-03	4.5E-03									
Thiamine diphosphate	3.0E-03	3.0E-03	3.1E-03	2.9E-03	3.1E-03	2.8E-03									
Adenosine 5'-phosphosulfate	1.5E-02	2.3E-02	2.0E-02	1.5E-02	1.6E-02	1.4E-02									
ADP	1.0E+00	5.2E-01	5.6E-01	8.4E-01	6.7E-01	9.9E-01									
"3',5'-ADP"	1.2E-02	9.5E-03	9.0E-03	1.1E-02	8.9E-03	1.0E-02									
Methylmalonyl CoA_divalent"	N.D.	2.5E-04	N.D.	N.D.	N.D.	N.D.									
GDP	1.8E-01	9.5E-02	1.1E-01	1.7E-01	1.2E-01	1.7E-01									
HMG CoA_divalent	2.7E-03	4.1E-03	2.1E-03	9.5E-04	2.7E-03	1.5E-03									
FMN	8.2E-04	8.9E-04	7.1E-04	6.6E-04	5.1E-04	5.5E-04									
Adenylosuccinic acid	2.4E-04	N.D.	N.D.	N.D.	N.D.	N.D.									
dCTP	9.7E-03	9.9E-03	9.8E-03	5.9E-03	7.1E-03	7.0E-03									
dTTP	2.2E-02	2.3E-02	2.3E-02	1.4E-02	1.6E-02	1.5E-02									
CTP	7.6E-01	7.6E-01	7.5E-01	7.3E-01	7.6E-01	7.4E-01									
UTP	2.2E+00	2.2E+00	2.3E+00	2.1E+00	2.2E+00	2.3E+00									
CDP-choline	5.5E-03	5.2E-03	5.3E-03	5.0E-03	5.1E-03	5.0E-03									
dATP	8.3E-03	8.6E-03	9.5E-03	4.6E-03	5.2E-03	5.3E-03									
dGTP	4.6E-03	3.7E-03	3.2E-03	2.2E-03	2.2E-03	2.2E-03									
ATP	7.5E+00	7.6E+00	8.1E+00	6.9E+00	7.0E+00	7.4E+00									
GTP	1.3E+00	1.2E+00	1.2E+00	1.2E+00	1.1E+00	1.2E+00									
ADP-ribose	4.5E-03	1.2E-02	1.2E-02	4.3E-03	3.6E-03	4.4E-03									
dTDP-glucose	1.5E-01	1.5E-01	1.5E-01	1.7E-01	1.6E-01	1.9E-01									
UDP-glucose"	1.1E+00	1.2E+00	1.1E+00	9.5E-01	1.1E+00	9.5E-01									
UDP-glucuronic acid	4.6E-01	5.0E-01	4.9E-01	4.2E-01	4.6E-01	3.9E-01									
ADP-glucose"	5.9E-02	5.3E-02	5.0E-02	5.2E-02	5.4E-02	5.6E-02									
GDP-glucose"	2.5E-02	2.2E-02	2.1E-02	2.2E-02	2.2E-02	2.3E-02									
UDP-N-acetylgalactosamine"	2.4E+00	2.2E+00	2.3E+00	2.5E+00	2.4E+00	2.7E+00									
CMP-N-acetylneuraminate	1.0E-01	9.2E-02	9.2E-02	8.9E-02	7.7E-02	9.4E-02									
NAD+	7.4E-01	6.9E-01	7.1E-01	7.5E-01	6.9E-01	7.9E-01									
Deamido-NAD+	N.D.	3.1E-04	4.8E-04	2.7E-04	3.9E-04	N.D.									
NADH	1.6E-01	1.7E-01	1.2E-01	1.3E-01	1.2E-01	1.2E-01									
NADP+	5.0E-02	2.2E-02	3.6E-02	4.5E-02	3.3E-02	4.8E-02									
MS_METABOLITE_DATA_END
#METABOLITES
METABOLITES_START
metabolite_name
Glyoxylic acid
Propionic acid
Glycolic acid
Pyruvic acid
Isobutyric acid"
Oxamic acid
Lactic acid
Phenol
2-Hydroxypyridine
Valeric acid"
N-Formylglycine
2-Hydroxybutyric acid
3-Hydroxybutyric acid
Glyceric acid
Fumaric acid
Maleic acid
4-Oxovaleric acid
2-Oxoisovaleric acid
4-Methylpentanoic acid"
N-Acetylglycine
Succinic acid
2-Hydroxyisovaleric acid-1"
2-Hydroxyisovaleric acid-2"
5-Hydroxypentanoic acid"
2-Ethylhydracrylic acid-2
Benzoic acid
Isethionic acid
5-Oxoproline
Citraconic acid
4-Oxohexanoic acid"
2-Oxohexanoic acid"
Heptanoic acid
N-Acetyl- -alanine"
Methylsuccinic acid"
2-Hydroxy-3-methylvaleric acid"
3-Hydroxyhexanoic acid"
Iminodiacetic acid
Malic acid
Threonic acid
m-Toluic acid"
4-Hydroxyphenylacetaldehyde
o-Hydroxybenzoic acid
p-Hydroxybenzoic acid"
6-Hydroxynicotinic acid
Ethanolamine phosphate
5-Hydroxymethyluracil
Octanoic acid-2
Octanoic acid-1"
N-Propionylalanine-1"
Isobutyrylglycine"
2-Oxoglutaric acid
2-Methylglutaric acid"
3-Ureidoisobutyric acid
2-Hydroxyglutaric acid
Citramalic acid
Mevalonic acid
Pantoic acid
Tartaric acid
2-Deoxyribonic acid-2
2-Deoxyribonic acid-1
3-Phenylpropionic acid
2-(Hydroxymethyl)benzoic acid"
Cysteinesulfinic acid
Phosphoglycolic acid
Orotic acid
Dihydroorotic acid
Succinylacetone
Pelargonic acid
2-Methylbutyrylglycine-1"
2-Methylbutyrylglycine-2
3-Methyladipic acid"
3-Hydroxyoctanoic acid-2"
3-Hydroxyoctanoic acid-1"
Indole-3-carboxylic acid
N-Acetylthreonine
3-Hydroxy-3-methylglutaric acid
2-Hydroxyadipic acid
N-Acetylcysteine
Phenylpyruvic acid
N-Formylanthranilic acid
Phthalic acid
Terephthalic acid
Arabinonic acid
p-Methoxyphenylacetic acid"
N-Acetyltaurine
Phosphoenolpyruvic acid
Uric acid
Cysteic acid
Glyceraldehyde 3-phosphate
Dihydroxyacetone phosphate
Glycerol 2-phosphate
Glycerol 3-phosphate
Decanoic acid
N-Hexanoylglycine"
Phenol sulphate
p-Phenolsulfonic acid
cis-Aconitic acid
N-Acetylasparagine
Suberic acid
N-Acetylaspartic acid
Glucurone
"1,2,3-Propanetricarboxylic acid"
N-Carbamoylaspartic acid
N-Formylmethionine
Hippuric acid
Caffeic acid"
Hydroxyphenyllactic acid"
Homocysteic acid
3-Methoxy-4-hydroxyphenylethyleneglycol
O-Phosphoserine
2-Phosphoglyceric acid
3-Phosphoglyceric acid
Undecanoic acid
p-Cresol sulfate
N-Acetylglutamine
Azelaic acid
3-Hydroxydecanoic acid"
Indole-3-glyoxylic acid
N-Acetylglutamic acid
"2,4-Dichlorobenzoic acid"
N-Acetylmethionine
Citric acid
Isocitric acid
Quinic acid
Phenaceturic acid"
Glucuronic acid"
Gluconic acid
Lauric acid
Capryloylglycine
p-Sulfobenzoic acid
Sebacic acid
5-Methoxyindoleacetic acid"
Phenylpropionylglycine"
p-Hydroxyphenylacetylglycine
Glucaric acid
Mucic acid
Phosphocreatine
3-Indoxylsulfuric acid
Deoxyxylulose 5-phosphate
2-Deoxyribose 1-phosphate
Tridecanoic acid
Undecanedioic acid
O-Succinylhomoserine
Pantothenic acid
N-Acetyltyrosine
Myristoleic acid
Myristic acid
Ribose 5-phosphate
Ribulose 5-phosphate
Dodecanedioic acid
N-Lactoylphenylalanine
7-Amino-4-hydroxy-2-naphthalenesulfonic acid
Dimethylallylpyrophosphate
-Glu-Taurine
myo-Inositol 1-phosphate"
Fructose 6-phosphate
myo-Inositol 2-phosphate
Glucose 1-phosphate
Glucose 6-phosphate
Sulfotyrosine
Sorbitol 6-phosphate
N2-Phenylacetylglutamine
"2,3-Diphosphoglyceric acid"
6-Phosphogluconic acid
Xanthosine
Orotidine
Sedoheptulose 7-phosphate
N-Acetylmuramic acid
Retinoic acid
N-Acetylgalactosamine 4-sulfate
N-Acetylglucosamine 6-phosphate
N-Acetylglucosamine 1-phosphate
N-Acetylaspartylglutamic acid
dCMP
5-Diphosphomevalonic acid
dUMP
N-Acetylneuraminic acid
"Ribulose 1,5-diphosphate"
Geranyl diphosphate
dTMP
CMP
3'-CMP
3'-UMP
UMP
N-Glycolylneuraminic acid
cAMP
Phytic acid_divalent
5-Aminoimidazole-4-carboxamide ribotide
Ascorbate 2-glucoside
"Fructose 1,6-diphosphate"
3'-AMP
AMP
IMP
Maltobionic acid
GMP
XMP
NADPH_divalent
Farnesyl pyrophosphate
CoA_divalent
dCDP
PRPP
FAD_divalent
dTDP
CDP
UDP
dADP
"P1, P4-Di(adenosine-5') tetraphosphate_divalent"
Thiamine diphosphate
Adenosine 5'-phosphosulfate
ADP
"3',5'-ADP"
Methylmalonyl CoA_divalent"
GDP
HMG CoA_divalent
FMN
Adenylosuccinic acid
dCTP
dTTP
CTP
UTP
CDP-choline
dATP
dGTP
ATP
GTP
ADP-ribose
dTDP-glucose
UDP-glucose"
UDP-glucuronic acid
ADP-glucose"
GDP-glucose"
UDP-N-acetylgalactosamine"
CMP-N-acetylneuraminate
NAD+
Deamido-NAD+
NADH
NADP+
METABOLITES_END
#END