#METABOLOMICS WORKBENCH tetsuya326_20221129_065219 DATATRACK_ID:3611 STUDY_ID:ST002376 ANALYSIS_ID:AN003872 PROJECT_ID:PR001529
VERSION             	1
CREATED_ON             	December 1, 2022, 9:57 am
#PROJECT
PR:PROJECT_TITLE                 	Hepatic Phosphatidylcholine Catabolism Driven by PNPLA7 and PNPLA8 Supplies
PR:PROJECT_TITLE                 	Endogenous Choline to Replenish the Methionine Cycle with Methyl Groups
PR:PROJECT_SUMMARY               	Choline supplies methyl groups for regeneration of methionine and the methyl
PR:PROJECT_SUMMARY               	donor S-adenosylmethionine in the liver. Here we demonstrate that the catabolism
PR:PROJECT_SUMMARY               	of membrane phosphatidylcholine (PC) into water-soluble glycerophosphocholine
PR:PROJECT_SUMMARY               	(GPC) by the phospholipase/lysophospholipase PNPLA8-PNPLA7 axis enables
PR:PROJECT_SUMMARY               	endogenous choline stored in hepatic PC to be utilized in methyl metabolism.
PR:PROJECT_SUMMARY               	PNPLA7-deficient mice show marked decreases in hepatic GPC, choline, and several
PR:PROJECT_SUMMARY               	metabolites related to the methionine cycle, accompanied by various signs of
PR:PROJECT_SUMMARY               	methionine insufficiency including growth retardation, hypoglycemia,
PR:PROJECT_SUMMARY               	hypolipidemia, increased energy consumption, reduced adiposity, increased FGF21,
PR:PROJECT_SUMMARY               	and an altered histone/DNA methylation landscape. Moreover, PNPLA8-deficient
PR:PROJECT_SUMMARY               	mice recapitulate most of these phenotypes. In contrast to wild-type mice fed a
PR:PROJECT_SUMMARY               	methionine/choline-deficient diet, both knockout strains display a decreased
PR:PROJECT_SUMMARY               	hepatic triglyceride likely via reductions of lipogenesis and GPC-derived
PR:PROJECT_SUMMARY               	glycerol flux. Collectively, our findings highlight the biological importance of
PR:PROJECT_SUMMARY               	phospholipid catabolism driven by PNPLA8/PNPLA7 in methyl group flux and
PR:PROJECT_SUMMARY               	triglyceride synthesis in the liver.
PR:INSTITUTE                     	Tokyo Metropolitan Institute of Medical Science
PR:LAST_NAME                     	Hirabayashi
PR:FIRST_NAME                    	Tetsuya
PR:ADDRESS                       	2-6-1 Kamikitazawa, Setagaya-ku, Tokyo, 156-8506, Japan
PR:EMAIL                         	hirabayashi-tt@igakuken.or.jp
PR:PHONE                         	+81-3-5316-3100
#STUDY
ST:STUDY_TITLE                   	Hepatic Phosphatidylcholine Catabolism Driven by PNPLA7 and PNPLA8 Supplies
ST:STUDY_TITLE                   	Endogenous Choline to Replenish the Methionine Cycle with Methyl
ST:STUDY_TITLE                   	Groups(Pnpla8-knockout)
ST:STUDY_SUMMARY                 	Choline supplies methyl groups for regeneration of methionine and the methyl
ST:STUDY_SUMMARY                 	donor S-adenosylmethionine in the liver. Here we demonstrate that the catabolism
ST:STUDY_SUMMARY                 	of membrane phosphatidylcholine (PC) into water-soluble glycerophosphocholine
ST:STUDY_SUMMARY                 	(GPC) by the phospholipase/lysophospholipase PNPLA8-PNPLA7 axis enables
ST:STUDY_SUMMARY                 	endogenous choline stored in hepatic PC to be utilized in methyl metabolism.
ST:STUDY_SUMMARY                 	PNPLA7-deficient mice show marked decreases in hepatic GPC, choline, and several
ST:STUDY_SUMMARY                 	metabolites related to the methionine cycle, accompanied by various signs of
ST:STUDY_SUMMARY                 	methionine insufficiency including growth retardation, hypoglycemia,
ST:STUDY_SUMMARY                 	hypolipidemia, increased energy consumption, reduced adiposity, increased FGF21,
ST:STUDY_SUMMARY                 	and an altered histone/DNA methylation landscape. Moreover, PNPLA8-deficient
ST:STUDY_SUMMARY                 	mice recapitulate most of these phenotypes. In contrast to wild-type mice fed a
ST:STUDY_SUMMARY                 	methionine/choline-deficient diet, both knockout strains display a decreased
ST:STUDY_SUMMARY                 	hepatic triglyceride likely via reductions of lipogenesis and GPC-derived
ST:STUDY_SUMMARY                 	glycerol flux. Collectively, our findings highlight the biological importance of
ST:STUDY_SUMMARY                 	phospholipid catabolism driven by PNPLA8/PNPLA7 in methyl group flux and
ST:STUDY_SUMMARY                 	triglyceride synthesis in the liver.
ST:INSTITUTE                     	Tokyo Metropolitan Institute of Medical Science
ST:LAST_NAME                     	Hirabayashi
ST:FIRST_NAME                    	Tetsuya
ST:ADDRESS                       	2-6-1 Kamikitazawa, Setagaya-ku, Tokyo, 156-8506, Japan
ST:EMAIL                         	hirabayashi-tt@igakuken.or.jp

ST:PHONE                         	+81-3-5316-3100
#SUBJECT
SU:SUBJECT_TYPE                  	Mammal
SU:SUBJECT_SPECIES               	Mus musculus
SU:TAXONOMY_ID                   	10090
SU:GENOTYPE_STRAIN               	C57BL/6N
SU:AGE_OR_AGE_RANGE              	6-weeks old
#FACTORS
#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           	-	WT1	Genotype:Wild-type	
SUBJECT_SAMPLE_FACTORS           	-	WT2	Genotype:Wild-type	
SUBJECT_SAMPLE_FACTORS           	-	WT3	Genotype:Wild-type	
SUBJECT_SAMPLE_FACTORS           	-	WT4	Genotype:Wild-type	
SUBJECT_SAMPLE_FACTORS           	-	WT5	Genotype:Wild-type	
SUBJECT_SAMPLE_FACTORS           	-	WT6	Genotype:Wild-type	
SUBJECT_SAMPLE_FACTORS           	-	KO1	Genotype:Pnpla8-knockout	
SUBJECT_SAMPLE_FACTORS           	-	KO2	Genotype:Pnpla8-knockout	
SUBJECT_SAMPLE_FACTORS           	-	KO3	Genotype:Pnpla8-knockout	
SUBJECT_SAMPLE_FACTORS           	-	KO4	Genotype:Pnpla8-knockout	
SUBJECT_SAMPLE_FACTORS           	-	KO5	Genotype:Pnpla8-knockout	
SUBJECT_SAMPLE_FACTORS           	-	KO6	Genotype:Pnpla8-knockout	
#COLLECTION
CO:COLLECTION_SUMMARY            	Mice were deeply anesthetized and perfused intracardially with saline containing
CO:COLLECTION_SUMMARY            	1 mM MOPS (pH 7.4). Liver was rapidly removed, frozen on liquid nitrogen and
CO:COLLECTION_SUMMARY            	stored at –80°C until further processing.
CO:SAMPLE_TYPE                   	Liver
CO:STORAGE_CONDITIONS            	-80℃
#TREATMENT
TR:TREATMENT_SUMMARY             	No treatment in this study.
#SAMPLEPREP
SP:SAMPLEPREP_SUMMARY            	Tissues with internal standards were homogenized with ice-cold
SP:SAMPLEPREP_SUMMARY            	acetonitrile:water (50:50) and centrifuged at 2,300 × g for 5 min at 4 °C.
SP:SAMPLEPREP_SUMMARY            	The supernatant was filtered through a 5-kDa cut-off filter (Ultrafree-MC-PLHCC,
SP:SAMPLEPREP_SUMMARY            	Human Metabolome Technologies) at 9,100 × g for 2 h at 4 °C, dried in a
SP:SAMPLEPREP_SUMMARY            	centrifugal evaporator at 1,500 rpm at 1,000 Pa, and resuspended in 50 μl
SP:SAMPLEPREP_SUMMARY            	of ultrapure water before metabolome analysis.
#CHROMATOGRAPHY
CH:CHROMATOGRAPHY_TYPE           	CE
CH:INSTRUMENT_NAME               	Agilent 7100 CE
CH:COLUMN_NAME                   	Fused silica capillary i.d. 50 μm × 80 cm
#ANALYSIS
AN:ANALYSIS_TYPE                 	MS
#MS
MS:INSTRUMENT_NAME               	Agilent CE-TOFMS
MS:INSTRUMENT_TYPE               	Other
MS:MS_TYPE                       	ESI
MS:ION_MODE                      	NEGATIVE
MS:MS_COMMENTS                   	The spectrometer was scanned from m/z 50 to 1,000. Peaks were extracted using
MS:MS_COMMENTS                   	automatic integration software MasterHands (ver.2.16.0.15 Keio University).
MS:MS_COMMENTS                   	Signal peaks corresponding to isotopomers, adduct ions, and other product ions
MS:MS_COMMENTS                   	of known metabolites were excluded, and remaining peaks were annotated with
MS:MS_COMMENTS                   	putative metabolites from the HMT metabolite database based on their migration
MS:MS_COMMENTS                   	time and m/z values. Peak areas were normalized to internal standards and sample
MS:MS_COMMENTS                   	amounts.
#MS_METABOLITE_DATA
MS_METABOLITE_DATA:UNITS	Peak area
MS_METABOLITE_DATA_START
Samples	WT1	WT2	WT3	WT4	WT5	WT6	KO1	KO2	KO3	KO4
Factors	Genotype:Wild-type	Genotype:Wild-type	Genotype:Wild-type	Genotype:Wild-type	Genotype:Wild-type	Genotype:Wild-type	Genotype:Pnpla8-knockout	Genotype:Pnpla8-knockout	Genotype:Pnpla8-knockout	Genotype:Pnpla8-knockout
2-Amino-3-phosphonopropionic acid	N.D.	N.D.	2.1E-04	N.D.	N.D.	N.D.	2.3E-04	2.5E-04	2.5E-04	N.D.
2-Hydroxybutyric acid	2.3E-03	1.8E-03	2.3E-03	2.6E-03	1.8E-03	1.6E-03	1.5E-03	2.1E-03	1.6E-03	2.0E-03
2-Hydroxyglutaric acid	3.5E-03	1.2E-03	8.4E-04	2.2E-03	8.8E-04	1.9E-03	6.6E-04	8.1E-04	4.9E-04	1.5E-03
2-Hydroxyvaleric acid	N.D.	4.1E-04	N.D.	5.8E-04	N.D.	N.D.	N.D.	2.5E-04	N.D.	N.D.
2,3-Diphosphoglyceric acid	2.5E-03	3.1E-03	9.1E-04	3.4E-03	2.3E-03	3.0E-03	1.3E-03	9.3E-04	3.9E-03	3.6E-03
3-Hydroxybutyric acid	9.4E-03	7.4E-03	1.0E-02	1.3E-02	8.5E-03	5.8E-03	1.8E-02	1.2E-02	9.2E-03	1.1E-02
3-Indoxylsulfuric acid	4.5E-04	N.D.	2.3E-04	5.2E-04	2.9E-04	2.1E-04	N.D.	2.1E-04	6.6E-04	1.9E-04
3-Phenylpropionic acid	1.4E-03	2.4E-04	3.3E-04	6.4E-04	3.4E-04	3.6E-04	2.4E-04	3.1E-04	3.0E-04	4.2E-04
3-Phosphoglyceric acid	5.0E-04	3.9E-04	N.D.	6.6E-04	5.8E-04	5.5E-04	5.0E-04	5.0E-04	7.4E-04	7.2E-04
3-Ureidopropionic acid	7.7E-04	6.9E-04	5.9E-04	3.8E-04	N.D.	4.4E-04	2.9E-04	4.9E-04	3.5E-04	3.2E-04
3'-Dephospho CoA	1.5E-03	6.6E-04	1.0E-03	8.1E-04	5.9E-04	6.3E-04	6.1E-04	5.1E-04	6.7E-04	7.7E-04
3',5'-ADP	N.D.	N.D.	N.D.	N.D.	3.7E-04	N.D.	3.7E-04	2.6E-04	4.7E-04	5.2E-04
4-Acetamidobutanoic acid	5.6E-04	5.6E-04	N.D.	N.D.	7.6E-04	9.3E-04	2.0E-04	7.0E-04	2.1E-04	8.7E-04
5-Methoxyindoleacetic acid	N.D.	N.D.	N.D.	N.D.	1.6E-04	N.D.	N.D.	3.4E-04	4.2E-04	N.D.
5-Oxoproline	1.7E-03	1.4E-03	8.2E-04	5.0E-03	8.3E-04	8.0E-04	1.2E-03	8.7E-04	7.7E-04	7.1E-04
6-Phosphogluconic acid	2.8E-03	3.1E-03	2.2E-03	2.9E-03	3.0E-03	2.6E-03	1.5E-03	2.2E-03	1.5E-03	2.4E-03
Acetyl CoA_divalent	3.8E-03	4.1E-03	5.3E-03	6.8E-03	6.1E-03	5.9E-03	2.9E-03	4.9E-03	4.2E-03	4.1E-03
Adenylosuccinic acid	2.7E-03	2.2E-03	3.1E-03	3.6E-03	1.2E-03	1.3E-03	4.9E-03	2.7E-03	2.3E-03	1.7E-03
Adipic acid	N.D.	N.D.	N.D.	N.D.	3.1E-04	5.4E-04	N.D.	N.D.	N.D.	N.D.
ADP	4.2E-02	7.9E-02	6.1E-02	7.7E-02	7.9E-02	7.3E-02	9.2E-02	8.5E-02	6.7E-02	6.6E-02
ADP-glucose or GDP-fucose	1.1E-03	1.1E-03	1.1E-03	1.2E-03	8.4E-04	1.1E-03	7.2E-04	7.3E-04	7.4E-04	7.5E-04
ADP-ribose	1.4E-02	7.9E-03	1.0E-02	1.4E-02	6.2E-03	4.8E-03	2.9E-03	3.8E-03	4.5E-03	3.8E-03
Allantoic acid	2.9E-04	3.6E-04	2.4E-04	3.3E-04	4.7E-04	3.5E-04	4.7E-04	3.0E-04	4.2E-04	3.9E-04
AMP	2.1E-01	1.1E-01	1.8E-01	1.5E-01	1.2E-01	1.2E-01	1.5E-01	1.1E-01	1.2E-01	1.4E-01
Ascorbate 2-glucoside	3.5E-04	3.1E-04	2.0E-04	N.D.	2.5E-04	2.6E-04	2.4E-04	2.1E-04	N.D.	N.D.
Ascorbate 2-sulfate	N.D.	N.D.	N.D.	N.D.	3.9E-04	3.0E-04	4.4E-04	2.7E-04	3.1E-04	2.4E-04
Ascorbic acid	6.1E-02	5.7E-02	5.8E-02	5.3E-02	3.7E-02	4.7E-02	5.1E-02	4.2E-02	3.9E-02	3.8E-02
ATP	1.1E-02	1.0E-01	3.0E-02	7.7E-02	9.2E-02	7.8E-02	8.9E-02	9.9E-02	5.2E-02	5.1E-02
CDP	N.D.	4.5E-04	1.7E-04	7.1E-04	3.5E-04	3.7E-04	2.5E-04	3.7E-04	N.D.	N.D.
CDP-choline	2.0E-03	8.9E-04	1.1E-03	1.6E-03	1.4E-03	1.2E-03	1.1E-03	1.0E-03	9.8E-04	9.5E-04
Cholic acid	4.4E-04	1.5E-03	N.D.	3.8E-03	2.3E-04	4.3E-04	N.D.	1.4E-04	N.D.	N.D.
Citric acid	5.9E-03	1.5E-02	1.1E-02	1.1E-02	7.6E-03	8.7E-03	1.1E-02	9.1E-03	8.4E-03	7.9E-03
CMP	4.3E-03	2.0E-03	2.0E-03	3.5E-03	1.6E-03	1.8E-03	1.3E-03	2.1E-03	1.2E-03	1.7E-03
CMP-N-acetylneuraminate	3.4E-04	3.4E-04	2.9E-04	3.2E-04	2.4E-04	2.6E-04	2.0E-04	1.9E-04	1.1E-04	2.4E-04
CoA_divalent	2.2E-02	2.2E-02	2.2E-02	1.9E-02	1.9E-02	1.6E-02	2.4E-02	2.0E-02	1.5E-02	1.6E-02
CTP	N.D.	4.1E-04	N.D.	3.9E-04	2.5E-04	N.D.	1.8E-04	3.9E-04	N.D.	N.D.
Decanoic acid	N.D.	N.D.	N.D.	N.D.	N.D.	N.D.	2.9E-04	N.D.	N.D.	N.D.
Dihydroxyacetone phosphate	2.2E-03	2.9E-03	2.0E-03	4.4E-03	2.4E-03	4.5E-03	5.6E-04	5.5E-04	2.5E-03	3.3E-03
dTDP-glucose	3.2E-04	3.6E-04	2.3E-04	3.3E-04	2.4E-04	2.8E-04	2.4E-04	2.5E-04	N.D.	2.1E-04
Ethanolamine phosphate	1.4E-02	1.4E-02	1.3E-02	1.1E-02	8.0E-03	9.3E-03	8.8E-03	7.7E-03	6.5E-03	7.6E-03
Ethyl glucuronide	4.1E-03	N.D.	5.3E-03	1.3E-03	1.3E-03	1.4E-03	1.3E-02	4.3E-03	6.3E-03	1.0E-03
FAD_divalent	2.1E-03	2.1E-03	2.1E-03	2.0E-03	2.8E-03	2.4E-03	3.1E-03	3.0E-03	2.4E-03	2.6E-03
Fructose 1,6-diphosphate	5.8E-04	1.1E-03	5.0E-04	2.3E-03	3.6E-04	1.5E-03	N.D.	N.D.	4.4E-04	9.6E-04
Fructose 6-phosphate	9.7E-03	1.2E-02	8.7E-03	1.1E-02	8.0E-03	1.1E-02	4.8E-03	7.2E-03	6.0E-03	5.9E-03
Fumaric acid	7.5E-03	1.7E-02	1.4E-02	1.6E-02	8.2E-03	7.6E-03	1.9E-02	1.5E-02	1.3E-02	8.0E-03
Galacturonic acid	8.8E-04	5.8E-04	5.5E-04	5.8E-04	6.6E-04	5.3E-04	4.8E-04	6.9E-04	4.2E-04	3.3E-04
GDP	2.8E-03	8.1E-03	3.7E-03	5.9E-03	8.5E-03	7.8E-03	9.2E-03	5.5E-03	4.6E-03	4.2E-03
GDP-glucose	1.9E-03	2.3E-03	1.4E-03	2.3E-03	2.2E-03	2.1E-03	1.2E-03	1.7E-03	1.3E-03	1.5E-03
Gluconic acid	5.6E-02	3.8E-02	4.0E-02	4.1E-02	3.5E-02	3.0E-02	3.3E-02	3.3E-02	2.8E-02	2.3E-02
Glucose 1-phosphate	1.3E-02	5.8E-03	4.1E-03	1.5E-02	4.2E-03	5.5E-03	1.8E-03	3.4E-03	2.6E-03	3.2E-03
Glucose 6-phosphate	3.7E-02	4.6E-02	3.2E-02	4.4E-02	3.4E-02	3.8E-02	1.7E-02	2.9E-02	2.1E-02	2.7E-02
Glucuronic acid	3.7E-03	2.5E-03	2.7E-03	2.0E-03	7.0E-03	6.7E-03	3.8E-03	4.9E-03	3.5E-03	3.7E-03
Glutaric acid	N.D.	N.D.	N.D.	N.D.	1.6E-03	2.2E-03	N.D.	N.D.	N.D.	2.4E-03
Glycerol 3-phosphate	1.6E-01	6.0E-02	1.3E-01	1.1E-01	1.0E-01	1.3E-01	7.0E-02	1.0E-01	9.2E-02	8.9E-02
GMP	2.5E-02	1.4E-02	2.2E-02	1.9E-02	1.5E-02	1.5E-02	1.5E-02	1.9E-02	1.4E-02	1.6E-02
GTP	5.1E-04	6.9E-03	1.2E-03	3.7E-03	6.4E-03	5.7E-03	5.9E-03	4.3E-03	2.4E-03	2.0E-03
Hexanoic acid	5.7E-04	N.D.	2.6E-04	3.3E-04	N.D.	3.5E-04	N.D.	N.D.	N.D.	N.D.
Hippuric acid	1.4E-03	6.2E-04	7.3E-04	2.5E-03	N.D.	N.D.	N.D.	2.9E-04	6.9E-04	2.0E-04
IMP	1.2E-02	1.0E-02	9.8E-03	7.4E-03	1.8E-02	1.9E-02	5.8E-03	1.3E-02	7.7E-03	1.0E-02
Isethionic acid	1.0E-03	N.D.	1.2E-03	N.D.	1.5E-03	1.2E-03	2.9E-03	3.0E-03	2.5E-03	1.8E-03
Isobutyryl CoA_divalent	3.1E-03	6.1E-04	2.4E-04	1.3E-03	6.4E-04	7.6E-04	2.1E-04	9.6E-04	3.1E-04	7.9E-04
Isovalerylalanine	3.0E-04	4.0E-04	3.8E-04	2.1E-04	3.0E-04	2.0E-04	2.5E-04	3.2E-04	2.4E-04	N.D.
Lactic acid	4.1E-01	4.7E-01	4.0E-01	6.1E-01	3.3E-01	4.3E-01	1.4E-01	2.2E-01	2.1E-01	3.7E-01
Lauric acid	7.3E-04	1.0E-03	1.1E-03	1.0E-03	9.6E-04	8.4E-04	1.1E-03	9.1E-04	9.8E-04	7.8E-04
Malic acid	2.6E-02	1.1E-01	6.8E-02	8.3E-02	2.6E-02	3.4E-02	8.7E-02	7.3E-02	5.5E-02	2.6E-02
myo-Inositol 1-phosphate,myo-Inositol 3-phosphate	1.1E-03	7.7E-04	8.1E-04	1.0E-03	7.8E-04	8.4E-04	3.4E-04	3.8E-04	5.2E-04	7.8E-04
myo-Inositol 2-phosphate	6.4E-04	6.5E-04	8.8E-04	8.0E-04	6.1E-04	N.D.	3.5E-04	4.1E-04	3.6E-04	3.8E-04
N-Acetylalanine	1.6E-04	2.4E-04	1.9E-04	2.0E-04	1.2E-04	N.D.	1.1E-04	1.6E-04	N.D.	N.D.
N-Acetylasparagine	3.5E-04	2.6E-04	2.8E-04	2.3E-04	2.0E-04	N.D.	N.D.	2.6E-04	N.D.	N.D.
N-Acetylglucosamine 1-phosphate	4.8E-04	4.7E-04	5.3E-04	3.5E-04	4.2E-04	5.3E-04	4.5E-04	3.2E-04	3.3E-04	4.3E-04
N-Acetylglucosamine 6-phosphate	4.1E-04	3.1E-04	2.9E-04	3.5E-04	3.1E-04	3.5E-04	2.8E-04	3.9E-04	2.5E-04	3.2E-04
N-Acetylglutamic acid	8.6E-03	4.7E-03	3.5E-03	5.5E-03	4.6E-03	6.7E-03	1.5E-02	9.7E-03	7.0E-03	6.8E-03
N-Acetylglutamine	2.3E-03	1.9E-03	2.5E-03	2.1E-03	1.0E-03	9.8E-04	1.5E-03	1.5E-03	1.5E-03	7.4E-04
N-Acetylglycine	N.D.	N.D.	N.D.	N.D.	2.2E-04	1.7E-04	3.7E-04	3.3E-04	2.6E-04	1.8E-04
N-Acetylleucine	N.D.	N.D.	N.D.	N.D.	N.D.	N.D.	N.D.	N.D.	2.6E-04	2.2E-04
N-Acetylneuraminic acid	5.1E-04	6.4E-04	5.0E-04	3.9E-04	3.3E-04	6.3E-04	2.6E-04	3.0E-04	2.3E-04	4.2E-04
N-Glycolylneuraminic acid	2.2E-03	2.1E-03	1.8E-03	2.0E-03	2.2E-03	2.4E-03	1.3E-03	1.2E-03	1.0E-03	1.7E-03
N2-Acetylaminoadipic acid	N.D.	N.D.	N.D.	N.D.	N.D.	N.D.	N.D.	2.0E-04	N.D.	N.D.
NAD+	2.3E-02	4.3E-02	2.9E-02	4.1E-02	5.9E-02	4.6E-02	4.6E-02	5.2E-02	3.1E-02	4.3E-02
NADH	7.7E-04	9.0E-04	1.0E-03	1.4E-03	2.7E-03	1.3E-03	2.9E-03	2.1E-03	1.8E-03	8.8E-04
NADP+	9.0E-03	1.1E-02	9.5E-03	1.2E-02	1.3E-02	1.2E-02	1.3E-02	1.1E-02	8.2E-03	1.0E-02
NADPH_divalent	3.9E-04	3.6E-03	1.8E-03	3.5E-03	N.D.	N.D.	5.6E-04	N.D.	3.3E-04	2.8E-04
Pantothenic acid	5.0E-04	7.5E-04	6.3E-04	6.2E-04	4.3E-04	2.6E-04	8.7E-04	6.4E-04	5.2E-04	2.4E-04
Pelargonic acid	6.3E-04	4.3E-04	4.1E-04	4.5E-04	3.6E-04	5.7E-04	5.0E-04	3.4E-04	4.0E-04	4.2E-04
Phenaceturic acid	N.D.	N.D.	N.D.	1.8E-04	N.D.	N.D.	N.D.	N.D.	3.2E-04	N.D.
Phosphocreatine	N.D.	2.5E-04	N.D.	1.7E-04	4.4E-04	5.6E-04	1.9E-04	5.9E-04	2.4E-04	4.0E-04
Propionyl CoA_divalent	8.0E-04	2.9E-04	4.1E-04	7.2E-04	2.1E-04	3.2E-04	2.3E-04	3.2E-04	3.8E-04	2.6E-04
PRPP	2.0E-04	2.3E-04	3.2E-04	3.6E-04	1.7E-04	N.D.	2.2E-04	N.D.	1.8E-04	1.6E-04
Pyruvic acid	5.9E-03	8.9E-03	6.2E-03	8.4E-03	5.6E-03	6.1E-03	5.2E-03	4.6E-03	5.2E-03	6.0E-03
Rhein	6.1E-04	8.2E-04	6.8E-04	8.7E-04	6.8E-04	7.9E-04	4.9E-04	3.4E-04	3.9E-04	5.3E-04
Ribose 5-phosphate	1.5E-03	1.2E-03	1.4E-03	1.6E-03	1.7E-03	1.1E-03	8.2E-04	1.1E-03	2.8E-03	2.0E-03
Ribulose 5-phosphate	1.5E-02	1.0E-02	1.0E-02	1.1E-02	1.3E-02	1.4E-02	8.9E-03	1.2E-02	1.0E-02	1.1E-02
Sedoheptulose 7-phosphate	5.0E-03	1.1E-02	4.4E-03	7.2E-03	6.8E-03	5.0E-03	5.0E-03	8.5E-03	4.0E-03	5.1E-03
Succinic acid	5.4E-02	6.8E-02	4.9E-02	6.9E-02	4.3E-02	5.1E-02	3.6E-02	2.9E-02	3.2E-02	3.5E-02
Taurocholic acid	3.7E-02	2.2E-02	7.4E-02	5.9E-02	2.0E-02	3.3E-02	3.6E-02	2.1E-02	1.6E-02	4.5E-02
Thiamine diphosphate	4.2E-04	6.1E-04	5.4E-04	7.0E-04	1.2E-03	1.0E-03	1.2E-03	1.1E-03	9.0E-04	9.2E-04
Threonic acid	1.4E-03	1.4E-03	1.0E-03	2.1E-03	9.9E-04	8.7E-04	1.1E-03	1.0E-03	6.6E-04	1.1E-03
UDP	1.7E-03	8.8E-03	2.9E-03	5.9E-03	8.6E-03	7.5E-03	7.2E-03	5.2E-03	3.3E-03	2.7E-03
UDP-glucose or UDP-galactose	4.4E-02	6.5E-02	5.0E-02	5.8E-02	4.9E-02	5.5E-02	3.0E-02	2.2E-02	2.2E-02	4.1E-02
UDP-glucuronic acid	1.1E-03	1.1E-03	1.7E-03	7.4E-04	3.3E-03	3.0E-03	7.1E-03	6.1E-03	2.6E-03	1.5E-03
UDP-N-acetylgalactosamine or UDP-N-acetylglucosamine	4.2E-02	4.0E-02	2.9E-02	4.1E-02	2.8E-02	2.9E-02	2.6E-02	2.7E-02	1.9E-02	2.4E-02
UMP	3.9E-02	2.2E-02	3.2E-02	2.5E-02	2.7E-02	2.7E-02	2.2E-02	2.8E-02	1.8E-02	2.4E-02
Uric acid	2.9E-04	N.D.	N.D.	N.D.	2.7E-04	3.4E-04	N.D.	N.D.	N.D.	N.D.
UTP	4.2E-04	9.4E-03	1.1E-03	4.4E-03	8.0E-03	6.4E-03	6.5E-03	5.6E-03	2.1E-03	1.9E-03
XA0003	2.5E-04	N.D.	4.7E-04	2.2E-04	2.4E-04	3.0E-04	1.4E-03	5.3E-04	7.4E-04	2.3E-04
XA0012	2.1E-03	3.9E-04	2.8E-03	7.2E-04	1.1E-03	9.1E-04	2.7E-03	2.7E-03	2.0E-03	1.0E-03
XA0013	2.4E-04	3.8E-04	1.8E-04	2.3E-04	N.D.	1.7E-04	N.D.	1.7E-04	5.7E-04	2.3E-04
XA0019	1.8E-03	4.0E-03	1.3E-03	2.0E-03	3.8E-03	2.5E-03	4.3E-03	3.8E-03	7.2E-04	2.5E-03
XA0033	6.2E-03	5.5E-03	1.1E-02	2.4E-03	9.6E-03	1.5E-02	3.7E-03	5.1E-03	5.1E-03	8.3E-03
XA0055	9.2E-04	5.3E-04	5.6E-04	8.3E-04	7.3E-04	1.4E-03	2.1E-04	3.6E-04	7.7E-04	8.6E-04
XA0065	8.1E-03	5.5E-03	9.6E-03	5.2E-03	5.6E-03	4.5E-03	5.0E-03	5.2E-03	2.3E-03	3.3E-03
Xanthine	2.8E-03	8.3E-04	1.7E-03	2.3E-03	4.7E-03	4.5E-03	2.3E-03	1.6E-03	2.5E-03	4.7E-03
Xanthosine	7.2E-04	3.5E-04	4.7E-04	5.8E-04	1.4E-03	1.4E-03	2.6E-04	5.2E-04	4.8E-04	9.0E-04
MS_METABOLITE_DATA_END
#METABOLITES
METABOLITES_START
metabolite_name	KEGG ID	m/z	migration time
2-Amino-3-phosphonopropionic acid	C05672	168.008	12.54
2-Hydroxybutyric acid	C05984	103.041	9.56
2-Hydroxyglutaric acid	C02630,C01087,C03196	147.030	16.68
2-Hydroxyvaleric acid	No ID	117.057	9.03
2,3-Diphosphoglyceric acid	C01159	264.954	18.32
3-Hydroxybutyric acid	C01089,C03197	103.041	9.33
3-Indoxylsulfuric acid	No ID	212.003	9.34
3-Phenylpropionic acid	C05629	149.060	8.58
3-Phosphoglyceric acid	C00197	184.986	19.55
3-Ureidopropionic acid	C02642	131.046	9.05
3'-Dephospho CoA	C00882	686.143	7.82
3',5'-ADP	C00054	426.024	13.49
4-Acetamidobutanoic acid	C02946	144.067	8.40
5-Methoxyindoleacetic acid	No ID	204.068	7.85
5-Oxoproline	C01879	128.036	9.28
6-Phosphogluconic acid	C00345	275.018	14.47
Acetyl CoA_divalent	C00024	403.558	10.04
Adenylosuccinic acid	C03794	462.068	13.53
Adipic acid	C06104	145.051	14.73
ADP	C00008	426.024	10.66
ADP-glucose or GDP-fucose	C00498,C00325	588.078	8.11
ADP-ribose	C00301	558.066	8.30
Allantoic acid	C00499	175.046	8.51
AMP	C00020	346.057	9.10
Ascorbate 2-glucoside	C18339	337.079	6.96
Ascorbate 2-sulfate	C02812	254.984	14.12
Ascorbic acid	C00072	175.026	8.29
ATP	C00002	505.990	11.54
CDP	C00112	402.012	11.23
CDP-choline	C00307	487.102	6.63
Cholic acid	C00695	407.281	6.69
Citric acid	C00158	191.021	26.45
CMP	C00055	322.046	9.37
CMP-N-acetylneuraminate	C00128	613.142	7.98
CoA_divalent	C00010	382.552	10.41
CTP	C00063	481.978	12.11
Decanoic acid	C01571	171.140	7.79
Dihydroxyacetone phosphate	C00111	168.992	12.43
dTDP-glucose	C00842	563.070	8.25
Ethanolamine phosphate	C00346	140.012	7.84
Ethyl glucuronide	No ID	221.068	7.57
FAD_divalent	C00016	391.573	7.73
Fructose 1,6-diphosphate	C00354	338.990	14.37
Fructose 6-phosphate	C05345,C00085	259.024	9.74
Fumaric acid	C00122	115.004	25.37
Galacturonic acid	C00333	193.037	8.07
GDP	C00035	442.018	10.46
GDP-glucose	C00394	604.072	8.09
Gluconic acid	C00257	195.052	8.01
Glucose 1-phosphate	C00103	259.024	9.91
Glucose 6-phosphate	C00668,C01172,C00092	259.024	9.64
Glucuronic acid	C00191	193.036	7.90
Glutaric acid	C00489	131.035	16.65
Glycerol 3-phosphate	C00093	171.007	11.92
GMP	C00144	362.052	8.95
GTP	C00044	521.985	11.23
Hexanoic acid	C01585	115.077	8.71
Hippuric acid	C01586	178.051	8.24
IMP	C00130	347.042	9.34
Isethionic acid	C05123	124.991	11.39
Isobutyryl CoA_divalent	C00630	417.574	9.77
Isovalerylalanine	No ID	172.099	7.83
Lactic acid	C00186,C00256,C01432	89.025	10.62
Lauric acid	C02679	199.171	7.47
Malic acid	C00149,C00497,C00711	133.015	21.23
myo-Inositol 1-phosphate,myo-Inositol 3-phosphate	C01177,C04006	259.024	10.06
myo-Inositol 2-phosphate	No ID	259.024	10.24
N-Acetylalanine	No ID	130.051	8.67
N-Acetylasparagine	No ID	173.057	8.21
N-Acetylglucosamine 1-phosphate	C04256	300.050	9.34
N-Acetylglucosamine 6-phosphate	C00357	300.051	8.96
N-Acetylglutamic acid	C00624	188.057	12.98
N-Acetylglutamine	No ID	187.073	7.91
N-Acetylglycine	No ID	116.035	9.34
N-Acetylleucine	C02710	172.099	7.91
N-Acetylneuraminic acid	C00270	308.101	7.02
N-Glycolylneuraminic acid	C03410	324.096	7.00
N2-Acetylaminoadipic acid	C12986	202.073	12.01
NAD+	C00003	662.104	6.41
NADH	C00004	664.119	7.99
NADP+	C00006	742.070	9.17
NADPH_divalent	C00005	371.540	11.05
Pantothenic acid	C00864	218.104	7.48
Pelargonic acid	C01601	157.124	7.95
Phenaceturic acid	C05598	192.068	8.01
Phosphocreatine	C02305	210.030	12.03
Propionyl CoA_divalent	C00100	410.564	9.90
PRPP	C00119	388.947	16.56
Pyruvic acid	C00022	87.010	12.69
Rhein	C10401	283.024	8.43
Ribose 5-phosphate	C00117	229.013	10.34
Ribulose 5-phosphate	C00199,C01101	229.013	10.77
Sedoheptulose 7-phosphate	C05382	289.034	9.40
Succinic acid	C00042	117.020	20.80
Taurocholic acid	C05122	514.286	6.57
Thiamine diphosphate	C00068	423.032	7.79
Threonic acid	C01620	135.031	9.05
UDP	C00015	402.997	11.41
UDP-glucose or UDP-galactose	C00029,C00052	565.050	8.43
UDP-glucuronic acid	C00167	579.029	10.80
UDP-N-acetylgalactosamine or UDP-N-acetylglucosamine	C00203,C00043	606.076	8.26
UMP	C00105	323.030	9.58
Uric acid	C00366	167.022	8.70
UTP	C00075	482.964	12.33
XA0003	No ID	124.991	12.34
XA0012	No ID	166.018	9.21
XA0013	No ID	172.993	10.64
XA0019	No ID	191.020	8.11
XA0033	No ID	242.081	7.45
XA0055	No ID	369.000	14.08
XA0065	No ID	445.055	6.77
Xanthine	C00385	151.026	8.14
Xanthosine	C01762	283.069	7.44
METABOLITES_END
#END