#METABOLOMICS WORKBENCH tetsuya326_20221130_231541 DATATRACK_ID:3616 STUDY_ID:ST002377 ANALYSIS_ID:AN003873 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 Groups
ST:STUDY_TITLE                   	(Pnpla7-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:Pnpla7-knockout	
SUBJECT_SAMPLE_FACTORS           	-	KO2	Genotype:Pnpla7-knockout	
SUBJECT_SAMPLE_FACTORS           	-	KO3	Genotype:Pnpla7-knockout	
SUBJECT_SAMPLE_FACTORS           	-	KO4	Genotype:Pnpla7-knockout	
SUBJECT_SAMPLE_FACTORS           	-	KO5	Genotype:Pnpla7-knockout	
SUBJECT_SAMPLE_FACTORS           	-	KO6	Genotype:Pnpla7-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 methanol and
SP:SAMPLEPREP_SUMMARY            	extracted by the Bligh–Dyer method using chloroform and methanol to separate
SP:SAMPLEPREP_SUMMARY            	and recover the water-soluble fractions. The supernatant was filtered through a
SP:SAMPLEPREP_SUMMARY            	5-kDa cut-off filter (Ultrafree-MC-PLHCC, Human Metabolome Technologies) at
SP:SAMPLEPREP_SUMMARY            	9,100 × g for 2 h at 4 °C, dried in a centrifugal evaporator at 1,500 rpm
SP:SAMPLEPREP_SUMMARY            	at 1,000 Pa, and resuspended in 50 μl of ultrapure water before metabolome
SP:SAMPLEPREP_SUMMARY            	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 6224 TOF
MS:INSTRUMENT_TYPE               	Other
MS:MS_TYPE                       	ESI
MS:ION_MODE                      	POSITIVE
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                   	Putative metabolites were assigned based on the m/z value and migration time
MS:MS_COMMENTS                   	using Human Metabolomic Technologies’ standard library and known–unknown
MS:MS_COMMENTS                   	peak library. Peak areas were normalized to internal standards and sample
MS:MS_COMMENTS                   	amounts.
#MS_METABOLITE_DATA
MS_METABOLITE_DATA:UNITS	nmol
MS_METABOLITE_DATA_START
Samples	WT1	WT2	WT3	WT4	WT5	KO1	KO2	KO3	KO4	KO5
Factors	Genotype:Wild-type	Genotype:Wild-type	Genotype:Wild-type	Genotype:Wild-type	Genotype:Wild-type	Genotype:Pnpla7-knockout	Genotype:Pnpla7-knockout	Genotype:Pnpla7-knockout	Genotype:Pnpla7-knockout	Genotype:Pnpla7-knockout
1-Methyladenosine	1.17	1.17	0.77	1.39	1.08	1.45	1.47	1.53	1.69	1.55
1-Methylhistamine	0.61	1.41	1.05	1.94	0.67	1.32	0.80	1.20	0.69	0.76
1-Methylnicotinamide	11.82	18.47	14.61	13.28	13.84	19.97	5.83	6.91	13.61	14.80
2,4-Diaminobutyrate	2.40	3.52	1.38	2.42	3.71	1.07	1.17	1.97	1.62	1.45
D-2-aminobutyrate	146.59	94.45	69.64	92.47	119.73	217.96	87.39	174.42	188.13	184.11
3-Aminoisobutyrate	22.78	11.09	13.78	12.34	10.80	16.42	16.81	13.56	14.51	14.21
3-Methylhistidine	3.24	2.97	1.54	1.89	3.81	2.57	2.85	3.26	2.67	3.00
5-Aminoimidazole-4-carboxamide ribotide	3.35	3.42	4.10	3.21	2.55	2.89	3.42	3.11	3.33	3.96
5-Aminolevulinate	11.65	9.64	10.55	10.00	8.01	6.57	4.28	8.77	11.03	8.58
5-Hydroxyindoleacetate	1.89	0.68	1.62	0.88	1.47	0.94	N.D.	0.66	0.79	0.39
5-Methyltetrahydrofolate	20.73	8.08	5.00	6.41	31.76	2.34	1.83	5.86	3.31	6.20
5-Methylthioadenosine	7.91	8.59	15.76	6.76	6.77	27.63	3.11	2.93	6.80	1.56
7,8-Dihydrobiopterin	7.49	9.31	6.48	9.87	8.01	9.06	7.92	8.61	9.40	9.45
Adenine	8.53	11.14	6.63	11.61	11.73	10.04	8.35	11.31	10.06	12.33
Adenosine	146.46	171.75	106.67	240.21	159.42	265.68	118.55	173.16	217.52	117.69
ADMA	13.11	4.66	8.66	7.93	10.66	3.17	7.99	6.71	6.25	9.65
Ala	4440.49	3186.85	3787.94	4982.90	4649.72	4901.84	2710.51	4836.44	3711.94	3187.41
Ala-Ala	4.13	4.87	5.26	3.73	3.16	3.76	2.19	3.01	3.43	1.55
Allantoin	153.79	237.43	137.17	227.40	436.77	182.11	190.22	353.82	147.80	149.83
alpha-Aminoadipate	146.56	35.43	162.91	121.00	35.22	723.85	10.99	36.26	21.03	18.21
alpha-Lipoamide	3.93	3.32	3.06	3.20	3.43	4.08	3.73	3.43	3.26	3.44
Alpha-Methylserine	1.33	2.56	2.64	1.75	1.37	1.45	1.03	1.18	1.86	0.95
Arg	3.88	1.88	12.12	2.26	3.97	3.23	5.32	4.49	2.23	3.44
Asn	107.10	100.52	222.79	106.53	118.81	122.37	102.22	89.63	90.17	52.29
Asp	1161.92	368.46	775.66	668.93	654.36	480.44	538.48	745.69	515.88	561.15
beta-Ala	291.61	246.82	150.89	172.31	215.52	236.47	216.03	244.76	293.75	318.39
Betaine	1267.25	488.16	298.34	363.46	738.17	155.76	187.88	470.57	336.14	488.13
Betaine aldehyde (+H2O)	73.13	23.81	30.87	29.98	95.63	29.06	25.31	36.59	32.23	46.07
Cadaverine	0.20	N.D.	N.D.	N.D.	N.D.	0.24	0.33	0.12	0.31	0.21
Carnitine	209.46	176.07	185.92	182.33	188.74	130.81	109.34	163.38	136.18	146.04
Carnosine	0.74	0.86	0.56	0.68	0.61	0.62	0.62	0.55	0.80	0.48
Choline	365.26	276.24	201.57	262.21	348.66	178.85	121.75	168.84	167.32	136.37
Citrulline	12.77	25.62	17.63	39.92	31.47	33.59	17.28	26.09	17.06	18.55
Creatine	136.38	251.02	296.78	171.45	267.62	281.27	169.88	225.50	94.68	231.74
Creatinine	3.41	4.60	4.31	4.25	4.69	5.07	3.07	5.01	1.74	2.80
Cyclohexylamine	0.50	0.47	0.74	0.37	0.61	0.62	0.60	0.59	0.37	0.63
Cys	3.44	5.57	3.75	4.16	3.68	4.37	2.82	4.90	4.17	4.17
Cystathionine	40.66	43.80	73.15	170.27	36.90	135.73	10.37	26.98	79.48	17.13
Cysteine-glutathione disulphide -Divalent	7.10	15.18	8.82	11.80	10.87	8.00	7.27	12.86	13.45	9.29
Cystine	N.D.	N.D.	N.D.	N.D.	N.D.	N.D.	N.D.	N.D.	N.D.	N.D.
Cytidine	7.51	5.56	6.16	10.69	11.93	6.15	22.54	13.64	8.00	26.05
Cytosine	N.D.	N.D.	N.D.	N.D.	0.19	N.D.	N.D.	N.D.	N.D.	N.D.
Dihydrouracil	14053.29	13742.22	13865.25	12654.31	14504.59	16067.03	14808.92	12000.47	14005.38	10394.78
Ethanolamine phosphate	471.70	381.30	262.91	321.57	458.52	302.08	375.94	346.34	394.23	405.61
GABA	73.54	26.13	75.17	52.25	55.95	24.56	64.40	46.25	36.54	57.02
gamma-Butyrobetaine	6.38	4.32	3.31	3.74	5.25	2.48	3.32	4.43	2.86	3.76
gamma-Glu-cys	29.86	21.79	25.06	20.01	13.49	18.12	12.08	24.38	15.06	19.09
gamma-Guanidinobutyrate	1.16	0.94	1.80	2.15	0.75	2.11	0.45	0.63	1.30	0.28
Gln	1958.33	2050.79	2021.76	1659.82	1945.21	2613.65	2847.26	2917.43	2063.06	2141.05
Glu	2290.52	1687.37	1567.87	1490.12	1466.39	1963.92	1471.35	1409.73	1485.53	1630.63
Glu-Glu	1.07	0.55	0.70	0.48	0.49	0.51	0.70	0.89	0.57	0.76
Glutathione(ox)	1288.84	1288.38	984.89	1339.05	1382.50	1199.01	1187.65	1136.94	1101.41	1202.38
Glutathione(red)	2294.16	1793.76	1683.72	1764.82	1906.51	2222.62	1516.73	1653.14	1354.40	1840.73
Gly	3349.37	2990.04	2174.01	2991.86	3841.31	2077.93	2835.11	3431.24	2751.71	3354.78
Gly-Gly	28.80	18.83	24.86	21.14	24.48	14.14	18.48	23.76	20.67	21.11
Gly-Leu	0.49	1.02	0.56	0.49	0.46	0.37	0.38	0.21	0.85	0.14
Glycerophosphorylcholine	1645.22	937.73	719.98	622.87	1759.73	81.21	37.70	267.70	83.81	95.30
Guanidinoacetate	5.79	4.12	2.68	5.15	4.58	3.42	14.52	16.87	5.78	5.77
Guanidinosuccinate	7.95	13.37	5.35	11.43	12.69	7.16	8.53	15.81	4.16	7.20
Guanine	2.52	2.85	1.53	2.15	2.06	1.91	1.65	2.39	1.71	2.02
Guanosine	38.40	23.49	33.21	34.86	28.69	24.78	57.55	41.12	34.16	52.10
His	510.22	467.22	524.63	588.39	602.28	708.51	598.57	551.80	505.96	500.76
Histamine	0.18	0.20	0.38	0.23	0.19	0.22	0.22	0.26	0.15	0.17
Homoserine	7.92	7.74	9.95	13.01	6.27	8.87	2.73	6.98	7.49	4.49
Hydroxyproline	48.46	21.42	22.47	27.48	25.99	23.67	16.36	25.05	25.07	15.85
Hypotaurine	284.19	170.79	195.32	571.84	87.30	94.99	67.08	66.85	115.83	133.21
Hypoxanthine	1053.13	664.00	743.22	973.85	1202.88	497.11	713.14	716.58	617.25	972.61
Ile	358.01	265.80	293.24	303.04	396.73	313.81	267.06	369.44	287.74	294.94
Imidazole-4-acetate	N.D.	0.93	0.80	1.77	2.34	1.51	1.37	0.95	1.19	1.18
Inosine	2296.72	1764.87	1686.95	2146.62	1986.27	1582.34	2350.78	2328.89	1937.86	2581.76
Isobutylamine	0.77	1.08	0.74	0.69	1.03	1.16	1.05	0.96	0.86	0.60
Kynurenine	1.42	1.80	0.66	1.59	1.51	1.80	0.84	2.03	1.13	1.10
Leu	779.22	550.91	686.62	646.50	753.94	574.62	618.44	721.54	556.04	588.08
Lys	1602.51	1116.98	1460.91	1445.30	1251.38	1526.84	1509.38	1156.23	1437.28	1307.96
Met	368.61	207.97	293.04	277.63	281.70	206.41	241.84	223.40	225.64	270.89
Methionine sulfoxide	21.28	12.01	20.67	21.71	15.53	12.20	10.53	14.45	14.66	9.28
N-Acetylglucosamine	151.46	94.06	97.09	152.23	122.80	71.33	94.77	135.07	92.73	130.57
N-Acetylglucosylamine	1.43	1.22	1.64	1.26	1.54	0.00	1.20	1.25	1.50	1.51
N-Acetylhistidine	9.76	5.97	6.85	7.20	7.23	5.22	5.14	6.93	4.47	4.21
N-Acetylornithine	2.45	2.38	3.90	1.76	2.07	2.48	2.83	2.68	1.97	1.60
N-Acetylputrescine	N.D.	N.D.	N.D.	N.D.	N.D.	0.91	1.79	N.D.	1.46	1.17
N-Acetylvaline	3.68	4.19	1.42	2.34	5.69	1.66	3.68	4.94	3.28	6.20
N-epsilon-Acetyllysine	5.35	3.16	4.73	3.83	2.98	3.67	3.39	2.55	4.48	3.53
N-gamma-Ethylglutamine	1.45	1.47	1.27	0.75	0.47	1.10	0.48	0.62	1.03	0.93
N-Methylalanine	0.87	0.63	2.87	2.33	0.58	6.38	N.D.	0.53	1.61	0.31
N,N-Dimethylglycine	42.53	30.98	53.64	95.01	57.31	64.25	58.99	54.57	47.96	42.59
N6,N6,N6-Trimethyllysine	2.23	1.85	1.52	2.47	2.67	1.10	1.99	2.52	2.20	2.02
N8-Acetylspermidine	0.67	0.73	0.52	0.16	0.15	0.67	0.56	0.28	0.61	0.56
Nicotinamide	1064.48	1090.80	909.86	1219.19	1217.79	968.34	740.36	989.09	985.05	948.69
o-Acetylcarnitine	8.44	22.43	24.19	12.35	14.22	10.60	10.16	6.66	10.93	4.31
Ophthalmate	60.62	43.60	35.23	24.47	54.37	61.42	20.91	89.21	84.54	34.08
Ornithine	542.18	367.94	574.69	451.16	391.81	539.22	352.36	381.82	503.73	449.55
Phe	395.49	224.32	345.02	290.14	374.43	174.38	278.41	336.83	211.87	288.16
Phosphorylcholine	461.25	355.09	282.56	227.79	484.08	126.12	227.49	258.85	276.29	290.05
Pipecolate	2.88	3.72	1.95	2.56	2.46	3.48	2.57	3.46	3.10	2.09
Pro	946.50	516.18	840.38	764.82	711.55	1032.44	522.31	589.24	647.94	579.61
Pterin	5.40	3.36	5.91	5.19	3.59	3.13	2.38	2.83	N.D.	1.74
Purine	2.32	1.06	0.99	1.94	1.95	0.78	0.90	1.12	1.35	2.03
Putrescine(1,4-Butanediamine)	3.75	1.84	1.09	2.76	1.96	21.14	27.57	6.65	21.05	11.97
Pyridoxal	1.73	1.30	1.92	1.85	2.30	0.97	1.65	1.60	1.53	1.57
Pyridoxamine	0.78	0.54	0.61	0.64	0.73	0.49	0.33	0.48	0.56	0.38
Pyridoxamine 5'-phosphate	28.73	28.16	24.16	28.04	27.16	31.82	23.30	26.24	31.85	26.62
Riboflavin	2.88	3.92	2.83	3.40	4.99	3.33	4.51	3.68	3.66	3.96
S-Lactoylglutathione	18.51	10.33	13.07	11.41	15.41	16.63	7.23	8.64	10.78	6.33
S-Methylmethionine	1.42	0.69	0.75	1.11	1.06	0.34	0.50	0.53	1.03	0.76
SAH	40.44	53.46	104.66	46.01	44.51	130.78	19.97	24.13	53.60	22.82
SAM+	61.95	55.90	58.28	101.78	63.44	105.14	73.11	78.85	78.98	67.52
Saccharopine	25.08	9.03	11.32	27.29	20.06	34.95	2.87	8.00	6.78	1.70
Sarcosine	70.53	66.55	108.78	167.90	57.04	146.86	90.08	131.33	151.25	76.66
SDMA	1.28	0.71	0.72	0.85	1.06	0.64	0.91	0.96	0.79	0.85
Ser	1159.63	627.46	864.08	768.30	992.26	530.50	954.22	877.69	977.73	962.46
Serotonin	3.16	4.29	2.41	3.92	3.64	4.08	3.84	3.37	3.49	2.99
Spermidine	15.00	15.83	15.94	18.99	17.75	33.20	22.61	18.12	26.93	24.19
Spermine	0.75	0.77	0.94	1.20	0.78	1.21	0.68	0.81	1.07	0.77
Taurine	4181.08	4413.32	2291.07	3177.03	1586.92	4673.67	5259.21	4388.27	5387.06	4224.19
Taurocyamine	82.37	102.13	50.69	83.78	63.22	84.45	51.22	109.52	57.86	84.30
Thiamine	8.22	2.89	16.69	5.10	10.98	1.27	1.52	2.10	2.90	1.98
Thiamine monophosphate	2.89	2.79	9.10	4.24	6.86	1.48	N.D.	N.D.	2.38	N.D.
Thr	757.58	584.41	594.80	716.03	742.25	470.50	494.47	650.94	658.60	608.20
Thymidine	22.21	17.20	15.49	16.79	16.73	19.98	19.07	15.34	16.97	14.67
Thymine	60.61	32.96	72.95	61.30	67.47	62.06	57.00	85.03	44.85	44.51
Trigonelline	1.50	1.18	1.48	1.84	0.99	1.48	N.D.	1.14	1.53	N.D.
Trimethylamine N-oxide	6.99	4.27	22.84	30.20	12.51	9.94	10.12	2.74	0.91	0.95
Trp	58.36	50.86	53.76	55.75	71.70	46.90	51.62	76.89	45.27	51.80
Tyr	478.81	311.53	380.03	388.25	464.54	291.03	358.09	422.31	328.54	392.09
Tyramine	0.34	0.36	0.25	0.42	0.36	0.29	0.54	0.65	0.38	0.29
Uracil	124.82	48.16	114.38	122.34	113.90	65.33	146.92	112.62	75.52	132.16
Urea	1702.24	5356.31	2980.95	8140.89	4188.28	4501.14	2631.33	5244.81	1226.98	1258.09
Uridine	531.05	295.89	519.42	819.24	709.33	366.07	656.56	768.15	372.41	659.72
Val	621.32	502.70	562.32	568.46	680.71	546.89	486.06	594.90	528.41	516.60
Xanthine	429.75	403.24	295.46	483.73	557.89	296.33	406.08	545.03	371.97	449.81
Xanthosine	54.02	90.38	33.18	39.42	44.33	46.38	55.55	135.09	79.51	62.01
MS_METABOLITE_DATA_END
#METABOLITES
METABOLITES_START
metabolite_name	KEGG ID	m/z
1-Methyladenosine	C02494	282.1197
1-Methylhistamine	C05127	126.1026
1-Methylnicotinamide	C02918	137.0715
2,4-Diaminobutyrate	C03283	119.0815
D-2-aminobutyrate	C02261	104.0706
3-Aminoisobutyrate	C03284	104.0706
3-Methylhistidine	C01152	170.0924
5-Aminoimidazole-4-carboxamide ribotide	C04677	339.0700
5-Aminolevulinate	C00431	132.0655
5-Hydroxyindoleacetate	C05635	192.0655
5-Methyltetrahydrofolate	C00440	460.1939
5-Methylthioadenosine	C00170	298.0968
7,8-Dihydrobiopterin	C02953	240.1091
Adenine	C00147	136.0618
Adenosine	C00212	268.1040
ADMA	C03626	203.149
Ala	C00041,C00133,C01401	90.0550
Ala-Ala	C00993	161.0921
Allantoin	C01551	159.0513
alpha-Aminoadipate	C00956	162.0761
alpha-Lipoamide	No ID	206.0668
Alpha-Methylserine	C02115	120.0655
Arg	C00062,C00792	175.1190
Asn	C00152,C01905,C16438	133.0608
Asp	C00049,C00402,C16433	134.0448
beta-Ala	C00099	90.0550
Betaine	C00719	118.0863
Betaine aldehyde (+H2O)	C00576	120.102
Cadaverine	C01672	103.1230
Carnitine	C00318,C00487,C15025	162.1130
Carnosine	C00386	114.0606
Choline	C00114	104.1075
Citrulline	C00327	176.1030
Creatine	C00300	132.0768
Creatinine	C00791	114.0662
Cyclohexylamine	C00571	100.1121
Cys	C00097,C00736,C00793	122.0270
Cystathionine	C00542,C02291	223.0747
Cysteine-glutathione disulphide -Divalent	C05526	214.0512
Cystine		241.0311
Cytidine	C00475	244.0928
Cytosine	C00380	112.0505
Dihydrouracil	C00429	115.0502
Ethanolamine phosphate	C00346	142.0264
GABA	C00334	104.0706
gamma-Butyrobetaine	C01181	146.1181
gamma-Glu-cys	C00669	251.0696
gamma-Guanidinobutyrate	C01035	146.0924
Gln	C00064,C00303,C00819	147.0764
Glu	C00025,C00217,C00302	148.0604
Glu-Glu	C01425	277.1030
Glutathione(ox)	C00127	307.0833
Glutathione(red)	C00051	308.0911
Gly	C00037	76.0393
Gly-Gly	C02037	133.0608
Gly-Leu	No ID	189.1234
Glycerophosphorylcholine	C00670	258.1107
Guanidinoacetate	C00581	118.0611
Guanidinosuccinate	C03139	176.0666
Guanine	C00242	152.0567
Guanosine	C00387	284.0989
His	C00135,C00768,C06419	156.0768
Histamine	C00388	112.0869
Homoserine	C00263	120.0655
Hydroxyproline	C01157	132.0655
Hypotaurine	C00519	110.0270
Hypoxanthine	C00262	137.0458
Ile	C00407,C06418,C16434	132.1019
Imidazole-4-acetate	C02835	127.0502
Inosine	C00294	269.0880
Isobutylamine	C02787	74.0964
Kynurenine	C00328,C01718	209.0921
Leu	C00123,C01570,C16439	132.1019
Lys	C00047,C00739,C16440	147.1128
Met	C00073,C00855,C01733	150.0583
Methionine sulfoxide	C02989	166.0532
N-Acetylglucosamine	C01132,C00645	222.0972
N-Acetylglucosylamine	C01239	221.1132
N-Acetylhistidine	C02997	198.0873
N-Acetylornithine	C00437	175.1077
N-Acetylputrescine	C02714	131.1179
N-Acetylvaline	No ID	160.0968
N-epsilon-Acetyllysine	C12989	189.1234
N-gamma-Ethylglutamine	No ID	175.1077
N-Methylalanine	C02721	104.0706
N,N-Dimethylglycine	C01026	104.0706
N6,N6,N6-Trimethyllysine	C03793	189.1598
N8-Acetylspermidine	C01029	188.1757
Nicotinamide	C00153	123.0553
o-Acetylcarnitine	C02571	204.1236
Ophthalmate	No ID	290.1347
Ornithine	C00077,C00515,C01602	133.0972
Phe	C00079,C02057,C02265	166.0863
Phosphorylcholine	C00588	184.0739
Pipecolate	C00408	130.0863
Pro	C00148,C00763,C16435	116.0706
Pterin	C00715	164.0567
Purine	C15587	121.0509
Putrescine(1,4-Butanediamine)	C00134	89.1073
Pyridoxal	C00250	168.0655
Pyridoxamine	C00534	169.0972
Pyridoxamine 5'-phosphate	C00647	249.0635
Riboflavin	C00255	377.1456
S-Lactoylglutathione	C03451	380.1122
S-Methylmethionine	C03172	164.0745
SAH	C00021	193.0681
SAM+	C00019	200.0762
Saccharopine	C00449	277.139
Sarcosine	C00213	90.0550
SDMA	No ID	203.150
Ser	C00065,C00716,C00740	106.0499
Serotonin	C00780	177.1022
Spermidine	C00315	146.1652
Spermine	C00750	102.1151
Taurine	C00245	126.0219
Taurocyamine	C01959	168.044
Thiamine	C00378	265.1123
Thiamine monophosphate	C01081	345.0786
Thr	C00188,C00820	120.0655
Thymidine	C00214	243.0975
Thymine	C00178	127.0502
Trigonelline	C01004	138.0550
Trimethylamine N-oxide	C01104	76.0757
Trp	C00078,C00525,C00806	205.0972
Tyr	C00082,C01536,C06420	182.0812
Tyramine	C00483	138.0913
Uracil	C00106	113.0346
Urea	C00086	61.0396
Uridine	C00299	245.0768
Val	C00183,C06417,C16436	118.0863
Xanthine	C00385	153.0407
Xanthosine	C01762	285.0830
METABOLITES_END
#END