#METABOLOMICS WORKBENCH agoldman_20250918_123454 DATATRACK_ID:6450 STUDY_ID:ST004228 ANALYSIS_ID:AN007037 PROJECT_ID:PR002668
VERSION             	1
CREATED_ON             	September 26, 2025, 4:27 pm
#PROJECT
PR:PROJECT_TITLE                 	Aromatic Microbial Metabolite Hippuric Acid Potentiates Pro-Inflammatory
PR:PROJECT_TITLE                 	Responses in Macrophages through TLR-MyD88 Signaling and Lipid Remodeling
PR:PROJECT_SUMMARY               	The gut microbiome generates a diverse array of metabolites that actively shape
PR:PROJECT_SUMMARY               	host immunity, yet the pro-inflammatory potential of microbial metabolites
PR:PROJECT_SUMMARY               	remains incompletely understood. Using a non-targeted, liquid
PR:PROJECT_SUMMARY               	chromatography-tandem mass spectrometry (LC-MS/MS)-based metabolomics, we
PR:PROJECT_SUMMARY               	identified hippuric acid, an aromatic gut microbe-derived metabolite, as a
PR:PROJECT_SUMMARY               	potent enhancer of pro-inflammatory responses in Escherichia coli infection
PR:PROJECT_SUMMARY               	model. Intraperitoneal administration of hippuric acid significantly heightened
PR:PROJECT_SUMMARY               	pro-inflammatory responses, promoted innate immune cell activation, and reduced
PR:PROJECT_SUMMARY               	survival in infected mice. Similar pro-inflammatory effects were observed in an
PR:PROJECT_SUMMARY               	LPS-induced inflammation model. In vitro, hippuric acid selectively potentiated
PR:PROJECT_SUMMARY               	M1-like macrophage polarization (LPS + IFNγ) but had no effect on M2-like
PR:PROJECT_SUMMARY               	polarization (IL-4). Hippuric acid further augmented responses to multiple
PR:PROJECT_SUMMARY               	myeloid differentiation primary response 88 (MyD88)-dependent toll-like receptor
PR:PROJECT_SUMMARY               	(TLR) ligands, but not to TRIF-dependent TLR3, or to cytosolic innate immune
PR:PROJECT_SUMMARY               	stimuli such as STING and NOD2 agonists, implicating TLR-MyD88 signaling as a
PR:PROJECT_SUMMARY               	likely mechanism of action. Genetic deletion of MyD88 abrogated the
PR:PROJECT_SUMMARY               	pro-inflammatory effects of hippuric acid both in vitro and in vivo, confirming
PR:PROJECT_SUMMARY               	its dependence on the MyD88 pathway. Transcriptomic and lipidomic analyses
PR:PROJECT_SUMMARY               	revealed that hippuric acid upregulated cholesterol biosynthesis and induced
PR:PROJECT_SUMMARY               	lipid accumulation. Pharmacological reduction of cellular cholesterol using
PR:PROJECT_SUMMARY               	fluvastatin or 25-hydroxycholesterol attenuated its pro-inflammatory effects.
PR:PROJECT_SUMMARY               	Notably, hippuric acid also enhanced pro-inflammatory responses in human
PR:PROJECT_SUMMARY               	macrophages, and its elevated levels correlated with increased sepsis mortality,
PR:PROJECT_SUMMARY               	underscoring its clinical relevance. Together, these findings identify hippuric
PR:PROJECT_SUMMARY               	acid as a previously unrecognized microbial-derived pro-inflammatory modulator
PR:PROJECT_SUMMARY               	that links gut microbial metabolism, lipid remodeling, and innate immune
PR:PROJECT_SUMMARY               	signaling, and offer new insights into its role in infection and inflammation.
PR:INSTITUTE                     	The Wistar Institute
PR:LAST_NAME                     	Shinde
PR:FIRST_NAME                    	Rahul
PR:ADDRESS                       	3601 Spruce Street, Philadelphia, PA, 19104, USA
PR:EMAIL                         	rshinde@wistar.org
PR:PHONE                         	215-898-3717
#STUDY
ST:STUDY_TITLE                   	Aromatic Microbial Metabolite Hippuric Acid Potentiates Pro-Inflammatory
ST:STUDY_TITLE                   	Responses in Macrophages through TLR-MyD88 Signaling and Lipid Remodeling -
ST:STUDY_TITLE                   	Non-targeted metabolomics of C57BL/6 mice infected with Escherichia coli
ST:STUDY_SUMMARY                 	Authors have investigated changes in microbial metabolites during bacterial
ST:STUDY_SUMMARY                 	infection. In this study, C57BL/6 mice were infected intraperitoneally with
ST:STUDY_SUMMARY                 	Escherichia coli (2 × 10⁷ CFU), and non-targeted metabolomics using liquid
ST:STUDY_SUMMARY                 	chromatography-tandem mass spectrometry (LC-MS/MS) was performed on sera
ST:STUDY_SUMMARY                 	collected 48 hours post-infection. The metabolomics screen revealed significant
ST:STUDY_SUMMARY                 	shifts in metabolic profiles, including altered levels of 2/3-hydroxybutyrate (a
ST:STUDY_SUMMARY                 	marker of fatty acid metabolism), hypoxanthine (a marker of purine metabolism),
ST:STUDY_SUMMARY                 	and N-acetylglutamine (involved in nitrogen metabolism), indicating broad
ST:STUDY_SUMMARY                 	metabolic reprogramming during infection. Among the most significantly altered
ST:STUDY_SUMMARY                 	metabolites, hippuric acid—an aromatic compound produced by microbial
ST:STUDY_SUMMARY                 	metabolism of dietary polyphenols and amino acids was markedly depleted, showing
ST:STUDY_SUMMARY                 	a 24-fold reduction in infected mice compared to uninfected controls (p <
ST:STUDY_SUMMARY                 	0.001). These findings establish an association between bacterial infection and
ST:STUDY_SUMMARY                 	the depletion of hippuric acid, indicating its role in modulating immune
ST:STUDY_SUMMARY                 	responses during infection.
ST:INSTITUTE                     	The Wistar Institute
ST:LAST_NAME                     	Shinde
ST:FIRST_NAME                    	Rahul
ST:ADDRESS                       	3601 Spruce Street, Philadelphia, PA, 19104, USA
ST:EMAIL                         	rshinde@wistar.org
ST:PHONE                         	215-898-3717
#SUBJECT
SU:SUBJECT_TYPE                  	Mammal
SU:SUBJECT_SPECIES               	Mus musculus
SU:TAXONOMY_ID                   	10090
#SUBJECT_SAMPLE_FACTORS:         	SUBJECT(optional)[tab]SAMPLE[tab]FACTORS(NAME:VALUE pairs separated by |)[tab]Raw file names and additional sample data
SUBJECT_SAMPLE_FACTORS           	-	QC-6	Treatment:n/a | Sample source:Serum	RAW_FILE_NAME(raw_data)=m23-L034-QC-FullMS-6.raw
SUBJECT_SAMPLE_FACTORS           	-	QC-7	Treatment:n/a | Sample source:Serum	RAW_FILE_NAME(raw_data)=m23-L034-QC-FullMS-7.raw
SUBJECT_SAMPLE_FACTORS           	-	QC-8	Treatment:n/a | Sample source:Serum	RAW_FILE_NAME(raw_data)=m23-L034-QC-FullMS-8.raw
SUBJECT_SAMPLE_FACTORS           	-	QC-9	Treatment:n/a | Sample source:Serum	RAW_FILE_NAME(raw_data)=m23-L034-QC-FullMS-9.raw
SUBJECT_SAMPLE_FACTORS           	-	C1	Treatment:Control | Sample source:Serum	RAW_FILE_NAME(raw_data)=m23-L034-C1.raw
SUBJECT_SAMPLE_FACTORS           	-	C2	Treatment:Control | Sample source:Serum	RAW_FILE_NAME(raw_data)=m23-L034-C2.raw
SUBJECT_SAMPLE_FACTORS           	-	C3	Treatment:Control | Sample source:Serum	RAW_FILE_NAME(raw_data)=m23-L034-C3.raw
SUBJECT_SAMPLE_FACTORS           	-	C4	Treatment:Control | Sample source:Serum	RAW_FILE_NAME(raw_data)=m23-L034-C4.raw
SUBJECT_SAMPLE_FACTORS           	-	C5	Treatment:Control | Sample source:Serum	RAW_FILE_NAME(raw_data)=m23-L034-C5.raw
SUBJECT_SAMPLE_FACTORS           	-	E1	Treatment:E. coli | Sample source:Serum	RAW_FILE_NAME(raw_data)=m23-L034-E1.raw
SUBJECT_SAMPLE_FACTORS           	-	E2	Treatment:E. coli | Sample source:Serum	RAW_FILE_NAME(raw_data)=m23-L034-E2.raw
SUBJECT_SAMPLE_FACTORS           	-	E3	Treatment:E. coli | Sample source:Serum	RAW_FILE_NAME(raw_data)=m23-L034-E3.raw
SUBJECT_SAMPLE_FACTORS           	-	E4	Treatment:E. coli | Sample source:Serum	RAW_FILE_NAME(raw_data)=m23-L034-E4.raw
SUBJECT_SAMPLE_FACTORS           	-	E5	Treatment:E. coli | Sample source:Serum	RAW_FILE_NAME(raw_data)=m23-L034-E5.raw
#COLLECTION
CO:COLLECTION_SUMMARY            	Serum samples were collected 48 hours post-infection
CO:SAMPLE_TYPE                   	Blood (serum)
#TREATMENT
TR:TREATMENT_SUMMARY             	Escherichia coli peritoneal infection was performed as previously described.
TR:TREATMENT_SUMMARY             	Briefly, E. coli (ATCC 25922) was cultured in LB medium with 100 µg/mL
TR:TREATMENT_SUMMARY             	ampicillin overnight at 37 °C with gentle shaking to an optical density at
TR:TREATMENT_SUMMARY             	wavelength 600 nm of 0.5−0.6 to achieve a logarithmic growth phase. C57BL/6J
TR:TREATMENT_SUMMARY             	or MyD88 KO mice of 8–12 weeks of age received an intraperitoneal (i.p.)
TR:TREATMENT_SUMMARY             	injection of 100 μl PBS with 2 × 10^7 E. coli.
#SAMPLEPREP
SP:SAMPLEPREP_SUMMARY            	Polar metabolites were extracted from serum samples with 10-times the volume of
SP:SAMPLEPREP_SUMMARY            	ice-cold 80% methanol spiked with 1 μM HA-13C6 as an internal standard for HA
SP:SAMPLEPREP_SUMMARY            	in isotope dilution MS.
#CHROMATOGRAPHY
CH:CHROMATOGRAPHY_TYPE           	HILIC
CH:INSTRUMENT_NAME               	Thermo Vanquish
CH:COLUMN_NAME                   	SeQuant ZIC- pHILIC (150 x 2.1mm,5um)
CH:SOLVENT_A                     	100% water; 20 mM ammonium carbonate; 5 µM medronic acid; 0.1% ammonium
CH:SOLVENT_A                     	hydroxide; pH 9.2
CH:SOLVENT_B                     	100% Acetonitrile
CH:FLOW_GRADIENT                 	85% B for 2 min, 85% B to 20% B over 15 min, 20% B to 85% B over 0.1 min,
CH:FLOW_GRADIENT                 	and 85% B for 8.9 min
CH:FLOW_RATE                     	0.2 ml/min
CH:COLUMN_TEMPERATURE            	45
#ANALYSIS
AN:ANALYSIS_TYPE                 	MS
#MS
MS:INSTRUMENT_NAME               	Thermo Q Exactive HF-X Orbitrap
MS:INSTRUMENT_TYPE               	Orbitrap
MS:MS_TYPE                       	ESI
MS:ION_MODE                      	POSITIVE
MS:MS_COMMENTS                   	All samples were analyzed by full MS with polarity switching. A quality control
MS:MS_COMMENTS                   	(QC) sample pool was also analyzed by data-dependent MS/MS with separate runs
MS:MS_COMMENTS                   	for positive and negative ion modes. Full MS scans were acquired at 120,000
MS:MS_COMMENTS                   	resolution with a scan range of 50-750 m/z for positive ion mode and 65-975 m/z
MS:MS_COMMENTS                   	for negative ion mode. Data-dependent MS/MS scans were acquired for the top 10
MS:MS_COMMENTS                   	highest intensity ions at 15,000 resolution with 1.0 m/z isolation width and
MS:MS_COMMENTS                   	stepped normalized collision energy (NCE) of 20/40/60. Global metabolite
MS:MS_COMMENTS                   	profiling was performed using Compound Discoverer 3.3 SP1 (Thermo Fisher
MS:MS_COMMENTS                   	Scientific). Periodic technical injections of the QC pool were used to correct
MS:MS_COMMENTS                   	metabolite quantifications over the course of a batch analysis. Serum data were
MS:MS_COMMENTS                   	normalized per volume serum injected, which was equivalent for all samples.
#MS_METABOLITE_DATA
MS_METABOLITE_DATA:UNITS	Peak Area
MS_METABOLITE_DATA_START
Samples	QC-6	QC-7	QC-8	QC-9	C1	C2	C3	C4	C5	E1	E2	E3	E4	E5
Factors	Treatment:n/a | Sample source:Serum	Treatment:n/a | Sample source:Serum	Treatment:n/a | Sample source:Serum	Treatment:n/a | Sample source:Serum	Treatment:Control | Sample source:Serum	Treatment:Control | Sample source:Serum	Treatment:Control | Sample source:Serum	Treatment:Control | Sample source:Serum	Treatment:Control | Sample source:Serum	Treatment:E. coli | Sample source:Serum	Treatment:E. coli | Sample source:Serum	Treatment:E. coli | Sample source:Serum	Treatment:E. coli | Sample source:Serum	Treatment:E. coli | Sample source:Serum
(9cis)-Retinal	34620230.1	37010476.34	31742155.14	32583470.82	43804242.78	33974195.28	37025358.65	40723769.3	49849305.15	73890815.61	89420017.61	55782893.11	25014000.2	32755940.4
gamma-L-Glutamyl-L-glutamic acid	20454333.22	19764932.77	19363931.93	20100813.52	18890145.11	12921795.76	14913903.43	15676738.07	20588611.88	26648570.55	19342213.01	7509820.503	26644397.62	13527942
15-Deoxy-delta12,14-prostaglandin A1	14163832.31	14453184.92	14813485.02	13971517.72	16653064.45	16900942.31	18624936.91	17602633.41	18215385.59	13449029.21	13286098.45	13630907.66	10290858.21	11893437.58
1-Methylhistidine	442740556.5	442266028.6	443980217.3	438349257.5	235255934.1	356860853.3	207424729.6	383956794.7	216089571.8	696780779.7	480958110.6	671604652	247998190.6	166680176.7
1-Methylnicotinamide	94566600.56	94245554.98	92830405.09	94615454.91	80830733.55	62394381.79	59360509.97	55514560.52	102336971.6	220626611.5	411782438.4	104279495.5	71873637.3	53725007.98
2-hydroxy-6-[(8Z,11Z)-pentadeca-8,11,14-trien-1-yl]benzoic acid	3540505.761	3730527.536	3521659.698	3793074.657	4861979.144	4803906.629	4478163.252	4578801.867	4854307.268	7748354.117	7227793.721	4356369.155	2760123.31	5517190.192
2-Oxindole	333354026.9	336865792.4	333959313.1	333732109.7	958775207.5	318763199.8	839063234.8	569042839.2	620880105	136604453.3	66696856.67	134703468.1	74478508.61	109340743.5
3-Hydroxyanthranilic acid	52069833.86	52659497.79	48800919.9	48398048.09	56728541.06	29348104.38	19599151.89	46035169.93	40381579.73	278570746.2	170077756.8	227204524.4	18913772.13	10935225.99
4-Hydroxyproline	809539866.8	803271976.1	778266983.1	801745928.2	850967254.4	828778207.9	1108788254	775791431	545297890.7	46130467.34	28977522.6	49869463.89	274822171.4	193900257
5-Aminolevulinic acid	16046250.31	15277249.32	15304510.64	15258754.98	18530143.86	15837333.25	16450642.54	13783372.79	10153019.76	9319270.811	6672734.565	8249164.456	13094555.01	9643235.601
5-Methylcytosine	35482164.95	35654200.82	35845356.81	34608723.74	40275792.99	57910815.21	36642892.88	40174333.63	45448426.92	8721594.317	7854273.915	38706659.34	24473172.37	34357795.34
7-Methylguanine	68258207	67433214.97	67711126.41	67906847.9	58002614.04	61954345.6	53582463.14	63933267.96	66112891.44	86005637.97	110553555	140109783.9	59710662.67	58188268.77
Adenine	20922584.69	20310521.29	20581413.56	20637648.99	24418047.36	30368403.95	16607108.43	12352819.23	45651575	3281411.806	7032965.493	9574663.259	55227861.11	16774035.78
Adenosine	95309036.13	96553204.65	95322048.52	93163630.38	123231369.8	189244079.6	85879246.88	61675274.96	305906720.1	7135508.686	17041219.67	47149580.01	110778047.2	31102217.02
Aminoadipic acid	514943347.4	516319102	515608364.6	514651777	207909812.9	148102634.8	218197229.2	248818881.8	234830696.2	1330714449	1032592356	851354077.7	1143521899	746182646.3
Argininosuccinic acid	9474673.406	9054583.062	9032431.615	9004535.503	9205679.997	5703608.454	9273577.641	9250826.38	11583036.05	9095224.495	4016341.384	5752782.904	18091142.03	18955722.18
Betaine	26479671271	26574489347	26410153517	26188460146	28184500858	35373214238	28210840922	26388405402	22762412452	24757529237	45120450327	34038579636	24569571072	12754679687
Carnosine	63576507.78	62378505.72	63357492.77	63719863.97	71578708.27	55420872.72	79265519.75	54299764.75	35783027.25	138549841.3	90173313.88	264309815.5	27067518.59	33894438.48
Choline	6159304848	6064853975	6070144610	6113837725	7021312715	5998737233	6949554114	6306718788	6805583983	5109579650	4574588890	3386704452	7767043002	7783370922
Citrulline	3436226950	3391351433	3351100054	3346545396	4489702799	4032365946	3677125137	3696382497	3965129734	2952741402	2203003956	1603172786	1882184914	1689766995
Creatine	37476435543	37687123528	37518130495	37640311583	28009708428	31718463288	25344975732	28570463406	23794638424	56364021030	55452147397	69856485312	42143765820	33817262218
Creatinine	4996807674	5017281932	4979495080	4984787771	4203478561	5985353286	5871553857	4928448357	5111640008	4880914372	4476517290	6131691600	3499306797	4475422928
Cytidine	213327776.7	208809726.9	208464385.7	207202306.9	239356189.8	220527289.6	251289584.4	261843714.5	247081889.3	58228174.09	14644723.5	94912783.07	369270156.4	297165458
Cytosine	365676543	365138966	361536851.5	358053001.9	426566839.5	545561955.4	382043781.1	425476936.3	487963428.1	18235262.49	21783906.39	283488322.9	293083633.7	503900223.6
D-Erythro-sphingosine 1-phosphate	52365486.93	53655643.93	52738162	52416414.27	64697450.33	67971638.17	57757499.54	54395389.23	46034649.14	26924682.82	7362399.843	22106738.86	69066634.03	82388118.89
Diaminopimelic acid	8871947.53	8588921.82	8681426.89	8799273.986	9309393.643	20034153.53	16536002.6	16361831.99	17373837.89	1923947.24	2519083.464	3981599.49	1218399.091	1066164.523
DL-Stachydrine	231336520.5	228973044.2	230340720.6	246060746.9	322388049.4	369199006.9	678514229.8	420471259.6	312346633.7	151126811.9	116287078.8	130930617.5	23085621.75	58140063.7
Glucosamine	50576589.99	46984717.11	50532025.79	50581908.41	56057649.05	56957782.92	49249161.75	69342181.68	69911605.58	11507927.81	4677309.593	14851942.22	30791005.09	58530891.59
Glucose 1-phosphate	1856392.858	1915441.303	1883208.473	1894509.323	1944950.582	1470169.257	1571725.826	1319718.116	1452305.494	6464914.889	5668983.047	4326400.3	2108693.633	1041739.982
Glycine	222100602	223148528	222278410.2	220345417.1	220203615.3	243132009.2	240914007.1	213944836	198454651.8	180034655.1	192800880.7	130883418.6	181185009.6	139436243.1
Guanidineacetic acid	377449825.6	375264291.8	373689079.7	370835891.8	258777199.7	608666836.6	295484245.2	241323147.9	287490771.4	276382899.6	224096098.2	219254462.9	464592974.6	197686210.7
Guanine	2780781.704	2236109.079	2855828.231	2847601.547	949177.1062	1813130.084	935436.8352	956572.1386	3277082.64	454769.8082	507301.8895	600080.5855	24154425.95	7342357.968
Hexanoylcarnitine	67108645.48	67842878.4	67766908.97	66655674.41	87496065.12	70215654.14	81150537.1	72715150.09	100461619.2	16716112.47	14935047.65	21754042.11	72451394.94	118726531.9
Hypoglycin A	43172120.17	43718813.42	42782595.77	43082451.82	39572186.7	47430199.46	47586218.38	77666374.67	52128607.58	46015232.31	27918511.2	42819768.14	22368427.81	4959041.315
Hypotaurine	73713977.16	71149884.53	71056691.47	72097595.8	85774413.79	195759705.8	76021423.29	102560819.8	86067236.96	17413046.66	20509569.07	16095570	78761655.87	26350834.47
Hypoxanthine	286262738.5	293699737.1	287151500.3	271940459.6	857891798.4	7540048.988	299411515.5	1556928306	902775833.6	1249354.792	11369862.18	7156417.825	10247415.72	1176835.75
Indole-3-lactic acid	31761028.93	31857387.36	31776650.14	32627113.36	23447140.18	38993429.85	31334990.45	30232743.64	27948219.89	35136416.21	41081768.96	44795856.45	16257279.87	40072308.38
Indoleacrylic acid	7188636.693	7181113.636	7306223.785	7245819.835	9007614.976	18433416.59	9142825.498	16991608.88	18445834.63	1079948.771	2748059.832	3611368.076	7957805.173	4940904.098
L-Acetylcarnitine	13051825616	13021548597	12910224345	12801459443	19875868379	15989798127	17354018872	16720681935	19618748163	8683046122	4730290806	7910791991	13344498084	21227764219
L-Alanine	1826589923	1835929102	1817149463	1818965381	1597423124	1806181879	1659183212	1904600897	1727677099	1002104724	1007042292	1122827206	1520092812	1330152005
L-Arginine	2603943945	2553382957	2566539182	2590975795	3724347431	2959709816	3336949647	2648315006	3072118380	1249087987	287297163.7	988506509.2	3703745344	3301743422
L-Asparagine	324438299.5	314937117.8	314166637	292597793.8	428464968.8	627749672.9	295597394.8	306070251.8	219672960	57445545.25	418093.5778	107099993.2	312112880.1	171699514.6
L-Carnitine	11721690183	11758338403	11793704662	11727196000	17511314145	14572536056	17535470381	15186287927	13964464242	4446271930	6845435203	3505254385	8013436818	10672346656
L-Cystine	166993650.1	165301945.9	159346634	162959413.1	196614112.8	81826045.46	125970615.3	121133067.6	159630822.9	176366855.3	44588251.32	151424581.3	78217469.86	75524141.39
L-Ergothioneine	754422556.6	737368272.3	737977650.2	739863309.5	352663795.3	451197915.4	290051048.3	491890881.3	487533800.2	307913872.8	2177441968	410622074.4	493437707.3	575273639.3
Leucylproline	143657891.4	147924804.8	145573546.6	146305309.1	141834434.6	128162346.8	137095671.1	138161712.4	105742834.1	247700788.8	314656915.5	290309811.9	219944625.8	165515904.8
L-Glutamic acid	419536612.9	423847447.4	425482772.6	433957852.6	398468956.9	389362170.2	487161406.3	462731924.6	424324649.4	412813079.7	536638343.7	301865563.9	570209475	315288671.8
L-Glutamine	20554767861	20244322349	20373276021	20503317311	20059301290	21597507719	19298669574	20178666310	19692202552	24164007537	12163223494	15801048245	21022946193	20358423118
L-Isoleucine	4199836843	4317915111	4092493949	4273343171	4888649752	3930012255	4285501242	4972774437	5498196916	5752572786	3149362758	2949599902	3325498135	3342208567
L-Kynurenine	108739824.8	106953755.6	107627254.6	108493505.7	76642423.31	98057468.23	74543191.53	119827811.8	61920685.5	98274818.54	69171333.49	54370606.22	65728625.53	201228660.9
L-Leucine	4833960210	4673405944	4827212678	4708731431	4201844332	3215133835	4663091446	4951482701	4980253492	7278282116	4053189190	3885521574	3750120481	4110219187
L-Lysine	825290652.3	818355577.3	819098656.4	831548223.6	1499907696	739872210.4	1069234700	813171109	978551335.1	939108569.7	585650186.1	482648168	894455540.9	714117797.6
L-Methionine	3232047955	3194648129	3202403799	3212947931	4187243679	3969434857	4782989221	3328636640	3285434768	1209676070	203673968	838032955.2	2729626138	2291608285
L-Phenylalanine	5031582830	5041227242	5011259985	4925931217	4776586647	5971848457	4789665597	4807011121	5022018440	3656323107	3925574933	3312321894	7122499994	6405140049
L-Proline	9757841766	9745829815	9719892279	9563039886	8754197903	11796332507	8687058746	8759647147	7600247766	7561187929	6110510604	6242005026	8085475966	5379923608
L-Saccharopine	2653904.173	2639516.224	2637239.991	2853107.79	1241834.519	875299.7724	1028859.495	790913.9726	738463.486	9158724.95	10138784.14	5763858.21	1831114.082	1492488.517
L-Serine	552011089	541658957.4	542252501.9	549347235.8	717559092.6	685308966.2	708277724	573796297.1	526850706.8	57560629.03	9772473.912	286666713.1	495811432.1	347458531.6
L-Threonine	3148356666	3117458477	3163264930	3148594601	3567821084	3120857823	3072092912	3320918534	2984449055	2262582716	182134253.3	1437022455	2629496431	2283777422
L-Tryptophan	2528377866	2499146152	2511686865	2491249057	3491607687	3473234787	3248995119	3701566303	3544670866	690061066.5	552556077.6	458755325.9	1883982497	2497391595
L-Tyrosine	2008646591	2006701966	1983848113	1941878723	2267875558	3084771233	1847115540	2244713634	2207056008	943131589.9	1006525859	737307728	1706641734	1303071862
L-Valine	3866628023	3737471188	3970343862	3901532285	4345241524	3264220478	3667631453	4132526399	4280708312	4759686762	3918426374	3765040201	3173459269	2796659058
Methionine sulfoxide	205080997.8	203075867.7	205294472.9	202027445.4	142850933.1	204039622	337963529.7	160135560.4	159731642.7	94792758.97	21841501.06	50303882.97	137868964.6	97475205.64
Methylimidazoleacetic acid	208333805.7	211101939.3	209552465.5	209686884.4	69870131.24	82967656.48	89418698.2	70801333.46	88691664.68	539482604.5	696154612.9	778197595.8	151539266	122196404
N-alpha-L-Acetyl-arginine	13463481.78	13668896.07	13463914.23	13874654.96	13108837.06	19316542.71	15939541.7	12386917.36	13902154.23	8127891.997	23544914.86	17759538.03	4906346.152	6101457.698
N4-Acetylcytidine	6810922.627	6522168.763	6771451.386	6469598.899	5280090.246	7280704.421	5631247.682	10754068.2	5853918.558	332785.2903	308719.3993	4942476.118	6668065.09	7195432.939
N6,N6,N6-Trimethyl-L-lysine	378091946.9	382363317.2	370853504.1	370200840.5	219013545.8	143963397.8	192556405.7	188027419.2	221156743.8	633011510.8	1816207121	259701405.9	199499267.9	290891076
N6-Acetyl-L-lysine	152499046.2	151745746.9	151328203.3	152139993.9	124741429.5	163962314.4	110061646.9	155303053	139564723.2	178138880.5	134589981.8	151272978.3	107481959.7	93579709.15
N-Acetylglutamine	613953787.3	669083044.2	666202744.4	670325543.3	68637260.8	77685786.1	86671794.35	119142142.8	118603864.5	1690968264	1595557677	2028840779	192486252.4	245993890
N-Acetyl-L-alanine	49213239.59	48534661.48	47920218.92	50044333.72	40500642.49	34644045.47	46014641.36	46136766.97	44052650.39	45665991.96	52569768.97	52768963.74	46890305.78	47930346.49
N-Acetyl-L-aspartic acid	26809263.38	26522758.79	28698553.38	26983252.04	25872411.48	19139375.82	26164102.11	25665966.08	28072668.39	7647837.813	46477958.52	9203441.762	37291880.22	18137588.17
N-Acetyl-L-tyrosine	48246829.09	48434272.55	48223225.57	47848258.48	21239811.8	73650929.81	25008042.64	30415660.02	31250301.2	69826531.59	122747787.1	191648496.9	18022793.01	11121395.05
N-Acetylornithine	534992881.8	529344902.8	529928294.5	527789772.3	650563246.5	657033593.7	875478480.1	711858950.5	947432213.6	182005597.6	223275338.5	298599850.1	316836412.3	412542108.1
N-Acetylputrescine	23912369.55	23410887.28	23527794.44	23531245.62	924070.3346	1929258.707	2397684.269	2857514.669	2646638.555	26736729.61	284049480.8	9198025.124	2617883.818	3280458.269
Nicotinamide	738492998.7	760205579.2	744420189.9	688012033	689001776.6	629686084.6	645125962.3	734276706.6	776284752.6	1195904920	994419681.9	601818540.1	861456035.9	714045429.6
Nicotinamide 1-oxide	115060282.9	114022687.6	113958617	113099147.4	305243385.4	77154420.2	100657711	174217779.2	193632523.1	284481131.5	70193723.39	58505340.82	25042002.13	21099352.96
Nicotinic acid	29141936.76	29867856.87	30664800.45	29037388.93	594299.7514	497149.6994	361111.2215	1607704.144	275195.4223	33304095.65	345788074.1	20968699.28	875742.8966	413064.6695
Ornithine	213690391.1	208831311.4	208426416.5	211162172.2	273071456.2	258000895.1	211571913	146018206.8	195408658.7	401876090.2	118339370.1	172486669.1	227301515.3	297652017.6
Palmitoyl sphingomyelin	35090957.6	38136108.52	35391710.45	35753342.84	7897403.437	53723381.7	4354698.932	19187073.63	7373112.227	37628380.98	58325088.36	114420161.5	46044071.91	5870722.862
Palmitoylcarnitine	67156706.32	66218845.22	66665407.4	66492501.89	35396980.37	49552137.67	28999219.39	37548800.59	42382530.6	167161284.5	144307643.3	150457733.4	140369691.3	115595970.8
Pantothenic acid	1267737237	1264044796	1263804995	1255853949	1074125113	1376849870	1190934470	1308870766	1053839614	1108648893	1479868198	1145581583	2308317170	2604241058
Phosphoenolpyruvic acid	4839916.759	4677224.796	4903504.11	5087490.235	3160415.387	1449462.025	2239784.232	2306682.553	1864004.655	14052242.33	18876595.58	5437633.777	2580712.164	2437905.04
Pipecolic acid	280197268.5	276942966.1	280778181.4	279710271.9	471938989.1	306214965.9	411323297.3	409405627.1	421129344.3	414061663.4	230741299.1	294607624.3	128796492.9	173716817.3
PLK	15783524.59	15733118.51	15252950.94	15767497.35	3733023.138	1820351.424	3248879.971	2829695.139	2829448.243	40516329.34	82525072.56	70192301.95	4954422.636	4032372.24
Propionylcarnitine	520709952.9	537608425.9	536625959.4	541834518.5	546517773.6	470098873.7	805421522.8	651638585.1	525903569	82933749.08	191514305.3	67168943.13	424964580.3	1154244394
S-Adenosylhomocysteine	4947903.582	4768345.108	5037967.822	4827948.483	3601597.554	3355556.895	3179618.603	5230224.074	4408276.236	1814075.384	702795.5668	1534594.908	12835116.97	8844538.668
S-Adenosylmethionine	5316869.474	5098563.066	5212602.462	5372601.026	6849292.815	5528682.267	6006767.545	7098546.115	7170520.103	419959.073	1069469.834	518075.1012	4831835.212	5910543.445
Sarcosine	43372035.85	43401420.73	43438673.22	41848781.23	32190051.21	31452199.53	43674935.44	49871268.09	36985476.18	17174864.77	28476044.37	14519877.17	23124448.41	15067169.46
Symmetric dimethylarginine	251683357.9	246023692.4	244395936.3	245738010.2	311293966.9	236554418.8	252815459.1	266860565.4	297855820.2	262632972.7	198904159.1	106125694.6	196204871	213567075
Taurocholic acid	31304767.44	30804636.42	30616666.39	30792841.79	2535753.408	290358094	3819011.796	2766258.738	2517921.002	2165586.171	10177611.61	1969509.424	140148531.8	2103117.287
Thiamine	19608582.98	18897151.17	18981298.73	19078310.48	32459446.93	13998835.98	27313528.24	33431680.59	25528534.76	5141190.283	8235772.083	1725492.277	5172179.685	12914729.73
Thymidine	7115264.842	6820614.911	6570818.321	7413246.647	11124953.08	17414831.01	8477985.997	7690647.701	10370502.69	390215.2182	372949.1202	9768107.68	10736943.2	12243371.98
Trigonelline	679164485.8	679022682.1	678013850.2	673697844	622407437	1091023971	1271833053	927978202.2	859500466.2	551168666.3	485448854.4	490231510.7	173654742.5	235566413.8
Trimethylamine N-oxide	772092846.5	775885018.7	774149325	766777169.2	581489208.1	659400613.8	1794857358	707995552.5	556105528.3	141315857.2	19105800.39	239862116.9	241984110.5	1412329462
Uracil	53782903.73	53938857.16	54316395.66	55516016.39	58443242.94	69713525.91	46372121.55	52083745.95	51442282.95	29625509.18	7059456.501	36986258.47	86908873.96	81913800.27
Urea	11476057017	11502034415	11510963475	11330462059	11006321076	11986785203	10375497938	12176542039	11252018842	16738890974	11119311557	16246964002	4793131838	8760348314
MS_METABOLITE_DATA_END
#METABOLITES
METABOLITES_START
metabolite_name	m/z	RT [min]
(9cis)-Retinal	285.22188	1.309
gamma-L-Glutamyl-L-glutamic acid	277.10364	10.727
15-Deoxy-delta12,14-prostaglandin A1	319.22743	1.327
1-Methylhistidine	170.09289	7.648
1-Methylnicotinamide	137.07133	13.134
2-hydroxy-6-[(8Z,11Z)-pentadeca-8,11,14-trien-1-yl]benzoic acid	343.22592	1.319
2-Oxindole	134.06039	2.817
3-Hydroxyanthranilic acid	154.05021	2.812
4-Hydroxyproline	132.06674	8.731
5-Aminolevulinic acid	132.0659	8.219
5-Methylcytosine	126.06656	4.407
7-Methylguanine	166.07283	4.636
Adenine	136.06223	4.053
Adenosine	268.1046	4.001
Aminoadipic acid	162.07649	9.381
Argininosuccinic acid	291.13043	10.524
Betaine	118.08652	6.037
Carnosine	227.11436	9.452
Choline	104.10722	11.403
Citrulline	176.10339	9.625
Creatine	132.077	8.846
Creatinine	114.0665	4.281
Cytidine	244.09334	6.92
Cytosine	112.05087	5.716
D-Erythro-sphingosine 1-phosphate	380.25671	2.972
Diaminopimelic acid	191.10309	8.922
DL-Stachydrine	144.1023	5.353
Glucosamine	180.08716	8.164
Glucose 1-phosphate	261.03754	10.387
Glycine	76.03954	9.465
Guanidineacetic acid	118.06143	9.54
Guanine	152.05716	7.116
Hexanoylcarnitine	260.18619	2.93
Hypoglycin A	142.08669	3.057
Hypotaurine	110.02737	8.92
Hypoxanthine	137.04618	5.143
Indole-3-lactic acid	206.0817	2.994
Indoleacrylic acid	188.07112	2.792
L-Acetylcarnitine	204.12354	6.086
L-Alanine	90.05524	8.825
L-Arginine	175.11941	14.032
L-Asparagine	133.06113	9.296
L-Carnitine	162.1128	7.766
L-Cystine	241.03168	9.881
L-Ergothioneine	230.0963	8.751
Leucylproline	229.1552	4.84
L-Glutamic acid	148.06072	9.212
L-Glutamine	147.07672	9.107
L-Isoleucine	132.10226	6.427
L-Kynurenine	209.09263	6.467
L-Leucine	132.10226	6.127
L-Lysine	147.11317	13.568
L-Methionine	150.05873	6.705
L-Phenylalanine	166.08668	5.424
L-Proline	116.07088	7.434
L-Saccharopine	277.13998	9.806
L-Serine	106.05019	9.469
L-Threonine	120.06586	8.547
L-Tryptophan	205.09767	7.053
L-Tyrosine	182.08166	7.88
L-Valine	118.08652	7.281
Methionine sulfoxide	166.0537	7.956
Methylimidazoleacetic acid	141.06622	4.281
N-alpha-L-Acetyl-arginine	217.13007	8.957
N4-Acetylcytidine	286.10392	3.473
N6,N6,N6-Trimethyl-L-lysine	189.16021	12.322
N6-Acetyl-L-lysine	189.12381	7.706
N-Acetylglutamine	189.08742	5.94
N-Acetyl-L-alanine	132.06592	3.213
N-Acetyl-L-aspartic acid	176.05588	9.374
N-Acetyl-L-tyrosine	224.09223	3.284
N-Acetylornithine	175.1082	8.098
N-Acetylputrescine	131.11826	11.381
Nicotinamide	123.0556	2.777
Nicotinamide 1-oxide	139.05059	3.873
Nicotinic acid	124.03966	2.844
Ornithine	133.09753	12.825
Palmitoyl sphingomyelin	703.57634	2.746
Palmitoylcarnitine	400.34286	1.823
Pantothenic acid	220.11849	3.336
Phosphoenolpyruvic acid	168.99008	11.19
Pipecolic acid	130.08664	7.23
PLK	357.25015	12.103
Propionylcarnitine	218.13922	4.763
S-Adenosylhomocysteine	385.12951	8.348
S-Adenosylmethionine	399.14531	9.993
Sarcosine	90.05526	8.349
Symmetric dimethylarginine	203.15081	12.031
Taurocholic acid	516.30034	1.745
Thiamine	265.11224	11.553
Thymidine	243.09814	2.811
Trigonelline	138.05533	6.587
Trimethylamine N-oxide	76.07591	5.353
Uracil	113.03488	3.335
Urea	61.03991	4.955
METABOLITES_END
#END