#METABOLOMICS WORKBENCH WXIAOLAB_20230807_084934 DATATRACK_ID:4206 STUDY_ID:ST003455 ANALYSIS_ID:AN005676 PROJECT_ID:PR002128
VERSION             	1
CREATED_ON             	September 4, 2024, 7:56 am
#PROJECT
PR:PROJECT_TITLE                 	Metabolic reprogramming of pulmonary artery smooth muscle cells of idiopathic
PR:PROJECT_TITLE                 	pulmonary arterial hypertension
PR:PROJECT_SUMMARY               	This project aims to delineate the possible mediators of aerobic activation of
PR:PROJECT_SUMMARY               	HIF1alpha in normal primary cells and its biological consequences related to
PR:PROJECT_SUMMARY               	pulmonary vascular pathobiology.
PR:INSTITUTE                     	Peking University
PR:DEPARTMENT                    	Department of Toxicology
PR:LABORATORY                    	WXIAO
PR:LAST_NAME                     	Xiao
PR:FIRST_NAME                    	Wusheng
PR:ADDRESS                       	38 Xueyuan Rd, Haidian District, Beijing, Beijing, 100191, China
PR:EMAIL                         	wxiao@bjmu.edu.cn
PR:PHONE                         	+1-010-82801628
#STUDY
ST:STUDY_TITLE                   	Metabolic alterations in pulmonary artery smooth muscle cells of idiopathic
ST:STUDY_TITLE                   	pulmonary arterial hypertension (IPAH) patients.
ST:STUDY_SUMMARY                 	Hypoxia-inducible factor 1α (HIF1α) is a master regulator of biological
ST:STUDY_SUMMARY                 	processes in hypoxia. Yet, the mechanisms and biological consequences of aerobic
ST:STUDY_SUMMARY                 	HIF1α activation by intrinsic factors, particularly in normal (primary) cells,
ST:STUDY_SUMMARY                 	remain elusive. Here, we show that HIF1α signalling is activated in several
ST:STUDY_SUMMARY                 	human primary vascular cells in normoxia, and in vascular smooth muscle cells
ST:STUDY_SUMMARY                 	(VSMCs) of normal human lungs. Mechanistically, aerobic HIF1α activation is
ST:STUDY_SUMMARY                 	mediated by paracrine secretion of three branched chain α-ketoacids (BCKAs),
ST:STUDY_SUMMARY                 	which suppress PHD2 activity via direct inhibition and via LDHA-mediated
ST:STUDY_SUMMARY                 	generation of L-2-hydroxyglutarate. BCKA-mediated HIF1α signalling activation
ST:STUDY_SUMMARY                 	stimulated glycolytic activity and governed a phenotypic switch of pulmonary
ST:STUDY_SUMMARY                 	artery SMCs, which correlated with BCKA metabolic dysregulation and
ST:STUDY_SUMMARY                 	pathophenotypic changes in pulmonary arterial hypertension patients and male rat
ST:STUDY_SUMMARY                 	models. We thus identify BCKAs as novel signalling metabolites that aerobically
ST:STUDY_SUMMARY                 	activate HIF1α and that the BCKA-HIF1α pathway modulates VSMC function, an
ST:STUDY_SUMMARY                 	effect that may be relevant to pulmonary vascular pathobiology.
ST:INSTITUTE                     	Peking University
ST:DEPARTMENT                    	Department of Toxicology
ST:LAST_NAME                     	Xiao
ST:FIRST_NAME                    	Wusheng
ST:ADDRESS                       	38 Xueyuan Rd, Haidian District, Beijing, Beijing, 100191, China
ST:EMAIL                         	wxiao@bjmu.edu.cn
ST:PHONE                         	+1-010-82801628
#SUBJECT
SU:SUBJECT_TYPE                  	Cultured cells
SU:SUBJECT_SPECIES               	Homo sapiens
SU:TAXONOMY_ID                   	9606
SU:GENDER                        	Male and female
#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           	1	PASMC-d#3	Treatment:control | Sample source:Vascular smooth muscle cells
SUBJECT_SAMPLE_FACTORS           	2	PASMC-D#4	Treatment:control | Sample source:Vascular smooth muscle cells	
SUBJECT_SAMPLE_FACTORS           	3	PASMC-D#1	Treatment:control | Sample source:Vascular smooth muscle cells
SUBJECT_SAMPLE_FACTORS           	4	PASMC-D#2	Treatment:control | Sample source:Vascular smooth muscle cells
SUBJECT_SAMPLE_FACTORS           	5	PASMC-D#5	Treatment:control | Sample source:Vascular smooth muscle cells
SUBJECT_SAMPLE_FACTORS           	6	PASMC-IPAH L75	Treatment:IPAH | Sample source:Vascular smooth muscle cells
SUBJECT_SAMPLE_FACTORS           	7	PASMC-IPAH L82	Treatment:IPAH | Sample source:Vascular smooth muscle cells
SUBJECT_SAMPLE_FACTORS           	8	PASMC-IPAH L89	Treatment:IPAH | Sample source:Vascular smooth muscle cells
SUBJECT_SAMPLE_FACTORS           	9	PASMC-IPAH L95	Treatment:IPAH | Sample source:Vascular smooth muscle cells
SUBJECT_SAMPLE_FACTORS           	10	PASMC-IPAH L105	Treatment:IPAH | Sample source:Vascular smooth muscle cells
#COLLECTION
CO:COLLECTION_SUMMARY            	Intracellular metabolites were collected and stored at -80 degree before LC-MS
CO:COLLECTION_SUMMARY            	analysis.
CO:SAMPLE_TYPE                   	Vascular smooth muscle cells
CO:COLLECTION_METHOD             	-80 C precold 80% LC-MS grade methanol was used to collect cell metabolites by
CO:COLLECTION_METHOD             	scraping and centrifugation
CO:COLLECTION_LOCATION           	on dry ice
CO:COLLECTION_DURATION           	1 min
CO:STORAGE_CONDITIONS            	-80℃
CO:TISSUE_CELL_IDENTIFICATION    	Pulmonary artery smooth muscle cells (PASMC)
#TREATMENT
TR:TREATMENT_SUMMARY             	human primary pulmonary artery smooth muscle cells from idiopathic pulmonary
TR:TREATMENT_SUMMARY             	arterial hypertension patients and normal control individuals.
TR:TREATMENT                     	normal vs diseased
TR:TREATMENT_COMPOUND            	N/A
TR:TREATMENT_ROUTE               	N/A
TR:TREATMENT_DOSE                	N/A
TR:TREATMENT_DOSEVOLUME          	N/A
TR:TREATMENT_DOSEDURATION        	N/A
TR:TREATMENT_VEHICLE             	N/A
TR:CELL_GROWTH_CONTAINER         	75 cm flasks
TR:CELL_GROWTH_CONFIG            	1200 rpm
TR:CELL_GROWTH_RATE              	30-40 hours
TR:CELL_MEDIA                    	Complete vascular smooth muscle cell growth medium supplemented with growth
TR:CELL_MEDIA                    	factors and 5% FBS
TR:CELL_ENVIR_COND               	37 C and 5% CO2
TR:CELL_PCT_CONFLUENCE           	70-80%
TR:CELL_MEDIA_LASTCHANGED        	Every 48 hours
#SAMPLEPREP
SP:SAMPLEPREP_SUMMARY            	PASMCs were quickly washed with two volumes of ice-cold PBS, lysed for 15 min in
SP:SAMPLEPREP_SUMMARY            	pre-chilled 80% liquid chromatography-mass spectrometry (LC-MS)-grade methanol,
SP:SAMPLEPREP_SUMMARY            	and harvested by scraping on dry ice followed by centrifugation at maximal speed
SP:SAMPLEPREP_SUMMARY            	for 30 min at 4°C. For medium samples, 50 μL of medium were incubated in 200
SP:SAMPLEPREP_SUMMARY            	μL of pre-cooled 100% LC-MS-grade methanol for 15 min on dry ice and then
SP:SAMPLEPREP_SUMMARY            	centrifuged as cell samples did. The supernatants of cell and medium samples
SP:SAMPLEPREP_SUMMARY            	were collected and evaporated to dryness on an Integrated SpeedVac System
SP:SAMPLEPREP_SUMMARY            	(Thermo Fisher Scientific; Waltham, MA) at 42°C. The resulting pellets were
SP:SAMPLEPREP_SUMMARY            	resuspended in 50 μL of LC-MS-grade water. Twenty microliters of sample were
SP:SAMPLEPREP_SUMMARY            	loaded in an autosampler vial for analysis.
SP:PROCESSING_STORAGE_CONDITIONS 	Described in summary
SP:EXTRACT_STORAGE               	Described in summary
#CHROMATOGRAPHY
CH:CHROMATOGRAPHY_SUMMARY        	Vanquish ultra-high performance liquid chromatography system coupled to a Q
CH:CHROMATOGRAPHY_SUMMARY        	Exactive mass spectrometer
CH:CHROMATOGRAPHY_TYPE           	HILIC
CH:INSTRUMENT_NAME               	Thermo Vanquish
CH:COLUMN_NAME                   	Merck ZIC-pHILIC(150 mm × 2.1 mm,3.5um)
CH:SOLVENT_A                     	100% water; 20 mM ammonium carbonate; 0.1% ammonium hydroxide
CH:SOLVENT_B                     	100% acetonitrile
CH:FLOW_GRADIENT                 	gradient (%B) was 0 min, 80%; 20 min, 20%; 20.5 min, 80%; 28 min, 80%; and 42
CH:FLOW_GRADIENT                 	min
CH:FLOW_RATE                     	100
CH:COLUMN_TEMPERATURE            	4
#ANALYSIS
AN:ANALYSIS_TYPE                 	MS
#MS
MS:INSTRUMENT_NAME               	Thermo Q Exactive Focus
MS:INSTRUMENT_TYPE               	Triple quadrupole
MS:MS_TYPE                       	MALDI
MS:ION_MODE                      	UNSPECIFIED
MS:MS_COMMENTS                   	The mass spectrometer was operated in polarity-switching full scan mode from
MS:MS_COMMENTS                   	70-1000 m/z. Resolution was set to 70,000, and the AGC target was 1×106 ions.
MS:MS_COMMENTS                   	Data were acquired and analyzed using TraceFinder 4.1 (Thermo) with peak
MS:MS_COMMENTS                   	identifications based on an in-house library of authentic metabolite standards
MS:MS_COMMENTS                   	previously analyzed utilizing this method. Missing values were imputed using
MS:MS_COMMENTS                   	random forest. Sample peak areas were normalized using probabilistic quotient
MS:MS_COMMENTS                   	normalization
#MS_METABOLITE_DATA
MS_METABOLITE_DATA:UNITS	ion intensity
MS_METABOLITE_DATA_START
Samples	PASMC-d#3	PASMC-D#4	PASMC-D#5	PASMC-D#2	PASMC-D#1	PASMC-IPAH L75	PASMC-IPAH L82	PASMC-IPAH L89	PASMC-IPAH L95	PASMC-IPAH L105
Factors	Treatment:control | Sample source:Vascular smooth muscle cells
	Treatment:control | Sample source:Vascular smooth muscle cells	Treatment:control | Sample source:Vascular smooth muscle cells
	Treatment:control | Sample source:Vascular smooth muscle cells
	Treatment:control | Sample source:Vascular smooth muscle cells
	Treatment:IPAH | Sample source:Vascular smooth muscle cells
	Treatment:IPAH | Sample source:Vascular smooth muscle cells
	Treatment:IPAH | Sample source:Vascular smooth muscle cells
	Treatment:IPAH | Sample source:Vascular smooth muscle cells
	Treatment:IPAH | Sample source:Vascular smooth muscle cells

oleate	5387421.726	7888655.636	6837485.286	6526834.873	7134537.822	3719243.589	3035371.117	3128002.562	2738702.053	4320416.019
ketoleucine	468513284.6	267358762.1	305936336	277391185.8	369145498	940616369.2	1146769765	630910237.1	575504199.2	832058560.2
methylthioadenosine	173831340.6	82841763.59	57587092.22	87612434.27	77812872.88	68489641.68	93318926.79	73631443.01	79515562	31896060.49
pyridoxine	1007981179	948083129.3	951265289.8	989151026.8	1140136302	1761064941	2099723724	1291856779	1514697040	1832474804
2-hydroxybutyrate	2042648.896	1915483.714	1963514.875	2575008.155	2736049.012	3773031.281	3807016.261	2474615.195	3007558.997	3450904.902
butyrylcarnitine	40416872.24	27409015.88	26511657.04	25586319.52	28795112.36	71794248.56	122888267	54647816.52	119566350.3	60418302
pantothenate	5232115582	3356041954	3502858664	3750728383	4047827777	6603517869	8259192500	5822782897	10799060409	6492477637
pyruvate	31043174.82	51570168.4	46903147.43	58763296.13	65366202.01	65000478.96	54931623.97	58927195.19	113822582.6	99153735.43
acetylalanine	14371676.94	8670893.946	9079316.3	8959820.879	9089299.654	16151601.98	28963398.36	19974974.63	31226556.13	18566668.42
creatinine	474963414.8	387373256.6	398653311.9	428411960.3	478604929.1	706736431	851545840.5	548905295.2	662480134.7	729800885.8
3-hydroxybutyrate	2977890.443	1927915.863	3902284.749	3493322.012	4185173.606	4839638.834	4792094.997	3411610.175	4917828.219	2308229.363
uridine	328647.89	482204.7912	396351.9262	516372.2895	522974.8337	412422.6498	269787.4088	122376.9368	211003.9032	135096.9175
deoxycytidine	299996.5347	23815.63189	57817.46483	130547.5522	12852.56584	858500.3807	609468.9255	388789.2437	193647.6208	169773.3014
hypoxanthine	20638750.66	58431043.47	59080099.42	62732393.71	67103910.58	9483664.883	4175348.545	13880399.09	6142810.602	14057696.21
glycerol	11261092.73	7965982.714	7368705.228	9513509.913	9745251.691	5157515.531	2899664.803	16692505.68	2229107.391	3628929.126
kynurenine	2788920.959	2546607.612	2610610.247	2860302.018	3103621.566	6982410.714	4298138.947	4838714.849	3429219.752	4866892.451
leucine	7367995448	5603292128	5715494732	5854376372	6485979062	12496487671	11697202223	8812537010	8228504251	10740627265
orotate	1091109.564	38370.81763	64804.07085	184726.081	71306.42072	742873.3424	640792.1512	312034.2298	1065300.511	589554.0773
o-acetylcarnitine	294741728.6	446164778.2	430117292.7	456596373.4	465021896	449069066.3	483733590.5	498004775.2	556254642.2	543932366.8
acetylglutamine	4628053.154	2920068.804	3129428.378	3365558.787	3478346.362	3835626.454	7447891.648	6476997.943	10177721.8	5977491.289
betaine	354091324	305686485	329896759.2	330422284.9	365708001.7	577453574.8	640635707.5	449578310.1	745608890.7	529315715.8
isoleucine	3549725099	2419319370	2499922757	2568502642	2718153218	6464756137	5391823708	4174956697	3602527701	4892838767
methionine	926953329.2	632840489.1	630753269.3	638878787	700495269.5	1682593066	1367066266	1071050364	959900592.4	1239946452
tryptophan	158790009.6	96884596.12	97118709.59	99425607.91	109140791.8	282367055.4	246622966.2	186289871.3	145642345.9	213619085.7
xanthine	34299662.84	25820959.5	27804324.77	29440825.51	33387768.69	57829790.75	61775457.79	40990669.13	44919862.55	55686447.26
glycerate	3033833.277	3578012.865	4034219.776	3856338.47	4133203.09	3430128.15	3589151.137	3003121.366	3638472.721	3588402.322
valine	2847349731	2071001815	2101849389	2221842356	2424495790	4238421720	3980105975	3019258457	2572762316	3847992572
acetylcholine	142999971.1	108493549.6	113154985.7	106785400.8	111409429.1	245426411.1	276134649.6	224200739.5	299391466.5	175797146.9
tyrosine	367448560.5	244179356.9	251125958.3	253448869.6	285975523.4	596281124.1	509371879.2	383784792.9	332067211.6	471112810.4
methionine sulfoxide	22513332.63	17694163.81	18990547.94	23205046.05	23454537.94	38242073.44	26940065.23	21600704.68	22775835.44	24643468.32
1-methyladenosine	11727725.23	4517378.049	4161728.717	6331165.386	3698341.855	11594082.07	18192894.92	8274496.879	7739860.69	8615408.301
AMP	109570517.8	41985618.56	39299626.26	45073446.39	47462361.82	72008232.63	65531515.48	65100629.84	68392544.17	56901927.16
sorbitol	13495072.9	37189593.39	35002892.06	14376158.67	17986236.53	25018607.43	29777689.28	17841180.11	18807770.05	22918907.49
threonine	238113177.9	207549929.3	211993585	216457270.8	222238390.9	312077130.2	272230341.2	258518397.3	191919489.8	290442929.1
allantoin	27379194.14	23266032.14	23226154.34	26691941.86	29039811.09	49359394.56	51006825.17	38502237.77	41886523.08	46874184.59
creatine	6775045437	4155700496	4100488413	4397971112	4232822460	7283086864	14719035828	5310300527	13432293477	6515288684
acetylglutamate	43380868.77	35427731.08	36705754.44	42127177.52	40532707.34	49642178.1	264434506.7	78133877.98	148004382.5	53454888.56
glutamine	22037935185	18233476606	18366953602	19115589350	18921368301	26746565649	23356154500	21991522224	23152143309	24967125722
alanine	218888026.4	157472606.6	152139459.2	151775961.5	147683481.3	459080694.2	348335188.4	229556919.7	249638728.5	335745893
glucose	17522730.96	66991946.83	47184237.62	57264806.06	62936160.91	43869045.68	62873832.03	35584397.32	37147812.27	79374450.44
histidine	1458633556	968726794.9	974364305.5	1014743844	964947314.3	2430158457	2261640428	1652215108	1201642118	2119270235
phosphocholine	9127462351	7983421135	7974903878	7363270611	8202320408	9112402838	8868941135	10857323155	10215621139	8166171608
aminoadipate	22035464.12	13950107.1	13255731.86	13644316.86	13311201.08	10166908.16	43897839.46	51428948.34	61409584.19	17240522.37
asparagine	201150290.8	138279781.5	136207168.8	137667002.1	136299759.9	273465860	225855323.1	221545401.5	192923956.8	226665818.7
SAM	16852951.08	20474484.79	20691930.76	20186172.49	19444152.92	49343373.9	48470706.91	35518093.76	59247936.99	42422287.5
taurine	37461815.04	21704963.23	21178804.73	21814097.59	23655688.51	128994555.3	169257092.1	120319367	132056576	45883676.73
beta-alanine	18957808.15	15354246.98	13193653.38	13959961.02	12690724.29	44469962.36	78421637.12	30346696.51	34370047.4	30283004.73
choline	5388399.222	3429638.253	2812766.058	3483621.051	4187156.56	9158678.739	4857412.149	4475530.965	8078821.852	5101699.238
glycine	117254098.2	81212436.19	75822897.68	81438764.36	80652844.98	151845515	199541652.8	164163705.8	124176407	119408872.2
serine	179556761.6	147711506.2	140218270.6	142498945.3	155960732.9	163616067	216378693.2	178138515.5	160777877.4	209482681.2
2-hydroxyglutarate	103596187.5	68338826.67	77444880.36	73925729.51	79615389.95	140446799.1	178578458.4	126384380.2	151748042.2	120440412.7
citrulline	23409890.85	11267339.22	11177202.49	12674616.31	14372491	40833622.83	46425561.62	28898855.84	27654020.8	37140936.97
guanidinoacetate	653345.2805	713824.5085	748817.6859	845707.7761	943598.6723	1766551.995	1651455.258	917912.2963	834329.2876	1407371.01
o-phosphoethanolamine	6710668.352	18017557.75	17502751.86	15074919.44	16470528.06	1791779.875	17217248.42	12241442.56	3885570.372	33376504.68
2-oxoglutarate	128703827.1	87268498.46	87114462.4	83701214.58	85866541.43	209333591.3	234682182.6	195174092.4	265787530.7	213055902.5
glucose 1-phosphate	8251580.55	1829998.129	2434057.428	3864573.487	4214114.82	10185041.57	9180474.949	6743092.01	15813979.41	4283052.183
cystine	4548466.513	3194316.92	1709224.26	2240520.816	1892054.367	1958934.617	1565038.438	948924.5483	740520.7003	1187804.922
fumarate	55550255.39	30478629.8	27887687.88	31719867.31	30418102.24	89253074	65527883.94	51730348.65	80733428.08	60679243.96
malate	1047297804	557506004.6	513075416.7	592943043.5	559905983.6	1548198665	1149072203	906557466.5	1392003785	1032089925
glucuronate	6691305.142	5181745.661	4762837.727	5192469.786	5605125.901	5423716.438	9618722.177	7096765.359	5877404.784	4802835.303
cystathionine	10919300.07	3911229.974	3569071.93	3928550.134	4070087.968	25088652.85	13675627.03	13960112.35	12736009.38	9854734.073
glucose 6-phosphate	7322348.57	7144175.08	6363834.293	6481336.404	6737743.447	14081335.38	10266160.31	11327877.4	18868984.83	9133951.37
CDP	10951055.25	3698799.219	2617429.601	4121133.77	4528584.978	2545224.175	5046326.804	3420293.486	4048282.068	2385044.185
GSSG	25761631.29	30549979.94	28920734.9	34498820.24	34363298.92	51470135.31	46551190.87	30375505.18	39356167.23	33556797.59
myo-inositol	62784669.76	74319094.37	71080672.58	71978215.27	76124391.33	49344039.97	101929411.2	71006875.29	20963708.33	38853177.92
3-phosphoglycerate	122963459.9	53777815.13	51612347.69	49006818.26	64501551.38	87249837.29	123433574.1	85718600.42	106860181	112188897
phosphoenolpyruvate	15016673.76	3354774.797	3562928.252	3241426.536	4525920.208	8528104.642	12316668.4	7048357.638	8422551.514	12597787.29
aconitate	112550889.6	75625836.58	75833580.26	74387970.49	78985117.85	201389050.4	135265408.1	138011206.7	218956046.2	158344834.7
citrate	1005390749	617677168.5	646800680.4	621114871	712604717.3	1492473087	1198113229	1080586800	1644580336	1167973441
trimethyllysine	77524242.47	40755263.94	44920891.71	45236701.99	46864568.2	129608478.7	126401268.2	95718882.43	111864148	81123917.23
lysine	511574262.4	398891385.2	481333284.1	492223929.9	607219393.3	905504389.4	1439584159	713508483	818830605.3	1036804754
arginine	1102715709	956484048.6	1045321813	1054923894	1208220919	1554315403	2210626356	1377836422	1499448142	1724942379
palmitate	171884387.7	182772569.4	188273937.8	220949398.1	205158455.1	121642806.2	84703983.23	87180965.82	117687442.1	79038731.87
stearate	301115136.1	350248603.9	372407521	399268329.6	408264220.2	58422971.52	43222653.46	45289310.28	62521815.79	48534171.89
thymidine	576809.7144	363935.231	233056.4517	249983.6389	395891.1189	570953.4626	586263.0372	393526.8353	445674.5844	415691.4698
niacinamide	1447766940	1627529127	1521167229	1547590712	1794928578	2634958128	3270509188	1962581648	2428648286	2772271205
pyridoxal	54729197.25	30911115.49	34593133.66	32258326.72	35093911.22	95485874.16	74960343.83	73320734.45	59406401.8	56568670.66
propionylcarnitine	77632836.77	81077492.54	81419193.66	75141575.57	86705794.3	180095275.1	177295134.6	155467295.4	179152735.5	142802348.2
phenylalanine	2549137423	1663855168	1714165555	1721557681	1921312922	4771507336	4054384359	2967098003	2626549698	3586968899
inosine	3932327.198	1420202.976	1490375.818	1614086.57	2372913.745	2644889.75	603509.4294	2400477.455	1698795.444	973366.2206
cytidine	1855247.993	605726.2852	597994.3817	580458.832	703744.2107	3896927.232	2003170.204	1246680.278	1568847.906	1471265.663
FAD	515092.2491	310799.7835	209910.7857	148942.1494	45517.9879	388811.5805	287794.5424	185178.318	284234.0378	219137.4452
proline	13202065641	9508153860	9221102994	9239163088	9577482057	19320631797	19314948391	17317461011	20627108946	15259662843
xanthosine	52279.20842	155032.6635	101457.9733	149090.9043	197509.2916	16723.68851	38579.93668	38579.93668	44078.52751	54937.59404
ribitol	8775012.017	7221458.99	7009393.128	6770879.197	7215865.755	10041464.46	17314487.77	8816218.337	8475479.603	9473784.13
fructose	23704996.62	32813116.34	28530696.25	31404117.78	33425478.02	39396564.23	58051693.65	28452522.6	33160537.89	52589341.32
carnitine	367941128.2	413872679.2	428181426.7	406663795.3	436645539.2	800437167.8	880244424.7	555750894.5	776033487.1	681269538.4
SAH	87617160.51	25273833.29	16594424.25	29416094.45	24507079.04	30922321.46	31284893.23	25102682.1	24234705.54	16819485.41
dTMP	66797.13335	5877.532759	26735.61327	26735.61327	7532.173693	83157.95501	57926.66883	29740.77419	29928.55676	38486.38659
coenzyme A	3395632.325	2162678.214	2263834.481	1689618.022	2332865.883	2892233.361	4151367.794	2603230.487	4059355.724	2703649.725
urate	11941398.47	7656536.829	9115964.899	8401800.669	10648072.81	19357680.29	27364066.78	20252844.09	15273530.1	23179017.95
o-acetylserine	1323124.636	969585.9849	1191186.143	1280847.809	1191186.143	1419450.204	1077234.672	1113127.896	838620.7701	937739.8164
NAD	223246147.6	169280784.9	162372368	173171812.2	184331467.1	372063031.9	283545449.2	292983446.7	334165395.2	234941626.5
glycerophosphocholine	1971693227	1331391178	1325241510	1323147705	1362174852	2743604605	3121849881	1965468177	4103913704	1752034018
pseudouridine	4182433.176	4898557.476	4475351.644	5220884.328	4703055.781	6531043.625	8546865.561	7281097.687	10303843.16	4986046.922
hydroxyproline	230476149.5	169735721	168636787.3	191024970.4	191230082.7	409265708.1	258556642	243096306.4	462340953.4	307650049.4
GSH	5091918826	3907696316	3736266004	3945184724	3914858747	5028816046	5259772496	3976504333	5869100301	5364624347
hypotaurine	1353419.422	353029.0293	142981.147	218083.6938	516878.3229	1234251.431	3430585.178	1879415.048	1359459.624	389623.6113
acetylaspartate	107453396.2	184881220	197317429.2	166858214.2	203335973.9	51179969.92	278132074.9	121535410.2	365504463.5	78602051.39
glutamate	3743374018	3807452121	3793646503	3795472758	3815519187	5024875789	3907242210	5366676018	5058470713	4415756745
carnosine	8546989.351	6573334.365	6832202.859	7164897.848	7791910.1	13227178.27	17774539.87	10185269.65	10797197.73	13846179.65
citicoline	10278022.04	12577850.73	10482463.48	11169607.9	9347273.566	12037280.92	13667074.47	11421415.91	18528479.78	18282034.62
glycerol 3-phosphate	17259261.16	21873895.29	24250930.18	17178511.5	21150555.42	15401928.48	22833616.05	17920842.25	45273219.4	28997859.64
phosphocreatine	381698846.2	220440186.1	209572265.5	210518232.6	202945846	120617541.1	567745605.3	177411719.8	451618731.7	201345384
UDP-GlcNAc	180853731.1	160440403.4	147316011	148608649.8	152070946.1	148090694.2	288089300.7	149909277.1	145930538.3	272644498.5
UMP	12483920.07	3105961.216	2777028.295	4116161.604	4104739.978	2975515.028	4488671.873	4233203.043	3268409.583	3092125.082
ADP	142061736.1	42032458.52	30754254.09	50687194.43	52135179.69	36601102.44	59568578.81	51091011.4	41316136.12	30009005.16
aspartate	833731244.3	912340773.9	866615291.6	1010005404	924390261.4	1183874294	589532828.3	849329197.4	1426343877	992626499.7
DHAP	8207481.675	3623901.36	3941780.067	3280394.066	3118304.109	9456321.899	11958086.4	4364693.6	9647730.743	11830151.21
GABA	51420973.02	26284234.01	26786662.12	29611358.51	27374288.35	45558926.23	59615168.61	40354099.09	75648238.36	61371658.79
IMP	546818.4623	382519.2112	350592.5744	308238.3451	272847.5892	418110.1178	643500.531	298101.5491	454856.2842	409704.464
ribose 5-phosphate	779857.4704	734883.1846	731357.9503	538559.0247	554783.6589	1287434.101	1743352.689	1177066.881	1405701.334	1473902.261
succinate	49053101.73	43370438.4	43379481.73	42100897.35	47480815.76	129989567.9	77508176.27	72541702.13	80152798.46	83019762.36
CMP	1401424.752	713439.7507	617756.7616	772327.9386	876237.3007	919536.1181	0	0	0	851408.5995
ATP	262668299.1	211892547.3	202843495.7	177334402.2	228786233	241525554.5	331416289.4	257205559.4	309350099.2	267847232
CDP-ethanolamine	2318851.365	3059313.74	2508082.572	2952330.245	2885433.105	856893.7863	2468390.02	3068733.995	2110887.463	3248059.005
phosphoserine	7972295.602	19860075.41	15135294.22	20135151.66	19092545.12	459773.1949	3640609.322	2666363.072	2149573.742	4182578.924
glyceraldehyde 3-phosphate	72003169.83	35707529.73	33695306.62	32432137.79	34395942.44	33218540.98	87258362.72	65626823.75	35600182.5	53646694.47
sedoheptulose 7-phosphate	2747008.492	813875.0593	703473.5357	580373.4529	813796.8503	2614484.747	3845791.236	2320070.337	5735128.863	1575912.052
UDP	44820187.96	15268813.02	11038334.09	18376712.1	19928972.19	16356420.37	22513425.41	17561286.38	21010316.13	10413699.68
argininosuccinate	5413820.335	1688362.204	1528435.749	1562714.599	1611176.421	4778411.838	6335545.986	3434742.708	4605005.511	3488634.792
carbamoylaspartate	7311471.309	3461991.115	2725261.508	3419304.372	2984474.061	8489880.6	12664976.2	5140923.711	10897084.07	9116628.247
UDP-glucose	95307226.33	83255885.76	73342764.48	72410676.68	80965470.38	139445380.8	99865766.89	112843032.4	147660580	87869567.57
GMP	1954713.151	764828.4648	593827.9594	894704.6684	930207.0455	324188.188	798498.4965	1140950.231	601010.6749	399752.2335
NADP	2622504.71	1525685.291	1465407.325	1409394.887	1807925.655	1732069.016	2434842.994	1812639.704	1742656.307	1686578.591
NADPH	3567647.564	2349128.192	2201025.738	1730876.415	2387620.388	2519121.728	4552625.602	1962872.477	2991970.736	3063520.392
GDP	9352080.729	3971868.891	3248803.826	3995148.465	4882169.992	3038290.64	5639877.808	4189797.186	3873506.628	3075401.473
glucaric acid	3107435.571	3017432.108	3226285.616	3023245.776	3735665.352	3647270.693	6152209.431	5782239.453	6233251.539	3846079.324
CTP	16523708.35	13393381.07	14261568.87	11365929.37	15157940.26	14029441.58	21023056.19	11420236.17	23073870.92	16395939.72
fructose 1,6-bisphosphate	46157755.78	20286652.62	19681240.04	16057182.16	21105233.59	48563380.48	76057168.76	33428305.32	45810242.81	37088558.2
UTP	47110625.95	40927650.95	40726318.89	33981971.17	45833515.04	51292402.63	65912094.73	37379777.11	76480923.6	46596873.41
thiamine	414931450.6	341825677.9	345567566.3	354538703.3	387567669.4	813618244.7	855947649.5	633434454.7	581939687.7	666031048.7
GDP-mannose	1563921.861	1157751.381	1166983.585	1006022.93	1310977.222	2857221.794	2167484.338	1970399.689	2678107.247	1994324.098
UDP-glucuronate	17995462.38	10784073.01	10710316.23	8849838.382	12600629.02	9102414.925	26792537.86	12142453.16	5507713.121	15629236.15
GTP	11897400.42	10114112.61	11038531.06	8415811.803	12114216.65	9488949.642	16615713.16	9726001.062	12886945.02	12810130.25
acetylmethionine	44623722.5	19419165.02	20672041.25	20929262.23	21361466.58	67412302.3	59597597.95	38809069.34	49640803.78	58440526.26
lactate	1761275373	932186132.2	1031450859	1054881249	1161030085	2858476296	3702914513	1942709202	2201474706	2567957323
NADH	13034161.86	4711547.708	4275575.807	4271109.437	4883897.138	7446223.583	12672812.08	5672611.644	4659664.865	7533119.437
ornithine	9023343.905	10316315.39	12235884.45	12524849.86	14153514.93	22994912.56	26105821.8	18260800.99	27484208.59	16669595.93
MS_METABOLITE_DATA_END
#METABOLITES
METABOLITES_START
metabolite_name
oleate
ketoleucine
methylthioadenosine
pyridoxine
2-hydroxybutyrate
butyrylcarnitine
pantothenate
pyruvate
acetylalanine
creatinine
3-hydroxybutyrate
uridine
deoxycytidine
hypoxanthine
glycerol
kynurenine
leucine
orotate
o-acetylcarnitine
acetylglutamine
betaine
isoleucine
methionine
tryptophan
xanthine
glycerate
valine
acetylcholine
tyrosine
methionine sulfoxide
1-methyladenosine
AMP
sorbitol
threonine
allantoin
creatine
acetylglutamate
glutamine
alanine
glucose
histidine
phosphocholine
aminoadipate
asparagine
SAM
taurine
beta-alanine
choline
glycine
serine
2-hydroxyglutarate
citrulline
guanidinoacetate
o-phosphoethanolamine
2-oxoglutarate
glucose 1-phosphate
cystine
fumarate
malate
glucuronate
cystathionine
glucose 6-phosphate
CDP
GSSG
myo-inositol
3-phosphoglycerate
phosphoenolpyruvate
aconitate
citrate
trimethyllysine
lysine
arginine
palmitate
stearate
thymidine
niacinamide
pyridoxal
propionylcarnitine
phenylalanine
inosine
cytidine
FAD
proline
xanthosine
ribitol
fructose
carnitine
SAH
dTMP
coenzyme A
urate
o-acetylserine
NAD
glycerophosphocholine
pseudouridine
hydroxyproline
GSH
hypotaurine
acetylaspartate
glutamate
carnosine
citicoline
glycerol 3-phosphate
phosphocreatine
UDP-GlcNAc
UMP
ADP
aspartate
DHAP
GABA
IMP
ribose 5-phosphate
succinate
CMP
ATP
CDP-ethanolamine
phosphoserine
glyceraldehyde 3-phosphate
sedoheptulose 7-phosphate
UDP
argininosuccinate
carbamoylaspartate
UDP-glucose
GMP
NADP
NADPH
GDP
glucaric acid
CTP
fructose 1,6-bisphosphate
UTP
thiamine
GDP-mannose
UDP-glucuronate
GTP
acetylmethionine
lactate
NADH
ornithine
METABOLITES_END
#END