#METABOLOMICS WORKBENCH spinelli_lab_20240514_125536 DATATRACK_ID:4843 STUDY_ID:ST003214 ANALYSIS_ID:AN005270 PROJECT_ID:PR001988
VERSION             	1
CREATED_ON             	May 21, 2024, 11:49 am
#PROJECT
PR:PROJECT_TITLE                 	Rhodoquinone is an Electron Carrier in the Mammalian Electron Transport Chain
PR:PROJECT_SUMMARY               	Ubiquinone (UQ), the only known electron carrier in the mammalian electron
PR:PROJECT_SUMMARY               	transport chain (ETC), delivers electrons to both oxygen (O2) and fumarate as
PR:PROJECT_SUMMARY               	terminal electron acceptors. As fumarate has a lower reduction potential than
PR:PROJECT_SUMMARY               	UQ, fumarate reduction is only thermodynamically favorable when ubiquinol, the
PR:PROJECT_SUMMARY               	reduced form of UQ, accumulates. Paradoxically, some tissues reduce fumarate
PR:PROJECT_SUMMARY               	without ubiquinol buildup, suggesting another mechanism enables fumarate
PR:PROJECT_SUMMARY               	reduction in mammals. Here, we identify rhodoquinone (RQ), a novel component of
PR:PROJECT_SUMMARY               	the mammalian ETC that carries electrons to fumarate, instead of O2, as the
PR:PROJECT_SUMMARY               	terminal electron acceptor. RQ, which is undetectable in cultured mammalian
PR:PROJECT_SUMMARY               	cells, is enriched in mitochondria from mouse and human tissues that catalyze
PR:PROJECT_SUMMARY               	high levels of fumarate reduction. UQ and RQ-directed ETC circuits support
PR:PROJECT_SUMMARY               	unique programs of mitochondrial function. Through expression of a bacterial
PR:PROJECT_SUMMARY               	enzyme that converts UQ into RQ and development of a novel RQ analog, we
PR:PROJECT_SUMMARY               	demonstrate that reprogramming the mammalian ETC from the UQ to RQ circuit
PR:PROJECT_SUMMARY               	renders cells highly resistant to hypoxia exposure in vitro and in vivo. Thus,
PR:PROJECT_SUMMARY               	we establish RQ as a fundamental component of the mammalian ETC and unveil that
PR:PROJECT_SUMMARY               	reprogramming the ETC to the RQ-circuit is a tractable strategy to ameliorate
PR:PROJECT_SUMMARY               	hypoxia-related conditions.
PR:INSTITUTE                     	UMass Chan Medical School
PR:LAST_NAME                     	UMass Chan
PR:FIRST_NAME                    	Spinelli Lab
PR:ADDRESS                       	55 Lake Avenue North, Worcester, Massachusetts, 01605, USA
PR:EMAIL                         	spinellilab@gmail.com
PR:PHONE                         	(508) 856-8989 ext. 68148
#STUDY
ST:STUDY_TITLE                   	Glutamine Tracing Assay in RquA AAV Injected Mice with a Standard Curve
ST:STUDY_SUMMARY                 	The extraction of RquA AAV injected livers from C57BL/6 mice. Metabolites from
ST:STUDY_SUMMARY                 	the liver were used to measure fumarate reduction and succinate oxidation.
ST:STUDY_SUMMARY                 	Glutamine tracing was used to determine forward and reverse direction of the TCA
ST:STUDY_SUMMARY                 	cycle. Standards were used to create a standard curve by diluting down a stock
ST:STUDY_SUMMARY                 	of fumarate and succinate standard mixture. The standard curve was used to
ST:STUDY_SUMMARY                 	determine picomoles of metabolites in the TCA cycle.
ST:INSTITUTE                     	UMass Chan Medical School
ST:LAST_NAME                     	UMass Chan
ST:FIRST_NAME                    	Spinelli Lab
ST:ADDRESS                       	55 Lake Avenue North, Worcester, Massachusetts, 01605, USA
ST:EMAIL                         	spinellilab@gmail.com
ST:PHONE                         	(508) 856-8989 ext. 68148
#SUBJECT
SU:SUBJECT_TYPE                  	Mammal
SU:SUBJECT_SPECIES               	Mus musculus
SU:TAXONOMY_ID                   	10090
#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           	-	Standard 2	Sample source:Succinate and Fumarate Reagent Mixture | Standards for Standard Curve and Treatment:Measurable Standard Curve	RAW_FILE_NAME(File Name )=RquA_AAV_mouse_polar01
SUBJECT_SAMPLE_FACTORS           	-	Standard 3	Sample source:Succinate and Fumarate Reagent Mixture | Standards for Standard Curve and Treatment:Measurable Standard Curve	RAW_FILE_NAME(File Name )=RquA_AAV_mouse_polar02
SUBJECT_SAMPLE_FACTORS           	-	Standard 4	Sample source:Succinate and Fumarate Reagent Mixture | Standards for Standard Curve and Treatment:Measurable Standard Curve	RAW_FILE_NAME(File Name )=RquA_AAV_mouse_polar03
SUBJECT_SAMPLE_FACTORS           	-	Standard 5	Sample source:Succinate and Fumarate Reagent Mixture | Standards for Standard Curve and Treatment:Measurable Standard Curve	RAW_FILE_NAME(File Name )=RquA_AAV_mouse_polar04
SUBJECT_SAMPLE_FACTORS           	-	Standard 6	Sample source:Succinate and Fumarate Reagent Mixture | Standards for Standard Curve and Treatment:Measurable Standard Curve	RAW_FILE_NAME(File Name )=RquA_AAV_mouse_polar05
SUBJECT_SAMPLE_FACTORS           	-	Standard 7	Sample source:Succinate and Fumarate Reagent Mixture | Standards for Standard Curve and Treatment:Measurable Standard Curve	RAW_FILE_NAME(File Name )=RquA_AAV_mouse_polar06
SUBJECT_SAMPLE_FACTORS           	-	Standard 8	Sample source:Succinate and Fumarate Reagent Mixture | Standards for Standard Curve and Treatment:Measurable Standard Curve	RAW_FILE_NAME(File Name )=RquA_AAV_mouse_polar07
SUBJECT_SAMPLE_FACTORS           	-	Liver 1	Sample source:C57/BL6 mouse liver tissue | Standards for Standard Curve and Treatment:RquA AAV injected	RAW_FILE_NAME(File Name )=RquA_AAV_mouse_polar08
SUBJECT_SAMPLE_FACTORS           	-	Liver 2	Sample source:C57/BL6 mouse liver tissue | Standards for Standard Curve and Treatment:RquA AAV injected	RAW_FILE_NAME(File Name )=RquA_AAV_mouse_polar09
SUBJECT_SAMPLE_FACTORS           	-	Liver 3	Sample source:C57/BL6 mouse liver tissue | Standards for Standard Curve and Treatment:RquA AAV injected	RAW_FILE_NAME(File Name )=RquA_AAV_mouse_polar10
SUBJECT_SAMPLE_FACTORS           	-	Liver 4	Sample source:C57/BL6 mouse liver tissue | Standards for Standard Curve and Treatment:RquA AAV injected	RAW_FILE_NAME(File Name )=RquA_AAV_mouse_polar11
SUBJECT_SAMPLE_FACTORS           	-	Liver 5	Sample source:C57/BL6 mouse liver tissue | Standards for Standard Curve and Treatment:RquA AAV injected	RAW_FILE_NAME(File Name )=RquA_AAV_mouse_polar12
SUBJECT_SAMPLE_FACTORS           	-	Liver 6	Sample source:C57/BL6 mouse liver tissue | Standards for Standard Curve and Treatment:RquA AAV injected	RAW_FILE_NAME(File Name )=RquA_AAV_mouse_polar13
SUBJECT_SAMPLE_FACTORS           	-	Liver 7	Sample source:C57/BL6 mouse liver tissue | Standards for Standard Curve and Treatment:Vehicle	RAW_FILE_NAME(File Name )=RquA_AAV_mouse_polar14
SUBJECT_SAMPLE_FACTORS           	-	Liver 8	Sample source:C57/BL6 mouse liver tissue | Standards for Standard Curve and Treatment:Vehicle	RAW_FILE_NAME(File Name )=RquA_AAV_mouse_polar15
SUBJECT_SAMPLE_FACTORS           	-	Liver 9	Sample source:C57/BL6 mouse liver tissue | Standards for Standard Curve and Treatment:Vehicle	RAW_FILE_NAME(File Name )=RquA_AAV_mouse_polar16
SUBJECT_SAMPLE_FACTORS           	-	Liver 10	Sample source:C57/BL6 mouse liver tissue | Standards for Standard Curve and Treatment:Vehicle	RAW_FILE_NAME(File Name )=RquA_AAV_mouse_polar17
SUBJECT_SAMPLE_FACTORS           	-	Liver 11	Sample source:C57/BL6 mouse liver tissue | Standards for Standard Curve and Treatment:Vehicle	RAW_FILE_NAME(File Name )=RquA_AAV_mouse_polar18
SUBJECT_SAMPLE_FACTORS           	-	Liver 12	Sample source:C57/BL6 mouse liver tissue | Standards for Standard Curve and Treatment:Vehicle	RAW_FILE_NAME(File Name )=RquA_AAV_mouse_polar19
SUBJECT_SAMPLE_FACTORS           	-	Liver 13	Sample source:C57/BL6 mouse liver tissue | Standards for Standard Curve and Treatment:Vehicle	RAW_FILE_NAME(File Name )=RquA_AAV_mouse_polar20
SUBJECT_SAMPLE_FACTORS           	-	Liver 15	Sample source:C57/BL6 mouse liver tissue | Standards for Standard Curve and Treatment:Vehicle	RAW_FILE_NAME(File Name )=RquA_AAV_mouse_polar21
#COLLECTION
CO:COLLECTION_SUMMARY            	13C515N2-glutamine (Cambridge Isotope labs) was resuspended to 50 mg/mL in 1X
CO:COLLECTION_SUMMARY            	PBS. C57BL/6 mice between the ages of 10-16 weeks were weighed to allow
CO:COLLECTION_SUMMARY            	injection of 0.75 g/kg intraperitoneally and 0.2 g/kg intravenously via the tail
CO:COLLECTION_SUMMARY            	vein. Mice were injected with the respective amounts of 13C515N2-glutamine, were
CO:COLLECTION_SUMMARY            	sacrificed after 45 minutes, and tissues were harvested and flash frozen in
CO:COLLECTION_SUMMARY            	Liquid Nitrogen. Samples were stored at -80°C until their extraction and run on
CO:COLLECTION_SUMMARY            	the polar LC-MS method.
CO:SAMPLE_TYPE                   	Mouse Liver
#TREATMENT
TR:TREATMENT_SUMMARY             	Adeno-associated viruses (AAVs) were used for expression of RquA in mice.
TR:TREATMENT_SUMMARY             	Briefly, rAAV was produced by transient HEK 293 cell transfection and CsCl
TR:TREATMENT_SUMMARY             	sedimentation by the University of Massachusetts Medical School Viral Vector
TR:TREATMENT_SUMMARY             	Core. Vector genome titers of the rAAV preparations for control virus
TR:TREATMENT_SUMMARY             	(AAV9.Tre3G-mCherry SV40 CB6 Tet-on 3G RBG) and RquA virus (AAV9.Tre3G-RquA SV40
TR:TREATMENT_SUMMARY             	CB6 Tet-on 3G RBG) were determined by ddPCR, and purity was assessed by 4%–12%
TR:TREATMENT_SUMMARY             	SDS-acrylamide gel electrophoresis and silver staining (Invitrogen). Mice were
TR:TREATMENT_SUMMARY             	intravenously injected with 6 X 10^11 genome copies of either virus and given 1
TR:TREATMENT_SUMMARY             	mg/mL doxycycline in the drinking water for 7 days to induce either mCherry or
TR:TREATMENT_SUMMARY             	RquA expression.
#SAMPLEPREP
SP:SAMPLEPREP_SUMMARY            	Tissues were flash frozen in liquid nitrogen and powderized using a mortar and
SP:SAMPLEPREP_SUMMARY            	pestle. Approximately 10 mg of tissue powder was transferred into an Eppendorf
SP:SAMPLEPREP_SUMMARY            	tube. The tissue powder was re-suspended in 800 µL pre-cooled HPLC-grade 60:40
SP:SAMPLEPREP_SUMMARY            	Methanol:Water (Sigma) and then vortexed for 15 minutes at 4°C. 500 µL of
SP:SAMPLEPREP_SUMMARY            	pre-cooled LC-MS grade chloroform (Sigma) was added to the lysate and again
SP:SAMPLEPREP_SUMMARY            	vortexed for 15 minutes at 4°C. Samples were then centrifuged at 16,000 x g for
SP:SAMPLEPREP_SUMMARY            	10 minutes at 4°C, creating three layers: the top layer containing polar
SP:SAMPLEPREP_SUMMARY            	metabolites, the middle layer containing protein, and the bottom layer
SP:SAMPLEPREP_SUMMARY            	containing non-polar metabolites. The top layer was transferred into a new
SP:SAMPLEPREP_SUMMARY            	Eppendorf tube, dried down in a Refrigerated CentriVap Benchtop Vacuum
SP:SAMPLEPREP_SUMMARY            	Concentrator connected to a CentriVap-105 Cold Trap (Labconco), and stored at
SP:SAMPLEPREP_SUMMARY            	-80°C until they were re-suspended for LC-MS analysis. The non-polar layer was
SP:SAMPLEPREP_SUMMARY            	discarded, and the remaining protein layer was saved for protein quantification.
SP:SAMPLEPREP_SUMMARY            	The protein layer from the metabolite isolation was re-suspended in 1 mL of RIPA
SP:SAMPLEPREP_SUMMARY            	buffer (150 mM NaCl, 50 mM Tris HCl pH 7.5, 0.1% SDS, 1% Triton-X 100 (Sigma),
SP:SAMPLEPREP_SUMMARY            	0.5% deoxycholate (Sigma), cOmplete EDTA-free protease inhibitor (Sigma)). The
SP:SAMPLEPREP_SUMMARY            	samples were vortexed for 10 minutes at 4°C and then centrifuged at 16,000 x g
SP:SAMPLEPREP_SUMMARY            	for 10 minutes at 4°C. Protein concentrations for each sample were calculated
SP:SAMPLEPREP_SUMMARY            	using the Pierce BCA Protein Assay Kit (Life Technologies). The protein
SP:SAMPLEPREP_SUMMARY            	concentrations were used to calculate the re-suspension volume to normalize all
SP:SAMPLEPREP_SUMMARY            	samples for LC-MS analysis to equal (1 µg/µL ) concentration.
#CHROMATOGRAPHY
CH:CHROMATOGRAPHY_TYPE           	HILIC
CH:INSTRUMENT_NAME               	Thermo Vanquish
CH:COLUMN_NAME                   	Merck SeQuant ZIC-HILIC (150 x 2.1mm,5um)
CH:SOLVENT_A                     	100% water; 0.1% ammonium hydroxide; 20mM ammonium carbonate
CH:SOLVENT_B                     	100% acetonitrile
CH:FLOW_GRADIENT                 	20 min, 80% - 20% B; 0.5 min, 20% - 80% B; 7.5min, 80% B
CH:FLOW_RATE                     	0.15ml/min
CH:COLUMN_TEMPERATURE            	25
#ANALYSIS
AN:ANALYSIS_TYPE                 	MS
#MS
MS:INSTRUMENT_NAME               	Thermo Q Exactive Plus Orbitrap
MS:INSTRUMENT_TYPE               	Orbitrap
MS:MS_TYPE                       	ESI
MS:ION_MODE                      	POSITIVE
MS:MS_COMMENTS                   	The mass spectrometer was set to full scan (70-1000 m/z), with the spray voltage
MS:MS_COMMENTS                   	set to 4.0 kV, heated capillary to 350°C, and the HESI probe at 30 °C. The
MS:MS_COMMENTS                   	sheath gas flow was set at 10 units, auxiliary gas at 1 units, and sweep gas
MS:MS_COMMENTS                   	flow at 1 unit. The resolution of scan was set to 70,000, AGC target to 1x106,
MS:MS_COMMENTS                   	and maximum injection time at 20 msec. Data acquired by Thermo Fisher's Xcalibur
MS:MS_COMMENTS                   	software and analyzed by their Tracefinder software. The raw files provided
MS:MS_COMMENTS                   	contain data from both positive and negative ion mode.
#MS_METABOLITE_DATA
MS_METABOLITE_DATA:UNITS	peak area
MS_METABOLITE_DATA_START
Samples	Standard 2	Standard 3	Standard 4	Standard 5	Standard 6	Standard 7	Standard 8	Liver 1	Liver 2	Liver 3	Liver 4	Liver 5	Liver 6	Liver 7	Liver 8	Liver 9	Liver 10	Liver 11	Liver 12	Liver 13	Liver 15
Factors	Sample source:Succinate and Fumarate Reagent Mixture | Standards for Standard Curve and Treatment:Measurable Standard Curve	Sample source:Succinate and Fumarate Reagent Mixture | Standards for Standard Curve and Treatment:Measurable Standard Curve	Sample source:Succinate and Fumarate Reagent Mixture | Standards for Standard Curve and Treatment:Measurable Standard Curve	Sample source:Succinate and Fumarate Reagent Mixture | Standards for Standard Curve and Treatment:Measurable Standard Curve	Sample source:Succinate and Fumarate Reagent Mixture | Standards for Standard Curve and Treatment:Measurable Standard Curve	Sample source:Succinate and Fumarate Reagent Mixture | Standards for Standard Curve and Treatment:Measurable Standard Curve	Sample source:Succinate and Fumarate Reagent Mixture | Standards for Standard Curve and Treatment:Measurable Standard Curve	Sample source:C57/BL6 mouse liver tissue | Standards for Standard Curve and Treatment:RquA AAV injected	Sample source:C57/BL6 mouse liver tissue | Standards for Standard Curve and Treatment:RquA AAV injected	Sample source:C57/BL6 mouse liver tissue | Standards for Standard Curve and Treatment:RquA AAV injected	Sample source:C57/BL6 mouse liver tissue | Standards for Standard Curve and Treatment:RquA AAV injected	Sample source:C57/BL6 mouse liver tissue | Standards for Standard Curve and Treatment:RquA AAV injected	Sample source:C57/BL6 mouse liver tissue | Standards for Standard Curve and Treatment:RquA AAV injected	Sample source:C57/BL6 mouse liver tissue | Standards for Standard Curve and Treatment:Vehicle	Sample source:C57/BL6 mouse liver tissue | Standards for Standard Curve and Treatment:Vehicle	Sample source:C57/BL6 mouse liver tissue | Standards for Standard Curve and Treatment:Vehicle	Sample source:C57/BL6 mouse liver tissue | Standards for Standard Curve and Treatment:Vehicle	Sample source:C57/BL6 mouse liver tissue | Standards for Standard Curve and Treatment:Vehicle	Sample source:C57/BL6 mouse liver tissue | Standards for Standard Curve and Treatment:Vehicle	Sample source:C57/BL6 mouse liver tissue | Standards for Standard Curve and Treatment:Vehicle	Sample source:C57/BL6 mouse liver tissue | Standards for Standard Curve and Treatment:Vehicle
Ciliatine	11051.43194	0	0	9724.664092	10670.39539	0	9781.925008	0	27202.39279	0	187578.293	818868.1641	0	597918.1888	2859809.336	153218.9769	48776.91288	292948.5785	188037.8957	339856.9906	38800.06084
1-Aminocyclopropanecarboxylic acid	646044.8933	1153666.022	560562.4349	0	108918.0819	56453.74518	241357.7766	130464673.5	161015343	144478095.9	68759487.66	59827623.23	118104622.1	102221415.4	155347154.3	38784103.8	35963421.48	69791614.71	49490150.55	72252372.14	40205051.64
1-Methyladenosine	0	0	0	0	0	0	0	88625134.47	39012482.63	15000085.44	9028027.435	2406027.513	65612677.24	13094359.81	1787341.872	254272.2657	2083234.77	3242927.414	361732.5706	543033.8178	442451.7941
1-Methyl nicotinamide	0	0	0	0	0	24781.65838	0	17968123.31	13331640.22	15903889.94	14626345.86	16844032.93	19392876.41	24426396.51	18109050.11	2497738.36	3547724.815	6203371.797	3510165.721	3918855.313	1976101.067
Aminoisobutyric acid	113938372.8	0	0	4288877.088	2930946.94	5774474.303	4402364.826	721099561.8	547749199.9	244932785.3	493519619.5	235020981.6	641260426.4	862047719.9	946089011.8	342360158.5	296027995.3	484813340.9	317450846.1	478681406.6	287562646.1
2-Aminophenol	0	0	265677.942	217154.2185	68893.17763	51710.28146	0	1921448.999	2265160.89	2563277.042	2706621.644	7446274.888	2178637.536	3031570.875	4725003.652	1443670.291	2102701.668	2306407.986	1580114.361	2546642.352	1776640.646
2-Hydroxypyridine	226510.598	256881.2528	0	316614.0451	0	110765.0777	161736.653	21562639.49	18892104.47	12191737.07	19183382.19	31316683.01	19462655.85	44470162.88	41914694.18	13818962.75	11913902.96	20592324.63	13034154.65	19511380.84	12464445.7
3-Hydroxyanthranilic acid	0	0	0	59634.09886	21728.87179	9996.593766	12408.91446	1721432.427	1787170.691	1970163.861	4374901.839	604969.8698	2586190.546	7133619.382	911731.6019	1348337.564	2580199.524	1370259.75	71841.18267	75146.08868	110147.4283
3-Methylhistidine	2923726.578	812612.9533	474588.6675	119870.4236	0	0	56844.40058	66969836.05	43801912.89	45857569.3	136521920	320024061.2	127901755.3	275947953.4	170557162.2	135215731.1	202146401.1	190226153.4	167625832	176118486.9	170557248.5
Nitrotyrosine	0	0	0	0	0	0	0	448322.4007	177976.1997	534016.1744	199019.8096	725863.4152	517564.9504	3840242.88	3604160.619	672428.869	641395.257	1372590.337	681418.9669	1472705.76	646433.8613
4-Guanidinobutanoic acid	3581979.213	2315336.162	2243459.182	5032507.272	1928660.047	1905355.557	4829938.969	1370948956	693499967.3	691176629.3	4017383150	1201570761	2076183762	3091714340	2703692839	1578940721	893440543.5	2703764029	1059874258	2447304627	817923901.5
5-Amino-levulinic acid	987232.3142	199154.2033	0	0	168809.6982	0	465280.1338	90826122.22	63765787.14	18200960.6	358247101.4	102144650.9	60856547.73	252119341.9	413981038.6	261361399.3	191754010.9	249229325.6	183610872.8	280926356.9	164085233.2
5-Aminopentanoic acid	240670.9102	296983.9515	230421.9219	295625.4811	0	589286.6254	120687.3758	67226708.77	46331812.53	28253243.95	231241420.7	34432423.69	70424398.88	58903085.82	49016189.47	23907010.59	17049387.87	22055452.2	17368036.21	28416060.35	12831723.93
5-Methylcytosine	0	290619.4945	76191.7815	327280.1936	35187.5901	186867.634	78217.871	12891645.14	10039138.67	4777203.253	9077296.849	13060748.91	7886601.476	29262883.1	33692751.54	5158580.277	4602661.912	11969482.95	5740319.594	8913551.213	4531875.265
Acetylcholine	76821.14049	0	0	0	0	0	0	79664526.91	69690007.28	63900534.97	187556888.4	47110712.18	147450401.2	174817672.4	144243450.9	26775544.94	37304559.57	48868498.16	29197694.51	45600355.83	23236833.38
Adenine	42606328.92	23447273	10871271.84	5583411.442	6269368.715	4953405.217	661176.3521	1364276324	765625755.1	1134861728	1275686830	1665339047	1069697209	4387203437	3905178708	808792242.9	819784104.3	1666762428	1418063640	1061035821	547334298.2
Allothreonine	3715012.898	3311323.432	1675551.135	948281.8234	0	777707.9781	829976.8639	977798389.4	1144486373	1018726198	514894436.7	426131097.6	906552818.6	614081258.9	995107570.8	274521322	238814456.2	461738033.9	363372944.6	552742492.9	295500699.1
alpha-Aminoadipic acid	350366.8331	44350.6019	213452.6622	167671.8448	120218.9629	194559.3686	128695.6382	8582947278	5424830514	2756523911	6678039636	460685956.8	8397629964	436564160.8	313899983	226467753.4	160023841.9	103064075.5	241762384.4	222979968.2	240844488.7
3-Aminoisobutanoic acid	0	0	0	4191847.051	3626721.19	6015251.719	5366620.981	924713429.2	688162805.1	399884711.7	774905959.8	429853536.8	812649676.5	969328337.2	1051179606	402123908.7	360210393.6	552148808.5	383358851.6	563468479.8	321575504.8
Anserine	25277.11792	0	0	0	0	0	24660.84	8390346.524	11306322.44	9284732.693	4297505.108	6998066.062	20433048.77	12692239.89	8122612.011	9542419.993	8660714.202	13168520.18	10461073.21	13974490.13	9593287.425
Arginine	8166098095	5021941933	2770062878	1419656846	209978379.4	103113861.6	57157875.16	1204953585	768183364.2	740578701.8	526973080.9	200088433.3	1882754392	671915569.2	409679480.8	68229518.84	149616025	308311136.4	59178623.48	106603812.1	109349966.5
Asparagine	323552.6379	237833.9586	157663.5734	217132.4563	0	87958.05794	159779.5765	80505074.93	75300350.85	35057488.09	51110287.31	71068297.8	78366749.06	59934369.3	51345817.12	68550297.98	63277767.42	86412333.35	103779013	63262205.15	85455152.7
Asparagine_15N1	55084.55101	12280.71789	44162.28617	110036.5411	25598.36001	0	52928.66928	37469613.31	34150840.82	19172063.57	21145436.84	27949726.21	31000303.06	23220946.77	3767923.079	17492820.98	27947888.51	40363708.36	45832683.68	11873376.5	30024176.31
beta-Alanine	2715457.225	1291594.37	1025567.227	886680.715	855807.7506	1034719.112	907904.7666	1117263631	1050230235	1046958598	1308788990	863113594.9	1247954110	1517565172	1336512943	720251715	729654903.7	614222748.7	786163226.6	1118932766	1010036876
Betaine	1157142593	604229332.6	289783235.5	129958787.6	32292865.14	36156111.18	33504466.23	97312858398	59359110083	36047499314	90260243156	53708417374	76254472679	1.09393E+11	88419273186	32172839611	58035128998	59545405679	46066825030	45602420636	26884140255
NAD+	277884.9755	46075.94026	0	0	0	0	0	173337486.3	103791347.1	35393041.88	200227421.5	459997485.1	107124377	858232829.6	770206576.4	366918562.4	435705368	537490446.6	475676280.8	513169794.6	456959023
Caffeine	145685.3678	92626.69224	304839.0072	0	262989.256	136928.451	94477.35441	1342473.46	746331.0169	2964042.362	642106.7448	2041971.387	819992.9076	2455224.178	6692724.217	1025227.743	743271.7873	2673074.571	1403141.998	1784682.955	938667.8167
Carnosine	0	0	0	0	0	0	0	2290944.787	3957827.346	6167263.169	1594434.105	2001100.282	4945643.449	3580007.473	2742781.755	2364043.283	2337796.489	3544931.743	2508041.552	3209365.025	1825505.288
Choline	3181046.465	924692.2017	707181.2389	502418.6963	524221.4618	498447.3916	503527.3699	401653229.8	589388880.2	858400533.7	432146210.8	224691469.9	881117712.3	512801948.4	1505105221	295548689.6	91617218.48	651607406.4	421168538.5	661831649.9	264648606.9
cis-4-Hydroxy-D-proline	987232.3142	198529.5643	34517.01082	772669.565	231343.8337	0	0	90826122.22	63765787.14	18200960.6	358251525.6	102162359.3	60856547.73	252119341.9	413976952	261361399.3	191754010.9	249229325.6	183610872.8	280999428.4	164085233.2
Citrulline	1182349.766	947306.6562	0	684958.346	317276.8666	798599.9902	693990.4221	947211830.9	1826490359	2285949978	395596581.8	448009067.2	671150001.7	395905917.9	244876657.7	159919793.5	129185238.9	191254958.6	157847618.6	267055648.3	187899620.6
Coenzyme A	0	0	0	0	0	0	0	919962.9395	0	0	318465.326	4139163.873	251540.1147	39113204.37	19014060.65	1255772.538	1496527.509	4105191.432	2184965.232	3590297.787	1455596.45
Creatine	148687221.2	26533009.44	49414895.91	37251727.6	61658566.27	103196740.2	54646716.62	24211794242	25720263639	27102517660	19441359925	16471644046	31340300542	31080125174	16149345084	9057664118	13134412098	17241043572	9893090640	11299476843	10198526056
Creatinine	38274050.15	7609462.381	5985785.488	4214688.159	3643196.811	4061908.187	3609540.301	878279832.7	650569026.4	806916276.5	827926836.6	654258324.2	844462732.7	1744871967	2264811750	441411846	430253462.5	1138994537	526638696.3	835516042.2	420509662.1
Cystathionine	9283.034456	0	9936.736011	23292.44407	0	0	9419.625218	59180015.24	50544295.94	65069091.63	54198920.35	12275286.83	68603398.15	5008806.286	9110534.45	7257125.963	2262540.732	5333537.502	10568469.59	20533038.6	10087344.04
Cysteic acid	0	0	0	0	0	10997.79947	0	2323366.381	1430582.711	696949.421	1012197.446	640818.5421	988996.1558	3313971.297	5075529.723	265038.4556	308660.5396	1250142.982	313936.4303	1061072.844	420293.5986
Cystine	0	0	0	0	0	0	0	21434545.52	21459454.43	18086046.72	5033559.42	488885.8566	42996513.5	1491760.679	1555639.413	398080.3407	399875.331	1898386.562	742546.5483	1392811.136	811930.2158
Cytidine	0	470323.958	0	880373.4769	1377563.652	929705.6381	515438.6033	218578766	182821620.7	367395885.1	145490259.3	80362788.03	346129439	318000606.7	277391206.6	63033456.07	117985251.4	135708722.4	57078696.11	95736332.34	56734869.91
D-Alanine	2715457.225	1221321.621	1025567.227	968474.9576	845565.6579	1034719.112	847853.3682	1117263631	1050230235	1046958598	1308788990	863113594.9	1247954110	1517565172	1336512943	720251715	729654903.7	614222748.7	786163226.6	1118932766	1010036876
D-Alanine_13C1	0	0	164151.7386	149511.2419	136587.4063	0	188733.9003	83482876.94	70360896.07	50202820.19	88184143.11	69262177	85998909.69	88478487.03	57264183.25	34954442.51	41836961.11	36476254.01	46995014.05	46250521.87	62168608.92
D-Alanine_13C2	0	10886.39436	0	0	11313.83141	0	0	46798211.8	44526959.41	29536586.4	40863873.81	33197715.32	54931429.29	20909620.6	5184250.808	7931727.812	14305649.32	9793795.662	16067804.34	10389078.4	21819504.29
D-Alanine_13C3	0	0	0	0	0	0	0	106462882.3	87922154.69	48107116.7	68012746.55	48595131.61	80491998.65	36464126.04	348789.0944	8920622.855	23409544.9	11827144.38	23008225.96	7344607.205	25602646.73
D-Alanine_15N1	0	0	0	175149.7592	256154.179	32000.63992	78808.59051	404972833.6	348382595.9	345089987	379273846.6	227700840.8	357111073.8	360393465.3	71956896.37	133938575.8	254090272.8	173835725.8	242726983.2	126994486.3	286107122.9
3-Dehydroxycarnitine	2678396.865	625780.3072	463362.3053	451954.1621	333210.2962	510564.617	422688.0716	1052476545	963116887.9	835805188.4	2472087742	642904954	2013515912	2529625986	1939759938	366993447.5	526658161	642232154.6	381932210.4	626304574.3	329142471.7
Dethiobiotin	382453.5302	74110.92919	31540.31612	85030.81812	82458.357	82227.36133	40784.31728	21722927.74	16655856.69	11762686.78	8372178.328	15270874.14	32751602.95	32176786.91	22047501.92	4865634.391	5663472.741	9094044.96	5252771.472	7206943.954	4906601.503
Diethanolamine	6019818.662	4578297.583	2739641.831	2536239.324	28246204.35	13087365.92	0	37950713.52	29398288.76	56009352	69212838.81	228769832.8	70248253.12	52636474.02	55481761.37	24393194.77	38210790.49	24552438.02	21014388.54	26033452.51	32240561.79
2-Amino-2-deoxy-D-mannose	0	0	0	0	19859.84139	0	113603.2744	7703582.81	4600777.394	1854919.658	6570753.866	18083507.67	5092050.848	58193443.52	52915250.37	17916933.49	21443727.24	27059563.97	25758773.73	31732073.71	23617624.79
D-Ornithine	1867536.692	1950273.923	2512058.879	3608446.325	796664.7927	859082.5488	870435.5374	2294659072	2024330669	1402673279	1946519646	759177398.7	2095061296	951389809.8	677380159.1	529663920.4	470506522.1	500177448.7	499516522.9	745234880.3	494868369.6
Ethyl 3-indoleacetate	162591.2987	189713.1094	17104.88771	11044.86584	154784.7349	95459.59066	128529.4367	5986975.068	11526885.14	9848942.627	15020790.8	5067606.82	5242953.964	0	701814.8561	3655865.454	7984336.553	1704780.372	3948798.678	5985532.578	4209466.161
FAD	0	0	0	0	0	0	0	13608951.14	21597601.61	1038570.249	17599709.8	45699838.06	17641787.66	82958499.99	21061223.11	30828733.06	32890370.83	22340999.08	39048608.66	39903666.33	32151264.53
Glucosamine	0	0	0	0	19859.84139	101792.2275	111943.1755	7703582.81	4600777.394	1854919.658	6570753.866	18083507.67	5092050.848	58193443.52	52831861.22	18023675.13	21443727.24	27059563.97	25758773.73	31732073.71	23617624.79
Glutamine_13C1	257354.0765	22222.23958	59004.80537	174961.6141	177768.3909	327040.9348	137022.5791	341147351.8	323281396.4	252586937.7	225302803.1	283094149.4	316320971.7	363391840.8	688949602.5	297497583.7	179664193.1	268277226.3	349524742	457888650.7	292041386.6
Glutamine_13C2	15141.3651	0	21145.58161	12520.56339	12836.53061	24764.76342	34424.30615	100007885.5	90814165	37025238.56	63725794.03	94795235.42	97064417	111639928.6	127158438.2	101310289.9	59176150.54	93138690.68	127323279	116648210.5	96157755.7
Glutamine_13C3	23621.5434	108265.2524	109155.5777	78584.08207	79710.73563	138508.6267	160263.7667	82524812.66	71867252.75	23034201.31	44262578.96	79670863.67	65448284.96	78036368.29	64295058.88	70658414.03	47707768.68	72624922.02	102743701.3	75051380.91	87378868.01
Glutamine_13C4	390541.8204	179783.2034	0	0	73072.22088	0	0	13175818.93	12535680.33	5116155.347	5219725.789	12880478.78	9958972.095	11916603.36	9276376.372	12870965.73	8672632.126	12212861.83	19861759.31	11451428.78	16026721.79
Glutamine_13C5	42821.70213	50769.5278	81128.08976	50541.99593	278005.5592	263902.423	44670.04201	249745426.1	194859141.9	111312107	104206062.5	237838616.3	157878591.2	240648817.5	242050193.1	218715498.2	161192351.6	240839814.1	383718703.8	248880123.1	319845108.6
Glutamine_13C5_15N2	3226016.655	915607.1799	1908013.745	42333058.58	2305718.508	2419937.575	1195250.491	4831717415	5219623508	7614313092	2262684046	1889201308	2450137707	1158084215	792586377.3	726793580.7	1058153448	2858091048	1670923275	600624743	1259804808
Glutamine_15N1	52914.10905	28757.17407	0	25443.31372	37937.90829	87458.91897	69927.9327	1908355663	1638474879	936511032.5	1034033339	1295922645	1609394351	1559351550	1650760119	1092570068	1070966497	1639546337	1887233853	1368779992	1672928346
Glutamine_15N2	32221.02866	11549.73076	44077.84512	10930.43442	8933.091032	9206.807063	22163.42292	312553087.5	265644880.2	94862745.6	178927069.2	203963028.6	303891930.8	187722449.7	77142744.15	126628224.9	205889708.5	340851289.4	364574628.3	99612975.96	282598102.8
CAR DC5:0	45464.53429	44742.65374	34409.47561	36752.49863	14062.48677	59530.49782	63984.68777	504658405.9	338698455.2	44781587.51	1153717317	837645817.7	376859101.1	2296808823	1152947533	162822482.7	365383831.6	333467572.5	234709829	306629255.4	229935395
Glutathione	741630.2461	489534.0044	395112.1328	277826.7152	74546.1334	245116.5559	114432.3139	1882649.785	2148473.952	420889.8665	5452265.451	811011.4548	1881140.633	0	8970034.393	6429510.823	310832216.8	7191074.782	358172.9772	615447.701	8362938.57
Glycine	75419561.14	39236120.42	19507988.59	8371694.8	1357990.104	2573744.486	583186.6824	137664048.4	120895101.2	111107155.4	93223790.3	67148670.56	139615556	213561118.7	314754244	122571950.5	71039940.9	173559561.2	117011225.3	191673431.1	103192631.6
Glycine_13C1	1610101.94	845143.6608	413859.3186	119365.2141	0	0	9743.5814	3150731.662	2297590.335	2738365.373	2199904.354	1293195.821	2707606.59	4985027.454	6477895.001	3565449.552	1792103.047	4723777.797	2885860.879	4539357.595	2630265.952
Glyoxylic acid	50028.89954	45624.16804	113589.7659	49675.25197	9938.741911	42484.76928	56275.88394	1648006.47	1375606.528	715503.8247	1595200.962	2614521.721	1765920.838	9958183.364	7577863.659	2234058.578	2137733.522	3854078.052	3298868.793	4528552.555	2862272.518
Oxidized glutathione	0	0	0	0	0	0	0	688835966.8	463239374.8	448567243.4	925709024.2	879609755.5	494889645.8	2092210069	2416366214	603678330.2	473043824.5	958057062.6	728234643.2	941727141	588560410.5
Guanidinosuccinic acid	0	0	0	0	0	0	0	364292.5081	198590.3398	246725.0677	922312.513	5475565.802	149750.2724	2026841.54	10767605.48	2473103.282	331033.4371	4236933.67	2024241.058	5125783.245	6057348.444
Gulose	192983.6416	28309.04825	110957.231	115973.8339	75842.62006	104257.9937	187092.0435	63891299.93	37296897.59	22342201.38	59642803.61	122921462.5	61894111.2	653556700.5	505532983.4	118131841.7	123261778.6	218099055.9	181088341.3	230045987.1	171860701.1
Homocysteine	0	0	0	0	7747.224169	0	0	8100853.636	7610999.96	5410988.931	5108937.475	1577158.582	8329585.312	5361130.956	0	222906.7526	2147244.619	1443871.913	827369.8693	121033.592	1019376.121
Homoserine	3715012.898	3308982.089	1526036.344	963486.8492	724152.7533	783632.0425	806094.7905	977730869.9	1144486373	1018726198	512324848.5	426279708.5	906552776.5	614706440.5	995142661.5	274366535.9	238814444.7	461591759.2	362324761.3	541857309.3	295500699.1
Hypotaurine	0	0	0	0	0	0	0	80247693.51	50064253.56	43236027.56	35684393.21	14418088.77	49453303.54	5328105.998	0	134062273.9	55362620.95	12604746.18	66414357.95	53614206.02	90697964.02
Hypoxanthine	1174279.59	913545.0465	533199.1126	459357.0607	241145.5136	290010.3883	298703.6792	522384470.6	837437782.7	385966815.6	564265593.1	839294381.2	977376176.3	881971638.3	652511986.8	179432161.6	276267473.2	182461056.5	165530601.8	529333373.7	100555150.1
Indole-3-methyl acetate	85727.40713	18338.06331	34672.34019	0	0	0	39225.75907	93373.48946	0	1754758.009	3590530.006	3469783.886	1537528.706	627041.8366	1529510.155	889795.5032	1832326.321	1118640.802	624527.2961	639287.2036	1013092.725
Inosine	183857.7448	125223.2403	151243.4303	203126.7551	111516.1333	219309.7817	67602.36642	1098438345	1151198025	2281802653	1434100063	514854978	1670250701	2093436227	2364965427	612666926.6	997781018.3	883308881.9	231301112.3	985477023.2	966339581.7
Kynurenine	0	0	0	0	0	0	0	24125508.98	22853879.72	15408863.32	18130321.89	6004757.728	26415401.39	22536672.19	18044335.14	3438849.657	4017827.157	5684036.86	3147879.603	9370399.485	4859958.409
Alanine	4345236.001	2428377.475	1800045.591	1891064.191	1384982.817	1500292.546	997620.5206	1127973287	1055727319	1156332143	1316253812	982004212.8	1253692621	1768364648	1508170027	722892079.3	731974162	679868120.1	872650802	1123818717	1114797037
Alanine_13C1	1784654.053	1759923.101	2010200.391	1556141.156	1403989.709	980155.9214	1617681.377	83574520.5	70478524.99	50331417.17	88360767.4	69284788.31	86187012.98	98838479.22	57264183.25	35172643.4	41885615.93	36476254.01	47046729.5	46347318.54	62256461.35
Alanine_13C2	168463.2897	106401.4466	208400.8181	102727.4894	103756.3332	70718.37472	82283.58666	46798211.8	44526959.41	29549705.41	40863873.81	33197715.32	54931429.29	20909620.6	5184250.808	7931727.812	14305649.32	9793795.662	16067804.34	10389078.4	21819504.29
Alanine_13C3	11767.25736	8721.158554	0	8561.105372	8706.965484	9128.670938	0	106462882.3	87922154.69	48107116.7	68012746.55	48595131.61	80491998.65	36464126.04	348789.0944	8920622.855	23409544.9	11827144.38	23008225.96	7344607.205	25602646.73
CAR 12:0	0	0	0	0	0	0	0	6929698.47	3074435.17	3395218.528	3111439.716	4520160.589	4921923.006	91994.8096	471240.3915	0	491460.4248	701206.5252	125936.879	348602.6867	183936.6423
Carnitine	25926780.45	4033089.526	6796833.568	5219733.286	8475929.883	13505088.52	7598545.135	26454952799	25649640685	8776827061	25657822849	37510462182	25953958975	84911426233	42683702066	10725933694	16633589827	20582202519	12290905919	15525435208	11734021312
Leucine	2694126037	1398909361	631130081.4	230673138.2	27490347.51	12790217.67	7407309.137	3197115803	2889774005	2381152014	1898332067	1508683775	4081078018	5220693968	5081289542	1168213796	1486609224	2004003453	1806802208	2661390367	1707205746
Leucine_15N1	8386507.448	5575240.302	2298736.011	826216.2194	166624.6129	0	0	94404858.91	116770592.1	97581814.74	54245202.7	53527396.47	85158650.38	96943085.63	34232499.76	28306022.35	32776524.77	31980949.3	41049646.28	32393928.79	41299702.1
Ornithine	1867536.692	1950273.923	2512058.879	3608446.325	796664.7927	846578.0408	892383.8934	2291049211	2024330132	1399736513	1946519646	759177398.7	2088967555	950411883.8	676241293.7	528519659.8	468934090.2	500035761.9	498060900.4	745234880.3	494868369.6
Lumichrome	10018.24245	0	0	0	0	0	0	43922592.1	15182489.02	14965459.33	19059918.53	36998700.77	20487736.04	224622306.7	143752351	5820164.099	12756970.71	61280214.68	8931889.915	23327540.63	11008713.56
Lysine	4500974.565	2296212.393	1571610.79	957232.2778	441648.6233	658697.7646	606859.9313	5026132510	4201317270	2604594418	1796615363	896767851.2	3203839171	1994451765	1812714932	547236325.5	550599090	866290632.3	603006016	1156102968	755840508.2
Methionine	44023.62514	24602.23137	57996.04123	0	53545.02804	0	9725.421354	600333162.4	1212518428	1101782506	187616822.7	131785427.3	659308500.7	90401087.73	88375265.71	208907865.4	138316141.2	224201154.8	253967448.9	272176724.7	260131945.1
5'-Methylthioadenosine	0	0	0	0	0	0	0	249980764.9	128004391	92269833.63	180502440	264341835.2	164185752.7	1001510713	586248358.4	87411489.52	143506069.9	303733661.5	147756460	129570833.9	107762225.8
N-6-Trimethyllysine	220681.818	68275.99301	0	24544.74364	23369.71838	133458.849	23524.83597	289379200.3	366920022.5	221463618.1	246685309.5	192698064.2	287128306.4	248333918.4	246413991.1	69465352.55	118477776.1	123962098.6	66038306.34	101568184.1	93964569.76
Dimethylarginine	41233.78066	12277.73221	0	28404.50022	0	14019.53589	0	252879092.5	194373974.3	141757002.5	270271948.9	170587192.7	214023075.3	170617703.2	124622046.1	51874412.8	79746348.92	75798001.22	61739249.79	89197850.93	57079861.86
N-Acetylasparagine	11318.03604	0	25877.29487	0	0	0	0	39195903.84	31085649.06	23582490.19	15987476.81	32272491.61	14918145.4	55648306.85	97449997.54	33430893.28	14504945.04	33104993.33	29145800.95	53670984.27	27810435.47
N-Acetyl-D-galactosamine	6781106.346	2693262.17	1457318.431	681389.2024	24738.60077	22605.30522	0	46046923.62	36302889.88	30192155.73	22460785.19	8453017.886	49451614.62	40009297.15	44841723.86	5363712.489	7689464.348	11819562.44	6246106.813	11431420.43	6121344.243
N-Acetyl-D-glucosamine	6781106.346	2693262.17	1457318.431	681389.2024	24738.60077	22605.30522	0	46046923.62	36302889.88	30192155.73	22460785.19	0	49451614.62	40009297.15	44841723.86	5363712.489	7689529.3	11502426.43	6242824.113	11201041.17	6121344.243
N-Acetyl-mannosamine	6781106.346	2693262.17	1457318.431	681389.2024	24738.60077	22605.30522	0	46046923.62	36302889.88	30182258.44	22460785.19	8054703.398	49451614.62	40009297.15	44841723.86	5363712.489	7689529.3	11644884.23	6242824.113	11265541.45	6121344.243
NADP+	0	0	0	0	0	0	0	9376744.483	5172694.766	47803.55358	5243438.267	72163998.12	3623400.782	57617780.13	39331181.38	23276770.4	24653224.09	45627693.53	44639189.83	35541392.75	28669160.8
N(2)-Acetyllysine	246239.9815	0	155442.3814	104475.7203	234631.1094	52149.46856	0	169299295.4	187738699.8	132668341.2	86600230.19	74045205.06	76673833.3	262478755.8	235111104	108337232.4	86099288.09	144502623.3	102538697.5	136336398.2	85244936.26
N-ETHYL-5-METHYL-2-(1-METHYLETHYL)-CYCLOHEXANECARBOXAMIDE	23664.92331	38505.75254	40277.94997	0	0	59292.4087	12811.15666	490720.8361	130913.4799	160744.5731	1575850.614	3219193.281	462647.8041	376495.3128	938715.3381	525723.4853	1197265.211	561382.9819	382478.3843	477917.53	540096.1327
N-Formylglycine	10842.74011	41714.48453	48689.03164	0	107890.6289	54884.86436	0	6232223.024	4258554.917	2273955.216	6072689.103	3585849.832	3072691.594	9426003.969	7473946.287	2208769.367	1914607.697	3741448.533	3316862.048	3494378.131	1994971.838
Niacinamide	16021288.05	8546419.898	5545531.477	3743243.834	2060444.056	414910.9213	1070706.631	17005389309	14701288914	7896402665	12522682321	19769081081	14338188655	33676570029	31867207197	9384857317	8992051223	16406063539	9856767012	14328279772	9681309438
Nicotinamide ribotide	0	0	0	0	0	0	0	9507010.394	2947698.848	2072885.847	7676590.089	13159958.54	3133844.05	97799837.67	88756093.66	5038220.21	11000766.89	30600979.46	7091707.904	12099494.68	10246337.16
Nicotinic acid	391441.0066	65346.745	127501.1139	146473.321	0	142998.5632	0	56119839.93	6849570.352	6900846.492	15116930.88	16803744.14	4371587.92	10121713.78	25136506.8	9719800.174	13904499.18	8270066.89	25113848.42	15217731.33	36128444.07
N-METHYL-ALANINE	0	0	0	0	0	0	5317027.259	948560198.4	738455236.4	244422660.2	499677174	234238141.6	810169503.4	966607497.8	1049761573	414711949.4	379094708.4	561652225.4	385962412.8	557929588.9	359910867
Norleucine	2694126037	1398909361	631132089.5	230782124.8	27857334.42	12897482.28	7409403.643	3197115803	2889774005	2381152014	1898332067	1508683775	4081078018	5220693968	5081289542	1168213796	1486609224	2004003453	1806802208	2661390367	1707205746
Norvaline	1157142593	604225273.7	289786183.5	129953749.4	30552067.58	34290156.24	33483767.48	97312858398	59359110083	36047499314	90260243156	53708417374	76254472679	1.09393E+11	88419273186	32172839611	58035128998	59545405679	46066825030	45602420636	26884140255
CAR 2:0	15819715.54	1281054.437	2612055.492	2121132.03	2615244.164	3878304.256	2233287.562	13340523368	11247635319	4533443794	13397814310	19840095345	14123597077	44030199591	25105592587	6597154553	12066693347	15473591130	8569381968	11165088722	8577756980
Phosphoethanolamine	15000.36621	0	0	0	0	0	0	543382363.3	580384272.5	212537796.4	315866548.1	161313103.4	487319922.3	313136036.8	251246765.3	51535007.16	71966188.42	121519270.6	61960285.35	88282996.23	51586180.57
Ophthalmic acid	0	0	0	0	0	0	0	470900044.8	343002270.6	131125430.5	253514313.1	132555319.5	362573814	445530905.3	524821636.8	100884520.3	102753102.5	82660668.5	78244176.8	84206454.37	64013318.85
o-Succinylhomoserine																					
Pantothenic acid	2591125.312	970873.1673	1098795.612	775992.9859	913745.2766	1075121.94	860513.9024	455840557.1	439317403.8	537043219.9	277831185.4	343710684.2	390678926.2	1564435629	840242497.4	140948822.5	256810520.1	327331776.2	162078011.2	206533491.2	147470832.3
Phenylalanine	6372480.686	3999699.798	2007119.715	1309018.52	560355.5691	439905.8607	694966.1719	3105521168	2283857620	4358332991	1695593673	1096536185	3448623721	4790254385	3406240554	539680002.1	782560181.6	1315909493	870083828.1	1345222234	888809110.1
Choline phosphate	9439424.044	1064247.944	1288437.459	1231007.359	1651740.473	2016866.983	1077709.333	4800408507	5258729950	1276793761	5769057551	7243775883	7275927447	10704067160	16337459162	5792034877	1733874165	8839936461	5769948722	6153731374	3432473633
Octopamine	3425087.597	1126961.43	2129058.679	41992944.23	2273724.893	2721646.553	1525585.263	4840444313	5226278298	7785168813	2257050522	1883231173	2454703069	1162635950	796004400.6	722741887.5	1051149395	2852597897	1662843748	598610047	1245515394
Proline	11282641533	6465763308	3325791336	1274659527	152724373.5	67144557.55	40271993.52	10965031876	9959739733	9010053811	9597406403	4922277458	11265130202	13392809895	11854273323	3334970023	3810980992	5253107447	5166507093	8075713222	4821826179
Pterin	0	0	0	0	0	0	0	966124.9197	5371836.124	0	0	18854391.95	0	13443826.12	23239246.05	9247846.565	12112607.87	32640083.92	16399195.9	15367874.44	12703715.23
Pyridoxal	367921.8375	110174.0744	795603.0633	91412.90749	79511.37205	200437.6451	48944.32847	271266169.1	205161807.6	361041254.8	446870810.3	156884107.8	444292727.2	1066174798	544954599.5	224170904	408769851	207174026.8	101050260.3	223809575	181226871.2
Pyridoxamine	468628.8112	436377.5349	192491.3011	0	0	0	111421.3925	23304741.29	15477471.39	59686148.88	58729355.73	12742810.68	34512984.83	18713999.22	11303891.54	11289016.79	29210341.25	6623132.347	7748763.863	10342268.95	12712713.18
Pyridoxine	0	734364.5803	604684.058	425290.0051	441276.3358	334520.0925	295866.4657	3578989.414	7988225.435	3415185.15	4655594.371	2952905.861	4639763.618	5874700.712	8046348.449	5246154.481	3602312.515	4839072.788	4824650.851	5997569.588	3526035.403
Riboflavin	0	0	0	0	0	0	0	31410233.78	10813566.08	54859599.74	33193810.01	3560292.449	22380559.72	60633989.9	55872057.06	2890268.58	9058268.44	11939136.46	1962187.679	6636626.32	3709439.459
S-Adenosylhomocysteine	12862.11243	0	0	0	0	0	0	429581768.2	412355665	183998802.1	504687018.9	450592596.9	336054699	716181988	800868968.7	449399089.9	472775828.4	395759638.4	511478668.5	794370150.2	362283247
S-Adenosylmethionine	13081.00159	0	0	0	0	0	0	162744254.1	125270736.6	103320084.7	146145456	138051166.1	159639932.1	307049465.7	206985636.9	97994959.52	110785645.8	138055426.6	125115687.2	95643336.81	111375629.9
Sarcosine	3227066.988	1417116.911	1102998.076	1924304.263	905779.1565	1386116.725	944008.6941	1162018286	1083659380	1195562846	1359430585	1008017644	1298587731	1870684111	1560646446	743082297.8	747143091.4	697560101.8	890025970.6	1152039321	1132736753
Serine	221650072.5	106804821.9	54275914.69	26002173.22	2474251.722	1436052.465	1104740.623	102543796.7	116213113.4	132222232.3	79196208.83	64951836.54	148896732.4	110054836.9	181933535.4	53397446.68	37707369.86	86261517.37	62694357.94	96568648.81	56575805.96
Taurine	3753564.792	1167583.311	2593221.989	1342538.485	1936032.308	3448185.652	1521408.844	4793248468	3873020252	3349332722	5440274425	10183332950	4907139242	21487639026	16663670766	6639845685	7045283273	10829554193	7254806108	9476420885	7087942540
trans-4-Hydroxyproline	987232.3142	198529.5643	34517.01082	772669.565	231343.8337	0	0	90826122.22	63765787.14	18200960.6	358251525.6	88507258.46	60856547.73	228354129.4	413976952	261361399.3	191754010.9	249229325.6	183610872.8	280999428.4	164085233.2
Trigonelline	1508541.961	785502.6769	461682.6579	540065.1142	235521.8785	445170.7828	406591.9676	777371998.2	339403104.3	185424106.9	1701157820	3896108960	624665245.9	9514999962	11091071141	3299345635	1873681626	6667662927	3241640521	5010003913	1857632088
Tryptamine	93008.07796	33426.26289	60959.00828	69687.68828	0	33498.17754	124701.5058	248964.1513	308644.5576	52615.14483	2029933.643	625486.0908	811665.8259	1527669.232	690584.6608	670869.3801	562112.7791	411520.4746	603454.725	672823.3644	522477.4222
Tryptophan	69934.80939	65521.18859	133210.7338	40180.67545	10449.55997	12110.70505	12322.17521	77580073.7	145346752.4	114775538.2	98537150.24	29979268.86	302794725.9	7577179.565	834733.5685	73805344.68	90188083.94	1218733.279	91939074.41	60594072.05	87282960.24
Tyramine	167039.8724	70458.87787	54388.59192	38284.57282	271207.437	21746.50161	82562.44377	504645.7554	519775.0957	497668.6719	1059813.427	596649.6741	467566.446	316589.719	528260.8391	350709.4334	544398.1988	411646.0678	343756.3052	500004.7526	319794.7523
Tyrosine	264682.9568	136168.433	405492.5729	750594.9028	194346.7372	281438.7569	366891.268	1300404119	1577564758	2127451788	628647687.3	320427218.6	1250824455	839783479.9	526119959	165407569.3	245355095.2	293863166.8	223717949.7	343774140.6	188794474
UDP-N-acetylgalactosamine	0	0	0	0	0	0	0	40742695.36	25683452.21	29200313.33	36129988.17	45544548.04	40992867.53	150458386.4	146470663.2	26560087.31	32057561.65	43441004.94	33464561.49	48946165.38	28637000.92
Valine	1156975910	604217890.2	289822697.4	129895967.1	33456324.78	34245332.41	33483767.48	97312858398	59359110083	36047499314	90260243156	53708417374	76254472679	1.09393E+11	88419273186	32172839611	58035128998	59545405679	46066825030	45602420636	26884140255
Xanthine	0	0	0	0	0	0	0	20405837.68	9085560.686	6791820.384	20522647.75	6134308.644	28048830.23	73802581.07	67799715.83	3691056.942	7983769.916	14511501.28	3362289.989	13898119.08	2904724.576
XMP	0	0	0	0	0	0	0	5829406.843	1494320.384	0	1560330.739	60072.67543	3877124.779	13051685.7	8285497.425	187991.7765	1533710.252	4811013.662	251602.3206	1298636.476	171848.6971
Xylose	445617.5206	194487.1369	473887.837	320280.1758	370551.8849	97868.12311	76703.88105	3625597.916	3126393.583	3389269.576	6067020.805	3969839.632	2879348.184	17150822.54	13476567.83	4507801.368	4091408.834	9167023.697	5434335.787	6414018.875	4318557.8
Adonitol	48997.07996	76069.80304	17011.85558	72189.94106	58809.08286	24679.20839	49287.70523	892411637.9	655635449.4	362180577	171564008.8	48585290.08	314013052.7	130834180.3	26108010.12	27888918.11	65090055.13	48095702.77	49897616.91	19410612.99	27597190.02
Ribose 5-phosphate_13C1	0	0	0	0	0	0	0	6023444.565	3672025.832	494082.2878	2744322.422	9156713.304	6192068.91	12135556.33	9833930.832	2722274.877	2220827.527	5517954.806	2980006.175	3975305.222	2760116.039
Ribose 5-phosphate_13C2	236004.1589	57670.0095	784.5369307	0	0	0	0	1908732.9	882601.8133	87446.27878	486608.5498	1695260.336	1264817.591	2471405.103	2350155.379	512431.0487	391837.1013	1253162.209	560585.8907	744607.1703	482651.4111
Methylmalonic acid_13C1	14185366.71	6657027.534	2912891.212	1083032.94	96822.97577	33114.63614	12321.39779	52805770.25	52663388.13	22624130.68	67379711.59	76430703.76	35973810.54	197838929.1	61169233.7	30078404.3	52140182.97	53386050.31	41224486.33	37864078.56	31979125.16
Methylmalonic acid_13C2	2622626.178	1208798.779	469068.8922	0	0	0	0	59276075.99	58695304.91	27560024.62	42451620.34	35107337.44	28384035.1	72786859.11	15168474.83	11388497.22	23449298.93	24342875.58	18288223.97	11658412.35	14227499.24
Methylmalonic acid_13C3	20381.63653	22597.8821	4696.84661	0	0	3715.527674	0	33195607.68	31671196.97	15491428.18	22990894.07	18725877.47	11679826.02	54703488.36	4581995.817	7128356.154	19067007.63	13267371.93	12554041.71	6912906.606	10132728.52
Serine_13C1	7357278.431	3549214.705	1766617.101	811124.6126	0	0	0	3387653.665	4094223.426	4602041.668	1867320.097	1822430.271	4931188.394	2551828.137	4574412.179	1738495.14	870040.8525	2983668.368	2017822.149	3329149.023	1501122.832
UDP-glucose_13C1	0	0	0	0	0	0	0	22144430.17	17372085.32	8368527.639	34732749.28	29782499.76	40253226.56	164457711.1	143839606	39693074.58	42605385.14	65461257.32	44852016.33	53608877.68	40661786.76
UDP-glucose_13C2	0	0	0	0	0	0	0	15463850.05	11075543.44	5377811.833	17275045.25	13821062.28	22941202.53	57337414.8	41158177.1	13571207.35	16434334.25	24297555.34	16741117.22	16976158.78	14418557.47
UDP-glucose_13C3	0	0	0	0	0	0	0	22506898.58	14651385.65	7145824.593	16967379.23	12771902.45	26944032.6	31743896.8	8353220.642	7581228.776	11972430.09	16293471.79	11236198.94	7355914.017	8677512.013
UDP-glucose_13C4	0	0	0	0	0	0	0	7904243.814	5072810.803	2143494.884	7124923.674	3526768.324	9516138.906	8320214.118	1835348.385	1391027.792	5817687.133	2703732.288	96026.47617	18280.63777	278995.9403
UDP-glucose_13C5	1906.140614	0	0	0	0	0	0	5000231.844	3030365.604	1225680.149	3664744.318	1549761.488	5161596.717	1919047.059	0	0	2023.242134	0	0	0	0
UDP-glucose_13C6	0	0	0	0	0	0	0	4383583.771	2515642.636	1001589.252	2562576.509	1054616.411	3587644.602	2128003.616	0	49534.56371	52329.23504	36057.84005	0	0	9791.694925
MS_METABOLITE_DATA_END
#METABOLITES
METABOLITES_START
metabolite_name	Retention index	Quantified m/z	PubChem ID	KEGG ID
Ciliatine	9.82	126.03146	339	C03557
1-Aminocyclopropanecarboxylic acid	6.86	102.05496	535	C01234
1-Methyladenosine	11.3	282.11968	27476	C02494
1-Methyl nicotinamide	12.3	138.07876	457	C02918
Aminoisobutyric acid	7.45	104.07061	6119	C03665
2-Aminophenol	3.08	110.06004	5801	C01987
2-Hydroxypyridine	4	96.04439	8871	C02502
3-Hydroxyanthranilic acid	6.61	154.04987	86	C00632
3-Methylhistidine	6.97	170.0924	64969	C01152
Nitrotyrosine	8.66	227.06625	65124	-
4-Guanidinobutanoic acid	8.38	146.0924	500	C01035
5-Amino-levulinic acid	7.66	132.06552	137	C00430
5-Aminopentanoic acid	8.71	118.08626	138	C00431
5-Methylcytosine	4.66	126.06619	65040	C02376
Acetylcholine	7.78	147.12538	187	C01996
Adenine	4.38	136.06177	190	C00147
Allothreonine	7.89	120.06552	99289	C05519
alpha-Aminoadipic acid	9.22	162.07608	469	C00956
3-Aminoisobutanoic acid	7.7	104.07061	64956	C05145
Anserine	7.56	241.12952	112072	C01262
Arginine	13.19	175.11895	6322	C00062
Asparagine	8.46	133.06077	6267	C00152
Asparagine_15N1	8.46	134.0578
beta-Alanine	8.64	90.05496	239	C00099
Betaine	5.62	118.08626	247	C00719
NAD+	8.62	664.1164	5893	C00003
Caffeine	2.51	195.08765	2519	C07481
Carnosine	8.77	227.11387	439224	C00386
Choline	9.75	105.11482	305	C00114
cis-4-Hydroxy-D-proline	8.37	132.06552	440014	C03440
Citrulline	9.09	176.10297	9750	C00327
Coenzyme A	8.42	768.12248	87642	C00010
Creatine	8.09	132.07675	586	C00300
Creatinine	4.56	114.06619	588	C00791
Cystathionine	9.83	223.0747	439258	C02291
Cysteic acid	9.84	170.01177	25701	C00506
Cystine	9.85	241.03112	67678	C00491
Cytidine	6.13	244.0928	6253	C00475
D-Alanine	8.11	90.05496	71080	C00133
D-Alanine_13C1	8.11	91.05831
D-Alanine_13C2	8.11	92.06166
D-Alanine_13C3	8.11	93.06502
D-Alanine_15N1	8.11	91.05199
3-Dehydroxycarnitine	7.16	146.11756	134	C01181
Dethiobiotin	3.95	215.13902	445027	C01909
Diethanolamine	7.88	106.08626	8113	C06772
2-Amino-2-deoxy-D-mannose	7.81	180.08665	440049	C03570
D-Ornithine	11.73	133.09715	71082	C00515
Ethyl 3-indoleacetate	2.23	204.10191	13067	NA
FAD	6.75	786.16441	643975	C00016
Glucosamine	7.88	180.08665	439213	C00329
Glutamine_13C1	8.48	148.07977
Glutamine_13C2	8.48	149.08313
Glutamine_13C3	8.48	150.08648
Glutamine_13C4	8.48	151.08984
Glutamine_13C5	8.48	152.09319
Glutamine_13C5_15N2	8.18	154.08726
Glutamine_15N1	8.48	148.07345
Glutamine_15N2	8.48	149.07049
CAR DC5:0	7.47	276.14416	71317118	NA
Glutathione	9.5	308.09108	124886	C00051
Glycine	8.93	76.0393	750	C00037
Glycine_13C1	8.93	77.04266
Glyoxylic acid	7.94	72.99312	760	C00048
Oxidized glutathione		613.15924	65359	C00127
Guanidinosuccinic acid	9.51	174.05203	439918	C03139
Gulose	7.97	179.05611	10130220	C15923
Homocysteine	9.38	136.04268	91552	C00155
Homoserine	8.32	120.06552	12647	C00263
Hypotaurine	8.55	110.02703	107812	C00519
Hypoxanthine	5.21	137.04579	135398638	C00262
Indole-3-methyl acetate	2.39	190.08626	74706	NA
Inosine	5.59	269.08805	135398641	C00294
Kynurenine	5.4	209.09207	161166	C00328
Alanine	8.16	90.05496	5950	C00041
Alanine_13C1	8.16	91.05831
Alanine_13C2	8.16	92.06166
Alanine_13C3	8.16	93.06502
CAR 12:0	2.37	345.28736	168381	NA
Carnitine	7.19	162.11247	10917	C00318
Leucine	5.38	132.10191	6106	C00123
Leucine_15N1	5.38	133.09894
Ornithine	11.72	133.09715	6262	C00077
Lumichrome	2.8	243.08765	5326566	C01727
Lysine	12.71	147.1128	5962	C00047
Methionine	5.95	150.05833	6137	C00073
5'-Methylthioadenosine	2.76	298.09684	439176	C00170
N-6-Trimethyllysine	11.4	189.15975	440120	C03793
Dimethylarginine	10.64	203.15025	123831	C03626
N-Acetylasparagine	6.72	175.07133	99715	NA
N-Acetyl-D-galactosamine	6.02	222.09721	35717	C01074
N-Acetyl-D-glucosamine	6.34	222.09721	439174	C00140
N-Acetyl-mannosamine	6.54	222.09721	439281	C00645
NADP+	10.69	744.08273	5886	C00006
N(2)-Acetyllysine	8.34	189.12337	192590	C12989
N-ETHYL-5-METHYL-2-(1-METHYLETHYL)-CYCLOHEXANECARBOXAMIDE	2.35	212.20089	62907	NA
N-Formylglycine	6.15	104.03422	75606	NA
Niacinamide	3.33	123.05529	936	C00153
Nicotinamide ribotide	9.28	335.06388	14180	C00455
Nicotinic acid	4.14	124.0393	938	C00253
N-METHYL-ALANINE	7.03	104.07061
Norleucine	5.25	132.10191	21236	C01933
Norvaline	6.3	118.08626	439575	C01799
CAR 2:0	5.34	204.12303	7045767	C02571
Phosphoethanolamine	9.76	142.02637	1015	C00346
Ophthalmic acid	7.88	290.13466	7018721	C21016
o-Succinylhomoserine	7.95	220.08156	439406	C01118 
Pantothenic acid	4.41	220.11795	6613	C00864
Phenylalanine	4.87	166.08626	6140	C00079
Choline phosphate	9.06	184.07332	1014	C00588
Octopamine	7.73	154.08626	440266	C04227
Proline	6.76	116.07061	145742	C00148
Pterin	5.73	164.05669	135398660	C00715
Pyridoxal	4.11	168.06552	1050	C00250
Pyridoxamine	5.34	169.09715	1052	C00534
Pyridoxine	3.86	170.08117	1054	C00314
Riboflavin	3.68	377.14556	493570	C00255
S-Adenosylhomocysteine	7.3	385.12886	439155	C00021
S-Adenosylmethionine	8.24	400.15234	34756	C00019
Sarcosine	7.67	90.05496	1088	C00213
Serine	9.02	106.04987	5951	C00716
Taurine	8.37	126.02194	1123	C00245
trans-4-Hydroxyproline	8.16	132.06552	5810	C01157
Trigonelline	5.94	138.05496	5570	C01004
Tryptamine	10.28	161.10732	1150	C00398
Tryptophan	5.9	205.09715	6305	C00078
Tyramine	9.34	138.09134	5610	C00483
Tyrosine	6.9	182.08117	6057	C00082
UDP-N-acetylgalactosamine	9.61	608.08885	1167	C00203
Valine	6.55	118.08626	6287	C00183
Xanthine	6.4	153.0407	1188	C00385
XMP	11.63	363.03474	73323	C00655
Xylose	6.97	149.04555	135191	C00181
Adonitol		151.0612
Ribose 5-phosphate_13C1	9.59	230.01523
Ribose 5-phosphate_13C2	9.59	231.01859
Methylmalonic acid_13C1	9.38	118.02269
Methylmalonic acid_13C2	9.38	119.02604
Methylmalonic acid_13C3	9.38	120.0294
Serine_13C1	9.02	107.05322
UDP-glucose_13C1	10.4	566.0511
UDP-glucose_13C2	10.4	567.05445
UDP-glucose_13C3	10.4	568.05781
UDP-glucose_13C4	10.4	569.06116
UDP-glucose_13C5	10.4	570.06452
UDP-glucose_13C6	10.4	571.06787
METABOLITES_END
#END