#METABOLOMICS WORKBENCH alanyl_20250321_120547 DATATRACK_ID:5767 STUDY_ID:ST003821 ANALYSIS_ID:AN007472 PROJECT_ID:PR002390
VERSION             	1
CREATED_ON             	December 17, 2025, 12:58 pm
#PROJECT
PR:PROJECT_TITLE                 	In vivo CRISPR screen identifies copper metabolism as a vulnerability in acute
PR:PROJECT_TITLE                 	lymphoblastic leukemia
PR:PROJECT_SUMMARY               	The nutrient-sparse cerebrospinal fluid (CSF) poses a significant challenge to
PR:PROJECT_SUMMARY               	spreading cancer cells. Despite this challenge, leukemia often spreads to the
PR:PROJECT_SUMMARY               	CSF and represents a significant clinical complication. To uncover nutritional
PR:PROJECT_SUMMARY               	dependencies of leukemia cells in the CSF that could be targeted
PR:PROJECT_SUMMARY               	therapeutically, we conducted an in vivo targeted CRISPR screen in a xenograft
PR:PROJECT_SUMMARY               	model of leukemia. We found that SLC31A1, the primary cell surface copper
PR:PROJECT_SUMMARY               	importer, is a genetic dependency of leukemia in both the central nervous system
PR:PROJECT_SUMMARY               	as well as in the hematopoietic organs. Perturbation of copper metabolism leads
PR:PROJECT_SUMMARY               	to complex IV deficiency, perturbed nucleotide metabolism and slowed leukemia
PR:PROJECT_SUMMARY               	cell proliferation. Furthermore, nutritional copper depletion reduced cancer
PR:PROJECT_SUMMARY               	progression in cell line based and patient-derived xenograft models of leukemia.
PR:PROJECT_SUMMARY               	Copper thus appears to be an actionable micronutrient in leukemia.
PR:INSTITUTE                     	Boston Children's Hospital
PR:DEPARTMENT                    	Pathology
PR:LABORATORY                    	Naama Kanarek
PR:LAST_NAME                     	Wong
PR:FIRST_NAME                    	Alan
PR:ADDRESS                       	300 Longwood Avenue, Boston, MA, 02115, USA
PR:EMAIL                         	alan.wong@childrens.harvard.edu
PR:PHONE                         	(617) 355-7433
PR:FUNDING_SOURCE                	NCI 1R01CA282477-01A1
#STUDY
ST:STUDY_TITLE                   	Polar metabolite profiling of BCS-treated SEM cells with or without rescue with
ST:STUDY_TITLE                   	copper (ii) chloride
ST:STUDY_SUMMARY                 	To investigate the effects of bathocuproinedisulfonic acid (BCS) treatment (a
ST:STUDY_SUMMARY                 	copper chelator) on steady state metabolite levels, SEM cells were treated for
ST:STUDY_SUMMARY                 	14 days with vehicle, 50uM BCS, 50uM CuCl2, or 50uM of both. Cells were seeded
ST:STUDY_SUMMARY                 	at 0.25 million/mL and counted and passaged every two days. This revealed that
ST:STUDY_SUMMARY                 	copper depletion with BCS lead to electron transport chain dysfunction,
ST:STUDY_SUMMARY                 	resulting in decreased aspartate levels, increased levels of ureidosuccinic
ST:STUDY_SUMMARY                 	acid/carbamoyl aspartic acid, and changes in nucleotide levels.
ST:INSTITUTE                     	Boston Childrens Hospital
ST:LAST_NAME                     	Wong
ST:FIRST_NAME                    	Alan
ST:ADDRESS                       	300 Longwood Avenue
ST:EMAIL                         	alan.wong@childrens.harvard.edu
ST:PHONE                         	(617) 355-7433
ST:NUM_GROUPS                    	4
#SUBJECT
SU:SUBJECT_TYPE                  	Cultured cells
SU:SUBJECT_SPECIES               	Homo sapiens
SU:TAXONOMY_ID                   	9606
SU:CELL_STRAIN_DETAILS           	SEM leukemia cells
#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           	-	20240717_QE2_HILIC_BCSd14_AYW1157	Sample source:SEM leukemia cells | Treatment1:Vehicle	RAW_FILE_NAME=20240717_QE2_HILIC_BCSd14_AYW1157.raw
SUBJECT_SAMPLE_FACTORS           	-	20240717_QE2_HILIC_BCSd14_AYW1158	Sample source:SEM leukemia cells | Treatment1:Vehicle	RAW_FILE_NAME=20240717_QE2_HILIC_BCSd14_AYW1158.raw
SUBJECT_SAMPLE_FACTORS           	-	20240717_QE2_HILIC_BCSd14_AYW1159	Sample source:SEM leukemia cells | Treatment1:Vehicle	RAW_FILE_NAME=20240717_QE2_HILIC_BCSd14_AYW1159.raw
SUBJECT_SAMPLE_FACTORS           	-	20240717_QE2_HILIC_BCSd14_AYW1160	Sample source:SEM leukemia cells | Treatment1:BCS	RAW_FILE_NAME=20240717_QE2_HILIC_BCSd14_AYW1160.raw
SUBJECT_SAMPLE_FACTORS           	-	20240717_QE2_HILIC_BCSd14_AYW1161	Sample source:SEM leukemia cells | Treatment1:BCS	RAW_FILE_NAME=20240717_QE2_HILIC_BCSd14_AYW1161.raw
SUBJECT_SAMPLE_FACTORS           	-	20240717_QE2_HILIC_BCSd14_AYW1162	Sample source:SEM leukemia cells | Treatment1:BCS	RAW_FILE_NAME=20240717_QE2_HILIC_BCSd14_AYW1162.raw
SUBJECT_SAMPLE_FACTORS           	-	20240717_QE2_HILIC_BCSd14_AYW1163	Sample source:SEM leukemia cells | Treatment1:CuCl2	RAW_FILE_NAME=20240717_QE2_HILIC_BCSd14_AYW1163.raw
SUBJECT_SAMPLE_FACTORS           	-	20240717_QE2_HILIC_BCSd14_AYW1164	Sample source:SEM leukemia cells | Treatment1:CuCl2	RAW_FILE_NAME=20240717_QE2_HILIC_BCSd14_AYW1164.raw
SUBJECT_SAMPLE_FACTORS           	-	20240717_QE2_HILIC_BCSd14_AYW1165	Sample source:SEM leukemia cells | Treatment1:CuCl2	RAW_FILE_NAME=20240717_QE2_HILIC_BCSd14_AYW1165.raw
SUBJECT_SAMPLE_FACTORS           	-	20240717_QE2_HILIC_BCSd14_AYW1166	Sample source:SEM leukemia cells | Treatment1:BCS+CuCl2	RAW_FILE_NAME=20240717_QE2_HILIC_BCSd14_AYW1166.raw
SUBJECT_SAMPLE_FACTORS           	-	20240717_QE2_HILIC_BCSd14_AYW1167	Sample source:SEM leukemia cells | Treatment1:BCS+CuCl2	RAW_FILE_NAME=20240717_QE2_HILIC_BCSd14_AYW1167.raw
SUBJECT_SAMPLE_FACTORS           	-	20240717_QE2_HILIC_BCSd14_AYW1168	Sample source:SEM leukemia cells | Treatment1:BCS+CuCl2	RAW_FILE_NAME=20240717_QE2_HILIC_BCSd14_AYW1168.raw
#COLLECTION
CO:COLLECTION_SUMMARY            	One and a half million cells from culture were collected via centrifugation for
CO:COLLECTION_SUMMARY            	20 seconds at 18,000xG at 4C, washed once with ice-cold 0.9% NaCl, and collected
CO:COLLECTION_SUMMARY            	via centrifugation for 20 seconds at 18,000xG at 4C. Cells were cultured in
CO:COLLECTION_SUMMARY            	RPMI-1640 with 10% FBS and penicillin/streptomycin in a 37C incubator with 5%
CO:COLLECTION_SUMMARY            	CO2.
CO:SAMPLE_TYPE                   	Leukemia cells
#TREATMENT
TR:TREATMENT_SUMMARY             	Cells were treated for 14 days with vehicle, 50uM BCS, 50uM CuCl2, or 50uM of
TR:TREATMENT_SUMMARY             	both. Culture media was RPMI-1640 containing 10% FBS and penicillin and
TR:TREATMENT_SUMMARY             	streptomycin in 6-well plates. Cells were seeded at 0.25 million/mL in 4mL and
TR:TREATMENT_SUMMARY             	counted and passaged every two days.
#SAMPLEPREP
SP:SAMPLEPREP_SUMMARY            	Cell pellet was resuspended in 400uL of 100% LC-MS grade methanol supplemented
SP:SAMPLEPREP_SUMMARY            	with isotopically-labelled amino acid standards [Cambridge Isotope Laboratories,
SP:SAMPLEPREP_SUMMARY            	MSK-A2-1.2], aminopterin, and reduced glutathione standard [Cambridge Isotope
SP:SAMPLEPREP_SUMMARY            	Laboratories, CNLM-6245-10]). with repeated pipetting up and down and vortexing
SP:SAMPLEPREP_SUMMARY            	for 10 seconds. Then, 100uL of LCMS-grade water containing 125 mM Ammonium
SP:SAMPLEPREP_SUMMARY            	Acetate, 10 mM Na-Ascorbate, and 7.9 mg/mL 5,5-dithio-bis-(2-nitrobenzoic acid
SP:SAMPLEPREP_SUMMARY            	(Ellman's reagent) was added, and the sample vortex for another 10 seconds.
SP:SAMPLEPREP_SUMMARY            	Samples were then centrifuged for 10 minutes at 18,000 g to pellet cell debris.
SP:SAMPLEPREP_SUMMARY            	The supernatant was transferred to a new tube and dried on ice using a liquid
SP:SAMPLEPREP_SUMMARY            	nitrogen dryer. The dried metabolites were then resuspended in 30uL and 2uL was
SP:SAMPLEPREP_SUMMARY            	injected.
#CHROMATOGRAPHY
CH:CHROMATOGRAPHY_SUMMARY        	2 μL of each sample was injected into a ZIC-pHILIC 150 x 2.1 mm (5 μm particle
CH:CHROMATOGRAPHY_SUMMARY        	size) column (EMD Millipore) operated on a Vanquish™ Flex UHPLC system (Thermo
CH:CHROMATOGRAPHY_SUMMARY        	Fisher Scientific). Chromatographic separation was achieved using the following
CH:CHROMATOGRAPHY_SUMMARY        	conditions: buffer A was 95% acetonitrile and 5% 20 mM ammonium carbonate, 0.1%
CH:CHROMATOGRAPHY_SUMMARY        	ammonium hydroxide in water; buffer B was 95% 20 mM ammonium carbonate, 0.1%
CH:CHROMATOGRAPHY_SUMMARY        	ammonium hydroxide in water and 5% acetonitrile. Gradient conditions used were:
CH:CHROMATOGRAPHY_SUMMARY        	0-20 min: linear gradient from 16.6% to 83.4% B; 20-24 min: hold at 83.4% B;
CH:CHROMATOGRAPHY_SUMMARY        	24-24.1 min: from 83.4% to 16.6% B; 24.1-32 min: hold at 20% B at 0.150 mL/min
CH:CHROMATOGRAPHY_SUMMARY        	flow rate. The column oven and autosampler tray were held at 25 °C and 4 °C,
CH:CHROMATOGRAPHY_SUMMARY        	respectively.
CH:CHROMATOGRAPHY_TYPE           	HILIC
CH:INSTRUMENT_NAME               	Thermo Vanquish
CH:COLUMN_NAME                   	SeQuant ZIC-HILIC (150 x 2.1mm,5um)
CH:SOLVENT_A                     	95% acetonitrile/5% water; 20mM ammonium carbonate; 0.1% ammonium hydroxide
CH:SOLVENT_B                     	95% water/5% acetonitrile; 20mM ammonium carbonate; 0.1% ammonium hydroxide
CH:FLOW_GRADIENT                 	0-20 min: linear gradient from 16.6% to 83.4% B; 20-24 min: hold at 83.4% B;
CH:FLOW_GRADIENT                 	24-24.1 min: from 83.4% to 16.6% B; 24.1-32 min: hold at 20% B
CH:FLOW_RATE                     	0.15 mL/min
CH:COLUMN_TEMPERATURE            	25
#ANALYSIS
AN:ANALYSIS_TYPE                 	MS
#MS
MS:INSTRUMENT_NAME               	Thermo Q Exactive Orbitrap
MS:INSTRUMENT_TYPE               	Orbitrap
MS:MS_TYPE                       	ESI
MS:ION_MODE                      	UNSPECIFIED
MS:MS_COMMENTS                   	MS data acquisition was performed using a QExactive benchtop orbitrap mass
MS:MS_COMMENTS                   	spectrometer equipped with an Ion Max source and a HESI II probe (Thermo Fisher
MS:MS_COMMENTS                   	Scientific) and polarity switching was used. Four scans were used: full scans in
MS:MS_COMMENTS                   	both positive and negative ionization mode in a range of m/z = 70–1000, with
MS:MS_COMMENTS                   	the resolution set at 70,000, the AGC target at 1 × 106, and the maximum
MS:MS_COMMENTS                   	injection time (Max IT) at 20 msec from 0-20 minutes. A third scan in the
MS:MS_COMMENTS                   	negative mode was used with range of m/z = 220-700 from 0-20 minutes and the
MS:MS_COMMENTS                   	same resolution, AGC settings with 30ms Max IT. Lastly, a targeted-SIM scan was
MS:MS_COMMENTS                   	added with a resolution of 35k, AGC target 1e5, and max IT 20ms, isolation
MS:MS_COMMENTS                   	window = 1.0 m/z, with an inclusion m/z of 503.0552 (corresponding to
MS:MS_COMMENTS                   	Ellman-derivatized glutathione). Tune file parameters were: spray voltage =
MS:MS_COMMENTS                   	3.5kV, capillary temperature = 320C, S-lens RF = 50, auxillary gas temperature =
MS:MS_COMMENTS                   	350C.
#MS_METABOLITE_DATA
MS_METABOLITE_DATA:UNITS	Normalized peak area
MS_METABOLITE_DATA_START
Samples	20240717_QE2_HILIC_BCSd14_AYW1157	20240717_QE2_HILIC_BCSd14_AYW1158	20240717_QE2_HILIC_BCSd14_AYW1159	20240717_QE2_HILIC_BCSd14_AYW1160	20240717_QE2_HILIC_BCSd14_AYW1161	20240717_QE2_HILIC_BCSd14_AYW1162	20240717_QE2_HILIC_BCSd14_AYW1163	20240717_QE2_HILIC_BCSd14_AYW1164	20240717_QE2_HILIC_BCSd14_AYW1165	20240717_QE2_HILIC_BCSd14_AYW1166	20240717_QE2_HILIC_BCSd14_AYW1167	20240717_QE2_HILIC_BCSd14_AYW1168
Factors	Sample source:SEM leukemia cells | Treatment1:Vehicle	Sample source:SEM leukemia cells | Treatment1:Vehicle	Sample source:SEM leukemia cells | Treatment1:Vehicle	Sample source:SEM leukemia cells | Treatment1:BCS	Sample source:SEM leukemia cells | Treatment1:BCS	Sample source:SEM leukemia cells | Treatment1:BCS	Sample source:SEM leukemia cells | Treatment1:CuCl2	Sample source:SEM leukemia cells | Treatment1:CuCl2	Sample source:SEM leukemia cells | Treatment1:CuCl2	Sample source:SEM leukemia cells | Treatment1:BCS+CuCl2	Sample source:SEM leukemia cells | Treatment1:BCS+CuCl2	Sample source:SEM leukemia cells | Treatment1:BCS+CuCl2
2-hydroxyglutarate	609429440.8	710931883.8	1193141252	780683135.7	867630537.9	1002826794	815309072.5	1085515400	1232656842	639545928.6	917515351.8	899038982.8
3-methyl-2-oxopentanoic_acid	38993550.5	35124296.49	38814172.31	13793833.21	22212218.26	18272208.08	45613051.22	47500181.97	53423182.79	45431214.82	54840809.3	54098436.43
3-phosphoglycerate	8177900.594	7564221.404	5963963.324	5918079.98	5991852.041	6130959.94	11767799.72	10706247.16	8883104.973	11990236.94	12272773.15	10426755.42
Acetyl.CoA	5193795.634	5346153.428	4295017.236	3834326.703	3341341.064	2890920.222	5147166.922	4578764.562	5009843.338	5277033.154	5245082.992	5041596.537
acetylcarnitine	33717709.01	37560202.84	35287403.26	45845751.26	39723209.29	36528663.65	35216581.28	40221542.1	46141624.98	38325422.74	46567368.86	33163948.89
ADP	78647871.46	85584498.79	77353280.66	77286618.89	98083701.08	68175329.88	70315645.48	57849841.49	58931189.11	64207390.21	60442880.52	60148186.09
alanine	105952567.4	105546406.1	119877209	123785593.7	124571657.8	123551557.8	108846440.2	102265927.4	100264428.8	110995623.1	92755332.33	104708673.8
Alpha.Ketoglutarate	128041608.9	128923620.3	115447571.3	44012694.06	45280106.71	48581811.46	151341065.4	174361083	153815426.2	130687355.2	173695993.1	151837919.3
AMP	11799699.19	11997643.23	11893943.81	32714373.41	38223116.02	30797476.68	9437866.106	9635229.902	9388971.646	11516108.88	10853040.52	12428014.28
arginine	2356681665	2291293792	2228461576	2107500756	1875340829	1992143649	2287770082	2250638724	2261476732	2221421456	2122374597	2257473684
argininosuccinate	24662518.52	22305683.86	24998722.13	21216598.27	21361744.56	21973195.85	26855883.5	26788851.41	25422853.58	27513388.28	29660360.46	29738647.82
asparagine	440798017.2	402117034.7	446396790.1	327950225.7	306677645.6	339752611.2	413572160	390416934	393555687.2	420676195.7	371293907.3	400843151.8
aspartate	72058014.23	78037063.03	72956429.84	24513913.56	25991724.55	17763910.11	63331078.95	52027431.56	60308474.8	73093032.21	57805168.7	60930601.74
asymmetric.dimethylarginine	13379803.31	13998278.72	12076841.17	10992441.52	10682452.54	9873612.329	13620870.23	14493441.43	13578950.02	12991414.82	14066613.28	13906288.52
ATP	427548108.3	424914398.9	387773340.8	312883593.4	398059063	310650425.3	402807564	379750785.7	398866332.1	413634252.2	392948719.8	369439740.7
beta.alanine	20519834.77	18430769.1	18235568.69	20082257.95	22004695.41	19909469.71	23124464.63	21300301.57	18965440.43	22547804.14	19103180.64	20228861.21
betaine	1143138247	1133355636	1070008892	821763430.2	656847889.7	677239599.8	1094138895	1280886285	1332541978	1147511993	1254832908	1198142756
Butyrylcarnitine	132827539.4	149249449	128827609.3	117196299.2	121859436.1	86703375.14	159396522.6	160275459.4	159774972.9	189392939.6	171146200.2	185959723.8
C5.Carnitines	13640845.47	16037516.51	13869155.93	3245874.461	2997039.765	3003848.874	10973513.28	10746326	11203722.18	11523361.54	11706643.5	11162539.23
carnitine	141453597.6	155335729.1	135120269.1	169696747.4	159160900	141253912.4	161560251.1	151852684.7	161842935.7	165428808.1	159356814.2	162584639.6
carnosine	4177062.115	4532821.824	4018555.329	4737689.431	4575768.907	4628094.114	4160430.275	3165316.283	3802478.263	3611573.129	4119336.823	4095879.152
CDP	4123339.154	4402781.788	4139398.336	1157924.787	890794.398	1491402.837	3501876.85	3057345.463	2887589.731	3200739.016	2731911.437	2943151.181
cis.aconitate	23205332.46	24697412.84	15437506.01	5006065.817	3637204.291	3870854.156	26981182.61	29899374.49	25622341.42	24883006.9	25476878.23	27014456.31
citrate	984430536.8	1053830412	842349742.1	128948010.3	150365846.9	134735232.7	1088630759	1129085860	1074524128	1064876625	1091682239	1030246915
citrulline	19547414.16	21144697.14	22266684.15	22348412.82	17263587.48	22733031.69	21321700	19865502.47	18612727.16	17588459.06	17943583.01	17644144.45
CMP	514788.8246	565805.6071	573774.4487	566883.674	543324.7214	874736.4127	561312.3186	523873.6332	442972.5351	500531.0055	539878.9125	472085.7102
creatine	448956896.7	412346068.3	409588610.2	435045665.1	458497257.3	394172553	452605072.9	401593338.2	456159158.5	381177036.6	357151146.7	410846913.1
creatinine	65737321.7	68715261.23	64113684.82	54024054.72	59532669.76	54193430.05	67668686.64	72288918.03	71195974.62	64099489.12	66093102.82	62656549.17
CTP	42663805	40751993.81	39064714.57	5759314.832	4368714.541	7883338.462	39456943.86	40501904.52	39752849.26	44925223.23	42875802.3	41306748.44
Cysteine_Ellmans	23561488.77	21373239.05	24934971.8	27520235.72	27290129.85	31265359.05	15896909.56	14375753.6	16470404.41	11292093.33	14134180.26	15693803.62
cystathionine	10713646.9	8407619.377	12390406.37	5848341.324	6570511.147	7607067.921	5514612.91	8072823.569	9024458.097	6345369.241	5712286.955	6730760.621
cystine	4114967.06	4449474.657	7048167.26	7619570.034	5202806.174	7618934.207	5907534.472	5817978.56	7679312.817	4178900.1	5135266.804	5682921.343
dihydroxyacetone_phosphate	1138213.907	1051519.767	2458464.175	1884287.652	1625400.347	4404144.591	2073976.835	3534869.74	4219028.033	1938657.955	6602989.661	3004540.344
F6P_andor_G1P	6301413.081	6770942.27	5878464.484	19137645.29	14119922.34	21598243.59	7091367.821	6559958.922	6785590.817	7194482.13	8330628.541	6745772.952
FAD	3202333.718	3363111.656	3007310.302	2789832.111	3338075.455	2447710.729	3084175.753	3230171.259	3110398.602	3184374.14	2972105.42	2989256.007
formyl_methionine	3257123.343	3121508.626	2959707.815	2156895.087	2651492.133	2037399.851	2920583.794	3933068.252	3463509.811	2654442.155	2848067.445	2676871.159
Fructose.1.6.bisphosphate	2307440.559	2598214.898	2229126.141	5463260.29	2714432.457	7245185.319	3170618.229	2974412.003	2485751.554	4344021.446	4332537.016	3612326.736
fumarate	64837803.02	68075355	62723740.2	51669832.43	52266559.26	43710380.21	74311459.1	78809620.61	74216637.63	75023898.65	79957696.99	76879929.5
gamma.aminobutyric_acid	42253215.73	41053973.85	43268362.05	41952691.08	50961941.93	40381206.38	47878548.43	50624281.57	48662489.3	70923958.77	69614544.48	73648304.4
GDP	8743765.597	9566675.359	8122358.193	13527999.91	14212323.86	12125336.92	7156555.046	6097130.18	5525150.725	6634347.065	5874492.536	6143907.979
Glucose.6.phosphate	1211283.671	1270530.15	1198864.113	2924543.771	2394006.937	2306345.82	1392567.669	1170961.953	1367423.847	1709085.072	1533488.243	1580160.255
glutamate	2793917180	2829735806	2797189648	1842826492	1696511149	1670332828	2641715218	2494913506	2569210435	2581978037	2443696358	2402996869
glutamine	3188891666	3157670705	3476348225	2945981678	2684316253	2966696385	3175940125	2938482409	3031116550	3114435813	2846886040	3024433925
glycerate	606528159.1	679780130.5	690200331.6	678806429.5	550846185.9	615946760.6	755597415.6	679200819.3	672566544.9	640247846.4	484845999.1	623594569.5
Glycerol.3.Phosphate	45881414.31	45620997.38	43740739.86	177411632.9	164300891.5	178870445.8	40775790.14	39656055.24	38819080.52	29252088.08	33866354.3	31296766.11
Glycerophosphocholine	3263734473	3151031440	3488285082	3281814538	3743057701	3144941007	3625180821	3334801374	3693238595	3168062384	2608134918	2998923872
glycine	22074197.63	23577679.63	24609918.61	22461746.49	20683144.06	21033274.21	20212492.49	20912251.91	18657856.8	21467624.42	21558503.02	21110522.51
GMP	1147538.931	1281732.096	1371556.514	6927971.308	7893845.083	5927857.947	955008.7422	780160.0408	830296.8675	1115249.408	874118.9235	985225.0311
GSH_Ellmans	909134494.2	986167962	857246437.4	856854938.4	831569087.4	702321485.5	920815442.9	839617543.7	895351584.2	829976717.7	767671036.7	794669444.9
GSSG	6799483.115	3481633.92	5662069.225	3193813.64	6989650.392	4962015.501	2336926.074	4606618.889	5159123.536	3145602.195	2645887.477	4109663.211
GTP	38506610.87	36138040.53	36311634	37566969.38	39853775.72	40266725.41	38955229.08	36811570.87	36015694.28	38297549.46	35746472.65	32931281.66
homocitrulline	2871722.13	3017688.299	2534596.583	2182297.461	2473708.43	2214585.379	3252621.284	2840915.501	2319992.223	3152105.622	2913722.827	2762926.701
IMP	1424129.422	1226015.985	1142859.999	8749191.722	5095935.793	12839354.51	1281285.538	1278187.936	1053117.945	1163500.314	1456367.428	1302203.149
isoleucine	918226009.8	880674414.7	971603388.3	942483129.2	780207486.9	817560821.6	819986422.2	868447376.5	953870242	894766666.9	1001926396	918447144.8
lactic_acid	485526357.2	431267905.8	383184548.2	407937623	526438083.5	468433339.8	578179249.2	558786466.6	496918794.9	673350808.1	720404749.6	764123559.9
lysine	47376572.92	45393104.4	50184123.81	50884935.33	51188953.35	52935465.64	44090365.61	42292827.65	44065478.77	42414423.45	39378009.66	42326823.03
malate	1000611781	1037830567	982739494.7	825245039.3	816000667.4	705707175.3	1130670954	1213290504	1162301799	1176810137	1237720777	1151588560
mannose	4820305.497	5777995.85	6252361.528	4055900.449	3345922.739	2888264.548	6570511.287	6541388.586	6039678.099	4863772.491	4479653.224	6046389.981
Methionine.sulfoxide	178572855.8	191239276.4	171845411.4	147343784.2	135076310.9	139265237.6	191540038	210251303	203271266.1	205572028.1	187040445.9	207636672
methionine	283798636.7	293744873.5	326896136.4	259233480.8	264459507.8	262321539.9	273972154.8	272401156.4	280736030.1	280919217.1	287491967.1	278877698.2
methylthioadenosine	9933648.641	10460256.32	7638078.187	6866693.51	4116039.857	3497529.219	9800057.731	8970024.266	8035151.019	9625438.591	8349671.87	8875129.112
N.acetylglutamate	11238807.54	11239821.71	10411252.95	8938957.741	8713803.748	9559395.978	9222765.899	11411481.03	9741689.799	10226493.16	10018804.66	10882399.71
N.acetylmethionine	4482718.636	3837104.485	3794110.772	1902971.583	1880381.091	1863203.724	3751302.085	4297316.066	3904709.924	4822264.63	4925445.635	4937551.485
NAD.	86519633	89618157.95	84485696.55	62248980.15	71397143.25	57583800.7	83137708.35	77270376.02	80431272.86	87822020.73	88565845.48	91355634.73
NADH	17682894.04	16537548.93	15562392.61	28115942.25	34430321.4	26935937.5	18831415.48	20225037.69	17606226.86	16775422.7	16688003.88	17951438.77
NADP	1244044.376	1356097.966	1113400.633	1049779.998	1073773.612	925738.8336	1123057.491	1197404.267	1060951.026	1100273.864	1301568.509	1144946.081
NADPH	5708205.716	5787729.7	5679931.996	3680822.211	4247666.013	3468082.001	5764682.081	5849105.23	5535604.599	5731491.188	5702151.96	5654115.389
niacinamide	43700328.11	47312704.67	54806356.2	75782218.44	76440695.72	82097695	62535161.29	75805318.63	68217323.64	65095428.04	64507067.44	82186413.1
ornithine	34448223.36	30687749.72	35965338.69	26614198.73	24808650.75	26308974.49	31174304.02	33198256.7	31308410.28	31788245.71	30350670.26	33230120.45
palmitate	144712633.5	184347346.9	221642567.8	180339849.6	166520677	243642479.9	180140905.4	138860629.4	183453120.9	150373290.4	93498527.58	130038714.5
Pantothenate	435297719.2	504893092.3	432146595.8	275922014	255361027	211434209.8	632245809.2	637424092.2	674077233.4	518178142.8	525554541.8	483624398.1
phosphocholine	15419655204	15322436387	17014592653	10227067687	11966395387	10059392075	15560925333	16021900633	16673272031	16023436100	16225786011	16419930130
phosphocreatine	1651344.213	1631387.024	1715242.806	1762305.023	2115776.036	1655831.781	1672215.172	1465003.259	1549744.097	1177892	1323100.444	1160232.542
phosphoenolpyruvate	3328226.516	3059120.696	2647981.299	1832033.779	1357643.95	1765551.448	4241426.01	4359827.099	4080681.435	5716659.64	5779923.465	5414500.345
proline	4249484454	4093621873	4032473552	3342916647	3314479120	3243597561	3862533132	3946797514	3820043748	3903951813	3637687055	3940381373
Pyridoxine	93938593.65	98323828.05	86241890.51	80021665.18	84878290.79	73849233.43	98226571	94807782.9	93941714.84	90842694.36	87638861.86	93043919.05
S.Adenosyl.L.Homocysteine	18325959.65	17532654.31	14001225.52	10815734.94	11829096.88	9891523.725	16109244.32	16831850.6	15387820.56	16318542.62	13546798.88	15758139.15
S.Adenosyl.L.methionine	136186661.6	132562513.2	128433688.8	109566501.2	115791763	89737645.23	139272922.7	125358388.8	128226122.4	118922283.5	109615559.5	106273475.4
saccharopine	2171774.429	1693427.053	1919445.414	589723.1643	952115.176	745322.5801	2301106.098	2387579.023	2422450.93	2751506.448	2900284.566	2756645.089
sarcosine	105952567.4	105835864.2	119877209	127212300.6	123511870.8	123221347.6	108846440.2	102056730.5	100065390.1	111842799.9	92752193.03	104696423
Sedoheptulose.7.phosphate	6219246.863	5909967.852	5136483.217	28645862.73	24060000.22	28302171.45	6128741.389	5635080.399	4958552.951	6788935.357	7733890.501	6681674.366
serine	33514171.72	37300095.63	47722215.89	58005168.71	49824422.65	58104600.88	34733699.64	30998177.82	38237137.63	42389928.44	33865011.4	36624789.1
sorbitol	15284552.99	10422359.69	10744696.41	12142445	11333299.78	13196983.47	12168759.8	12898219.89	13612535.71	15102519.9	12612612	10704164.27
succinate	31589864.34	36243415.31	43895724.82	153311557.7	192464420.2	166793574.1	46693261.55	39482615.21	41329450.68	38060584.43	38506019.23	40363028.59
taurine	360403521.8	341414050.5	346870086.7	403754062.2	411334841.5	384887129.5	362459250.3	333200987.9	344723715.5	322775459.6	313615289.1	305711851.4
threonine	278121088.2	279128205.4	315166525	306143359.8	261097026.2	299432119	270526941.7	274920572.8	299352884.3	268494264.2	257907622.2	272267139.3
tryptophan	113602153.8	115218404.5	128550166.2	104835856.9	111539730.4	106217921.2	110223845.9	111623345.9	116175900	117416549.5	116171823	118197960.8
tyrosine	294080721	289895891	361956165.3	252038303.8	270871228.8	282483581.2	288763864.8	297286989.5	313014106.7	292839295.6	304780549.9	304352191.5
UDP.GlcNAc	76005516.22	75321069.79	76677428.9	13806600.6	12855092.41	14583392.06	78196816.23	75502363.99	77327862.63	77335507.49	80083128.71	79168279.95
UDP	11518157.44	13043390.54	10791986.97	3021746.494	2136763.346	3488791.475	9225206.712	7629943.054	7657385.804	9269961.793	7580010.02	8182529.263
UMP	2177469.927	2172289.274	2000345.016	1904846.411	1917974.393	2178238.626	1523157.209	1654594.367	1036536.275	1598169.075	1641830.778	1769201.518
Ureidosuccinic_acid	13791089.34	15307012.68	17136118.57	566229109	793592862.2	380609288.7	16524130.53	16509214.83	19840523.92	21600486.25	20705506.11	21538079.11
uric.acid	4607820.821	4469359.345	5151666.257	2296800.577	3161701.12	1996347.24	4868299.624	5190741.979	4715991.092	3408400.941	4183680.446	3479829.549
UTP	124343508.5	117765503.7	113796251.8	13126711.2	8224664.571	17221647.13	115798116.5	113853874.9	117731879.4	132520708.5	130990813.8	122361828.5
valine	127094366.4	117007536.6	117869100.1	142797717.1	121906474.7	146564652.8	95685118.91	84393228.4	101122111.5	114674325.2	78780379.21	123763107.3
dihydroorotate	450794.0579		1015073.091	37102800.37	57371566.6	22807347.95	127653.8731	722282.507	969746.4736	954675.0119	661475.1478	1555103.151
MS_METABOLITE_DATA_END
#METABOLITES
METABOLITES_START
metabolite_name
2-hydroxyglutarate
3-methyl-2-oxopentanoic_acid
3-phosphoglycerate
Acetyl.CoA
acetylcarnitine
ADP
alanine
Alpha.Ketoglutarate
AMP
arginine
argininosuccinate
asparagine
aspartate
asymmetric.dimethylarginine
ATP
beta.alanine
betaine
Butyrylcarnitine
C5.Carnitines
carnitine
carnosine
CDP
cis.aconitate
citrate
citrulline
CMP
creatine
creatinine
CTP
Cysteine_Ellmans
cystathionine
cystine
dihydroxyacetone_phosphate
F6P_andor_G1P
FAD
formyl_methionine
Fructose.1.6.bisphosphate
fumarate
gamma.aminobutyric_acid
GDP
Glucose.6.phosphate
glutamate
glutamine
glycerate
Glycerol.3.Phosphate
Glycerophosphocholine
glycine
GMP
GSH_Ellmans
GSSG
GTP
homocitrulline
IMP
isoleucine
lactic_acid
lysine
malate
mannose
Methionine.sulfoxide
methionine
methylthioadenosine
N.acetylglutamate
N.acetylmethionine
NAD.
NADH
NADP
NADPH
niacinamide
ornithine
palmitate
Pantothenate
phosphocholine
phosphocreatine
phosphoenolpyruvate
proline
Pyridoxine
S.Adenosyl.L.Homocysteine
S.Adenosyl.L.methionine
saccharopine
sarcosine
Sedoheptulose.7.phosphate
serine
sorbitol
succinate
taurine
threonine
tryptophan
tyrosine
UDP.GlcNAc
UDP
UMP
Ureidosuccinic_acid
uric.acid
UTP
valine
dihydroorotate
METABOLITES_END
#END