#METABOLOMICS WORKBENCH alanyl_20250321_114326 DATATRACK_ID:5766 STUDY_ID:ST003820 ANALYSIS_ID:AN007471 PROJECT_ID:PR002390
VERSION             	1
CREATED_ON             	December 17, 2025, 12:48 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 SLC31A1 knockout cells with or without rescue with
ST:STUDY_TITLE                   	over-expression of SLC31A1, and control intergenic cells
ST:STUDY_SUMMARY                 	To investigate whether the effects of SLC31A1 knockout on steady state
ST:STUDY_SUMMARY                 	metabolite levels is specific to SLC31A1 knockout, SEM cells containing a
ST:STUDY_SUMMARY                 	SLC31A1-targeting sgRNA (guide #2) or a intergenic -targetting sgRNA (i.e. a
ST:STUDY_SUMMARY                 	control sgRNA, "Intergenic1") and Cas9 were FACS-purified based on SLC31A1
ST:STUDY_SUMMARY                 	expression, and then engineered to stably over-express either eGFP (control) or
ST:STUDY_SUMMARY                 	a CRISPR-resistant form of SLC31A1. Cells were then cultured in RPMI-1640
ST:STUDY_SUMMARY                 	containing 10% FBS and penicillin and streptomycin in 6-well plates, and then
ST:STUDY_SUMMARY                 	collected for metabolomics. This demonstrated that the changes in aspartate,
ST:STUDY_SUMMARY                 	ureidosuccinic acid/carbamoyl aspartate and nucleotides were largely reverted by
ST:STUDY_SUMMARY                 	genetic overexpression of SLC31A1.
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           	-	20230712_QE1_HILIC_SEM_sgSLC31A1KOandRescue_AYW961	Sample source:SEM leukemia cells | sgRNA:Intergenic1 | overexpression:GFP	RAW_FILE_NAME=20230712_QE1_HILIC_SEM_sgSLC31A1KOandRescue_AYW961.raw
SUBJECT_SAMPLE_FACTORS           	-	20230712_QE1_HILIC_SEM_sgSLC31A1KOandRescue_AYW962	Sample source:SEM leukemia cells | sgRNA:Intergenic1 | overexpression:GFP	RAW_FILE_NAME=20230712_QE1_HILIC_SEM_sgSLC31A1KOandRescue_AYW962.raw
SUBJECT_SAMPLE_FACTORS           	-	20230712_QE1_HILIC_SEM_sgSLC31A1KOandRescue_AYW963	Sample source:SEM leukemia cells | sgRNA:Intergenic1 | overexpression:GFP	RAW_FILE_NAME=20230712_QE1_HILIC_SEM_sgSLC31A1KOandRescue_AYW963.raw
SUBJECT_SAMPLE_FACTORS           	-	20230712_QE1_HILIC_SEM_sgSLC31A1KOandRescue_AYW964	Sample source:SEM leukemia cells | sgRNA:Intergenic1 | overexpression:SLC31A1	RAW_FILE_NAME=20230712_QE1_HILIC_SEM_sgSLC31A1KOandRescue_AYW964.raw
SUBJECT_SAMPLE_FACTORS           	-	20230712_QE1_HILIC_SEM_sgSLC31A1KOandRescue_AYW965	Sample source:SEM leukemia cells | sgRNA:Intergenic1 | overexpression:SLC31A1	RAW_FILE_NAME=20230712_QE1_HILIC_SEM_sgSLC31A1KOandRescue_AYW965.raw
SUBJECT_SAMPLE_FACTORS           	-	20230712_QE1_HILIC_SEM_sgSLC31A1KOandRescue_AYW966_rerun	Sample source:SEM leukemia cells | sgRNA:Intergenic1 | overexpression:SLC31A1	RAW_FILE_NAME=20230712_QE1_HILIC_SEM_sgSLC31A1KOandRescue_AYW966_rerun.raw
SUBJECT_SAMPLE_FACTORS           	-	20230712_QE1_HILIC_SEM_sgSLC31A1KOandRescue_AYW973	Sample source:SEM leukemia cells | sgRNA:SLC31A1_#2 | overexpression:GFP	RAW_FILE_NAME=20230712_QE1_HILIC_SEM_sgSLC31A1KOandRescue_AYW973.raw
SUBJECT_SAMPLE_FACTORS           	-	20230712_QE1_HILIC_SEM_sgSLC31A1KOandRescue_AYW974	Sample source:SEM leukemia cells | sgRNA:SLC31A1_#2 | overexpression:GFP	RAW_FILE_NAME=20230712_QE1_HILIC_SEM_sgSLC31A1KOandRescue_AYW974.raw
SUBJECT_SAMPLE_FACTORS           	-	20230712_QE1_HILIC_SEM_sgSLC31A1KOandRescue_AYW975	Sample source:SEM leukemia cells | sgRNA:SLC31A1_#2 | overexpression:GFP	RAW_FILE_NAME=20230712_QE1_HILIC_SEM_sgSLC31A1KOandRescue_AYW975.raw
SUBJECT_SAMPLE_FACTORS           	-	20230712_QE1_HILIC_SEM_sgSLC31A1KOandRescue_AYW976	Sample source:SEM leukemia cells | sgRNA:SLC31A1_#2 | overexpression:SLC31A1	RAW_FILE_NAME=20230712_QE1_HILIC_SEM_sgSLC31A1KOandRescue_AYW976.raw
SUBJECT_SAMPLE_FACTORS           	-	20230712_QE1_HILIC_SEM_sgSLC31A1KOandRescue_AYW977	Sample source:SEM leukemia cells | sgRNA:SLC31A1_#2 | overexpression:SLC31A1	RAW_FILE_NAME=20230712_QE1_HILIC_SEM_sgSLC31A1KOandRescue_AYW977.raw
SUBJECT_SAMPLE_FACTORS           	-	20230712_QE1_HILIC_SEM_sgSLC31A1KOandRescue_AYW978	Sample source:SEM leukemia cells | sgRNA:SLC31A1_#2 | overexpression:SLC31A1	RAW_FILE_NAME=20230712_QE1_HILIC_SEM_sgSLC31A1KOandRescue_AYW978.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 seeded 1million/mL into 2 mL of RPMI-1640 + 10%FBS +
TR:TREATMENT_SUMMARY             	penicillin/streptomycin the day prior to experiment in 6 well plates.
#SAMPLEPREP
SP:SAMPLEPREP_SUMMARY            	Cell pellet was resuspended in 160uL 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, 40uL 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 20uL 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 acetonitrile; buffer B was 20 mM ammonium carbonate,
CH:CHROMATOGRAPHY_SUMMARY        	0.1% ammonium hydroxide in water; resulting pH is around 9 without pH
CH:CHROMATOGRAPHY_SUMMARY        	adjustment. Gradient conditions used were: 0-20 min: linear gradient from 20% to
CH:CHROMATOGRAPHY_SUMMARY        	80% B; 20-24 min: hold at 80% B; 24-24.1 min: from 80% to 20% B; 24.1-32 min:
CH:CHROMATOGRAPHY_SUMMARY        	hold at 20% B at 0.150 mL/min flow rate. The column oven and autosampler tray
CH:CHROMATOGRAPHY_SUMMARY        	were held at 25 °C and 4 °C, respectively.
CH:CHROMATOGRAPHY_TYPE           	HILIC
CH:INSTRUMENT_NAME               	Thermo Vanquish
CH:COLUMN_NAME                   	SeQuant ZIC-HILIC (150 x 2.1mm,5um)
CH:SOLVENT_A                     	100% acetonitrile
CH:SOLVENT_B                     	100% water; 20mM ammonium carbonate; 0.1% ammonium hydroxide
CH:FLOW_GRADIENT                 	Gradient conditions were as follows: linear gradient from 20 to 80% B;
CH:FLOW_GRADIENT                 	20–20.5 min: from 80 to 20% B; 20.5–28 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	20230712_QE1_HILIC_SEM_sgSLC31A1KOandRescue_AYW961	20230712_QE1_HILIC_SEM_sgSLC31A1KOandRescue_AYW962	20230712_QE1_HILIC_SEM_sgSLC31A1KOandRescue_AYW963	20230712_QE1_HILIC_SEM_sgSLC31A1KOandRescue_AYW964	20230712_QE1_HILIC_SEM_sgSLC31A1KOandRescue_AYW965	20230712_QE1_HILIC_SEM_sgSLC31A1KOandRescue_AYW966_rerun	20230712_QE1_HILIC_SEM_sgSLC31A1KOandRescue_AYW973	20230712_QE1_HILIC_SEM_sgSLC31A1KOandRescue_AYW974	20230712_QE1_HILIC_SEM_sgSLC31A1KOandRescue_AYW975	20230712_QE1_HILIC_SEM_sgSLC31A1KOandRescue_AYW976	20230712_QE1_HILIC_SEM_sgSLC31A1KOandRescue_AYW977	20230712_QE1_HILIC_SEM_sgSLC31A1KOandRescue_AYW978
Factors	Sample source:SEM leukemia cells | sgRNA:Intergenic1 | overexpression:GFP	Sample source:SEM leukemia cells | sgRNA:Intergenic1 | overexpression:GFP	Sample source:SEM leukemia cells | sgRNA:Intergenic1 | overexpression:GFP	Sample source:SEM leukemia cells | sgRNA:Intergenic1 | overexpression:SLC31A1	Sample source:SEM leukemia cells | sgRNA:Intergenic1 | overexpression:SLC31A1	Sample source:SEM leukemia cells | sgRNA:Intergenic1 | overexpression:SLC31A1	Sample source:SEM leukemia cells | sgRNA:SLC31A1_#2 | overexpression:GFP	Sample source:SEM leukemia cells | sgRNA:SLC31A1_#2 | overexpression:GFP	Sample source:SEM leukemia cells | sgRNA:SLC31A1_#2 | overexpression:GFP	Sample source:SEM leukemia cells | sgRNA:SLC31A1_#2 | overexpression:SLC31A1	Sample source:SEM leukemia cells | sgRNA:SLC31A1_#2 | overexpression:SLC31A1	Sample source:SEM leukemia cells | sgRNA:SLC31A1_#2 | overexpression:SLC31A1
2-hydroxyglutarate	531714363.8	858665498.1	659099187.9	721954609.1	673442542.7	1060096513	1050508030	1111278106	1357606126	647133200.1	758451480.6	746114200.6
3-methyl-2-oxopentanoic_acid	89643048.9	91732793.09	94420644.29	125002913.5	120292073.2	163178357.9	79750567.17	91523955.95	96124577	83149654.24	112524478	113365786.7
3-phosphoglycerate	3360988.145	6915521.602	7492752.843	8292540.148	10288542.46	4082204.256	4236084.177	3689597.481	4592034.107	5728460.415	5012861.812	6088818.443
Acetyl.CoA	24689661.95	18142765	18964035.6	18798835.3	18064836.39	16714085.83	15333216.48	13235283.62	11772520.86	14108184.27	17872372.3	19495759.02
acetylcarnitine	509062967.8	491657971.9	447882998	480830013.5	413902300.8	141265404.4	598927839.8	671696180.2	726450514.2	577554380.4	634696635.1	651888532
alanine	436490151.3	292777158.9	299078826.3	296711236.2	279384144.3	565253279.4	295142129.1	308910053.6	320219048.1	289975720.8	318957330.8	316206828.1
Alpha.Ketoglutarate	138209833.3	234917226.6	205721336.1	301775143.4	272125325.9	416458364.4	183100414.9	206587683.5	235673112.1	227251954.7	253996383.9	283252303.9
amidoadipate	23246917.67	19772746.02	17686721.36	20167739.6	21211337.74	24776008.71	18522594.56	19365195.13	19276206.52	18813846.01	19440705.46	19651591.86
AMP	33685807.68	23057623.34	24048393.79	21890768.37	26115025.32	42474744.87	67422378.95	69514320.99	58404840.59	25602091.32	31893452.3	25773676.58
argininosuccinate	27723839.72	65938761.24	57180227.65	70986327.17	76227366.92	49945594.66	72474578.81	70623992.83	74866965.27	59774039.31	79789434.02	78023160.15
ascorbate	10523359.92	9207194.022	9001965.97	11315390.93	10651071.2	15725009.75	10186312.84	9868532.115	9349997.131	7662127.972	10347155.7	9502677.444
asparagine	999742456	670979392.7	666692745.1	674694361.7	667705703.9	1012805796	451290041.5	448084800.3	482316928.6	557087391.6	647516737.6	667986495.5
aspartate	189883460.6	143325176.6	139036610.6	108756174.5	110893574.2	184020103.6	46272948.46	49057330.38	51474539.57	132237934.9	143858970.6	139219059
asymmetric.dimethylarginine	43025794.88	101818766.7	106318989.9	110561354.6	118985634.6	49311301.11	77509715.91	81921277.18	78674518.28	90778101.4	114756897.1	111142809.1
ATP	512156836.7	1190180437	1081048647	1017868362	1056884926	669835380	822873062.2	684780336.7	683268914.8	890619655.3	1015812673	1042190968
beta.alanine	97600497.69	97710593.61	97741088.6	96593858.61	96821548.92	171730934.6	93632646.68	95602061.99	99998749.19	94500744.04	106784054.6	94434571.96
betaine	11660380134	9930827891	9400757744	11404313440	9618697465	5994858542	6766703445	7261294144	7646142322	10346602434	10075605089	11128803133
Butyrylcarnitine	612061592.2	618973947.7	615415332.4	766761547.2	644277870.3	382185908.5	628785663.3	654297743.8	767445395.4	599462171	720449717.8	916050270.8
C5.Carnitines	36053742.97	30670798.95	31443601.91	32475526.42	25856463.68	14150234.38	111132238.6	128522879.3	131383098.5	63617697.94	40354134.8	53970493.49
carnitine	1090947444	842206586.7	866182578.7	955425921.7	801327944.9	704847542.1	1063966347	1141941588	1240714488	1058192115	980872592.6	1163430793
CDP.choline	4184761.506	4424631.342	4506016.668	2389939.167	2845064.798	2679961.033	5754669.692	5531955.698	5452694.009	2840558.4	3332773.138	3124696.424
CDP	3890810.96	8452912.796	8619221.19	8248378.872	8339883.297	3781116.737	10636786.25	11151954.75	8035436.109	8579365.293	10410756.34	8716478.065
citrate	1362568002	1131393863	961080129.9	1509510846	1509227642	1868291428	771043695.1	724730433.2	706093251.5	1783361427	1285927830	1201616973
citrulline	33081636.09	38923186.85	72487556.96	37973102.86	35848381.27	54528209.33	38959697.98	38208884.72	35928494.85	37862968.98	41351252.89	35152301.58
creatine	3887286471	3004811227	2749443051	3032606344	2753060117	4604056956	2738875842	2861900663	2823282534	2964148653	3303214387	3586747624
creatinine	565862768	561679784.5	632173704	602119634.3	579490428.7	276506545.6	468860792.9	473581138.4	494952681.9	513313476.9	644566767.9	541530455.7
CTP	148747132	105151832.5	97191523.15	91353232.97	94170154.02	97554482.4	48848128.11	38873990.41	40193677.29	76914434.61	89066775.85	89648240.79
cystathionine	24867014.17	21693429.76	20076672.58	18125496.55	19931122.7	26698953.28	15978408.96	14027798.65	14535593.72	14699258.51	22322841.44	20679851.57
dATP	3893401.154	4039292.546	3761134.275	3268771.501	3618791.095	3549508.121	2772938.506	2107399.314	2129342.271	2986583.646	3495089.913	3537123.025
dCTP	985734.458	1447345.173	1447189.291	1230359.745	1426907.498	1068175.047	673988.8676	511938.2868	520371.8659	1150907.176	1437829.788	1521149.476
dihydroxyacetone_phosphate	37397234.68	54395469.3	48206953.53	62138392.63	63891544.42	70953547.58	106147289.2	106797339	101700730.5	52471306.3	64666055.46	58707749.5
dTMP	21953100.17	16996220.89	12457554.41	19049475.84	13575512.03	17464749.76	12576913.08	14292429.5	12069823.29	14020421.19	13663877.22	16431137.98
dTTP	3113573.57	4186259.047	4103272.693	4119008.669	2046392.379	752055.3188	1034318.885	1929209.265	2185621.884	2288553.712	3634790.088	3393020.947
F6P_andor_G1P	8640378.529	12827965.12	14234149.55	14026210.99	15504976.53	20656158.73	11148577.32	10370211.63	9026773.929	8707572.773	7820874.888	7277866.655
FAD	6555226.563	6143991.679	5548043.647	5685913.504	5646958.478	2210016.968	5180159.913	4730514.836	4152327.707	4721926.166	5635306.421	6500835.212
formyl_methionine	3132119.608	3207138.46	3467919.243	4471948.41	2760649.363	2726998.24	4402235.732	3545094.533	3460958.682	4082271.414	1926279.7	2666118.638
Fructose.1.6.bisphosphate	4355618.45	3721564.6	4316113.383	4410783.934	4477170.18	5092129.685	3014396.969	2556363.542	2351742.411	2894726.403	3328496.797	3704410.047
fumarate	93734821.82	116558247.5	106676089.5	137520860.4	120465576.8	154904913.4	123129794	135280968.6	134606430.7	127473053.9	138958264.9	146383147.5
gamma.aminobutyric_acid	375212928.9	430771014.1	396491956.4	408685795.4	435306346.5	600409306.7	293298166.5	307250038.6	329551827.2	345083228.7	397740551.6	379356642
GDP	15305308.04	17851445	18144590.43	18319410.56	16645612.94	17877939.91	31207239	29554800.55	25127656.18	14117557.28	18580313.53	17226180.92
glutamate	6447616944	5534727805	4942665316	5118368962	5034489997	7439418908	3944147913	3652010632	3790014905	4395664814	5417451683	5650515523
glutamine	9833324591	8787628299	8298939901	7673474104	7772545923	13060743729	4877819038	4827278179	5323159752	6230183209	7862348414	7453325048
glyceraldehyde_3.phosphate	37397234.68	54395469.3	48206953.53	62138392.63	63891544.42	70953547.58	106147289.2	106797339	101700730.5	52471306.3	64666055.46	58707749.5
glycerate	4577383332	3497415298	3349015976	3517289586	3165002641	3743854209	2565057187	2392638292	2543033160	2753196548	3049138253	3313823402
Glycerophosphocholine	37214188419	26856711779	26412739305	22270501533	20928396415	33171212370	10196472262	10310276370	10336335109	17953341394	20316636939	23026953007
GMP	292412.6827	1598782.014	2084940.747	960009.4271	1928207.298	856975.5038	7665025.271	8005698.89	6384422.641	1739115.575	2311775.373	1970751.379
GSH_Ellmans	1386991233	1472436827	1463346231	1303418915	1258355908	1288731581	1081515375	1014587494	1061007517	985326431.8	1320190789	1463189371
GSSG	71098000.05	23329240.89	27850518.76	109034848.3	127817662.2	53870773.01	52198357.96	67917168.92	39896806.65	55966339.66	84810852.54	32458272.98
GTP	82460249.4	93649217.38	86658618.72	84100335.59	92597787.14	166434757.2	76793969.09	62384982.03	65616300.82	73786749.94	82480521.53	83506074.29
histidine	2470676235	1508308496	1604290193	1605017665	1516724482	2422223864	1393424852	1451459185	1423095975	1267289399	1588699830	1627363900
homocitrulline	12178956.45	8470014.312	9243186.775	11781640.9	11707772.67	14371406.82	10558008.25	8190725.832	8667162.885	8430828.055	11236176.67	9238299.627
hypotaurine	9620924.264	24320067.84	10656651.02	7927598.933	9345460.414	14837055.53	9608845.451	8220871.003	24664626.56	9151854.839	8264095.627	11465897.46
IMP	2794248.293	2461011.483	1989801.775	3976161.404	4234694.464	5929329.681	11026563.3	10603461.1	9767493.54	3131068.806	3389354.895	3701451.166
isoleucine	2550811935	3589388679	3481161085	3578687437	3138866797	809955181	2876559704	3007966168	3051554189	2528765772	3328222638	3411053379
lactic_acid	1793038032	1336353568	1463977324	1883966532	1972392596	1635393074	2648296502	2888340225	2831948235	1825105719	1983136770	2033098986
leucine	2323222931	3462638548	2967546497	2642927351	2627345186	1079473179	2092609389	2312467210	2616054071	2380713841	3408472836	2832841236
malate	884741337.6	986551138.9	898127960.2	1111210019	1057023809	1310045730	1027902647	1053040127	1086079607	983599600.3	1123785187	1145851114
mannose	27363088.01	13739337.56	14504467.84	15947170.76	15300823.57	19570231.59	5570710.841	10107886.5	7213968.046	18389505.56	16589279.82	13401572.32
methionine	730771009.8	1160056275	989310965.5	1059586491	950425072.7	237243770.7	813946178.4	803003115.1	1001516281	700840180.6	949250083.5	923113711.5
methylthioadenosine	27739420.47	38685111.11	42929532.16	47062758.27	47905389.98	11420714.16	40359198.49	32862035.54	25155092.29	26370090.73	40518780.47	44877839.7
N.acetylglutamate	38591791.29	26138975.04	25357754.37	24977770.19	28545141.24	47700217.72	21005307.73	19853634.43	24614638.39	19081705.61	22439147.04	19300026.31
NAD.	393741059.2	287823798.5	287153000.9	296314790.4	325713959.3	374496101.5	246065964.8	231482027.8	223458195.6	245437119.8	271835402	287171372.5
NADH	24888817.23	23917126.67	20319373.62	23944040.55	27163025.8	23046132.67	37710298.55	40748180.72	36199618.12	10782392.79	26727550.02	26012278.14
NADP	4513770.315	8099492.437	8171009.01	8074122.256	9338739.289	4584280.645	7770178.986	6878931.394	5704808.672	8689906.21	8016433.193	7684556.52
NADPH	3768138.292	8677818.059	8895274.555	8553693.652	9054714.365	6835528.42	5862591.035	5329903.753	5196809.199	4972042.05	8114364.318	9558103.158
niacinamide	193359811.3	274075830	303119846.7	302378897.1	345443827.5	128405588.3	180100938.8	251806907.1	294688383.7	216488739.7	376319973.8	405366637.6
O.phosphoethanolamine	6077243.051	13877742.32	13172806.86	5119049.044	5992420.04	7049539.887	38171882.08	36408467.81	32691880.08	4280734.404	5294857.757	5392131.634
ornithine	35224159.91	88359294.33	103007787.2	91049793.36	93333742.57	45840065.1	64046169.49	62534256.95	70963395.67	87534904.83	95172402.27	82529997.48
palmitate	594487616	301521024.8	343720907.4	262471050.2	290868551	279441014.1	182798789.7	244884396.2	234421506.7	410346053.3	358694918.7	328756561.6
phosphocholine	54361413971	61949734832	60329008159	57650795587	58172470823	76288312337	38690988019	37236133092	38132948415	44531553575	55630280330	53078004312
phosphocreatine	7218891.347	4358531.839	4117527.129	5409907.198	5155528.099	5999087.782	3300960.502	3506517.468	3152517.853	4207615.394	4158260.907	4212447.084
phosphoenolpyruvate	3097463.522	6066907.444	5204625.389	5786589.898	7089963.485	6392482.483	2063058.502	1461596.905	2258058.204	4184183.64	4310486.162	5055785.939
Pipecolate	28381246.78	43968673.54	42056458.58	40956343.64	36459429.53	20985827.24	32150466.77	34816384.07	35594207.47	42494058.91	47994209.74	51509727.59
proline	21463040696	21430080384	19849079397	23079199031	20876236106	16260646082	18633055667	18177208374	19914134325	16933960874	20661403453	21030982438
propionylcarnitine	21926212.58	29167348.28	32783723.19	36462796	34191163.82	19991754.73	23611680.97	24469076.65	23280741.54	45946418.02	53511134.29	45412085.8
Pyridoxine	195362854.4	295634619.1	275955391.9	273876478.8	274186441.8	100831899.7	193977553.4	214016523.1	228355227.6	211634415.2	282602912.2	297616213.6
Ribose.Ribulose.5.phosphate.3Me.Lys	3656063.955	5445800.572	6218953.803	5858481.609	7552450.381	12460700.94	6057564.649	5001304.109	3949177.035	7775272.071	5540912.915	5400921.898
S.Adenosyl.L.Homocysteine	36636034.41	36745594.84	40908900.95	40137150.12	43882407.08	21283920.28	38591057.01	35499093.77	25648958.44	35234668.88	44643253.35	41403279.54
S.Adenosyl.L.methionine	957280229.4	627953306	618110452.8	628636521.8	587809407.6	734463827	557628975.6	504036707.5	602984704.9	530266807.1	659131870.1	683569181.8
saccharopine	9138518.876	10422596.72	8965711.258	9248796.376	9549059.547	13517866.07	5578769.456	5083568.414	5823083.163	416241522.7	8810417.545	8022169.388
Sedoheptulose.7.phosphate	3965655.687	8391874.55	10369644.47	8395131.712	11098406.14	8838182.518	14411668.34	11808817.2	11011061.4	5350812.787	5904371.695	4984596.375
serine	295367172.9	163820848.9	188276362.2	156604157	153883234.3	205816074.7	106331898	104493010.3	135045030.6	132855066.7	139617063.9	163183566.6
sorbitol	11164850.73	8173768.156	9428102.362	10047830.62	10790860.17	12032355.85	7168524.743	9806770.257	8014285.375	8346833.356	9810874.986	7772247.816
succinate	65092955.27	93213785.52	83093316.43	85610220.56	86576035.75	122937642.6	236909775	246993390.5	234380508.7	98114855.04	92494378.28	90212495.64
taurine	1170967012	777012997.9	752837141.1	801289424.9	832718176	1108076661	843144118.2	738072029.6	761687611	682147619.5	831545690.6	853681005
threonine	1305758816	773913128.9	791708921.1	796494259.5	766064717.3	1367315023	567929021.6	624554592.5	612285678.6	1282250912	736605607.7	827047723
trans.urocanate	147986279.7	84724436.72	316029614.5	113219067	89086623.77	26303938.62	66673635.53	66059388.25	64235053.83	138218483.9	105755908.1	116500136.2
tryptophan	298214917.1	363450071.3	345315775	388841262.3	330819481.3	82399144.12	281983318.8	276571085.6	328045374.7	226166058.5	284751189.3	332888216.6
tyrosine	678793954.8	807522520.9	778672818	698367531	677989476.2	317268051.3	570187192.3	543281184.7	603883052.7	454080177.6	706516343.5	692749730
UDP.GlcNAc	105574483.7	90452571.58	82817367.62	91508514.08	102153776.2	142941574.7	52597124.48	46095269.32	46679130.12	73160286.47	89517366.71	93750933.63
UDP	16401406.01	28006785.76	26879120.17	28142250.19	26294233.12	14761214.9	33557607.78	34807810.86	26354379.83	28231670.42	32943291.46	30042160.45
UMP	4925173.549	4142524.417	4294753.027	4179842.681	4088010.695	5745381.098	9573972.462	10284863.66	8909021.646	9725670.916	6257581.95	4891685.687
Ureidosuccinic_acid	9901550.834	12607140.27	11741299.97	12663365.51	11295998.13	8211255.496	255566495.7	244567035.6	259933951.2	18485558.29	23052575.01	21660527.51
uric.acid	17326346.97	12336535.41	11703498.22	11195110.48	15042547.52	13662889.53	7444000.16	7694553.013	7045318.795	8748616.532	13692766.92	11221631.76
UTP	195819918.4	337638863.3	285028848.9	294086399.8	307622916.7	255310813.6	156183860.8	126384657	129711667	222534560.7	270464272.6	273892288.6
valine	527016020.8	739442958.4	674443399.3	536432697.3	605974174.2	176248562.1	419674706.9	541301975.4	452210112.2	529331441.8	715637635.6	661280069.5
xanthine	13731409.93	9089744.936	8537706.416	9156735.864	9238435.718	9437393.761	6737949.943	7186614.233	9220709.739	8364893.514	10743112.26	12617423.02
dihydroorotate	2413443.846	2204383.905	1813214.738	1479125.765	1075462.725	2858491.141	40305046.79	43467967.56	50602430.4	4836593.668	3842461.257	4836015.247
MS_METABOLITE_DATA_END
#METABOLITES
METABOLITES_START
metabolite_name
2-hydroxyglutarate
3-methyl-2-oxopentanoic_acid
3-phosphoglycerate
Acetyl.CoA
acetylcarnitine
alanine
Alpha.Ketoglutarate
amidoadipate
AMP
argininosuccinate
ascorbate
asparagine
aspartate
asymmetric.dimethylarginine
ATP
beta.alanine
betaine
Butyrylcarnitine
C5.Carnitines
carnitine
CDP.choline
CDP
citrate
citrulline
creatine
creatinine
CTP
cystathionine
dATP
dCTP
dihydroxyacetone_phosphate
dTMP
dTTP
F6P_andor_G1P
FAD
formyl_methionine
Fructose.1.6.bisphosphate
fumarate
gamma.aminobutyric_acid
GDP
glutamate
glutamine
glyceraldehyde_3.phosphate
glycerate
Glycerophosphocholine
GMP
GSH_Ellmans
GSSG
GTP
histidine
homocitrulline
hypotaurine
IMP
isoleucine
lactic_acid
leucine
malate
mannose
methionine
methylthioadenosine
N.acetylglutamate
NAD.
NADH
NADP
NADPH
niacinamide
O.phosphoethanolamine
ornithine
palmitate
phosphocholine
phosphocreatine
phosphoenolpyruvate
Pipecolate
proline
propionylcarnitine
Pyridoxine
Ribose.Ribulose.5.phosphate.3Me.Lys
S.Adenosyl.L.Homocysteine
S.Adenosyl.L.methionine
saccharopine
Sedoheptulose.7.phosphate
serine
sorbitol
succinate
taurine
threonine
trans.urocanate
tryptophan
tyrosine
UDP.GlcNAc
UDP
UMP
Ureidosuccinic_acid
uric.acid
UTP
valine
xanthine
dihydroorotate
METABOLITES_END
#END