#METABOLOMICS WORKBENCH alanyl_20250326_082250 DATATRACK_ID:5783 STUDY_ID:ST003824 ANALYSIS_ID:AN007476 PROJECT_ID:PR002390
VERSION             	1
CREATED_ON             	December 17, 2025, 1:32 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 pyruvate and
ST:STUDY_TITLE                   	uridine supplementation
ST:STUDY_SUMMARY                 	To investigate whether the effects of bathocuproinedisulfonic acid (BCS)
ST:STUDY_SUMMARY                 	treatment (a copper chelator) on steady state metabolite levels can be rescued
ST:STUDY_SUMMARY                 	by supplementation with pyruvate and uridine, SEM cells were treated for 14 days
ST:STUDY_SUMMARY                 	with vehicle or 50uM BCS, and vehicle or 1mM pyruvate/400uM uridine. Cells were
ST:STUDY_SUMMARY                 	seeded at 0.25 million/mL and counted and passaged every two days. This
ST:STUDY_SUMMARY                 	experiment revealed that pyruvate and uridine supplementation significantly
ST:STUDY_SUMMARY                 	rescues levels of nucleotides.
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           	-	20240812_QE2_HILIC_BCSPU_BCSAOX_AYW1172	Sample source:SEM leukemia cells | treatment:Vehicle | treatment2:Vehicle	RAW_FILE_NAME(raw file name)=20240812_QE2_HILIC_BCSPU_BCSAOX_AYW1172.raw
SUBJECT_SAMPLE_FACTORS           	-	20240812_QE2_HILIC_BCSPU_BCSAOX_AYW1173	Sample source:SEM leukemia cells | treatment:Vehicle | treatment2:Vehicle	RAW_FILE_NAME(raw file name)=20240812_QE2_HILIC_BCSPU_BCSAOX_AYW1173.raw
SUBJECT_SAMPLE_FACTORS           	-	20240812_QE2_HILIC_BCSPU_BCSAOX_AYW1174	Sample source:SEM leukemia cells | treatment:Vehicle | treatment2:Vehicle	RAW_FILE_NAME(raw file name)=20240812_QE2_HILIC_BCSPU_BCSAOX_AYW1174.raw
SUBJECT_SAMPLE_FACTORS           	-	20240812_QE2_HILIC_BCSPU_BCSAOX_AYW1175	Sample source:SEM leukemia cells | treatment:BCS | treatment2:Vehicle	RAW_FILE_NAME(raw file name)=20240812_QE2_HILIC_BCSPU_BCSAOX_AYW1175.raw
SUBJECT_SAMPLE_FACTORS           	-	20240812_QE2_HILIC_BCSPU_BCSAOX_AYW1176	Sample source:SEM leukemia cells | treatment:BCS | treatment2:Vehicle	RAW_FILE_NAME(raw file name)=20240812_QE2_HILIC_BCSPU_BCSAOX_AYW1176.raw
SUBJECT_SAMPLE_FACTORS           	-	20240812_QE2_HILIC_BCSPU_BCSAOX_AYW1177	Sample source:SEM leukemia cells | treatment:BCS | treatment2:Vehicle	RAW_FILE_NAME(raw file name)=20240812_QE2_HILIC_BCSPU_BCSAOX_AYW1177.raw
SUBJECT_SAMPLE_FACTORS           	-	20240812_QE2_HILIC_BCSPU_BCSAOX_AYW1178	Sample source:SEM leukemia cells | treatment:Vehicle | treatment2:PyruvateAndUridine	RAW_FILE_NAME(raw file name)=20240812_QE2_HILIC_BCSPU_BCSAOX_AYW1178.raw
SUBJECT_SAMPLE_FACTORS           	-	20240812_QE2_HILIC_BCSPU_BCSAOX_AYW1179	Sample source:SEM leukemia cells | treatment:Vehicle | treatment2:PyruvateAndUridine	RAW_FILE_NAME(raw file name)=20240812_QE2_HILIC_BCSPU_BCSAOX_AYW1179.raw
SUBJECT_SAMPLE_FACTORS           	-	20240812_QE2_HILIC_BCSPU_BCSAOX_AYW1180	Sample source:SEM leukemia cells | treatment:Vehicle | treatment2:PyruvateAndUridine	RAW_FILE_NAME(raw file name)=20240812_QE2_HILIC_BCSPU_BCSAOX_AYW1180.raw
SUBJECT_SAMPLE_FACTORS           	-	20240812_QE2_HILIC_BCSPU_BCSAOX_AYW1181	Sample source:SEM leukemia cells | treatment:BCS | treatment2:PyruvateAndUridine	RAW_FILE_NAME(raw file name)=20240812_QE2_HILIC_BCSPU_BCSAOX_AYW1181.raw
SUBJECT_SAMPLE_FACTORS           	-	20240812_QE2_HILIC_BCSPU_BCSAOX_AYW1182	Sample source:SEM leukemia cells | treatment:BCS | treatment2:PyruvateAndUridine	RAW_FILE_NAME(raw file name)=20240812_QE2_HILIC_BCSPU_BCSAOX_AYW1182.raw
SUBJECT_SAMPLE_FACTORS           	-	20240812_QE2_HILIC_BCSPU_BCSAOX_AYW1183	Sample source:SEM leukemia cells | treatment:BCS | treatment2:PyruvateAndUridine	RAW_FILE_NAME(raw file name)=20240812_QE2_HILIC_BCSPU_BCSAOX_AYW1183.raw
#COLLECTION
CO:COLLECTION_SUMMARY            	One million cells from culture were collected via centrifugation for 20 seconds
CO:COLLECTION_SUMMARY            	at 18,000xG at 4C, washed once with ice-cold 0.9% NaCl, and collected via
CO:COLLECTION_SUMMARY            	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 or 50uM BCS, and vehicle or 1mM
TR:TREATMENT_SUMMARY             	pyruvate and 400uM uridine. Culture media was RPMI-1640 containing 10% FBS and
TR:TREATMENT_SUMMARY             	penicillin and streptomycin in 6-well plates. Cells were seeded at 0.25
TR:TREATMENT_SUMMARY             	million/mL in 4mL and 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 at 0.150 mL/min
CH:FLOW_GRADIENT                 	flow rate. The column oven and autosampler tray were held at 25 °C and 4 °C,
CH:FLOW_GRADIENT                 	respectively.
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 × 10e6, 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	20240812_QE2_HILIC_BCSPU_BCSAOX_AYW1172	20240812_QE2_HILIC_BCSPU_BCSAOX_AYW1173	20240812_QE2_HILIC_BCSPU_BCSAOX_AYW1174	20240812_QE2_HILIC_BCSPU_BCSAOX_AYW1175	20240812_QE2_HILIC_BCSPU_BCSAOX_AYW1176	20240812_QE2_HILIC_BCSPU_BCSAOX_AYW1177	20240812_QE2_HILIC_BCSPU_BCSAOX_AYW1178	20240812_QE2_HILIC_BCSPU_BCSAOX_AYW1179	20240812_QE2_HILIC_BCSPU_BCSAOX_AYW1180	20240812_QE2_HILIC_BCSPU_BCSAOX_AYW1181	20240812_QE2_HILIC_BCSPU_BCSAOX_AYW1182	20240812_QE2_HILIC_BCSPU_BCSAOX_AYW1183
Factors	Sample source:SEM leukemia cells | treatment:Vehicle | treatment2:Vehicle	Sample source:SEM leukemia cells | treatment:Vehicle | treatment2:Vehicle	Sample source:SEM leukemia cells | treatment:Vehicle | treatment2:Vehicle	Sample source:SEM leukemia cells | treatment:BCS | treatment2:Vehicle	Sample source:SEM leukemia cells | treatment:BCS | treatment2:Vehicle	Sample source:SEM leukemia cells | treatment:BCS | treatment2:Vehicle	Sample source:SEM leukemia cells | treatment:Vehicle | treatment2:PyruvateAndUridine	Sample source:SEM leukemia cells | treatment:Vehicle | treatment2:PyruvateAndUridine	Sample source:SEM leukemia cells | treatment:Vehicle | treatment2:PyruvateAndUridine	Sample source:SEM leukemia cells | treatment:BCS | treatment2:PyruvateAndUridine	Sample source:SEM leukemia cells | treatment:BCS | treatment2:PyruvateAndUridine	Sample source:SEM leukemia cells | treatment:BCS | treatment2:PyruvateAndUridine
2-hydroxyglutarate	1065808736	779922427.1	832256953.6	515787446.1	649832967.7	681754375.5	697544519.3	511912520.2	901894277.3	735141646.8	674072960	750219690.8
3-methyl.2.oxopentanoic_acid	21207892.57	21572184.46	25534204.38	11944333.91	11322613.32	11283419.89	47953256.01	44528420.13	47465428.11	54463987.6	55052056.39	57069862.38
3-phosphoglycerate	2310071.763	2565997.146	1996021.371	1661579.298	1533582.401	1513399.265	2919569.3	2615957.692	2592540.836	2785113.81	3794238.72	3217534.438
Acetyl.CoA	4447057.318	3926478.251	3973766.879	2833933.514	2589540.889	2834431.123	3298657.461	3274750.021	3400433.619	2207545.915	2367930.204	2389210.401
acetylcarnitine	64146026.2	75995650.56	73152216	69510337.33	71588333.53	68824382.92	74374850.88	86986956.53	93025711.89	70911469.86	70158649.48	72539230.27
ADP	52456826.67	56767925.52	57572056.8	77884750.95	84123150.48	81847414.16	45826536.38	40814710.15	39107808.3	54495636.77	51481284.01	52552392.52
alanine	93139908.66	90811525.37	88710310.43	89187472.3	83753337.12	79028889.21	148764333.1	146482610.8	151447300.2	127009796.9	121680146	126297992.3
Alpha.Ketoglutarate	25081264.66	26256736.38	28531985.33	18033467.07	15484831.68	12188544.76	80578632.14	74074928.91	65789504.96	72004342.82	72545301.14	69807693.15
AMP	1405219.833	1434684.452	1697024.144	4509750.611	5138965.409	4647662.763	763749.366	1379767.24	1431279.083	2514749.636	2853131.129	3002197.61
arginine	934257459.4	973250799.4	953781904.7	713936142.2	698643729.8	704981787.7	778034013.1	806091117.7	817520703	699925105.1	695926104.8	674450014.9
argininosuccinate	12678865.02	11674038.32	11492591.64	8889269.191	7791026.797	7830831.606	14705187.46	12916333.23	15717646.7	18935278.08	20299077.11	19241447.37
ascorbate	1.07953E+11	92468967249	89307494588	71046275556	70171785565	70134509659	86989122817	83665857394	82470059392	79931054350	76283144094	75191820253
asparagine	1290766892	1289750811	1289074666	870857957.9	844493305.3	913136407	1066745327	1110655978	1068344209	852046490.5	889148810	843531660.2
aspartate	25146407.48	25990337.25	28031463.28	10351050.37	8905118.082	9053222.402	20192843.97	28175603.07	24272751.34	16352460.66	14394745.84	15669145.73
asymmetric.dimethylarginine	8432100.282	9234762.876	9320971.124	6573644.4	6702099.37	6631690.579	7837682.164	7618890.9	7715744.195	6197998.831	6237449.38	6190886.415
ATP	179664065.7	232599015.5	209595471.4	192096656.1	194427275.9	181480082.9	159846044.4	194328314.9	119011520.2	130222672.9	138868044.2	136741268.6
beta.alanine	22642137.15	28420287.32	25518975.64	26744158.37	27867683.28	26577425.32	31663487.93	29595794.02	30738796.72	31664202.13	36076655.54	32301585.24
betaine	814436957.2	839050653.5	767934951	540939645.6	508510447.7	463197676.3	678924301.2	655444941.1	726833720.7	534775979.7	549726885.4	562424367.3
Butyrylcarnitine	71134031.4	69361172.66	68198359.98	59114598.08	52849983.8	50255560.03	52635861.62	53797704.95	54259196.76	42348035.31	43404391.38	39132498.2
C5.Carnitines	11562637.6	11458008.35	11117933.04	16174509.57	13347669.27	12228819.12	6119986.115	5581544.945	5511310.847	6028989.852	5832119.657	5781374.628
carnitine	144345243.5	142179603.7	138562993.7	150905609.4	149495798.4	151299115.1	90860452.89	91783586.65	93994084.6	77160943.67	80621697.28	78243573.01
carnosine	2804937.905	3074778.496	4185688.023	3213951.686	3169902.782	3499234.537	2337509.535	3163536.613	2272881.741	2381379.687	2246092.024	2693871.091
CDP.choline	395257.2997	232191.2237	169715.2154	1063632.865	1291743.066	1327721.136	387071.7238	756336.9344	645313.5319	1570064.849	1347796.197	1174242.809
CDP	1463358.804	1691805.022	1874815.484	1618040.889	1862714.394	1646042.376	2696512.643	2296010.892	2153259.649	3424170.863	3055734.392	3146606.029
cis.aconitate	5443653.571	5727774.835	5038818.779	1749887.071	1888818.839	1329413.904	6836753.333	6910786.656	5649214.213	4307659.95	4606635.906	5160219.861
citrate	221262843.1	260314343.6	233812218.1	83449400.46	78789507.62	66827389.96	283125802.8	282289772.6	249018465.6	168613833.2	196888478.3	181025365.1
citrulline	15934633.56	15431321.33	16052780.56	11736047.7	12923908.56	13600204.6	16837461.56	14395756.33	17380608.02	16100300.85	14575286.47	16027212.64
CMP	224783.3564	214818.3357	238485.7208	439531.8917	350349.9797	311740.4279	329867.6042	338408.5045	334167.2756	733566.8342	729235.7641	711063.2942
creatine	179531917.5	186363437.4	217524001.2	228905904.1	169656633.5	143804739.8	141705571.4	173740528.9	157327566.2	139976196.8	155653434	183126970.9
creatinine	42127930.64	45080269.12	47197730.78	38518568.68	37146420.44	38165036.65	33991215.55	35682223.91	33786469.73	30680908.15	30243207.57	32589327.08
CTP	17499807.7	21892087.47	18473692.3	8522316.481	9662528.487	9133312.362	27564208.46	32909901.86	21588398.56	17519192.54	18492576.82	17913305.15
Cysteine_Ellmans_conjugated	15507412.87	20258294.85	24995511.04	15599862.95	17510884.29	18529520.26	13971103.63	15512850.53	14775633.1	17551773.46	14558587.12	17634582.64
cystathionine	15656291.83	14311978.84	14988414.43	6228190.116	5029191.302	5554434.169	14229331.38	12340583.69	13877461.36	8696213.949	7922609.841	8302632.369
cytidine	393491.8469	123236.3908	137378.7109	213055.178	148661.0034	46590.23156	3263175.397	3299277.743	3859683.518	3328244.177	3120538.387	3391968.093
dihydroxyacetone_phosphate	3600053.267	4034297.959	3755141.158	12949419.79	11114155.87	9233460.374	3332570.976	2733800.325	2897936.565	7193296.002	8716378.192	7624275.735
dTMP	3674391.307	2757888.02	2959326.205	2388863.631	2416238.575	2346144.977	2416610.755	2685323.475	1956973.675	2862255.132	2604278.6	2376003.145
F6P_or_G1P	2723383.055	2639446.788	2788151.435	5033771.424	5628033.541	5516740.748	1643364.039	1366503.66	1474232.039	1627635.286	1660447.685	1726321.228
FAD	1721218.254	1770012.139	1590030.911	1683117.971	1628326.675	1621148.733	1461744.847	1503184.495	1127886.003	1256204.438	1269787.786	1199912.013
Fructose.1.6.bisphosphate	1191353.049	1174167.644	990964.3632	906125.5751	902889.3918	946656.3563	1047597.074	1077146.498	1095585.128	810267.4742	830840.7588	800423.5809
fumarate	40771408.82	32066831.73	33891989.53	21436454.11	19679436.09	21667944.56	33770342.53	37324613.93	33603102.2	41588758.66	36910100.13	34939332.26
gamma.aminobutyric_acid	62246335.9	69373214.81	66185678.88	59158288.72	67473067.15	65521969.97	63475037.49	68834064.79	70218040.91	60616514.03	61928819.05	60065340.08
GDP	3419218.471	3914199.72	3794543.415	6377378.171	7578105.168	7235788.178	3356823.833	2745336.325	2712662.015	3999391.08	3930869.922	4046267.554
Glucose.6.phosphate	301506.8381	307953.3686	300508.2153	367645.6179	382238.9855	340325.4428	275250.0257	232044.4234	235432.2143	245728.3935	215597.4084	209917.9401
glutamate	813995528.4	842598397.5	850346991.1	615511230.8	610878258.6	617201034.2	606373131	676043175.7	658905368.6	399787829.1	353767926.7	383029837.3
glutamine	3136937282	3241255171	3102998822	2283695638	2367118627	2466590143	3078633746	3167140896	3165524990	2377416661	2449087613	2430490070
glyceraldehyde_3.phosphate	3600689.636	4035010.552	3690852.183	12950670.87	11049624.2	9235053.574	3333062.859	2734228.116	2898288.553	7194327.557	8717433.247	7625112.572
glycerate	36599217.78	30893597.08	25396377.64	20551078.07	18286837.07	22104894.68	25293422.89	24637629.11	26230110.62	22952317.24	21609152.49	20351759.99
Glycerol.3.Phosphate	12288848.63	11198586.69	12414740.93	49944332.27	51703634.75	55318980.42	2336222.621	2123665.401	2500243.464	11069144.57	12219718.67	11769360.01
Glycerophosphocholine	1394745827	1313984529	1325672718	959151282.1	866844080	917099100.4	1241420821	1226801487	1351219820	982769330.6	867215098.3	940941092.6
glycine	10725611.32	9315751.846	9940006.253	8385333.004	7936786.177	8501915.325	9936694.022	10080121.53	10026372.63	8584761.573	6667188.978	7640976.969
GMP	592671.7263	492210.13	710288.7164	2306344.065	2431270.106	2451526.881	571880.8208	560417.7871	576228.4088	1434889.678	1502298.518	1376094.058
GSH_Ellmans	287304130.2	285530353.5	261425422.4	272212616.3	262238402.5	261267271.6	252207234.9	261731089.7	244852511.1	214059221.3	225591397.9	211315734.9
GSSG	2709686.619	2874639.126	2645927.734	3902787.663	3508313.184	3486372.525	2751512.579	3223025.24	2034691.417	2272120.847	2186081.634	2283448.684
GTP	12884198.16	16226850.7	13418322.38	16429736.6	16998591.25	15280677.55	12685068.53	15466498.27	7544711.994	9582691.976	11733241.31	10605088.26
histidine	330064441.9	349289833.5	361657644.7	283049509.5	286534048.1	291805484.5	289089788.8	260193766	269508348.6	225808380.8	182149197.7	217364923.3
hypotaurine	51525584.94	48992030.73	59477650.93	29502118.16	43805384.55	48381979.09	43439645.9	29992719.65	45813673.64	38304486.97	44423578.7	53413120.61
IMP	677902.3972	698658.9201	728881.1777	2650178.07	2881965.392	2856098.372	385750.5831	325435.2483	298976.9525	417322.1887	583648.1607	462932.9462
isoleucine	755869007.3	736495529.7	649082342.6	569412512.8	564075231.8	518812591.5	456885631.3	415288128	619356124.1	421103382.3	384309542.1	404226360.9
lactic_acid	315317042.1	376849799.1	400447723.2	440971389.7	465057274	392406555.1	360861094.8	315720216.4	349409768.9	578763578.4	668746151.3	661799529.9
lysine	14602087.11	15528924.93	16407290.01	12497587.96	12363325.32	12925791.35	12358833.82	12881128.17	12732599.05	12035894.15	11587394.34	11169835.03
mannose	5397943.337	5077858.897	5872857.601	2937295.349	3743076.457	3611474.641	3635198.243	4112188.784	4038061.22	3976212.717	3169748.11	3267416.789
Methionine.sulfoxide	81842545.16	82967993.6	73860827.99	57302682.01	60347551.19	65563499.68	68584399.89	57967004.37	85257489.01	51113135.18	51557802.93	55246563.41
methionine	267504091.1	246613524.3	244682200.6	194763980	197420165.8	200571653.7	199678159.7	189367372.9	244841184.5	177104526.7	168916297.8	176742578.3
methylthioadenosine	8281501.23	8465158.667	7424748.079	5025908.876	5107538.624	4951293.198	7001775.634	6098430.615	7440812.702	4459743.132	4368081.988	3923954.039
myo.inositol	205859566.7	199591468	199162518.7	218795311.9	212145862.3	202481537.5	171844472.8	177343025.4	175843536.1	165216356.3	162066195	160397128.8
N.acetylglutamate	8225156.695	8046001.913	8073400.619	6780497.553	6092654.936	7056994.03	4701555.319	4320595.947	5216968.569	4738692.727	4461512.379	4078095.349
NAD.	92078852.59	96151825.31	92714405.65	78903724.69	78631322.64	78321827.97	82599796.44	86078273.6	77943819.37	73850805.06	75134458.81	72279555.14
NADH	13631584.54	14810139.81	14145124.52	26632525.41	23488756.31	23574578.93	9366140.211	10760600.93	7778307.571	16412183.12	18138463.19	17375907.78
NADP	741259.5987	715983.8452	647489.0119	754662.8313	725391.4013	665567.1159	639223.7904	608566.356	696541.8669	547242.7534	504167.8576	534011.7235
NADPH	3633346.104	4039895.927	3755292.028	2990383.949	2742855.542	2835207.271	2903792.866	3298636.569	3000127.407	2439903.62	2558617.534	2586726.166
niacinamide	34925646.58	36776606.49	38306099.56	30844239.36	33049672.63	39174906.86	23431278.54	31844173.38	31599820.66	29479265.44	30345896.33	32813448.82
O.phosphoethanolamine	1029402.677	952353.5607	917574.0307	12243738	14763606.21	18350839.92	654737.1699	1239306.044	1196992.14	3855654.204	3219273.702	3705172.732
ornithine	37843297.51	39915580.06	43926473.66	29643208.33	29375680.39	31533061.57	32295812.65	32499301.27	28216922.32	27808007.45	26630366.3	27364427.06
palmitate	162012400	94211605	88870302.53	80545336.59	75559345.31	87137428.95	78790045.3	68114808.22	99562781.99	83051212.14	91493509.55	110661142.3
Pantothenate	363324490.3	385762974.6	373312077.8	251534105	229473352.7	233494555.7	274359208.1	280392900.2	284487830.7	207487685	210980107	216938703.8
phosphocholine	10290246640	9976774879	9862630496	5842922726	6206304592	6328950913	6684217257	6206618894	7432416379	4655126504	4460125432	4617816906
phosphocreatine	1274195.759	1221960.501	1060278.915	1032023.447	1063058.34	1151992.462	697372.5598	621062.5788	733962.8439	606574.9364	594760.9898	669661.3821
phosphoenolpyruvate	866865.0805	807339.6787	737006.4503	289818.0334	287211.7705	308466.0247	1013506.56	1312336.263	1087430.581	854391.1413	1341492.721	1091580.947
proline	2461352126	2396191212	2412543510	2596376848	2455825253	2267307350	2039380516	1803901079	2052407888	2293902888	2244931972	2246587394
propionylcarnitine	4347787.453	4446381.311	4849461.869	2369738.752	1898441.364	2361758.625	3880937.253	4277068.96	3907996.137	2044323.128	2160424.032	2177030.388
Pyridoxine	52332044.06	57898793.99	58575096.48	47612806.53	44079978.71	48218189.59	45682212.27	48506971.86	45159265.18	39208589.37	39867365.05	41979597.17
S.Adenosyl.L.Homocysteine	7840923.079	8496416.847	7937695.196	6040276.367	5801799.776	6138038.964	8189380.37	7106210.304	7909784.804	6233294.998	6262912.459	5744234.417
S.Adenosyl.L.methionine	120805032.7	116101579.8	121386704.8	95239514.02	94291992.95	92291934.26	104483454.1	120490899.3	102780903	93340907.42	99181112.28	94280795.03
sarcosine	93991357.22	90811525.37	89607010.67	88811253.68	83753337.12	79028889.21	148017845.6	146482610.8	151702421.6	126714640.8	121525385.3	126297992.3
Sedoheptulose.7.phosphate	1703736.364	1683710.693	1777551.091	5380565.149	5391273.54	6196895.538	238282.5345	224058.9872	138842.6995	677033.8798	853872.2987	847233.1736
serine	44961820.2	38398095.45	39637919.62	37547049.32	36745691.76	41133578.73	45150430.17	48387622.21	46586714.43	56465153.4	43037722.67	49157129.39
succinate	21511327.42	18928216.58	14370729.13	50824787.99	51681558.59	46144412.18	23861612.49	21220564.14	30593316.68	63694593.34	66975180.07	66338336.38
taurine	145676304.3	142377854.2	137086091.4	152007409	150539695.9	141985007.4	162593101.7	139476136.3	154795576.7	167619475.7	183736551.9	167404888.8
threonine	119911897.5	108348060.9	114168083.1	87357636.89	80438491.46	89393043.76	94548837.1	101100886.6	110254989.5	89763784.86	84028930.35	84817312
tryptophan	115374508.5	109198330.9	109961283.6	93142973.23	94041398.56	93002098.37	94737267.31	91143418.11	101590411.6	83909187.04	85399139.32	87473530.13
tyrosine	228864053.8	218842987.4	226792618.1	160146750.2	169932268.6	176256241.7	184114061.6	168059431.7	208255949.3	158541927.4	136473811.6	149416240.4
UDP.GlcNAc	46375281.33	46849481.89	44345189.79	17116515.73	16312137.73	15836538.38	72530043.69	72923539.61	72222123.09	49200485.48	49514522.58	46160105.03
UDP	6987779.638	7980177.248	8250433.038	7344300.914	7690648.353	7321240.054	14510591.56	11762021.19	11612578.65	17858445.6	15916252.13	16077691.79
UMP	656704.3614	490398.9553	748567.4479	1739072.678	1415862.17	1508653.469	1373705.637	1536489.632	1455949.714	3528203.752	3455057.981	3331897.075
Ureidosuccinic_acid	13282789.77	14990111.88	15538939.64	146044924.3	146287817.6	147117117.3	226888.0629	841730.0126	1135244.114	17712565.57	17757496.1	16728123.69
uric.acid	2884812.99	3707150.25	4099083.978	1949024.656	2126299.361	1824996.554	2802705.557	3376833.112	2774653.806	2753936.945	2690469.952	2518631.42
UTP	50940061.97	66235303.29	55589401.14	27061768.71	27592608.21	24624693.27	101660620.4	112570671.1	73389753.19	60848348.07	67684571.7	65069701.06
dihydroorotate	1930081.225	1952680.836	1902981.966	20953757.04	19731003.94	20434405.78	134515.556	206766.9632	31548.25774	1127209.812	1748286.957	1333667.131
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
ascorbate
asparagine
aspartate
asymmetric.dimethylarginine
ATP
beta.alanine
betaine
Butyrylcarnitine
C5.Carnitines
carnitine
carnosine
CDP.choline
CDP
cis.aconitate
citrate
citrulline
CMP
creatine
creatinine
CTP
Cysteine_Ellmans_conjugated
cystathionine
cytidine
dihydroxyacetone_phosphate
dTMP
F6P_or_G1P
FAD
Fructose.1.6.bisphosphate
fumarate
gamma.aminobutyric_acid
GDP
Glucose.6.phosphate
glutamate
glutamine
glyceraldehyde_3.phosphate
glycerate
Glycerol.3.Phosphate
Glycerophosphocholine
glycine
GMP
GSH_Ellmans
GSSG
GTP
histidine
hypotaurine
IMP
isoleucine
lactic_acid
lysine
mannose
Methionine.sulfoxide
methionine
methylthioadenosine
myo.inositol
N.acetylglutamate
NAD.
NADH
NADP
NADPH
niacinamide
O.phosphoethanolamine
ornithine
palmitate
Pantothenate
phosphocholine
phosphocreatine
phosphoenolpyruvate
proline
propionylcarnitine
Pyridoxine
S.Adenosyl.L.Homocysteine
S.Adenosyl.L.methionine
sarcosine
Sedoheptulose.7.phosphate
serine
succinate
taurine
threonine
tryptophan
tyrosine
UDP.GlcNAc
UDP
UMP
Ureidosuccinic_acid
uric.acid
UTP
dihydroorotate
METABOLITES_END
#END