#METABOLOMICS WORKBENCH Anderson222_20251028_110231 DATATRACK_ID:6608 STUDY_ID:ST004440 ANALYSIS_ID:AN007436 PROJECT_ID:PR002804
VERSION             	1
CREATED_ON             	December 15, 2025, 11:48 am
#PROJECT
PR:PROJECT_TITLE                 	The Nicotinamide Salvage Pathway is a Unique Metabolic target in High-Risk MDS
PR:PROJECT_TITLE                 	Stem Cells
PR:PROJECT_TYPE                  	Primary Research Article
PR:PROJECT_SUMMARY               	High-risk myelodysplastic syndrome (HR-MDS) is an incurable malignant clonal
PR:PROJECT_SUMMARY               	disorder originating in the hematopoietic stem and progenitor cells (HSPC). The
PR:PROJECT_SUMMARY               	current standard of care for HR-MDS patients is hypomethylating agents, like
PR:PROJECT_SUMMARY               	azacitidine; however, the response rate is poor, usually with remission of less
PR:PROJECT_SUMMARY               	than two years. Thus, to improve HR-MDS patient outcomes, an unmet clinical
PR:PROJECT_SUMMARY               	need, it is essential to identify better therapeutic targets by exploring
PR:PROJECT_SUMMARY               	vulnerabilities of HR-MDS HSPCs. We have previously demonstrated that inhibiting
PR:PROJECT_SUMMARY               	protein synthesis is a vulnerability for HR-MDS. Subsequently, we identified
PR:PROJECT_SUMMARY               	that HR-MDS HSPCs have a significant upregulation of metabolic proteins required
PR:PROJECT_SUMMARY               	for glycolysis, TCA cycle and oxidative phosphorylation. Consistently, we see
PR:PROJECT_SUMMARY               	reduced glycolytic and TCA cycle metabolites, but an increased oxygen
PR:PROJECT_SUMMARY               	consumption rate in HR-MDS HSPCs compared to healthy, suggesting an increased
PR:PROJECT_SUMMARY               	metabolic rate. Most of the enriched proteins in HR-MDS either use NAD for
PR:PROJECT_SUMMARY               	energy production, maintain NAD(H) redox balance or use NAD as a cofactor for
PR:PROJECT_SUMMARY               	their function. Therefore, we inhibited NAMPT, the rate-limiting enzyme in the
PR:PROJECT_SUMMARY               	nicotinamide salvage pathway of NAD anabolism, using small molecule inhibitors
PR:PROJECT_SUMMARY               	and genetic approaches. NAMPT inhibition significantly decreased NAD levels,
PR:PROJECT_SUMMARY               	reducing the oxygen consuming capacity of HR-MDS-HSPCs compared to normal.
PR:PROJECT_SUMMARY               	Consequently, to compensate, HR-MDS HSPCs, upon NAMPT inhibition positively
PR:PROJECT_SUMMARY               	enriched metabolic proteins associated with amino acid metabolism, lipid
PR:PROJECT_SUMMARY               	metabolism, and the citric acid cycle increasing carbon flux into the
PR:PROJECT_SUMMARY               	aspartate-malate shuttle and the pentose phosphate pathway, while reducing flux
PR:PROJECT_SUMMARY               	through glycolysis and citric acid cycle. Finally, from a functional
PR:PROJECT_SUMMARY               	perspective, NAMPT significantly impaired self-renewal and colony forming
PR:PROJECT_SUMMARY               	potential of HR-MDS HSPCs compared to normal. Importantly, we observed increased
PR:PROJECT_SUMMARY               	cell death of HR-MDS HSPCs compared to normal in both in vitro cultures and in
PR:PROJECT_SUMMARY               	vivo xenograft studies, indicating NAMPT as a tractable target for therapeutic
PR:PROJECT_SUMMARY               	inhibition in HR- MDS patients. Collectively, our data suggest that NAMPT is
PR:PROJECT_SUMMARY               	uniquely required for the function and survival of HR-MDS HSPCs compared to
PR:PROJECT_SUMMARY               	normal and thus can serve as a promising therapeutic target.
PR:INSTITUTE                     	University of Colorado School of Medicine
PR:DEPARTMENT                    	Hematology
PR:LABORATORY                    	Jordan / Pietras
PR:LAST_NAME                     	Anderson
PR:FIRST_NAME                    	Colin
PR:ADDRESS                       	12801 East 17th Avenue, Aurora, CO 80045
PR:EMAIL                         	Colin.c.anderson@cuanschutz.edu
PR:PHONE                         	303-724-3339
PR:FUNDING_SOURCE                	NIH
PR:CONTRIBUTORS                  	Sweta B. Patel, Daniel Moskop, Steven Moriera, Stephanie Gipson, Colin C.
PR:CONTRIBUTORS                  	Anderson, Alexendra Crook, Maxwell McCabe, Daniel Stephenson, Hannah E. Terry,
PR:CONTRIBUTORS                  	Andrew Kent, Tracy Young, Anna Krug, Caitlin Price, Monica Ransom, Regan Miller,
PR:CONTRIBUTORS                  	Ana Vujovic, Mohammad Minhajuddin, Mark J. Althoff, The CUIJBP Consortium,
PR:CONTRIBUTORS                  	Anthony Saviola, Brett M. Stevens, Robert S. Welner, Ekaterina L. Andrianova,
PR:CONTRIBUTORS                  	Andrei V. Gudkov, Travis Nemkov, Angelo D’Alessandro, Austin E. Gillen, Craig
PR:CONTRIBUTORS                  	T. Jordan*, Eric M. Pietras*
#STUDY
ST:STUDY_TITLE                   	Glutamine and Glucose stable-isotope tracing in NAMPT Inhibition
ST:STUDY_TYPE                    	SIL Tracing Metabolomics by HPLC/MS
ST:STUDY_SUMMARY                 	Using cell media-supplemented heavy carbon-labeled glucose and glutamine,
ST:STUDY_SUMMARY                 	samples (N=4 per group) were collected at baseline and 3 hours (glucose) or 12
ST:STUDY_SUMMARY                 	hours (glutamine) after OT82 or DMSO exposure. We observed major shifts in
ST:STUDY_SUMMARY                 	metabolic intermediates across multiple pathways with OT82 treatment including
ST:STUDY_SUMMARY                 	TCA cycle and glycolysis.
ST:INSTITUTE                     	University of Colorado School of Medicine
ST:DEPARTMENT                    	Hematology
ST:LABORATORY                    	Jordan / Pietras
ST:LAST_NAME                     	Anderson
ST:FIRST_NAME                    	Colin
ST:ADDRESS                       	13001 East 17th Place
ST:EMAIL                         	Colin.c.anderson@cuanschutz.edu
ST:PHONE                         	303-724-3339
#SUBJECT
SU:SUBJECT_TYPE                  	Cultured cells
SU:SUBJECT_SPECIES               	Homo sapiens
SU:TAXONOMY_ID                   	9606
#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           	-	CA24_52-1	Treatment:DMSO | Timepoint:12H | Sample source:MDS-L Cells	Tracer=GLUT; Injection order=29; Injection order=5; RAW_FILE_NAME(Raw data file name NEG)=CA24_52-1_r29-.raw; RAW_FILE_NAME(Raw data file name POS)=CA24_52-1_r5+.raw
SUBJECT_SAMPLE_FACTORS           	-	CA24_52-2	Treatment:DMSO | Timepoint:12H | Sample source:MDS-L Cells	Tracer=GLUT; Injection order=13; Injection order=13; RAW_FILE_NAME(Raw data file name NEG)=CA24_52-2_r13-.raw; RAW_FILE_NAME(Raw data file name POS)=CA24_52-2_r13+.raw
SUBJECT_SAMPLE_FACTORS           	-	CA24_52-3	Treatment:DMSO | Timepoint:12H | Sample source:MDS-L Cells	Tracer=GLUT; Injection order=19; Injection order=8; RAW_FILE_NAME(Raw data file name NEG)=CA24_52-3_r19-.raw; RAW_FILE_NAME(Raw data file name POS)=CA24_52-3_r8+.raw
SUBJECT_SAMPLE_FACTORS           	-	CA24_52-4	Treatment:DMSO | Timepoint:12H | Sample source:MDS-L Cells	Tracer=GLUT; Injection order=11; Injection order=2; RAW_FILE_NAME(Raw data file name NEG)=CA24_52-4_r11-.raw; RAW_FILE_NAME(Raw data file name POS)=CA24_52-4_r2+.raw
SUBJECT_SAMPLE_FACTORS           	-	CA24_52-5	Treatment:OT | Timepoint:12H | Sample source:MDS-L Cells	Tracer=GLUT; Injection order=6; Injection order=15; RAW_FILE_NAME(Raw data file name NEG)=CA24_52-5_r6-.raw; RAW_FILE_NAME(Raw data file name POS)=CA24_52-5_r15+.raw
SUBJECT_SAMPLE_FACTORS           	-	CA24_52-6	Treatment:OT | Timepoint:12H | Sample source:MDS-L Cells	Tracer=GLUT; Injection order=25; Injection order=7; RAW_FILE_NAME(Raw data file name NEG)=CA24_52-6_r25-.raw; RAW_FILE_NAME(Raw data file name POS)=CA24_52-6_r7+.raw
SUBJECT_SAMPLE_FACTORS           	-	CA24_52-7	Treatment:OT | Timepoint:12H | Sample source:MDS-L Cells	Tracer=GLUT; Injection order=1; Injection order=1; RAW_FILE_NAME(Raw data file name NEG)=CA24_52-7_r1-.raw; RAW_FILE_NAME(Raw data file name POS)=CA24_52-7_r1+.raw
SUBJECT_SAMPLE_FACTORS           	-	CA24_52-8	Treatment:OT | Timepoint:12H | Sample source:MDS-L Cells	Tracer=GLUT; Injection order=3; Injection order=25; RAW_FILE_NAME(Raw data file name NEG)=CA24_52-8_r3-.raw; RAW_FILE_NAME(Raw data file name POS)=CA24_52-8_r25+.raw
SUBJECT_SAMPLE_FACTORS           	-	CA24_52-17	Treatment:DMSO | Timepoint:3H | Sample source:MDS-L Cells	Tracer=GLUC; Injection order=7; Injection order=3; RAW_FILE_NAME(Raw data file name NEG)=CA24_52-17_r7-.raw; RAW_FILE_NAME(Raw data file name POS)=CA24_52-17_r3+.raw
SUBJECT_SAMPLE_FACTORS           	-	CA24_52-18	Treatment:DMSO | Timepoint:3H | Sample source:MDS-L Cells	Tracer=GLUC; Injection order=15; Injection order=22; RAW_FILE_NAME(Raw data file name NEG)=CA24_52-18_r15-.raw; RAW_FILE_NAME(Raw data file name POS)=CA24_52-18_r22+.raw
SUBJECT_SAMPLE_FACTORS           	-	CA24_52-19	Treatment:DMSO | Timepoint:3H | Sample source:MDS-L Cells	Tracer=GLUC; Injection order=2; Injection order=29; RAW_FILE_NAME(Raw data file name NEG)=CA24_52-19_r2-.raw; RAW_FILE_NAME(Raw data file name POS)=CA24_52-19_r29+.raw
SUBJECT_SAMPLE_FACTORS           	-	CA24_52-20	Treatment:DMSO | Timepoint:3H | Sample source:MDS-L Cells	Tracer=GLUC; Injection order=9; Injection order=18; RAW_FILE_NAME(Raw data file name NEG)=CA24_52-20_r9-.raw; RAW_FILE_NAME(Raw data file name POS)=CA24_52-20_r18+.raw
SUBJECT_SAMPLE_FACTORS           	-	CA24_52-21	Treatment:OT | Timepoint:3H | Sample source:MDS-L Cells	Tracer=GLUC; Injection order=30; Injection order=21; RAW_FILE_NAME(Raw data file name NEG)=CA24_52-21_r30-.raw; RAW_FILE_NAME(Raw data file name POS)=CA24_52-21_r21+.raw
SUBJECT_SAMPLE_FACTORS           	-	CA24_52-22	Treatment:OT | Timepoint:3H | Sample source:MDS-L Cells	Tracer=GLUC; Injection order=8; Injection order=19; RAW_FILE_NAME(Raw data file name NEG)=CA24_52-22_r8-.raw; RAW_FILE_NAME(Raw data file name POS)=CA24_52-22_r19+.raw
SUBJECT_SAMPLE_FACTORS           	-	CA24_52-23	Treatment:OT | Timepoint:3H | Sample source:MDS-L Cells	Tracer=GLUC; Injection order=20; Injection order=31; RAW_FILE_NAME(Raw data file name NEG)=CA24_52-23_r20-.raw; RAW_FILE_NAME(Raw data file name POS)=CA24_52-23_r31+.raw
SUBJECT_SAMPLE_FACTORS           	-	CA24_52-24	Treatment:OT | Timepoint:3H | Sample source:MDS-L Cells	Tracer=GLUC; Injection order=18; Injection order=27; RAW_FILE_NAME(Raw data file name NEG)=CA24_52-24_r18-.raw; RAW_FILE_NAME(Raw data file name POS)=CA24_52-24_r27+.raw
#COLLECTION
CO:COLLECTION_SUMMARY            	Cells were pelleted by gentle centrifugation and media was removed. The cells
CO:COLLECTION_SUMMARY            	were washed several times with PBS before finally being pelleted. The remaining
CO:COLLECTION_SUMMARY            	PBS was aspirated and the cell pellet was flash frozen in liquid nitrogen and
CO:COLLECTION_SUMMARY            	stored at -80C.
CO:SAMPLE_TYPE                   	Stem cells
#TREATMENT
TR:TREATMENT_SUMMARY             	500,000 MDS-L cells were treated with DMSO and 100nM OT82 for 24h. At the final
TR:TREATMENT_SUMMARY             	3h and 12h, 2.5mM heavy labeled glucose (13C6; Cambridge Isotope Laboratories,
TR:TREATMENT_SUMMARY             	CLM-1396-1) and 0.5mM heavy labeled glutamine (13C6,15N2; Cambridge Isotope
TR:TREATMENT_SUMMARY             	Laboratories, CNLM-1275-H-0.1) were spiked into the culture respectively.
#SAMPLEPREP
SP:SAMPLEPREP_SUMMARY            	Cells were extracted to a final concentration of 2E06 per mL of cold
SP:SAMPLEPREP_SUMMARY            	MeOH:ACN:H2O (5:3:2, v:v:v). Samples were then vortexed at 4 °C for 30 minutes.
SP:SAMPLEPREP_SUMMARY            	Following vortexing, samples were centrifuged at 12700 RPM for 10 minutes at 4
SP:SAMPLEPREP_SUMMARY            	°C and supernatant was transferred to a new autosampler vial for analysis.
#CHROMATOGRAPHY
CH:CHROMATOGRAPHY_SUMMARY        	5 Min Positive: After sample randomization, 10 μL of extracts were injected
CH:CHROMATOGRAPHY_SUMMARY        	into a Thermo Vanquish UHPLC system (San Jose, CA, USA) and resolved on a Waters
CH:CHROMATOGRAPHY_SUMMARY        	Acquity BEH C18 column (2.1 x 100 mm, 1.7 um) at 450 μL/min through a 5 min
CH:CHROMATOGRAPHY_SUMMARY        	gradient from 5 to 95% organic solvent B (mobile phases: A = water, 0.1% formic
CH:CHROMATOGRAPHY_SUMMARY        	acid; B = acetonitrile, 0.1% formic acid) in positive ion mode. Solvent
CH:CHROMATOGRAPHY_SUMMARY        	gradient: 0-0.5 min 5% B, 0.5-1.1 min 5-95% B, 1.1-2.75 min hold at 95% B,
CH:CHROMATOGRAPHY_SUMMARY        	2.75-3 min 95-5% B, 3-5 min hold at 5% B.
CH:CHROMATOGRAPHY_TYPE           	Reversed phase
CH:INSTRUMENT_NAME               	Thermo Vanquish
CH:COLUMN_NAME                   	Waters ACQUITY UPLC BEH C18 (100 x 2.1 mm, 1.7 μm)
CH:SOLVENT_A                     	100% Water; 0.1% Formic acid
CH:SOLVENT_B                     	100% Acetonitrile; 0.1% Formic acid
CH:FLOW_GRADIENT                 	0-0.5 min 5% B, 0.5-1.1 min 5-95% B, 1.1-2.75 min hold at 95% B, 2.75-3 min
CH:FLOW_GRADIENT                 	95-5% B, 3-5 min hold at 5% B
CH:FLOW_RATE                     	450 μL/min
CH:COLUMN_TEMPERATURE            	45°C
#ANALYSIS
AN:ANALYSIS_TYPE                 	MS
#MS
MS:INSTRUMENT_NAME               	Thermo Orbitrap Exploris 120
MS:INSTRUMENT_TYPE               	Orbitrap
MS:MS_TYPE                       	ESI
MS:ION_MODE                      	POSITIVE
MS:MS_COMMENTS                   	Following data acquisition, .raw files were converted to .mzXML using
MS:MS_COMMENTS                   	RawConverter. Metabolites were then annotated based on intact mass, 13C natural
MS:MS_COMMENTS                   	isotope pattern and retention times in conjunction with the KEGG database and an
MS:MS_COMMENTS                   	in-house standard library. Peaks were integrated using El-Maven (Elucidata).
MS:MS_COMMENTS                   	Quality control was assessed as using technical replicates run at the beginning,
MS:MS_COMMENTS                   	end, and middle of each sequence as previously described.
#MS_METABOLITE_DATA
MS_METABOLITE_DATA:UNITS	A.U.
MS_METABOLITE_DATA_START
Samples	CA24_52-1	CA24_52-2	CA24_52-3	CA24_52-4	CA24_52-5	CA24_52-6	CA24_52-7	CA24_52-8	CA24_52-17	CA24_52-18	CA24_52-19	CA24_52-20	CA24_52-21	CA24_52-22	CA24_52-23	CA24_52-24
Factors	Treatment:DMSO | Timepoint:12H | Sample source:MDS-L Cells	Treatment:DMSO | Timepoint:12H | Sample source:MDS-L Cells	Treatment:DMSO | Timepoint:12H | Sample source:MDS-L Cells	Treatment:DMSO | Timepoint:12H | Sample source:MDS-L Cells	Treatment:OT | Timepoint:12H | Sample source:MDS-L Cells	Treatment:OT | Timepoint:12H | Sample source:MDS-L Cells	Treatment:OT | Timepoint:12H | Sample source:MDS-L Cells	Treatment:OT | Timepoint:12H | Sample source:MDS-L Cells	Treatment:DMSO | Timepoint:3H | Sample source:MDS-L Cells	Treatment:DMSO | Timepoint:3H | Sample source:MDS-L Cells	Treatment:DMSO | Timepoint:3H | Sample source:MDS-L Cells	Treatment:DMSO | Timepoint:3H | Sample source:MDS-L Cells	Treatment:OT | Timepoint:3H | Sample source:MDS-L Cells	Treatment:OT | Timepoint:3H | Sample source:MDS-L Cells	Treatment:OT | Timepoint:3H | Sample source:MDS-L Cells	Treatment:OT | Timepoint:3H | Sample source:MDS-L Cells
L-alanine	2031438	1988058.62	1758875.38	1581238.38	2768658	1308516.12	2174317.75	3124574	2165236.25	2490067.25	2537569.25	2495891	938460.94	1503643.62	1424950	2297973.25
L-arginine	9218863	9682687	9871843	11576488	18368530	15417128	15569296	18856006	9567759	11419887	12672481	10653211	17600594	17218726	20063534	19576570
L-asparagine	3566498.75	4282168.5	3239703.75	2447658.25	5878665.5	3071357.75	3915281.75	6908689.5	3194388.75	4932597	5125377.5	4598408.5	3048580.75	4125116.25	4107786.25	5201759.5
L-cysteine	534976.19	383840	367909.25	335154.19	243610.64	167976.97	199040.27	240590.2	455073.12	362658.78	427910.09	446927.16	166232.55	210182.39	230953.17	222679.05
L-glutamate	29320214	24086368	22896726	18421516	16306049	10457959	14642483	18160450	31438902	28391120	29873912	29385146	13009880	13772315	15210860	16971532
L-glutamate 13C5	5731802	4930176.5	4492844.5	3725777	1849179	1256030	1777514.88	2048494.38	0	0	0	0	10078.39	10655.36	8910.59	26554.65
L-glutamate 13C5 15N1	933348.19	754761.44	640712.69	546870.25	850256	535716.69	700404.25	979944.56	0	0	0	0	0	0	0	0
L-glutamate 15N1	2798573.25	2265361.75	2041645.62	1705095	926653.31	590689.38	875681.94	1072049.62	104620	105277.87	89300.27	102364.79	37395.65	41982.18	32326.19	60590.09
L-glutamine	24861366	27813354	22604352	17000170	40213820	20190966	28692706	42496120	21163420	28264630	29657870	28092982	18290366	23646522	23021850	32396886
L-glutamine 13C5 15N2	7942246.5	8817869	7491206.5	5665280.5	12916933	6398327.5	9472141	14040043	0	0	4512.35	0	5409.06	0	6709.62	4664.28
glycine	526617.94	698313.06	494324.72	397021.59	681809.94	243336.45	318527.75	846497.5	518574.88	785019	778867.5	737631.81	366718.22	323363.53	356070.34	630130.12
L-leucine/isoleucine	11292873	12777531	10804775	10341331	19787198	12892680	14750211	22118608	12670173	15136068	16423569	14700841	16908562	17936542	21412426	20470726
L-lysine	235548.27	215491.92	256576.62	557539.56	421810.59	305604.72	386423.34	434088.66	251309.3	277329.78	269204.12	243793	327891.09	364364.91	415357.25	394709.62
L-methionine	1878526.62	1571606	1672208.12	1406882.88	2078870.38	1622145.88	2289227	2281739	1959957.38	1795730.62	1617322	1727505.38	1542736.88	1819926.38	1807429.62	2168355.25
L-phenylalanine	10626863	10299380	11148902	14429819	15641192	16045764	11688133	17705576	13268364	16097497	16666176	13570237	20030050	21644074	26219562	21512390
L-proline	61028588	40427112	48633124	49103140	33815516	30941126	39367196	37966052	88141032	69546680	71767336	58769812	35059916	40505372	42402116	44002620
L-serine	1323356	1560563.88	1222974.5	1215523.5	2611265.75	1224032.12	1664548.38	2865786.75	1090402.12	1540429.62	1737185.88	1535939.12	1223506.5	1593861	1623123.12	2139694.75
L-threonine	2124862	1456261.88	1443223.5	1352228.75	2350101.25	1173399.25	2158974.75	2542397	1583193.5	1406462	1504778	1272965.62	1213620.88	1361702.88	1439501.5	1842654.88
L-tryptophan	2341749	2384198	2485896	2888708	3684138	3450517.25	3275439.25	3887983.25	3555214.75	3917418.75	3781125.25	3166755.25	4276049.5	4814901.5	5683640.5	4603945.5
L-tyrosine	3740060.75	2771013.75	3008266.75	3594602.25	3692333	3172841.75	4807933.5	4171310.75	4129060.75	3267304	2813826	2997550.75	2772701	3000374.25	3136818	3351456
AMP	2694331.5	1567699.88	1798299.88	3052516.75	2983495	3205038.25	5813598.5	3483372	3785748.75	1655860.38	1547888.88	1398046.38	1645594.62	2435535.75	2126975.75	3448429.25
dAMP	143263.39	165436	198186.89	153194.31	216684.62	237290.36	194800.45	133544.75	845808.06	467938.59	471352.03	446970.88	161981.2	329335.44	173570.25	230733.33
Adenine	1713525.38	2142315	1469482.5	1067352.38	2769592.25	1391102.62	2115988.75	3016203.25	19339.43	29807.2	26658.26	34363.05	17868.06	26493.32	36747.36	25534.21
Guanine	70231.66	56850.05	75023.48	47890.71	69431.66	74640.14	104997.69	107966.95	69757.12	56948.69	73656.24	90049.5	79460.51	69629.5	63419.29	88722.53
CMP	239514.12	110166.52	155091.23	167618.53	189511.48	201500.8	276592.09	238434.31	341736.44	208094.08	203776.58	202449.02	139260.69	190868.3	201496.69	290383.59
Cytosine	82367.63	30291.95	67843.7	329005	28400.99	29618.88	39738.79	33617.38	96558.27	36219.23	62347.34	67451.34	20407.83	11296.85	48805.07	34198.96
IDP	22687.93	27911.21	15047.85	44507.17	6909.63	5435.84	0	11808.19	45661.03	13587.13	36520.47	18399.67	32506.4	17099.86	17834.19	0
5-Hydroxyisourate	3379679.25	3281901.25	3512432.75	2732750.75	3572124.75	2706076.25	4230753	3175589	3959133	3380158	3764001.25	3737034	2302044.5	2961812.25	3201676.25	3959547.25
Nicotinamide	3626488	1796896.88	2659788.25	3025876.75	128210.94	172245.17	223648.92	189201.44	3767674.25	2112868	2798722.75	2461709	150864.64	156510.89	196436.11	158757.45
1/2-3-Bisphosphoglycerate	0	10529.82	20801.68	47469.71	0	48692.47	33637.29	7577.52	16739.33	0	18301.54	26056.45	50649.84	49989.28	36443.36	18500.05
Maltotriose	105067.28	73797.49	82434.5	113984.87	139093.88	84583.85	94618.02	89870.49	46442.04	103331.41	98724.03	90312.97	94318.47	111274.41	145216.58	125902.01
D-Rhamnose	6804.31	0	0	0	114336.13	55920.55	86163.9	128484.4	6494.52	6421.23	0	0	57004.79	52412.17	52266.89	67470.57
D-Arabitol	5731802	4930176.5	4492844.5	3725777	1849179	1256030	1777514.88	2048494.38	1748.3	3938.54	3052.96	2059.76	10078.39	10655.36	8910.59	26554.65
Glutathione disulfide	243804.56	208546.89	388578.34	127778.23	308298.75	278892.47	166739.52	432991.91	166394.3	316526.66	392009.41	258711.94	387686.84	239150.2	356692.16	343697.25
Glutathione disulfide 13C7	384690.53	65955.85	274509.59	228509.95	11593.86	52671.59	140030.83	0	0	0	0	0	0	0	0	0
5-Oxoproline	8170469.5	7748894.5	6219756	5033684.5	11031213	5310109	7880630	10997571	6533201.5	7882180	8424491	7976058	4581318	6265668.5	6252394	8652519
5-Oxoproline 13C3	3566498.75	4282168.5	3239703.75	2447658.25	5878665.5	3071357.75	3915281.75	6908689.5	3194388.75	4932597	5125377.5	4598408.5	3048580.75	4125116.25	4107786.25	5201759.5
5-Oxoproline 13C5	587399.56	448800.91	503863.09	384887.53	199295.33	115205	189089.06	241847.7	9986.11	22774.6	46657.34	12240.59	34956.46	26545.29	30035.86	20180.44
5-Oxoproline 13C4 15N1	51286.18	43970.65	62153.61	47422.02	96332.8	25544.61	81031.75	105215.3	0	0	3789.01	0	0	0	0	0
5-Oxoproline 13C5 15N1	1713525.38	2142315	1469482.5	1067352.38	2769592.25	1391102.62	2115988.75	3016203.25	24409.82	73667.1	48776.36	25321.62	31128.38	51015.76	65738.32	78154.54
5-Oxoproline 15N1	361803.5	244462.45	213801.42	181720.56	102313.85	73252.54	114225.45	147412.86	19727.5	18136.85	8802.86	8410	12208.29	7990.59	6988.65	6626.44
S-Glutathionyl-L-cysteine	71925.88	60813.97	75531.88	55497.76	98329.59	63110.72	94440.59	79531.23	146993.03	112458.27	136559.7	82112.93	69098.7	81933.14	143886	118497.52
Cys-Gly	1385097.62	443443.22	1074660.5	1105317	311994.88	642045.81	792967.5	460837.91	1462827	421205.88	487629.72	416690.91	210674.25	303403.22	301762.56	347550.72
gamma-L-Glutamyl-L-cysteine	61529.06	73442.93	54441.11	92039.91	6160.41	29926.07	39757.82	10269.58	118196.5	65375.31	43100.79	53652.64	8285.83	14059.87	6393.13	13978.48
gamma-Glutamyl-Se-methylselenocysteine	17871.47	27776.48	15680.62	11599.89	570649.31	457989.84	602923.38	798055.25	8451.5	11762.03	4914.31	14047.28	302683.12	376315.97	334606.41	365074.09
(5-L-Glutamyl)-L-glutamine	1423274.62	838860	907385.56	1011058.56	738459.94	388884.25	1017102.69	878274.5	2347225.25	1346227.12	1421587.88	1373569.88	472462.72	593887.75	624803	904753.31
Cystathionine	705247.44	757792.75	584030.94	315979.97	523885.16	190172.86	388321.25	706862	450239.16	598047.44	735897.06	582004.31	233106.58	293876.28	351495.38	480783.72
Dimethylglycine	1149348.62	1070613.62	909668.69	778519.5	298149.59	234664.17	328832.91	308286.88	1405139.88	1445152.12	1482143	1347760.5	442946.12	461805.47	442909.22	419574.88
Phosphoserine	1115655.12	1000132.19	917280.5	659669.88	558284.88	258230.92	480674.91	603792.75	1387132	1228748.62	1440357.62	1245868.62	333485.09	378738.09	492943.97	580383.31
3-Phosphonooxypyruvate	19089502	25051562	20242222	15717080	25066874	20915992	15583737	29403576	17592344	28421766	29953270	26469512	27581330	24248470	30181200	28218370
S-Adenosyl-L-methionine	2356799.5	2731060.25	2036246	1658139	4936824.5	3332131	3516786	5003915.5	1576850.38	2340428.75	2322445	2577515	2903964	3564427	3456463	4734445.5
Dihydrofolate	45851.94	123230.22	0	208052.77	265943.53	84454.56	58593.09	147826.2	54757.02	130706.4	113452.88	170309.42	88000.78	305816.84	242421.69	189108.33
Ornithine	800390.94	915769	653930.94	615590.75	680482	405817.75	474268.25	765175.81	23453.99	44718.88	49775.5	38865.31	49481.67	55115.71	70894.12	65128.93
L-Citrulline	130309.63	93073.41	74810.48	402514	142109.39	107033.47	136158	157569.98	108648.07	117298.52	131520.94	102320.74	118356.09	115758.26	133464.23	127408.28
Argininosuccinate	199570.2	187657.67	168031.67	143259.12	331765.62	178703.75	318775.66	382954.78	235650.14	196100.52	245090.55	224584.11	248712.12	283963.22	297516.91	308793.97
Putrescine	59358.95	75263.6	80089.12	83520.68	61251.46	93770.7	56579.61	65281.95	76520.25	89625.02	101298.35	96519	129214.34	125199.4	124548.79	95019.46
Spermidine	365561.28	602473.81	765845.44	576827.62	1159880.5	2077284.88	1049615.5	1255661	644184.31	955319.06	1134057	980284.19	3291185.75	2748235.75	3483141	2395685
Spermine	181961.38	251536.08	446233.78	312056.59	375442.12	636527.69	431725.66	346023.44	378953.66	559814.19	614110.06	586657.69	1113033.38	818505.81	1006311.56	835795.69
D-Glucosamine	6775.83	3633.03	10166.11	16446.82	214562	118983.66	291280.41	218813.95	11362.67	5112.71	4511.23	1156	59826.86	96822.72	58462.02	74272.86
CMP-N-acetylneuraminate	2518244.75	2239297.5	2352231	2451342.75	1911799.62	2321573.75	2289311	1439964.12	3232226.25	1574798.62	1130740.62	1425437.12	1728181.12	1559868.62	1326906.38	1514304.38
Phosphocreatine	117913.02	120869.12	76612.22	86130.88	34862.48	17849	10366.1	25210.23	97996.75	154815.84	157739.55	135474.95	24069.59	19014.83	38218.94	30300.46
Creatine	14838995	13535992	13888459	14222273	12848711	11597836	14385260	13284693	18576982	16830882	17954842	15331032	14063347	15126136	15065216	15897849
N-Acetylornithine	162642.8	81924.81	133481.09	175814.62	129984.37	115070.49	202973.48	139959.38	190455.33	109677.73	109681.75	115231.91	77757.1	122452.88	138432.45	174981.02
trans-4-Hydroxy-L-proline	3700582.75	2887377	2886317.75	2101543.75	4112528.75	2237286	3656646.75	4803996.5	3088429.25	3149519.25	3510219.75	3241494.75	2149391.25	2587513	2531833.75	3604760
Pantothenate	10153862	11469848	9861872	11267128	7372888.5	7641392	8366640.5	6675060	12559100	11214645	13539769	9877441	8966245	8096584	8853613	8080284
Hypotaurine	165596.7	185513.02	152188.33	93799.78	183372.73	102155.62	108975.62	208010.02	151519.05	199324.92	244421.3	201019.92	107326.04	137057.56	164253.5	192541.23
(R)-S-Lactoylglutathione	23871.52	23193.18	22090.89	28223.27	15405.47	26211.07	32687.05	22063.95	36414.67	22550.72	18556.25	19426.79	20805.33	7859.34	26316.86	29088.71
L-Methionine S-oxide	75148.88	48096.54	63104.96	113195.21	90748.55	72301.43	97373.45	81620.18	59188.31	61017.13	86331.19	56762.07	78881.1	71150.01	80020.31	90159.37
Indole-3-acetate	254829.86	452017.03	407913.53	300548.84	319906.22	331965.88	181026.83	324461.78	296415.75	490734.78	544449.31	415789.66	484923.47	462949.41	527561.5	369869.28
Indolepyruvate	214922.3	270048.66	206200.2	435452.62	402361.53	413601.28	404159.16	406783.62	294941.72	408824.84	424820.59	385410.41	584486.19	592282.31	583712.25	527687
kynurenine	22384.33	17314.06	22072.29	30542.71	40083.79	38081.16	37756.38	40001.59	28828.68	39692.06	39698.58	34077.49	60159.09	38470.65	58714.06	43234.02
Anthranilate	418914.75	736304.81	498376.25	250954.69	452595.12	471969.34	194537.95	477236.34	386041.91	1375151.38	1084714.38	1143573.62	849700.31	950611.19	811027.5	627016.75
2-Aminomuconate	544950.75	470769	499379.5	517248.5	411731.34	340548.16	523756.72	405037.59	695996	556507.56	502826.41	543418.88	358716.16	325301.41	311391.59	362989.72
Kynurenate	0	1546.76	2436.71	0	20514.88	16566.46	17485.1	21134.01	0	1427.02	1551.33	2817.2	24966.57	9438.53	27662.27	25680.88
3-5-hydroxykynurenamine	6896.05	21011.03	24736.11	22661.34	15170.58	14194.29	19609.36	10453.33	17972.53	9786.81	22315.88	13223.18	23094.78	29866.7	12376.87	6838.66
5-hydroxytryptophan	8704.95	5543.83	14472.75	11597.02	10634.5	11728.63	9024.25	13884.24	8170.04	12588.19	19361.12	8114.41	11979.14	9957.59	17046	6203.5
2-Oxoadipate	24103.89	28822	12738.7	39408.97	32390.7	23209.88	15779.91	33137.89	36485.28	55503.17	56543.94	47714.49	65052.33	62822.5	64643.59	27457.04
3-Methyleneoxindole	37759.81	33547.66	47278.46	54684.57	59863.11	54146.49	41878.79	52365.89	49575.88	47887.14	60599.58	47888.57	64630.54	62169.36	83622.95	62892.21
L-Adrenaline	85429.18	94244.91	99721.76	87843.16	54694.34	63804.73	59442.67	60020.84	111487.6	96137.47	99079.45	78352.57	71632.16	61964.61	74791.09	65973.59
Dopamine	7942246.5	8817869	7491206.5	5665280.5	12916933	6398327.5	9472141	14040043	7813.57	11239.91	6006.14	7896.86	10854.76	9721.49	8362.18	8423.67
Inositol 1-2-3-5-6-pentakisphosphate	300464.34	112141.88	455475.91	207698.5	189031.98	204072.98	320252.72	221224.56	361865.47	132913.8	173340.7	133569.98	154407.62	128955.98	84297.37	193068.06
Ethanolamine phosphate	3237151.25	4051258.75	2663637.5	1782124	3778548.75	1495367.88	2217374.75	4317699.5	2357333	4039721.25	4101334.75	3699525.75	1942309.88	2403927.75	2592457.5	2906364
N-Methylethanolamine phosphate	372442.22	343957.03	270029.56	190236.92	360446.5	178785.42	205444.92	287642.47	209160.73	319494.03	363897.25	367941.28	163159.17	229339.27	212856.17	270629.44
Sphingosine	227257.39	306938.56	270373.66	322091.62	263015.81	186795.61	165164.06	211275.39	241696.42	396209.47	426772	437111.28	282197.53	260438.75	314297.03	263834.88
Acetylcholine	1063428.75	850195.44	1047108.5	1122382.38	714792.31	795648.56	950662.75	879242	1442519	1292809.38	1448818.38	1300855.88	780315.81	1003456.94	966616.31	1023922.19
CDP-choline	69672.9	115727.29	65038.29	71354.73	297202.09	138853.22	186898.83	276097.66	164126.52	185240.08	190009.8	191241.19	213356.2	283515.28	241735.77	332778.38
Choline	54538400	56365836	56795660	48779300	54581636	47714516	51002204	47307060	40582956	42029148	44944832	45058928	41891356	42176628	45583728	48771644
L-Carnitine	5001356.5	6095418.5	5730151.5	5261699	7408319.5	6760980	6715872	7556351.5	7397473.5	8761719	9158101	8111460.5	10723561	10830772	12254901	10174737
acyl-C2 (acetyl-carnitine)	7545296	3918496.25	5440371.5	5485057.5	3137518	4564300.5	6139159.5	3591360	10732442	4208954.5	4727920.5	4236587.5	3999085.25	4958733.5	4707559	4877212.5
acyl-C3 (propionyl-carnitine)	6225776	4303973.5	6121872.5	5682003.5	977801.31	1267278.75	1438078.62	1156911.38	9290453	6622453.5	6194908	6350797.5	1541471.38	1575842	1792065.12	1437953.5
acyl-C4 (butanoyl-l-carnitine)	1229306.12	1305628.12	1557647.12	1244229.38	473170.22	503945.41	580314	501138	2758770	2101012.25	2466019.75	2185594.75	1123468.38	1047972.44	1195785.5	942443.69
acyl-C4-OH (Hydroxybutyrylcarnitine)	128443.77	10577.54	67978.8	41034.18	63174.3	104572.41	136720.11	63257.86	101548.25	80127.9	81138.22	85389.88	106246.99	105981.69	167445.27	85480.4
acyl-C5 (isovalerylcarnitine)	1690014.62	1522224.12	1617123.5	1774990.5	572497.5	351329.09	485515.25	569879.12	2588040	2978987	3587154	2489295.75	976657.5	995702.25	931876.19	747566.25
acyl-C5-OH	27111.74	22676.11	23643.91	8947.94	15382.4	15025.23	22168.73	19075.71	38042.92	23528.79	28965.65	22317.5	26464.63	29181.28	37140.4	32066.81
acyl-C6 (hexanoyl-l-carnitine)	24302.16	41343.59	22744.24	22375.91	15508.6	27441.49	36773.41	30818.42	27357.33	19533.03	41660.18	20328.58	46903.49	48840.93	14800.55	17999.47
acyl-C6-DC	79593.41	114984.13	64046.14	102616.59	87975.85	76640.18	74670.16	96241.22	71554.49	84774.44	87763.02	60714.04	74344.25	65148.03	68924.79	80201.09
acyl-C14 (O-tetradecanoyl-L-carnitine)	352366.25	420196.03	335392.41	378204.25	328682.53	258938.75	385690.59	368396.97	601127.31	626569.06	523356.09	550920.75	655849.44	668844.69	468662.91	728458.94
acyl-C14:1 (Tetradecenoyl Carnitine)	38124.11	60341.2	18437.48	35766.25	40017.51	55456.46	73335.1	44431.33	72604.51	86669.02	54626.18	98126.04	111263.34	75097.91	88623.65	110524.16
acyl-C16 (L-Palmitoylcarnitine)	2666147.75	2819460	2375892	3021549	2177049.75	1769142.12	2077103.88	2129321.75	4260233.5	3797583	3848147.75	4315240.5	2851388.25	2950793.75	2532658.5	3336746.75
acyl-C16:1 (Hexadecenoyl-carnitine)	472509.75	503964.91	357286.34	538487	386751.34	289928.81	477654.34	297988.12	781053.31	841905.94	703063.56	750815.69	583586.31	655165.25	518445.25	845137.94
acyl-C18 (Octadecanoyl-L-carnitine)	169664.23	233448.67	219947.27	152817.61	339728	295855.59	168664.19	462766	232575.94	326237.91	312730.03	299420.09	754195.31	579422.31	619126.81	689250.5
acyl-C18:1 (O-octadecenoyl-L-carnitine)	1228023.38	941035.75	898612.19	1227373.5	758754.44	604591.5	779898.19	688378.06	1861641.88	1385751	1337634.12	1755862.62	889480.5	1018210.44	938151	1264134.88
acyl-C18:2 (Linoleoyl-CoA)	120286.19	119983.29	91042.79	54379.93	128374.32	67625.73	67493	70498.87	142575.17	117688.27	125358.01	114068.73	86766.07	111112.4	79555.59	111089.65
acyl-C20	254493.17	195199.3	271878.5	295346	217631.67	216194.44	270336.59	160187.39	286753.03	177044.7	167617.52	200138.77	165706.47	187311.42	232341.2	203347.05
MS_METABOLITE_DATA_END
#METABOLITES
METABOLITES_START
metabolite_name	KEGG	m/z	RT
L-alanine	C00041	90.055115	0.54
L-arginine	C00062	175.118927	0.501
L-asparagine	C00152	133.060684	0.515
L-cysteine	C00097	122.027168	0.546
L-glutamate	C00025	148.060516	0.534
L-glutamate 13C5	C00025	153.076599	0.534
L-glutamate 13C5 15N1	C00025	154.07428	0.535
L-glutamate 15N1	C00025	149.057892	0.538
L-glutamine	C00064	147.076508	0.52
L-glutamine 13C5 15N2	C00064	154.086838	0.539
glycine	C00037	76.039307	0.511
L-leucine/isoleucine	C00123	132.102036	0.702
L-lysine	C00047	147.112808	0.461
L-methionine	C00073	150.058395	0.604
L-phenylalanine	C00079	166.086304	1.631
L-proline	C00148	116.070801	0.577
L-serine	C00065	106.050087	0.511
L-threonine	C00188	120.065689	0.536
L-tryptophan	C00078	205.097488	1.639
L-tyrosine	C00082	182.081085	0.611
AMP	C00020	348.070282	0.578
dAMP	C00360	332.075317	0.589
Adenine	C00147	136.062805	0.863
Guanine	C00242	152.054764	0.606
CMP	C00055	324.059174	0.578
Cytosine	C00380	112.050797	0.576
IDP	C00104	429.018799	0.522
5-Hydroxyisourate	C11821	185.032227	0.52
Nicotinamide	C00153	123.055481	0.591
1/2-3-Bisphosphoglycerate	C00236	266.970154	0.523
Maltotriose	C01835	505.181519	2.01
D-Rhamnose	C01684	165.075714	0.542
D-Arabitol	C01904	153.075897	0.585
Glutathione disulfide	C00127	613.149109	1.81
Glutathione disulfide 13C7	C00127	620.192139	0.588
5-Oxoproline	C01879	130.049988	0.521
5-Oxoproline 13C3	C01879	133.060501	0.517
5-Oxoproline 13C5	C01879	135.065948	0.543
5-Oxoproline 13C4 15N1	C01879	135.060333	0.525
5-Oxoproline 13C5 15N1	C01879	136.062622	0.55
5-Oxoproline 15N1	C01879	131.046722	0.54
S-Glutathionyl-L-cysteine	C05526	427.094971	0.571
Cys-Gly	C01419	179.048492	0.589
gamma-L-Glutamyl-L-cysteine	C00669	251.069702	0.618
gamma-Glutamyl-Se-methylselenocysteine	C05695	313.029694	0.529
(5-L-Glutamyl)-L-glutamine	C05283	276.119049	0.57
Cystathionine	C00542	223.074677	0.51
Dimethylglycine	C01026	104.070847	0.558
Phosphoserine	C02532	186.016144	0.534
3-Phosphonooxypyruvate	C03232	184.985474	3.687
S-Adenosyl-L-methionine	C00019	399.144501	0.515
Dihydrofolate	C00415	444.16864	1.952
Ornithine	C01602	133.098831	0.702
L-Citrulline	C00327	176.102463	0.551
Argininosuccinate	C03406	291.129883	0.535
Putrescine	C00134	89.10746	0.462
Spermidine	C00315	146.165207	0.442
Spermine	C00750	203.223038	0.449
D-Glucosamine	C00329	180.0867	0.552
CMP-N-acetylneuraminate	C00128	615.161926	1.817
Phosphocreatine	C02305	212.043015	0.553
Creatine	C00300	132.076797	0.566
N-Acetylornithine	C00437	175.107758	0.583
trans-4-Hydroxy-L-proline	C01157	132.065613	0.528
Pantothenate	C00864	220.118042	1.634
Hypotaurine	C00519	110.027191	0.521
(R)-S-Lactoylglutathione	C03451	380.112213	1.632
L-Methionine S-oxide	C02989	166.052841	0.548
Indole-3-acetate	C00954	176.070633	1.786
Indolepyruvate	C00331	204.063126	0.595
kynurenine	C00328	209.091965	1.632
Anthranilate	C00108	138.053146	0.577
2-Aminomuconate	C02220	158.0448	0.618
Kynurenate	C01717	190.052216	0.709
3-5-hydroxykynurenamine	C05638	181.095154	0.495
5-hydroxytryptophan	C00643	221.09198	1.631
2-Oxoadipate	C00322	161.046051	1.786
3-Methyleneoxindole	C02796	146.060089	1.642
L-Adrenaline	C00788	184.096725	1.634
Dopamine	C03758	154.08606	0.548
Inositol 1-2-3-5-6-pentakisphosphate	C04579	580.901062	2.019
Ethanolamine phosphate	C00346	142.026398	0.512
N-Methylethanolamine phosphate	C01210	156.042023	0.519
Sphingosine	C00319	300.289795	1.847
Acetylcholine	C01996	146.117645	0.565
CDP-choline	C00307	489.114685	0.556
Choline	C00114	104.107201	0.517
L-Carnitine	C00318	162.112427	0.537
acyl-C2 (acetyl-carnitine)	C02571	204.123047	0.582
acyl-C3 (propionyl-carnitine)	C03017	218.138672	0.604
acyl-C4 (butanoyl-l-carnitine)	C02862	232.154327	1.643
acyl-C4-OH (Hydroxybutyrylcarnitine)	HMDB13127	248.149323	0.596
acyl-C5 (isovalerylcarnitine)	C20826	246.169968	1.669
acyl-C5-OH	ac107	262.164978	1.635
acyl-C6 (hexanoyl-l-carnitine)	HMDB00756	260.185638	1.721
acyl-C6-DC	ac109	290.159912	1.708
acyl-C14 (O-tetradecanoyl-L-carnitine)	HMDB05066	372.310699	1.842
acyl-C14:1 (Tetradecenoyl Carnitine)	HMDB13329	370.295074	1.825
acyl-C16 (L-Palmitoylcarnitine)	C02990	400.342041	1.888
acyl-C16:1 (Hexadecenoyl-carnitine)	HMDB06317	398.326324	1.864
acyl-C18 (Octadecanoyl-L-carnitine)	HMDB00848	428.373352	1.922
acyl-C18:1 (O-octadecenoyl-L-carnitine)	HMDB06351	426.357666	1.886
acyl-C18:2 (Linoleoyl-CoA)	HMDB01064	424.342224	1.861
acyl-C20	ac124	458.420288	1.967
METABOLITES_END
#END