#METABOLOMICS WORKBENCH epmosher_20210121_142232 DATATRACK_ID:2414 STUDY_ID:ST001658 ANALYSIS_ID:AN002707 PROJECT_ID:PR001063
VERSION             	1
CREATED_ON             	January 25, 2021, 11:40 am
#PROJECT
PR:PROJECT_TITLE                 	Control of Topoisomerase II Activity and Chemotherapeutic Inhibition by TCA
PR:PROJECT_TITLE                 	Cycle Metabolites
PR:PROJECT_SUMMARY               	Topoisomerase II (topo II) is essential for disentangling newly-replicated
PR:PROJECT_SUMMARY               	chromosomes. DNA unlinking involves the physical passage of one DNA duplex
PR:PROJECT_SUMMARY               	through another and depends on the transient formation of double-strand DNA
PR:PROJECT_SUMMARY               	breaks, a step exploited by frontline chemotherapies to kill cancer cells.
PR:PROJECT_SUMMARY               	Although anti-topo II drugs are efficacious, they also elicit cytotoxic side
PR:PROJECT_SUMMARY               	effects in normal cells; insights into how topo II is regulated in different
PR:PROJECT_SUMMARY               	cellular contexts is essential to improve their targeted use. Using chemical
PR:PROJECT_SUMMARY               	fractionation and mass spectrometry, we have discovered that topo II is subject
PR:PROJECT_SUMMARY               	to metabolic control through the TCA cycle. We show that TCA metabolites
PR:PROJECT_SUMMARY               	stimulate topo II activity in vitro and that levels of TCA flux modulate
PR:PROJECT_SUMMARY               	cellular sensitivity to anti-topo II drugs in vivo. Our works reveals an
PR:PROJECT_SUMMARY               	unanticipated connection between the control of DNA topology and cellular
PR:PROJECT_SUMMARY               	metabolism, a finding with important ramifications for the clinical use of
PR:PROJECT_SUMMARY               	anti-topo II therapies.
PR:INSTITUTE                     	Johns Hopkins University
PR:LAST_NAME                     	Mosher
PR:FIRST_NAME                    	Eric
PR:ADDRESS                       	725 North Wolfe Street, Biophysics 307
PR:EMAIL                         	emosher2@jhmi.edu
PR:PHONE                         	410-952-9154
#STUDY
ST:STUDY_TITLE                   	Control of Topoisomerase II Activity and Chemotherapeutic Inhibition by TCA
ST:STUDY_TITLE                   	Cycle Metabolites
ST:STUDY_SUMMARY                 	Topoisomerase II (topo II) is essential for disentangling newly-replicated
ST:STUDY_SUMMARY                 	chromosomes. DNA unlinking involves the physical passage of one DNA duplex
ST:STUDY_SUMMARY                 	through another and depends on the transient formation of double-strand DNA
ST:STUDY_SUMMARY                 	breaks, a step exploited by frontline chemotherapies to kill cancer cells.
ST:STUDY_SUMMARY                 	Although anti-topo II drugs are efficacious, they also elicit cytotoxic side
ST:STUDY_SUMMARY                 	effects in normal cells; insights into how topo II is regulated in different
ST:STUDY_SUMMARY                 	cellular contexts is essential to improve their targeted use. Using chemical
ST:STUDY_SUMMARY                 	fractionation and mass spectrometry, we have discovered that topo II is subject
ST:STUDY_SUMMARY                 	to metabolic control through the TCA cycle. We show that TCA metabolites
ST:STUDY_SUMMARY                 	stimulate topo II activity in vitro and that levels of TCA flux modulate
ST:STUDY_SUMMARY                 	cellular sensitivity to anti-topo II drugs in vivo. Our works reveals an
ST:STUDY_SUMMARY                 	unanticipated connection between the control of DNA topology and cellular
ST:STUDY_SUMMARY                 	metabolism, a finding with important ramifications for the clinical use of
ST:STUDY_SUMMARY                 	anti-topo II therapies.
ST:INSTITUTE                     	Johns Hopkins University
ST:LAST_NAME                     	Mosher
ST:FIRST_NAME                    	Eric
ST:ADDRESS                       	725 North Wolfe Street, Biophysics 307
ST:EMAIL                         	emosher2@jhmi.edu
ST:PHONE                         	410-952-9154
#SUBJECT
SU:SUBJECT_TYPE                  	Yeast
SU:SUBJECT_SPECIES               	Saccharomyces cerevisiae
SU:TAXONOMY_ID                   	4932
SU:CELL_STRAIN_DETAILS           	BY4741
#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           	-	F4	Treatment:HPLC fraction 4	RAW_FILE_NAME=f4negR1.mzXML f4negR2.mzXML f4negR3.mzXML f4posR1.mzXML f4posR2.mzXML f4posR3.mzXML nf4negR1.mzXML nf4negR2.mzXML nf4negR3.mzXML nf4posR1.mzXML nf4posR2.mzXML nf4posR3.mzXML
SUBJECT_SAMPLE_FACTORS           	-	F5	Treatment:HPLC fraction 5	RAW_FILE_NAME=f5negR1.mzXML f5negR2.mzXML f5negR3.mzXML f5posR1.mzXML f5posR2.mzXML f5posR3.mzXML nf5negR1.mzXML nf5negR2.mzXML nf5negR3.mzXML nf5posR1.mzXML nf5posR2.mzXML nf5posR3.mzXML
SUBJECT_SAMPLE_FACTORS           	-	F6	Treatment:HPLC fraction 6	RAW_FILE_NAME=f6negR1.mzXML f6negR2.mzXML f6negR3.mzXML f6posR1.mzXML f6posR2.mzXML f6posR3.mzXML nf6negR1.mzXML nf6negR2.mzXML nf6negR3.mzXML nf6posR1.mzXML nf6posR2.mzXML nf6posR3.mzXML
#COLLECTION
CO:COLLECTION_SUMMARY            	Yeast cultures were grown in SC-sulfate media and were harvested at OD600
CO:COLLECTION_SUMMARY            	0.4-0.8 by vacuum filtration then washed with 100mM ammonium acetate - TEA (pH
CO:COLLECTION_SUMMARY            	8.0). Metabolites were extracted by the addition of pre-chilled 10mL 90%
CO:COLLECTION_SUMMARY            	methanol, 10mM ammonium acetate - TEA (pH 8.0). Cell debris was removed by
CO:COLLECTION_SUMMARY            	centrifugation at 4000g for 10-15 minutes. Extracts were subsequently passed
CO:COLLECTION_SUMMARY            	through 3 kDa MWCO filters. Filtrate was diluted 2-fold with water and
CO:COLLECTION_SUMMARY            	lyophilized. Lyophilized metabolite extracts were resuspended with water and pH
CO:COLLECTION_SUMMARY            	was adjusted to 10 with TEA. The extract was then passed through a mixed-mode
CO:COLLECTION_SUMMARY            	anion exchange solid phase extraction cartridge and fractionated by
CO:COLLECTION_SUMMARY            	reverse-phase HPLC on a C18 column. One column volume of water plus 0.1% formic
CO:COLLECTION_SUMMARY            	acid and eight column volumes of methanol were passed through the column.
CO:COLLECTION_SUMMARY            	Fractions that eluted during the aqueous phase were then lyophilized.
CO:SAMPLE_TYPE                   	Yeast cells
#TREATMENT
TR:TREATMENT_SUMMARY             	Active fractions were run on a normal-phase HPLC on an amide column and
TR:TREATMENT_SUMMARY             	fractions were collected. Fractions 4, 5, and 6 were subjected to metabolomics
TR:TREATMENT_SUMMARY             	analyses.
#SAMPLEPREP
SP:SAMPLEPREP_SUMMARY            	Fractions of interest were lyophilized then reconstituted in water plus 0.1%
SP:SAMPLEPREP_SUMMARY            	formic acid such that samples reached a final concentration of 20 mg/mL.
#CHROMATOGRAPHY
CH:CHROMATOGRAPHY_TYPE           	Reversed phase
CH:INSTRUMENT_NAME               	Thermo Dionex Ultimate 3000 RS
CH:COLUMN_NAME                   	Thermo Hypersil Gold aQ (150 x 2.1mm, 1.9um)
CH:FLOW_GRADIENT                 	0-2min 0% B, 2-13min 0-60% B, 13-15min 60-90% B, 15-16min 90-0% B, 16-20min 0% B
CH:FLOW_RATE                     	0.2 mL/min
CH:COLUMN_TEMPERATURE            	30
CH:SOLVENT_A                     	1mM ammonium acetate + 0.1% formic acid in water
CH:SOLVENT_B                     	1mM ammonium acetate + 0.1% formic acid in 20/80 water/acetonitrile
#ANALYSIS
AN:ANALYSIS_TYPE                 	MS
#MS
MS:INSTRUMENT_NAME               	Thermo Q Exactive Orbitrap
MS:INSTRUMENT_TYPE               	Orbitrap
MS:MS_TYPE                       	ESI
MS:ION_MODE                      	NEGATIVE
MS:MS_COMMENTS                   	MS1 data was acquired at a resolution of 140,000 over a scan range of 65-850
MS:MS_COMMENTS                   	m/z. Data was analyzed with Thermo Compound Discoverer software.
#MS_METABOLITE_DATA
MS_METABOLITE_DATA:UNITS	Peak Area
MS_METABOLITE_DATA_START
Samples	F4	F5	F6
Factors	Treatment:HPLC fraction 4	Treatment:HPLC fraction 5	Treatment:HPLC fraction 6
(±)-Ibotenic acid	9540737.349	44452.64866	334588.7782
(1R,2R,3S,5R,7R)-2-Acetamido-7-(1,2-dihydroxyethyl)-3-hydroxy-6,8-dioxabicyclo[3.2.1]octane-5-carboxylic acid	1446887.385	51910445.09	20059523.08
(1R,2R,3S,5R,7R)-2-Acetamido-7-(1,2-dihydroxyethyl)-3-hydroxy-6,8-dioxabicyclo[3.2.1]octane-5-carboxylic acid (2)	409229.6609	6963219.568	5217140.513
(2S)-2-({[(3S,4S,5R)-2,3,4-Trihydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]methyl}amino)propanoic acid (non-preferred name)	140312.5155	61999860.06	202544290.5
(2S)-3-Hydroxy-2-({[(3S,4S,5R)-2,3,4-trihydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]methyl}amino)butanoic acid (non-preferred name)	85017.00804	610761.7381	302258175.3
[Similar to: (2-{[(1S,11aS)-7-(1,3-Benzodioxol-5-yl)-5,11-dioxo-2,3,5,10,11,11a-hexahydro-1H-pyrrolo[2,1-c][1,4]benzodiazepin-1-yl]amino}-2-oxoethoxy)acetic acid; ΔMass: 305.0813 Da]	2271432.095	25991345.78	52658334.14
[Similar to: (2-{[(1S,11aS)-7-(1,3-Benzodioxol-5-yl)-5,11-dioxo-2,3,5,10,11,11a-hexahydro-1H-pyrrolo[2,1-c][1,4]benzodiazepin-1-yl]amino}-2-oxoethoxy)acetic acid; ΔMass: 306.0654 Da]	108952.6459	10995521.48	30121306.41
[Similar to: (2-{[7-(2-Fluorophenyl)-5,11-dioxo-2,3,5,10,11,11a-hexahydro-1H-pyrrolo[2,1-c][1,4]benzodiazepin-1-yl]amino}-2-oxoethoxy)acetic acid; ΔMass: 106.0721 Da]	64482.58995	43474871.62	21536961.28
[Similar to: (2-{[7-(2-Fluorophenyl)-5,11-dioxo-2,3,5,10,11,11a-hexahydro-1H-pyrrolo[2,1-c][1,4]benzodiazepin-1-yl]amino}-2-oxoethoxy)acetic acid; ΔMass: 278.0869 Da]	93018.43073	249763.5055	17548427.85
[Similar to: (3R,4R,6R)-6-{[4-(1-Hydroxycyclopentyl)-1H-1,2,3-triazol-1-yl]methyl}-N-(2-methoxybenzyl)quinuclidine-3-carboxamide; ΔMass: 301.1805 Da]	2553051.337	14657356.15	43537.99421
[Similar to: (4S,6S)-N-(Cyclopropylmethyl)-6-isobutyl-1-[(1-methyl-1H-imidazol-2-yl)methyl]-3,4,5,6-tetrahydro-1H-azepino[5,4,3-cd]indole-4-carboxamide; ΔMass: 142.1527 Da]	11984.03968	5739785.708	6323601.988
[Similar to: (4S,6S)-N-(Cyclopropylmethyl)-6-isobutyl-1-[(1-methyl-1H-imidazol-2-yl)methyl]-3,4,5,6-tetrahydro-1H-azepino[5,4,3-cd]indole-4-carboxamide; ΔMass: 247.1849 Da]	33181.98808	10404801.1	14944115.49
[Similar to: 2-Methoxy-N-{2-[1-(2-naphthyl)-1H-1,2,3,4-tetraazol-5-yl]vinyl}-5-(trifluoromethyl)aniline; ΔMass: 43.0187 Da]	44113.04533	18292988.55	57228293.75
[Similar to: 2-Methoxy-N-{2-[1-(2-naphthyl)-1H-1,2,3,4-tetraazol-5-yl]vinyl}-5-(trifluoromethyl)aniline; ΔMass: 43.2561 Da]	616930.9926	17492918.87	433282.9275
[Similar to: 2-Methoxy-N-{2-[1-(2-naphthyl)-1H-1,2,3,4-tetraazol-5-yl]vinyl}-5-(trifluoromethyl)aniline; ΔMass: 44.0152 Da]	62548.9873	19690062.81	23559367.49
[Similar to: 4-Guanidinobutyric acid; ΔMass: 43.0549 Da]	2926865.168	31214369.51	72334998.83
[Similar to: 4-Oxoproline; ΔMass: -0.9228 Da]	91839007.76	63348124.67	2325794.071
[Similar to: 4-Oxoproline; ΔMass: -0.9825 Da]	78309.40354	770076.5059	10375369.51
[Similar to: 4-Oxoproline; ΔMass: -67.9864 Da]	245187.9668	12327821.8	7583362.223
[Similar to: Argininosuccinic acid; ΔMass: 158.0342 Da]	112287.7725	78267.69396	207646775.2
[Similar to: Argininosuccinic acid; ΔMass: 158.1592 Da]	7100825.405	80900492.86	423799.3258
[Similar to: Argininosuccinic acid; ΔMass: 159.1223 Da]	5204505.731	47144.07436	262912.4296
[Similar to: D-(-)-Glutamine; ΔMass: -71.9041 Da]	38196.38007	4803452.923	45109.00764
[Similar to: DL-Arginine; ΔMass: 0.1561 Da]	1347863.565	13032309.99	562774.8554
[Similar to: DL-Arginine; ΔMass: 1.0828 Da]	69012.18631	65380.54409	43182292.95
[Similar to: DL-Homoserine ; ΔMass: -161.0380 Da]	55427.50573	3164047.383	1414936.46
[Similar to: DL-Malic acid; ΔMass: 0.9854 Da]	89572.5854	13937171.73	608977.4718
[Similar to: Guanidinosuccinic acid; ΔMass: 43.0073 Da]	203781.2851	165463.8067	94509107.54
[Similar to: L-(-)-Malic acid; ΔMass: -156.0032 Da]	9069.583177	2214338.769	11425.197
[Similar to: L-Glutamic acid; ΔMass: 0.0481 Da]	42909.6235	44803.68093	7722835.007
[Similar to: L-Glutamic acid; ΔMass: -147.0028 Da]	88407.6981	15219565.6	3454727.853
[Similar to: L-Glutamic acid; ΔMass: -161.0684 Da]	47801.12506	51500.40876	76906907.02
[Similar to: L-Glutamic acid; ΔMass: -168.0507 Da]	79376.445	59148.23729	45544875.22
[Similar to: L-Glutamic acid; ΔMass: -168.6796 Da]	116112985.2	199683.6544	624895.6296
[Similar to: L-Glutamic acid; ΔMass: -169.0348 Da]	71878.2626	82855.15019	233585524.2
[Similar to: L-Glutamic acid; ΔMass: -184.6535 Da]	115351455.3	130395.9992	336129.3037
[Similar to: L-Glutamic acid; ΔMass: -250.1156 Da]	82102.10185	57950.94874	13484818.5
[Similar to: L-Glutamic acid; ΔMass: -251.0997 Da]	61250.90347	54770.41534	127150760.5
[Similar to: L-Histidine; ΔMass: -0.8350 Da]	41157152.81	142735.5264	861135.6052
[Similar to: Microcystin LF; ΔMass: 855.5507 Da]	99832171.41	1104853913	6463195.797
[Similar to: N-(2,3-Dihydro-1,4-benzodioxin-6-yl)-1,2-dimethyl-1H-imidazole-4-sulfonamide; ΔMass: 122.9789 Da]	755798.4658	34536491.91	335434.9508
[Similar to: N-1-({2-[4-(Dimethylamino)benzoyl]hydrazino}carbothioyl)-2-methylbut-2-enamide; ΔMass: 118.1227 Da]	36174.236	10273961.97	69661.57013
[Similar to: N'1-(2-Chlorobenzylidene)-4-hydroxy-3-(methylthio)-4,5,6,7-tetrahydrobenzo[c]thiophene-1-carbohydrazide; ΔMass: 120.2707 Da]	139110702.9	145238.9977	407234.887
[Similar to: N4-Acetylcytidine; ΔMass: 127.0282 Da]	93765.21746	6470334.73	17697533.25
[Similar to: N4-Acetylcytidine; ΔMass: 128.0123 Da]	108182.0285	79935.7704	20965216.49
[Similar to: Pyridoxamine; ΔMass: -18.0095 Da]	1489195.783	9912274.055	147887.3019
[Similar to: S-Lactoylglutathione; ΔMass: 51.9888 Da]	82279.9459	89427.86984	390082595.6
[Similar to: S-Lactoylglutathione; ΔMass: 52.9728 Da]	74886.02663	42359.54456	370091566.5
[Similar to: S-Lactoylglutathione; ΔMass: 53.9569 Da]	67009.70144	49513.51145	10919869.39
[Similar to: SSR504734; ΔMass: 124.0210 Da]	17749522.38	4020957.085	45320.18126
[Similar to: Threonine; ΔMass: -162.8571 Da]	4262248.335	85964807.91	178390.2567
[Similar to: Threonine; ΔMass: -179.0789 Da]	60432.75647	45326.29388	26344774.47
[Similar to: Threonine; ΔMass: -180.0629 Da]	80827.61568	448935.9608	377716623.9
[Similar to: Threonine; ΔMass: -180.8291 Da]	1412775.372	61509833.11	235176.2829
[Similar to: Threonine; ΔMass: -181.0458 Da]	72084.83028	53263.52741	4484628.325
[Similar to: Threonine; ΔMass: -72.0200 Da]	368896.313	1422774.349	26639274.44
[Similar to: Uracil; ΔMass: -176.0656 Da]	104483.622	93429.01165	16657748.66
1-(beta-D-Ribofuranosyl)-1,2-dihydropyrimidine	35034.90177	114165.7271	6659161.034
1-[5-(2,3,4-Trihydroxybutyl)-2-pyrazinyl]-1,2,3,4-butanetetrol	105073.7353	2065587.428	634325882.7
2,3,4,5,6,7-Hexahydroxyheptanoic acid	617892.7008	395414191	718715994.1
3-(3,4-dihydroxyphenyl)lactamide	26412.72795	3311067.718	12356.56919
3,4-Dihydroxy-5-(1,2,3-trihydroxypropyl)dihydro-2(3H)-furanone	1523433.459	1119066.461	18927665.92
4-Hydroxyprolylthreonine	510156.2404	3457825.832	17715469.14
4-Oxoproline	1603103.271	84775188.31	47794515.49
6-deoxyinosine 5'-phosphate	70875.86718	61958.45485	21362590.9
AC-benzyl	6454952.694	1029803.466	334603.3165
Bisphenol S	19436822.08	2513059.403	2556635.851
Bluensidine	136569.0882	101840.7823	7114171.782
D-(-)-Glutamine	252689.6501	262898.8427	1704079020
D-(-)-Glutamine (2)	88179.06901	1809381.556	76076651.08
D-(+)-Glucose	3528143.011	628428000.7	1145309760
D-Glucono-delta-lactone	199728.8439	13343796.53	58988883.81
Dinoterb	20312.00758	22922.68007	9389437.505
DL-Arginine	403963.821	293616.7443	778072378.7
DL-Arginine (2)	168693.019	126524.5837	55938900.97
DL-Glutamine	76189.16393	47931.64732	17099749.17
Ethylene glycol tetraacetic acid	13557.39738	32755.92506	8310556.495
Fenson	24443433.45	2012210.391	2944473.254
Galactosamine	391041.2314	15027349.12	234719463.2
Gluconic acid	4072601.333	10947594.08	49636292.09
Gluconic acid (2)	1565414.121	5146194.945	47293213.5
L-(-)-Malic acid	692182.0606	116901561.6	739222.8033
L-Aspartic acid	364455.4919	279213.8128	476247407.1
L-Aspartic acid (2)	147065.7769	162552.0329	465071040.1
L-Glutamic acid	20942420.78	1860818.323	7500495918
L-Histidine	103174.4911	81644.21257	71158955.36
MFCD00037215	22486.27512	130696.1291	33595517.12
Midodrine	5142940.189	63962.90147	11244.72468
N-(3-Carboxy-3-hydroxypropyl)-4-[(carboxymethyl)amino]homoserine	58986.03273	67994.08367	39710253.03
N-(4-Amino-1-carboxybutyl)glutamic acid	25746.25009	26128.73052	11039273.79
N-Acetyl-DL-glutamic acid	64164.42301	10291216.61	26937.02965
N-Acetylneuraminic acid	147443.0336	799110.1127	183786604.8
neuraminic acid	36769.2801	5762179.774	126284.027
N-hexadecanoylsphinganine	29288334.06	110656.1614	167881.9188
N-Methyl-<scp>D</scp>-aspartic acid	71662.74167	68809.91406	39710253.03
Orotidine	35254.80068	8313332.247	30795374.93
shinorine	10235015.58	534090.617	580146.4383
Trabodenoson	25996.0409	354740.7964	6464568.01
Υ-Aminobutyric acid (GABA)	878396.9767	73580.40888	428733204
MS_METABOLITE_DATA_END
#METABOLITES
METABOLITES_START
metabolite_name	Formula	Molecular Weight	Retention times [min]
(±)-Ibotenic acid	C5 H6 N2 O4	158.03334	1.976
(1R,2R,3S,5R,7R)-2-Acetamido-7-(1,2-dihydroxyethyl)-3-hydroxy-6,8-dioxabicyclo[3.2.1]octane-5-carboxylic acid	C11 H17 N O8	291.09521	3.506
(1R,2R,3S,5R,7R)-2-Acetamido-7-(1,2-dihydroxyethyl)-3-hydroxy-6,8-dioxabicyclo[3.2.1]octane-5-carboxylic acid (2)	C11 H17 N O8	291.09526	2.613
(2S)-2-({[(3S,4S,5R)-2,3,4-Trihydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]methyl}amino)propanoic acid (non-preferred name)	C9 H17 N O7	251.09995	1.954
(2S)-3-Hydroxy-2-({[(3S,4S,5R)-2,3,4-trihydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]methyl}amino)butanoic acid (non-preferred name)	C10 H19 N O8	281.11064	1.996
[Similar to: (2-{[(1S,11aS)-7-(1,3-Benzodioxol-5-yl)-5,11-dioxo-2,3,5,10,11,11a-hexahydro-1H-pyrrolo[2,1-c][1,4]benzodiazepin-1-yl]amino}-2-oxoethoxy)acetic acid; ΔMass: 305.0813 Da]		162.05153	1.923
[Similar to: (2-{[(1S,11aS)-7-(1,3-Benzodioxol-5-yl)-5,11-dioxo-2,3,5,10,11,11a-hexahydro-1H-pyrrolo[2,1-c][1,4]benzodiazepin-1-yl]amino}-2-oxoethoxy)acetic acid; ΔMass: 306.0654 Da]		161.06751	1.954
[Similar to: (2-{[7-(2-Fluorophenyl)-5,11-dioxo-2,3,5,10,11,11a-hexahydro-1H-pyrrolo[2,1-c][1,4]benzodiazepin-1-yl]amino}-2-oxoethoxy)acetic acid; ΔMass: 106.0721 Da]	C11 H9 N7 O6	335.06151	1.945
[Similar to: (2-{[7-(2-Fluorophenyl)-5,11-dioxo-2,3,5,10,11,11a-hexahydro-1H-pyrrolo[2,1-c][1,4]benzodiazepin-1-yl]amino}-2-oxoethoxy)acetic acid; ΔMass: 278.0869 Da]		163.04671	1.929
[Similar to: (3R,4R,6R)-6-{[4-(1-Hydroxycyclopentyl)-1H-1,2,3-triazol-1-yl]methyl}-N-(2-methoxybenzyl)quinuclidine-3-carboxamide; ΔMass: 301.1805 Da]		138.07787	2.211
[Similar to: (4S,6S)-N-(Cyclopropylmethyl)-6-isobutyl-1-[(1-methyl-1H-imidazol-2-yl)methyl]-3,4,5,6-tetrahydro-1H-azepino[5,4,3-cd]indole-4-carboxamide; ΔMass: 142.1527 Da]	C6 H16 N9 O2 P	277.11577	2.425
[Similar to: (4S,6S)-N-(Cyclopropylmethyl)-6-isobutyl-1-[(1-methyl-1H-imidazol-2-yl)methyl]-3,4,5,6-tetrahydro-1H-azepino[5,4,3-cd]indole-4-carboxamide; ΔMass: 247.1849 Da]		172.08362	2.111
[Similar to: 2-Methoxy-N-{2-[1-(2-naphthyl)-1H-1,2,3,4-tetraazol-5-yl]vinyl}-5-(trifluoromethyl)aniline; ΔMass: 43.0187 Da]	C18 H16 N4 O5	368.11199	1.938
[Similar to: 2-Methoxy-N-{2-[1-(2-naphthyl)-1H-1,2,3,4-tetraazol-5-yl]vinyl}-5-(trifluoromethyl)aniline; ΔMass: 43.2561 Da]	C7 H4 N2 O6 P4 S	367.87461	1.817
[Similar to: 2-Methoxy-N-{2-[1-(2-naphthyl)-1H-1,2,3,4-tetraazol-5-yl]vinyl}-5-(trifluoromethyl)aniline; ΔMass: 44.0152 Da]		367.11548	1.944
[Similar to: 4-Guanidinobutyric acid; ΔMass: 43.0549 Da]		102.03026	1.936
[Similar to: 4-Oxoproline; ΔMass: -0.9228 Da]		129.96544	2.072
[Similar to: 4-Oxoproline; ΔMass: -0.9825 Da]		130.02513	1.934
[Similar to: 4-Oxoproline; ΔMass: -67.9864 Da]	C5 H14 N O P3	197.02904	3.595
[Similar to: Argininosuccinic acid; ΔMass: 158.0342 Da]		132.08842	1.859
[Similar to: Argininosuccinic acid; ΔMass: 158.1592 Da]		131.96345	1.816
[Similar to: Argininosuccinic acid; ΔMass: 159.1223 Da]	C H2 N5 O P	131.00029	1.928
[Similar to: D-(-)-Glutamine; ΔMass: -71.9041 Da]	C5 H3 N2 O6 P	217.9732	2.41
[Similar to: DL-Arginine; ΔMass: 0.1561 Da]	C5 H5 O P3	173.95553	1.865
[Similar to: DL-Arginine; ΔMass: 1.0828 Da]		173.02889	1.812
[Similar to: DL-Homoserine ; ΔMass: -161.0380 Da]	C7 H18 N6 O2 P2	280.0962	2.016
[Similar to: DL-Malic acid; ΔMass: 0.9854 Da]		133.03612	2.417
[Similar to: Guanidinosuccinic acid; ΔMass: 43.0073 Da]		132.05203	1.841
[Similar to: L-(-)-Malic acid; ΔMass: -156.0032 Da]	C6 H6 N6 O8	290.02473	2.414
[Similar to: L-Glutamic acid; ΔMass: 0.0481 Da]		147.00505	1.924
[Similar to: L-Glutamic acid; ΔMass: -147.0028 Da]	C6 H10 N6 O8	294.05597	1.942
[Similar to: L-Glutamic acid; ΔMass: -161.0684 Da]	C11 H20 N2 O8	308.12158	1.994
[Similar to: L-Glutamic acid; ΔMass: -168.0507 Da]	C7 H17 N5 O9	315.10383	1.904
[Similar to: L-Glutamic acid; ΔMass: -168.6796 Da]		315.73276	1.836
[Similar to: L-Glutamic acid; ΔMass: -169.0348 Da]	C8 H20 N4 O5 S2	316.08793	1.954
[Similar to: L-Glutamic acid; ΔMass: -184.6535 Da]		331.70662	1.84
[Similar to: L-Glutamic acid; ΔMass: -250.1156 Da]	C10 H23 N9 O8	397.1688	1.908
[Similar to: L-Glutamic acid; ΔMass: -251.0997 Da]	C17 H27 N4 O3 P S	398.15289	1.955
[Similar to: L-Histidine; ΔMass: -0.8350 Da]		155.90452	2.019
[Similar to: Microcystin LF; ΔMass: 855.5507 Da]		129.96539	1.824
[Similar to: N-(2,3-Dihydro-1,4-benzodioxin-6-yl)-1,2-dimethyl-1H-imidazole-4-sulfonamide; ΔMass: 122.9789 Da]		186.09943	2.525
[Similar to: N-1-({2-[4-(Dimethylamino)benzoyl]hydrazino}carbothioyl)-2-methylbut-2-enamide; ΔMass: 118.1227 Da]	C4 H13 O3 P3	202.00801	2.417
[Similar to: N'1-(2-Chlorobenzylidene)-4-hydroxy-3-(methylthio)-4,5,6,7-tetrahydrobenzo[c]thiophene-1-carbohydrazide; ΔMass: 120.2707 Da]		259.77129	1.845
[Similar to: N4-Acetylcytidine; ΔMass: 127.0282 Da]		158.06785	1.871
[Similar to: N4-Acetylcytidine; ΔMass: 128.0123 Da]		157.08381	1.856
[Similar to: Pyridoxamine; ΔMass: -18.0095 Da]		186.09936	2.213
[Similar to: S-Lactoylglutathione; ΔMass: 51.9888 Da]	C11 H21 N O10	327.11613	1.925
[Similar to: S-Lactoylglutathione; ΔMass: 52.9728 Da]	C11 H22 N2 O9	326.13211	1.885
[Similar to: S-Lactoylglutathione; ΔMass: 53.9569 Da]	C11 H23 N3 O8	325.14802	1.844
[Similar to: SSR504734; ΔMass: 124.0210 Da]	C11 H16 N2 O6	272.10065	6.542
[Similar to: Threonine; ΔMass: -162.8571 Da]	C6 H2 O9 S2	281.9153	1.81
[Similar to: Threonine; ΔMass: -179.0789 Da]	C10 H22 N2 O8	298.13713	1.854
[Similar to: Threonine; ΔMass: -180.0629 Da]	C10 H21 N O9	299.12119	1.889
[Similar to: Threonine; ΔMass: -180.8291 Da]	C3 H5 N4 O P5 S	299.88734	1.818
[Similar to: Threonine; ΔMass: -181.0458 Da]	C7 H12 N10 O4	300.10408	1.845
[Similar to: Threonine; ΔMass: -72.0200 Da]		191.07826	1.998
[Similar to: Uracil; ΔMass: -176.0656 Da]	C16 H17 O3 P	288.09284	1.983
1-(beta-D-Ribofuranosyl)-1,2-dihydropyrimidine	C9 H14 N2 O4	214.09469	3.086
1-[5-(2,3,4-Trihydroxybutyl)-2-pyrazinyl]-1,2,3,4-butanetetrol	C12 H20 N2 O7	304.12694	3.09
2,3,4,5,6,7-Hexahydroxyheptanoic acid	C7 H14 O8	226.06821	1.916
3-(3,4-dihydroxyphenyl)lactamide	C9 H11 N O4	197.06785	8.838
3,4-Dihydroxy-5-(1,2,3-trihydroxypropyl)dihydro-2(3H)-furanone	C7 H12 O7	208.05737	1.948
4-Hydroxyprolylthreonine	C9 H16 N2 O5	232.10532	2.292
4-Oxoproline	C5 H7 N O3	129.04115	3.595
6-deoxyinosine 5'-phosphate	C10 H13 N4 O7 P	332.05276	1.963
AC-benzyl	C11 H12 O3	192.07952	2.045
Bisphenol S	C12 H10 O4 S	250.02955	12.231
Bluensidine	C8 H16 N4 O6	264.10658	1.858
D-(-)-Glutamine	C5 H10 N2 O3	146.06776	1.878
D-(-)-Glutamine (2)	C5 H10 N2 O3	146.06779	2.08
D-(+)-Glucose	C6 H12 O6	180.06239	1.913
D-Glucono-delta-lactone	C6 H10 O6	178.04682	1.919
Dinoterb	C10 H12 N2 O5	240.07166	2.515
DL-Arginine	C6 H14 N4 O2	174.11054	1.857
DL-Arginine (2)	C6 H14 N4 O2	174.11142	1.859
DL-Glutamine	C5 H10 N2 O3	146.06895	1.876
Ethylene glycol tetraacetic acid	C14 H24 N2 O10	380.14271	2.998
Fenson	C12 H9 Cl O3 S	267.9959	15.934
Galactosamine	C6 H13 N O5	179.07863	1.815
Gluconic acid	C6 H12 O7	136.03593	1.951
Gluconic acid (2)	C6 H12 O7	196.05729	1.941
L-(-)-Malic acid	C4 H6 O5	134.0201	2.412
L-Aspartic acid	C4 H7 N O4	73.01495	1.87
L-Aspartic acid (2)	C4 H7 N O4	133.03603	1.873
L-Glutamic acid	C5 H9 N O4	147.05178	1.932
L-Histidine	C6 H9 N3 O2	155.06814	1.83
MFCD00037215	C8 H14 N2 O5	218.08957	2.515
Midodrine	C12 H18 N2 O4	254.12626	8.065
N-(3-Carboxy-3-hydroxypropyl)-4-[(carboxymethyl)amino]homoserine	C10 H18 N2 O8	294.10602	1.947
N-(4-Amino-1-carboxybutyl)glutamic acid	C10 H18 N2 O6	262.11613	2.326
N-Acetyl-DL-glutamic acid	C7 H11 N O5	189.0627	4.216
N-Acetylneuraminic acid	C11 H19 N O9	309.10572	2.027
neuraminic acid	C9 H17 N O8	267.09509	2.114
N-hexadecanoylsphinganine	C34 H69 N O3	539.52716	1.826
N-Methyl-<scp>D</scp>-aspartic acid	C5 H9 N O4	147.05297	1.936
Orotidine	C10 H12 N2 O8	288.05907	2.073
shinorine	C13 H20 N2 O8	332.12179	6.556
Trabodenoson	C15 H20 N6 O6	380.1427	2.159
Υ-Aminobutyric acid (GABA)	C4 H9 N O2	103.06166	1.931
METABOLITES_END
#END