#METABOLOMICS WORKBENCH epmosher_20210121_142232 DATATRACK_ID:2414 STUDY_ID:ST001658 ANALYSIS_ID:AN002709 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 Normal phase
CH:INSTRUMENT_NAME Thermo Dionex Ultimate 3000 RS
CH:COLUMN_NAME PolyLC Polyhydroxyethyl A (200 x 2.1mm, 5um)
CH:FLOW_GRADIENT 0-2min 80% B, 2-13min 80-40% B, 13-15min 40-10% B, 15-16min 10-80% B, 16-20min
CH:FLOW_GRADIENT 80% 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
(1R,2S,3R,5R,6R)-8-Azabicyclo[3.2.1]octane-1,2,3,6-tetrol 874098.4314 18570163.85 284002.0094
(2S)-3-Hydroxy-2-({[(3S,4S,5R)-2,3,4-trihydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]methyl}amino)butanoic acid (non-preferred name) 125367.2435 103451.6316 146271919
.alpha.-Aminoadipic acid 39046.06332 48099896.66 24208.1683
[Similar to: (1S)-1,5-Anhydro-1-[2,4,6-trihydroxy-3-(4-hydroxybenzoyl)phenyl]-D-glucitol; ΔMass: 185.0967 Da] 11142577.71 6133851.132 5832954.247
[Similar to: (1S)-1,5-Anhydro-1-[2,4,6-trihydroxy-3-(4-hydroxybenzoyl)phenyl]-D-glucitol; ΔMass: 186.0288 Da] 1502793.549 19284677.88 72793.22825
[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: 106.9957 Da] 218875.806 182242.752 24848456.81
[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: 190.0220 Da] 102349.1118 51988.57315 20865428.03
[Similar to: (3β,5ξ,9ξ,18ξ)-22-Hydroxyolean-12-en-3-yl 6-deoxyhexopyranosyl-(1->2)pentopyranosyl-(1->2)hexopyranosiduronic acid; ΔMass: 746.4617 Da] 354474.8822 8788353.897 77311576.98
[Similar to: (3β,5ξ,9ξ,18ξ)-22-Hydroxyolean-12-en-3-yl 6-deoxyhexopyranosyl-(1->2)pentopyranosyl-(1->2)hexopyranosiduronic acid; ΔMass: 752.4722 Da] 307779.3704 20970082.7 192102821
[Similar to: 1-O-[(2β,3β,5ξ,9ξ,18ξ)-3-(β-D-Glucopyranuronosyloxy)-2,23-dihydroxy-28-oxoolean-12-en-28-yl]-β-D-glucopyranose; ΔMass: 694.3943 Da] 1876475.941 50030119.3 495395727.3
[Similar to: 1-O-[(2β,3β,5ξ,9ξ,18ξ)-3-(β-D-Glucopyranuronosyloxy)-2,23-dihydroxy-28-oxoolean-12-en-28-yl]-β-D-glucopyranose; ΔMass: 711.3731 Da] 174027.8295 16006573.83 4593519.772
[Similar to: 1-O-[(2β,3β,5ξ,9ξ,18ξ)-3-(β-D-Glucopyranuronosyloxy)-2,23-dihydroxy-28-oxoolean-12-en-28-yl]-β-D-glucopyranose; ΔMass: 712.4048 Da] 1284583.497 43572088.82 415790837.9
[Similar to: 2-(Methylsulfonyl)-3-(pyrazin-2-ylamino)acrylonitrile; ΔMass: 108.0159 Da] 12025536.13 4341652.18 3417493.971
[Similar to: 2-(Methylsulfonyl)-3-(pyrazin-2-ylamino)acrylonitrile; ΔMass: 108.0272 Da] 94671.71479 209769.7613 23872300.77
[Similar to: 3-({[6-(Acetylamino)-3-pyridinyl]amino}carbonyl)-2-pyrazinecarboxylic acid; ΔMass: 195.1213 Da] 48302391.98 876028.5721 612817.5557
[Similar to: 3-O-β-D-Glucopyranosylandrographolide; ΔMass: 351.1943 Da] 202601.25 1664699.129 241990523
[Similar to: 4-Benzyl-N-(3,5-dimethyl-4-isoxazolyl)tetrahydro-1(2H)-pyrazinecarboxamide; ΔMass: 156.1061 Da] 748726.4194 10136686.25 417623968.4
[Similar to: 4-Hydroxybenzoic acid; ΔMass: -0.0100 Da] 23003001.82 7924715.424 4323484.533
[Similar to: 4-Hydroxybenzoic acid; ΔMass: -0.0464 Da] 34470268.61 70334119.31 1088630.075
[Similar to: 5-Methyltetrahydrofolic acid; ΔMass: 329.2210 Da] 4106917610 1036392619 6711475.129
[Similar to: 9-Nitrooleate; ΔMass: 202.1946 Da] 80267.10589 8504389.873 113553.7029
[Similar to: Acetylarginine; ΔMass: -305.7956 Da] 288420.3098 15163506.45 2982847.775
[Similar to: Argininosuccinic acid; ΔMass: 157.0863 Da] 14235047.74 6811077.885 10682736
[Similar to: Argininosuccinic acid; ΔMass: 80.1812 Da] 22991994.07 98135.37167 1096011.319
[Similar to: Argininosuccinic acid; ΔMass: 80.2706 Da] 139564877.7 64475.95677 554103.4581
[Similar to: Colistin; ΔMass: 804.8467 Da] 250608.5039 903781.9942 150270.1653
[Similar to: D-(-)-Glutamine; ΔMass: -0.8868 Da] 10450968.87 98030.71973 175076.9868
[Similar to: D-(-)-Glutamine; ΔMass: -141.0403 Da] 120512.5825 46406.73578 110047317.8
[Similar to: D-(-)-Glutamine; ΔMass: -156.0422 Da] 188685.4112 88773.87192 50089389.41
[Similar to: D-(-)-Glutamine; ΔMass: -161.0149 Da] 75491.96907 86298.52465 29122435.87
[Similar to: D-(-)-Glutamine; ΔMass: -162.0530 Da] 172840.5268 130646.993 307197007.3
[Similar to: D-(-)-Glutamine; ΔMass: -168.0513 Da] 162667.4789 76028.25576 359389500.3
[Similar to: D-(-)-Glutamine; ΔMass: -168.8110 Da] 4794916.799 25291.37041 189301.4767
[Similar to: D-(-)-Glutamine; ΔMass: -169.0353 Da] 113141.2622 59419.79634 41793102.31
[Similar to: DL-Arginine; ΔMass: -173.9140 Da] 95063.31833 84659.86786 19941783.13
[Similar to: DL-Dihydroorotic acid; ΔMass: 0.9487 Da] 204154.6733 107218.4354 191100469.9
[Similar to: Ethyl 4-[2-(2,4-dinitrophenyl)hydrazono]piperidine-1-carboxylate; ΔMass: 213.1625 Da] 11823408.43 10229279.59 8081039.722
[Similar to: FMOC-L-α-alanine; ΔMass: -191.0859 Da] 311139.6125 316859.8104 338250790.5
[Similar to: Guanidinosuccinic acid; ΔMass: -158.9411 Da] 269653.2205 5371639.749 1336304.806
[Similar to: L-Aspartic acid; ΔMass: 0.9489 Da] 159237.7025 72942.7706 371384690.5
[Similar to: L-Aspartic acid; ΔMass: -0.9828 Da] 2561358.522 1015625.932 37732172.22
[Similar to: L-Glutamic acid; ΔMass: -0.9190 Da] 48860.07588 53106.05201 1918142.891
[Similar to: L-Glutamic acid; ΔMass: -147.0533 Da] 143634.667 100997.4976 662641033
[Similar to: L-Glutamic acid; ΔMass: -162.9859 Da] 91125.97412 42616.72632 17248129.56
[Similar to: L-Glutamic acid; ΔMass: -169.0354 Da] 208779.5691 99606.48224 1142026759
[Similar to: L-Glutamic acid; ΔMass: -174.1117 Da] 72777.83029 71937.20534 503210781.7
[Similar to: L-Glutamic acid; ΔMass: -185.0090 Da] 75093.09996 70182.39295 49445922.18
[Similar to: L-Glutamic acid; ΔMass: -191.0172 Da] 93124.55977 74437.92387 66001736.93
[Similar to: L-Glutamic acid; ΔMass: -347.2398 Da] 222355.8935 110856.2272 875129599.1
[Similar to: L-Glutamic acid; ΔMass: -348.2240 Da] 71997.94713 60768.02622 744003755.3
[Similar to: L-Histidinol; ΔMass: 17.0278 Da] 883533.5493 25221184.29 20600247.7
[Similar to: Lincomycin; ΔMass: 286.1724 Da] 5568505.832 738919839.1 6591217757
[Similar to: Microcystin RR; ΔMass: 907.5404 Da] 1610136.467 608742.7191 26982629.49
[Similar to: N-(4,6-Dimethyl-2-pyrimidinyl)-4-({[2-(trifluoromethyl)anilino]carbonyl}amino)benzenesulfonamide; ΔMass: 339.0667 Da] 2414374.667 4187347.608 90031440.18
[Similar to: N-(4,6-Dimethyl-2-pyrimidinyl)-4-({[2-(trifluoromethyl)anilino]carbonyl}amino)benzenesulfonamide; ΔMass: 359.0852 Da] 4100875.74 698252.1718 15453747.86
[Similar to: N-{2-[(4-Chlorobenzyl)thio]ethyl}-2-furamide; ΔMass: 56.2014 Da] 6259705.982 23236.43832 300871.5789
[Similar to: N4-(2,1,3-Benzoxadiazol-5-yl)morpholine-4-carboxamide; ΔMass: 131.0498 Da] 23197533.09 5553627.372 3659176.138
[Similar to: N4-(2,1,3-Benzoxadiazol-5-yl)morpholine-4-carboxamide; ΔMass: 132.0813 Da] 459057.8492 23213719.9 2937632.857
[Similar to: N4-(2,1,3-Benzoxadiazol-5-yl)morpholine-4-carboxamide; ΔMass: 132.0813 Da] (2) 447538.4191 15433485.6 1184075.799
[Similar to: N4-Acetylcytidine; ΔMass: 127.0280 Da] 1126057.622 25109099.31 13856508.25
[Similar to: N4-Acetylcytidine; ΔMass: 175.0494 Da] 527687.2245 7101038.052 96586429.94
[Similar to: N-Acetyl-1-aspartylglutamic acid; ΔMass: 12.9949 Da] 1229873.209 163705416.2 27884236.03
[Similar to: N-Acetyl-1-aspartylglutamic acid; ΔMass: 12.9949 Da] (2) 359631.8382 85680302.76 10952399.03
[Similar to: N-Acetyl-1-aspartylglutamic acid; ΔMass: 12.9951 Da] 14155153.79 67780908.61 496413218
[Similar to: N-Acetyl-L-alanyl-L-alanyl-L-alanine; ΔMass: 111.2107 Da] 17234329.59 60536.05804 487953.2144
[Similar to: NAT19-353652_NEG; ΔMass: 209.1544 Da] 1273299.829 30747602.95 293658756.4
[Similar to: NAT19-353652_NEG; ΔMass: 227.1646 Da] 3909259.153 87189038.09 830163124
[Similar to: Niflumic acid; ΔMass: -83.0869 Da] 315535.7072 336740.3429 798676147.3
[Similar to: Niflumic acid; ΔMass: -84.0833 Da] 350066.8864 373592.0869 549608393.6
[Similar to: N-Methyl-D-aspartic acid (NMDA); ΔMass: -522.3354 Da] 67818.55002 57240.51296 226238645.4
[Similar to: N-Phenylacetylglutamine; ΔMass: -23.7500 Da] 18129971.65 11780.50611 98443.67407
[Similar to: N-Phenylacetylglutamine; ΔMass: 50.0549 Da] 159317.9575 244938.6959 133627256.6
[Similar to: N-Phenylacetylglutamine; ΔMass: 50.2648 Da] 47476376.1 57428.60342 513958.4064
[Similar to: S-Methyl-L-thiocitrulline; ΔMass: 47.0567 Da] 500341.8549 2355216.984 2239533.183
[Similar to: Testosterone sulfate; ΔMass: 130.0495 Da] 171310.1919 56692.12248 168375252.2
[Similar to: Threonine; ΔMass: -140.9466 Da] 408901.0857 27015407.95 1094538.637
[Similar to: Threonine; ΔMass: -141.0403 Da] 198258.1248 75329.85875 730103246.7
[Similar to: Threonine; ΔMass: -157.0143 Da] 172221.0109 65436.83614 26678652.22
[Similar to: Threonine; ΔMass: -162.8575 Da] 3689647.139 76629524.37 876484.2291
[Similar to: Threonine; ΔMass: -162.9285 Da] 244221.9119 23674905.18 681594.9251
[Similar to: Threonine; ΔMass: -308.6362 Da] 3374576.548 6820.957815 76590.27592
[Similar to: Threonine; ΔMass: -314.8063 Da] 177516.7025 17022959.84 498871.5307
[Similar to: Threonine; ΔMass: -320.1220 Da] 212585.9641 106744.4903 22950741.32
[Similar to: Threonine; ΔMass: -334.8719 Da] 252214.1565 192025.9718 342813.4566
[Similar to: Threonine; ΔMass: -67.9866 Da] 322548.618 383175.6394 245704300.3
[Similar to: Threonine; ΔMass: -84.8407 Da] 9373673.573 16944.22639 143988.3096
[Similar to: Trigoneoside Xb; ΔMass: 758.4463 Da] 3053311.765 74552838.5 724219550.1
[Similar to: Tyrosylalanine; ΔMass: -56.0112 Da] 141902.3828 79701.7296 67494083.99
1-(beta-D-Ribofuranosyl)-1,2-dihydropyrimidine 261508.6637 312056.729 34612865.23
1-[(3-Carboxypropyl)amino]-1-deoxy-beta-D-fructofuranose 321197.0417 1785056.548 21581065.07
1D-3-amino-1-guanidino-1,3-dideoxy-scyllo-inositol 329710.371 173158.0743 99213149.36
2,3,4,5,6,7-Hexahydroxyheptanoic acid 9917012.68 1420008377 11457587552
2-Acetamido-2-deoxy-3-O-(6-deoxy-alpha-L-galactopyranosyl)-D-glucose 315180.0761 336360.8126 73924401
2-amino-2,3,7-trideoxy-D-lyxo-hept-6-ulosonic acid 755019.0694 9603395.622 2624863251
2'-deamino-2'-hydroxy-6'-dehydroparomamine 624369.1352 653899.0674 92487224.96
2'-deamino-2'-hydroxy-6'-dehydroparomamine (2) 35467.32174 48099896.66 21989.38435
2'-deoxymugineic acid 503227.7326 4976182.843 2365839854
3-(3,4-dihydroxyphenyl)lactamide 64307.33027 23363626.63 51135.36487
4,4'-Dihydroxydiphenylsulfone 41243374.94 11741627.64 8073808.319
4-Hydroxyprolylalanine 214148.8177 13405119.08 13393217.55
4-O-Acetyl-N-acetylmannosamine 180482.2139 206652.2615 10836055.39
4-Oxoproline 1694739.892 2842615.664 549831365.7
6-(alpha-D-glucosaminyl)-1D-myo-inositol 426617.779 280968.066 138658035.9
7,8-dihydroneopterin 3'-phosphate 249079.3434 27749439.96 7409741.117
Adenosine 232188.0576 233365.3569 35400082.42
ALA-GLU 608554.7095 350863.4546 244870480.1
ALA-GLU (2) 77874.63782 578459.9481 48376265.11
Alanylclavam 300548.6534 117200.893 17152485.42
Alanylthreonine 256431.4973 274215.5864 40510531.08
ALA-PRO 47607309.84 372206289 48431685.61
ALA-PRO (2) 6572270.43 211244737.1 47681103.92
Asparagine 1123438.76 1105758.723 229278934.9
Azelaic acid 9346339.135 4681019.827 2671543.016
beta-D-hamamelose 11906832.51 2134371502 17917433537
Citric acid 5192047.981 357867.4496 16119301.92
D-(-)-Glutamine 1530816.858 1790019.392 17053586696
D-(-)-Glutamine (2) 140503.9829 62627.18647 1042048419
D-Glucono-delta-lactone 591112.04 1886157.05 32542986.97
DL-Arginine 263607.5482 99867.58459 4581202895
DL-Arginine (2) 344137.046 151167.2685 1620001771
entecavir 144099.8338 12571888.83 28134044.46
Fenson 44608488.45 8631722.665 7695119.331
Galactosamine 501320.977 530517.7499 552539492.2
Glucosamine 161874.2029 163260385.9 1667523.684
Glucosamine (2) 45518.25665 21754536.79 238232.377
Glu-Gly 314371.9918 224614.0377 18962060.4
glu-pro 1279562.486 10436299.55 25331583.73
Glycylglutamine 221418.3899 236774.2429 19769466.53
Gly-l-pro 697727.8419 34495259.12 93401725.47
HEPES 214901.8048 155401.2865 35977108.51
Hexitol 1597667.5 145981577.1 333846834.9
L-Aspartic acid 4974175.479 704090.2143 1633147425
L-Aspartic acid (2) 1454203.528 67410547.79 6706229.667
L-Glutamic acid 253208302.9 6684312.672 31319749739
L-Glutamic acid (2) 523111.6109 9054938.326 74134043.39
L-Theanine 209742.3693 223495.0168 24378999.91
Lysylvaline 190380.2521 203583.5418 23272445.56
MFCD01664827 899472.166 12550743.03 10676966.73
MFCD01664827 (2) 312763.0649 207437785.2 1003931.113
muramic acid 237732.8774 6467889.753 2550377018
muramic acid (2) 1077633.821 11804249.98 2195833046
muramic acid (3) 50766.90435 120716949 486294.2968
N(2)-succinyl-L-ornithine 2543405.885 38392771.37 47616675.86
N-(4-Amino-1-carboxybutyl)glutamic acid 280811.8379 318640.0723 28248790.23
N(6)-Methyladenosine 179560.2529 472659.4936 2486124790
N,N-diacetyllegionaminic acid 514449.4636 547334.149 87455020.09
N-acetyl-beta-D-glucosaminylamine 252858.1867 266166.0028 117736858.9
N-Acetyl-DL-glutamic acid 215836.5075 11820859.12 167164.7477
N-Acetyl-L-serine 84400.84799 61226.27193 612287925
N-Acetylneuraminic acid 161432.3433 23361221.21 1646016007
N-Acetylneuraminic acid (2) 1879118.199 2093852.34 627501012
N-Nitrosoguvacoline 20080104.21 4242627.236 441887.8004
N-Phenylacetyl pyroglutamic acid 981608.2849 1285007.208 51591684.19
N-Undecanoylglycine 28544667.85 5939166.893 2531967.793
Ornithine 270167.6119 141887.2669 1689654082
Orotidine (2) 135009.7482 22218354.38 149631023.6
Orotidine (3) 80310.96624 37558.89033 127748209.4
Orotidine (4) 269513.298 571829.3628 313340.4409
Oxaceprol 417161.7797 516232.4547 61871295.44
Phosphoaspartate 316890.0048 51262673.57 746154.0255
Threonine 1075492.557 8038594.32 12059509396
Threonylserine 162882.6716 208793.4596 56726250.51
val-arg 228202.6458 244029.0019 11808661.78
β-Alanine 277906.3601 214729.5701 50809933.79
Υ-Aminobutyric acid (GABA) 12149052.3 149810.5237 1810321712
MS_METABOLITE_DATA_END
#METABOLITES
METABOLITES_START
metabolite_name Formula Molecular Weight Retention times [min]
(1R,2S,3R,5R,6R)-8-Azabicyclo[3.2.1]octane-1,2,3,6-tetrol C7 H13 N O4 175.08363 4.582
(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 281.11119 4.964
.alpha.-Aminoadipic acid C6 H11 N O4 161.06899 6.28
[Similar to: (1S)-1,5-Anhydro-1-[2,4,6-trihydroxy-3-(4-hydroxybenzoyl)phenyl]-D-glucitol; ΔMass: 185.0967 Da] C7 H6 N5 P S 223.00892 3.021
[Similar to: (1S)-1,5-Anhydro-1-[2,4,6-trihydroxy-3-(4-hydroxybenzoyl)phenyl]-D-glucitol; ΔMass: 186.0288 Da] C8 H15 Cl N2 O3 222.07681 3.267
[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: 106.9957 Da] C14 H18 N6 O4 334.13788 4.542
[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: 190.0220 Da] C8 H17 N3 O6 251.11159 5.408
[Similar to: (3β,5ξ,9ξ,18ξ)-22-Hydroxyolean-12-en-3-yl 6-deoxyhexopyranosyl-(1->2)pentopyranosyl-(1->2)hexopyranosiduronic acid; ΔMass: 746.4617 Da] 150.05163 4.35
[Similar to: (3β,5ξ,9ξ,18ξ)-22-Hydroxyolean-12-en-3-yl 6-deoxyhexopyranosyl-(1->2)pentopyranosyl-(1->2)hexopyranosiduronic acid; ΔMass: 752.4722 Da] 144.04109 4.323
[Similar to: 1-O-[(2β,3β,5ξ,9ξ,18ξ)-3-(β-D-Glucopyranuronosyloxy)-2,23-dihydroxy-28-oxoolean-12-en-28-yl]-β-D-glucopyranose; ΔMass: 694.3943 Da] 132.0408 4.3
[Similar to: 1-O-[(2β,3β,5ξ,9ξ,18ξ)-3-(β-D-Glucopyranuronosyloxy)-2,23-dihydroxy-28-oxoolean-12-en-28-yl]-β-D-glucopyranose; ΔMass: 711.3731 Da] 115.06195 4.405
[Similar to: 1-O-[(2β,3β,5ξ,9ξ,18ξ)-3-(β-D-Glucopyranuronosyloxy)-2,23-dihydroxy-28-oxoolean-12-en-28-yl]-β-D-glucopyranose; ΔMass: 712.4048 Da] 114.03032 4.334
[Similar to: 2-(Methylsulfonyl)-3-(pyrazin-2-ylamino)acrylonitrile; ΔMass: 108.0159 Da] 116.02086 2.849
[Similar to: 2-(Methylsulfonyl)-3-(pyrazin-2-ylamino)acrylonitrile; ΔMass: 108.0272 Da] 116.00962 7.586
[Similar to: 3-({[6-(Acetylamino)-3-pyridinyl]amino}carbonyl)-2-pyrazinecarboxylic acid; ΔMass: 195.1213 Da] 105.95979 5.375
[Similar to: 3-O-β-D-Glucopyranosylandrographolide; ΔMass: 351.1943 Da] 161.06788 4.23
[Similar to: 4-Benzyl-N-(3,5-dimethyl-4-isoxazolyl)tetrahydro-1(2H)-pyrazinecarboxamide; ΔMass: 156.1061 Da] 158.0682 3.441
[Similar to: 4-Hydroxybenzoic acid; ΔMass: -0.0100 Da] 138.04168 3.235
[Similar to: 4-Hydroxybenzoic acid; ΔMass: -0.0464 Da] 138.07814 3.181
[Similar to: 5-Methyltetrahydrofolic acid; ΔMass: 329.2210 Da] 129.96563 4.772
[Similar to: 9-Nitrooleate; ΔMass: 202.1946 Da] 125.04641 2.777
[Similar to: Acetylarginine; ΔMass: -305.7956 Da] C9 H15 N6 O6 P5 S2 521.91786 5.749
[Similar to: Argininosuccinic acid; ΔMass: 157.0863 Da] 133.03633 5.549
[Similar to: Argininosuccinic acid; ΔMass: 80.1812 Da] C H3 Cl O10 209.9414 5.508
[Similar to: Argininosuccinic acid; ΔMass: 80.2706 Da] 209.85205 5.377
[Similar to: Colistin; ΔMass: 804.8467 Da] C4 H6 N2 O9 P4 349.90324 4.623
[Similar to: D-(-)-Glutamine; ΔMass: -0.8868 Da] C3 H4 N P3 146.95592 5.164
[Similar to: D-(-)-Glutamine; ΔMass: -141.0403 Da] C7 H13 N9 O4 287.10945 5.131
[Similar to: D-(-)-Glutamine; ΔMass: -156.0422 Da] C7 H15 N10 O2 P 302.11138 5.181
[Similar to: D-(-)-Glutamine; ΔMass: -161.0149 Da] C11 H13 N7 O2 S 307.08406 5.912
[Similar to: D-(-)-Glutamine; ΔMass: -162.0530 Da] C12 H16 N6 O4 308.1221 5.726
[Similar to: D-(-)-Glutamine; ΔMass: -168.0513 Da] C6 H19 N8 O5 P 314.12046 5.246
[Similar to: D-(-)-Glutamine; ΔMass: -168.8110 Da] C3 H2 Cl N5 O3 P4 314.88011 5.158
[Similar to: D-(-)-Glutamine; ΔMass: -169.0353 Da] C8 H23 N5 O2 P2 S 315.10446 5.422
[Similar to: DL-Arginine; ΔMass: -173.9140 Da] C9 H15 N6 O P3 S 348.02571 5.665
[Similar to: DL-Dihydroorotic acid; ΔMass: 0.9487 Da] 157.08404 5.397
[Similar to: Ethyl 4-[2-(2,4-dinitrophenyl)hydrazono]piperidine-1-carboxylate; ΔMass: 213.1625 Da] C2 H5 O P3 137.95542 2.657
[Similar to: FMOC-L-α-alanine; ΔMass: -191.0859 Da] C19 H30 N6 O10 502.20168 4.14
[Similar to: Guanidinosuccinic acid; ΔMass: -158.9411 Da] C5 H13 N4 O7 P3 334.00041 5.217
[Similar to: L-Aspartic acid; ΔMass: 0.9489 Da] 132.08865 5.109
[Similar to: L-Aspartic acid; ΔMass: -0.9828 Da] 134.02027 7.576
[Similar to: L-Glutamic acid; ΔMass: -0.9190 Da] 147.97218 6.108
[Similar to: L-Glutamic acid; ΔMass: -147.0533 Da] C11 H14 N6 O4 294.10643 5.698
[Similar to: L-Glutamic acid; ΔMass: -162.9859 Da] C7 H10 N4 O10 310.03908 7.574
[Similar to: L-Glutamic acid; ΔMass: -169.0354 Da] C8 H12 N8 O6 316.08855 5.653
[Similar to: L-Glutamic acid; ΔMass: -174.1117 Da] C11 H23 N5 O6 321.1649 5.523
[Similar to: L-Glutamic acid; ΔMass: -185.0090 Da] C9 H13 N6 O6 P 332.06221 5.662
[Similar to: L-Glutamic acid; ΔMass: -191.0172 Da] C13 H16 N4 O3 P2 338.07034 5.719
[Similar to: L-Glutamic acid; ΔMass: -347.2398 Da] C17 H38 N10 O7 494.293 5.33
[Similar to: L-Glutamic acid; ΔMass: -348.2240 Da] C17 H37 N9 O8 495.27714 5.505
[Similar to: L-Histidinol; ΔMass: 17.0278 Da] 124.06238 3.354
[Similar to: Lincomycin; ΔMass: 286.1724 Da] 120.0414 4.319
[Similar to: Microcystin RR; ΔMass: 907.5404 Da] 130.02539 5.618
[Similar to: N-(4,6-Dimethyl-2-pyrimidinyl)-4-({[2-(trifluoromethyl)anilino]carbonyl}amino)benzenesulfonamide; ΔMass: 339.0667 Da] 126.04159 5.275
[Similar to: N-(4,6-Dimethyl-2-pyrimidinyl)-4-({[2-(trifluoromethyl)anilino]carbonyl}amino)benzenesulfonamide; ΔMass: 359.0852 Da] 106.02308 3.454
[Similar to: N-{2-[(4-Chlorobenzyl)thio]ethyl}-2-furamide; ΔMass: 56.2014 Da] 238.84196 5.247
[Similar to: N4-(2,1,3-Benzoxadiazol-5-yl)morpholine-4-carboxamide; ΔMass: 131.0498 Da] 117.04116 3.727
[Similar to: N4-(2,1,3-Benzoxadiazol-5-yl)morpholine-4-carboxamide; ΔMass: 132.0813 Da] 116.00962 4.95
[Similar to: N4-(2,1,3-Benzoxadiazol-5-yl)morpholine-4-carboxamide; ΔMass: 132.0813 Da] (2) 116.0096 4.776
[Similar to: N4-Acetylcytidine; ΔMass: 127.0280 Da] 158.0681 3.751
[Similar to: N4-Acetylcytidine; ΔMass: 175.0494 Da] 110.04665 3.442
[Similar to: N-Acetyl-1-aspartylglutamic acid; ΔMass: 12.9949 Da] C12 H13 N5 O4 291.09577 6.18
[Similar to: N-Acetyl-1-aspartylglutamic acid; ΔMass: 12.9949 Da] (2) C12 H13 N5 O4 291.09575 6.405
[Similar to: N-Acetyl-1-aspartylglutamic acid; ΔMass: 12.9951 Da] C12 H13 N5 O4 291.09559 5.711
[Similar to: N-Acetyl-L-alanyl-L-alanyl-L-alanine; ΔMass: 111.2107 Da] 161.92175 5.38
[Similar to: NAT19-353652_NEG; ΔMass: 209.1544 Da] 120.04069 4.335
[Similar to: NAT19-353652_NEG; ΔMass: 227.1646 Da] 102.03049 4.344
[Similar to: Niflumic acid; ΔMass: -83.0869 Da] 365.14851 3.859
[Similar to: Niflumic acid; ΔMass: -84.0833 Da] C16 H27 Cl O7 366.14491 3.854
[Similar to: N-Methyl-D-aspartic acid (NMDA); ΔMass: -522.3354 Da] C22 H55 N9 O14 669.38852 5.497
[Similar to: N-Phenylacetylglutamine; ΔMass: -23.7500 Da] C3 H2 Cl2 N4 P4 287.86104 5.185
[Similar to: N-Phenylacetylglutamine; ΔMass: 50.0549 Da] C4 H6 N8 O3 214.05607 5.228
[Similar to: N-Phenylacetylglutamine; ΔMass: 50.2648 Da] 213.84617 5.373
[Similar to: S-Methyl-L-thiocitrulline; ΔMass: 47.0567 Da] C7 H11 P S 158.03178 5.715
[Similar to: Testosterone sulfate; ΔMass: 130.0495 Da] C8 H18 N2 O6 238.11629 5.012
[Similar to: Threonine; ΔMass: -140.9466 Da] C5 H5 N6 O5 P 260.00482 4.968
[Similar to: Threonine; ΔMass: -141.0403 Da] C6 H12 N8 O4 260.09851 4.98
[Similar to: Threonine; ΔMass: -157.0143 Da] C9 H8 N8 O3 276.07258 4.973
[Similar to: Threonine; ΔMass: -162.8575 Da] C6 H6 O5 P4 281.91575 5.054
[Similar to: Threonine; ΔMass: -162.9285 Da] C4 H8 N6 O3 P2 S 281.98679 5.063
[Similar to: Threonine; ΔMass: -308.6362 Da] C2 H2 Cl2 O3 P4 S5 427.69446 5.199
[Similar to: Threonine; ΔMass: -314.8063 Da] C5 H3 Cl N6 O8 P4 433.86453 5.067
[Similar to: Threonine; ΔMass: -320.1220 Da] C13 H31 N9 O2 P2 S 439.18022 4.869
[Similar to: Threonine; ΔMass: -334.8719 Da] C10 H9 N4 O9 P3 S 453.93019 4.829
[Similar to: Threonine; ΔMass: -67.9866 Da] C3 H5 N7 O3 187.04488 4.955
[Similar to: Threonine; ΔMass: -84.8407 Da] C2 H5 Cl O P4 203.89894 5.189
[Similar to: Trigoneoside Xb; ΔMass: 758.4463 Da] 162.05179 4.322
[Similar to: Tyrosylalanine; ΔMass: -56.0112 Da] C12 H16 N6 O4 308.12218 5.463
1-(beta-D-Ribofuranosyl)-1,2-dihydropyrimidine C9 H14 N2 O4 214.09496 4.167
1-[(3-Carboxypropyl)amino]-1-deoxy-beta-D-fructofuranose C10 H19 N O7 265.11616 4.986
1D-3-amino-1-guanidino-1,3-dideoxy-scyllo-inositol C7 H16 N4 O4 220.11669 5.383
2,3,4,5,6,7-Hexahydroxyheptanoic acid C7 H14 O8 226.06857 4.319
2-Acetamido-2-deoxy-3-O-(6-deoxy-alpha-L-galactopyranosyl)-D-glucose C14 H25 N O10 367.1479 3.861
2-amino-2,3,7-trideoxy-D-lyxo-hept-6-ulosonic acid C7 H13 N O5 191.07941 4.231
2'-deamino-2'-hydroxy-6'-dehydroparomamine C12 H22 N2 O8 322.13773 3.911
2'-deamino-2'-hydroxy-6'-dehydroparomamine (2) C12 H22 N2 O8 322.13787 6.267
2'-deoxymugineic acid C12 H20 N2 O7 304.12741 4.182
3-(3,4-dihydroxyphenyl)lactamide C9 H11 N O4 197.06825 2.784
4,4'-Dihydroxydiphenylsulfone C12 H10 O4 S 250.03002 2.517
4-Hydroxyprolylalanine C8 H14 N2 O4 202.09476 3.371
4-O-Acetyl-N-acetylmannosamine C10 H17 N O7 263.10052 4.221
4-Oxoproline C5 H7 N O3 129.04134 5.263
6-(alpha-D-glucosaminyl)-1D-myo-inositol C12 H23 N O10 341.13239 4.703
7,8-dihydroneopterin 3'-phosphate C9 H14 N5 O7 P 335.06206 4.354
Adenosine C10 H13 N5 O4 267.09566 5.946
ALA-GLU C8 H14 N2 O5 218.08989 4.884
ALA-GLU (2) C8 H14 N2 O5 218.08987 5.815
Alanylclavam C8 H12 N2 O4 200.0791 4.861
Alanylthreonine C7 H14 N2 O4 190.09467 3.822
ALA-PRO C8 H14 N2 O3 186.09984 3.274
ALA-PRO (2) C8 H14 N2 O3 186.09999 3.391
Asparagine C4 H8 N2 O3 132.05225 5.723
Azelaic acid C9 H16 O4 188.10418 2.567
beta-D-hamamelose C6 H12 O6 180.06292 4.354
Citric acid C6 H8 O7 192.02626 5.739
D-(-)-Glutamine C5 H10 N2 O3 146.06802 5.266
D-(-)-Glutamine (2) C5 H10 N2 O3 146.06926 5.271
D-Glucono-delta-lactone C6 H10 O6 178.04712 4.378
DL-Arginine C6 H14 N4 O2 174.11079 5.386
DL-Arginine (2) C6 H14 N4 O2 174.11081 5.159
entecavir C12 H15 N5 O3 277.11616 4.945
Fenson C12 H9 Cl O3 S 267.99634 2.447
Galactosamine C6 H13 N O5 179.07859 3.809
Glucosamine C6 H13 N O5 179.07883 6.272
Glucosamine (2) C6 H13 N O5 179.07861 6.445
Glu-Gly C7 H12 N2 O5 204.07409 4.214
glu-pro C10 H16 N2 O5 244.10583 3.354
Glycylglutamine C7 H13 N3 O4 203.09006 3.852
Gly-l-pro C7 H12 N2 O3 172.08396 3.35
HEPES C8 H18 N2 O4 S 238.09858 4.678
Hexitol C6 H14 O6 182.07831 4.258
L-Aspartic acid C4 H7 N O4 133.03631 7.582
L-Aspartic acid (2) C4 H7 N O4 133.0363 5.058
L-Glutamic acid C5 H9 N O4 147.05202 5.608
L-Glutamic acid (2) C5 H9 N O4 147.05208 6.347
L-Theanine C7 H14 N2 O3 174.09964 3.778
Lysylvaline C11 H23 N3 O3 245.17383 3.823
MFCD01664827 C5 H8 N2 O5 176.04252 5.567
MFCD01664827 (2) C5 H8 N2 O5 176.0425 5.06
muramic acid C9 H17 N O7 251.1004 4.239
muramic acid (2) C9 H17 N O7 251.10054 4.019
muramic acid (3) C9 H17 N O7 251.1006 6.264
N(2)-succinyl-L-ornithine C9 H16 N2 O5 232.1057 3.368
N-(4-Amino-1-carboxybutyl)glutamic acid C10 H18 N2 O6 262.11659 3.711
N(6)-Methyladenosine C11 H15 N5 O4 281.11119 5.191
N,N-diacetyllegionaminic acid C13 H22 N2 O8 334.13802 3.744
N-acetyl-beta-D-glucosaminylamine C8 H16 N2 O5 220.10561 3.914
N-Acetyl-DL-glutamic acid C7 H11 N O5 189.06301 3.885
N-Acetyl-L-serine C5 H9 N O4 147.05327 5.612
N-Acetylneuraminic acid C11 H19 N O9 309.10625 4.362
N-Acetylneuraminic acid (2) C11 H19 N O9 309.1064 6.741
N-Nitrosoguvacoline C7 H10 N2 O3 170.06829 3.12
N-Phenylacetyl pyroglutamic acid C14 H15 N O3 245.10574 5.05
N-Undecanoylglycine C13 H25 N O3 243.18341 2.5
Ornithine C5 H12 N2 O2 132.08862 5.386
Orotidine (2) C10 H12 N2 O8 288.05976 10.097
Orotidine (3) C10 H12 N2 O8 288.05719 7.578
Orotidine (4) C10 H12 N2 O8 288.05961 8.935
Oxaceprol C7 H11 N O4 173.06815 4.237
Phosphoaspartate C4 H8 N O7 P 213.00354 4.358
Threonine C4 H9 N O3 119.05694 5.032
Threonylserine C7 H14 N2 O5 206.08972 4.249
val-arg C11 H23 N5 O3 273.18032 3.802
β-Alanine C3 H7 N O2 89.04621 7.585
Υ-Aminobutyric acid (GABA) C4 H9 N O2 103.06185 5.605
METABOLITES_END
#END