{
"METABOLOMICS WORKBENCH":{"STUDY_ID":"ST001658","ANALYSIS_ID":"AN002707","VERSION":"1","CREATED_ON":"January 25, 2021, 11:40 am"},

"PROJECT":{"PROJECT_TITLE":"Control of Topoisomerase II Activity and Chemotherapeutic Inhibition by TCA Cycle Metabolites","PROJECT_SUMMARY":"Topoisomerase II (topo II) is essential for disentangling newly-replicated chromosomes. DNA unlinking involves the physical passage of one DNA duplex through another and depends on the transient formation of double-strand DNA breaks, a step exploited by frontline chemotherapies to kill cancer cells. Although anti-topo II drugs are efficacious, they also elicit cytotoxic side effects in normal cells; insights into how topo II is regulated in different cellular contexts is essential to improve their targeted use. Using chemical fractionation and mass spectrometry, we have discovered that topo II is subject to metabolic control through the TCA cycle. We show that TCA metabolites stimulate topo II activity in vitro and that levels of TCA flux modulate cellular sensitivity to anti-topo II drugs in vivo. Our works reveals an unanticipated connection between the control of DNA topology and cellular metabolism, a finding with important ramifications for the clinical use of anti-topo II therapies.","INSTITUTE":"Johns Hopkins University","LAST_NAME":"Mosher","FIRST_NAME":"Eric","ADDRESS":"725 North Wolfe Street, Biophysics 307","EMAIL":"emosher2@jhmi.edu","PHONE":"410-952-9154"},

"STUDY":{"STUDY_TITLE":"Control of Topoisomerase II Activity and Chemotherapeutic Inhibition by TCA Cycle Metabolites","STUDY_SUMMARY":"Topoisomerase II (topo II) is essential for disentangling newly-replicated chromosomes. DNA unlinking involves the physical passage of one DNA duplex through another and depends on the transient formation of double-strand DNA breaks, a step exploited by frontline chemotherapies to kill cancer cells. Although anti-topo II drugs are efficacious, they also elicit cytotoxic side effects in normal cells; insights into how topo II is regulated in different cellular contexts is essential to improve their targeted use. Using chemical fractionation and mass spectrometry, we have discovered that topo II is subject to metabolic control through the TCA cycle. We show that TCA metabolites stimulate topo II activity in vitro and that levels of TCA flux modulate cellular sensitivity to anti-topo II drugs in vivo. Our works reveals an unanticipated connection between the control of DNA topology and cellular metabolism, a finding with important ramifications for the clinical use of anti-topo II therapies.","INSTITUTE":"Johns Hopkins University","LAST_NAME":"Mosher","FIRST_NAME":"Eric","ADDRESS":"725 North Wolfe Street, Biophysics 307","EMAIL":"emosher2@jhmi.edu","PHONE":"410-952-9154"},

"SUBJECT":{"SUBJECT_TYPE":"Yeast","SUBJECT_SPECIES":"Saccharomyces cerevisiae","TAXONOMY_ID":"4932","CELL_STRAIN_DETAILS":"BY4741"},
"SUBJECT_SAMPLE_FACTORS":[
{
"Subject ID":"-",
"Sample ID":"F4",
"Factors":{"Treatment":"HPLC fraction 4"},
"Additional sample data":{"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 ID":"-",
"Sample ID":"F5",
"Factors":{"Treatment":"HPLC fraction 5"},
"Additional sample data":{"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 ID":"-",
"Sample ID":"F6",
"Factors":{"Treatment":"HPLC fraction 6"},
"Additional sample data":{"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":{"COLLECTION_SUMMARY":"Yeast cultures were grown in SC-sulfate media and were harvested at OD600 0.4-0.8 by vacuum filtration then washed with 100mM ammonium acetate - TEA (pH 8.0). Metabolites were extracted by the addition of pre-chilled 10mL 90% methanol, 10mM ammonium acetate - TEA (pH 8.0). Cell debris was removed by centrifugation at 4000g for 10-15 minutes. Extracts were subsequently passed through 3 kDa MWCO filters. Filtrate was diluted 2-fold with water and lyophilized. Lyophilized metabolite extracts were resuspended with water and pH was adjusted to 10 with TEA. The extract was then passed through a mixed-mode anion exchange solid phase extraction cartridge and fractionated by reverse-phase HPLC on a C18 column. One column volume of water plus 0.1% formic acid and eight column volumes of methanol were passed through the column. Fractions that eluted during the aqueous phase were then lyophilized.","SAMPLE_TYPE":"Yeast cells"},

"TREATMENT":{"TREATMENT_SUMMARY":"Active fractions were run on a normal-phase HPLC on an amide column and fractions were collected. Fractions 4, 5, and 6 were subjected to metabolomics analyses."},

"SAMPLEPREP":{"SAMPLEPREP_SUMMARY":"Fractions of interest were lyophilized then reconstituted in water plus 0.1% formic acid such that samples reached a final concentration of 20 mg/mL."},

"CHROMATOGRAPHY":{"CHROMATOGRAPHY_TYPE":"Reversed phase","INSTRUMENT_NAME":"Thermo Dionex Ultimate 3000 RS","COLUMN_NAME":"Thermo Hypersil Gold aQ (150 x 2.1mm, 1.9um)","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","FLOW_RATE":"0.2 mL/min","COLUMN_TEMPERATURE":"30","SOLVENT_A":"1mM ammonium acetate + 0.1% formic acid in water","SOLVENT_B":"1mM ammonium acetate + 0.1% formic acid in 20/80 water/acetonitrile"},

"ANALYSIS":{"ANALYSIS_TYPE":"MS"},

"MS":{"INSTRUMENT_NAME":"Thermo Q Exactive Orbitrap","INSTRUMENT_TYPE":"Orbitrap","MS_TYPE":"ESI","ION_MODE":"NEGATIVE","MS_COMMENTS":"MS1 data was acquired at a resolution of 140,000 over a scan range of 65-850 m/z. Data was analyzed with Thermo Compound Discoverer software."},

"MS_METABOLITE_DATA":{
"Units":"Peak Area",

"Data":[{"Metabolite":"(±)-Ibotenic acid","F4":"9540737.349","F5":"44452.64866","F6":"334588.7782"},{"Metabolite":"(1R,2R,3S,5R,7R)-2-Acetamido-7-(1,2-dihydroxyethyl)-3-hydroxy-6,8-dioxabicyclo[3.2.1]octane-5-carboxylic acid","F4":"1446887.385","F5":"51910445.09","F6":"20059523.08"},{"Metabolite":"(1R,2R,3S,5R,7R)-2-Acetamido-7-(1,2-dihydroxyethyl)-3-hydroxy-6,8-dioxabicyclo[3.2.1]octane-5-carboxylic acid (2)","F4":"409229.6609","F5":"6963219.568","F6":"5217140.513"},{"Metabolite":"(2S)-2-({[(3S,4S,5R)-2,3,4-Trihydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]methyl}amino)propanoic acid (non-preferred name)","F4":"140312.5155","F5":"61999860.06","F6":"202544290.5"},{"Metabolite":"(2S)-3-Hydroxy-2-({[(3S,4S,5R)-2,3,4-trihydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]methyl}amino)butanoic acid (non-preferred name)","F4":"85017.00804","F5":"610761.7381","F6":"302258175.3"},{"Metabolite":"[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]","F4":"2271432.095","F5":"25991345.78","F6":"52658334.14"},{"Metabolite":"[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]","F4":"108952.6459","F5":"10995521.48","F6":"30121306.41"},{"Metabolite":"[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]","F4":"64482.58995","F5":"43474871.62","F6":"21536961.28"},{"Metabolite":"[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]","F4":"93018.43073","F5":"249763.5055","F6":"17548427.85"},{"Metabolite":"[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]","F4":"2553051.337","F5":"14657356.15","F6":"43537.99421"},{"Metabolite":"[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]","F4":"11984.03968","F5":"5739785.708","F6":"6323601.988"},{"Metabolite":"[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]","F4":"33181.98808","F5":"10404801.1","F6":"14944115.49"},{"Metabolite":"[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]","F4":"44113.04533","F5":"18292988.55","F6":"57228293.75"},{"Metabolite":"[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]","F4":"616930.9926","F5":"17492918.87","F6":"433282.9275"},{"Metabolite":"[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]","F4":"62548.9873","F5":"19690062.81","F6":"23559367.49"},{"Metabolite":"[Similar to: 4-Guanidinobutyric acid; ΔMass: 43.0549 Da]","F4":"2926865.168","F5":"31214369.51","F6":"72334998.83"},{"Metabolite":"[Similar to: 4-Oxoproline; ΔMass: -0.9228 Da]","F4":"91839007.76","F5":"63348124.67","F6":"2325794.071"},{"Metabolite":"[Similar to: 4-Oxoproline; ΔMass: -0.9825 Da]","F4":"78309.40354","F5":"770076.5059","F6":"10375369.51"},{"Metabolite":"[Similar to: 4-Oxoproline; ΔMass: -67.9864 Da]","F4":"245187.9668","F5":"12327821.8","F6":"7583362.223"},{"Metabolite":"[Similar to: Argininosuccinic acid; ΔMass: 158.0342 Da]","F4":"112287.7725","F5":"78267.69396","F6":"207646775.2"},{"Metabolite":"[Similar to: Argininosuccinic acid; ΔMass: 158.1592 Da]","F4":"7100825.405","F5":"80900492.86","F6":"423799.3258"},{"Metabolite":"[Similar to: Argininosuccinic acid; ΔMass: 159.1223 Da]","F4":"5204505.731","F5":"47144.07436","F6":"262912.4296"},{"Metabolite":"[Similar to: D-(-)-Glutamine; ΔMass: -71.9041 Da]","F4":"38196.38007","F5":"4803452.923","F6":"45109.00764"},{"Metabolite":"[Similar to: DL-Arginine; ΔMass: 0.1561 Da]","F4":"1347863.565","F5":"13032309.99","F6":"562774.8554"},{"Metabolite":"[Similar to: DL-Arginine; ΔMass: 1.0828 Da]","F4":"69012.18631","F5":"65380.54409","F6":"43182292.95"},{"Metabolite":"[Similar to: DL-Homoserine ; ΔMass: -161.0380 Da]","F4":"55427.50573","F5":"3164047.383","F6":"1414936.46"},{"Metabolite":"[Similar to: DL-Malic acid; ΔMass: 0.9854 Da]","F4":"89572.5854","F5":"13937171.73","F6":"608977.4718"},{"Metabolite":"[Similar to: Guanidinosuccinic acid; ΔMass: 43.0073 Da]","F4":"203781.2851","F5":"165463.8067","F6":"94509107.54"},{"Metabolite":"[Similar to: L-(-)-Malic acid; ΔMass: -156.0032 Da]","F4":"9069.583177","F5":"2214338.769","F6":"11425.197"},{"Metabolite":"[Similar to: L-Glutamic acid; ΔMass: 0.0481 Da]","F4":"42909.6235","F5":"44803.68093","F6":"7722835.007"},{"Metabolite":"[Similar to: L-Glutamic acid; ΔMass: -147.0028 Da]","F4":"88407.6981","F5":"15219565.6","F6":"3454727.853"},{"Metabolite":"[Similar to: L-Glutamic acid; ΔMass: -161.0684 Da]","F4":"47801.12506","F5":"51500.40876","F6":"76906907.02"},{"Metabolite":"[Similar to: L-Glutamic acid; ΔMass: -168.0507 Da]","F4":"79376.445","F5":"59148.23729","F6":"45544875.22"},{"Metabolite":"[Similar to: L-Glutamic acid; ΔMass: -168.6796 Da]","F4":"116112985.2","F5":"199683.6544","F6":"624895.6296"},{"Metabolite":"[Similar to: L-Glutamic acid; ΔMass: -169.0348 Da]","F4":"71878.2626","F5":"82855.15019","F6":"233585524.2"},{"Metabolite":"[Similar to: L-Glutamic acid; ΔMass: -184.6535 Da]","F4":"115351455.3","F5":"130395.9992","F6":"336129.3037"},{"Metabolite":"[Similar to: L-Glutamic acid; ΔMass: -250.1156 Da]","F4":"82102.10185","F5":"57950.94874","F6":"13484818.5"},{"Metabolite":"[Similar to: L-Glutamic acid; ΔMass: -251.0997 Da]","F4":"61250.90347","F5":"54770.41534","F6":"127150760.5"},{"Metabolite":"[Similar to: L-Histidine; ΔMass: -0.8350 Da]","F4":"41157152.81","F5":"142735.5264","F6":"861135.6052"},{"Metabolite":"[Similar to: Microcystin LF; ΔMass: 855.5507 Da]","F4":"99832171.41","F5":"1104853913","F6":"6463195.797"},{"Metabolite":"[Similar to: N-(2,3-Dihydro-1,4-benzodioxin-6-yl)-1,2-dimethyl-1H-imidazole-4-sulfonamide; ΔMass: 122.9789 Da]","F4":"755798.4658","F5":"34536491.91","F6":"335434.9508"},{"Metabolite":"[Similar to: N-1-({2-[4-(Dimethylamino)benzoyl]hydrazino}carbothioyl)-2-methylbut-2-enamide; ΔMass: 118.1227 Da]","F4":"36174.236","F5":"10273961.97","F6":"69661.57013"},{"Metabolite":"[Similar to: N'1-(2-Chlorobenzylidene)-4-hydroxy-3-(methylthio)-4,5,6,7-tetrahydrobenzo[c]thiophene-1-carbohydrazide; ΔMass: 120.2707 Da]","F4":"139110702.9","F5":"145238.9977","F6":"407234.887"},{"Metabolite":"[Similar to: N4-Acetylcytidine; ΔMass: 127.0282 Da]","F4":"93765.21746","F5":"6470334.73","F6":"17697533.25"},{"Metabolite":"[Similar to: N4-Acetylcytidine; ΔMass: 128.0123 Da]","F4":"108182.0285","F5":"79935.7704","F6":"20965216.49"},{"Metabolite":"[Similar to: Pyridoxamine; ΔMass: -18.0095 Da]","F4":"1489195.783","F5":"9912274.055","F6":"147887.3019"},{"Metabolite":"[Similar to: S-Lactoylglutathione; ΔMass: 51.9888 Da]","F4":"82279.9459","F5":"89427.86984","F6":"390082595.6"},{"Metabolite":"[Similar to: S-Lactoylglutathione; ΔMass: 52.9728 Da]","F4":"74886.02663","F5":"42359.54456","F6":"370091566.5"},{"Metabolite":"[Similar to: S-Lactoylglutathione; ΔMass: 53.9569 Da]","F4":"67009.70144","F5":"49513.51145","F6":"10919869.39"},{"Metabolite":"[Similar to: SSR504734; ΔMass: 124.0210 Da]","F4":"17749522.38","F5":"4020957.085","F6":"45320.18126"},{"Metabolite":"[Similar to: Threonine; ΔMass: -162.8571 Da]","F4":"4262248.335","F5":"85964807.91","F6":"178390.2567"},{"Metabolite":"[Similar to: Threonine; ΔMass: -179.0789 Da]","F4":"60432.75647","F5":"45326.29388","F6":"26344774.47"},{"Metabolite":"[Similar to: Threonine; ΔMass: -180.0629 Da]","F4":"80827.61568","F5":"448935.9608","F6":"377716623.9"},{"Metabolite":"[Similar to: Threonine; ΔMass: -180.8291 Da]","F4":"1412775.372","F5":"61509833.11","F6":"235176.2829"},{"Metabolite":"[Similar to: Threonine; ΔMass: -181.0458 Da]","F4":"72084.83028","F5":"53263.52741","F6":"4484628.325"},{"Metabolite":"[Similar to: Threonine; ΔMass: -72.0200 Da]","F4":"368896.313","F5":"1422774.349","F6":"26639274.44"},{"Metabolite":"[Similar to: Uracil; ΔMass: -176.0656 Da]","F4":"104483.622","F5":"93429.01165","F6":"16657748.66"},{"Metabolite":"1-(beta-D-Ribofuranosyl)-1,2-dihydropyrimidine","F4":"35034.90177","F5":"114165.7271","F6":"6659161.034"},{"Metabolite":"1-[5-(2,3,4-Trihydroxybutyl)-2-pyrazinyl]-1,2,3,4-butanetetrol","F4":"105073.7353","F5":"2065587.428","F6":"634325882.7"},{"Metabolite":"2,3,4,5,6,7-Hexahydroxyheptanoic acid","F4":"617892.7008","F5":"395414191","F6":"718715994.1"},{"Metabolite":"3-(3,4-dihydroxyphenyl)lactamide","F4":"26412.72795","F5":"3311067.718","F6":"12356.56919"},{"Metabolite":"3,4-Dihydroxy-5-(1,2,3-trihydroxypropyl)dihydro-2(3H)-furanone","F4":"1523433.459","F5":"1119066.461","F6":"18927665.92"},{"Metabolite":"4-Hydroxyprolylthreonine","F4":"510156.2404","F5":"3457825.832","F6":"17715469.14"},{"Metabolite":"4-Oxoproline","F4":"1603103.271","F5":"84775188.31","F6":"47794515.49"},{"Metabolite":"6-deoxyinosine 5'-phosphate","F4":"70875.86718","F5":"61958.45485","F6":"21362590.9"},{"Metabolite":"AC-benzyl","F4":"6454952.694","F5":"1029803.466","F6":"334603.3165"},{"Metabolite":"Bisphenol S","F4":"19436822.08","F5":"2513059.403","F6":"2556635.851"},{"Metabolite":"Bluensidine","F4":"136569.0882","F5":"101840.7823","F6":"7114171.782"},{"Metabolite":"D-(-)-Glutamine","F4":"252689.6501","F5":"262898.8427","F6":"1704079020"},{"Metabolite":"D-(-)-Glutamine (2)","F4":"88179.06901","F5":"1809381.556","F6":"76076651.08"},{"Metabolite":"D-(+)-Glucose","F4":"3528143.011","F5":"628428000.7","F6":"1145309760"},{"Metabolite":"D-Glucono-delta-lactone","F4":"199728.8439","F5":"13343796.53","F6":"58988883.81"},{"Metabolite":"Dinoterb","F4":"20312.00758","F5":"22922.68007","F6":"9389437.505"},{"Metabolite":"DL-Arginine","F4":"403963.821","F5":"293616.7443","F6":"778072378.7"},{"Metabolite":"DL-Arginine (2)","F4":"168693.019","F5":"126524.5837","F6":"55938900.97"},{"Metabolite":"DL-Glutamine","F4":"76189.16393","F5":"47931.64732","F6":"17099749.17"},{"Metabolite":"Ethylene glycol tetraacetic acid","F4":"13557.39738","F5":"32755.92506","F6":"8310556.495"},{"Metabolite":"Fenson","F4":"24443433.45","F5":"2012210.391","F6":"2944473.254"},{"Metabolite":"Galactosamine","F4":"391041.2314","F5":"15027349.12","F6":"234719463.2"},{"Metabolite":"Gluconic acid","F4":"4072601.333","F5":"10947594.08","F6":"49636292.09"},{"Metabolite":"Gluconic acid (2)","F4":"1565414.121","F5":"5146194.945","F6":"47293213.5"},{"Metabolite":"L-(-)-Malic acid","F4":"692182.0606","F5":"116901561.6","F6":"739222.8033"},{"Metabolite":"L-Aspartic acid","F4":"364455.4919","F5":"279213.8128","F6":"476247407.1"},{"Metabolite":"L-Aspartic acid (2)","F4":"147065.7769","F5":"162552.0329","F6":"465071040.1"},{"Metabolite":"L-Glutamic acid","F4":"20942420.78","F5":"1860818.323","F6":"7500495918"},{"Metabolite":"L-Histidine","F4":"103174.4911","F5":"81644.21257","F6":"71158955.36"},{"Metabolite":"MFCD00037215","F4":"22486.27512","F5":"130696.1291","F6":"33595517.12"},{"Metabolite":"Midodrine","F4":"5142940.189","F5":"63962.90147","F6":"11244.72468"},{"Metabolite":"N-(3-Carboxy-3-hydroxypropyl)-4-[(carboxymethyl)amino]homoserine","F4":"58986.03273","F5":"67994.08367","F6":"39710253.03"},{"Metabolite":"N-(4-Amino-1-carboxybutyl)glutamic acid","F4":"25746.25009","F5":"26128.73052","F6":"11039273.79"},{"Metabolite":"N-Acetyl-DL-glutamic acid","F4":"64164.42301","F5":"10291216.61","F6":"26937.02965"},{"Metabolite":"N-Acetylneuraminic acid","F4":"147443.0336","F5":"799110.1127","F6":"183786604.8"},{"Metabolite":"neuraminic acid","F4":"36769.2801","F5":"5762179.774","F6":"126284.027"},{"Metabolite":"N-hexadecanoylsphinganine","F4":"29288334.06","F5":"110656.1614","F6":"167881.9188"},{"Metabolite":"N-Methyl-<scp>D</scp>-aspartic acid","F4":"71662.74167","F5":"68809.91406","F6":"39710253.03"},{"Metabolite":"Orotidine","F4":"35254.80068","F5":"8313332.247","F6":"30795374.93"},{"Metabolite":"shinorine","F4":"10235015.58","F5":"534090.617","F6":"580146.4383"},{"Metabolite":"Trabodenoson","F4":"25996.0409","F5":"354740.7964","F6":"6464568.01"},{"Metabolite":"Υ-Aminobutyric acid (GABA)","F4":"878396.9767","F5":"73580.40888","F6":"428733204"}],

"Metabolites":[{"Metabolite":"(±)-Ibotenic acid","Formula":"C5 H6 N2 O4","Molecular Weight":"158.03334","Retention times [min]":"1.976"},{"Metabolite":"(1R,2R,3S,5R,7R)-2-Acetamido-7-(1,2-dihydroxyethyl)-3-hydroxy-6,8-dioxabicyclo[3.2.1]octane-5-carboxylic acid","Formula":"C11 H17 N O8","Molecular Weight":"291.09521","Retention times [min]":"3.506"},{"Metabolite":"(1R,2R,3S,5R,7R)-2-Acetamido-7-(1,2-dihydroxyethyl)-3-hydroxy-6,8-dioxabicyclo[3.2.1]octane-5-carboxylic acid (2)","Formula":"C11 H17 N O8","Molecular Weight":"291.09526","Retention times [min]":"2.613"},{"Metabolite":"(2S)-2-({[(3S,4S,5R)-2,3,4-Trihydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]methyl}amino)propanoic acid (non-preferred name)","Formula":"C9 H17 N O7","Molecular Weight":"251.09995","Retention times [min]":"1.954"},{"Metabolite":"(2S)-3-Hydroxy-2-({[(3S,4S,5R)-2,3,4-trihydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]methyl}amino)butanoic acid (non-preferred name)","Formula":"C10 H19 N O8","Molecular Weight":"281.11064","Retention times [min]":"1.996"},{"Metabolite":"[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]","Formula":"","Molecular Weight":"162.05153","Retention times [min]":"1.923"},{"Metabolite":"[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]","Formula":"","Molecular Weight":"161.06751","Retention times [min]":"1.954"},{"Metabolite":"[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]","Formula":"C11 H9 N7 O6","Molecular Weight":"335.06151","Retention times [min]":"1.945"},{"Metabolite":"[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]","Formula":"","Molecular Weight":"163.04671","Retention times [min]":"1.929"},{"Metabolite":"[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]","Formula":"","Molecular Weight":"138.07787","Retention times [min]":"2.211"},{"Metabolite":"[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]","Formula":"C6 H16 N9 O2 P","Molecular Weight":"277.11577","Retention times [min]":"2.425"},{"Metabolite":"[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]","Formula":"","Molecular Weight":"172.08362","Retention times [min]":"2.111"},{"Metabolite":"[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]","Formula":"C18 H16 N4 O5","Molecular Weight":"368.11199","Retention times [min]":"1.938"},{"Metabolite":"[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]","Formula":"C7 H4 N2 O6 P4 S","Molecular Weight":"367.87461","Retention times [min]":"1.817"},{"Metabolite":"[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]","Formula":"","Molecular Weight":"367.11548","Retention times [min]":"1.944"},{"Metabolite":"[Similar to: 4-Guanidinobutyric acid; ΔMass: 43.0549 Da]","Formula":"","Molecular Weight":"102.03026","Retention times [min]":"1.936"},{"Metabolite":"[Similar to: 4-Oxoproline; ΔMass: -0.9228 Da]","Formula":"","Molecular Weight":"129.96544","Retention times [min]":"2.072"},{"Metabolite":"[Similar to: 4-Oxoproline; ΔMass: -0.9825 Da]","Formula":"","Molecular Weight":"130.02513","Retention times [min]":"1.934"},{"Metabolite":"[Similar to: 4-Oxoproline; ΔMass: -67.9864 Da]","Formula":"C5 H14 N O P3","Molecular Weight":"197.02904","Retention times [min]":"3.595"},{"Metabolite":"[Similar to: Argininosuccinic acid; ΔMass: 158.0342 Da]","Formula":"","Molecular Weight":"132.08842","Retention times [min]":"1.859"},{"Metabolite":"[Similar to: Argininosuccinic acid; ΔMass: 158.1592 Da]","Formula":"","Molecular Weight":"131.96345","Retention times [min]":"1.816"},{"Metabolite":"[Similar to: Argininosuccinic acid; ΔMass: 159.1223 Da]","Formula":"C H2 N5 O P","Molecular Weight":"131.00029","Retention times [min]":"1.928"},{"Metabolite":"[Similar to: D-(-)-Glutamine; ΔMass: -71.9041 Da]","Formula":"C5 H3 N2 O6 P","Molecular Weight":"217.9732","Retention times [min]":"2.41"},{"Metabolite":"[Similar to: DL-Arginine; ΔMass: 0.1561 Da]","Formula":"C5 H5 O P3","Molecular Weight":"173.95553","Retention times [min]":"1.865"},{"Metabolite":"[Similar to: DL-Arginine; ΔMass: 1.0828 Da]","Formula":"","Molecular Weight":"173.02889","Retention times [min]":"1.812"},{"Metabolite":"[Similar to: DL-Homoserine ; ΔMass: -161.0380 Da]","Formula":"C7 H18 N6 O2 P2","Molecular Weight":"280.0962","Retention times [min]":"2.016"},{"Metabolite":"[Similar to: DL-Malic acid; ΔMass: 0.9854 Da]","Formula":"","Molecular Weight":"133.03612","Retention times [min]":"2.417"},{"Metabolite":"[Similar to: Guanidinosuccinic acid; ΔMass: 43.0073 Da]","Formula":"","Molecular Weight":"132.05203","Retention times [min]":"1.841"},{"Metabolite":"[Similar to: L-(-)-Malic acid; ΔMass: -156.0032 Da]","Formula":"C6 H6 N6 O8","Molecular Weight":"290.02473","Retention times [min]":"2.414"},{"Metabolite":"[Similar to: L-Glutamic acid; ΔMass: 0.0481 Da]","Formula":"","Molecular Weight":"147.00505","Retention times [min]":"1.924"},{"Metabolite":"[Similar to: L-Glutamic acid; ΔMass: -147.0028 Da]","Formula":"C6 H10 N6 O8","Molecular Weight":"294.05597","Retention times [min]":"1.942"},{"Metabolite":"[Similar to: L-Glutamic acid; ΔMass: -161.0684 Da]","Formula":"C11 H20 N2 O8","Molecular Weight":"308.12158","Retention times [min]":"1.994"},{"Metabolite":"[Similar to: L-Glutamic acid; ΔMass: -168.0507 Da]","Formula":"C7 H17 N5 O9","Molecular Weight":"315.10383","Retention times [min]":"1.904"},{"Metabolite":"[Similar to: L-Glutamic acid; ΔMass: -168.6796 Da]","Formula":"","Molecular Weight":"315.73276","Retention times [min]":"1.836"},{"Metabolite":"[Similar to: L-Glutamic acid; ΔMass: -169.0348 Da]","Formula":"C8 H20 N4 O5 S2","Molecular Weight":"316.08793","Retention times [min]":"1.954"},{"Metabolite":"[Similar to: L-Glutamic acid; ΔMass: -184.6535 Da]","Formula":"","Molecular Weight":"331.70662","Retention times [min]":"1.84"},{"Metabolite":"[Similar to: L-Glutamic acid; ΔMass: -250.1156 Da]","Formula":"C10 H23 N9 O8","Molecular Weight":"397.1688","Retention times [min]":"1.908"},{"Metabolite":"[Similar to: L-Glutamic acid; ΔMass: -251.0997 Da]","Formula":"C17 H27 N4 O3 P S","Molecular Weight":"398.15289","Retention times [min]":"1.955"},{"Metabolite":"[Similar to: L-Histidine; ΔMass: -0.8350 Da]","Formula":"","Molecular Weight":"155.90452","Retention times [min]":"2.019"},{"Metabolite":"[Similar to: Microcystin LF; ΔMass: 855.5507 Da]","Formula":"","Molecular Weight":"129.96539","Retention times [min]":"1.824"},{"Metabolite":"[Similar to: N-(2,3-Dihydro-1,4-benzodioxin-6-yl)-1,2-dimethyl-1H-imidazole-4-sulfonamide; ΔMass: 122.9789 Da]","Formula":"","Molecular Weight":"186.09943","Retention times [min]":"2.525"},{"Metabolite":"[Similar to: N-1-({2-[4-(Dimethylamino)benzoyl]hydrazino}carbothioyl)-2-methylbut-2-enamide; ΔMass: 118.1227 Da]","Formula":"C4 H13 O3 P3","Molecular Weight":"202.00801","Retention times [min]":"2.417"},{"Metabolite":"[Similar to: N'1-(2-Chlorobenzylidene)-4-hydroxy-3-(methylthio)-4,5,6,7-tetrahydrobenzo[c]thiophene-1-carbohydrazide; ΔMass: 120.2707 Da]","Formula":"","Molecular Weight":"259.77129","Retention times [min]":"1.845"},{"Metabolite":"[Similar to: N4-Acetylcytidine; ΔMass: 127.0282 Da]","Formula":"","Molecular Weight":"158.06785","Retention times [min]":"1.871"},{"Metabolite":"[Similar to: N4-Acetylcytidine; ΔMass: 128.0123 Da]","Formula":"","Molecular Weight":"157.08381","Retention times [min]":"1.856"},{"Metabolite":"[Similar to: Pyridoxamine; ΔMass: -18.0095 Da]","Formula":"","Molecular Weight":"186.09936","Retention times [min]":"2.213"},{"Metabolite":"[Similar to: S-Lactoylglutathione; ΔMass: 51.9888 Da]","Formula":"C11 H21 N O10","Molecular Weight":"327.11613","Retention times [min]":"1.925"},{"Metabolite":"[Similar to: S-Lactoylglutathione; ΔMass: 52.9728 Da]","Formula":"C11 H22 N2 O9","Molecular Weight":"326.13211","Retention times [min]":"1.885"},{"Metabolite":"[Similar to: S-Lactoylglutathione; ΔMass: 53.9569 Da]","Formula":"C11 H23 N3 O8","Molecular Weight":"325.14802","Retention times [min]":"1.844"},{"Metabolite":"[Similar to: SSR504734; ΔMass: 124.0210 Da]","Formula":"C11 H16 N2 O6","Molecular Weight":"272.10065","Retention times [min]":"6.542"},{"Metabolite":"[Similar to: Threonine; ΔMass: -162.8571 Da]","Formula":"C6 H2 O9 S2","Molecular Weight":"281.9153","Retention times [min]":"1.81"},{"Metabolite":"[Similar to: Threonine; ΔMass: -179.0789 Da]","Formula":"C10 H22 N2 O8","Molecular Weight":"298.13713","Retention times [min]":"1.854"},{"Metabolite":"[Similar to: Threonine; ΔMass: -180.0629 Da]","Formula":"C10 H21 N O9","Molecular Weight":"299.12119","Retention times [min]":"1.889"},{"Metabolite":"[Similar to: Threonine; ΔMass: -180.8291 Da]","Formula":"C3 H5 N4 O P5 S","Molecular Weight":"299.88734","Retention times [min]":"1.818"},{"Metabolite":"[Similar to: Threonine; ΔMass: -181.0458 Da]","Formula":"C7 H12 N10 O4","Molecular Weight":"300.10408","Retention times [min]":"1.845"},{"Metabolite":"[Similar to: Threonine; ΔMass: -72.0200 Da]","Formula":"","Molecular Weight":"191.07826","Retention times [min]":"1.998"},{"Metabolite":"[Similar to: Uracil; ΔMass: -176.0656 Da]","Formula":"C16 H17 O3 P","Molecular Weight":"288.09284","Retention times [min]":"1.983"},{"Metabolite":"1-(beta-D-Ribofuranosyl)-1,2-dihydropyrimidine","Formula":"C9 H14 N2 O4","Molecular Weight":"214.09469","Retention times [min]":"3.086"},{"Metabolite":"1-[5-(2,3,4-Trihydroxybutyl)-2-pyrazinyl]-1,2,3,4-butanetetrol","Formula":"C12 H20 N2 O7","Molecular Weight":"304.12694","Retention times [min]":"3.09"},{"Metabolite":"2,3,4,5,6,7-Hexahydroxyheptanoic acid","Formula":"C7 H14 O8","Molecular Weight":"226.06821","Retention times [min]":"1.916"},{"Metabolite":"3-(3,4-dihydroxyphenyl)lactamide","Formula":"C9 H11 N O4","Molecular Weight":"197.06785","Retention times [min]":"8.838"},{"Metabolite":"3,4-Dihydroxy-5-(1,2,3-trihydroxypropyl)dihydro-2(3H)-furanone","Formula":"C7 H12 O7","Molecular Weight":"208.05737","Retention times [min]":"1.948"},{"Metabolite":"4-Hydroxyprolylthreonine","Formula":"C9 H16 N2 O5","Molecular Weight":"232.10532","Retention times [min]":"2.292"},{"Metabolite":"4-Oxoproline","Formula":"C5 H7 N O3","Molecular Weight":"129.04115","Retention times [min]":"3.595"},{"Metabolite":"6-deoxyinosine 5'-phosphate","Formula":"C10 H13 N4 O7 P","Molecular Weight":"332.05276","Retention times [min]":"1.963"},{"Metabolite":"AC-benzyl","Formula":"C11 H12 O3","Molecular Weight":"192.07952","Retention times [min]":"2.045"},{"Metabolite":"Bisphenol S","Formula":"C12 H10 O4 S","Molecular Weight":"250.02955","Retention times [min]":"12.231"},{"Metabolite":"Bluensidine","Formula":"C8 H16 N4 O6","Molecular Weight":"264.10658","Retention times [min]":"1.858"},{"Metabolite":"D-(-)-Glutamine","Formula":"C5 H10 N2 O3","Molecular Weight":"146.06776","Retention times [min]":"1.878"},{"Metabolite":"D-(-)-Glutamine (2)","Formula":"C5 H10 N2 O3","Molecular Weight":"146.06779","Retention times [min]":"2.08"},{"Metabolite":"D-(+)-Glucose","Formula":"C6 H12 O6","Molecular Weight":"180.06239","Retention times [min]":"1.913"},{"Metabolite":"D-Glucono-delta-lactone","Formula":"C6 H10 O6","Molecular Weight":"178.04682","Retention times [min]":"1.919"},{"Metabolite":"Dinoterb","Formula":"C10 H12 N2 O5","Molecular Weight":"240.07166","Retention times [min]":"2.515"},{"Metabolite":"DL-Arginine","Formula":"C6 H14 N4 O2","Molecular Weight":"174.11054","Retention times [min]":"1.857"},{"Metabolite":"DL-Arginine (2)","Formula":"C6 H14 N4 O2","Molecular Weight":"174.11142","Retention times [min]":"1.859"},{"Metabolite":"DL-Glutamine","Formula":"C5 H10 N2 O3","Molecular Weight":"146.06895","Retention times [min]":"1.876"},{"Metabolite":"Ethylene glycol tetraacetic acid","Formula":"C14 H24 N2 O10","Molecular Weight":"380.14271","Retention times [min]":"2.998"},{"Metabolite":"Fenson","Formula":"C12 H9 Cl O3 S","Molecular Weight":"267.9959","Retention times [min]":"15.934"},{"Metabolite":"Galactosamine","Formula":"C6 H13 N O5","Molecular Weight":"179.07863","Retention times [min]":"1.815"},{"Metabolite":"Gluconic acid","Formula":"C6 H12 O7","Molecular Weight":"136.03593","Retention times [min]":"1.951"},{"Metabolite":"Gluconic acid (2)","Formula":"C6 H12 O7","Molecular Weight":"196.05729","Retention times [min]":"1.941"},{"Metabolite":"L-(-)-Malic acid","Formula":"C4 H6 O5","Molecular Weight":"134.0201","Retention times [min]":"2.412"},{"Metabolite":"L-Aspartic acid","Formula":"C4 H7 N O4","Molecular Weight":"73.01495","Retention times [min]":"1.87"},{"Metabolite":"L-Aspartic acid (2)","Formula":"C4 H7 N O4","Molecular Weight":"133.03603","Retention times [min]":"1.873"},{"Metabolite":"L-Glutamic acid","Formula":"C5 H9 N O4","Molecular Weight":"147.05178","Retention times [min]":"1.932"},{"Metabolite":"L-Histidine","Formula":"C6 H9 N3 O2","Molecular Weight":"155.06814","Retention times [min]":"1.83"},{"Metabolite":"MFCD00037215","Formula":"C8 H14 N2 O5","Molecular Weight":"218.08957","Retention times [min]":"2.515"},{"Metabolite":"Midodrine","Formula":"C12 H18 N2 O4","Molecular Weight":"254.12626","Retention times [min]":"8.065"},{"Metabolite":"N-(3-Carboxy-3-hydroxypropyl)-4-[(carboxymethyl)amino]homoserine","Formula":"C10 H18 N2 O8","Molecular Weight":"294.10602","Retention times [min]":"1.947"},{"Metabolite":"N-(4-Amino-1-carboxybutyl)glutamic acid","Formula":"C10 H18 N2 O6","Molecular Weight":"262.11613","Retention times [min]":"2.326"},{"Metabolite":"N-Acetyl-DL-glutamic acid","Formula":"C7 H11 N O5","Molecular Weight":"189.0627","Retention times [min]":"4.216"},{"Metabolite":"N-Acetylneuraminic acid","Formula":"C11 H19 N O9","Molecular Weight":"309.10572","Retention times [min]":"2.027"},{"Metabolite":"neuraminic acid","Formula":"C9 H17 N O8","Molecular Weight":"267.09509","Retention times [min]":"2.114"},{"Metabolite":"N-hexadecanoylsphinganine","Formula":"C34 H69 N O3","Molecular Weight":"539.52716","Retention times [min]":"1.826"},{"Metabolite":"N-Methyl-<scp>D</scp>-aspartic acid","Formula":"C5 H9 N O4","Molecular Weight":"147.05297","Retention times [min]":"1.936"},{"Metabolite":"Orotidine","Formula":"C10 H12 N2 O8","Molecular Weight":"288.05907","Retention times [min]":"2.073"},{"Metabolite":"shinorine","Formula":"C13 H20 N2 O8","Molecular Weight":"332.12179","Retention times [min]":"6.556"},{"Metabolite":"Trabodenoson","Formula":"C15 H20 N6 O6","Molecular Weight":"380.1427","Retention times [min]":"2.159"},{"Metabolite":"Υ-Aminobutyric acid (GABA)","Formula":"C4 H9 N O2","Molecular Weight":"103.06166","Retention times [min]":"1.931"}]
}

}