#METABOLOMICS WORKBENCH boryana_ptrva_20210429_064236 DATATRACK_ID:2611 STUDY_ID:ST001773 ANALYSIS_ID:AN002880 PROJECT_ID:000000 VERSION 1 CREATED_ON May 5, 2021, 1:42 pm #PROJECT PR:PROJECT_SUMMARY This study aimed to optimize the detection of several key redox-reactive PR:PROJECT_SUMMARY metabolites from mammalian cells and tissues. We explored three different PR:PROJECT_SUMMARY chromatographic methods and optimized sample preparation, extraction buffer and PR:PROJECT_SUMMARY conditions as well as mass spectrometry detection parameters. The established PR:PROJECT_SUMMARY method was tested and validated using biologically relevant ROS-inducing PR:PROJECT_SUMMARY conditions. This study can be a valuable resource for the metabolomics PR:PROJECT_SUMMARY community. PR:INSTITUTE Boston Childrens Hospital PR:DEPARTMENT Pathology PR:LABORATORY Naama Kanarek PR:FIRST_NAME Boryana PR:ADDRESS 300 Longwood Av, Boston, MA, 2115, USA PR:EMAIL boryana.petrova@childrens.harvard.edu PR:PHONE 6173557433 PR:PROJECT_TITLE Redox metabolism measurement in mammalian cells and tissues by quantitative PR:PROJECT_TITLE LC/MS method (part XV) PR:LAST_NAME Petrova #STUDY ST:STUDY_TITLE Application of the redox metabolite detection method for mouse biofluids (part ST:STUDY_TITLE II) ST:STUDY_SUMMARY This study was aimed at optimizing redox metabolites detection from mammalian ST:STUDY_SUMMARY biofluids. Three different extraction conditions were compared, including ST:STUDY_SUMMARY derivatization of glutathione. This study was with mouse plasma. ST:INSTITUTE Boston Children's Hospital, Harvard Medical School ST:DEPARTMENT Pathology ST:LABORATORY Naama Kanarek ST:LAST_NAME Petrova ST:FIRST_NAME Boryana ST:ADDRESS 300 Longwood Av, Boston, MA, 2115, USA ST:EMAIL boryana.petrova@childrens.harvard.edu ST:PHONE 6173557433 #SUBJECT SU:SUBJECT_TYPE Mammal SU:SUBJECT_SPECIES Mus musculus SU:TAXONOMY_ID 10090 #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 - blank1 Factor:- RAW_FILE_NAME=2021425_QEF1_HILIC_plasma3buffer_poolOptis_blank1; Other=- SUBJECT_SAMPLE_FACTORS - blank2 Factor:- RAW_FILE_NAME=2021425_QEF1_HILIC_plasma3buffer_poolOptis_blank2; Other=- SUBJECT_SAMPLE_FACTORS - blank3 Factor:- RAW_FILE_NAME=2021425_QEF1_HILIC_plasma3buffer_poolOptis_blank3; Other=- SUBJECT_SAMPLE_FACTORS - blank4 Factor:- RAW_FILE_NAME=2021425_QEF1_HILIC_plasma3buffer_poolOptis_blank4; Other=- SUBJECT_SAMPLE_FACTORS - blank5 Factor:- RAW_FILE_NAME=2021425_QEF1_HILIC_plasma3buffer_poolOptis_blank5; Other=- SUBJECT_SAMPLE_FACTORS - blank6 Factor:- RAW_FILE_NAME=2021425_QEF1_HILIC_plasma3buffer_poolOptis_blank6; Other=- SUBJECT_SAMPLE_FACTORS - E14.5 CD1 212_1 Factor:Buffer B RAW_FILE_NAME=2021425_QEF1_HILIC_plasma3buffer_poolOptis_BP902; Other="isoAAs, GSH, aminopterin, QReSS" SUBJECT_SAMPLE_FACTORS - E14.5 CD1 212_2 Factor:Buffer B RAW_FILE_NAME=2021425_QEF1_HILIC_plasma3buffer_poolOptis_BP903; Other="isoAAs, GSH, aminopterin, QReSS" SUBJECT_SAMPLE_FACTORS - E14.5 CD1 212_7 Factor:Buffer B RAW_FILE_NAME=2021425_QEF1_HILIC_plasma3buffer_poolOptis_BP904; Other="isoAAs, GSH, aminopterin, QReSS" SUBJECT_SAMPLE_FACTORS - E14.5 CD1 212_8 Factor:Buffer B RAW_FILE_NAME=2021425_QEF1_HILIC_plasma3buffer_poolOptis_BP905; Other="isoAAs, GSH, aminopterin, QReSS" SUBJECT_SAMPLE_FACTORS - E14.5 CD1 212_1.1 Factor:Buffer C RAW_FILE_NAME=2021425_QEF1_HILIC_plasma3buffer_poolOptis_BP906; Other="isoAAs, GSH, aminopterin, QReSS" SUBJECT_SAMPLE_FACTORS - E14.5 CD1 212_2.1 Factor:Buffer C RAW_FILE_NAME=2021425_QEF1_HILIC_plasma3buffer_poolOptis_BP907; Other="isoAAs, GSH, aminopterin, QReSS" SUBJECT_SAMPLE_FACTORS - E14.5 CD1 212_7.1 Factor:Buffer C RAW_FILE_NAME=2021425_QEF1_HILIC_plasma3buffer_poolOptis_BP908; Other="isoAAs, GSH, aminopterin, QReSS" SUBJECT_SAMPLE_FACTORS - E14.5 CD1 212_8.1 Factor:Buffer C RAW_FILE_NAME=2021425_QEF1_HILIC_plasma3buffer_poolOptis_BP909; Other="isoAAs, GSH, aminopterin, QReSS" SUBJECT_SAMPLE_FACTORS - E14.5 CD1 212_1.2 Factor:Buffer C + Ellmans RAW_FILE_NAME=2021425_QEF1_HILIC_plasma3buffer_poolOptis_BP910; Other="isoAAs, GSH, aminopterin, QReSS" SUBJECT_SAMPLE_FACTORS - E14.5 CD1 212_2.2 Factor:Buffer C + Ellmans RAW_FILE_NAME=2021425_QEF1_HILIC_plasma3buffer_poolOptis_BP911; Other="isoAAs, GSH, aminopterin, QReSS" SUBJECT_SAMPLE_FACTORS - E14.5 CD1 212_7.2 Factor:Buffer C + Ellmans RAW_FILE_NAME=2021425_QEF1_HILIC_plasma3buffer_poolOptis_BP912; Other="isoAAs, GSH, aminopterin, QReSS" SUBJECT_SAMPLE_FACTORS - E14.5 CD1 212_8.2 Factor:Buffer C + Ellmans RAW_FILE_NAME=2021425_QEF1_HILIC_plasma3buffer_poolOptis_BP913; Other="isoAAs, GSH, aminopterin, QReSS" SUBJECT_SAMPLE_FACTORS - pool 902-913 1x a Factor:- RAW_FILE_NAME=2021425_QEF1_HILIC_plasma3buffer_poolOptis_BP914_pool1x_a; Other=- SUBJECT_SAMPLE_FACTORS - pool 902-913 1x b Factor:- RAW_FILE_NAME=2021425_QEF1_HILIC_plasma3buffer_poolOptis_BP914_pool1x_b; Other=- SUBJECT_SAMPLE_FACTORS - pool 902-913 1x c Factor:- RAW_FILE_NAME=2021425_QEF1_HILIC_plasma3buffer_poolOptis_BP914_pool1x_c; Other=- SUBJECT_SAMPLE_FACTORS - pool 902-913 03x Factor:- RAW_FILE_NAME=2021425_QEF1_HILIC_plasma3buffer_poolOptis_BP915_poo03x; Other=- SUBJECT_SAMPLE_FACTORS - pool 902-913 01x Factor:- RAW_FILE_NAME=2021425_QEF1_HILIC_plasma3buffer_poolOptis_BP916_pool01x; Other=- SUBJECT_SAMPLE_FACTORS - pool 902-913 01x a Factor:- RAW_FILE_NAME=2021425_QEF1_HILIC_plasma3buffer_poolOptis_BP916_pool01x_a; Other=- #COLLECTION CO:COLLECTION_SUMMARY All animal care and experimental procedures were approved by the Institutional CO:COLLECTION_SUMMARY Animal Care and Use Committees of Boston Children’s Hospital. Mouse strain CO:COLLECTION_SUMMARY used was C57BL/6. Pure CSF samples were collected from the cisterna magna [39]. CO:COLLECTION_SUMMARY Blood samples were collected from the retromandibular vein. The samples were CO:COLLECTION_SUMMARY coagulated and centrifuged. Liver and kidney were collected and flash frozen. CO:COLLECTION_SUMMARY Tissue chunks were cut on a glass plate while kept chilled on top of dry ice. CO:COLLECTION_SUMMARY K562 cells used in this manuscript were authenticated by short tandem repeat CO:COLLECTION_SUMMARY analysis and tested negative for mycoplasma. Cells were cultured in RPMI CO:COLLECTION_SUMMARY (Genesee Scientific) up to a density of 2 Million cells per ml. For redox CO:COLLECTION_SUMMARY chemical treatment experiments, cells were seeded at 1 Million cells per ml cell CO:COLLECTION_SUMMARY density in 6-well plates and drugs were added for 4h at the following CO:COLLECTION_SUMMARY concentrations: methotrexate: 5 µM; oligomycin: 80 µg/ml; H2O2: 1 mM; diamide: CO:COLLECTION_SUMMARY 0.5 mM; DMSO, which served as control: 0.6 µl per 1 mL of cell culture media CO:COLLECTION_SUMMARY (equivalent to volume used for oligomycin). CO:SAMPLE_TYPE Plasma #TREATMENT TR:TREATMENT_SUMMARY Plasma + Buffers #SAMPLEPREP SP:SAMPLEPREP_SUMMARY Metabolites were quenched as quickly as possible while working with the samples SP:SAMPLEPREP_SUMMARY at low temperatures. Cells were handled at 4ºC or on dry ice, extraction buffer SP:SAMPLEPREP_SUMMARY was pre-chilled at -20ºC. Samples were analyzed by LC-MS on the same day of SP:SAMPLEPREP_SUMMARY extraction (if impractical, best alternative is to store dried samples at SP:SAMPLEPREP_SUMMARY -80ºC). Unless indicated otherwise, 1 million cells or about 2 mg of tissue was SP:SAMPLEPREP_SUMMARY extracted per condition and a minimum of three replicates per condition was used SP:SAMPLEPREP_SUMMARY in each experiment. K562 cells that are non-adherent, were collected by brief SP:SAMPLEPREP_SUMMARY centrifugation at 4ºC using a table-top centrifuge (4,500 rpm, 1.5 min) and SP:SAMPLEPREP_SUMMARY washed briefly in 0.9% NaCl (high grade salt and LC-MS-grade water Fisher SP:SAMPLEPREP_SUMMARY Scientific W6500 or Sigma Aldrich 1.15333). 300 µl of prechilled extraction SP:SAMPLEPREP_SUMMARY buffer were added per sample. For tissues – chunks were crushed using a SP:SAMPLEPREP_SUMMARY hand-held homogenizer (VWR 47747-370) with several pulses while keeping the SP:SAMPLEPREP_SUMMARY samples on ice. 300 µl of prechilled extraction buffer was used per 2 mg of SP:SAMPLEPREP_SUMMARY tissue. Extraction buffer “A”: 40:40:20 of acetonitrile:methanol:water, SP:SAMPLEPREP_SUMMARY supplemented with 0.1M formic acid and isotopically-labeled internal standards SP:SAMPLEPREP_SUMMARY (17 amino acids and reduced glutathione, Cambridge Isotope Laboratories, SP:SAMPLEPREP_SUMMARY MSK-A2-1.2 and CNLM-6245-10). Extraction buffer “B”: 80% LC-MS-grade SP:SAMPLEPREP_SUMMARY methanol, 20% 25 mM Ammonium Acetate and 2.5 mM Na-Ascorbate prepared in LC-MS SP:SAMPLEPREP_SUMMARY water and supplemented with isotopically labeled internal standards (17 amino SP:SAMPLEPREP_SUMMARY acids and isotopically labelled reduced glutathione, Cambridge Isotope SP:SAMPLEPREP_SUMMARY Laboratories, MSK-A2-1.2 and CNLM-6245-10). Extraction buffer “C” and “C + SP:SAMPLEPREP_SUMMARY Ellman’s”: Solution 1: 100% LC-MS Methanol Solution 2: 25mM Ammonium Acetate SP:SAMPLEPREP_SUMMARY and 2.5mM Na-Ascorbate in LC-MS water supplemented with isotopically labelled SP:SAMPLEPREP_SUMMARY reduced glutathione and isotopically labeled internal standards (17 amino acids SP:SAMPLEPREP_SUMMARY and reduced glutathione, Cambridge Isotope Laboratories, MSK-A2-1.2 and SP:SAMPLEPREP_SUMMARY CNLM-6245-10). Ellman’s reagent (5,5′-Dithiobis(2-nitrobenzoic acid),D8130, SP:SAMPLEPREP_SUMMARY Sigma Aldrich): 20 mM in “Solution 2”. Final composition is 80% solution 1 SP:SAMPLEPREP_SUMMARY and 20% solution 2. Samples were vortexed briefly (10 sec) and sonicated for 3 SP:SAMPLEPREP_SUMMARY min in a 4ºC water bath. Samples were then centrifuged for 10 min, 4ºC, at SP:SAMPLEPREP_SUMMARY maximum speed on a benchtop centrifuge (Eppendorf) and the cleared supernatant SP:SAMPLEPREP_SUMMARY was transferred to a new tube. Samples were dried using a nitrogen dryer while SP:SAMPLEPREP_SUMMARY on ice, and special attention was given to minimize the time of drying and to SP:SAMPLEPREP_SUMMARY not let samples idle in the dryer (Reacti-Vap™ Evaporator, Thermo Fisher SP:SAMPLEPREP_SUMMARY Scientific, TS-18826) once the drying process was completed. Needles were SP:SAMPLEPREP_SUMMARY continuously adjusted to the surface of the liquid as the samples evaporated to SP:SAMPLEPREP_SUMMARY expedite the drying process. Samples were reconstituted in 30 µl LC-MS-grade SP:SAMPLEPREP_SUMMARY water by brief sonication in a 4ºC water bath. Extracted metabolites were spun SP:SAMPLEPREP_SUMMARY for 2 min at maximum speed on a bench-top centrifuge and cleared supernatant was SP:SAMPLEPREP_SUMMARY transferred to LC-MS micro vials (National Scientific, C5000-45B). A small SP:SAMPLEPREP_SUMMARY amount of each sample was pooled and serially diluted 3- and 10-fold to be used SP:SAMPLEPREP_SUMMARY as quality controls throughout the run of each batch. #CHROMATOGRAPHY CH:CHROMATOGRAPHY_SUMMARY ZIC-pHILIC chromatography: One ml of reconstituted sample was injected into a CH:CHROMATOGRAPHY_SUMMARY ZIC-pHILIC 150 × 2.1 mm (5 µm particle size) column (EMD Millipore) CH:CHROMATOGRAPHY_SUMMARY operated on a Vanquish™ Flex UHPLC Systems (Thermo Fisher Scientific, San CH:CHROMATOGRAPHY_SUMMARY Jose, CA). Chromatographic separation was achieved using the following CH:CHROMATOGRAPHY_SUMMARY conditions: buffer A was acetonitrile; buffer B was 20 mM ammonium carbonate, CH:CHROMATOGRAPHY_SUMMARY 0.1% ammonium hydroxide. Gradient conditions were: linear gradient from 20% to CH:CHROMATOGRAPHY_SUMMARY 80% B; 20–20.5 min: from 80% to 20% B; 20.5–28 min: hold at 20% B. The CH:CHROMATOGRAPHY_SUMMARY column oven and autosampler tray were held at 25 °C and 4 °C, CH:CHROMATOGRAPHY_SUMMARY respectively. CH:CHROMATOGRAPHY_TYPE HILIC CH:INSTRUMENT_NAME Thermo Vanquish CH:COLUMN_NAME EMD Millipore ZIC HILIC (150 x 2.1mm, 5um) #ANALYSIS AN:ANALYSIS_TYPE MS #MS MS:INSTRUMENT_NAME Thermo Q Exactive Orbitrap MS:INSTRUMENT_TYPE Orbitrap MS:MS_TYPE ESI MS:ION_MODE UNSPECIFIED MS:MS_COMMENTS HESI #MS_METABOLITE_DATA MS_METABOLITE_DATA:UNITS ppm MS_METABOLITE_DATA_START Samples blank1 blank2 blank3 blank4 blank5 blank6 E14.5 CD1 212_1 E14.5 CD1 212_2 E14.5 CD1 212_7 E14.5 CD1 212_8 E14.5 CD1 212_1.1 E14.5 CD1 212_2.1 E14.5 CD1 212_7.1 E14.5 CD1 212_8.2 E14.5 CD1 212_1.2 E14.5 CD1 212_2.2 E14.5 CD1 212_7.2 E14.5 CD1 212_8.2 pool 902-913 1x a pool 902-913 1x b pool 902-913 1x c pool 902-913 03x pool 902-913 01x pool 902-913 01x a Factors Factor:- Factor:- Factor:- Factor:- Factor:- Factor:- Factor:Buffer B Factor:Buffer B Factor:Buffer B Factor:Buffer B Factor:Buffer C Factor:Buffer C Factor:Buffer C Factor:Buffer C + Ellmans Factor:Buffer C + Ellmans Factor:Buffer C + Ellmans Factor:Buffer C + Ellmans Factor:Buffer C + Ellmans Factor:- Factor:- Factor:- Factor:- Factor:- Factor:- CTP N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F AMP N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F glutamine N/F N/F N/F N/F N/F N/F 1129791765 1129147396 911073719 925206962 1653509505 1852116629 1298347655 1572016157 1638720622 1859991983 1368277532 1119779749 1513688021 1407138148 1513432645 621852478 175651970 N/F UDP N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F 2-oxoadipate_unc N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F tyrosine-13C9-15N N/F N/F N/F N/F N/F N/F 40984383 30128411 41232260 30860040 22454257 25276915 25502776 22385288 26521995 26136812 27676711 17934590 26483478 29890018 30006031 8341683 2078617 N/F alanine-13C3-15N N/F N/F N/F N/F N/F N/F 2068882 1787840 1955437 1714000 3235228 2847599 2925805 3148398 3205198 3197139 3374289 2091856 2736453 3006435 2564544 902054 182084 N/F succinyl-CoA N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F ornithine N/F N/F N/F N/F N/F N/F 28107486 30692634 14402859 17722264 28245312 29215300 14817530 17371493 27404963 31247777 13997382 12533206 24525990 22150535 22804369 9283871 3671293 N/F threonine N/F N/F N/F N/F N/F N/F 308136601 266137863 314501627 203203937 299202944 264697976 307247009 219353540 304586295 273798917 295799877 161257321 295340945 286849953 294359608 83180598 20240287 15313508 CDP-choline N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F guanosine N/F N/F N/F N/F N/F N/F 13227596 7349986 4794090 5155579 11925628 7490602 4357468 4739676 12841791 7197017 4553874 3560457 7717492 7839587 7345911 2200269 448567 N/F saccharopine_unc N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F 39216 97121 68734 45899 N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F threonine-13C4-15N N/F N/F N/F N/F N/F N/F 10445888 8454295 10103193 8360281 7571120 7430755 7912814 7269523 8229382 8426179 8327682 5259883 8447074 8764810 8599613 2374303 579132 N/F cystine-13C6-15N2 N/F N/F N/F N/F N/F N/F 2727324 1773850 2313218 1656717 3674176 5027807 4658710 4574835 4373331 4441252 3539027 3278130 3343138 3789504 4498636 928467 88433 N/F phosphocholine N/F N/F N/F N/F N/F N/F 8228833 5971047 6116379 4057032 10637722 8985451 9805955 5135124 13568462 8833534 9688378 2693446 8385215 8351475 8817025 2321253 465760 N/F phosphocreatine N/F N/F N/F N/F N/F N/F 876638 1059123 773938 853816 633568 1076863 695980 672934 600238 893518 619317 479913 739693 817331 869169 240324 N/F N/F AICAR N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F indolelactate N/F N/F N/F N/F N/F N/F 317216 344462 678016 436833 695642 522346 947846 843835 N/F N/F 462201 210204 311864 376146 N/F 206526 N/F N/F Ribose_Ribulose 5-phosphate_3Me-Lys N/F N/F N/F N/F N/F N/F 2305392 1283600 1625770 1285518 2171952 1411572 1030785 1113431 2563168 1467752 1242008 975303 1686710 1572711 1509846 450985 45596 N/F ATP N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F CMP N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F biotin N/F N/F N/F N/F N/F N/F N/F N/F 158298 N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F Picolinate N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F malonyl-CoA N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F NADP N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F isocitrate_unc N/F N/F N/F N/F N/F N/F 1961677 N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F Glucose 6-phosphate N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F acetylglutamate N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F 1661130 GMP N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F Pipecolate N/F N/F N/F N/F N/F N/F 30621326 38118767 30574908 22621935 25349972 33376395 29586574 21945484 28700241 31938087 31686070 15844999 28554131 29199670 29723843 7943293 1898205 N/F serotonin N/F N/F N/F N/F N/F N/F 8585685 7534203 6144824 5771420 6945024 6320624 6341342 5782421 7433695 7161403 7433232 4760278 8248442 7925171 6124585 2224732 619058 N/F homocysteine N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F GAR N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F Pyridoxine N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F valine N/F N/F N/F N/F N/F N/F 121682194 125486438 65278786 78145005 96433419 106815224 55092552 85965700 120169342 93825238 74019973 73392847 86353517 87942018 89563567 27065999 9421542 24008704 palmitate N/F N/F N/F N/F N/F N/F 217733236 168035807 197316886 349285745 229009820 159656648 249697797 312009629 184539311 136926694 198632176 198206004 213606095 206807144 202648561 63068702 13851834 16051908 Butyrylcarnitine N/F N/F N/F N/F N/F N/F 70179493 105911102 81890218 116897186 69237445 96680490 83466802 111328056 67545742 96727191 80758660 88093944 95323443 92918759 95876664 28770339 7324991 8927222 dTMP N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F glutamate N/F N/F N/F N/F N/F N/F 16718850 6243897 7883062 6608474 10372614 4325588 4753021 3604411 10428891 4691986 4855299 2615376 6812987 6553195 6385814 2674174 975174 N/F acetylaspartate N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F alpha-keto-isovalerate N/F N/F N/F N/F N/F N/F 1152877 940709 2108796 3982639 3195423 3559297 3357890 6334660 4607684 5000572 4399920 4026034 3594865 3576136 4216973 1377729 N/F N/F xanthine N/F N/F N/F N/F N/F N/F 62739926 69836533 54506580 48058359 69648728 71703369 50176131 50083620 62417550 59884592 49596086 37697440 53037918 55713875 57391844 27430167 12716079 N/F trans-urocanate N/F N/F N/F N/F N/F N/F 133732696 92693544 132564513 140476076 153934988 91529823 124478302 145836387 148493513 161429549 128997657 108250892 142344147 146973696 142204845 50761050 18851638 N/F 3-hydroxybutyric_acid N/F N/F N/F N/F N/F N/F 14233792 21500457 24969850 22272932 18089156 25197497 23698650 22173729 16709899 23642507 23259297 17296997 24220369 25381546 23652385 9741217 3223540 N/F dTTP N/F N/F N/F N/F N/F N/F 2561790 2031186 2487408 2429292 1966352 1943619 2223734 2122809 2190271 1907291 1888682 1825203 2071164 2132181 2208285 1682072 579317 N/F S-methylcysteine_unc N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F cytosine_unc N/F N/F N/F N/F N/F N/F 1128409 N/F 1165678 1199597 1534933 N/F 990195 N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F aspartate N/F N/F N/F N/F N/F N/F 2054301 1533825 1479063 1929177 1274979 1256313 1055871 931138 1422937 1279575 1167243 842004 1439400 1374185 1243780 636125 306921 171784 cis-aconitate N/F N/F N/F N/F N/F N/F 11869484 14657686 10929533 13527812 13073353 12674950 8952804 10114022 13749860 11803510 11347956 6895355 10760104 10681702 10961521 2852202 755892 N/F aspartate-13C6-15N4 N/F N/F N/F N/F N/F N/F 3381734 2832652 3114273 2818784 1354893 1450347 1231095 1259983 1419275 1370558 1383944 928181 1789268 1566363 1790330 659969 119384 N/F GTP N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F Itaconic Acid N/F N/F N/F N/F N/F N/F 18243124 19230862 20189896 22655844 128853594 168161186 146089702 244927735 182750259 190648396 170093994 212684347 145163521 139974798 138948636 75612493 30004302 N/F 2-hydroxyglutarate N/F N/F N/F N/F N/F N/F 36569498 28089827 31096303 37383842 234069347 282418248 261159491 364968768 312234650 294974278 260999386 333670793 253712319 233958304 227541482 111552245 45328023 N/F HIAA N/F N/F N/F N/F N/F N/F 225148 138394 213022 227937 N/F N/F N/F 143432 N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F tyrosine N/F N/F N/F N/F N/F N/F 75772258 65278096 40641674 38770173 58723410 69861674 31531049 35833453 66021758 66494093 35349851 27898104 50648557 56493515 55029571 16890430 4347403 N/F cysteine_13C3_15N1 N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F 3-ureidopropionate N/F N/F N/F N/F N/F N/F 1642751 18256165 19152065 918393 1384716 18553719 16685909 754530 1420095 15841606 18044924 555081 9643147 9945492 9524099 3286108 1023737 N/F homocitrulline N/F N/F N/F N/F N/F N/F 30427160 46041083 34671166 20727596 35813949 50419952 37251942 27643506 33648163 50163949 38925540 19656514 32840766 37477397 36959002 13725508 3660757 N/F argininosuccinate_unc N/F N/F N/F N/F N/F N/F 1023435 707751 762566 706568 1146367 994951 849504 652660 1155378 832774 924364 579202 852159 785138 802929 235395 N/F N/F tryptamine N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F O-phosphoethanolamine_unc N/F N/F N/F N/F N/F N/F 750281 465345 541046 376231 668793 560862 430873 276386 789250 419775 523053 216844 495923 543556 461896 127178 N/F N/F "glutamate-13C5,15N" N/F N/F N/F N/F N/F N/F 3678436 3199790 3110414 2738257 1331426 1632341 1549046 1374635 1444327 1397835 1432363 1108193 1966666 1764607 1712980 695216 185068 N/F Isoleucine-13C6-15N N/F N/F N/F N/F N/F N/F 29846268 25964502 29937586 24396800 21408696 20462437 21949336 20651772 20527069 21573538 24874846 15444610 22729549 25485217 23294371 9002570 2598831 N/F GSH_13C2-15N-Ellmans N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F choline 3401692 N/F N/F N/F N/F N/F 1801735 905604 1305206 969731 2328354 1424964 2877853 1427110 1897673 1145566 1465512 886332 1802969 1477382 1400758 N/F N/F N/F PRPP_unc N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F anserine_unc N/F N/F N/F N/F N/F N/F 1277744 4468630 2454811 3972904 1920597 7413757 3884461 4111605 2470022 6450810 3779133 2814525 4132470 4310922 4156333 1052603 226307 N/F propionylcarnitine N/F N/F N/F N/F N/F N/F 38230665 64684506 40999967 44152745 39524080 63184436 42004120 40258395 26355826 39842246 26559764 24048322 40094248 41122624 40748559 13243748 3506831 4131089 fructose N/F N/F N/F N/F N/F N/F 633672 539175 754310 953281 535964 656334 760418 667906 N/F 641032 832656 N/F N/F 616687 552538 N/F N/F N/F succinate N/F N/F N/F N/F N/F N/F 3704301 3584941 2556965 2075790 2883901 4150271 4582305 5759678 5730400 4182648 5080608 5741335 5255734 5050165 3792185 1774727 592621 N/F N-acetylphenylalanine N/F N/F N/F N/F N/F N/F 1280716 1306125 1023228 1153150 1595295 1505278 779339 1221478 1527922 1325300 1049227 802638 1110688 1257967 1235017 414942 99520 160788 lysine-13C6-15N2 N/F N/F N/F N/F N/F N/F 5661450 6069910 5254455 5136835 3583313 3358719 3606210 3420229 3669780 4057055 3753773 2796861 4542084 4191623 4331759 1493996 399598 N/F Ureidosuccinic_acid N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F acetylserine N/F N/F N/F N/F N/F N/F 586449 633200 535419 652453 1414723 1656063 1293862 1128448 1574977 1271592 1604225 1151249 1127051 1037240 1158888 428450 N/F N/F creatine N/F N/F 950294 1309700 865129 1178587 1250266334 1979773230 1213600991 1227891132 1323150517 1992203114 1212122728 1337061751 1242806606 1934771374 1178449253 954395784 1466753892 1526062319 1410822333 519548674 164931196 N/F 3-hydroxyisobutyric_acid N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F tryptophan N/F N/F N/F N/F N/F N/F 178666750 200829602 110874569 120662626 174805252 210882276 102277521 104841855 212261368 223785843 123075892 98504735 159307762 160899772 161084567 59863940 15324755 N/F dihydroxyacetone_phosphate N/F N/F N/F N/F N/F N/F 43339 N/F 78924 113517 N/F N/F N/F 83339 49255 66051 N/F N/F N/F 44390 N/F N/F N/F N/F ascorbate_unc N/F N/F N/F N/F N/F N/F 903449565 979395365 979157249 1129653167 19909036479 18351453825 17656795680 19543768564 18877116147 19197804410 19126564599 14660111515 13054945019 12961966828 12857176249 6476011149 3025224960 11734276 isoleucine N/F N/F N/F N/F N/F N/F 99943464 89627325 59077629 60696631 86443612 89393486 52904050 58052709 101244714 82114717 59008798 41133052 78280032 74433713 78639049 26143826 6552099 N/F thymidine N/F 13701 N/F N/F 9963 18394 249175 412918 595744 378368 183617 322218 571992 250793 N/F N/F 443997 63848 176611 268233 256111 109548 N/F N/F GSH_Ellmans N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F 138053 56058 74682 20649 N/F N/F N/F N/F N/F N/F "2,3-BPG_unc" N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F niacinamide N/F N/F N/F N/F N/F N/F 83259642 74207777 69952475 54298514 81338163 66894800 65189213 55195377 78848091 59107735 64652675 38241484 62970324 64771792 63394546 23075954 6625303 7637862 serine N/F N/F N/F N/F N/F N/F 13323301 12508602 9331397 7374330 19834954 24241727 16841778 13794259 23205102 24251274 17392205 9024558 15889002 16098292 17814727 4293932 1099274 N/F cystathionine N/F N/F N/F N/F N/F N/F 1073548 752843 863043 719652 643427 764062 664834 543884 822558 686832 600548 430642 739853 720367 903870 119889 N/F N/F formyl_methionine N/F N/F N/F N/F N/F N/F 148429 136793 214518 395432 722691 550102 546542 534133 228241 117225 206833 155980 403056 178437 395569 36103 N/F N/F Ribose 1-phosphate_unc N/F N/F N/F N/F N/F N/F 1560220 2941587 1669537 1797030 1462967 3030701 1544626 1624871 1696122 3182920 1653088 1457765 2327467 1889603 2184017 653266 57975 N/F lactic_acid N/F N/F N/F N/F N/F N/F 662808704 840965238 775539685 584391523 664895788 865217841 768526133 564317693 716453601 917830321 827467618 469802273 748380504 746574070 777661156 278506949 83501910 341974919 betaine N/F N/F N/F N/F N/F N/F 1599561356 1891726343 1489578152 1378193770 1652932835 1808050552 1566501232 1355284921 1501141905 1546808533 1510649514 960204802 1621914660 1579278921 1547538664 518268414 143762565 N/F cysteic_acid N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F anthranilic_acid N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F FAD N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F 2-oxobutyric_acid_unc N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F 10252606 9459268 9850494 8745528 10475155 10274758 10162642 6164015 6634522 7684209 7738158 2989887 1412543 374133 Alpha-Lipoic Acid_unc N/F N/F N/F N/F N/F N/F 29146757 28619254 28707878 26257323 N/F N/F N/F N/F N/F N/F N/F N/F 8176936 7994808 7909050 2392619 599833 953042 proline-13C5-15N N/F N/F N/F N/F N/F N/F 160906499 134928419 149390446 132736549 114571397 115354467 108734071 107484256 109850732 111436418 116325749 78590534 122721662 128500446 121952096 39152111 10615326 N/F N-acetylcysteine N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F amidoadipate N/F N/F N/F N/F N/F N/F 3960817 4295051 2671262 3001160 18164717 18966458 13507828 19166963 25356455 21924769 26395848 15867164 13266825 15162347 12378418 5795974 1096948 N/F sarcosine_unc N/F N/F N/F N/F N/F N/F 54424259 72512212 47331111 40018539 58996340 84995138 51831582 50588312 60758417 78315792 51309744 35277088 60417403 62941510 58456892 18932457 4581750 N/F dUMP N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F methionine N/F N/F N/F N/F N/F N/F 63898012 86834348 97580220 95107700 140456006 216880636 120234071 96037496 158656165 210085946 138390951 81881607 124188765 129488835 127659169 52447950 13848629 N/F methionine-13C5-15N N/F N/F N/F N/F N/F N/F 12828562 10885634 22719141 26558432 29783191 30844450 29991782 28588891 33341517 31632028 34775269 24150638 25757165 27639379 26371492 10293549 2590230 N/F asparagine N/F N/F N/F N/F N/F N/F 9340004 7982474 6228382 5592784 32373642 32232337 20865898 21798992 31545156 30840939 21494990 13942266 21649225 20421417 23105381 5256334 917805 844523 proline N/F N/F N/F N/F N/F N/F 480869781 552808192 310936431 317153795 479299535 589601978 301328968 296257010 453092760 533010035 315762998 208147582 422331306 432524285 409089676 125558343 33337299 N/F Acetyl CoA N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F GSSG N/F N/F N/F N/F N/F N/F 400729 81954 127673 199996 290631 130058 94851 141797 217774 63029 89632 61481 211234 243881 135662 33904 N/F N/F C5 Carnitines N/F N/F N/F N/F N/F N/F 10573245 12853806 8001129 9133883 11771793 12614175 8184374 9732370 10630741 11805192 8468210 6829956 10784600 10378460 9988313 3399590 997272 1431314 S-Adenosyl-L-Homocysteine N/F N/F N/F N/F N/F N/F 301188 91064 193708 209470 308246 150101 195687 201471 428884 393173 223629 157165 299514 313264 303575 21220 N/F N/F allantoin N/F N/F N/F N/F N/F N/F 899026 990040 1013937 658897 2736353 2351809 2299136 2120853 2466872 2178047 2315319 1568553 1750556 1753063 1977672 505809 390958 N/F taurine N/F N/F N/F 24586 N/F N/F 97108333 102146490 92000156 82406392 85937611 87735607 82109510 72376967 85248064 82048579 84143909 51814605 84583720 80801427 81667003 30278734 9760194 N/F GSH-13C2_15N N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F xanthosine_unc N/F N/F N/F N/F N/F N/F 281397 264518 583635 175498 380808 368784 675792 253937 326466 345198 607834 177890 352221 354777 403698 138875 32421 N/F glucose N/F N/F N/F N/F N/F N/F 5528946 6049854 5226852 5512832 3308044 3575188 4236565 3624816 3810497 3848973 4060901 2584766 4348333 4307145 3713562 1522627 956773 N/F methylthioadenosine N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F 150259 44472 N/F N/F N/F N/F N/F N/F N/F N/F Glycerol 3-Phosphate N/F N/F N/F N/F N/F N/F 1761830 1337438 1404567 1361088 N/F N/F N/F N/F N/F N/F N/F N/F 174018 171340 218422 N/F N/F N/F 2-hydroxybutyric_acid N/F N/F N/F N/F N/F N/F 4733290 4591397 4018022 3703539 5134532 5224982 4210706 3623025 N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F asymmetric dimethylarginine (ADMA) N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F 118549 N/F N/F N/F N/F 135258 N/F N/F N/F N/F N/F 2-aminobutyric_acid N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F mannose N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F acetylalanine N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F erythrose_4-phosphate_unc N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F citrulline N/F N/F N/F N/F N/F N/F 164960461 115523211 102070383 80922493 190714596 209611974 137755660 116001885 226688461 197155657 134999224 91572954 156280921 155890104 175617726 47824159 11676726 N/F histidine N/F N/F N/F N/F N/F N/F 413140520 634979729 294695548 198842327 341077767 319316570 252609128 206546998 353017320 329206704 235475064 169699521 317527460 334697184 344323712 133025943 46313332 N/F GDP N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F Kynurenic Acid N/F 2089194 3256879 3105919 2289020 2346394 1581445 2370146 1494860 1984931 2296959 2926680 1626800 2282418 1937954 2372081 1509166 1491306 1968490 2008421 1831244 887790 402065 N/F myo-inositol N/F N/F N/F N/F N/F N/F 2281336 2729667 1520170 2044694 2989034 2535582 2891403 2175722 2960154 3483491 2837764 1986930 2858958 2841038 2252746 1170942 555718 699036 phosphoenolpyruvate N/F N/F N/F N/F N/F N/F 1722570 649972 447104 344220 1452186 519752 381693 273236 1469878 511398 349021 186876 807606 727296 697699 91457 N/F N/F inosine N/F N/F N/F N/F N/F N/F 362306940 302483306 192613750 242520937 381610800 313033172 187028222 255204466 384866937 309858389 198466022 209291803 305171458 298093749 310257829 110170207 39708582 N/F 1-methylnicotinamide N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F cysteine_unc N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F adenosine_unc N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F glycine_13C2-15N N/F N/F N/F N/F N/F N/F 143748 19169 109295 95632 102657 62779 53246 83048 128681 95516 77007 27244 90525 129982 82581 N/F N/F N/F arginine-13C6-15N4 N/F N/F N/F N/F N/F N/F 49386567 51319804 50660935 53040380 36503328 36028875 36506161 37236274 33948248 40364148 34093765 31266278 41583139 41735216 44100969 18828288 5753892 N/F acetylcarnitine N/F N/F N/F N/F N/F N/F 1217090468 1683637668 1424170923 1634540946 1310915103 1666474536 1464795638 1562528089 1157109694 1431854440 1442939309 1138936100 1525097233 1490890926 1504814398 474093280 138284451 N/F uridine N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F 163954 81493 96842 74635 N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F thiamine N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F dCytidine N/F N/F N/F N/F N/F 126458 4840658 5949710 5930648 5448614 6139876 6424125 5882989 5258308 1990342 2482364 3075051 1722090 3944097 4059181 3980553 1299098 386825 28607 Coenzyme A N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F 3-phosphoglycerate N/F N/F N/F N/F N/F N/F 1821008 907041 626327 456905 1592406 769606 446528 236193 1778991 812755 484708 196785 754497 896196 874303 51890 N/F N/F UDP-GlcNAc N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F UTP N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F p-aminobenzoate N/F N/F N/F N/F N/F N/F 709461 862386 902299 679336 636008 844857 941667 695482 699439 1308546 1208437 646084 709517 725212 954508 421061 N/F N/F carnitine N/F N/F N/F N/F N/F N/F 940412032 1322177226 1184100939 1155441036 950006129 1322919815 1173952531 1123826778 890269436 1181156455 1196152210 820150194 1152380742 1165636025 1156555352 385795053 109623906 N/F cystine N/F N/F N/F N/F N/F N/F 6028764 5645883 7396402 2559507 7540747 11578255 12849971 4902737 8944342 8380368 10127926 3361886 8332558 7690064 9946460 1874549 256999 N/F gamma-glutamyl-alanine N/F N/F N/F N/F N/F N/F 3168631 2187657 2112824 1809151 9261323 8339618 6075252 7208704 10592695 8494364 6764333 4300600 6312717 6478794 6777402 1693962 229833 N/F creatinine 568220 N/F N/F 563221 520708 N/F 159950092 183285386 140762217 131417306 192712927 203681284 158540994 127922238 66992428 72113205 64265961 42212174 101844402 100731858 98572524 45668285 15876922 16855527 guanidinoacetate N/F N/F N/F N/F N/F N/F 6851599 8357272 10245969 6564960 7464357 11363508 12227750 7470148 7743650 10147368 12437285 5132473 9631114 9505548 9707647 3206294 839937 N/F cysteine-glycine N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F CDP N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F alanine N/F N/F N/F N/F N/F N/F 53357168 72380390 44810885 40018539 58996340 84432165 50325807 50129750 62359405 80210954 51309744 35380485 62423738 62941510 60040543 18843553 4581750 N/F Phenylacetyl glutamine N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F ADP N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F leucine N/F N/F N/F N/F N/F N/F 119741610 114581103 56176158 76049590 125735266 106022177 59436106 64670327 139527686 133758981 76557297 62605699 105561228 103025586 97254938 32827875 8480239 N/F GSH N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F UMP N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F Pyridoxal N/F N/F N/F N/F 139505 N/F 3712846 3244510 3466918 2705581 5752960 3844782 4352208 3598466 3635167 3015656 3225989 2374681 3587695 3553029 3417937 1272689 290316 N/F N-acetyllysine N/F N/F N/F N/F N/F N/F 12897134 9201437 12695702 8516610 10499075 11652647 10879802 8225397 8720874 9411469 12632690 5945202 6635409 10260015 9473863 2609376 829550 N/F sorbitol N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F Riboflavin N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F citrate N/F N/F N/F N/F N/F N/F 283598001 236051216 242465780 176227177 269615160 248242599 220737386 174848278 258101231 206043573 182564013 108980116 202697293 208312209 266367514 46725286 3759586 29807998 pseudouridine_unc N/F N/F N/F N/F N/F N/F 18965589 20336794 17618988 13522685 23492704 23833855 19120783 16374743 21151670 20211670 18830661 11757970 18942849 18261015 19392670 7587896 3059875 N/F arginine N/F N/F 2176932 3642731 6091889 5527343 362056054 464199995 328067952 329439582 397109831 413793830 316156074 304940827 366338767 462539942 305391881 251919597 373728514 366888898 398630247 171031585 57856053 50161878 phenylalanine N/F 33106 13085 N/F N/F 10299 29358360 33309936 18189958 18875119 32721062 34027097 19352972 20310825 21633753 23119582 11595409 11890729 23159601 23411532 25152059 8331782 2348436 N/F S-Adenosyl-L-methionine N/F N/F N/F N/F N/F N/F 3992971 2919496 3768840 3375095 2850729 2606753 2757123 2586401 3199550 2189633 2458763 2172147 3124468 2909837 3217702 1080939 216002 N/F NADH N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F Alpha-Ketoglutarate N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F glycine N/F 47340 8380 N/F N/F N/F 694905 519891 655184 594189 527287 636801 681070 461036 727331 532378 671467 330564 757486 729015 720593 163299 N/F 296647 Glycerophosphocholine N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F adenine N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F hypoxanthine N/F N/F N/F N/F N/F 85030 1212564768 1024967505 741319728 708683677 1209971833 1049258336 760034692 765479014 920903196 749378645 549492205 518424486 899332920 934139841 921958768 413719241 154005946 315769567 carnosine N/F N/F N/F N/F N/F N/F 5569149 3717085 7491206 8612725 6822308 6191784 10178729 13636477 7464529 5759419 9301198 9697953 8868342 8598877 9681392 2996980 702612 N/F uric acid N/F N/F N/F N/F N/F N/F 20721238 28455170 26301407 17262747 23520519 30769377 29239329 19304235 22013119 26690531 28394043 16189488 22326851 22734651 23297188 11961231 6162626 N/F IMP N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F 3-methyl-2-oxopentanoic_acid N/F N/F N/F N/F N/F N/F 4450171 4561814 7702750 12664884 16070189 16408084 7770038 17249456 19644685 18514688 10287315 10970199 11412450 13442643 12830265 3852982 1387811 1356146 quinolinic_acid N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F Methionine sulfoxide N/F N/F N/F N/F N/F N/F 362602539 474041815 176060875 50437545 25290547 41023350 29603603 13867443 30999067 36522979 21740880 10247945 106262836 114803474 116742545 32740200 6427776 N/F N-acetylmethionine N/F N/F N/F N/F N/F N/F 1000881 1053865 1083038 934796 801393 660450 699663 569727 880882 532476 628675 346632 684515 782260 756106 268994 N/F N/F N-acetylglutamate N/F N/F N/F N/F N/F N/F 383706 234387 293218 217641 384246 208904 495917 209890 709931 654617 N/F 146574 523227 552533 449005 N/F N/F 1661130 glyceraldehyde_3-phosphate N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F dCTP N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F pyruvate N/F N/F N/F N/F N/F N/F N/F N/F 5137615 5199741 8830486 13451410 9570793 18580948 N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F UDP-hexose N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F serine-13C3-15N N/F N/F N/F N/F N/F N/F 1138763 965809 1125425 981836 1353900 1510498 1421676 1147631 1423109 1387945 1633574 860613 1333473 1348690 1337158 278536 N/F N/F valine-13C5-15N N/F N/F N/F N/F N/F N/F 19178653 17452166 17719786 15760986 12052186 12360137 12426217 12510195 12405983 13040177 13697365 8650293 15051501 14059652 13699189 4531738 1168048 N/F phosphoethanolamine N/F N/F N/F N/F N/F N/F 710937 382070 487481 258902 698153 384566 434405 303650 770103 401775 424000 216322 525532 415699 477756 84849 N/F N/F lysine N/F N/F N/F N/F N/F 41356 142999975 172515184 136866191 124435082 142214309 138481770 139408059 117981077 147744486 154987164 140853466 95635922 147448906 133498677 138421820 51426938 18097913 12517296 CoA-Ellmans_unc N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F dATP N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F orotate N/F N/F N/F N/F N/F N/F 3900928 4364020 4748211 8797793 3967035 4498070 4561158 8360210 3309306 3182105 3981475 5756650 5070520 4266032 4907152 2214900 862210 N/F leucine-13C6-15N N/F N/F N/F N/F N/F N/F 28745528 27204794 26659875 24399276 17938959 22830471 20173461 17998612 26435787 28186932 28994258 17635299 26133117 23796408 27038522 9418663 2357472 N/F "Fructose 1,6-bisphosphate" N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F gamma-aminobutyric_acid N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F 6-phosphogluconate N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F dihydroorotate_unc N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F fumarate N/F N/F N/F N/F N/F N/F N/F 3348254 N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F 5950381 folic_acid N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F hydroxyproline_gammaALA N/F N/F N/F N/F N/F N/F 3689174 4433672 3559679 2453198 3079115 3988045 3121867 3192164 2732164 2992335 2616440 1878147 2488040 3924321 3756383 842568 332541 N/F NADPH N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F Pantothenate N/F N/F N/F N/F N/F N/F 17593230 25569994 11754641 10043659 15625039 21753913 11490888 9655607 16715808 17198021 11352608 5727696 16318185 15269058 15647184 3777762 1680361 2013541 phenylalanine-13C9-15N N/F N/F N/F N/F N/F N/F 90600866 79078920 81984004 71278680 51350829 53460544 49115638 46756710 123209949 123570992 133272504 79190934 85807075 94476535 92257831 23095049 5379451 N/F cytidine N/F N/F N/F N/F N/F N/F 13203153 10525120 11313931 11832841 12907005 10298007 11498712 8865635 14499091 8895878 11216058 6484711 11838573 12212485 11565111 3186480 737069 N/F NAD+ N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F guanine N/F N/F N/F N/F N/F N/F 14985054 8374421 5762946 8628194 13081829 7873717 5128009 5193644 14523101 8478943 5281881 4149679 8732828 8877374 8826737 2814435 877041 N/F uracil N/F N/F N/F N/F N/F N/F N/F 1071792 N/F 365998 875370 N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F F6P_G1P_unc N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N-acetylglutamine N/F N/F N/F N/F N/F N/F 3919665 4383545 3968342 3619838 5204080 4455832 2500404 3550273 5090520 5083635 2274988 2615125 3808756 4237050 3930447 1520803 356833 N/F glycerate N/F N/F N/F N/F N/F N/F 1143580699 1052370085 1057505314 996122129 57097825 57447117 53063006 51333483 56831899 52397016 51461716 36277055 400825127 396788015 394622839 130879017 40944212 N/F dimethylglicine N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F acetoacetate N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F 10498574 10113768 10105737 9236699 10158336 9494848 11062713 6292243 5810004 7857684 8742718 2577625 982194 477127 beta-alanine N/F N/F N/F N/F N/F N/F 1674740 1206276 876098 1281124 1745204 1794280 1621796 1034316 2282863 1804360 2019377 768390 1560187 1215851 1509501 573131 203034 N/F hypotaurine N/F N/F N/F N/F N/F N/F N/F N/F N/F 98863 1082589 569741 921910 849196 890415 288616 490637 363345 341986 206168 357973 72847 N/F N/F N-acetylornithine N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F histidine-13C6-15N3 N/F N/F N/F N/F N/F N/F 89082557 66694947 76797314 60780625 84891982 90463603 81639829 94935952 101737887 99446700 92263850 79792850 82696471 87221190 92312726 36148523 11645911 N/F kynurenine N/F N/F N/F N/F N/F N/F 6854846 6610990 9809652 9464305 7333491 8375996 5340382 4357561 14846554 19678049 9399501 5044095 9179809 9040133 9813873 3155171 878373 N/F malate N/F N/F N/F N/F N/F N/F 34084590 46916741 28665019 37186413 34108668 41348143 23680881 26007133 28264132 36387230 21504422 19406229 33908940 33365241 29828608 15191425 6362746 N/F Sedoheptulose-7-phosphate N/F N/F N/F N/F N/F N/F 122522 N/F 25095 N/F 161693 22882 28344 N/F 133813 16140 11496 N/F 56842 34571 32140 N/F N/F N/F phosphoserine N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F cAMP_unc N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F Nicotinic Acid N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F ADP-ribose_unc N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F acetylglycine N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F MS_METABOLITE_DATA_END #METABOLITES METABOLITES_START metabolite_name CTP AMP glutamine UDP 2-oxoadipate_unc tyrosine-13C9-15N alanine-13C3-15N succinyl-CoA ornithine threonine CDP-choline guanosine saccharopine_unc threonine-13C4-15N cystine-13C6-15N2 phosphocholine phosphocreatine AICAR indolelactate Ribose_Ribulose 5-phosphate_3Me-Lys ATP CMP biotin Picolinate malonyl-CoA NADP isocitrate_unc Glucose 6-phosphate acetylglutamate GMP Pipecolate serotonin homocysteine GAR Pyridoxine valine palmitate Butyrylcarnitine dTMP glutamate acetylaspartate alpha-keto-isovalerate xanthine trans-urocanate 3-hydroxybutyric_acid dTTP S-methylcysteine_unc cytosine_unc aspartate cis-aconitate aspartate-13C6-15N4 GTP Itaconic Acid 2-hydroxyglutarate HIAA tyrosine cysteine_13C3_15N1 3-ureidopropionate homocitrulline argininosuccinate_unc tryptamine O-phosphoethanolamine_unc "glutamate-13C5,15N" Isoleucine-13C6-15N GSH_13C2-15N-Ellmans choline PRPP_unc anserine_unc propionylcarnitine fructose succinate N-acetylphenylalanine lysine-13C6-15N2 Ureidosuccinic_acid acetylserine creatine 3-hydroxyisobutyric_acid tryptophan dihydroxyacetone_phosphate ascorbate_unc isoleucine thymidine GSH_Ellmans "2,3-BPG_unc" niacinamide serine cystathionine formyl_methionine Ribose 1-phosphate_unc lactic_acid betaine cysteic_acid anthranilic_acid FAD 2-oxobutyric_acid_unc Alpha-Lipoic Acid_unc proline-13C5-15N N-acetylcysteine amidoadipate sarcosine_unc dUMP methionine methionine-13C5-15N asparagine proline Acetyl CoA GSSG C5 Carnitines S-Adenosyl-L-Homocysteine allantoin taurine GSH-13C2_15N xanthosine_unc glucose methylthioadenosine Glycerol 3-Phosphate 2-hydroxybutyric_acid asymmetric dimethylarginine (ADMA) 2-aminobutyric_acid mannose acetylalanine erythrose_4-phosphate_unc citrulline histidine GDP Kynurenic Acid myo-inositol phosphoenolpyruvate inosine 1-methylnicotinamide cysteine_unc adenosine_unc glycine_13C2-15N arginine-13C6-15N4 acetylcarnitine uridine thiamine dCytidine Coenzyme A 3-phosphoglycerate UDP-GlcNAc UTP p-aminobenzoate carnitine cystine gamma-glutamyl-alanine creatinine guanidinoacetate cysteine-glycine CDP alanine Phenylacetyl glutamine ADP leucine GSH UMP Pyridoxal N-acetyllysine sorbitol Riboflavin citrate pseudouridine_unc arginine phenylalanine S-Adenosyl-L-methionine NADH Alpha-Ketoglutarate glycine Glycerophosphocholine adenine hypoxanthine carnosine uric acid IMP 3-methyl-2-oxopentanoic_acid quinolinic_acid Methionine sulfoxide N-acetylmethionine N-acetylglutamate glyceraldehyde_3-phosphate dCTP pyruvate UDP-hexose serine-13C3-15N valine-13C5-15N phosphoethanolamine lysine CoA-Ellmans_unc dATP orotate leucine-13C6-15N "Fructose 1,6-bisphosphate" gamma-aminobutyric_acid 6-phosphogluconate dihydroorotate_unc fumarate folic_acid hydroxyproline_gammaALA NADPH Pantothenate phenylalanine-13C9-15N cytidine NAD+ guanine uracil F6P_G1P_unc N-acetylglutamine glycerate dimethylglicine acetoacetate beta-alanine hypotaurine N-acetylornithine histidine-13C6-15N3 kynurenine malate Sedoheptulose-7-phosphate phosphoserine cAMP_unc Nicotinic Acid ADP-ribose_unc acetylglycine METABOLITES_END #END