#METABOLOMICS WORKBENCH boryana_ptrva_20210421_122811 DATATRACK_ID:2582 STUDY_ID:ST001760 ANALYSIS_ID:AN002867 PROJECT_ID:000000 VERSION 1 CREATED_ON April 30, 2021, 5:12 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 II) PR:LAST_NAME Petrova #STUDY ST:STUDY_TITLE Application of the redox metabolite detection method for mouse kidney ST:STUDY_SUMMARY This study was aimed at optimizing redox metabolites detection from mammalian ST:STUDY_SUMMARY tissues. Three different chromatographic conditions were compared as well as ST:STUDY_SUMMARY three different extraction conditions. This study was run on ZIC-pHILIC ST:STUDY_SUMMARY chromatography. This study is an independent replicate 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 - A1- mouse A kidney in buffer B EXTRACTION BUFFER:buffer B RAW_FILE_NAME=20200716_QEF1_HILIC_mouse_kidney_AW130; DESCRIPTION="liver chunk extracted in 300ul buffer, reconstituted in 100ul water"; INTERNAL STANDARDS="aminopterin, isotopically labelled amino acids, GSH-13C2-15N-13C2-15N"; CHROMATOGRAPHY=HILIC SUBJECT_SAMPLE_FACTORS - B1- mouse B kidney in buffer B EXTRACTION BUFFER:buffer B RAW_FILE_NAME=20200716_QEF1_HILIC_mouse_kidney_AW131; DESCRIPTION="liver chunk extracted in 300ul buffer, reconstituted in 100ul water"; INTERNAL STANDARDS="aminopterin, isotopically labelled amino acids, GSH-13C2-15N-13C2-15N"; CHROMATOGRAPHY=HILIC SUBJECT_SAMPLE_FACTORS - C1- mouse C kidney in buffer B EXTRACTION BUFFER:buffer B RAW_FILE_NAME=20200716_QEF1_HILIC_mouse_kidney_AW132; DESCRIPTION="liver chunk extracted in 300ul buffer, reconstituted in 100ul water"; INTERNAL STANDARDS="aminopterin, isotopically labelled amino acids, GSH-13C2-15N-13C2-15N"; CHROMATOGRAPHY=HILIC SUBJECT_SAMPLE_FACTORS - D1- mouse D kidney in buffer B EXTRACTION BUFFER:buffer B RAW_FILE_NAME=20200716_QEF1_HILIC_mouse_kidney_AW133; DESCRIPTION="liver chunk extracted in 300ul buffer, reconstituted in 100ul water"; INTERNAL STANDARDS="aminopterin, isotopically labelled amino acids, GSH-13C2-15N-13C2-15N"; CHROMATOGRAPHY=HILIC SUBJECT_SAMPLE_FACTORS - A2- mouse A kidney in buffer C EXTRACTION BUFFER:buffer C RAW_FILE_NAME=20200716_QEF1_HILIC_mouse_kidney_AW134; DESCRIPTION="liver chunk extracted in 300ul buffer, reconstituted in 100ul water"; INTERNAL STANDARDS="aminopterin, isotopically labelled amino acids, GSH-13C2-15N-13C2-15N"; CHROMATOGRAPHY=HILIC SUBJECT_SAMPLE_FACTORS - B2- mouse B kidney in buffer C EXTRACTION BUFFER:buffer C RAW_FILE_NAME=20200716_QEF1_HILIC_mouse_kidney_AW135; DESCRIPTION="liver chunk extracted in 300ul buffer, reconstituted in 100ul water"; INTERNAL STANDARDS="aminopterin, isotopically labelled amino acids, GSH-13C2-15N-13C2-15N"; CHROMATOGRAPHY=HILIC SUBJECT_SAMPLE_FACTORS - C2- mouse C kidney in buffer C EXTRACTION BUFFER:buffer C RAW_FILE_NAME=20200716_QEF1_HILIC_mouse_kidney_AW136; DESCRIPTION="liver chunk extracted in 300ul buffer, reconstituted in 100ul water"; INTERNAL STANDARDS="aminopterin, isotopically labelled amino acids, GSH-13C2-15N-13C2-15N"; CHROMATOGRAPHY=HILIC SUBJECT_SAMPLE_FACTORS - D2- mouse D kidney in buffer C EXTRACTION BUFFER:buffer C RAW_FILE_NAME=20200716_QEF1_HILIC_mouse_kidney_AW137; DESCRIPTION="liver chunk extracted in 300ul buffer, reconstituted in 100ul water"; INTERNAL STANDARDS="aminopterin, isotopically labelled amino acids, GSH-13C2-15N-13C2-15N"; CHROMATOGRAPHY=HILIC SUBJECT_SAMPLE_FACTORS - A3- mouse A kidney in buffer C_Ellmans EXTRACTION BUFFER:buffer C_Ellmans RAW_FILE_NAME=20200716_QEF1_HILIC_mouse_kidney_AW138; DESCRIPTION=much smaller pellet - reconstituted in 30ul; INTERNAL STANDARDS="aminopterin, isotopically labelled amino acids, GSH-13C2-15N-13C2-15N"; CHROMATOGRAPHY=HILIC SUBJECT_SAMPLE_FACTORS - B3- mouse A kidney in buffer C_Ellmans EXTRACTION BUFFER:buffer C_Ellmans RAW_FILE_NAME=20200716_QEF1_HILIC_mouse_kidney_AW139; DESCRIPTION="liver chunk extracted in 300ul buffer, reconstituted in 100ul water"; INTERNAL STANDARDS="aminopterin, isotopically labelled amino acids, GSH-13C2-15N-13C2-15N"; CHROMATOGRAPHY=HILIC SUBJECT_SAMPLE_FACTORS - C3- mouse A kidney in buffer C_Ellmans EXTRACTION BUFFER:buffer C_Ellmans RAW_FILE_NAME=20200716_QEF1_HILIC_mouse_kidney_AW140; DESCRIPTION="liver chunk extracted in 300ul buffer, reconstituted in 100ul water"; INTERNAL STANDARDS="aminopterin, isotopically labelled amino acids, GSH-13C2-15N-13C2-15N"; CHROMATOGRAPHY=HILIC SUBJECT_SAMPLE_FACTORS - D3- mouse A lkidney in buffer C_Ellmans EXTRACTION BUFFER:buffer C_Ellmans RAW_FILE_NAME=20200716_QEF1_HILIC_mouse_kidney_AW141; DESCRIPTION="liver chunk extracted in 300ul buffer, reconstituted in 100ul water"; INTERNAL STANDARDS="aminopterin, isotopically labelled amino acids, GSH-13C2-15N-13C2-15N"; CHROMATOGRAPHY=HILIC SUBJECT_SAMPLE_FACTORS - pooled sample QC a EXTRACTION BUFFER:- RAW_FILE_NAME=20200716_QEF1_HILIC_mouse_kidney_AW142_pool_1x; DESCRIPTION=-; INTERNAL STANDARDS=-; CHROMATOGRAPHY=HILIC SUBJECT_SAMPLE_FACTORS - pooled sample QC b EXTRACTION BUFFER:- RAW_FILE_NAME=20200716_QEF1_HILIC_mouse_kidney_AW142_pool_1x_a; DESCRIPTION=-; INTERNAL STANDARDS=-; CHROMATOGRAPHY=HILIC SUBJECT_SAMPLE_FACTORS - pooled sample QC c EXTRACTION BUFFER:- RAW_FILE_NAME=20200716_QEF1_HILIC_mouse_kidney_AW142_pool_1x_b; DESCRIPTION=-; INTERNAL STANDARDS=-; CHROMATOGRAPHY=HILIC SUBJECT_SAMPLE_FACTORS - pooled sample QC 1/10 dilution EXTRACTION BUFFER:- RAW_FILE_NAME=20200716_QEF1_HILIC_mouse_kidney_AW143_pool_01x; DESCRIPTION=-; INTERNAL STANDARDS=-; CHROMATOGRAPHY=HILIC SUBJECT_SAMPLE_FACTORS - pooled sample QC 1/10 dilution a EXTRACTION BUFFER:- RAW_FILE_NAME=20200716_QEF1_HILIC_mouse_kidney_AW143_pool_01x_a; DESCRIPTION=-; INTERNAL STANDARDS=-; CHROMATOGRAPHY=HILIC SUBJECT_SAMPLE_FACTORS - pooled sample QC 1/3 dilution EXTRACTION BUFFER:- RAW_FILE_NAME=20200716_QEF1_HILIC_mouse_kidney_AW144_pool_03x; DESCRIPTION=-; INTERNAL STANDARDS=-; CHROMATOGRAPHY=HILIC SUBJECT_SAMPLE_FACTORS - pooled sample QC 1/3 dilution a EXTRACTION BUFFER:- RAW_FILE_NAME=20200716_QEF1_HILIC_mouse_kidney_AW144_pool_03x_a; DESCRIPTION=-; INTERNAL STANDARDS=-; CHROMATOGRAPHY=HILIC SUBJECT_SAMPLE_FACTORS - blank1 EXTRACTION BUFFER:- RAW_FILE_NAME=20200716_QEF1_HILIC_mouse_kidney_blank_end1; DESCRIPTION=-; INTERNAL STANDARDS=-; CHROMATOGRAPHY=HILIC SUBJECT_SAMPLE_FACTORS - blank2 EXTRACTION BUFFER:- RAW_FILE_NAME=20200716_QEF1_HILIC_mouse_kidney_blank_end2; DESCRIPTION=-; INTERNAL STANDARDS=-; CHROMATOGRAPHY=HILIC SUBJECT_SAMPLE_FACTORS - blank3 EXTRACTION BUFFER:- RAW_FILE_NAME=20200716_QEF1_HILIC_mouse_kidney_blank1; DESCRIPTION=-; INTERNAL STANDARDS=-; CHROMATOGRAPHY=HILIC #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 Kidney #TREATMENT TR:TREATMENT_SUMMARY buffer only #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 A1- mouse A kidney in buffer B B1- mouse B kidney in buffer B C1- mouse C kidney in buffer B D1- mouse D kidney in buffer B A2- mouse A kidney in buffer C B2- mouse B kidney in buffer C C2- mouse C kidney in buffer C D2- mouse D kidney in buffer C A3- mouse A kidney in buffer C_Ellmans B3- mouse A kidney in buffer C_Ellmans C3- mouse A kidney in buffer C_Ellmans D3- mouse A lkidney in buffer C_Ellmans pooled sample QC a pooled sample QC b pooled sample QC c pooled sample QC 1/10 dilution pooled sample QC 1/10 dilution a pooled sample QC 1/3 dilution pooled sample QC 1/3 dilution a blank1 blank2 blank3 Factors EXTRACTION BUFFER:buffer B EXTRACTION BUFFER:buffer B EXTRACTION BUFFER:buffer B EXTRACTION BUFFER:buffer B EXTRACTION BUFFER:buffer C EXTRACTION BUFFER:buffer C EXTRACTION BUFFER:buffer C EXTRACTION BUFFER:buffer C EXTRACTION BUFFER:buffer C_Ellmans EXTRACTION BUFFER:buffer C_Ellmans EXTRACTION BUFFER:buffer C_Ellmans EXTRACTION BUFFER:buffer C_Ellmans EXTRACTION BUFFER:- EXTRACTION BUFFER:- EXTRACTION BUFFER:- EXTRACTION BUFFER:- EXTRACTION BUFFER:- EXTRACTION BUFFER:- EXTRACTION BUFFER:- EXTRACTION BUFFER:- EXTRACTION BUFFER:- EXTRACTION BUFFER:- 1-methylnicotinamide_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 "2,3-BPG_unc" 403314 182063 472553 481170 2295950 297211 875582 598824 4988162 2388913 1847963 5424724 1503277 1858397 1741812 552779 460668 141979 111010 N/F N/F N/F 2-aminoadipate 15420402 7394364 7221941 9651160 N/F N/F 8007882 8063135 20953605 10826586 7485928 13982649 11173922 10339950 9253269 4446063 3325676 1686832 1593947 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 2-hydroxybutyric_acid 24651778 20173132 6443894 9990887 13713251 29800179 14103593 17153487 N/F 7436495 N/F N/F 7449590 N/F 7773575 2899559 2498093 1302711 1557887 N/F N/F N/F 2-hydroxyglutarate 57298801 60077035 30740914 34826367 85481635 183018399 256757630 261487454 200236414 211813072 208321436 222968510 135799909 177325095 169340690 70682312 93762965 32264918 48979981 N/F N/F N/F 2-oxoadipate_unc N/F N/F N/F N/F N/F 843704 606552 N/F N/F 566096 N/F N/F 288268 378548 552255 N/F N/F N/F N/F N/F N/F N/F 2-oxobutyric_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 3-hydroxybutyrate 30356150 39848900 15475861 34819912 15078216 62653473 32293899 59962620 5687471 47288635 22971904 93067343 44755539 39875329 39821708 16206561 13832316 5386811 4728203 N/F N/F N/F 3-methyl-2-oxobutyrate N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F 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 256743 N/F 242204 790749 594013 326414 N/F 1409193 568288 476900 N/F 2105596 917189 N/F 776718 N/F N/F N/F N/F N/F N/F N/F 3-phosphoglycerate 13481135 20397638 11333839 20262145 10356609 16822195 18381704 20213437 1057056 30226100 23050376 49332013 16035460 18727806 19278396 4036918 4567473 1130737 975177 N/F N/F N/F 3-ureidopropionate 9256063 11013948 3608405 6101374 3906541 16465142 8119214 10780549 1242417 13088039 5313613 14991085 7337267 8574641 9363831 2224871 2926454 789557 814372 N/F N/F N/F 5-Hydroxyindole-3-Acetate_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 6-phosphogluconate 258875 212484 70340 190470 104337 359595 200797 245085 28515 322411 106418 143214 158989 195602 173498 11678 21957 N/F 4205 N/F N/F N/F acetoacetate N/F N/F N/F N/F 1947315 1478891 989375 760133 N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F Acetyl CoA 1477986 2759216 1712417 1476578 971816 3977866 2635525 3734909 196130 3123446 1789937 6075976 2918374 2782192 2687753 750177 516033 223454 344548 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 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 acetylcarnitine 2307071706 1936281767 1219276641 1663349463 965323866 2611348624 1827915459 2470472591 372283494 2273328557 1566432128 3774821879 1676040750 1952762866 1844672423 716491550 739422886 287266774 257194530 N/F N/F N/F acetylglutamate 1261834 1517385 2411325 1312034 956703 2495316 2286143 2006305 746542 1526489 2242821 4152820 1612057 1992702 2030488 826900 855103 324646 386495 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 acetylmethionine 218330 410185 388670 386967 128624 460771 394292 243967 N/F N/F N/F N/F 234858 90389 72717 N/F 135296 N/F N/F N/F N/F N/F acetylserine 3541075 3169141 1497000 3275745 858772 3045244 1772486 2625913 1772764 2299017 1215827 3611550 1496552 1763366 2264908 999323 852088 409014 N/F N/F N/F N/F adenine 326501374 290532937 95344049 89590633 203526959 567416548 292746961 260247477 28622602 374511258 158182771 343503488 191468042 245786713 250653665 71211941 76999103 27907222 21462424 N/F N/F N/F adenosine_unc 2787486 1492378 N/F N/F 603079095 N/F 2734613 3446622 45691855 1303183183 588409951 1737949868 215042149 138454248 96573044 85951232 30998961 56051556 25799545 N/F N/F N/F ADP 28671736 33867457 19157653 24267071 10902569 49027726 27858919 40755413 2238609 42822253 22437721 45566193 25741581 27897183 27352285 9365446 9480924 3762336 3486832 N/F N/F N/F ADP-ribose_unc 99282 N/F 66185 N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F AICAR 742157 322144 252008 257825 282343 538310 450786 413012 N/F 400033 335106 544387 350553 364149 352962 103505 98322 23248 22132 N/F N/F N/F ALA_114 N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F 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 208762299 176885008 94550478 99191277 119311316 241292442 153303734 139588983 48032946 214048940 129211734 222392042 148607180 168957937 169260483 65732820 81303807 29763930 28127705 N/F N/F N/F alanine-13C3-15N N/F N/F 634658 N/F 280673 N/F N/F N/F 5833869 N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F allantoin N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F 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 1500835 1289221 816736 1421754 3621710 7263913 8677877 12921663 12661572 7449136 10426045 8300761 5512067 7363685 7009059 3009214 5276824 1561690 2815688 N/F N/F N/F Alpha-Lipoic Acid_unc 5575834 1504059 4900718 5034758 1654623 1454864 1194783 933337 837026 N/F 238635 283825 1605081 1698035 1789998 415881 477693 69578 N/F N/F N/F N/F AMP 173343060 232233123 136826398 197858498 60289008 275625224 194427119 215028767 728456 234197600 123083250 337455376 173844397 167557404 174810314 73180541 74867578 35937885 31583022 N/F N/F N/F anserine_unc 42167885 78109446 31367549 37811645 28136546 165981571 101218893 110205707 8696607 146675180 82176851 184110769 87455656 100157290 102609162 16968142 19232665 5476920 4928468 N/F N/F N/F arginine 716347037 574655543 266047396 346668280 443149865 776176808 546212443 512086790 195883449 680726141 393314650 812368683 400177661 540097305 544575469 208519767 252648102 115936901 113272196 N/F N/F N/F "arginine-13C6,15N4" 49967810 51519166 64583317 58099859 49311531 36329624 51187511 41106777 190410035 45784269 64152993 45223586 44972257 61035781 61672125 23208155 28534015 12802735 12748603 N/F N/F N/F argininosuccinate 16205367 23415622 5951848 13044146 10244895 23158880 15723640 22654474 989208 18506815 9814537 28586737 13344342 16042268 17408155 4056793 4253911 499432 442897 N/F N/F N/F ascorbate 161970836 357072474 136624282 131325687 16844359752 15945147515 16343591693 15686113559 33982129951 17939434626 18323020682 16764276067 14716763968 14905412876 15549901609 6780301206 7648916201 3479084479 3311712076 N/F N/F N/F asparagine 13546741 9863299 4702739 5752506 11091474 15391872 9069956 10412937 11303674 14110762 9107960 15929570 10348560 11163064 10845640 4119388 3881803 1304494 1101092 N/F N/F N/F aspartate 323447579 306259895 275946757 279356667 59161945 306936474 295911296 270189555 4925539 233362539 204998107 339136299 205103691 206305166 207005288 103792638 111680877 52348595 50821968 N/F N/F N/F aspartate-13C6-15N4 2795646 2690169 3481657 3105261 1208344 1279328 1383322 1363664 2150446 1391841 1469612 1204470 1796893 1875139 1774090 926372 985460 428555 443418 N/F N/F N/F asymmetric dimethylarginine (ADMA) 47877318 52335823 19269084 46372476 20873096 85457749 50490471 55477774 7563270 46390775 24194085 92053224 28410283 43463754 45839835 13487764 19061462 6314955 6695351 N/F N/F N/F ATP 3392487 3281251 2336998 2577839 2358811 3975850 1950900 5084802 N/F 4502325 2312458 4532655 2723554 3056268 2970099 883435 1009543 276271 333210 N/F N/F N/F beta-alanine 13350804 10821990 6728632 9450068 7026620 21882291 13309572 13772787 1931533 14791944 10153878 22641207 11245618 11427711 13688695 3380603 4718282 764061 695687 N/F N/F N/F betaine 7158237298 10287284097 3619861128 9193040168 2945460027 11735224551 7276943882 11065983003 703410209 9702116244 4509695668 14910580932 7146802261 8095722123 7941185183 2958054041 3129808050 1106225222 1048072713 N/F N/F N/F biotin N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F Butyrylcarnitine 300323869 309793220 141094815 170513875 121576934 474420770 222570474 304098591 25119994 288284212 143827044 324466007 175597950 199872863 197802586 68109400 71630992 32427624 26567647 N/F N/F N/F C5 Carnitines 64752020 48330686 17840569 27737166 27895564 67220472 29645949 46638563 6359025 50345584 26006829 66276714 33711351 37628850 37539667 12126029 12758123 5709330 3712828 N/F N/F N/F cAMP_unc 1168682 1252979 581486 877224 205318 2534870 1052036 2125287 N/F 2046834 749930 2803623 1323216 1228849 1239340 341755 297114 31061 31361 N/F N/F N/F Carbamoyl Aspartate 296555 234538 205431 316909 N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F carnitine 7644786343 7626684742 4061011682 5107308800 3173454420 10453336417 7753075513 8057336033 961078727 8064617617 5359652315 11016301240 6022495634 6871561297 6761849044 2329962397 2938872555 964187802 1067423406 N/F N/F N/F carnosine 40612792 55111409 37974416 39733413 18047801 62530650 65451624 53989134 3350122 57955123 51798660 71260797 43241388 48250945 52072163 19316334 22265243 5718737 5436166 N/F N/F N/F CDP 97198 110930 56947 48956 28079 171520 100221 199780 N/F 147966 67705 125496 94270 64045 95889 19110 23868 N/F N/F N/F N/F N/F 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 choline 90426428 110679059 46391373 84263104 49900258 135002195 88079952 156669185 12183480 122810157 63670678 149591674 90458444 104376694 105447047 39390682 50227937 18887148 17829915 N/F N/F N/F cis-aconitate 4356395 4016882 1737170 3033977 9456848 14089377 14060287 14210027 14870791 9858586 5423143 17149743 5230008 7203684 8827311 1411955 1671400 N/F N/F N/F N/F N/F citrate 71405774 61611007 15641175 39952988 20505774 117827902 51577337 107298118 46373198 55449514 19608339 150720621 26743631 42282564 64389192 2752988 3951900 N/F N/F N/F N/F N/F citrulline 33603312 26177127 16184310 19150176 20440547 29728606 25471903 30279609 37832244 26127312 21758612 43939231 24597569 30127346 29590119 12458104 13987217 3904170 3512257 N/F N/F N/F CMP 1685745 2162731 1130280 1922601 800201 2908499 2063720 2595876 N/F 2601554 1587096 4176503 1959882 1968748 1917769 818076 699272 336304 245966 N/F N/F N/F Coenzyme A 12036791 16872254 10602224 14586025 5957874 15542331 15352122 18280369 N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F creatine 5871770129 5597612882 3075450278 2914403939 2969508221 7374876429 4567421227 4188558267 948112093 6740339519 4028882993 6977274793 4322802219 5039371516 5161738775 2022118149 2609707850 960594475 1043771099 1178823 189930 298445 creatinine 92045067 126187974 54446337 146888300 44297517 196821141 112456503 246295700 18077123 128851647 60895349 288365017 102706724 119911885 119305244 33070580 39023044 12370081 11009373 N/F N/F N/F 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 cystathionine 6952495 6942749 3429615 4414574 4002755 10302535 6600786 7168121 557938 9707092 4647805 9399915 6351987 6311605 6461958 2494863 2274761 691123 532705 N/F N/F 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 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 cysteine-glycine 9045307 21295250 10862381 7403098 17612542 44368413 45120776 32173538 N/F 285142 36063 181116 210699 132607 187261 N/F N/F N/F N/F N/F N/F N/F cystine 80145634 115895701 26341667 51328871 49625900 130345339 93324837 79465328 1534263 4167076 10688284 11373496 19667356 13851862 10661933 10707533 7102321 4473186 3352719 N/F N/F N/F cytidine 6639970 5465450 2760849 2780829 3293750 8483978 3175992 12881649 7684872 10299731 1937202 12221658 6155801 6715688 7200785 1565978 1648684 480760 411542 N/F N/F N/F cytosine_unc N/F 1428643 191236 1197688 264137 2744086 726657 1579478 427712 1640102 357993 2010695 979116 1314059 1259848 344773 538758 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 dCytidine 2128212 1326984 623072 920088 1220350 1352622 1350300 1687496 705612 2257879 1150878 3260849 2088131 2225107 1738158 550016 497411 75925 85777 N/F N/F 13687 dihydrofolate_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 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 dihydroxyacetone_phosphate 1307589 2076907 520564 759367 296727 1809288 816631 1031287 N/F 1601293 370548 1165158 551381 861858 921535 199880 251577 N/F 213914 N/F N/F N/F dimethylglicine 18908161 26533700 8348646 19003176 11077889 54484764 17304520 20157371 N/F 31222828 14807852 30601801 15888304 15867708 19747009 4925725 7154481 1658972 1812306 N/F N/F N/F dTMP 50835 40149 14066 112419 N/F 277270 N/F 266967 352396 182949 N/F 468833 79951 379877 84181 N/F N/F N/F N/F N/F N/F N/F dTTP N/F N/F 16009 22385 257301 N/F 95286 74524 N/F N/F 199639 N/F 77409 69345 48402 169866 188357 121887 92052 N/F N/F 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 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 F6P_G1P_unc 1009939 1389430 679050 936885 1344939 1941091 1127411 1838165 N/F 1778638 870447 1888291 1589482 1261748 1229370 474637 467409 217534 200218 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 folate_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 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 formyl_methionine 1420703 478700 998288 2594244 850322 2355259 2276984 4673478 N/F 1049684 731994 3387406 1158412 1178411 1254320 462367 418139 192224 125353 N/F N/F N/F "Fructose 1,6-bisphosphate" 662212 1091995 801787 1443098 772835 741543 1303655 1545792 479149 3083160 1659489 4000654 1309306 1600322 1600147 536474 509690 206919 109502 N/F N/F N/F fumarate 17434037 26318428 9961065 20249020 11689611 19523237 12251205 26224255 N/F 17791552 12964321 30750872 13300861 18209929 16805340 6918917 9217591 3611211 4128023 N/F N/F N/F gamma-aminobutyric_acid 16423479 21615059 3873053 7961569 6919550 35148231 11443188 8499749 N/F 23362405 8882997 17482272 9599366 12354203 14758504 5224629 6854267 N/F N/F N/F N/F N/F gamma-glutamyl-alanine 15823533 16942995 6126894 10193432 11442358 19158540 16466428 15657836 5325876 17975563 12659390 31052699 13502336 15356384 16231367 3966649 4528651 1320956 1108302 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 GDP 2006569 2200746 987894 1106031 829387 3299448 1714076 2073330 153000 2725843 1357826 1490479 1631565 1593935 1619733 510077 485526 189994 137386 N/F N/F N/F glucose 10839325 26189724 11595969 23820898 3669895 31180636 10124909 27478095 1590063 22188254 5730434 28991442 17282079 16606579 12179107 6657899 4513758 2902154 2247303 N/F N/F N/F Glucose 6-phosphate 3189281 3489533 1642142 2109479 1934111 3818237 2153568 3180518 N/F 3379250 1483155 3703462 2719774 2597674 2458958 489926 905562 366334 347202 N/F N/F N/F glutamate 753089303 973632790 450577915 539169040 246351579 1024452221 669756488 646723030 20583407 767482866 400859651 924718054 553263101 561586454 582415449 250489566 257365056 123979800 119303669 N/F N/F N/F "glutamate-13C5,15N" 2665050 2439397 3086597 2751973 1379578 1447623 1425644 1426100 2436176 1669870 1743423 1227075 1992446 2041051 2118822 856088 825593 454511 366019 N/F N/F N/F glutamine 741769071 798311020 451031071 495319098 770449338 1304981320 916211990 871231315 509396869 1240312722 782824212 1335754289 824034035 949315905 970445349 399980626 435803995 173277759 169498888 N/F N/F N/F 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 glycerate 141076629 131218832 134598307 135823352 23084860 21555360 22578329 21953103 N/F 42686601 37171796 36298333 64909453 65334874 65708912 21915466 24424635 7257191 8558145 N/F N/F N/F Glycerol 3-Phosphate 47561352 47542686 22796041 31141360 28360420 69561606 45394083 48935312 4261089 54440995 31094309 81217559 45313351 42001391 42773446 17894193 16572728 7010592 5937127 N/F N/F N/F Glycerophosphocholine 17106902510 20223251422 9644217824 15947983105 10105327952 24589714714 16536303240 27302270344 3005041770 21710359521 12262183106 25741902026 16827598642 18838280177 19187322844 8287350650 10021112545 4159249187 4114062283 N/F N/F N/F glycine 23834198 29222580 13165168 15447795 13312151 43204707 29585277 26962353 2576968 31301800 18242215 39156759 21410689 21664758 23325429 7713574 8685885 2601496 2726275 N/F N/F N/F glycine_13C2-15N N/F N/F N/F N/F N/F N/F N/F N/F 264888 N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F GMP 24467290 31388163 17240208 23320458 11554234 37880001 26437614 28372391 N/F 38286495 20551083 44870623 26020793 24761274 25263880 10161617 9880264 4142420 3275011 N/F N/F N/F GSH 576250570 539956663 626103146 529126378 208231635 767446246 661656605 718584316 N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F GSH_13C2-15N-Ellmans N/F N/F N/F N/F N/F N/F N/F N/F N/F 2337355 1043071 1864859 779344 990809 1039651 139742 180723 40970 12849 N/F N/F N/F GSH_Ellmans N/F N/F N/F N/F N/F N/F N/F N/F 9473401 113870451 45130824 93830210 39127309 46546251 50451579 9170052 10353989 2554360 1810866 N/F N/F N/F GSH-13C2_15N 3579561 3921393 3282682 4351250 3432757 N/F 1225217 1071164 N/F N/F 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 48298417 30520313 23016178 19098567 3287492 124308244 44060462 48469355 789335 11153929 7617574 4122266 24524738 23804006 22640432 9029787 9467016 4072476 3296200 N/F N/F N/F GTP 137372 109138 77571 44482 98018 163746 59125 135410 24968 196747 42699 172803 54893 88265 81958 N/F 11963 4645 N/F N/F N/F N/F guanidinoacetate 467688873 467227041 206269565 284040117 229601496 638877487 420960021 505900682 50342039 534825795 315468570 676802681 342248246 419137585 433734067 155899768 189068606 53890815 60613652 N/F N/F N/F guanine_unc 22921936 23033159 6481803 9781026 19849660 29469638 13703386 19820237 3534409 19662643 9827665 21819773 17538238 16770038 17233531 5399649 5804051 2512557 2040237 N/F N/F N/F guanosine 34732795 35053425 8989551 14326260 31141408 44291184 21307509 31101303 4714057 31704238 15145973 33962187 27058085 25922573 27039834 8172612 8385766 3159052 2449109 N/F N/F N/F histidine 426558898 436486439 153410691 216670714 235972498 628611683 341314799 428997088 140474669 495664974 279981899 631223598 313776457 402895426 413168625 131295697 164253522 65903024 56391939 N/F N/F N/F histidine-13C6-15N3 30645436 34676849 35644825 31739219 40942661 27687975 29953500 29015306 203898718 30962214 47595379 29545710 36617872 44199450 46110997 15306922 18474988 6783278 7093660 N/F N/F N/F homocitrulline 10796270 8120456 9362928 9783348 5554679 11457504 19025662 15954110 2165659 9967800 15562224 22352617 10715647 12088074 12832350 4107063 5148306 1359354 1370633 N/F N/F 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 hydroxyproline_gammaALA N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F hypotaurine 18949234 23639075 12816117 14435495 18579025 38844003 32415445 28970119 6665092 16720369 9355487 22856639 18794854 20710031 21038634 7332213 8055855 2468038 2019605 N/F N/F N/F hypoxanthine 3249166388 2619920456 1079757436 1038727716 1914430703 3188180675 1823453893 1448877713 421492142 2886065281 1579726690 2154157077 1956879490 2019064263 2062276116 905874223 921188484 403897911 361740770 N/F N/F N/F IMP 66384107 60105612 23617947 44267728 26764566 82918244 42823225 66009986 2658549 78702085 31356640 103343261 50520202 52718404 52370740 18106764 17403068 7347503 6247823 N/F N/F N/F In [ ]: indolelactate N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F inosine 569208421 541110206 217181282 254838037 341285453 530237343 344838411 335757784 58894356 460524454 251169547 365180635 398010609 396345502 382343274 186698082 180711700 85327336 71140380 N/F N/F N/F isoleucine 110141313 75316713 25935555 44484109 41752211 81996486 43632957 56671269 31944802 79029598 35196540 91048005 55568383 63522916 59711612 19462301 20036826 7687924 7391368 N/F N/F N/F Isoleucine-13C6-15N 13552587 11526709 14467219 11858112 10578641 7151156 9827469 7855393 76760952 7782139 12927484 6925475 12917500 12437970 12273944 5020903 5434636 2241788 1851015 N/F N/F N/F Itaconic Acid 21228198 25474529 9021053 10006681 62168190 135182630 171598223 188363260 150821554 142517463 161223602 133566209 93967935 115428451 134833723 48240329 63828536 27377272 28091097 N/F N/F N/F Kynurenic Acid 713428 859417 219872 1177678 323593 1220271 832641 1637873 243942 865109 731499 1785554 825897 1053176 1039381 300464 318231 N/F N/F N/F N/F N/F kynurenine 389237 442627 420272 384572 205066 635131 653838 527443 498352 850654 590084 1329964 543822 658502 640390 109749 193033 N/F N/F N/F N/F N/F lactatic_acid 2277511694 2516881412 1079805108 1391577908 1034363608 3235660433 1914329435 1808813431 385512263 2776327982 1221929397 3007619747 2025175871 2037498659 1921757059 759212223 696998348 259369380 212359404 N/F N/F N/F leucine 178859691 140517570 71259812 79753413 83781894 203653241 99461145 137469004 41798155 173422560 73882976 252422944 111457892 128585824 127946829 34730943 38827518 12975951 12005550 N/F N/F N/F leucine-13C6-15N 14733420 14273380 15721072 15391183 11392923 10345100 10983049 12285540 52465073 15192471 16019623 14910405 14055115 18525347 15860131 5175514 5012322 2419927 1876642 N/F N/F N/F lysine 135127542 99815025 41713302 55710720 70124726 155545414 87495440 98331918 35159617 129639223 62099243 161211059 82058715 92327147 92978341 28732892 30410305 12255776 11221227 N/F N/F N/F lysine-13C6-15N2 6611603 6025951 6579176 5851008 5434929 4979786 5487982 5230466 19365698 6349037 6601857 5798518 6297869 7220065 7089829 2138434 2201057 765419 727898 N/F N/F N/F malate 172967859 249452643 100276736 202166805 115779980 183444691 136238382 256632965 N/F 162147568 144690367 332232464 127071344 170394255 179671628 75138746 108821292 33805271 45152971 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 methionine 129231359 94731323 70949580 64397900 72616609 130758208 141063934 110953681 44124760 118454883 96324250 156106100 99901157 109974708 113708515 36287602 37687876 15228382 12848201 N/F N/F N/F Methionine sulfoxide 6177513 4558414 7563482 4450168 2783258 5800799 12720028 6696706 5930638 5201140 11044254 12532315 6688374 9101711 9050341 2170083 2280228 489552 545020 N/F N/F N/F methionine-13C5-15N 19050255 16521475 21164261 18683981 18403642 12269475 14999484 15925426 103290731 16920794 21094624 13399806 19600748 21734128 22483227 6944821 7195161 2894190 2400910 N/F N/F N/F methylthioadenosine 2525652 2565428 1564671 2168477 1112462 4503320 2515079 3819262 65823 2436478 1436893 4799340 2007735 2169117 2401898 737660 1101504 385958 328172 N/F N/F N/F myo-inositol N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N2-acetyllysine 17329672 13176053 9744108 10970544 9238238 27136872 25675865 21209080 2647570 25136921 23282036 37415785 17838949 19972939 21745495 4485805 5381615 1457547 1393627 N/F N/F N/F N-acetylcysteine 865553 1331599 625991 1297298 1157088 1506063 1671486 1866290 N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N-acetylglutamate 1261834 1517385 2411325 1312034 956703 2495316 2286143 2006305 770160 1526489 2242821 4152820 1612057 1992702 2030488 826900 855103 324646 386495 N/F N/F N/F N-acetylglutamine 23850226 16699316 10939227 18635866 12659451 26749512 21531110 30801828 6249480 24710152 16607597 40843969 21294933 21729393 21734116 7741034 7674127 3008513 2582624 N/F N/F N/F N-acetylmethionine 276913 750123 256686 618662 164583 212367 536467 502433 N/F 103383 210026 856914 263767 331527 388711 106821 135296 N/F N/F N/F N/F N/F N-acetylornithine 412827 370985 197605 252685 164560 365484 321079 237532 182604 456451 354273 577196 380983 380525 397204 212649 198787 N/F N/F 10703 N/F N/F N-acetylphenylalanine N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F NAD+ 340352602 315942158 171732769 206613021 140543589 535881668 325814798 330208688 13729685 429116942 233824827 465045529 288132268 290103482 305678150 115484428 118067047 50763095 45367155 N/F N/F N/F NADH 13708043 12448831 4941254 2843607 528176 10429130 2267716 3285240 N/F 12120669 5079140 5093167 6510915 4121247 6239126 2418651 2455408 1039305 930081 N/F N/F N/F NADP 25247408 26609432 12817116 16746663 9117842 36687767 21924089 25780037 853415 40599809 19255261 40205709 22541008 23080192 24709647 7976909 7986929 3055568 3112020 N/F N/F 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 niacinamide 1356162034 2379216290 713352524 1241539531 1253281315 1813239767 1635767254 1883375580 105106245 1608383983 1123412321 3075266761 1308159056 1519123223 1554414210 493184828 567002729 201060712 178273224 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 O-phosphoethanolamine_unc 94416544 112924423 59684312 76619389 49710815 156861202 97366272 111615082 N/F 140796403 68848496 169778194 99681326 95803537 95222950 40548949 37487405 15989003 12738785 N/F N/F N/F ornithine 11259355 8365534 3105958 3843999 5174078 9938091 8294862 6602837 7290146 7934834 4933349 11444547 5677051 7155071 7597568 2345143 2947191 1079275 937928 N/F N/F N/F orotate 1912812 1647274 1027576 2101536 707205 2486692 1909500 3346453 176506 1656607 923724 4265034 1447350 1489343 1665976 550601 615390 223556 173467 N/F N/F N/F palmitate N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F 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 1805424 1390421 1518357 1373803 1056951 2070202 2224668 1751490 N/F 1952443 1602431 2673582 1802025 1431488 1606979 695211 604432 N/F N/F N/F N/F N/F Pantothenate 191149194 175150005 120657777 71637420 114249230 284157536 134741556 140004097 21138992 248744253 141553724 405175711 172499102 196961352 200696073 64564795 70081137 25464130 21708614 N/F N/F 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 phenylalanine 339983623 270826144 104232800 156035504 176775803 408123104 208425270 273856438 120637543 462016275 215315871 552660790 280903770 299175941 306395350 84235598 88088305 33156890 26559860 N/F N/F N/F phenylalanine-13C9-15N 39727229 38268923 39884634 40697308 33487622 30262486 30722313 31877924 196921484 49508711 54837920 45781298 49967331 54290539 53270841 14602364 15469133 5561693 4522569 N/F N/F N/F phosphocholine 3573947592 3842529093 1618786944 2230180386 1284481984 5416250958 3895496549 4304300551 107559897 4543769447 2841497507 5491314040 2553714572 3295004753 3384172268 885394330 1000849419 229548709 242287963 N/F N/F N/F phosphocreatine 5464321 3235757 2570495 2438354 1317092 10205111 3799794 4586152 682071 6723993 2626353 8049424 4458642 4092703 4368761 1523396 1456431 444603 444096 N/F N/F N/F phosphoenolpyruvate 3192420 4999709 1340684 3499110 2303464 4564120 4021331 5633330 281475 4994253 3645028 8226872 2981571 4320338 4486187 543619 606130 N/F 58395 N/F N/F N/F phosphoethanolamine 92347343 107095950 56731365 73985552 51058401 153604249 95434547 105726164 7116799 137861916 67199046 164365446 96837870 92860875 93544557 38832887 35609862 15403421 11578258 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 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 Pipecolate 25791070 29045566 9392297 16477222 10500178 39760313 22080623 32307268 5047289 31303932 13068939 48902086 20506453 22275731 21634339 5160211 7182613 2173574 1779706 N/F N/F N/F Piridoxine 484772 770220 436382 N/F N/F 870720 553762 491439 N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F proline 489608944 301542504 116981195 157029622 222900922 485265833 272186979 299639597 82674835 398448305 178300559 507444379 250484317 292328413 316590150 68892308 86686821 23519352 24657367 N/F N/F N/F proline-13C5-15N 62056279 54329566 54684007 55267251 48525660 45693951 47416989 45877061 162152290 54055260 56805131 52065251 54774640 63152347 68768557 16652260 20561079 6320851 6252028 N/F N/F N/F propionylcarnitine 215606181 181995423 66466688 122278271 96971474 269014189 125684523 202879406 20169343 208281295 101983302 324422400 134970716 153269434 150928420 46906925 52787161 19913828 18011077 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 pseudouridine_unc 8126930 8127261 3949399 11059679 3092140 8194522 4707790 10802012 1076544 7166061 3180262 12767492 5845821 5255139 6244313 2879962 2886612 1454811 1199352 N/F N/F N/F Pyridoxal 1124150 838632 331785 N/F 372107 1407534 887062 821199 N/F 1473189 481000 1266984 1096894 853072 908850 534618 319568 269689 N/F N/F N/F N/F pyruvate 4668062 5953977 3766028 4814177 1921101 4202373 3024180 4193522 N/F N/F 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 Ribose 1-phosphate_unc 3245277 3272225 745844 1104356 764192 3604636 1805714 2433348 N/F 3445009 918433 3210754 2007237 1938642 1962848 629291 592079 160568 147581 N/F N/F N/F Ribose_Ribulose 5-phosphate 3245277 3272225 745844 1091418 764192 3604636 1805714 2433348 N/F 3445009 918433 3210754 2007237 1938642 1962848 629291 592079 160568 147581 N/F N/F N/F saccharopine_unc 4860360 4592867 1743507 2493471 2169910 7466253 5566033 5560707 162248 7670534 3310880 7605517 4322978 4627588 4977899 902086 991736 153149 174796 N/F N/F N/F S-Adenosyl-L-Homocysteine 132130813 110429990 37112868 33328085 64803918 166502356 82648468 55125890 7542073 128173499 68682132 93825401 74842688 92122140 92397383 25842532 31024574 8685880 7684524 N/F N/F N/F S-Adenosyl-L-methionine 138648125 158391337 120623110 134277096 90205935 219278745 185542270 208184211 16446063 186854696 140232294 209884435 132758350 155352890 160228359 83877963 100123666 44233459 51113163 N/F N/F N/F sarcosine 841929 799659 486470 484625 733758 1263460 937232 948927 353255 837730 636994 1620847 580092 866560 791530 169333 269577 99416 151337 N/F N/F N/F Sedoheptulose-7-phosphate 4950999 4980136 1732236 2347920 1895583 6485498 2987300 2805670 N/F 5295824 1910358 4249062 3161845 3052193 2875431 1141123 1092879 431539 351226 N/F N/F N/F serine 15851584 13521472 4977520 7076630 7668025 19505177 9762029 13403345 5613697 15044368 6362034 17447647 10422770 10552304 11791491 3934755 3709557 1262469 1254765 N/F N/F N/F serine-13C3-15N 299075 368259 490888 519030 375908 N/F 262867 96187 1852135 344391 364811 36405 430648 381651 299808 104082 159649 9764 N/F N/F N/F N/F S-methylcysteine_unc 470497 648759 208811 207073 306892 1076449 653092 706035 N/F 808504 292448 1207934 434827 588606 603712 69172 71200 N/F N/F N/F N/F N/F succinate 131388908 114027104 37544775 59935595 45495135 201767198 83895559 118946339 17271695 166236013 52100518 200941919 92103482 101074854 97139739 30902991 35213592 11276829 10976287 N/F N/F N/F taurine 1626835546 2056786153 1029969965 1289035304 714712467 2473628863 1221598036 1475639764 146440410 1959107944 846207966 2223390881 1410378669 1316162039 1371199600 581649903 577254290 251074276 218923500 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 threonine 60535849 57372652 23293415 30682900 30976250 82571156 45212144 60700535 12783568 75179048 32405815 92964033 42953762 47781855 48219091 13675147 13822621 4923791 4430788 N/F N/F N/F threonine-13C4-15N 3236128 3301660 3833386 3691435 3124483 2806949 2568341 3062080 16747533 3533143 3933055 3450383 3692498 4141867 4378200 1240221 1309199 421337 384123 N/F N/F N/F thymidine 192649 N/F 53827 115319 98962 337987 130756 197589 11161 176228 59696 194848 148162 112569 109401 25337 33425 6140 N/F N/F N/F N/F trans-urocanic acid 33883121 13462508 7719785 11916232 4179121 6449827 12048150 14849951 49664340 10028068 4556918 26135286 16998240 15055985 18380058 5056605 6563362 2104385 1339272 N/F N/F N/F trimethyllysine N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F 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 77831512 61947387 26636409 38215294 44686735 94936948 49530527 67303541 29368628 82019198 38384535 91808866 59706480 62065123 63131373 19526977 19176744 8095778 6491224 N/F N/F N/F tyrosine 135446690 109640900 44581567 63971217 81401946 173939693 91926686 110813949 35047961 149428099 69401102 170446796 100458736 106761028 110601781 33224018 33912629 13507072 11073898 N/F N/F N/F tyrosine-13C9-15N 16304136 15501293 17416340 17540827 16307536 13660952 13456379 14455640 61364085 16858584 17733208 14808584 18424314 19894696 20384889 6142288 6021123 2350959 1880802 N/F N/F N/F UDP 15054525 15726559 8604787 12691088 7536981 23591383 13970484 21472938 941905 21851666 10820780 27604146 14991508 14929695 15062262 5380336 5114292 2251847 1851497 N/F N/F N/F UDP-GlcNAc 18278489 21874926 11150692 14950187 9193531 31299139 18793079 23685630 1376306 27727571 13449763 33858959 19961414 19284533 19535773 7998492 7474855 3125690 2618949 N/F N/F N/F UDP-hexose 15448873 18984790 7283474 12264778 5901150 21041362 12171609 16663964 N/F 18678579 8691371 25550122 12406468 12366273 12425858 4249024 4354258 1612892 1335492 N/F N/F N/F UMP 29402645 46383712 26078150 43186353 10680499 58933715 38351953 51647606 818112 45823227 27093888 92649657 36124254 37037648 37188511 13554005 13858478 5593111 4704087 N/F N/F N/F uracil 102609832 85112570 27837538 32274325 47165959 129492277 62154662 54237694 N/F 40180391 8723633 27113139 28723913 23173053 27158282 14301316 12371087 5656804 4598703 N/F N/F N/F uric acid_unc 82535181 82914621 35813492 55000268 40734797 89873216 39727230 60449364 15162096 57587860 27960939 65679895 46461995 21889941 46930845 23188819 26547446 10783689 10891498 28186 N/F N/F uridine 14961507 12611037 6366973 8561941 8843683 17339500 8853519 11988033 506110 9439164 3880840 12399197 11099711 7788556 6663282 4351724 3004394 1856903 1138192 N/F N/F N/F UTP N/F N/F N/F N/F N/F 127505 N/F 352967 N/F N/F 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 142116422 104886364 24719783 110181722 59295305 119197681 N/F 109178787 17991102 112321876 45412703 126285543 83673995 65369892 78225065 22231324 49457378 8999730 4593656 N/F N/F N/F valine-13C5-15N 8243338 7474143 7474160 7519059 5784429 5706988 5994109 6327660 19262556 6922925 7273767 6422378 7424497 8309257 8193689 2330470 2750249 982883 801587 N/F N/F N/F xanthine 362183780 293996567 138964269 131808134 107277031 258057000 124344454 99413890 20204945 217439282 93023519 138299373 130788098 118938540 128902015 70186097 76184934 36999036 33675090 N/F N/F N/F xanthosine_unc 3491136 2194849 821614 860087 1520101 2875888 1354516 1180943 186928 2230878 933543 1523611 1497843 1404339 1510494 577914 565900 238297 212081 N/F N/F N/F MS_METABOLITE_DATA_END #METABOLITES METABOLITES_START metabolite_name 1-methylnicotinamide_unc "2,3-BPG_unc" 2-aminoadipate 2-aminobutyric_acid 2-hydroxybutyric_acid 2-hydroxyglutarate 2-oxoadipate_unc 2-oxobutyric_acid 3-hydroxybutyrate 3-methyl-2-oxobutyrate 3-methyl-2-oxopentanoic_acid 3-phosphoglycerate 3-ureidopropionate 5-Hydroxyindole-3-Acetate_unc 6-phosphogluconate acetoacetate Acetyl CoA acetylalanine acetylaspartate acetylcarnitine acetylglutamate acetylglycine acetylmethionine acetylserine adenine adenosine_unc ADP ADP-ribose_unc AICAR ALA_114 alanine alanine-13C3-15N allantoin Alpha-Ketoglutarate Alpha-Lipoic Acid_unc AMP anserine_unc arginine "arginine-13C6,15N4" argininosuccinate ascorbate asparagine aspartate aspartate-13C6-15N4 asymmetric dimethylarginine (ADMA) ATP beta-alanine betaine biotin Butyrylcarnitine C5 Carnitines cAMP_unc Carbamoyl Aspartate carnitine carnosine CDP CDP-choline choline cis-aconitate citrate citrulline CMP Coenzyme A creatine creatinine CTP cystathionine cysteine_13C3_15N1 cysteine_unc cysteine-glycine cystine cytidine cytosine_unc dATP dCytidine dihydrofolate_unc dihydroorotate_unc dihydroxyacetone_phosphate dimethylglicine dTMP dTTP dUMP erythrose_4-phosphate_unc F6P_G1P_unc FAD folate_unc folic_acid formyl_methionine "Fructose 1,6-bisphosphate" fumarate gamma-aminobutyric_acid gamma-glutamyl-alanine GAR GDP glucose Glucose 6-phosphate glutamate "glutamate-13C5,15N" glutamine glyceraldehyde_3-phosphate glycerate Glycerol 3-Phosphate Glycerophosphocholine glycine glycine_13C2-15N GMP GSH GSH_13C2-15N-Ellmans GSH_Ellmans GSH-13C2_15N GSSG GTP guanidinoacetate guanine_unc guanosine histidine histidine-13C6-15N3 homocitrulline homocysteine hydroxyproline_gammaALA hypotaurine hypoxanthine IMP In [ ]: indolelactate inosine isoleucine Isoleucine-13C6-15N Itaconic Acid Kynurenic Acid kynurenine lactatic_acid leucine leucine-13C6-15N lysine lysine-13C6-15N2 malate mannose methionine Methionine sulfoxide methionine-13C5-15N methylthioadenosine myo-inositol N2-acetyllysine N-acetylcysteine N-acetylglutamate N-acetylglutamine N-acetylmethionine N-acetylornithine N-acetylphenylalanine NAD+ NADH NADP NADPH niacinamide Nicotinic Acid O-phosphoethanolamine_unc ornithine orotate palmitate p-aminobenzoate Pantothenate Phenylacetyl glutamine phenylalanine phenylalanine-13C9-15N phosphocholine phosphocreatine phosphoenolpyruvate phosphoethanolamine phosphoserine Picolinate Pipecolate Piridoxine proline proline-13C5-15N propionylcarnitine PRPP_unc pseudouridine_unc Pyridoxal pyruvate Riboflavin Ribose 1-phosphate_unc Ribose_Ribulose 5-phosphate saccharopine_unc S-Adenosyl-L-Homocysteine S-Adenosyl-L-methionine sarcosine Sedoheptulose-7-phosphate serine serine-13C3-15N S-methylcysteine_unc succinate taurine thiamine threonine threonine-13C4-15N thymidine trans-urocanic acid trimethyllysine tryptophan tyrosine tyrosine-13C9-15N UDP UDP-GlcNAc UDP-hexose UMP uracil uric acid_unc uridine UTP valine valine-13C5-15N xanthine xanthosine_unc METABOLITES_END #END