#METABOLOMICS WORKBENCH boryana_ptrva_20210422_082827_mwtab.txt DATATRACK_ID:2592 STUDY_ID:ST001769 ANALYSIS_ID:AN002876 PROJECT_ID:000000 VERSION 1 CREATED_ON May 4, 2021, 4:27 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 XI) PR:LAST_NAME Petrova #STUDY ST:STUDY_TITLE Application of the redox metabolite detection method for profiling redox state ST:STUDY_TITLE following pharmacologic perturbations of redox balance in cells (part I) ST:STUDY_SUMMARY This study aimed to test our optimized method for detection of redox metabolites ST:STUDY_SUMMARY from mammalian cells upon redox stress and metabolism perturbations. Redox ST:STUDY_SUMMARY balance was perturbed using H2O2 and diamide, metabolism was perturbed by ST:STUDY_SUMMARY methotrexate or oligomycin. ST:INSTITUTE Boston Childrens Hospital 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 Homo sapiens SU:TAXONOMY_ID 9606 #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=20201027_QEF1_HILIC_ROS_K562_BP_blank_end1; Suspension=-; Other=- SUBJECT_SAMPLE_FACTORS - blank2 Factor:- RAW_FILE_NAME=20201027_QEF1_HILIC_ROS_K562_BP_blank_end2; Suspension=-; Other=- SUBJECT_SAMPLE_FACTORS - blank3 Factor:- RAW_FILE_NAME=20201027_QEF1_HILIC_ROS_K562_BP_blank_strt1; Suspension=-; Other=- SUBJECT_SAMPLE_FACTORS - blank4 Factor:- RAW_FILE_NAME=20201027_QEF1_HILIC_ROS_K562_BP_blank_strt2; Suspension=-; Other=- SUBJECT_SAMPLE_FACTORS - 1M K562 cells treated 4h extracted in 300ul buffer a Factor:buffer C_Ell RAW_FILE_NAME=20201027_QEF1_HILIC_ROS_K562_BP445; Suspension="DA, 0.5mM"; Other="isotopically labelled amino acids, GSH-13C2-15N, aminopterin" SUBJECT_SAMPLE_FACTORS - 1M K562 cells treated 4h extracted in 300ul buffer b Factor:buffer C_Ell RAW_FILE_NAME=20201027_QEF1_HILIC_ROS_K562_BP446; Suspension="DA, 0.5mM"; Other="isotopically labelled amino acids, GSH-13C2-15N, aminopterin" SUBJECT_SAMPLE_FACTORS - 1M K562 cells treated 4h extracted in 300ul buffer c Factor:buffer C_Ell RAW_FILE_NAME=20201027_QEF1_HILIC_ROS_K562_BP447; Suspension="DA, 0.2mM"; Other="isotopically labelled amino acids, GSH-13C2-15N, aminopterin" SUBJECT_SAMPLE_FACTORS - 1M K562 cells treated 4h extracted in 300ul buffer d Factor:buffer C_Ell RAW_FILE_NAME=20201027_QEF1_HILIC_ROS_K562_BP448; Suspension="DA, 0.2mM"; Other="isotopically labelled amino acids, GSH-13C2-15N, aminopterin" SUBJECT_SAMPLE_FACTORS - 1M K562 cells treated 4h extracted in 300ul buffer e Factor:buffer C_Ell RAW_FILE_NAME=20201027_QEF1_HILIC_ROS_K562_BP449; Suspension="DA, 0.1mM"; Other="isotopically labelled amino acids, GSH-13C2-15N, aminopterin" SUBJECT_SAMPLE_FACTORS - 1M K562 cells treated 4h extracted in 300ul buffer f Factor:buffer C_Ell RAW_FILE_NAME=20201027_QEF1_HILIC_ROS_K562_BP450; Suspension="DA, 0.1mM"; Other="isotopically labelled amino acids, GSH-13C2-15N, aminopterin" SUBJECT_SAMPLE_FACTORS - 1M K562 cells treated 4h extracted in 300ul buffer g Factor:buffer C_Ell RAW_FILE_NAME=20201027_QEF1_HILIC_ROS_K562_BP451; Suspension="oligomycin, 20ug/ml"; Other="isotopically labelled amino acids, GSH-13C2-15N, aminopterin" SUBJECT_SAMPLE_FACTORS - 1M K562 cells treated 4h extracted in 300ul buffer h Factor:buffer C_Ell RAW_FILE_NAME=20201027_QEF1_HILIC_ROS_K562_BP452; Suspension="oligomycin, 20ug/ml"; Other="isotopically labelled amino acids, GSH-13C2-15N, aminopterin" SUBJECT_SAMPLE_FACTORS - 1M K562 cells treated 4h extracted in 300ul buffer i Factor:buffer C_Ell RAW_FILE_NAME=20201027_QEF1_HILIC_ROS_K562_BP453; Suspension="oligomycin, 40ug/ml"; Other="isotopically labelled amino acids, GSH-13C2-15N, aminopterin" SUBJECT_SAMPLE_FACTORS - 1M K562 cells treated 4h extracted in 300ul buffer j Factor:buffer C_Ell RAW_FILE_NAME=20201027_QEF1_HILIC_ROS_K562_BP454; Suspension="oligomycin, 40ug/ml"; Other="isotopically labelled amino acids, GSH-13C2-15N, aminopterin" SUBJECT_SAMPLE_FACTORS - 1M K562 cells treated 4h extracted in 300ul buffer k Factor:buffer C_Ell RAW_FILE_NAME=20201027_QEF1_HILIC_ROS_K562_BP455; Suspension=DMSO; Other="isotopically labelled amino acids, GSH-13C2-15N, aminopterin" SUBJECT_SAMPLE_FACTORS - 1M K562 cells treated 4h extracted in 300ul buffer l Factor:buffer C_Ell RAW_FILE_NAME=20201027_QEF1_HILIC_ROS_K562_BP456; Suspension=DMSO; Other="isotopically labelled amino acids, GSH-13C2-15N, aminopterin" SUBJECT_SAMPLE_FACTORS - pooled sample QC a Factor:- RAW_FILE_NAME=20201027_QEF1_HILIC_ROS_K562_BP457_pool1x; Suspension=-; Other=- SUBJECT_SAMPLE_FACTORS - pooled sample QC b Factor:- RAW_FILE_NAME=20201027_QEF1_HILIC_ROS_K562_BP457_pool1x_a; Suspension=-; Other=- SUBJECT_SAMPLE_FACTORS - pooled sample QC c Factor:- RAW_FILE_NAME=20201027_QEF1_HILIC_ROS_K562_BP457_pool1x_b; Suspension=-; Other=- SUBJECT_SAMPLE_FACTORS - pooled sample QC 1/3 dilution Factor:- RAW_FILE_NAME=20201027_QEF1_HILIC_ROS_K562_BP458_pool03x; Suspension=-; Other=- SUBJECT_SAMPLE_FACTORS - pooled sample QC 1/10 dilution Factor:- RAW_FILE_NAME=20201027_QEF1_HILIC_ROS_K562_BP459_pool01x; Suspension=-; Other=- SUBJECT_SAMPLE_FACTORS - pooled sample QC 1/10 dilution a Factor:- RAW_FILE_NAME=20201027_QEF1_HILIC_ROS_K562_BP459_pool01x_a; Suspension=-; 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 K562 Cells #TREATMENT TR:TREATMENT_SUMMARY (K562 cells) Methotrexate 5uM treatment + 300 uL Buffer C_Ell: 4h Treatment + DA TR:TREATMENT_SUMMARY 0.5mM x 2, 4h Treatment + DA 0.5mM x 2, 4h Treatment + DA 0.2mM x 2, 4h TR:TREATMENT_SUMMARY Treatment + DA 0.2mM x 2, 4h Treatment + DA 0.1mM x 2, 4h Treatment + DA 0.1mM x TR:TREATMENT_SUMMARY 2, 4h Treatment + oligomycin 20 ug/ml x2, 4h Treatment + oligomycin 40 ug/ml x TR:TREATMENT_SUMMARY 2, 4h Treatment + DMSO x2, #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 1M K562 cells treated 4h extracted in 300ul buffer a 1M K562 cells treated 4h extracted in 300ul buffer b 1M K562 cells treated 4h extracted in 300ul buffer c 1M K562 cells treated 4h extracted in 300ul buffer d 1M K562 cells treated 4h extracted in 300ul buffer e 1M K562 cells treated 4h extracted in 300ul buffer f 1M K562 cells treated 4h extracted in 300ul buffer g 1M K562 cells treated 4h extracted in 300ul buffer h 1M K562 cells treated 4h extracted in 300ul buffer i 1M K562 cells treated 4h extracted in 300ul buffer j 1M K562 cells treated 4h extracted in 300ul buffer k 1M K562 cells treated 4h extracted in 300ul buffer l pooled sample QC a pooled sample QC b pooled sample QC c pooled sample QC 1/3 dilution pooled sample QC 1/10 dilution pooled sample QC 1/10 dilution a Factors Factor:- Factor:- Factor:- Factor:- Factor:buffer C_Ell Factor:buffer C_Ell Factor:buffer C_Ell Factor:buffer C_Ell Factor:buffer C_Ell Factor:buffer C_Ell Factor:buffer C_Ell Factor:buffer C_Ell Factor:buffer C_Ell Factor:buffer C_Ell Factor:buffer C_Ell Factor:buffer C_Ell Factor:- Factor:- Factor:- Factor:- Factor:- Factor:- 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 "2,3-BPG" N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F 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-aminobutyric_acid N/F N/F N/F N/F 40124671 56964662 61909023 36925673 46192161 53738655 58861873 56532663 76718994 39322204 51601972 39125306 50225634 57083338 66291465 18122779 8818512 N/F 2-hydroxybutyric_acid N/F N/F N/F N/F 12088019 N/F N/F 8395132 N/F 10535428 N/F 11552884 17015076 10908274 8310590 17098650 N/F 6269027 8494441 N/F N/F N/F 2-hydroxyglutarate N/F N/F N/F N/F 2988522990 2603632978 2753227896 2523858298 2110585825 2257041728 2276621798 2218258926 2451667420 2647442665 2593681556 3020777735 2416867824 2833055302 2472798508 1184182507 432502758 486426819 2-oxoadipate N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F 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 N/F N/F N/F N/F 22641143 37931156 21994184 26304532 22291657 31302946 36671902 29916991 27015987 33321645 25094979 23469795 32481271 28628053 28400924 10682950 2443858 3223596 3-hydroxybutyric_acid N/F N/F N/F N/F 56426481 53905971 40916102 54984361 64671916 56485476 44085018 54104594 69810400 61258083 60989877 61031540 50768468 61763583 61154251 19488446 7256732 8622411 3-hydroxyisobutyric_acid N/F N/F N/F N/F 20962690 23098985 14960786 18972032 26503959 17868402 12715602 25157401 26861356 19792928 23637303 21111883 22978843 24445761 19796032 8041997 3020804 3802937 3-methyl-2-oxopentanoic_acid N/F N/F N/F N/F 1726447746 1862192044 2001676393 2331189634 2304757292 1998898808 1311882173 1916645809 1931336938 1713084327 2306643669 1884568793 1955517864 2199380735 2010113813 716271542 196829223 243154457 3-phosphoglycerate N/F N/F N/F N/F 28493287 29792153 24397080 24996757 31425910 31774424 32760032 30757727 30023136 26764738 30102781 33935273 27367055 32984155 30170648 10590514 2795758 3608938 3-ureidopropionate N/F N/F N/F N/F 2320541 2911277 2056698 2514779 2558001 3103073 3720867 2695026 3039884 2805369 2032795 2551012 2336277 3063701 2231854 1009443 303178 642980 5-Hydroxyindole-3-Acetate N/F N/F N/F N/F 2840506 1727631 2484575 2294516 1266909 2503581 N/F 2588468 2479036 3200335 2498050 2856660 2936457 2538221 1816732 1388827 403034 470006 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 acetoacetate N/F N/F N/F N/F 23273341 38371452 22504760 27033219 24141836 32036058 37081935 30503781 27710407 33943872 25880928 23940084 33315042 28941787 28994950 11263338 3476362 3427496 Acetyl CoA N/F N/F N/F N/F 8417837 10627693 7084807 8147786 6620392 7858424 11223282 9575784 8601146 10137215 6466591 7909665 8983783 8771981 8227319 1956988 563156 698684 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 12168819 14325599 18544142 17601746 16183833 20204940 20898666 18296029 16307537 20292276 20176579 18485821 18632062 21277187 17151291 10835571 4305343 5024254 acetylcarnitine N/F N/F N/F N/F 2008265433 2152412886 1809913402 2086706223 2016332135 2027647153 2124524562 1996401383 2236458264 1944185409 1895500089 2076515142 2031607697 2148743600 2039995676 869686050 282393072 334473812 acetylglutamate N/F N/F N/F N/F 1289940 1450144 4716471 5491037 7063256 6495844 7006066 7304353 6389392 6147639 5737053 5995037 4978710 5489226 5213381 3031069 1029615 1142973 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 N/F N/F N/F N/F N/F N/F N/F N/F 647577 425857 488687 1033057 N/F 510166 839388 557781 N/F N/F N/F N/F N/F N/F acetylserine N/F N/F N/F N/F 10408767 10765825 23296420 19866371 28181426 30758002 32261828 26731454 25935274 28606419 32796290 30656546 23719369 24450224 22837340 13099561 5241254 6903341 adenine N/F N/F N/F N/F 17729755 25636663 14550442 34067015 38094729 30052736 32142764 31693336 47820598 50186234 28637049 18106601 44125696 14578690 33675973 17817271 5338458 2059043 adenosine N/F N/F N/F N/F 2996622 5945296 769521 N/F N/F 464698 2521704 433449 N/F N/F N/F N/F 1223439 1982267 1028518 N/F N/F N/F ADP N/F N/F N/F N/F 19709821 24307135 22698083 25588413 26736662 25641510 38686106 33816653 34452693 32222109 24119542 24994199 25827162 30764764 27438402 10079909 2886487 4017898 ADP-ribose N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F 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 N/F N/F N/F N/F N/F N/F N/F N/F 2459052 1732116 N/F N/F N/F N/F 4902558 4560364 1152156 1242697 1190087 413358 113085 143866 alanine N/F N/F N/F N/F 677299514 768101048 645857652 635928011 544040624 655131712 766205936 762413138 781785064 691929796 563087954 679445563 699656860 717209879 708814702 263872375 106122356 116738459 alanine-13C3-15N N/F N/F N/F N/F 2367685 3350437 2847072 3581968 2280942 2830245 1973512 3061653 1861593 2270249 2662742 2050980 2836601 2788496 2564198 1284017 63595 136863 allantoin N/F N/F N/F N/F 43939943 40150390 35326108 31516732 38273868 35396590 33697543 42783019 50292780 41216661 36572467 37167700 43340656 41312088 37805624 15749332 8822438 9023545 Alpha-Ketoglutarate N/F N/F N/F N/F 125035283 101049299 89370282 75637485 60671178 73619108 84133741 63548778 47228023 75438895 90624726 85271759 54867686 132674509 69782802 36025521 14607670 N/F alpha-keto-isovalerate N/F N/F N/F N/F 159459763 149940774 136947532 160606361 136073663 129185507 112953000 134030081 165012610 159847470 162508129 157460805 153090123 161100919 150638652 50354322 15695078 15591694 Alpha-Lipoic Acid N/F N/F N/F N/F 1715880 3267590 N/F 1986100 3369197 3694978 2781493 3476724 3222368 2095497 1429825 583972 2260061 1738169 2302612 666708 131761 107126 amidoadipate N/F N/F N/F N/F 27088802 33670913 33989808 35149399 35699933 35485974 34203055 62494853 43187884 44697863 61856370 32564121 42799837 38414640 33148129 22531286 4992764 5483655 AMP N/F N/F N/F N/F 5912606 7617542 8283963 7513508 8020047 8786832 10017086 9603101 7006108 7048823 7414238 6981318 8036528 9808595 8130124 2398231 865699 1121233 anserine N/F N/F N/F N/F 24467954 24345109 20740073 19426427 19462700 23549808 19925618 23714755 22654128 21694763 19384832 24393164 22088651 27231142 23384111 8766555 1994758 3866129 arginine N/F 25582882 N/F N/F 20415469639 19863345699 18717178694 19137761932 19549201588 20060879708 19060011806 20505045283 23593618288 19871292896 19660420038 20641015524 19504244728 19784335985 20106486105 10202972960 4423967844 5954088806 arginine-13C6-15N4 N/F N/F N/F N/F 45498812 47840083 43515880 46983137 41712420 46964068 40280374 41404930 38113332 40266930 40503933 42202973 42580414 42828983 45284534 21437433 10224294 14516038 argininosuccinate N/F N/F N/F N/F 11988432 11570087 17069173 18142742 19096338 19798205 28921800 25660543 26089265 23089952 19638361 22662573 16973968 23153972 20226353 8099455 3375446 5110819 ascorbate N/F N/F N/F N/F 31577664942 34540596178 29677662894 33496776499 31338447087 28236688180 33917903233 31674148031 31446817015 28790265470 30454114796 32920455805 30331083166 33240421115 31970837820 15433422853 6565139903 7631467920 asparagine N/F 169189 N/F N/F 1301176730 1287785907 1014806934 1314485847 1270224385 1287050037 1249592111 1266906497 1347033422 1213624979 1249206189 1248776693 1228205841 1373886081 1279413444 475763928 128210867 180645843 aspartate N/F N/F N/F N/F 570480849 575881128 557122279 608552841 622849208 580310866 516315865 600077799 664058868 571371308 616976463 616691414 576583441 631166443 570967713 251494300 141286162 180588667 aspartate-13C6-15N4 N/F N/F N/F N/F 6280601 6830103 5159490 6354939 5752700 5958399 5183712 6142030 4901447 5850904 5520145 5682930 5140734 6168775 6647988 2631161 1304972 1803354 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 N/F N/F N/F N/F N/F N/F N/F N/F N/F ATP N/F N/F N/F N/F 433156432 501530035 266305695 285027280 273399621 340248026 435698909 267785023 266857456 271933804 237866261 346050598 275062590 363718384 295614341 77697428 17565649 24611175 beta-alanine N/F N/F N/F N/F 188518643 191395540 179213580 213266724 215499916 230173801 235725462 204948577 185414093 199662744 218675743 223230197 213706698 221166599 204951046 84338319 22687880 32064773 betaine N/F N/F N/F N/F 5324622412 5796714192 5520323277 6404289254 5917449276 5797207220 5131575997 5782266291 6754748270 5778774149 6307785448 5702588902 5871674027 6058683149 6320659847 2775186095 899916405 1106965152 biotin N/F N/F N/F N/F 109101066 101771798 80017342 81034688 84810252 88700077 78270457 91432764 109778425 87682757 84138918 87085383 78393346 96277436 91716360 57673613 26369877 30663156 Butyrylcarnitine N/F N/F N/F N/F 330813204 338398024 327716133 360200611 392136899 374240502 540031413 600810067 599383008 595116354 397614016 393283304 429556368 465195713 437715941 167979245 49239196 60672822 C5 Carnitines N/F N/F N/F N/F 632045804 683836056 1187284262 1297492117 1480857660 1423781999 1100868465 1103160382 880703850 1174004297 1500457259 1534916955 1232932699 1222918078 1182076424 498517114 144202814 174596490 cAMP N/F N/F N/F N/F N/F N/F 722974 880777 1141108 870259 504365 580171 514854 685195 1272893 952933 850863 441979 715778 250569 N/F N/F carnitine N/F 557968 N/F N/F 3124384075 3300081945 2502642415 2728474176 2485447574 2734955067 2525815145 2575121168 2638587994 2514258879 2384767515 2677679823 2752722481 2840039065 2648875350 1018755467 347861384 385406200 carnosine N/F N/F N/F N/F 217826601 203047183 226875965 244853626 255487114 242339432 211680562 257799802 285755775 251620134 254184626 269878034 242016302 255665338 243212961 129570724 37066479 58481109 CDP N/F N/F N/F N/F 615702 624674 631138 884277 960656 874203 1350367 975586 1385814 894180 1142236 1329626 908352 1109974 937919 315821 77947 101053 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 N/F N/F N/F N/F 22404940 24368648 25721139 20671602 21528522 23419509 34491880 33107540 23445821 28557258 14355354 21460528 26388174 29834679 23124885 6791752 2098740 2130873 cis-aconitate N/F N/F N/F N/F 40335047 49037016 59253166 62165626 64028765 60017457 50519567 55869161 43999823 50598906 58447365 64600237 52863878 59750672 58183296 22711982 8213899 11198750 citrate N/F N/F N/F N/F 1382153553 1412829112 1712710371 1691091458 1882557014 1754463964 1368848613 1554680523 1688766743 1526800001 1774769048 1854251189 1502270182 1790932705 1615311590 768941373 190211443 230539525 citrulline N/F 353603 818627 N/F 362135038 358799489 301624333 304469534 300715442 323430104 286638398 353554813 385947106 337260974 323740086 323991637 324773913 359118815 320616482 167712559 54486668 85522582 CMP N/F N/F N/F N/F 342319 314447 175870 253422 122550 138441 133656 197341 160279 226956 97783 100610 162020 197314 186119 95751 26346 27096 CoA-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 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 creatine N/F 8104032 N/F N/F 18827218121 21726261837 19328698275 18100455549 18317238391 18414240115 24841237089 23364902498 23438396854 21651586276 16680576967 17621104003 20624718537 23334091528 20813231988 9624924414 4632696441 5231451093 creatinine N/F N/F N/F N/F 1370062678 1237496688 1249045402 1254508334 1291287050 1329009425 1049132050 1367565837 1579123814 1311200052 1209403386 1351460442 1208970106 1299468174 1325294596 1134189831 474857540 643093132 CTP N/F N/F N/F N/F 11184952 13454826 9630586 12219895 12855373 14027421 13972746 8768124 9663543 9693179 13957022 18424620 10885023 13046410 11354797 3128880 731463 992731 cystathionine N/F N/F N/F N/F 22768982 20265589 27468748 27172931 28370147 28793607 24988182 27275925 28494692 27886978 32407442 36279080 26207532 28465395 28518695 9295136 2778235 3376399 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 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 N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F 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 N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F cystine N/F N/F N/F N/F 1619765663 1751080018 1036132667 1093344621 900105321 1041340754 1145535802 991035669 1078612992 986663448 690903361 939963611 903428654 1377832577 1069346380 489844708 141115773 217453139 cytidine N/F N/F N/F N/F 19513752 19385751 5850872 7142574 6795027 8272796 35048229 32840435 33880454 32602422 4534418 5471883 17308576 19319172 17734847 6244270 1335056 2000919 cytosine N/F N/F N/F N/F 3464760 5578191 6381330 6501803 8167353 7877326 14414637 6782436 5061059 7422988 5909828 7407094 6593012 5319161 6596354 3419278 1893234 2948187 dATP N/F N/F N/F N/F 1773830 2149283 2681339 3215716 3000971 3557817 5031331 3289024 3198027 3781018 2723234 3960058 3302319 3295386 2927127 762719 90908 115210 dCTP N/F N/F N/F N/F 272304 402621 602798 632913 670683 809826 843587 577383 515500 577929 589971 1014276 514424 683289 633072 108214 N/F N/F dCytidine N/F N/F N/F N/F 9654261 9716316 6637001 10671245 9384545 11008240 11020211 10749254 10617241 15152851 8333417 10941644 11712276 13490145 11893095 6397232 1976446 2746980 dihydroorotate N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F 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 N/F N/F N/F N/F 15106279 12331925 22693108 17843839 19864666 17757389 19516308 27076406 31117987 31546835 23626613 26939776 20447164 23226340 22830173 7761916 1703965 2533517 dimethylglicine N/F N/F N/F N/F 70050267 87944688 63651343 49698065 82960875 65642223 58547742 62523485 77162709 66435940 54833227 61000942 56361071 68806758 56347984 27167846 9482696 12826457 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 dTTP N/F N/F N/F N/F 603346 549901 137386 115505 242802 402144 479794 225590 205925 457737 283676 408864 170097 382858 279181 621810 644187 1185687 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 238297 327085 N/F N/F N/F N/F N/F N/F erythrose_4-phosphate N/F N/F N/F N/F N/F N/F 1038692 1021224 802792 1008294 1451797 1028000 1021217 702896 557224 929037 N/F 885586 918546 339833 N/F N/F F6P_G1P N/F N/F N/F N/F 12559561 13188804 14071038 16226910 13365045 14219425 20391567 18705951 16737268 17268859 11676203 13750452 14036028 16375468 14758203 5097345 1766147 2282655 FAD N/F N/F N/F N/F N/F 933177 N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F 102926 folic_acid N/F N/F N/F N/F 28111495 28758235 24625060 26411073 26273330 26502333 22757361 28042400 34232498 24878553 26601063 28089180 25833791 28977607 25133156 9546434 3239137 4391560 formyl_methionine N/F N/F N/F N/F 2528391 2616673 3646838 4439589 5414530 4805056 5442820 5484838 5258029 4441616 4367090 4684051 4078984 5258990 4252025 1628327 378984 666847 fructose N/F N/F N/F N/F 52664014 44810871 56291654 47507454 52322086 48686050 50905853 60041993 65629420 52957237 53481359 63112456 56514783 61632007 42738115 15168747 10237405 10553497 "Fructose 1,6-bisphosphate" N/F N/F N/F N/F 17269611 19467325 28224614 31168200 39825742 36609386 63516788 60076861 61703434 57040329 34564716 35540037 39506146 37549519 42154855 10288174 2502957 3232252 fumarate N/F N/F N/F N/F 20102140 21922265 34982028 35209400 50445150 48555795 30353805 40494464 43569972 33012051 51028225 53478040 38379967 43137614 35633629 17451226 5560588 7981167 gamma-aminobutyric_acid N/F N/F N/F N/F 118024263 132559733 107000400 139697837 138701738 141228994 196395204 176154138 153222516 166913479 134687897 148489685 146253044 157237976 148787177 53222147 13877407 22027657 gamma-glutamyl-alanine N/F N/F N/F N/F 10799375 15949187 12459169 14772605 14633373 12869618 8117354 5766208 6275993 6145788 4758099 5779385 6348603 5877126 7884373 3862622 1127304 1705867 GAR N/F N/F N/F N/F N/F N/F N/F N/F 297603 246561 N/F N/F N/F N/F 794209 936318 141353 184865 247579 39511 24018 23872 GDP N/F N/F N/F N/F 1489703 1918738 1519119 1698516 1691871 1704437 2971938 2058604 2355180 1912923 1726931 1769706 1766073 2132313 1840728 677367 209139 259186 glucose N/F N/F N/F N/F 399248591 346167693 305942322 307645378 261101235 310157288 251182003 370470626 323100689 332397068 385857557 341402185 288400838 440027583 319838185 167740743 74732895 99889496 Glucose 6-phosphate N/F N/F N/F N/F 11594037 11902126 18788938 22289542 19590606 19368562 24555543 21923090 21251361 21078514 15882506 19562417 17620615 19820439 18967052 6759832 2132636 2691536 glutamate N/F N/F N/F N/F 1491984870 1638675929 2138340240 2316587751 2344069569 2249458287 2077690678 2152254064 2249050014 2129126902 2316438401 1861572358 2036420150 2260101706 2076957055 913443083 367766509 464586400 "glutamate-13C5,15N" N/F N/F N/F N/F 7008775 7166251 6592324 6852327 6555202 6562938 5095262 6806697 5538665 6574433 6840740 4320066 6484992 6722319 6796975 2454073 923873 1399539 glutamine N/F 4061536 N/F N/F 15803300027 15803358006 13547244232 14961470537 14911621200 14987190993 12885013785 14744029643 15457365896 13989724740 14114594548 13486093143 14519170884 15472840011 14998315697 7493421839 2966509124 3861915297 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 N/F N/F N/F N/F 349979777 428086816 282768226 315684987 318384837 384486163 333090312 350475796 369172492 365709861 280926088 324145471 366010301 393679653 350244399 120294189 40480985 49644521 Glycerol 3-Phosphate N/F N/F N/F N/F 9517347 12191438 23914663 29022133 24050733 24026541 21966162 23460167 23196900 23107365 22882765 22071832 22257509 23532949 19414334 8682196 2823529 3275072 Glycerophosphocholine 195073 1545829 N/F 135458 6421819313 7078918174 7172260747 7310167280 6308772663 6618606697 10012360484 9436513420 7013439849 8656275650 5348040028 6271578419 7411421365 8659106331 7218114895 2064974009 701886448 915856723 glycine N/F N/F N/F N/F 71127196 70658388 62801920 76391264 67782884 68798518 59042651 66265617 68563288 66749144 66122740 66992176 66452856 79855805 68521170 24968558 7139644 8844280 glycine_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 GMP N/F N/F N/F N/F 802770 874625 511037 589325 597171 615334 1150761 936264 897602 915439 623381 683610 745954 976115 720647 256043 66443 115724 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 GSH_13C2-15N-Ellmans N/F N/F N/F N/F 3535229 4581920 N/F N/F N/F N/F 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_Ellmans N/F N/F N/F N/F 103195031 163977545 554155089 476707253 686394356 615260930 549019960 463544803 469061869 459266639 633832000 646256377 486282097 463797097 446242368 156765538 25197657 37160089 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 GSSG N/F N/F N/F N/F 18984052 22289172 6494487 15004824 19335385 16173765 7739935 6777544 8757253 4948485 4762796 8229227 9996160 12321416 10911537 3076358 747455 1013623 GTP N/F N/F N/F N/F 21973226 28193238 11380201 12784339 11683341 13272999 23235553 11194650 13374992 12288283 10017299 14591024 13170419 14647042 13084876 3662136 813063 1390313 guanidinoacetate N/F 47435 N/F N/F 10291596 12237749 10226674 9771651 11679212 10545199 7659309 12601839 11816072 11154889 10549115 10810972 10996759 10732137 11765816 5688468 1882911 2486602 guanine N/F N/F N/F N/F 9171802 10756636 12684401 17220296 5774363 6069522 16242771 15794038 14401371 21748253 3793913 2442425 13987367 9987677 11851478 7608290 2471445 2278783 guanosine N/F N/F N/F N/F 3017181 2046817 1220681 1248124 566606 871217 3047999 3115272 2216617 4503238 N/F 344573 1778512 1353588 2172246 623947 N/F 165324 histidine N/F N/F N/F N/F 6159345367 6499017661 5216474019 5122292714 5390883245 5704307073 4632893912 5263220297 6804747348 5889817648 5383874338 5510490983 6076900875 6185566709 5852338187 2960556013 1156628237 1512448585 histidine-13C6-15N3 N/F N/F N/F N/F 126793273 141861224 124640404 118115629 125040039 132843331 99295084 125775787 103411154 103454773 106968846 114063481 117515905 137115453 116696212 51262590 21202258 22721892 homocitrulline N/F N/F N/F N/F 20617206 23312182 19729627 19955178 21487662 21130823 18458447 24117637 25686568 22138924 21799349 19819347 20501421 24081061 21603456 10217745 3204684 4599023 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 227824083 192444759 217641946 165966569 163983275 190107363 180391484 182282597 167503536 181471840 182934683 182613431 183153842 192989228 193854213 127569452 50433415 65145692 hypotaurine N/F N/F N/F N/F 81384017 64778354 78326077 72986139 63094874 57979069 46616886 52469146 54458844 59625822 85524424 80280662 67524523 69397888 70567993 25884841 7094089 8656506 hypoxanthine N/F N/F N/F N/F 321854363 256391028 144650958 195658652 21783392 26330321 121237024 160099983 92340246 203521988 6719019 8030981 127209539 140930307 136248633 78181286 29958019 34427099 IMP N/F N/F N/F N/F 2806714 2343280 2371770 2280873 3473024 2706543 3842108 3462173 3522877 3587161 4182397 4380343 3365149 3351503 2801207 1160702 259425 288554 indolelactate N/F N/F N/F N/F 998031 387382 264340 755134 940285 798727 699881 1042551 1284838 840997 856861 1016635 796052 1085476 409273 526895 N/F 281129 inosine N/F 110802 N/F N/F 27726287 27285027 4199187 7864167 1691185 2032759 11287459 13881900 17669665 15026070 687695 937845 11518095 12155894 11235610 3988567 1095508 1512141 isocitrate N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F isoleucine N/F 520395 N/F N/F 6081114796 6714240043 5578027463 6989769138 6028419373 6478018137 5905705301 6818417479 7866982892 6362219836 6795332660 6421137060 6563690815 6931787979 7119534080 2460182374 735445877 940381737 Isoleucine-13C6-15N N/F N/F N/F N/F 55281025 63705335 55235995 68150734 57066230 61872064 52740778 58167571 55829523 53246577 62159268 56668661 58719809 59599906 62949317 23653348 7613077 8659957 Itaconic Acid N/F N/F N/F N/F 2135636343 1966716856 2033354846 1896782696 1609232848 1667834696 1686211226 1598811101 1769045821 1958924157 1898807003 2211824782 1742229850 1986685127 1890470445 791693144 299351998 470661951 Kynurenic Acid N/F N/F N/F N/F 13507988 15569327 15835222 17156939 21046918 19975262 20256858 22758636 24306452 20462517 21333712 22128653 17604509 18118433 15700250 10062450 3169248 4479395 kynurenine N/F N/F N/F N/F 114849612 111799166 106206523 104982805 110463891 108362273 101815278 115378307 129964093 111414541 113249216 129630774 114169427 126256493 114480173 39096724 8302111 10847821 lactic_acid N/F N/F N/F N/F 11630800073 13508506561 13515222274 16285671715 19340989052 16679520269 15643463897 21332547417 26470453298 19056898941 18867695208 16076964863 18879955275 18920186683 19041447850 7668187641 2438677620 2732787441 leucine N/F N/F N/F N/F 7903240624 7909223341 6560121363 7582679664 7352140680 7185880749 6381870301 7758876490 9074614971 7498717351 6977873887 7978675553 7540566891 8265247568 7437104863 2780242453 740918325 882354372 leucine-13C6-15N N/F N/F N/F N/F 67992525 73796982 63153020 76369736 68693318 70774629 56044072 66315928 60658959 63199993 61827358 69254124 66211835 72679263 66196228 27187132 7324328 8964860 lysine N/F N/F N/F N/F 2534311670 2503926208 2026772689 2269219395 2286645141 2183667165 2346199183 2484651418 2752357803 2286116372 2240115022 2487069337 2256204896 2558941807 2330528253 840765946 223356506 415281903 lysine-13C6-15N2 N/F N/F N/F N/F 26573987 27530482 22502999 26714080 24234181 25258512 24175443 25034755 21113940 24457776 23171052 26615140 23432545 25489087 24028133 8559059 2109090 3924859 malate N/F N/F N/F N/F 275009554 280183914 455939026 524248791 639054565 594933909 430275862 456485345 485586428 377801961 617909245 651845324 456924280 543954972 484196658 217750020 97588938 114949672 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 N/F N/F N/F N/F 3479962820 3213363168 2831531205 3294393587 3128456342 3043340539 2720764620 3369091542 3954561774 3455354819 3150612761 3324650782 3314166936 3361570733 3315247561 1583764231 449305341 566515603 Methionine sulfoxide N/F 342104 N/F N/F 397623406 424021468 284519452 299661969 308222912 363895357 340813081 353610799 410151330 333363182 274557431 334528681 362950449 409992194 376731824 102057173 21185844 34522375 methionine-13C5-15N N/F N/F N/F N/F 76479624 76693739 70103454 81941133 72304816 77674349 60267639 75876033 66311155 75166390 72737496 75086888 74902705 75017213 74474163 36165737 9334733 11530752 methylthioadenosine N/F N/F N/F N/F 64861821 72063700 184043884 174077412 284728027 262454505 377950500 413903141 492861298 378972618 413019957 421990382 219495620 235868722 242291234 110068025 42035045 50717622 myo-inositol N/F N/F N/F N/F 716312874 804626400 619029505 742169695 723339569 742224076 758221353 766790193 717670405 611765949 727525113 791061744 584280332 991049857 731124130 211618967 70292040 90116202 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-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-acetylglutamine N/F N/F N/F N/F 2542720 3055480 4122740 4653066 3991923 4104853 6367420 3958939 3123603 3895046 4536917 3091121 2998273 3734905 5778177 3764523 1312044 1200621 N-acetyllysine N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N-acetylmethionine N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F 487192 1004937 N/F 378083 863478 557781 N/F N/F N/F N/F 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-acetylphenylalanine N/F N/F N/F N/F 3810489 3858399 3877167 3988589 4377579 4817485 4641699 6194157 6852959 6041484 5827529 5500719 4720839 4497972 4469621 2172786 615237 773640 NAD+ N/F N/F N/F N/F 160987706 188594640 276076944 299790187 305185162 314645053 322054520 311580878 261297112 283870476 288011929 313962425 278986536 307232498 282476496 101833720 30516460 40847478 NADH N/F N/F N/F N/F 5528512 6142359 9815246 8633167 8732823 9809751 11837404 12377766 9776183 10778974 8152853 10504969 9163590 11620125 8302635 3535693 1167489 1728048 NADP N/F N/F N/F N/F 9297701 10949732 5991078 8066968 7724076 6739600 9288972 6650452 7898946 6837560 7889878 8786576 7194908 8885593 7515948 2486591 550609 737218 NADPH N/F N/F N/F N/F 18530921 21759088 4590319 4872798 4165750 4981401 2920988 3349510 2201775 3272829 3117168 3905335 5370037 7237589 5641331 1955801 571437 761498 niacinamide N/F N/F N/F N/F 1050456688 1098707900 1103793826 1249143403 1441282431 1342256655 854502010 1076288901 1145218751 832366311 913106912 1002276538 939021201 891815222 975619142 525213905 152215185 186956325 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 N/F N/F N/F N/F 4615337 4850934 5382537 7141789 6047351 6572837 12284536 11615804 9402490 8635032 4062715 5648864 6882620 6262049 6330069 3178406 1019723 1170702 ornithine N/F N/F N/F N/F 267743207 250416069 234472363 226744858 211397910 229193509 219750197 233850935 216472499 225712870 214750545 243445930 220436670 250851006 235343995 111618350 42349380 78180129 orotate N/F 457128 N/F N/F 3691439 2952155 26040884 17905201 56852784 47224956 4745803 5864096 7868429 6385057 53216778 52313042 26007090 24425034 24204244 14921789 4578191 7507142 palmitate N/F N/F N/F N/F 163106777 90498311 79484885 90088552 76425345 99751004 35523729 120352275 46001952 74821808 68302388 103401810 62911822 85205567 86036610 28315384 10105942 11207154 p-aminobenzoate N/F N/F N/F N/F 51576335 49209791 27542109 31992345 32652468 30870890 26508509 33126813 47618052 42221654 37522852 33883660 37354305 44150994 35992516 15581618 3715166 4589643 Pantothenate N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F Phenylacetyl glutamine N/F N/F N/F N/F 513969 1023892 1106739 1743759 1754528 1923831 4281305 3544466 2712664 3079552 3841752 3489117 1296623 1559242 2011162 243525 N/F N/F phenylalanine N/F N/F N/F N/F 1303465652 1361117364 1231549244 1279524361 1467393607 1149584836 1159679550 1225069192 1643652206 1417379003 1157401087 1489972117 1403160744 1479659473 1163790170 679494969 201541197 260455447 phenylalanine-13C9-15N N/F N/F N/F N/F 168047260 173116834 170745335 162239081 154416334 180154742 128208265 161128353 148348877 160297709 158290426 155346935 161630376 167096395 157998146 64811730 16832899 20663933 phosphocholine N/F 1524553 N/F N/F 13488224046 13905281436 16487417568 18127696766 18342723229 18457673963 17703096689 16109646800 15748010615 16519310060 17069149220 18093394553 16504965584 17499482828 16420593260 6734972413 1577019106 1989758203 phosphocreatine N/F N/F N/F N/F 1411962282 1595987496 1382407792 1574932368 1616756211 1538517168 1261224167 1281795797 1234696677 1254467465 1547142557 1546500628 1447004441 1503146408 1449313666 512459603 158988163 182717346 phosphoenolpyruvate N/F N/F N/F N/F 21811668 20316645 16879481 15077063 19041957 20876684 17161546 20263948 14723716 17835212 19947810 22447111 16915722 22171198 19116649 8167802 1514189 2951725 phosphoethanolamine N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F 137204 N/F N/F N/F N/F N/F N/F N/F N/F phosphoserine N/F N/F N/F N/F N/F N/F 3493109 3888217 4425359 3685337 1013553 1430395 1217614 1066274 2525718 3179973 1235123 1811169 1955461 920083 N/F 205895 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 N/F N/F N/F N/F 61068872 67392547 43433014 59845884 58579095 65085870 60686202 60789065 73383875 61817814 58357146 61775621 53908675 66386331 62774418 17059673 5196372 6776978 proline 1199954 2396796 N/F N/F 12556872868 13730820922 11164735379 11077863255 11656037348 12688402346 11844924907 12754071019 13031797943 12846342410 11025141586 12884117948 12241087737 12550708869 12421883548 5710439802 1815416672 2078356891 proline-13C5-15N N/F N/F N/F N/F 135992823 147557155 138313449 134996348 132119233 156615035 120531376 139615789 118824291 137064164 128594244 143313382 141124774 137020569 142167321 66310682 22959833 24656874 propionylcarnitine N/F N/F N/F N/F 193047933 179627653 252991404 289470297 300940070 294799385 252439000 282704635 307320983 319081209 281602025 323002326 255337245 267472330 270679430 149393357 61292303 72772570 PRPP N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F 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 N/F N/F N/F N/F 11395059 9928464 10467378 9366714 11074865 10570369 10250990 12427025 14013270 12370919 11917864 12221822 11378836 11048899 10721731 4989743 2117496 2587833 Pyridoxal N/F N/F N/F N/F 49525959 29769702 38648392 30114063 31007925 28129225 21450668 33512364 40113148 39395870 41950030 46710302 35660500 31939491 33157243 17002724 6269620 6373914 Pyridoxine N/F N/F N/F N/F 2355351195 2422298778 2158177597 2353839023 2528245430 2465720177 1963566174 2556803410 3056069705 2480291681 2615514191 2567056295 2407965099 2518848711 2386934816 1019191037 334059435 408425720 pyruvate N/F N/F N/F N/F 125875843 67248257 120767942 93444935 98045346 80274200 39983804 60605278 96608941 112627632 136101157 168329614 102566155 73594318 98332229 69279925 32057442 33510054 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 N/F N/F N/F N/F 13578071 12147575 4319487 4101986 4541534 4431783 4289895 4615039 5005237 4676611 4884436 5251178 5457313 6549747 5949672 1999080 607170 801826 Ribose_Ribulose 5-phosphate_3Me-Lys N/F N/F N/F N/F 13578071 14963942 4319487 4101986 4541534 4431783 4289895 4615039 5005237 4676611 4884436 5251178 5457313 6549747 5949672 1999080 607170 801826 saccharopine N/F N/F N/F N/F 856526 N/F 538079 596848 552055 N/F N/F 583838 742677 720963 725271 880051 745623 N/F N/F N/F N/F N/F S-Adenosyl-L-Homocysteine N/F N/F N/F N/F 6577054 5991670 6271591 6798900 6191048 7972271 6817405 5546465 10124238 5973807 7005658 8387660 7145062 7569210 7052428 1982138 419999 648007 S-Adenosyl-L-methionine N/F N/F N/F N/F 1054816013 1025216281 237189616 256483458 216221518 211411331 429304487 409612166 328486695 415414814 201453884 222771615 396927767 449486661 427463902 243084072 92310045 138208974 sarcosine N/F N/F N/F N/F 9275216 10759430 9822842 7486086 9747091 10907594 8384052 9190525 9086297 9762054 10249542 10057760 9688843 7700200 9198427 2313857 783592 921827 Sedoheptulose-7-phosphate N/F N/F N/F N/F 11219773 11408666 10298554 11136203 10358144 11702995 16630798 15377615 13792108 14368941 9739978 11732734 11292579 14250850 11737262 4215848 1233365 1929520 serine N/F N/F N/F N/F 373576569 356068064 294846075 360156062 347812689 331227073 278934710 366681139 372349174 341963005 336724815 327376649 321471804 395852621 347841239 125304081 32728809 44108756 serine-13C3-15N N/F N/F N/F N/F 1251561 1595385 1070261 1324613 1906129 787829 664925 1341020 917056 1333826 1187199 1154078 1811373 1308056 1537280 325582 123340 88049 S-methylcysteine N/F N/F N/F N/F 4342079 4020405 2561192 3584797 3550483 3583219 3042244 3713596 4710296 3528401 3733205 4149150 4145480 4125703 3774300 657537 113137 157994 sorbitol N/F 220889 N/F N/F 546814348 540721163 436737057 403080044 495148485 530370488 441763223 488921958 631531998 503281260 508678652 591840114 500631043 504911054 484257976 140083070 60508584 65722216 succinate N/F N/F N/F N/F 324854020 260719566 263949078 258700403 256448125 299249523 234567849 334385160 386768443 312293226 328971299 352698201 313753426 361751093 264547702 116827795 29043892 34528826 taurine N/F 1361484 N/F N/F 1301132924 1248826579 1194792089 1317284789 1407450720 1095696592 1204110774 1214739294 1239935887 1186395854 1317164989 1410939099 1235312455 1355051845 1298504117 538906383 178045169 215650406 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 N/F N/F N/F N/F 1464065910 1787252106 1376285211 1326013360 1169474645 1278074163 1534420746 1387675086 1444414008 1233204325 1191508072 1410507786 1318744888 1649843238 1372458803 525248002 136073826 163164672 threonine-13C4-15N N/F N/F N/F N/F 12802026 16220827 14103011 13225318 11490486 14359109 14181271 13209033 9681351 11194627 11177296 14429568 12736765 14983618 13462116 4700897 1547368 1610675 thymidine N/F N/F N/F N/F 704267 743734 413927 647168 513791 451967 523296 692183 681489 612105 308833 376244 510887 512969 596569 206054 87546 113162 trans-urocanate N/F N/F N/F N/F 150791211 97956474 99233929 103952402 110801741 117321978 91513174 114722562 137041728 124254462 123403104 111257953 114294591 117346733 117587165 51635627 14338329 18780739 tryptophan N/F N/F N/F N/F 1614343478 1582738856 1303855818 1557427586 1483478237 1410136026 1321489190 1610806674 1841353369 1581496338 1476752800 1559081468 1551637106 1666790710 1524195022 627379513 164463054 208186118 tyrosine N/F N/F N/F N/F 2815113446 2938268041 2468313005 2453573384 2800838643 2675529718 2396259949 3065915728 3275676482 2831706283 2463378673 2917210434 2718846353 2902543816 2813332306 1127585834 331315547 379384396 tyrosine-13C9-15N N/F N/F N/F N/F 49817240 57243914 53437207 51355290 54147320 56879761 43565161 56678285 47789071 52343001 47320762 56201231 51816336 53208592 54145368 20984199 5661307 6688990 UDP N/F N/F N/F N/F 2594190 3098618 3478950 3663364 5286191 5329788 5334153 4034492 5721321 3784704 6246243 7526480 4117021 5298303 4933767 1285918 374183 532248 UDP-GlcNAc N/F N/F N/F N/F 76786522 92976023 109895883 129629598 116889757 120273472 140074569 117616510 101058536 120535044 112059581 117372906 106058743 129739919 111810772 41535670 11528283 15950180 UDP-hexose N/F N/F N/F N/F 89594800 94692078 40504633 45778366 47525449 52467194 55859205 46791954 44270428 44715880 58231484 71255199 50779374 68852285 56426948 16488473 4921349 7782506 UMP N/F N/F N/F N/F 1321167 1496082 1071257 1115354 1373958 1283908 1541496 1371229 1495335 1262078 1574518 1605048 1234238 1638401 1395898 483996 122202 203844 uracil N/F N/F N/F N/F 26266877 27505689 21419888 25301933 22152403 21844690 17339087 28916979 36432582 26199415 23535327 22128878 21990434 38541811 26707038 9291504 2080943 N/F Ureidosuccinic_acid N/F N/F N/F N/F N/F N/F 3522462 1911751 13939742 13989515 N/F N/F N/F N/F 16445954 17496914 5040548 5223006 5368239 2265332 1337060 1587001 uric acid N/F N/F N/F N/F 203658019 205178351 166709238 145688625 176794105 200775868 163750600 178355445 227577241 180096673 183537234 213200086 188675509 196926346 183918741 76867924 35980618 44986403 uridine N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F 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 41117595 49667699 37199920 42492919 53626540 57233333 38885647 26231317 27694856 27232309 58548469 82055830 39400037 47411058 41003969 11253219 2793065 3811215 valine N/F N/F N/F N/F 2456368321 2415726663 1768564705 2140708507 1873433506 2053445643 2259711933 2203306335 3184791920 2507278811 2237739524 2438596351 2099376620 2429124590 2152970359 674140100 193799746 248150088 valine-13C5-15N N/F N/F N/F N/F 28898145 31258068 23200483 30164703 24914538 29157150 26227504 26164854 30237088 30236857 27423751 30006756 25443670 28240473 25637372 8056849 1639494 1576171 xanthine N/F N/F N/F N/F 120451849 114095015 114762718 102788852 122696789 122598568 100292173 108694348 137640875 126703173 120786431 137726662 129094563 128194253 119519067 56336106 26652416 31561097 xanthosine N/F N/F N/F N/F 1718514 1807194 1445503 1286812 1357221 1582128 1352731 1778476 1930864 1494381 1357407 1521330 1627853 1886045 1586023 493156 179836 215400 MS_METABOLITE_DATA_END #METABOLITES METABOLITES_START metabolite_name 1-methylnicotinamide "2,3-BPG" 2-aminobutyric_acid 2-hydroxybutyric_acid 2-hydroxyglutarate 2-oxoadipate 2-oxobutyric_acid 3-hydroxybutyric_acid 3-hydroxyisobutyric_acid 3-methyl-2-oxopentanoic_acid 3-phosphoglycerate 3-ureidopropionate 5-Hydroxyindole-3-Acetate 6-phosphogluconate acetoacetate Acetyl CoA acetylalanine acetylaspartate acetylcarnitine acetylglutamate acetylglycine acetylmethionine acetylserine adenine adenosine ADP ADP-ribose AICAR alanine alanine-13C3-15N allantoin Alpha-Ketoglutarate alpha-keto-isovalerate Alpha-Lipoic Acid amidoadipate AMP anserine arginine arginine-13C6-15N4 argininosuccinate ascorbate asparagine aspartate aspartate-13C6-15N4 asymmetric dimethylarginine (ADMA) ATP beta-alanine betaine biotin Butyrylcarnitine C5 Carnitines cAMP carnitine carnosine CDP CDP-choline choline cis-aconitate citrate citrulline CMP CoA-Ellmans Coenzyme A creatine creatinine CTP cystathionine cysteic_acid cysteine_13C3_15N1 cysteine cysteine-glycine cystine cytidine cytosine dATP dCTP dCytidine dihydroorotate dihydroxyacetone_phosphate dimethylglicine dTMP dTTP dUMP erythrose_4-phosphate F6P_G1P FAD folic_acid formyl_methionine fructose "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 guanosine histidine histidine-13C6-15N3 homocitrulline homocysteine hydroxyproline_gammaALA hypotaurine hypoxanthine IMP indolelactate inosine isocitrate isoleucine Isoleucine-13C6-15N Itaconic Acid Kynurenic Acid kynurenine lactic_acid leucine leucine-13C6-15N lysine lysine-13C6-15N2 malate mannose methionine Methionine sulfoxide methionine-13C5-15N methylthioadenosine myo-inositol N-acetylcysteine N-acetylglutamate N-acetylglutamine N-acetyllysine N-acetylmethionine N-acetylornithine N-acetylphenylalanine NAD+ NADH NADP NADPH niacinamide Nicotinic Acid O-phosphoethanolamine ornithine orotate palmitate p-aminobenzoate Pantothenate Phenylacetyl glutamine phenylalanine phenylalanine-13C9-15N phosphocholine phosphocreatine phosphoenolpyruvate phosphoethanolamine phosphoserine Picolinate Pipecolate proline proline-13C5-15N propionylcarnitine PRPP pseudouridine Pyridoxal Pyridoxine pyruvate Riboflavin Ribose 1-phosphate Ribose_Ribulose 5-phosphate_3Me-Lys saccharopine S-Adenosyl-L-Homocysteine S-Adenosyl-L-methionine sarcosine Sedoheptulose-7-phosphate serine serine-13C3-15N S-methylcysteine sorbitol succinate taurine thiamine threonine threonine-13C4-15N thymidine trans-urocanate tryptophan tyrosine tyrosine-13C9-15N UDP UDP-GlcNAc UDP-hexose UMP uracil Ureidosuccinic_acid uric acid uridine UTP valine valine-13C5-15N xanthine xanthosine METABOLITES_END #END