#METABOLOMICS WORKBENCH boryana_ptrva_20210222_181435 DATATRACK_ID:2506 STUDY_ID:ST001759 ANALYSIS_ID:AN002866 PROJECT_ID:PR001127 VERSION 1 CREATED_ON April 30, 2021, 4:41 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 I) PR:LAST_NAME Petrova #STUDY ST:STUDY_TITLE Application of the redox metabolite detection method for mouse liver 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 ST:EMAIL boryana.petrova@childrens.harvard.edu ST:PHONE 6173557433 #SUBJECT SU:SUBJECT_TYPE Mammal SU:SUBJECT_SPECIES Mus musculus SU:TAXONOMY_ID 10090 #FACTORS #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 liver in buffer B EXTRACTION BUFFER:buffer B RAW_FILE_NAME=20200715_QEF1_HILIC_mouse_liver_AW111; INTERNAL STANDARDS="aminopterin, isotopically labelled amino acids, GSH-13C2-15N-13C2-15N" SUBJECT_SAMPLE_FACTORS - B1- mouse B liver in buffer B EXTRACTION BUFFER:buffer B RAW_FILE_NAME=20200715_QEF1_HILIC_mouse_liver_AW112; INTERNAL STANDARDS="aminopterin, isotopically labelled amino acids, GSH-13C2-15N-13C2-15N" SUBJECT_SAMPLE_FACTORS - C1- mouse C liver in buffer B EXTRACTION BUFFER:buffer B RAW_FILE_NAME=20200715_QEF1_HILIC_mouse_liver_AW113; INTERNAL STANDARDS="aminopterin, isotopically labelled amino acids, GSH-13C2-15N-13C2-15N" SUBJECT_SAMPLE_FACTORS - D1- mouse D liver in buffer B EXTRACTION BUFFER:buffer B RAW_FILE_NAME=20200715_QEF1_HILIC_mouse_liver_AW114; INTERNAL STANDARDS="aminopterin, isotopically labelled amino acids, GSH-13C2-15N-13C2-15N" SUBJECT_SAMPLE_FACTORS - A2- mouse A liver in buffer C EXTRACTION BUFFER:buffer C RAW_FILE_NAME=20200715_QEF1_HILIC_mouse_liver_AW115; INTERNAL STANDARDS="aminopterin, isotopically labelled amino acids, GSH-13C2-15N-13C2-15N" SUBJECT_SAMPLE_FACTORS - B2- mouse B liver in buffer C EXTRACTION BUFFER:buffer C RAW_FILE_NAME=20200715_QEF1_HILIC_mouse_liver_AW116; INTERNAL STANDARDS="aminopterin, isotopically labelled amino acids, GSH-13C2-15N-13C2-15N" SUBJECT_SAMPLE_FACTORS - C2- mouse C liver in buffer C EXTRACTION BUFFER:buffer C RAW_FILE_NAME=20200715_QEF1_HILIC_mouse_liver_AW117; INTERNAL STANDARDS="aminopterin, isotopically labelled amino acids, GSH-13C2-15N-13C2-15N" SUBJECT_SAMPLE_FACTORS - D2- mouse D liver in buffer C EXTRACTION BUFFER:buffer C RAW_FILE_NAME=20200715_QEF1_HILIC_mouse_liver_AW118; INTERNAL STANDARDS="aminopterin, isotopically labelled amino acids, GSH-13C2-15N-13C2-15N" SUBJECT_SAMPLE_FACTORS - A3- mouse A liver in buffer C_Ellmans EXTRACTION BUFFER:buffer C_Ellmans RAW_FILE_NAME=20200715_QEF1_HILIC_mouse_liver_AW119; INTERNAL STANDARDS="aminopterin, isotopically labelled amino acids, GSH-13C2-15N-13C2-15N" SUBJECT_SAMPLE_FACTORS - B3- mouse A liver in buffer C_Ellmans EXTRACTION BUFFER:buffer C_Ellmans RAW_FILE_NAME=20200715_QEF1_HILIC_mouse_liver_AW120; INTERNAL STANDARDS="aminopterin, isotopically labelled amino acids, GSH-13C2-15N-13C2-15N" SUBJECT_SAMPLE_FACTORS - C3- mouse A liver in buffer C_Ellmans EXTRACTION BUFFER:buffer C_Ellmans RAW_FILE_NAME=20200715_QEF1_HILIC_mouse_liver_AW121; INTERNAL STANDARDS="aminopterin, isotopically labelled amino acids, GSH-13C2-15N-13C2-15N" SUBJECT_SAMPLE_FACTORS - D3- mouse A liver in buffer C_Ellmans EXTRACTION BUFFER:buffer C_Ellmans RAW_FILE_NAME=20200715_QEF1_HILIC_mouse_liver_AW122; INTERNAL STANDARDS="aminopterin, isotopically labelled amino acids, GSH-13C2-15N-13C2-15N" SUBJECT_SAMPLE_FACTORS - pooled sample QC a EXTRACTION BUFFER:- RAW_FILE_NAME=20200715_QEF1_HILIC_mouse_liver_AW127_pool1x_a; INTERNAL STANDARDS=- SUBJECT_SAMPLE_FACTORS - pooled sample QC b EXTRACTION BUFFER:- RAW_FILE_NAME=20200715_QEF1_HILIC_mouse_liver_AW127_pool1x_b; INTERNAL STANDARDS=- SUBJECT_SAMPLE_FACTORS - pooled sample QC c EXTRACTION BUFFER:- RAW_FILE_NAME=20200715_QEF1_HILIC_mouse_liver_AW127_pool1x_c; INTERNAL STANDARDS=- SUBJECT_SAMPLE_FACTORS - pooled sample QC 1/3 dilution EXTRACTION BUFFER:- RAW_FILE_NAME=20200715_QEF1_HILIC_mouse_liver_AW128_pool03x; INTERNAL STANDARDS=- SUBJECT_SAMPLE_FACTORS - pooled sample QC 1/10 dilution EXTRACTION BUFFER:- RAW_FILE_NAME=20200715_QEF1_HILIC_mouse_liver_AW129_pool01x; INTERNAL STANDARDS=- SUBJECT_SAMPLE_FACTORS - pooled sample QC 1/10 dilution a EXTRACTION BUFFER:- RAW_FILE_NAME=20200715_QEF1_HILIC_mouse_liver_AW129_pool01x_a; INTERNAL STANDARDS=- SUBJECT_SAMPLE_FACTORS - blank end1 EXTRACTION BUFFER:- RAW_FILE_NAME=20200715_QEF1_HILIC_mouse_liver_blank_end1; INTERNAL STANDARDS=- SUBJECT_SAMPLE_FACTORS - blank end2 EXTRACTION BUFFER:- RAW_FILE_NAME=20200715_QEF1_HILIC_mouse_liver_blank_end2; INTERNAL STANDARDS=- SUBJECT_SAMPLE_FACTORS - blank 1 EXTRACTION BUFFER:- RAW_FILE_NAME=20200715_QEF1_HILIC_mouse_liver_blank1; INTERNAL STANDARDS=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 Liver #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 liver in buffer B B1- mouse B liver in buffer B C1- mouse C liver in buffer B D1- mouse D liver in buffer B A2- mouse A liver in buffer C B2- mouse B liver in buffer C C2- mouse C liver in buffer C D2- mouse D liver in buffer C A3- mouse A liver in buffer C_Ellmans B3- mouse A liver in buffer C_Ellmans C3- mouse A liver in buffer C_Ellmans D3- mouse A liver in buffer C_Ellmans 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 blank end1 blank end2 blank 1 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:- 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 "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 2-aminoadipate 3031318 7161466 3348637 4285612 5042742 9386438 8103154 6787314 2235365 7684649 10421867 7538273 5737947 8975512 5713964 3626677 1242235 1928567 N/F N/F N/F 2-aminobutyric acid 6135126 12548966 9336314 6428620 13535794 15156927 10951936 15058603 3799729 6129266 22184755 15347053 6288843 12161755 12308635 3881525 1773288 2615237 N/F N/F N/F 2-hydroxybutyric acid 9790022 23752215 9134337 8599114 15754629 27938387 19968505 23929031 N/F 8645591 20656302 17773739 4890847 17628285 14815457 5783240 2398862 3313209 N/F N/F N/F 2-hydroxyglutarate 11795078 26723185 14560314 14597217 137699880 138417244 100981015 101609194 92647073 122912048 105284356 105888838 62511761 89171256 85395899 38534013 19140790 23334483 N/F N/F N/F 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 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 3-hydroxybutyrate 20939850 68437036 13616891 22045068 34167188 78083959 28757905 54175116 11178403 51508540 38744487 68569893 39911860 43139200 40061815 11565818 4285273 7991031 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 3-methyl-2-oxopentanoic 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 3-phosphoglycerate 1698187 4690411 1487338 2148294 3689077 6946808 4976957 10555958 1456305 5974058 12502259 10041837 4120089 5436626 5338978 1142045 261030 286962 N/F N/F N/F 3-ureidopropionate 3392349 10008576 5119689 1798921 5658581 10552871 10412087 5256527 1564918 6275417 16828125 6187516 5878767 6982767 6437579 2055402 715024 1150419 N/F N/F N/F 5-Hydroxyindole-3-Acetate N/F N/F N/F N/F N/F N/F N/F N/F N/F 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 496074 1170018 498084 544261 993160 1477110 1225744 1740632 265208 1053168 1812087 1453671 808835 1008471 1168068 284750 81082 56945 N/F N/F N/F acetoacetate N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F Acetyl CoA 6070167 14478798 8515191 5484283 11751365 18536259 15117586 10908870 4070885 13003350 28100801 14918396 10562542 11695349 12800132 3941579 1491848 2119983 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 acetylaspartate 794937 1308494 331388 591545 1156182 1351533 706448 1195960 418127 1010127 778349 1148821 761507 790407 843739 257038 38887 166658 N/F N/F N/F acetylcarnitine 928333730 1953615341 1046414009 985970850 1517162715 2311315679 2077480589 2421661442 480362748 1448662158 2878960124 2521341457 1471449075 1816762304 1705193448 593644820 242049002 343171941 N/F N/F N/F acetylglutamate 8760550 17744849 17072069 12772872 13007884 20319814 29585966 31142395 4566885 13875604 40753433 37550153 17333316 19365433 20973863 8003472 3006628 4840739 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 acetylmethionine 117859 404202 227443 249173 194586 513490 556262 874471 78823 365730 808829 843615 828859 502454 480227 87352 N/F N/F N/F N/F N/F acetylserine 2833785 6453391 2953272 2362674 4983874 5623768 4606476 5963026 917516 3669867 6828941 6553400 3857167 4690544 4244597 1476674 485053 762542 N/F N/F N/F adenine 18618171 28609509 16026376 7733861 51812554 74914672 52410363 62910046 14056561 48168581 99981293 52211528 42153476 49083548 53842770 13326795 5548845 6118644 N/F N/F N/F adenosine 131495081 39630959 57703224 34841483 67089784 8566223 1957589 1405698 43014301 136246653 291536796 229662971 176691613 95137791 68041165 44301487 24290086 37786566 N/F N/F N/F ADP 15616724 39064128 22324278 18954072 18941598 29775836 32385972 23779393 7080507 24853556 53940564 30824105 23528666 26160686 25882590 9085889 3605216 4322848 N/F N/F N/F 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 AICAR 259452 292772 133958 126563 338055 315594 340021 349212 73006 213828 583030 372029 231096 282739 272960 108298 33344 40935 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 alanine 162708525 138200048 79837441 45716849 288299647 171708259 150770513 160205776 103492752 119637187 187298397 160269899 125400463 137800354 144056362 47962485 18041394 26800852 N/F N/F N/F alanine-13C3-15N 378082 391930 540427 616027 215616 N/F 460620 294503 561328 287897 N/F 312751 208268 628015 337015 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 Alpha-Ketoglutarate 630397 1119118 682776 730857 4590855 5130015 5397011 4260296 5469563 5623597 4130696 4452340 4971067 4481250 3441082 1988311 N/F N/F N/F N/F N/F Alpha-Lipoic 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 AMP 77893532 205215849 101044275 95016984 87227258 175996075 160617812 186588297 30523208 124945402 217035213 216567388 122957558 134851190 131606346 51953368 23578496 31782523 N/F N/F N/F anserine 1131546 4592021 1260653 693961 3455009 6979377 5205315 5312313 2210196 3284135 9332436 5956237 3292794 4288910 4241813 581486 173635 230626 N/F N/F N/F arginine 33540393 22825089 19065100 23896141 18224361 19922231 6120616 20999006 23943326 46520145 64534460 73264411 22544067 34019248 33895926 13480282 5749016 6344114 N/F N/F N/F "arginine-13C6,15N4" 31886392 10766319 33165854 37560912 10634018 9086740 3875055 9496283 42160239 35098042 32310364 26872791 15925743 25761580 24384506 9536390 3426281 4211375 N/F N/F N/F argininosuccinate 1009516 5205794 1404443 1629946 2886352 6972686 3863625 8211000 588619 4460030 7193285 9146417 3774595 4796319 4842743 357039 N/F N/F N/F N/F N/F ascorbate 147587895 709402774 364070880 325620661 13098384852 12435490248 12289392419 12743844097 12545922751 12331010608 12505182000 12843096185 7344334899 9268948931 9371351927 4409122520 2319844489 2691077253 1317006 774827 N/F asparagine 5258809 10397571 4108991 4226367 9116093 11854844 7805908 11366745 3859207 8653758 12432987 13476282 7727346 8312827 9067053 3527228 1072768 1580012 N/F N/F N/F aspartate 22768838 34630158 24098764 20400986 23611974 28312855 22991252 26354338 7270297 16492423 25216975 20272755 17297404 18449183 18466552 10558987 4282361 5591845 N/F N/F N/F aspartate-13C6-15N4 1900406 1263764 1925286 2230087 938334 842108 716304 722078 907498 778229 471031 698274 705695 698669 751207 402916 147793 225842 N/F N/F N/F asymmetric dimethylarginine (ADMA) 9166739 21241512 9251605 9473824 19833944 24700885 16886338 24126511 4961673 14123193 21869382 21680607 12092586 17735905 14861493 4271049 2072326 2357172 N/F N/F N/F ATP 1904146 2928905 2924921 1999738 4077912 2892526 4669544 2528850 1267322 2738680 6691257 3439118 3023734 3275362 3079517 866130 259263 395126 N/F N/F N/F beta-alanine 11650163 13414001 8057699 4916525 16854515 18749299 15243520 13866066 5151847 13073733 20166486 16442286 11282755 13208818 13626110 3584100 1278603 1429761 N/F N/F N/F betaine 3165699315 6263764464 3616009381 2567461562 5366467830 7273095003 6722464472 6306248633 1393671847 4574736129 9543411255 6870949083 4317441587 5646496882 5251817481 1818707371 687685105 1050541721 N/F N/F N/F biotin N/F 12386 N/F 11389 111388 255153 N/F 148526 N/F 195317 49896 240828 47511 161675 116678 N/F N/F N/F N/F N/F N/F Butyrylcarnitine 295973291 427895805 177329084 251995506 590401769 717560737 228729661 253294046 77701883 176812404 278844425 411884961 247818964 305645377 301804935 106120261 43744816 58620218 N/F N/F N/F C5 Carnitines 31752615 44805351 21785754 16313394 66724521 62239966 35808152 22538368 11879244 22998317 51243855 36007814 29686720 35948006 34189930 12201864 4690358 6104971 N/F N/F N/F cAMP 303858 635077 312321 167633 523828 865104 921272 810057 113062 504126 1298345 925928 834119 648463 612055 120594 N/F 84351 N/F N/F N/F Carbamoyl Aspartate 76292 165980 124403 168035 N/F N/F N/F N/F N/F 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 1109804949 1849985643 921483118 708592657 1749825746 1913719224 1815714723 2193031475 553767086 1320097569 2950691927 2239336847 1204556074 1549225803 1573157264 509940426 203941093 316890759 N/F N/F N/F carnosine 929449 1519564 939590 905107 862585 1527120 1461024 1339508 1250280 1136816 2446570 1872418 1186489 1756561 1752067 350636 N/F N/F N/F N/F N/F CDP 38698 41117 61145 N/F 89597 22522 74702 N/F N/F N/F 89068 28236 N/F 56080 N/F N/F 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 choline 5431763 12328863 5515167 3123658 10301108 11414891 10782827 10855088 2071295 7442711 15762247 10741647 5566588 8252360 7703299 2191912 1068969 1707281 N/F N/F N/F cis-aconitate 328520 1140738 499529 318798 2384424 3218163 2491368 1486508 862144 997712 1435695 1469444 796035 1316133 1102060 N/F N/F N/F N/F N/F N/F citrate 1731264 16586785 2723883 3558873 11832879 27031894 14152734 34770295 N/F N/F 16499685 7933671 3817192 9653053 6802385 N/F N/F N/F N/F N/F N/F citrulline 17578285 31746299 20838242 18227460 29304319 41124246 37062157 35892543 12159191 33204360 48645635 42286688 27913382 33939380 32566002 12143810 3424454 5627794 N/F N/F N/F CMP 959040 1585000 996572 1084024 1322197 2101909 1710856 2676129 470807 1560111 2545575 2687089 1644361 1707060 1748646 638710 241981 292314 N/F N/F N/F Coenzyme A 4934439 16725180 8721191 6638921 20292186 20655304 17287091 24749971 N/F 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 612823308 1007480593 583560014 400856985 1094935552 1119117947 984335136 1172283248 365795704 812370177 1232441474 1135936109 623451711 860216882 833872399 318576623 141174702 211675319 N/F N/F N/F creatinine 13630295 29154228 17042927 9994397 24671296 35275155 34195361 30680924 7793539 17057502 50417410 26713569 21634483 24813845 23827373 7345420 2618027 4043880 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 cystathionine 3938264 2649632 2030910 1295319 6535967 3434137 3248743 4168516 2565537 2629486 6436138 4113127 2677133 3892260 3862953 973255 228905 220164 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 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 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 cystine N/F N/F N/F N/F 242522 196887 N/F 126980 N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F cytidine 935479 3048230 796166 1494450 1663381 4135161 1978774 3308365 571046 2411039 3206933 4826122 2465925 2450099 2242968 630562 163633 307499 N/F N/F N/F cytosine N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F dATP N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F dCytidine 2316971 1838977 1282295 669728 3430188 2481957 1333985 2108134 1721384 2093348 4335771 2711251 2742024 2763395 2706220 723233 272269 406602 N/F N/F N/F dihydrofolate N/F N/F N/F N/F N/F N/F N/F N/F N/F 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 N/F N/F N/F N/F N/F N/F N/F N/F N/F 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 1426212 4884194 1650098 1789056 2700345 4420415 2175521 3126360 266670 2483495 4679362 4110558 2137241 2976661 2735370 659731 224860 221973 N/F N/F N/F dimethylglicine 28549725 46740695 28861293 15293179 57176626 61254822 59234299 45282570 12868681 34417989 85477491 55167128 37328647 46638211 34773374 11738817 5053320 7249919 N/F N/F N/F 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 dTTP N/F N/F N/F 36373 141545 60488 43055 94814 874627 180608 15383 44833 79450 97621 94205 97197 N/F N/F 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 erythrose 4-phosphate 1268380 2239290 885706 596934 1592923 1649914 1416862 1156629 281143 1270475 2541781 1065518 1182954 1402421 1314843 442224 192659 170064 N/F N/F N/F F6P G1P 15377219 27945860 11543877 6331730 17179212 21417486 17221420 15927786 5026792 16234405 28827431 17078857 16344074 16662409 17117572 5809285 2362946 2996757 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 folate N/F N/F N/F N/F N/F N/F N/F N/F N/F 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 formyl methionine 527549 1314307 448221 402628 1211285 1298912 952060 1143628 N/F 554651 914054 823851 N/F 648804 603138 204091 N/F N/F N/F N/F N/F "Fructose 1,6-bisphosphate" 47679 327913 48537 332171 N/F 142920 N/F 511760 N/F 649107 1490799 1968609 461578 402240 509677 N/F N/F N/F N/F N/F N/F fumarate 5420293 13873640 9884187 13348858 15001829 20556855 16173097 30318751 8641184 14217901 15450252 21023908 10872260 15826364 15809051 5134976 1839880 2156818 N/F N/F N/F gamma-aminobutyric acid 6762759 16301610 7885933 4898513 11085417 15379285 16708844 10493616 2366746 11351619 23329502 10933695 8242986 11120661 12003075 2590208 878132 1401589 N/F N/F N/F gamma-glutamyl-alanine 1024762 1799914 963390 296837 1346397 2178713 1852958 1022097 576380 1668516 2369171 1283668 769596 1459694 1252336 364724 N/F 106613 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 74902 N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F GDP 610745 1804998 625875 364040 785205 493876 1235800 301301 265358 485868 1296821 571908 604604 749613 822073 154749 53510 72594 N/F N/F N/F glucose 49138344 74799871 45042465 28772988 54047609 67456997 52986737 45895294 13996760 40828543 65723750 51568650 43665528 41737240 44289535 18429940 9395970 11181706 N/F N/F N/F Glucose 6-phosphate 15377219 27945860 11475576 6195860 17179212 21401843 17221420 15914145 5014151 16166400 28802319 17078857 16173704 16645211 17117572 5809285 2362946 2996757 N/F N/F N/F glutamate 70307422 160864765 96097060 76865327 71731115 145412424 119685728 129747121 23162671 91591095 163873662 111213126 95527024 99024137 102296269 46650189 15753438 24813643 N/F N/F N/F "glutamate-13C5,15N" 2038150 1381045 1713274 2299037 1073895 1006039 736868 1083721 1137884 1060191 912452 698105 1003618 1044518 1082142 517747 169519 169568 N/F N/F N/F glutamine 1353493189 1787596272 940428237 799911692 2241645502 2243649457 1676944733 2045058445 1005589411 1599360956 2205989801 2261346691 1451604131 1633685616 1719849094 704661337 305565397 432451173 N/F N/F N/F glyceraldehyde 3-phosphate N/F 249674 63014 N/F N/F 214881 71854 N/F N/F 126712 206994 129776 54935 146689 98331 N/F N/F N/F N/F N/F N/F glycerate 69742155 70565840 74151136 73131307 11251648 11175042 11413941 13328846 24133212 22143951 22140180 21274847 28252771 32302250 33201209 10350810 3102684 5821719 N/F N/F N/F Glycerol 3-Phosphate 80222895 143886340 76777291 71374073 116467629 154270208 138768974 162208800 37672910 105383629 184507003 169011455 123366245 117958754 117493790 47225201 18546422 25181468 N/F N/F N/F Glycerophosphocholine 1311364561 2815614807 1248436224 809325854 2221672639 2632825172 2355777342 2386628849 615555311 1771295641 3358842232 2504048502 1508783462 1944527086 1908867319 681606499 276380702 420169864 N/F N/F N/F glycine 4949432 7209303 4645989 2789926 7290956 7849633 8204633 7740378 2163859 5185169 12329275 8092389 6120800 6412667 6090193 2115161 712205 1149008 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 N/F 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 9960651 21635043 10844246 11630498 14264133 26536834 19430749 25976486 5238857 19607566 30930561 28441134 18160218 19310678 19408277 6613871 2591796 3369662 N/F N/F N/F GSH 775647959 2097147379 1588186854 1016180492 2242854131 2106936553 2217259909 2311917269 153738 384979 769510 600039 636053 888287 1091495 315459 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 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 N/F N/F N/F N/F 38712941 148674621 349251390 197644331 107642681 127544884 121508873 30464277 7178485 11303195 N/F N/F N/F GSH-13C2 15N N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F GSSG 191361998 216264630 80264986 78812539 194265763 314637282 305821265 322484513 19315435 19896388 45936164 159460139 166004013 187711018 173491907 51854577 20909826 21995968 N/F N/F N/F GTP N/F N/F N/F N/F 110372 N/F 41567 N/F N/F N/F 88653 N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F guanidinoacetate 6292970 7498177 5365061 2850621 9835950 8312174 10755275 7583401 2983453 5358374 15035588 7825889 6337730 8084956 7573875 2571333 858295 1265792 N/F N/F N/F guanine 2215242 4408276 1741310 1710574 4650866 4928860 3145194 3851933 1714605 3481750 6061640 5206584 2776748 4128496 4238235 1359691 581511 601433 N/F N/F N/F guanosine 3747140 8310564 2733088 2616724 7072815 9276845 5521767 6944610 2435766 5511657 9333092 8154924 4914143 6409890 6071475 1662513 613837 880962 N/F N/F N/F histidine 938070321 1830926511 774981755 656542129 1766880733 1884273130 1367275527 2096457078 628066818 1399832999 1952847200 2152361053 951039388 1472075121 1508590646 515681788 196059243 197047241 N/F N/F N/F histidine-13C6-15N3 36576135 40782499 39620904 37707769 37887759 35740842 35244317 39885916 49477026 40935997 32616985 39051244 24207254 37373940 40012701 13812490 5038602 4878744 N/F N/F N/F homocitrulline 2439577 4298638 2874059 2345699 3534025 4441644 4545879 5216035 935208 2429146 6983376 6319640 2883639 3816502 3708548 1192568 331465 714961 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 hydroxyproline gammaALA 15379700 26249836 22641533 9667634 46190222 40019027 65588771 42542819 16454373 29345423 83868364 48569396 32224765 37642722 37766290 12374549 4600975 6436495 N/F 32868 N/F hypotaurine 3862020 3401458 4046684 1799972 8303221 5247326 9073748 5473481 1266799 1917121 6123973 2523894 3838395 4602696 3975939 1544091 465643 709632 N/F N/F N/F hypoxanthine 288421903 378680410 168736603 139852903 495075069 482537160 319618667 438472547 161729695 292842469 473075263 384163067 309949097 358611842 355111221 137290506 52788200 71618411 N/F N/F N/F IMP 31401182 41025995 12231485 11200419 49494118 46960599 21302316 32285770 15924528 34636444 35270927 30923807 29379440 31061220 29520326 9938144 3991616 5071952 N/F N/F N/F 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 inosine 193949421 205608417 81567740 64682599 295626720 206747333 141176900 190089026 109632964 134214125 203445543 162025518 128230971 184409640 176487242 67442623 26701192 31502366 N/F N/F N/F isoleucine 44177587 92980694 26524716 38828488 77962687 116430883 61424180 128493159 22129338 74732234 85531069 138936173 84548391 77228363 70717993 21768225 10464620 14049529 N/F N/F N/F Isoleucine-13C6-15N 7633862 6483161 7548291 7596165 5508059 5797334 7206783 6463514 7413530 6444154 5881204 7430737 7222858 7129007 6782145 2532424 1007909 1421810 N/F N/F N/F Itaconic Acid 4834515 13476215 3550190 4570693 86941373 89028724 59871479 59476613 66442491 73027644 68829600 64452819 41512019 56289001 51800748 23355974 12946678 14784755 N/F N/F N/F Kynurenic 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 kynurenine 691832 1226774 565691 615099 2269904 2215919 1424072 1435648 862516 1772048 1963457 2326714 1608199 1462216 1494628 446292 167538 210715 N/F N/F N/F lactatic acid 1633706084 2307487313 1171239439 727784842 2477752918 2344470283 2109476093 1929801338 773539088 1603949773 3165522878 2121910062 1742468970 1968130158 1809957820 643338278 213986343 349395431 N/F N/F N/F leucine 73558375 177981749 51304347 68900493 115146312 193951965 100324775 186509731 37612913 129068869 154250815 232196676 142463859 126811362 126251737 42472947 17036477 24669667 N/F N/F N/F leucine-13C6-15N 8043146 6920755 8329211 8028721 6534660 6597445 5843393 6055278 7414441 7811885 6644123 7567199 8587473 6731024 7385602 2356241 938078 1649492 N/F N/F N/F lysine 72481199 122086196 49611810 59825412 122283592 158502719 92434086 171426304 35621596 102918913 161938790 169061582 96597555 116968459 116335890 38116078 14502322 18143436 N/F N/F N/F lysine-13C6-15N2 2960142 2425225 2667271 3061750 2647756 2515433 2011956 2451740 2645651 2624059 2589689 2425936 2213997 2771722 2769822 873764 241049 301559 N/F N/F N/F malate 67151003 153134515 111822590 140939568 147630259 192768238 145759172 302834003 69729975 153992175 163230677 246591817 117063750 181393017 156675442 62615478 16920757 23353148 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 methionine 28951125 55876910 24780442 26893777 46510970 66193691 58025580 75500218 15826496 43608196 75833650 89636901 60962782 51294174 50603894 18343300 7848918 11635397 N/F N/F N/F Methionine sulfoxide 1500617 986090 1004638 408145 850474 884106 1421281 1064232 340548 647613 2292139 940393 933122 927791 1063546 228042 N/F 86184 N/F N/F N/F methionine-13C5-15N 9558288 8394565 10226664 10588437 8204265 8415966 8522604 8280550 10119718 9085468 8197047 9475369 10686225 9645789 9361364 3204851 1365944 2033448 N/F N/F N/F methylthioadenosine 1153739 1736606 617257 947418 732077 2279150 1292546 2670328 178322 1218048 1988172 2939386 1538811 1502395 1767973 619887 415170 240695 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 N2-acetyllysine 2205140 4425301 1466322 1247458 4020405 5363436 5076578 6663595 1111504 3620189 7579303 6476180 3174302 4265274 3924544 941658 395706 548117 N/F N/F N/F N-acetylcysteine 119405 326132 130154 213626 388403 290384 369136 472764 N/F N/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 365012 N/F N/F N/F N/F N/F N/F N/F N/F N-acetylglutamine 73021999 93435581 55735042 31272071 113541732 111466083 93542131 81791866 39287652 81100303 141752351 90490674 67884191 89383246 84801968 29561932 11276152 15841890 N/F N/F N/F N-acetylmethionine 212584 519753 310031 285341 251957 545683 587356 874466 78197 365726 808824 843609 828853 502448 480224 93844 N/F 54591 N/F N/F N/F N-acetylornithine 1058257 1630501 1204330 518760 1737980 1832303 2728468 1790012 538319 1393114 3985867 2327775 1373258 1730465 2026947 412854 123293 137038 N/F N/F N/F N-acetylphenylalanine N/F 552479 313506 348189 N/F 700676 913117 1109320 N/F 507549 903331 1421667 1054372 524089 638861 175756 75130 197958 N/F N/F N/F NAD+ 124699164 192687553 124335889 64971766 160970402 177780801 201632204 113292955 52450733 132611707 284578135 150701070 133441794 140456421 146021714 52747861 21953334 30205816 N/F N/F N/F NADH 7209997 16327536 5337637 4501956 11118688 14014397 10041959 8898254 1786559 9895008 13647025 18733743 8964024 9802881 9522059 3210266 1360549 1769262 N/F N/F N/F NADP 8780513 16764827 9144917 7818169 10082123 17797315 16962905 14141294 4797168 14498756 31546457 21007255 12943762 14350062 14833406 4992036 1840607 2075542 N/F N/F N/F NADPH 1343638 1936256 1370056 2146620 1296300 978374 421567 1050387 859089 4475451 1969508 2932521 1998601 1998830 1465286 463339 154474 191428 N/F N/F N/F niacinamide 523290830 1313293333 695585063 741416383 1555955203 2238957056 2148131858 2867840941 574426005 1268296798 2013571140 2673742315 2070879009 1577670788 1571687187 546871732 228046988 379008130 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 O-phosphoethanolamine 5521915 12409932 5873107 4357170 8009703 13582830 10674213 10748149 2539364 9524312 15749943 12462123 9464298 9717258 9599758 3282456 1204289 1694940 N/F N/F N/F ornithine 17387548 29304953 16565496 14772450 28970972 37273931 24791561 34913681 10304305 26059356 39568634 32914232 21259974 28945116 27086141 9974684 4689075 5321460 N/F N/F N/F orotate 390337 697476 454319 289601 609832 722097 922659 1057801 103885 245338 778446 605893 420749 610510 550042 172273 N/F 139354 N/F N/F N/F palmitate 8893596 21637764 9888716 17455482 26312946 37969773 29932454 54020303 10378599 20087610 21171855 49115117 N/F 29665976 21579315 10403794 5906990 6554899 N/F 5527993 N/F p-aminobenzoate 642021 743045 761750 333659 999738 907618 1318849 1359687 362336 635351 1668189 1234642 1092202 874846 882286 N/F N/F N/F N/F N/F N/F Pantothenate 20255003 51693101 22607827 23863468 37921566 63496584 46837353 67388394 13486986 49481000 88067616 91248458 59075196 56358179 56427977 17740929 6606046 9209176 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 phenylalanine 140115563 309159885 100088728 107734911 238300265 351390095 237786798 326597501 85990444 269452932 387183725 435987023 347424233 247792221 246587376 80745049 30673490 46758716 N/F N/F N/F phenylalanine-13C9-15N 19937126 18889380 20774364 20795624 17676363 18664675 18442531 18563160 23972377 22136444 21010065 22894770 28678577 20560324 20935650 6165420 2479917 3675426 N/F N/F N/F phosphocholine 978799443 1664013377 925937560 814706213 1833315052 1772796515 2082284978 2707651323 372699525 1077172561 2663080330 2487418675 1314414740 1614822273 1524934221 389655208 97585987 169611835 N/F N/F N/F phosphocreatine 2277613 3822084 2097407 1449256 3091612 2832166 3432639 2041830 670067 1883305 6975399 3181091 2606970 2878396 2800383 796322 233211 468895 N/F N/F N/F phosphoenolpyruvate 167983 691172 167470 182480 401527 890233 675946 1366125 97052 335317 1057637 870619 283321 567320 557931 57482 N/F N/F N/F N/F N/F phosphoethanolamine 5377251 12408534 5340860 4534034 8553202 14210743 10351713 11069062 2789018 9572841 16902153 12063395 9506255 9731782 9551518 2969685 1058423 1390440 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 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 Pipecolate 15293256 26199973 12970018 9020636 27323414 29082613 29674336 28298949 6369808 17497188 44366328 32569777 21927683 23637538 20984415 5655802 2749704 4057276 N/F N/F N/F Piridoxine N/F N/F N/F N/F N/F N/F N/F N/F N/F 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 192215964 377003222 131404366 143066970 333563252 465247794 292658495 475587465 86483820 281367665 491761094 518682906 270649084 325884860 293925688 86395131 32279994 48554690 N/F N/F N/F proline-13C5-15N 27460532 26219248 27950451 28024761 24647795 27133224 23562819 25505109 24893421 26368230 26239106 25716328 23391807 27263657 25406401 7756058 2948257 4299987 N/F N/F N/F propionylcarnitine 98164204 206774716 108394488 66414344 182519378 244568648 206062072 132673999 47821117 121269107 323913116 152506618 131787883 162371182 153186332 51032942 19229313 27370532 N/F N/F N/F PRPP N/F N/F N/F N/F N/F 4549 N/F N/F N/F 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 1971690 4260068 2015104 2106901 2642841 3616111 2381880 3402330 683507 2283900 3415688 3423527 2259352 2635708 2530628 1085234 437354 606346 N/F N/F N/F Pyridoxal N/F N/F N/F N/F 152013 164109 N/F N/F N/F 187637 577198 470083 313245 342227 384943 N/F N/F N/F N/F N/F N/F pyruvate 1295062 1387806 2105948 2059434 1262315 1482563 1116069 1609868 N/F N/F 1561369 N/F 1084873 2012499 2663671 919474 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 Ribose 1-phosphate 784891 1791931 746793 455462 1334773 1840061 1050037 1104183 353998 1124365 2337025 1233516 1009797 1179597 1049181 345894 111911 193235 N/F N/F N/F Ribose Ribulose 5-phosphate 346394 838476 365179 165477 558925 862519 575253 548840 116837 468918 2160255 622232 661556 708946 600278 182730 47743 92938 N/F N/F N/F saccharopine 371394 15907316 3662205 2379818 1389444 24708212 12232800 11247674 263414 14428900 25757685 13838764 8087732 9889666 9649618 1582917 495614 742430 N/F N/F N/F S-Adenosyl-L-Homocysteine 89329546 130164190 61679792 40697769 153610834 162639390 122111150 107263491 39187056 95725949 236491153 129675801 102815463 110147171 122826147 29887967 11875306 16033488 N/F N/F N/F S-Adenosyl-L-methionine 69189675 138072232 88953445 116361958 80899060 147198683 133118792 186619950 50470746 126134461 117483129 140328152 91317350 114276329 111990800 71018917 36594546 44641746 N/F N/F N/F sarcosine 4565813 3674672 3378457 1232727 7865108 6224580 6380833 3854641 1935922 2712019 14798439 6015999 3437879 4881397 5018804 827647 718219 597236 N/F N/F N/F Sedoheptulose-7-phosphate 7612934 16675308 7120304 5447760 11208449 16475741 11491082 11566420 3187652 11626519 16678542 12904652 10237114 11134860 11484567 3543250 1346540 1797714 N/F N/F N/F serine 4787927 8672189 3961410 4674606 6666061 9975028 7374942 12437570 2360414 7505203 10696860 13316146 7206543 7960834 7728779 2565873 786584 1257041 N/F N/F N/F serine-13C3-15N 238049 123533 219030 283163 197383 168929 155795 170928 236451 219067 125872 140913 197168 187942 170533 N/F N/F N/F N/F N/F N/F S-methylcysteine N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F succinate 34316727 110481062 46897733 35219923 48950156 113233694 91914177 83565225 10855202 70354416 145982339 99254319 68262347 78758765 74206086 23867700 7202977 11847190 N/F N/F N/F taurine 1672194336 2235221430 1476757154 1178008414 1377524352 1585989189 1597228612 1598256687 441194907 1074364963 2185460985 1714779446 1281394422 1313330892 1317213574 537080483 226534526 329237330 N/F N/F N/F thiamine N/F 12527 N/F N/F N/F N/F N/F 12317 N/F 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 24824927 65259176 20122647 20952208 46600228 81196082 51362370 86925100 11997449 47668084 72628492 94976554 49986417 47920005 45483320 12505979 3676066 5708060 N/F N/F N/F threonine-13C4-15N 2393119 2514256 2304702 2167669 2109721 2620519 2300793 2443174 2312074 2627610 2343892 2363673 2485592 2384382 2376370 711943 145982 289217 N/F N/F N/F thymidine N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F N/F trans-urocanic acid N/F N/F 4576106 N/F 6451639 5219644 4262334 4607766 2911161 9533738 2980439 4486886 4929141 4670876 4531772 1837352 518284 1504323 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 tryptophan 29341399 62368051 22485738 24218013 44892663 72822760 47177323 65729270 14709331 48479143 66465986 79018783 52576143 49597624 47592044 16301313 6605935 9388291 N/F N/F N/F tyrosine 43018566 96015895 31838914 38544575 73564246 118154658 73473401 122623463 22341887 75957465 109184024 120398293 78669100 79138701 77039280 25602362 10273123 14261358 N/F N/F N/F tyrosine-13C9-15N 8464922 7521038 8755414 9024151 7466510 7820564 7258473 7775569 7986858 8072303 7532236 7736981 8201169 8221971 7885162 2492559 921628 1312140 N/F N/F N/F UDP 8438451 23455975 15267255 11727816 15196686 26866400 28154802 29854030 4045329 17640072 43618155 28434723 19544022 21539790 20840999 7772473 3157812 3796806 N/F N/F N/F UDP-GlcNAc 14581431 28235195 15696079 13134853 25910337 31910535 28151517 32918024 7664299 21431787 40018862 32922188 24771886 25110471 24182601 9168319 4062529 5021039 N/F N/F N/F UDP-hexose 6010944 24587335 11728637 9997676 12136544 25872234 26442530 30729170 2875381 16322815 46113296 29982040 17528981 20311695 20143847 5696872 2116455 2773739 N/F N/F N/F UMP 49554308 98656432 48385800 49078364 64497492 97988607 81308077 100401366 20486863 69300998 125979214 100933301 68979911 78240974 74560750 26883149 10825821 13765999 N/F N/F N/F uracil 76745784 96367033 51014090 35767486 128942188 98928496 97928787 99698758 28863255 51008661 109311466 82819820 70949814 77401182 74850660 29210030 12974981 18497962 N/F N/F N/F uric acid 126988644 210659362 98704490 66428811 153986582 179442669 123181708 115248218 42845341 119213162 191840423 128401928 107748295 119254129 128189705 56759535 24768628 31950525 N/F N/F N/F uridine 3530771 4876948 2341347 1561999 6567038 4524462 4986107 5440896 893084 1654534 3848176 2814941 2987118 3063880 2962481 1231256 428414 794419 N/F N/F N/F UTP 142255 N/F 110549 N/F 888025 N/F 380723 N/F N/F 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 39245620 91605024 15443540 39753303 40912696 97431778 41788981 108999851 18413542 71495593 83764762 143605276 61648472 86926174 71865603 20849388 8371205 17271269 N/F N/F N/F valine-13C5-15N 3429909 3407301 3734165 3511199 3032793 3383648 3227530 3335806 3379845 3484816 3344999 3644532 3507378 3325485 3387309 985102 342718 553541 N/F N/F N/F xanthine 157669163 198268503 95146522 63398234 177539656 129640668 101440515 101682690 46090227 75851241 130334930 88780286 89603393 113208391 102278171 51291646 23421346 34721751 N/F N/F N/F xanthosine 12550825 11489171 4535903 2440919 18180541 10119824 7705845 6194315 5263573 6345274 11158385 6344237 7732685 8728225 8477715 3032191 1310055 1755598 N/F N/F N/F MS_METABOLITE_DATA_END #METABOLITES METABOLITES_START metabolite_name 1-methylnicotinamide "2,3-BPG" 2-aminoadipate 2-aminobutyric acid 2-hydroxybutyric acid 2-hydroxyglutarate 2-oxoadipate 2-oxobutyric acid 3-hydroxybutyrate 3-methyl-2-oxobutyrate 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 ALA 114 alanine alanine-13C3-15N allantoin Alpha-Ketoglutarate Alpha-Lipoic Acid 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 Carbamoyl Aspartate carnitine carnosine CDP CDP-choline choline cis-aconitate citrate citrulline CMP Coenzyme A creatine creatinine CTP cystathionine cysteine 13C3 15N1 cysteine cysteine-glycine cystine cytidine cytosine dATP dCytidine dihydrofolate dihydroorotate dihydroxyacetone phosphate dimethylglicine dTMP dTTP dUMP erythrose 4-phosphate F6P G1P FAD folate 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 guanosine histidine histidine-13C6-15N3 homocitrulline homocysteine hydroxyproline gammaALA hypotaurine hypoxanthine IMP 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 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 pseudouridine Pyridoxal pyruvate Riboflavin Ribose 1-phosphate Ribose Ribulose 5-phosphate saccharopine S-Adenosyl-L-Homocysteine S-Adenosyl-L-methionine sarcosine Sedoheptulose-7-phosphate serine serine-13C3-15N S-methylcysteine 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 uridine UTP valine valine-13C5-15N xanthine xanthosine METABOLITES_END #END