#METABOLOMICS WORKBENCH kapitsinou_20210701_053527 DATATRACK_ID:2732 STUDY_ID:ST001865 ANALYSIS_ID:AN003024 PROJECT_ID:PR001178 VERSION 1 CREATED_ON July 18, 2021, 8:30 am #PROJECT PR:PROJECT_TITLE Systemic metabolic responses to hypoxia PR:PROJECT_SUMMARY Prolonged cellular hypoxia leads to energetic failure and death. However, PR:PROJECT_SUMMARY sublethal hypoxia can trigger an adaptive response called hypoxic PR:PROJECT_SUMMARY preconditioning. While prolyl-hydroxylase (PHD) enzymes and hypoxia inducible PR:PROJECT_SUMMARY factors (HIFs) have been identified as key elements of oxygen sensing machinery, PR:PROJECT_SUMMARY the mechanisms by which hypoxic preconditioning protects against insults remain PR:PROJECT_SUMMARY unclear. Here, we perform serum metabolomic profiling to assess alterations PR:PROJECT_SUMMARY induced by hypoxic preconditioning. PR:INSTITUTE Northwestern University, Feinberg School of Medicine PR:LAST_NAME Kapitsinou PR:FIRST_NAME Pinelopi PR:ADDRESS 303 East Superior Street, Chicago, Il, 60611, USA PR:EMAIL pinelopi.kapitsinou@northwestern.edu PR:PHONE 312-503-8710 #STUDY ST:STUDY_TITLE Systemic metabolite changes due to Hypoxia ST:STUDY_SUMMARY Prolonged cellular hypoxia leads to energetic failure and death. However, ST:STUDY_SUMMARY sublethal hypoxia can trigger an adaptive response called hypoxic ST:STUDY_SUMMARY preconditioning. While prolyl-hydroxylase (PHD) enzymes and hypoxia inducible ST:STUDY_SUMMARY factors (HIFs) have been identified as key elements of oxygen sensing machinery, ST:STUDY_SUMMARY the mechanisms by which hypoxic preconditioning protects against insults remain ST:STUDY_SUMMARY unclear. Here, we perform serum metabolomic profiling to assess alterations ST:STUDY_SUMMARY induced by hypoxic preconditioning. We discover that hypoxic preconditioning ST:STUDY_SUMMARY increases serum kynurenine levels and enhance kynurenine biotransformation ST:STUDY_SUMMARY leading to preservation of NAD+ in the post-ischemic kidney. Furthermore, we ST:STUDY_SUMMARY show that Indoleamine 2,3-dioxygenase 1 (Ido1) deficiency abolishes the systemic ST:STUDY_SUMMARY increase of kynurenine and the subsequent renoprotection generated by hypoxic ST:STUDY_SUMMARY preconditioning. Importantly, exogenous administration of kynurenine restores ST:STUDY_SUMMARY the hypoxic preconditioning in the context of Ido1 deficiency. Collectively, our ST:STUDY_SUMMARY findings demonstrate a critical role of Ido1/kynurenine axis in mediating ST:STUDY_SUMMARY hypoxic preconditioning ST:INSTITUTE Northwestern University ST:DEPARTMENT Medicine/Nephrology ST:LABORATORY Kapitsinou ST:LAST_NAME Kapitsinou ST:FIRST_NAME Pinelopi ST:ADDRESS 303 East Superior Street ST:EMAIL pinelopi.kapitsinou@northwestern.edu ST:NUM_GROUPS 2 ST:TOTAL_SUBJECTS 16 ST:NUM_MALES 16 ST:STUDY_COMMENTS N/A ST:PUBLICATIONS Accepted in Cell Reports ST:STUDY_TYPE Comparative metabolomic analysis of serum metabolites detected by untargeted ST:STUDY_TYPE LC/MS and GC/MS platform ST:PHONE 312-503-8710 #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 - 31 Treatment:Hypoxia 8% SUBJECT_SAMPLE_FACTORS - 32 Treatment:Hypoxia 8% SUBJECT_SAMPLE_FACTORS - 34 Treatment:Hypoxia 8% SUBJECT_SAMPLE_FACTORS - 35 Treatment:Hypoxia 8% SUBJECT_SAMPLE_FACTORS - 42 Treatment:Hypoxia 8% SUBJECT_SAMPLE_FACTORS - 43 Treatment:Hypoxia 8% SUBJECT_SAMPLE_FACTORS - 44 Treatment:Hypoxia 8% SUBJECT_SAMPLE_FACTORS - 45 Treatment:Hypoxia 8% SUBJECT_SAMPLE_FACTORS - 37 Treatment:Normoxia SUBJECT_SAMPLE_FACTORS - 38 Treatment:Normoxia SUBJECT_SAMPLE_FACTORS - 39 Treatment:Normoxia SUBJECT_SAMPLE_FACTORS - 40 Treatment:Normoxia SUBJECT_SAMPLE_FACTORS - 47 Treatment:Normoxia SUBJECT_SAMPLE_FACTORS - 48 Treatment:Normoxia SUBJECT_SAMPLE_FACTORS - 49 Treatment:Normoxia SUBJECT_SAMPLE_FACTORS - 50 Treatment:Normoxia #COLLECTION CO:COLLECTION_SUMMARY Whole blood was collected in BD Microtainer Serum Separator Tubes. After CO:COLLECTION_SUMMARY collection of the whole blood, blood was allowed to clot by leaving it CO:COLLECTION_SUMMARY undisturbed at room temperature for 20 minutes. Clot was removed by centrifuging CO:COLLECTION_SUMMARY at 1,000–2,000 x g for 10 minutes in a refrigerated centrifuge. The resulting CO:COLLECTION_SUMMARY supernatant(serum) was transferred into clean polypropylene tubes and stored at CO:COLLECTION_SUMMARY –80°C until time of analysis. CO:SAMPLE_TYPE Blood (serum) #TREATMENT TR:TREATMENT_SUMMARY Serum was collected form mice subjected to 8% Hypoxia for 2 days (animal hypoxia TR:TREATMENT_SUMMARY chamber, Biospherix Ltd) and normoxic littermates. For The experiments of TR:TREATMENT_SUMMARY pharmacologic PHD inhibition, mice were treated with two doses of PHD inhibitor TR:TREATMENT_SUMMARY ( IOX2, 60 mg/kg by gavage, 48hrs and 6 hrs prior to collection time) while TR:TREATMENT_SUMMARY control mice received vehicle. #SAMPLEPREP SP:SAMPLEPREP_SUMMARY The metabolomic screening was conducted by Metabolon, Inc (Durham, NC). The SP:SAMPLEPREP_SUMMARY sample preparation process was carried out using the automated MicroLab STAR® SP:SAMPLEPREP_SUMMARY system from Hamilton Company. Sample preparation was conducted using a SP:SAMPLEPREP_SUMMARY proprietary series of organic and aqueous extractions to remove the protein SP:SAMPLEPREP_SUMMARY fraction while allowing maximum recovery of small molecules. The resulting SP:SAMPLEPREP_SUMMARY extract was divided into two fractions; one for analysis by LC and one for SP:SAMPLEPREP_SUMMARY analysis by GC. Samples were placed briefly on a TurboVap® (Zymark) to remove SP:SAMPLEPREP_SUMMARY the organic solvent. Each sample was then frozen and dried under vacuum. Samples SP:SAMPLEPREP_SUMMARY were then prepared for the appropriate instrument, either LC/MS or GC/MS. #CHROMATOGRAPHY CH:CHROMATOGRAPHY_SUMMARY The LC/MS portion of the platform was based on a Waters ACQUITY UPLC and a CH:CHROMATOGRAPHY_SUMMARY Thermo-Finnigan LTQ mass spectrometer, which consisted of an electrospray CH:CHROMATOGRAPHY_SUMMARY ionization (ESI) source and linear ion-trap (LIT) mass analyzer. The sample CH:CHROMATOGRAPHY_SUMMARY extract was split into two aliquots, dried, then reconstituted in acidic or CH:CHROMATOGRAPHY_SUMMARY basic LC-compatible solvents, each of which contained 11 or more injection CH:CHROMATOGRAPHY_SUMMARY standards at fixed concentrations. One aliquot was analyzed using acidic CH:CHROMATOGRAPHY_SUMMARY positive ion optimized conditions and the other using basic negative ion CH:CHROMATOGRAPHY_SUMMARY optimized conditions in two independent injections using separate dedicated CH:CHROMATOGRAPHY_SUMMARY columns. Extracts reconstituted in acidic conditions were gradient eluted using CH:CHROMATOGRAPHY_SUMMARY water and methanol both containing 0.1% Formic acid, while the basic extracts, CH:CHROMATOGRAPHY_SUMMARY which also used water/methanol, contained 6.5mM Ammonium Bicarbonate. CH:CHROMATOGRAPHY_TYPE LC/MS CH:INSTRUMENT_NAME Waters Acquity CH:COLUMN_NAME per Metabolon #ANALYSIS AN:ANALYSIS_TYPE MS #MS MS:INSTRUMENT_NAME Thermo LTQ-FT MS:INSTRUMENT_TYPE Single quadrupole MS:MS_TYPE ESI MS:ION_MODE POSITIVE MS:MS_COMMENTS Accurate Mass Determination and MS/MS fragmentation (LC/MS), (LC/MS/MS): The MS:MS_COMMENTS LC/MS portion of the platform was based on a Waters ACQUITY UPLC and a MS:MS_COMMENTS Thermo-Finnigan LTQ-FT mass spectrometer, which had a linear ion-trap (LIT) MS:MS_COMMENTS front end and a Fourier transform ion cyclotron resonance (FT-ICR) mass MS:MS_COMMENTS spectrometer backend. For ions with counts greater than 2 million, an accurate MS:MS_COMMENTS mass measurement could be performed. Accurate mass measurements could be made on MS:MS_COMMENTS the parent ion as well as fragments. The typical mass error was less than 5 ppm. MS:MS_COMMENTS Ions with less than two million counts require a greater amount of effort to MS:MS_COMMENTS characterize. Fragmentation spectra (MS/MS) were typically generated in data MS:MS_COMMENTS dependent manner, but if necessary, targeted MS/MS could be employed, such as in MS:MS_COMMENTS the case of lower level signals. Bioinformatics: The informatics system MS:MS_COMMENTS consisted of four major components, the Laboratory Information Management System MS:MS_COMMENTS (LIMS), the data extraction and peak-identification software, data processing MS:MS_COMMENTS tools for QC and compound identification, and a collection of information MS:MS_COMMENTS interpretation and visualization tools for use by data analysts. The hardware MS:MS_COMMENTS and software foundations for these informatics components were the LAN backbone, MS:MS_COMMENTS and a database server running Oracle 10.2.0.1 Enterprise Edition. LIMS: The MS:MS_COMMENTS purpose of the Metabolon LIMS system was to enable fully auditable laboratory MS:MS_COMMENTS automation through a secure, easy to use, and highly specialized system. The MS:MS_COMMENTS scope of the Metabolon LIMS system encompasses sample accessioning, sample MS:MS_COMMENTS preparation and instrumental analysis and reporting and advanced data analysis. MS:MS_COMMENTS All of the subsequent software systems are grounded in the LIMS data structures. MS:MS_COMMENTS It has been modified to leverage and interface with the in-house information MS:MS_COMMENTS extraction and data visualization systems, as well as third party MS:MS_COMMENTS instrumentation and data analysis software. Data Extraction and Quality MS:MS_COMMENTS Assurance: The data extraction of the raw mass spec data files yielded MS:MS_COMMENTS information that could loaded into a relational database and manipulated without MS:MS_COMMENTS resorting to BLOB manipulation. Once in the database the information was MS:MS_COMMENTS examined and appropriate QC limits were imposed. Peaks were identified using MS:MS_COMMENTS Metabolon’s proprietary peak integration software, and component parts were MS:MS_COMMENTS stored in a separate and specifically designed complex data structure. Compound MS:MS_COMMENTS identification: Compounds were identified by comparison to library entries of MS:MS_COMMENTS purified standards or recurrent unknown entities. Identification of known MS:MS_COMMENTS chemical entities was based on comparison to metabolomic library entries of MS:MS_COMMENTS purified standards. As of this writing, more than 1000 commercially available MS:MS_COMMENTS purified standard compounds had been acquired registered into LIMS for MS:MS_COMMENTS distribution to both the LC and GC platforms for determination of their MS:MS_COMMENTS analytical characteristics. The combination of chromatographic properties and MS:MS_COMMENTS mass spectra gave an indication of a match to the specific compound or an MS:MS_COMMENTS isobaric entity. Additional entities could be identified by virtue of their MS:MS_COMMENTS recurrent nature (both chromatographic and mass spectral). These compounds have MS:MS_COMMENTS the potential to be identified by future acquisition of a matching purified MS:MS_COMMENTS standard or by classical structural analysis. Curation: A variety of curation MS:MS_COMMENTS procedures were carried out to ensure that a high quality data set was made MS:MS_COMMENTS available for statistical analysis and data interpretation. The QC and curation MS:MS_COMMENTS processes were designed to ensure accurate and consistent identification of true MS:MS_COMMENTS chemical entities, and to remove those representing system artifacts, MS:MS_COMMENTS mis-assignments, and background noise. Metabolon data analysts use proprietary MS:MS_COMMENTS visualization and interpretation software to confirm the consistency of peak MS:MS_COMMENTS identification among the various samples. Library matches for each compound were MS:MS_COMMENTS checked for each sample and corrected if necessary. #MS_METABOLITE_DATA MS_METABOLITE_DATA:UNITS Peak MS_METABOLITE_DATA_START Samples 31 32 34 35 42 43 44 45 37 38 39 40 47 48 49 50 Factors Treatment:Hypoxia 8% Treatment:Hypoxia 8% Treatment:Hypoxia 8% Treatment:Hypoxia 8% Treatment:Hypoxia 8% Treatment:Hypoxia 8% Treatment:Hypoxia 8% Treatment:Hypoxia 8% Treatment:Normoxia Treatment:Normoxia Treatment:Normoxia Treatment:Normoxia Treatment:Normoxia Treatment:Normoxia Treatment:Normoxia Treatment:Normoxia 1-arachidonoyl-GPC* (20:4)* 2084194 2140221.75 1808815.25 1450876.5 2232387.5 1657345.375 1287738.5 3827081.75 2759397 3542242.75 2943209.5 2739263.25 2403906.25 3761476 2749210.5 2971130.75 1-arachidoyl-GPC (20:0) 110224.4063 44310.32813 71340.42969 109735.9766 97774.57813 266668.5 597943.25 85158.32031 81311.47656 1900085.625 151820.4219 148937.1719 1-docosahexaenoyl-GPC* (22:6)* 3865462.75 6117347.5 3856421.75 3285264 3804858 2543707 2459918 7260219.5 4160042.25 7186592 5394588.5 4730181 3381785.25 5461464 3420212.25 4153525.75 1-eicosatrienoyl-GPC* (20:3)* 364824.7188 320797.9688 211887.625 288666.0938 235062.9219 787013.125 1627996.75 2953364 2719580.5 1623236.875 1198517.25 2794404.25 1080399.625 1947544.125 1-heptadecanoyl-GPC (17:0) 349026.7813 675306.25 92184.50781 153915.9844 149396.7031 82272.32813 1237852.875 166799.8438 605046.5625 487535.7813 47321.23828 65618.14063 1663679.25 319562.5938 92119.39063 1-linoleoyl-GPC (18:2) 8653759 14904330 10954607 9158716 7346311 6939002 6383482.5 11840601 10289537 14402174 14696784 12453560 13498982 20964574 9317382 11557037 1-myristoyl-GPC (14:0) 161117.1875 499095.6875 245091.4531 169134.2969 202377.9063 121839.8594 82603.79688 323825.5313 255108.9375 355819.2813 311774.9063 171050.8281 195314.9219 557949.8125 142827.875 188950.1563 1-oleoyl-GPC (18:1) 2418135.25 3757840.75 1561287.25 1994542.25 2247355 1392400.125 1754602.5 6066679.5 2138430.5 5611005.5 6114801.5 1858590.25 2834686.5 7269970.5 4366289 3504670.75 1-palmitoleoyl-GPC* (16:1)* 500346.3125 982269.9375 564950 684036.375 487834.75 331404.6563 383399.5 1082473.75 638756.125 1347426 1109662.875 630369.4375 847394 1833404.5 588467.3125 877335.375 1-palmitoyl-GPC (16:0) 12414785 23683436 13197287 15006273 11641999 8971615 10530868 17766656 10270484 19711160 17613836 9187967 9807593 18868498 9989907 11294675 1-stearoyl-GPC (18:0) 6478152 16967702 3504575.75 6095740 5610078.5 3369410.5 3504686 12892090 5214526 15905241 13471343 3470815.25 2919193.5 23925718 6629315.5 4977523.5 2'-deoxycytidine 203252.5625 158838.3906 128103.0781 144919.0469 280135.0625 204143.9531 190690.5781 306692.375 148287.875 193526.0469 169630.4531 188182.1094 128913.6016 119058.6406 135060.0938 161908.0156 2-aminoadipate 353726.1563 544861.75 390142.4688 482464.4375 280720.6875 282280.9688 286461.3125 339529.3438 218464.8125 346997.2188 284553 322640.2813 229831.3906 277702.9063 266180.3438 311767.8125 2-arachidonoyl-GPC* (20:4)* 194208.5469 487741.375 373330.2813 153540.7969 243506.6094 160433.9063 618017.9375 369510.4375 923421.1875 654358.8125 332881.7188 208134.2813 784795.5 213426.4688 405777.2188 2-docosahexaenoylglycerophosphoethanolamine* 480768.375 533366.75 785274.3125 303077.9688 350025.1563 128146.5703 234020.3906 616374.9375 350266.5313 414497.5938 494421.6875 303326.0625 156218.0156 379662.75 287745.375 314792.0313 2-linoleoyl-GPC* (18:2)* 891141.25 1548498.125 971736.4375 749595.75 631752.375 657889.1875 401726.0625 1543264.5 1164658.25 2180509.25 2247964 1036438.188 1401578.125 2741720.75 1312836.125 1417457.25 2-methylbutyroylcarnitine (C5) 87808.29688 123979.0078 124266.3672 161880.4531 107479.2891 92356.60938 112854.6953 144649.3438 61229.49219 95983.47656 94629.85938 113648.3516 119565.1875 81759.21875 103122.3125 124570.0781 2-palmitoyl-GPC* (16:0)* 1758493.75 2883895.75 1834199.875 1222889 1512848.25 1027226.813 898059.75 3653334.75 1869321.5 4542629 3633204.5 1251589.875 1276849.625 1934916.75 1171691 1688051.125 2-stearoyl-GPC* (18:0)* 543702.0625 1070659.25 201746.7344 270582 418753.6875 98002.09375 212592.6563 1650945.125 330060.5625 1780750.625 1539752.75 135695.5313 114597.8906 3011382.75 615935.5 283906.3438 3-dehydrocarnitine* 1027399.25 920236.25 686799.5625 1308405.5 1783483.75 1429019.625 1882178.875 1820514.625 1372964 1913550.875 1327246.75 968857.4375 1632129.875 1685072.125 1451066.75 2029008.75 3-methylcrotonylglycine 67700.40625 112592.2188 104849.0703 96240.84375 41890.05859 34122.10156 43090.55078 67076.36719 28080.58789 26000.03906 41314.71094 71983.39844 31381.36719 28656.55859 28611.01953 54883.14063 3-methylglutaroylcarnitine (C6) 56008.66016 86507.39063 92819.89063 223610.4219 38565.62891 42483.08984 29639.16016 41053.5625 30984.6582 52067.30859 21989.32031 38705.32031 47712.76172 31265.50977 36747.19922 43093.26563 3-ureidopropionate 32751.58984 93169.86719 64497.80078 93957.70313 47966.44141 102289.7031 59852.85938 90713.78125 100709.8281 161317.9375 282530.7188 298920.875 200700.8438 168350.4063 144432.6094 173782.4531 4-acetamidobutanoate 39714.44922 47726.12109 31144.42969 32965.71875 27419.14063 26642.48047 53773.96875 42428.69141 20506.40039 37564.14844 47918.94922 21505.25 50360.10156 56042.94531 52283.67969 4-guanidinobutanoate 28566.60156 39940.44141 14108.48047 44370.28125 59428.58984 42610.35938 114081.3281 43093.51172 36048.03125 126946.6797 50247.30859 89620.65625 115568.5781 93127.07031 139627.625 5-methylthioadenosine (MTA) 56223.73828 53852.55078 51096.31641 90774.13281 42474.37891 45302.53906 52502.87891 32566.99219 47667.49219 55947.85156 38115.05078 46863.98828 42398.14844 45586.19531 38928.41016 37271.37891 5-oxoproline 1590259.75 1357682.75 1454435.375 1465421.875 1332767.625 1220104.75 1187251.5 1360341 1400476.625 1500155 1217559.75 1142320.625 1166792 1204256.375 1021168.563 1307738 7-methylguanine 92261.54688 92097.92969 39317.19141 63050.96875 56273.53906 58801.58984 34209.57031 36006.62109 102140.6406 37324.62891 40032.85156 37323.87891 74560.64063 67121.82031 37323.12891 85789.99219 acetylcarnitine (C2) 5331417 5711042.5 3787801.5 8938867 3480171 1221763.375 2145274 1686792.375 703711.25 1638032.875 233814.2188 482028.4375 438639.2188 276978.4688 195327.8594 424518.6563 adenosine 23358.82031 14106.05957 22282.32031 14698.74121 25279.26953 22078.63086 29769.56055 21806.93945 15335.04883 27839.19922 44081.35938 119429.0156 577649.8125 424953.1875 3631616 2119915.25 AMP 14893.61035 14185.84961 12778.40039 17936.07031 18923.93945 19223.69922 17470.08984 23312.25 744779.5625 538183.875 alanine 616470.25 553646.25 564523.75 639655.1875 959919.9375 881809.0625 988984.625 1489903.375 526435.875 708294.1875 566041.5 592878.0625 424153.5625 403908.75 498313.9688 460295.75 anthranilate 17103.51953 17446.9707 35023.80859 38285.39844 25442.84961 18406.83984 21288.5 42449.55859 16152.61035 34421.76172 19644.7207 20068.66016 41330.51953 35624.26172 34827.64063 arginine 606867.9375 571419.9375 585419.4375 704699 638724.8125 730021.4375 830995.75 763237.25 431560.0938 525316.5 376188.6563 467005.3125 380141.0625 355820.2188 331498.3125 478221.875 betaine 1374400.25 1130438.25 1113701.375 1569991.75 1412140.375 1182994.125 1099089.25 1278555.5 2176415.75 2451259.75 2133071.25 1481649.25 1388579.125 1187500.875 1582495.875 1757918.375 butyrylcarnitine (C4) 364692.8125 562097.875 459730.75 830263.5625 351362.5313 207688.4844 295817.0938 240090.9063 320559.3125 434709.9063 287128.9688 332198.625 237220.3125 203990.7188 189272.7656 345912.875 butyrylglycine (C4) 207255.6719 362249.875 319175.1563 401222.4375 143576.8125 104039.4219 125802.1406 152064.5938 198587.7188 170555.7031 255388.4375 173396.625 153489.2656 171242.4219 192340.3594 236541.2031 C-glycosyltryptophan* 50829.48828 62654.24219 62231.10938 58740.25 42126.30469 47012.37109 54973.35938 45553.67188 46194.53125 44809.26172 38275.48828 43452.64063 34740.37891 29426.00977 31770.11914 35565.85156 carnitine 4737347 3840802.25 3795539.75 2840287.5 4274756.5 3578058 3901349.75 3869391.25 4246473.5 4453113.5 4090309.25 3546581.75 3229761.25 3266134.5 3875650.75 4053002.75 choline 2354899.5 2402848.25 2456772.25 2452095.75 2015879.5 1930465.25 1920724.75 1913869.25 2342957.5 2121858.25 1879304.875 2088841.5 1722902.25 1832422 1663799.125 1732571.875 citrulline 433767.5 235112.4063 261701.7813 219323 445687.25 215179.7813 270987.5625 534654.4375 507559.8438 538355.5625 588958.9375 352013.75 484477.2813 448977.4063 522082.125 663629.3125 corticosterone 405727.125 448140 463473.9063 594176.0625 581053.6875 372778.3125 412378.625 690803.0625 475906.6563 820747.9375 345050.2813 723565.0625 365056 504804.0938 606590.8125 724152.875 creatine 6124689 6067575.5 5694081 7161380 4758276.5 3809573.75 4474102.5 5859657.5 3793720.5 4301961 4093416 4525102.5 3085572 3454522.25 3385426.25 4273439.5 creatinine 125407.3438 144297.5781 211512.75 182522.6563 168377.2344 216469.5469 92420.71094 253204.2969 193016.625 129759.4609 139404.7188 112284.0469 101680.5313 104500.5703 124787.0625 209823.1875 cysteine-glutathione disulfide 711826.25 265832.0625 287777.9688 385326.375 724571.9375 239953.9375 243593.8594 731892.1875 842618.8125 999845.625 788382.0625 247696.0156 234707.8281 207000.0156 563837.25 742464.9375 cytidine 353953.0313 228261.8438 221016.7344 278683.9063 358072.9063 186622.4375 206230.0156 288914.6875 341992.9688 329634.6563 264279.4688 187121.9063 135479.625 133115.2656 209030.6719 242727.8594 deoxycarnitine 304289.9375 236173.9219 199515.8125 165267.8906 313895.3125 274450.1875 233283.2344 366993.0625 264784.5 265671.9063 272284.1563 206350.125 251586.2813 228813.1563 249911.9063 321425.75 dimethylarginine (ADMA + SDMA) 451184.375 986086.125 759315.75 983678.3125 465564.5938 1070842.25 1440757.625 461896.0938 403393.6875 482771.6875 366218.5 3688920.5 1237735 1581147.875 366585.875 385049.6563 ectoine 55546.32031 65171.73828 100666.1719 105335.8906 148767.7969 186754.7969 150487.6563 343221.1875 272185.9688 275775.8125 238423.1719 167305.6719 234533.3438 233951.7031 284975.0625 ergothioneine 120472.1719 36785.30859 38497.80859 67407.29688 158406.0156 51888.83203 35863.19141 220507.0313 169857.25 281509.2813 114709.4609 46118.26953 69781.15625 72499.28125 180551.5625 159847.2969 gamma-glutamylalanine 144813.5938 129813.3672 132932.125 41976.14844 262418.2813 251815.0938 253899.7344 356103.8125 273778.8438 357839.4688 360303.1563 294168.7188 277105.875 253089.9375 245315.4063 252571.2344 gamma-glutamylglutamine 162882.4063 93865.96094 59435.03906 30862.4707 162701.3906 99652.53906 147094.3438 185669.0313 450476.1875 625222.8125 617618.9375 206332.0938 208320.8438 209568.9375 366386.6875 363448.2813 gamma-glutamylisoleucine* 185574.0625 195855.7969 165948.4688 172583.6563 126252.3828 160972.6094 143688.1406 138385.5625 111246.4219 134096.1563 143315.3594 149778.25 162006.1563 160824.3281 113597.7578 151695.1094 gamma-glutamylleucine 697704 588121.3125 666184.375 579853.5625 511825.5 588966.5625 601765.25 572605 481481.8438 640237.5 701678.5625 681412.875 717509.1875 743253.125 564729 707266.3125 gamma-glutamylmethionine 28691.11914 19667.90039 46334.73828 72948.67188 146587.6875 63006.57031 73569.67188 124127.6406 245111.0313 174603.7188 212374.875 165471.5469 130838.3516 96172.75 gamma-glutamylphenylalanine 343675.75 280793.2188 340341.7188 322757.0625 380894.3125 403076.2813 369928.125 448785.75 217186.4375 294115.0625 366042.375 373835.7813 350458.5313 358563.4063 328363.1875 342579.125 gamma-glutamyltryptophan 55369.69922 51439.26953 45588.71875 61925.35938 42368.5 60302.32813 42062.76172 71522.04688 50217.71875 74508.29688 63838.91016 81621.63281 76261.07813 78123.02344 72444.25781 97407.3125 gamma-glutamyltyrosine 230327.5156 283793.625 284945.375 309435.75 247337.75 267683.6563 234582.375 314303.4063 185757.0313 257332.2031 310477.2188 268633.4063 247284.6563 299177.8125 237337.7813 286904.0313 gamma-glutamylvaline 214708.1875 233139.4375 222801.2344 187290.2344 149245.5469 213177.2344 183121.2031 178481.8125 202442.1563 281786.6563 273694.0313 262422.7813 246300.375 233925.4375 182546.375 242901.9219 glutamine 1855415.75 1620526.375 1387096.125 1289785.625 1498045.25 1096523.75 1692165.25 1401462.125 1915396 2147287.25 1635654 1503516.375 1484044.25 1599599.125 1425121.375 1539422 glutathione, oxidized (GSSG) 773709.375 758946.5 736224.0625 1253377.375 673418.1875 524296.6875 539544.6875 671729.5 943397.625 997334.1875 829187.625 744867.0625 695678.4375 662544.0625 625214.75 880603.625 glycerophosphorylcholine (GPC) 1024244.813 570656.25 817667.125 390022.0625 802304.375 1012549.188 782411.0625 1092273.75 3405796.75 2549459.5 4177096.75 2205674.25 2358591 3554620 4036729.5 3832209.25 glycylvaline 38458.17969 28804.89063 26363.68945 30030.61914 18218.93945 20790.19922 43170.55078 15188.58984 11666.07031 25192.82031 43666.44141 20999.42969 15953.41992 21717.94922 heme 1539260.75 2905462.5 1312673.5 1855883.625 827010.25 188742.0625 614191.25 3846661.5 3454353.75 3960685.75 1405187.875 1682408.625 825970.375 2321007.5 967886.625 2015117.25 hexanoylcarnitine (C6) 212905.1094 592664.625 290487.5938 466321.375 172416.7656 63566.87891 128175.3828 51303.80078 184908.8125 250309.0781 90773.49219 125237.4453 91144.10156 57182.96094 67200.32813 97051.53906 homocitrulline 99162.15625 60683.64453 50763.71875 59594.24219 100054.0938 45856.21094 51962.96094 125237.0391 137168.5938 151942.4531 142328.0469 65983.52344 68621.07813 57521.55859 112087.0781 167680.125 homostachydrine* 54307.55859 70968.25 35251.76172 35573.57031 244523.7031 344716.3125 138618.1719 465074.7813 886598.1875 763640.4375 1169412.375 975295.25 854913.4375 699220.6875 817003.25 1056613.625 hydroxyisovaleroylcarnitine (C5) 92836.82813 83898.71875 51754.78906 110636.2422 60466.39063 45744.89844 55257.03125 58119.55078 90025.82031 121788.8906 99297.75 72214.17188 56393.42188 47664.62109 51452.67969 67876.11719 imidazole propionate 40583.82031 33810.03125 30921.58008 66788.11719 23154.78711 17003.23047 56599.92188 68257.53906 66656.57813 71910.17188 56600.46094 81702.00781 isobutyrylcarnitine (C4) 83686.57031 135320.7969 99984.39063 190734.7813 116004.8125 107887.8516 87469.52344 134978.3906 97492.35156 143344.5156 165871.125 156549.2344 119458.4063 117152.1797 96171.78125 175865.5938 isoleucine 27185036 25422326 23077098 19710104 22119270 22664960 23084476 23023108 14688702 15495795 15988148 20257798 21197746 21320906 16580260 20483138 isovalerylcarnitine (C5) 140717.7656 154008.6719 168820.2813 209076.9063 138165.7656 133344.4219 191813.2188 190677.625 120001.5625 183108.8438 150216.5469 195271.0625 132771.1719 115833.2266 136246.3125 144919.1875 kynurenine 518631.9375 423165.2188 543572.25 598408.4375 648705.75 753103.4375 824762.25 877862.6875 146456.125 237293.3906 285475.0313 343090.5625 190921.6875 187745.5938 177352.625 328377.5 laurylcarnitine (C12) 108821.9609 359254.9688 92979.97656 70962.29688 40100.60938 25887.30078 34178.01953 72144.64844 73910.53125 107279.5234 65658.89063 74148.09375 39257.12891 91718.92969 61821.03906 69247.67188 leucine 33511324 38299680 33011250 28742706 29124938 29808548 33480232 29892886 19792496 22614648 20595210 27431178 29407142 28840202 22242644 26671252 metacryloyl glycine 217021.9844 760716.6875 668189.5625 610936.4375 79656.52344 37277.76172 56386.03125 15341.38086 73494.52344 93509.28125 62620 67413.24219 48031.10156 41421.21875 19961.08984 54878.69922 methionine 6132862 5105321.5 5644709.5 5267080.5 7928424.5 7888027 7557169 11215904 4747326.5 5430157 6516562 6626033 6180880 6223251 6185563.5 5751263 N-acetyl-beta-alanine 144065.9844 142054.875 178017.7344 173850.2969 152892.8438 125540.6484 130551.4922 156972.0781 117904.6172 115654.6875 99749.78125 90546.5625 109848.2109 117644.4375 107716.3906 136361.0938 N-acetylisoleucine 75225.71875 110673.3984 88086.03125 79922.95313 54654.42188 69648.04688 71558.70313 111335.7734 61548.92969 71397.45313 68287.65625 69970.10938 101960.5391 78091.53906 94193.82031 76885.71875 N-acetylleucine 401285.9375 468860.1875 512063.2188 488529.5938 327538.8125 399710.7813 503207.5938 679514.9375 288601.1563 312235.25 359433.0938 416597.5625 509736.4063 439046.5313 410927.5 459702.9375 N-delta-acetylornithine* 418211.6563 85816.5 85534.50781 131120.0156 540272.125 173837.5156 174301.4375 738597 500511.4375 449338.8125 448786.375 175533.3125 241074.1094 231980.5 590973.625 787763.25 1-methyladenosine 44724.10938 50448.28906 65085.85156 47390.96875 54687.57422 73998.70313 53537.94922 33271.21875 32214.91797 67808.24219 32495.19922 41543.39063 52687.89844 51863.75391 21640.76953 23255.25977 1-methylguanosine 28803.14063 27884.91992 30855.25977 49449.57813 21826.19922 26048.50195 17124.4707 24556.9707 44247.05859 30400.89258 32416.17969 25979 15347.62891 23509.10938 21149.90039 26766.67188 N6-carbamoylthreonyladenosine 18951.19922 27430.61914 17827.13086 29553.96094 17164.2793 12471.51953 20801.61914 16260.21094 19713.10938 17701.73047 20835.5 20105.06055 11090.61035 14131.76953 15545.67871 nicotinamide 515845.8438 533788.3125 349800.0625 484005.5 481890.1875 294183.4375 229118.2969 566040.4375 867705.125 1159548.25 523978.4063 702439.875 456151.75 632494.3125 857684 560908.375 octanoylcarnitine (C8) 55527.30469 198658.8125 91863.67969 154124.9219 77635.11719 22343.0918 59505.96094 30130.2793 65480.07031 78352.3125 49626.23828 57453.53125 38713.25 31397.36914 33207.58984 36670.83984 oleoylcarnitine (C18) 412805 1834002.75 566131.8125 538060.625 315099.1875 171861.8125 320237.2188 596069.9375 354365 722056.375 576504.1875 346564.0625 130296.2578 396489 196205.1875 291034.0313 ophthalmate 61191.22656 79656.78125 74932.82031 208452.9375 35689.60938 38611.82813 29130.91016 39467.21094 43936.82813 59733.22266 95895.78906 56957.32813 32935.53125 41939 44900.03125 54945.41016 palmitoylcarnitine (C16) 502829.25 2013105.875 748164.3125 669420.625 338034.5938 184589.1719 316148.125 682178.4375 399194.4375 702921.1875 621162.0625 420110.9063 154478.25 388786.3438 215856.6719 254862.8438 pantothenate (Vitamin B5) 939125.6875 945997.0625 1282260 1626111.125 658015.0625 566616.75 679604.4375 886807.75 537212 618906.8125 454904.625 450782.5313 458176.0938 392105.9375 430832.5313 476869.8125 phenylalanine 26424416 26248646 24911938 23975786 27203166 28956886 30584108 31961812 17560702 20157206 20340590 23364834 22736768 21886142 19811316 23229176 pipecolate 1020915.25 943471.75 772503.4375 726723.875 1244192.25 717245.4375 814149.5 1555848 925486.8125 1020015.75 869711.5625 755836.375 681259.0625 612136.875 871792.0625 952207.75 prolylhydroxyproline 382247.125 234406.7813 174055.4063 269811.9375 186385.5781 87630.4375 84217.89844 237150.5625 245845.5625 252802.7656 187756.625 192142.875 114788.0234 71228.78125 125448.8906 158667.8281 proline 5747125 3585565.25 3202645.75 3689925 6118320.5 4323508.5 4217059 9199525 3208343.5 4774474.5 4265220 3451296.5 2931272.5 2878825.5 3322713.5 3753364.25 propionylcarnitine (C3) 440563.7813 423391.3438 398286.125 911706.875 446696.6875 388113.4063 510300.0625 548081.4375 158264.2031 288737.625 197483.6875 234577.4063 180736.4063 169080.6563 169604.375 254535.3281 serotonin (5HT) 2271976.25 1918190.625 2443841.75 2206139 1695350.625 2397797.5 2549264.25 24430.42969 2035891.75 2751137 2186913 2120997.5 1426754 1263046 2140818.5 2266315 sphinganine 152364.4063 563708.625 184824.2969 269862.25 94384.77344 57055.26172 91795.5 183711.2344 31362.61133 90794.36719 85750.6875 102132.25 72758.39844 140722.0156 42950.76953 sphingosine 269737.6875 1098975.375 301985.75 369854.3125 123930.3906 74611.6875 131945.2969 570665.1875 109880.9141 254422.2969 280939.8125 140450.3594 91924.03906 192380.8594 63048.80859 107900.9531 stachydrine 160306.8906 189124.7969 174404.6094 158243.75 1206616.75 1203262.125 689241.9375 2145286.5 2377688.5 2442773.25 2829384.25 2929296 2418719.25 2162424 2158725.25 2693736.75 succinylcarnitine (C4) 65832.20313 67319.13281 45180.32031 76428.75781 49625.14063 34860.85938 36861.83984 49817.33984 35169.57813 46949.46094 34158.78125 27958.10938 21113.56055 21303.61914 21297.58008 31594.71094 TDTEDKGEFLSEGGGV* 13970105 9435432 15262580 12447777 6520197.5 12536888 18256320 131612.0938 12460037 15197042 18045520 13680227 6263590.5 5576915 16224289 14205395 TDTEDKGEFLSEGGGVR* 75460.85938 65759.25 118067.4375 343148.3438 1295858.25 533565.625 638579.3125 323211.2188 187476.9531 229141.1563 169296.375 178379.0625 6682112.5 4087975.25 1014648.938 803950.75 tigloylglycine 85603.28125 219800.6563 187395.8906 143989.9844 42719.75391 18786.4707 47843.08984 46038.55859 33179.80859 27256.30078 41314.39844 50324.21094 16731.41992 19077.60938 24791.19922 35703.07813 trans-urocanate 290787.2813 304349.5313 381963.125 524632.3125 262776 270697.2813 240998.0156 437365.1563 288570.3125 363212 199657.3594 250294.6094 223496.9375 208983.3125 186260.3594 481863.625 tryptophan 23877240 13144603 23675390 21482832 27335798 30938898 26543884 36181172 18201104 24457844 22532664 24805062 24258108 24636658 24376552 27097868 tyrosine 10166545 8536448 9905584 11098055 13939688 15096242 12972268 18949314 8483246 10371493 9423976 11709490 10409601 10609994 9835209 8853914 valine 26389118 25054132 24399710 21320692 22968090 21314506 21794070 27104600 18782264 20522084 22167924 22407012 21954958 22579942 21861742 25951550 xanthosine 36673.75 29816.83008 41210.98828 51677.87109 32586.28906 26511.31055 14105.79981 28497.31055 42882.82813 32848.51953 24657.46094 31773.2207 22107.7207 22763.43945 33092.89063 27583.34961 MS_METABOLITE_DATA_END #METABOLITES METABOLITES_START metabolite_name RI MASS PUBCHEM KEGG HMDB 1-arachidonoyl-GPC* (20:4)* 5554 544.3 C05208 1-arachidoyl-GPC (20:0) 6100 552.4 HMDB10390 1-docosahexaenoyl-GPC* (22:6)* 5518 568.4 1-eicosatrienoyl-GPC* (20:3)* 5600 546.4 1-heptadecanoyl-GPC (17:0) 5750 510.4 HMDB12108 1-linoleoyl-GPC (18:2) 5574 520.4 11988421 C04100 1-myristoyl-GPC (14:0) 5481 468.3 460604 HMDB10379 1-oleoyl-GPC (18:1) 5700 522.4 16081932 1-palmitoleoyl-GPC* (16:1)* 5524 494.3 1-palmitoyl-GPC (16:0) 5671 496.4 86554 1-stearoyl-GPC (18:0) 5844 524.4 497299 2'-deoxycytidine 1256 228 13711 C00881 HMDB00014 2-aminoadipate 794 162.1 469 C00956 HMDB00510 2-arachidonoyl-GPC* (20:4)* 5524 544.3 2-docosahexaenoylglycerophosphoethanolamine* 5512 526.2 2-linoleoyl-GPC* (18:2)* 5544 520.4 2-methylbutyroylcarnitine (C5) 2439 246.1 6426901 HMDB00378 2-palmitoyl-GPC* (16:0)* 5604 496.3 2-stearoyl-GPC* (18:0)* 5780 524.4 10208382 3-dehydrocarnitine* 1020 160.2 6991982 C02636 HMDB12154 3-methylcrotonylglycine 2580 158.1 169485 HMDB00459 3-methylglutaroylcarnitine (C6) 1900 290.1 128145 HMDB00552 3-ureidopropionate 1062 133.1 111 C02642 HMDB00026 4-acetamidobutanoate 1724 146.1 18189 C02946 HMDB03681 4-guanidinobutanoate 1085 146.1 500 C01035 HMDB03464 5-methylthioadenosine (MTA) 2427 298.1 439176 C00170 HMDB01173 5-oxoproline 1446 130.1 7405 C01879 HMDB00267 7-methylguanine 1353 166.1 11361 C02242 HMDB00897 acetylcarnitine (C2) 1203 204.2 7045767 C02571 HMDB00201 adenosine 1650 268.1 60961 C00212 HMDB00050 AMP 1210 348.1 15938965 C00020 HMDB00045 alanine 650 90.1 59,507,311,724 C00041 HMDB00161 anthranilate 3213 138.1 3,734,162,227 C00108 HMDB01123 arginine 650 175.2 5,246,487,232 C00062 HMDB00517 betaine 721 118.2 247 C00719 HMDB00043 butyrylcarnitine (C4) 2007 232.2 213144 butyrylglycine (C4) 2077 146.1 88412 HMDB00808 C-glycosyltryptophan* 1912 367.1 carnitine 702 162.2 10917 C00318 choline 674 104.2 170746 C00114 citrulline 715 176.1 833 C00327 HMDB00904 corticosterone 4856 347.2 5753 C02140 HMDB01547 creatine 758 132.1 586 C00300 HMDB00064 creatinine 730 114.1 588 C00791 HMDB00562 cysteine-glutathione disulfide 821 427.1 4247235 HMDB00656 cytidine 1065 244 6175 C00475 HMDB00089 deoxycarnitine 759 146.1 725 C01181 HMDB01161 dimethylarginine (ADMA + SDMA) 812 203.2 123831 C03626 HMDB01539 ectoine 832 143.1 1,260,416,993,223 C06231 ergothioneine 847 230.2 3032311 C05570 HMDB03045 gamma-glutamylalanine 1108 219 440103 gamma-glutamylglutamine 806 276.1 150914 HMDB11738 gamma-glutamylisoleucine* 2644 261.2 HMDB11170 gamma-glutamylleucine 2744 261.2 151023 HMDB11171 gamma-glutamylmethionine 1993 279.2 7009567 gamma-glutamylphenylalanine 2846 295.1 111299 HMDB00594 gamma-glutamyltryptophan 3033 334.2 3038501 gamma-glutamyltyrosine 2073 311.2 94340 gamma-glutamylvaline 2040 247.2 HMDB11172 glutamine 684 147.2 5961 C00064 HMDB00641 glutathione, oxidized (GSSG) 1535 613.1 6,535,911,215,652 C00127 HMDB03337 glycerophosphorylcholine (GPC) 694 258.1 657272 C00670 HMDB00086 glycylvaline 1572 175.1 27,248,076,994,979 heme 5057 616.2 C00032 HMDB03178 hexanoylcarnitine (C6) 3174 260.2 6426853 HMDB00705 homocitrulline 832 190.1 650,726,991,977 C02427 HMDB00679 homostachydrine* 1199 158.2 441447 C08283 hydroxyisovaleroylcarnitine (C5) 1683 262.1 imidazole propionate 1011.7 141.1 70630 HMDB02271 isobutyrylcarnitine (C4) 1941 232.2 HMDB00736 isoleucine 1614 132.1 791 C00407 HMDB00172 isovalerylcarnitine (C5) 2533 246.2 6426851 HMDB00688 kynurenine 1902 209.1 1,611,666,971,029 C00328 HMDB00684 laurylcarnitine (C12) 5066 344.3 10427569 HMDB02250 leucine 1674 132.2 70,457,986,106 C00123 HMDB00687 metacryloyl glycine 1922 144 152645 methionine 1252 150.1 69,920,876,137 C00073 HMDB00696 N-acetyl-beta-alanine 1460 132.1 76406 C01073 N-acetylisoleucine 3370 174.1 2802421 N-acetylleucine 3444 174.1 70912 C02710 HMDB11756 N-delta-acetylornithine* 836.2 175.1 9920500 1-methyladenosine 1356 282.1 5460178 C02494 HMDB03331 1-methylguanosine 1850 298.1 96373 HMDB01563 N6-carbamoylthreonyladenosine 2656 413 nicotinamide 1267 123.1 936 C00153 HMDB01406 octanoylcarnitine (C8) 4100 288.3 123701 C02838 HMDB00791 oleoylcarnitine (C18) 5202 426.4 HMDB05065 ophthalmate 1457 290.1 9817431 HMDB05765 palmitoylcarnitine (C16) 5179 400.4 461 C02990 HMDB00222 pantothenate (Vitamin B5) 2218 220.1 6613 C00864 HMDB00210 phenylalanine 2056 166.1 69,256,656,140 C00079 HMDB00159 pipecolate 1120 130.1 849 C00408 HMDB00070 prolylhydroxyproline 960 229.2 11673055 HMDB06695 proline 796 116.1 1,457,426,971,047 C00148 HMDB00162 propionylcarnitine (C3) 1589 218.2 107738 C03017 HMDB00824 serotonin (5HT) 1660 177.1 5202 C00780 HMDB00259 sphinganine 5175 302.3 3126 C00836 HMDB00269 sphingosine 5197 300.2 5353955 C00319 HMDB00252 stachydrine 860 144.1 115244 C10172 HMDB04827 succinylcarnitine (C4) 1401 262.1 TDTEDKGEFLSEGGGV* 3301 821.1 TDTEDKGEFLSEGGGVR* 2880 600 tigloylglycine 2523 158.1 6441567 HMDB00959 trans-urocanate 1119 139.1 736715 C00785 HMDB00301 tryptophan 2445 205.1 69,235,166,305 C00078 HMDB00929 tyrosine 1516 182.1 60,576,942,100 C00082 HMDB00158 valine 1040 118.1 69,710,186,287 C00183 HMDB00883 xanthosine 1785 285 64959 C01762 HMDB00299 METABOLITES_END #END