#METABOLOMICS WORKBENCH kapitsinou_20210701_053527 DATATRACK_ID:2732 STUDY_ID:ST001865 ANALYSIS_ID:AN003023 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 samples destined for GC/MS analysis were re-dried under vacuum desiccation CH:CHROMATOGRAPHY_SUMMARY for a minimum of 24 hours prior to being derivatized under dried nitrogen using CH:CHROMATOGRAPHY_SUMMARY bistrimethyl-silyl-triflouroacetamide (BSTFA). The GC column was 5% phenyl and CH:CHROMATOGRAPHY_SUMMARY the temperature ramp is from 40° to 300° C in a 16 minute period. Samples were CH:CHROMATOGRAPHY_SUMMARY analyzed on a Thermo-Finnigan Trace DSQ fast-scanning single-quadrupole mass CH:CHROMATOGRAPHY_SUMMARY spectrometer using electron impact ionization. The instrument was tuned and CH:CHROMATOGRAPHY_SUMMARY calibrated for mass resolution and mass accuracy on a daily basis. CH:CHROMATOGRAPHY_TYPE GC CH:INSTRUMENT_NAME Thermo-Finnigan Trace DSQ 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 Bioinformatics: The informatics system consisted of four major components, the MS:MS_COMMENTS Laboratory Information Management System (LIMS), the data extraction and MS:MS_COMMENTS peak-identification software, data processing tools for QC and compound MS:MS_COMMENTS identification, and a collection of information interpretation and visualization MS:MS_COMMENTS tools for use by data analysts. The hardware and software foundations for these MS:MS_COMMENTS informatics components were the LAN backbone, and a database server running MS:MS_COMMENTS Oracle 10.2.0.1 Enterprise Edition. LIMS: The purpose of the Metabolon LIMS MS:MS_COMMENTS system was to enable fully auditable laboratory automation through a secure, MS:MS_COMMENTS easy to use, and highly specialized system. The scope of the Metabolon LIMS MS:MS_COMMENTS system encompasses sample accessioning, sample preparation and instrumental MS:MS_COMMENTS analysis and reporting and advanced data analysis. All of the subsequent MS:MS_COMMENTS software systems are grounded in the LIMS data structures. It has been modified MS:MS_COMMENTS to leverage and interface with the in-house information extraction and data MS:MS_COMMENTS visualization systems, as well as third party instrumentation and data analysis MS:MS_COMMENTS software. Data Extraction and Quality Assurance: The data extraction of the raw MS:MS_COMMENTS mass spec data files yielded information that could loaded into a relational MS:MS_COMMENTS database and manipulated without resorting to BLOB manipulation. Once in the MS:MS_COMMENTS database the information was examined and appropriate QC limits were imposed. MS:MS_COMMENTS Peaks were identified using Metabolon’s proprietary peak integration software, MS:MS_COMMENTS and component parts were stored in a separate and specifically designed complex MS:MS_COMMENTS data structure. Compound identification: Compounds were identified by comparison MS:MS_COMMENTS to library entries of purified standards or recurrent unknown entities. MS:MS_COMMENTS Identification of known chemical entities was based on comparison to metabolomic MS:MS_COMMENTS library entries of purified standards. As of this writing, more than 1000 MS:MS_COMMENTS commercially available purified standard compounds had been acquired registered MS:MS_COMMENTS into LIMS for distribution to both the LC and GC platforms for determination of MS:MS_COMMENTS their analytical characteristics. The combination of chromatographic properties MS:MS_COMMENTS and 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 1,2-dipalmitoylglycerol 377604.9688 285318.1563 447055.4063 408396.3125 190089.3438 180523.125 173762 126750.7109 99994.99219 151465.0156 120235 130839 111442.8125 138882 189001 65979 1,2-propanediol 10918184 9331721 11850241 17905306 8626940 10994990 13140047 11924772 11593338 8231413 9029462 11287543 7206468 6711062.5 15820992 8961329 1,3-dipalmitoylglycerol 115897.4219 132927.7813 192089.8594 164359.7031 119453.1719 87259 56488 48312.57813 28345 92668.52344 15968 65475 39768.60938 74770.71875 61195.14844 52084.89063 1,5-anhydroglucitol (1,5-AG) 4355634.5 3492490.25 4232856.5 3815824.75 8814141 7098456 9756499 9631169 4984921.5 5672478.5 3766404.5 5329701 8500716 7878876 9651582 9243765 1-methylhistidine 380912.2813 382113.375 335069.5313 491170.9063 189706.2813 97998.38281 98593 233143.6406 54809 55724 36999 45703.19141 49321.89063 26360.99805 1-stearoylglycerol (18:0) 289189 255858.9844 330473 368148 222429.9844 247289.0938 228195 178074 185183 203652.8438 230253.0156 182442 203072 210484 309961.125 182406 13-methylmyristic acid 74702.90625 26777 41888.44141 17918 65395.00391 56586.13281 68156.21094 43937 57917.32813 54410 59005.04688 2,3-dihydroxyisovalerate 66289.36719 96472.07031 106785.9375 49909 91815 52895 2-(4-hydroxyphenyl)propionate 121175.7031 272350.2813 107809 182480 431357.5938 318156.0313 799464.1875 538885.0625 573876.75 493967.125 465007.25 464842.2188 2-aminobutyrate 558936 952256.0625 963309.3125 517901.2813 347691.4688 479904.4063 501483.2188 548498.125 309247.9063 452285.4063 528916.5 332364.625 474341.1875 522956.2813 345421.4375 2-hydroxyadipate 15801 21724 42588 72923.74219 10941.00098 36893 67781 58384.99609 28749 36957 35873.46875 2-hydroxybutyrate (AHB) 4101204.25 12038767 12189647 23573784 1499135.125 1654457.125 2169964 1932607.5 1143533 1260689 2488174.5 1936453 1336693.75 1533591.25 1388703 1734365.125 2-hydroxyglutarate 279299.875 336726.9375 444516.9063 589850.125 199147.375 280311.9375 382149.9375 255256.9844 417041.625 295445.625 497871.6875 562992.6875 349351.6563 341627.7813 634515.25 474526.2813 2-hydroxyisobutyrate 2048418.125 1252945.5 820410.9375 678668 1608835.75 1703106.5 2120610 2076950.875 1301231.5 977050.75 1148036 1192373.375 1180134.5 1082144.75 1432926.125 1022809.313 2-oxoadipate 49877.92969 44798 11051 26820.33008 35265.69922 52903.66016 63840 103946.7969 89741.25781 46336 72730 92027.77344 93368.35938 2-palmitoylglycerol (16:0) 147681 159070 182432 250082 102768 82885 3-(4-hydroxyphenyl)propionate 34431 34750.55859 37148 37307 38037 36263 26964 36579 3-hydroxybutyrate (BHBA) 112655008 206428720 203568112 232387504 26596472 7582023 21045548 4656111 34758160 38564784 21033972 18981306 10080053 9193488 8105442 16531271 3-hydroxyisobutyrate 1182026 1712495 1951552 2061979 1280582 1278039 1538801 1648990.625 1229105 1591063 1899803 1984956.875 1377048 1452506 1331014 1687978 3-phosphoglycerate 148452 124479.0078 169641 233551 96129 90326 76613 46049.33984 64688 138085 103201.0078 88039 48928 61254.17969 59093 33978 4-hydroxyphenylacetate 48219.21875 113171.2188 43248.94141 38515 37782 85922.17969 36740.39844 77913.86719 67435 73404.15625 59562.69141 43097 27997.08008 43896.60156 5,6-dihydrouracil 144012.3438 161884.2031 172791 172518 157516 158413.1094 187935.4531 198859.6875 158814.4688 189000.1563 165999.1094 200316.2188 189402.9063 165988 163337 130900.5859 5-hydroxyindoleacetate 250120.3438 295709.3438 330802.8125 363678.3125 122279.0078 131408.4375 254283 171114 171864.6094 200222 205742.4063 147353.4375 42804.42969 41810.30859 24035 88681 5-hydroxymethyl-2-furoic acid 6078 10468 5-ketogluconate 62978 26880.00195 40086 42560 56606.00391 45633 49504 51561 52269.00391 92786 24249 105785.0078 63108.60938 7-beta-hydroxycholesterol 17987.59961 17865 26922.91992 28432.81055 9731 16331 9414 17446 25061.83984 15708 15145.75977 12737 18831.7793 12635 adipate 412502.7188 305417 380328.8125 513983.6875 272948.0625 343959.2813 212954 282466 310703.3438 282488.0938 292546.0625 264520 272552.25 275610.6563 340267.375 209102 alanylalanine 768557 723182.0625 1005833.25 949389.4375 754003.25 675123.5625 740410.3125 633445.1875 728882.875 870960.1875 518974.6875 867242.125 690554.875 607978.625 782058.375 623663.375 allantoin 1723799.625 1761959.875 1776815.5 1752314.375 1445179.375 1665132.625 2064972.375 2121998.5 1536286.375 1585505.125 1562397.375 1912792 2101764.5 1977140.375 1551321.125 1484987 alpha-hydroxyisovalerate 10224329 12317169 12987590 11797362 5422857.5 4323557 5370595 5362077 2012000.875 2095511 2424020.25 2167869.5 2350296 2172275.5 2508681.75 2079511.875 alpha-ketoglutarate 140267.4219 112293.3594 192006.375 259608.875 141441.4688 122502.7969 207010.4688 150868.2031 282674.7813 341032.4375 488716.0938 568932.625 401837.25 393281.0313 464079.5938 351554.1563 alpha-tocopherol 378733 343527 399750 373104 169595 218891 182049 230315 257698 337013 310754 267363 195381 216257.9844 275724 169907 arachidate (20:0) 64528 109262 104205 73115 92321 55579 67016 44196 158457 87855 100411 136141.1875 133644 143950 136616 149910.7813 ascorbate (Vitamin C) 1239901.5 916964.0625 1229065.5 1582904.375 1482970.5 1637766.375 1738892.375 85113 127678 534970 862740.875 998305 235804 222918 662962 249886 asparagine 665429.8125 483118.3438 485168.1875 263188 860035 1006521.5 889193.5625 1116284.375 642913.25 772828.1875 688659.5625 996199.9375 866900.5625 883208.1875 852608.1875 693222.9375 aspartate 2221039 2098210 2540835.75 2019661 1614723 1831016.75 1795649 1426620 2110926 2016339.625 2242997 2310437 2204224.25 2058148.625 2297577.5 2122062.75 benzoate 2427251.25 2956364.5 2689917.5 1685008 1260243 1096395.5 974462.8125 1131423.375 1277909.75 1572894.375 1764501.5 1008386.438 1529330.625 1921202 1573088.25 1640315.375 beta-alanine 61799.64844 42125 54344.10938 26874.75977 35220 54108.21875 40987 29496.57031 72704 64272 122807.0469 78613 154665.4375 145116 81064 79426.64844 beta-hydroxypyruvate 65978.65625 55985.79297 59682.41016 54312.05859 93997.6875 52612.30078 83479.10938 88954.78906 122338.9766 90524.20313 83508.59375 138871.875 116271.9688 123852.7109 109868.6563 107106.9688 beta-sitosterol 61095.03516 77243.00781 90143.60938 100072 43987 26446 79815.6875 81362.92969 60296 58945.23047 96615.36719 63724.99609 65052.94922 71061.34375 campesterol 444056.6875 584061.75 579630.125 603105.75 105338.7109 122803.0625 183478.5 98696.72656 346860.4063 311851.6875 296633.4375 334313.9375 254959.875 179529.2969 287026.2813 179843.125 chiro-inositol 241716.5938 316327 89379 500695.6875 165050.5938 163691 417761.4688 227890 476357.6875 569590.875 525129.8125 472592.1875 cholesterol 32002302 28507824 39235728 39452328 24724918 22207120 22935464 22524750 24615704 26214484 22237972 22576388 25503558 26513536 29073962 22903780 vaccenate (18:1n7) 1052460 1547811 1187394.75 935717.875 936262 664854 585706 655933 996409.5 1035994.313 765128.1875 923503.5 986281.8125 1029595.75 955535.375 710954.75 citrate 31573006 30774962 36148344 34876188 20999670 20132610 26365270 19813832 22758528 23001746 24840062 30140448 20278226 19480506 22240488 22333970 dihydrocholesterol 330472 423506 340146.5625 462167 254120 279371 239088 208102 328600 399861 315784 281664 280098.6875 231536 336633 170749.875 dimethylglycine 1863629.75 2958344.25 2326018 3414291.5 1062667.5 1108162.75 1837324 988083 1549735.5 1624686 1709452.25 3755074.25 1049279.75 945695.375 1003445.313 1326253 erythritol 380600.5625 415562 386461.0313 420897.9688 392264.1563 359008.4375 359817.375 488949.5938 406919.5313 327225.0313 376782 455997.875 414089.1875 375370.375 463458.9063 405069.25 erythronate* 320725.9375 315111.375 364600.625 351179.1875 239425.2969 221301.0469 250065.8438 288090.3125 227971.1719 278848.9375 240675.0938 350249.7813 242203.9531 206598.0625 255683.2031 271236.9063 fructose 3597831.25 3201457.5 4010916.5 3193398 3849343.5 4334353 6854021.5 4306431 11404241 4789443.5 11445490 14266583 5148993 5637784 17293570 10391354 fucose 735945.0625 547981 736516.5 730667.5625 538002.125 513337.0313 593498.875 458384.5625 776956.25 790253.0625 609423.75 699082.0625 633756.5625 768928.375 678830.125 445974.4375 fumarate 372005.5938 664550.9375 504561.4063 568854.5625 437207.75 297124.6563 524177.7813 474121.6563 544179.625 665817.375 611000.625 775439.25 526949.625 620110.5625 478702.8125 585700.9375 gluconate 142699 95231 83139 116205 115919 78799 146171 115551 191199 195818 204636.0156 221612 147440 185576 226799 196804 glucose 301502976 210483488 234704912 217019632 314568768 310186016 386506688 298108864 375723168 375511424 370091680 441619552 409413792 445575680 473740192 351853248 glutamate 1969592 1476652 2047245.875 649347 1653641 1683075 1516178 1692800.125 2964280.5 3122327.75 3329426 3138902.25 3031474.75 3128379 3021333.25 2772457.5 glutarate (pentanedioate) 48240.69922 52903.94531 68985 87967 35675 40509.26953 30287 39060 49750.99609 49119 67651 66471.17188 41268 32631 53041.91797 41917.17969 glycerate 360545.0313 349384.1875 390550.5 513888.5313 231684.3594 216718.3906 225588.1719 536487.0625 429439.4688 345981.1875 363468.9063 468077.9375 433926.1875 394572.2188 489893.5313 478931.3438 glycerol 29565768 62359260 54852252 69395944 38363640 23213716 35908536 26290352 67669520 73466344 44483636 64200992 41452316 34660348 52866320 43919504 glycerol 2-phosphate 158456 93551.3125 173785.8125 202494.1563 115892.7109 87177.52344 114317.0781 132570.4531 158779 172048.75 160053 154741.6406 182964.7344 175739.7031 163007 178307.2656 glycerol 3-phosphate (G3P) 1992229 1717708.375 2338241.5 2630959.5 1430529.875 1268148.625 1190867.75 1349511 2118800.25 1998564.25 1911117.25 2145082.25 1840988.75 1961726.375 2049931 1835988.625 glycine 17679742 12669205 16125276 4941033.5 16637980 21267422 17822496 21706406 18968836 27120110 23962032 24252912 37677076 37395084 27219684 26226354 glycolate (hydroxyacetate) 658452.375 534880.5625 681266.125 702409.375 570472.4375 758732.125 499246.0313 1173038.25 1013665.188 1138382.875 1432344.25 1226391.125 1227103.625 1271046.125 1391579 1412975 gulono-1,4-lactone 765861.4375 1016584.813 1081437.125 1350065.375 338849.1563 533130.75 655669.9375 374047.3438 475247.25 1145583.5 1072537.75 1091106.5 554264.125 766204.1875 646345.625 557582.4375 homoserine (homoserine lactone) 20636 18016 21402 18576 27970 31525 26301.7207 36493.32813 38168 52613.75 67576 67457 72221 84326 61266.00391 54555.75 indolelactate 1631782.75 2804484.5 3153220.25 3629437.5 871515.5 1031351.5 970976.9375 1135140.875 481863.625 415782.6563 733370.1875 733775.6875 970663.4375 690189.5 925277.25 781283.4375 inositol 1-phosphate (I1P) 395993.9375 331809.8438 596537.875 620335.3125 246738.3594 305832.5 233640.4063 167748.2656 332207.1875 292263.0313 221884.375 223085.2344 234986.375 192720.3594 331236.8438 229443.9219 Isobar: ribulose 5-phosphate, xylulose 5-phosphate 47097.99609 43618 82677 85287.5625 62055 43272 89002 86508 115180.7813 25329.00195 39039 35597 21324 22138 43326 isosorbide 871626.625 815047.75 1010468.813 1021635.375 815512.125 546249.3125 782506.5 575468.25 898176.375 498800.1563 698231.6875 664442.875 562600 575396.75 1001494.625 658421.125 lactate 743307840 624683776 753307328 990387968 669084672 645568640 727105920 716808000 783608512 974690560 762655552 915615360 662170112 522972800 766936320 574597120 lysine 4586919 2980734.25 3505417.5 2438296.75 4357712.5 4460824.5 3576764.75 6074922.5 1076156.125 2658227.25 1124443 1331383.875 1492485.375 1189808.75 882512 681491.375 malate 1848910.125 2731439.25 2826396 3587721.25 2031939.625 1285391.125 2011424.5 1819431.875 1743365.125 2127051.25 2502762 2683633.75 1858787.125 1500376.875 1715048.875 1889502 mannitol 41179.35547 47609.96875 37065.21875 76100.8125 187715.125 94683.67969 92336.95313 46899.89063 215884.8906 63314.87109 61604.10156 121180.5 58934.03906 55674.50781 100651.875 mannose 9958745 5404940 7238473.5 6422324.5 7598688.5 8313137 12139350 6519732 14035438 16403551 13343432 14868865 15789479 17679528 14737783 11092029 myo-inositol 28623388 24718578 29717846 41998448 25716164 23754418 22443400 24391144 20179822 17589728 20123510 21605744 19492226 16304379 23710492 19801326 N-acetylaspartate (NAA) 104627.9688 126248.6094 143580.125 176852.3438 90321.86719 74270.82813 68796.85938 82890.53125 97606.64063 89734.10938 90115.71875 77332.53125 70169.89063 53898.98828 61226.16406 59694.14844 N-acetylglycine 4168872.75 6173847.5 7122397 6029401.5 683602.3125 673030.125 1746929.625 595538 798866.125 841076.625 654459.6875 638611.1875 350995.0625 492299.0625 444468.5938 628498.75 N-acetylneuraminate 276940 296737 272255 310340.0313 175868 188084.8438 210792.5781 188964.9844 224868.9688 158068 313689.4063 191825.0781 166569.9063 155394 163965 173306.9063 N-acetylserine 204534.125 192022.0156 238112.7188 325066.6563 137161.4531 173883.125 202040.5938 216333.0469 169918.8125 167578.6719 152689.1563 181215.25 154373.1563 130538.3203 143428.1563 178706 oleate (18:1n9) 8178025 16409408 9340369 6539776 8998153 3373018.5 4765173.5 4108939.25 8148871 5830280.5 5086548 7279902 7428065 7577604.5 8592513 8223372 ornithine 1998505.75 1156787.125 1363048.25 920352.125 1766359.875 1849995.125 1341253.375 2470867.75 321752 818483 671192.5 653029.3125 716217.1875 435956.4688 402975.75 357148.9375 orotate 254903.3125 208595.2813 222038 205738.6719 476576.3125 416782 348877.4063 403094.7813 210459.4531 193268.4531 168451.2969 136258.4063 157006.2813 172570.8594 148060.4844 125068 oxalate (ethanedioate) 110824.8672 119718.8281 151650.0938 162087.8906 101229.7891 113754.6563 104201.8516 107552.4609 133459.8125 117337.3438 148953.6875 153573.7344 139861.6563 140600.9844 141096.0938 107722.9922 palmitoyl sphingomyelin 3003413 2245545.5 3549270 4085094.75 3189942.25 3043997.5 2337165.5 2521885.25 3176013.25 3247195.75 2514026.25 2724374.75 2388679.25 2172068.75 3547288.5 2199107.25 pentadecanoate (15:0) 359484.25 480700.25 326132.0625 354631.5 271753 192400 180890 225258 270980.8125 278718.2813 217378 235268 298624 293754 267617 280120 phosphate 233807024 244905632 253381840 313212192 193245728 241655920 229815184 154425840 207064528 182347632 155588112 157252032 144970464 110650400 168836592 145051984 phosphoenolpyruvate (PEP) 43360 25342 54680.57422 78917 22071 15583 17041 20247.85938 35857 46960 16291.99902 15984.08008 11153 15883.00098 20336 phosphoethanolamine (PE) 130532.7734 68414 111722 299971.2813 44874 77195.65625 68475.14063 37088 25574 38187 pimelate (heptanedioate) 473659 362485 435131 539187.875 275586 338496 295562 248736 321970 380493 284089 331800 357290 189152 379991 197853 pinitol 72706 177780 274135.375 110394.4531 415236.0625 135344 175828.3125 233680.0156 243623.0781 203416 222453.5781 220407 274204.8125 pyrophosphate (PPi) 3928032.75 2582566 3327810.25 1711999.375 2517134.75 3407039.25 1853498.125 2436840.25 2920086.25 1649512.5 2483007 1289257.375 1288730.125 1191725.75 2278187.75 2052299.125 pyruvate 433779.9375 435837 581343.4375 677618.875 500451.9688 431079 680303 498141.9688 947600.875 1053629 1059922 1261357.25 1079133 1084359.375 1124139.375 953163.1875 ribitol 175812.7344 162079.1094 141174 217131.0156 81605 115578 142146 103285.9922 153457 176004.0156 147122 141678 133604 143858 159201 ribose 355576.4063 375762 406263.125 357155 437203.75 463726.9063 609490.5625 296920 732075.1875 747633.625 1055153.125 1302698 940387.3125 1280089.125 709003.25 840406 ribulose 147397.9063 118212 128688 149234 106715.8906 71767.34375 85746.14844 82072.25781 124268.2813 95571.99219 61141.46875 98696.45313 54872.73047 67197.97656 67177 54138.10938 scyllo-inositol 812065.25 564382 756826.1875 1138438.375 610478.875 482960 591945.125 580965.9375 403771 437294 366323 409970 398957 285779 588435.3125 462099 serine 2130723.5 1279861.375 1651272.75 574782.25 2663652 3165712.75 3150689.25 3464464.25 2985231.5 3527284.25 3343636.5 3772114.5 5144967.5 4995605 4271776.5 3631522.5 sorbitol 972613 664390.875 609251 614320 788352 932904 922764.875 909670.0625 708105 1103707 767778 819275 717773 514335 586969 409637 stearamide 305430.75 304227 298625.4375 357568.9688 320589.2188 284041 251613.1875 197281 324558 292841.25 192559 302622 354319.5938 252399.5781 320224.0938 271390.9375 sphingomyelin 346980.3125 200241 288181.5625 383848.3438 237070.0156 243883.8438 235186.7969 199881.1719 255414 303875.4688 196550 191190.7656 192353.5625 155680.8906 322664 180705.6719 succinate 361591.5938 554241.75 579054.5 1082611.75 406786.7813 262769.2188 377986.2188 385526.9375 525943.1875 685106.4375 698215.1875 785733.25 515408.3125 330968.25 483283.0313 577039.0625 taurine 443324.2188 491521.5313 492436.2188 772262.4375 236442 190073.3438 189601.2656 212280 79307 142562.6563 77468 63252.99609 69965 69705 69141 58804.99609 threitol 60883 89188.99219 60145 65245 74994 66577 58579 63960.00391 79926 89025 53138 92705.9375 68824 59514.99609 99243 64716 threonate 3574376 3535317.25 4071250 5093212.5 3295205.25 2378616.25 3090232.75 3040130.5 3436668 3538360.25 4199928 4411371 4136785.75 3585226.75 4822814.5 3731848.5 threonine 1313046.125 938866.625 1051323.625 337121.75 1594020.625 2400066.5 1818635.5 2508941.25 1203939.25 1411969 1905666.5 1553581.125 3057205.25 3281211.75 2102539.75 1675558.75 hydroxyproline 1425939 932397 870130 725272 1490014.125 2165592 1506441.75 2284635 2771955.75 2700163.75 2689146 2605228 2809162 2665861 2575357.25 2248828.75 uracil 1084370.875 1118779.5 1257312.375 1602649.5 870970.25 798399.625 1097762.375 577258 987595.25 874633.6875 666012.625 935503 625438.25 373675.625 443422.75 547819 urea 159569520 195361984 204488640 170799680 167222208 185562720 171384816 205196016 145245728 143349104 163207136 181477040 166344496 170001104 180846704 169547200 xanthine 8437.75 8267.509766 15858.19141 134086.8125 249238.0781 573056.8125 7637.620117 77297.70313 1363904.875 403086.9375 500442.6563 958822 1277919.75 xylitol 65355 59643 64967 118124 40163 39369.67188 72329 28705 26546 48018.85938 42763 66280 30146.2793 28895 74663 53186.98047 xylonate 44482.67188 77559.89063 86848.70313 78587.85938 56969.32813 32376.91992 42508.85156 65778.9375 51294.76172 60680.83984 51299.32813 81354.57813 54359.78125 59567.39063 63317.80859 47577.42969 xylose 132298 124509.9922 138874 112927 109188 121927.5313 116544 210272 175736.4688 217708 195701 243120.8281 317921.4375 160676 113293.0078 xylulose 27027.92969 20656 28204.99805 29754.73828 15451.08008 20704 20143 11375 26919.99805 18037 28447 27478 11379 13500 10417 MS_METABOLITE_DATA_END #METABOLITES METABOLITES_START metabolite_name RI MASS PUBCHEM KEGG HMDB 1,2-dipalmitoylglycerol 2600 313.3 99931 HMDB07098 1,2-propanediol 1041 117 C00583 HMDB01881 1,3-dipalmitoylglycerol 2637 371.3 68149 1,5-anhydroglucitol (1,5-AG) 1788.7 217.1 C07326 HMDB02712 1-methylhistidine 1757.7 196 921,057,020,397 C01152 HMDB00001 1-stearoylglycerol (18:0) 2186.6 399.4 24699 D01947 13-methylmyristic acid 1833 299.2 151014 2,3-dihydroxyisovalerate 1422 131 677 C04039 2-(4-hydroxyphenyl)propionate 1635 193 102526 C03080 2-aminobutyrate 1537.5 246.2 4,396,916,971,251 C02261 HMDB00650 2-hydroxyadipate 1653 261 193530 C02360 HMDB00321 2-hydroxybutyrate (AHB) 1169.4 130.9 440864 C05984 HMDB00008 2-hydroxyglutarate 1576 247 43 C02630 HMDB00606 2-hydroxyisobutyrate 1107.5 130.9 11671 HMDB00729 2-oxoadipate 1676 258.08 71 C00322 HMDB00225 2-palmitoylglycerol (16:0) 2108 129 123409 3-(4-hydroxyphenyl)propionate 1727.9 179.1 10394 C01744 HMDB02199 3-hydroxybutyrate (BHBA) 1203.5 116.9 441 C01089 HMDB00357 3-hydroxyisobutyrate 1205 177.11 11966314 C06001 HMDB00336 3-phosphoglycerate 1754 299 C00597 HMDB00807 4-hydroxyphenylacetate 1630.6 179 4693933 C00642 HMDB00020 5,6-dihydrouracil 1505.2 243 649 C00429 HMDB00076 5-hydroxyindoleacetate 1983.2 290 1826 C05635 HMDB00763 5-hydroxymethyl-2-furoic acid 1559.1 271.1 80642 HMDB02432 5-ketogluconate 1841.1 333.1 5460352 C01062 HMDB11731 7-beta-hydroxycholesterol 2340 456.4 473141 C03594 HMDB06119 adipate 1520 110.9 196 C06104 HMDB00448 alanylalanine 1379.5 271.1 54,603,626,992,112 C00993 HMDB03459 allantoin 1809.8 518.3 204 C02350 HMDB00462 alpha-hydroxyisovalerate 1208 145.1 99823 HMDB00407 alpha-ketoglutarate 1779 419.1 51 C00026 HMDB00208 alpha-tocopherol 2305.4 502.5 14985 C02477 HMDB01893 arachidate (20:0) 2071.2 369.3 10467 C06425 HMDB02212 ascorbate (Vitamin C) 1850.1 332.1 C00072 HMDB00044 asparagine 1854 232.2 62,676,992,089 C00152 HMDB00168 aspartate 1763.1 348.2 5960 C00049 HMDB00191 benzoate 1291.5 179 243 C00180 HMDB01870 beta-alanine 1582.3 334.1 2,394,755,801 C00099 HMDB00056 beta-hydroxypyruvate 1425.1 221 964 C00168 HMDB01352 beta-sitosterol 2380.8 357.4 222284 C01753 HMDB00852 campesterol 2353 343.4 173183 C01789 HMDB02869 chiro-inositol 1857 318.1 cholesterol 2316.9 329.3 6432564 C00187 HMDB00067 vaccenate (18:1n7) 1987 339.3 5282761 C08367 citrate 1763.4 273.1 311 C00158 HMDB00094 dihydrocholesterol 2320.8 215.2 6665 HMDB00908 dimethylglycine 1030 57.9 6,971,056,673 C01026 HMDB00092 erythritol 1517.5 217 C00503 HMDB02994 erythronate* 1546.9 292.1 2781043 HMDB00613 fructose 1758 217 5984 C00095 HMDB00660 fucose 1682.2 204 3034656 C02095 HMDB00174 fumarate 1382.1 245 C00122 HMDB00134 gluconate 1879.4 333 10690 C00257 HMDB00625 glucose 1866.8 217.1 79025 C00031 HMDB00122 glutamate 1836.8 362.2 611 C00025 HMDB03339 glutarate (pentanedioate) 1433.6 261 4418048 C00489 HMDB00661 glycerate 1360.7 189 752 C00258 HMDB00139 glycerol 1311 205 753 C00116 HMDB00131 glycerol 2-phosphate 1691.8 243 2526 C02979 HMDB02520 glycerol 3-phosphate (G3P) 1719.7 357.1 754 C00093 HMDB00126 glycine 1486.9 218.1 5,257,127,750 C00037 HMDB00123 glycolate (hydroxyacetate) 1119 177 3,698,251,757 C00160 HMDB00115 gulono-1,4-lactone 1862 333.1 608 C01040 HMDB03466 homoserine (homoserine lactone) 1726.1 334.2 126,476,971,022 C00263 HMDB00719 indolelactate 1964.9 202 92904 C02043 HMDB00671 inositol 1-phosphate (I1P) 2057.8 318.1 C04006 HMDB00213 Isobar: ribulose 5-phosphate, xylulose 5-phosphate 1935 357.2 isosorbide 1522 100.9 12597 D00347 lactate 1102.8 116.9 612 C00186 HMDB00190 lysine 1910 172.1 5962 C00047 HMDB00182 malate 1502 233 525 C00149 HMDB00156 mannitol 1839 319.1 6251 C00392 HMDB00765 mannose 1753.5 203.9 161658 C00159 HMDB00169 myo-inositol 1924.9 217 C00137 HMDB00211 N-acetylaspartate (NAA) 1648.5 274 65065 C01042 HMDB00812 N-acetylglycine 1396.4 143.9 10972 HMDB00532 N-acetylneuraminate 2074.9 245 C00270 HMDB00230 N-acetylserine 1526 218 65249 HMDB02931 oleate (18:1n9) 1984.4 339.2 445639 C00712 HMDB00207 ornithine 1940.3 174.1 6262 C00077 HMDB03374 orotate 1709.6 254.1 967 C00295 HMDB00226 oxalate (ethanedioate) 1175.1 219 3,819,775,971 C00209 HMDB02329 palmitoyl sphingomyelin 2524 311.3 9939941 pentadecanoate (15:0) 1853.5 299.2 13849 C16537 HMDB00826 phosphate 1307.7 298.9 1061 C00009 HMDB01429 phosphoenolpyruvate (PEP) 1595.4 369 1005 C00074 HMDB00263 phosphoethanolamine (PE) 1577.3 299.1 52,323,241,015 C00346 HMDB00224 pimelate (heptanedioate) 1602.9 155 385 C02656 HMDB00857 pinitol 1773 318.1 C03844 pyrophosphate (PPi) 1642.3 451 644102 C00013 HMDB00250 pyruvate 1130.6 217 107735 C00022 HMDB00243 ribitol 1692.4 217 C00474 HMDB00508 ribose 1652 204 5311110 C00121 HMDB00283 ribulose 1662 306.1 79021 C00309 HMDB00621 scyllo-inositol 1893.8 318.2 C06153 HMDB06088 serine 1656.3 320.2 59,516,857,581 C00065 HMDB00187 sorbitol 1843 319.1 107428 C00794 HMDB00247 stearamide 2071 131 31292 C13846 sphingomyelin 2645 311.3 6453725 C00550 HMDB01348 succinate 1348 247 1110 C00042 HMDB00254 taurine 1616.4 254.1 11,234,068,592 C00245 HMDB00251 threitol 1513 217.1 169019 C16884 HMDB04136 threonate 1560.7 292.1 151152 C01620 HMDB00943 threonine 1687.4 407.1 69,710,196,288 C00188 HMDB00167 hydroxyproline 1733.1 274.1 58,106,971,053 C01157 HMDB00725 uracil 1370.4 241 1174 C00106 HMDB00300 urea 1223.9 171 117,616,150,869 C00086 HMDB00294 xanthine 1889.9 353 1188 C00385 HMDB00292 xylitol 1677.6 307.2 6912 C00379 HMDB02917 xylonate 1722 292 6602431 C05411 xylose 1723.9 204 95259 C00181 HMDB00098 xylulose 1668 306.1 5289590 C00310 HMDB00654 METABOLITES_END #END