#METABOLOMICS WORKBENCH kapitsinou_20210703_202324_mwtab.txt DATATRACK_ID:2739 STUDY_ID:ST001866 ANALYSIS_ID:AN003028 PROJECT_ID:000000 VERSION 1 CREATED_ON July 18, 2021, 8:33 am #PROJECT PR:PROJECT_TITLE Systemic metabolic responses to pharmacologic PHD inhibition PR:PROJECT_SUMMARY While prolyl-hydroxylase (PHD) enzymes and hypoxia inducible factors (HIFs) have PR:PROJECT_SUMMARY been identified as key elements of oxygen sensing machinery, the mechanisms by PR:PROJECT_SUMMARY which PHD inhibition protects against ischemic injury remain unclear. Here, we PR:PROJECT_SUMMARY have performed serum metabolomic profiling to assess alterations induced by PR:PROJECT_SUMMARY pharmacologic PHD inhibition. 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 PHD inhibition 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 14 ST:NUM_MALES 14 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 - PHI_1 Treatment:PHI SUBJECT_SAMPLE_FACTORS - PHI_2 Treatment:PHI SUBJECT_SAMPLE_FACTORS - PHI_3 Treatment:PHI SUBJECT_SAMPLE_FACTORS - PHI_4 Treatment:PHI SUBJECT_SAMPLE_FACTORS - PHI_5 Treatment:PHI SUBJECT_SAMPLE_FACTORS - PHI_6 Treatment:PHI SUBJECT_SAMPLE_FACTORS - PHI_7 Treatment:PHI SUBJECT_SAMPLE_FACTORS - Veh_6 Treatment:Vehicle SUBJECT_SAMPLE_FACTORS - Veh_7 Treatment:Vehicle SUBJECT_SAMPLE_FACTORS - Veh_8 Treatment:Vehicle SUBJECT_SAMPLE_FACTORS - Veh_9 Treatment:Vehicle SUBJECT_SAMPLE_FACTORS - Veh_10 Treatment:Vehicle SUBJECT_SAMPLE_FACTORS - Veh_11 Treatment:Vehicle SUBJECT_SAMPLE_FACTORS - Veh_12 Treatment:Vehicle #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 pharmacologic PHD inhibition or TR:TREATMENT_SUMMARY treatment with vehicle. Specifically, mice were treated with two doses of PHD TR:TREATMENT_SUMMARY inhibitor ( IOX2, 60 mg/kg by gavage, 48hrs and 6 hrs prior to collection time) TR:TREATMENT_SUMMARY while 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 NEGATIVE 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 PHI_1 PHI_2 PHI_3 PHI_4 PHI_5 PHI_6 PHI_7 Veh_6 Veh_7 Veh_8 Veh_9 Veh_10 Veh_11 Veh_12 Factors Treatment:PHI Treatment:PHI Treatment:PHI Treatment:PHI Treatment:PHI Treatment:PHI Treatment:PHI Treatment:Vehicle Treatment:Vehicle Treatment:Vehicle Treatment:Vehicle Treatment:Vehicle Treatment:Vehicle Treatment:Vehicle 1-arachidonoylglycerophosphoethanolamine* 849088 687526 782321 808774 701522 807251 833437 713779 760848 871872 819227 734909 764683 632703 1-arachidonoylglycerophosphoinositol* 348963 310406 213506 208856 412138 1110648 1071918 248452 870326 640561 398138 315952 1182872 711874 1-linoleoylglycerophosphoethanolamine* 633116 623540 983968 833132 588757 641316 495813 1237803 486487 534018 635315 742747 518353 347270 1-linoleoylglycerophosphoinositol* 67667 54490 55050 46686 104396 175963 112287 61251 117722 130738 81734 50063 164354 123250 1-oleoylglycerophosphoethanolamine 167585 139324 313220 313665 240880 125666 108557 325873 157071 133764 156169 220918 134570 89816 1-palmitoylglycerophosphoethanolamine 535977 479083 635070 660010 681774 308561 476773 702929 444878 463366 441430 507172 331109 255324 1-palmitoylglycerophosphoinositol* 14839 82236 37878 32866 72455 69080 92783 37145 103001 99957 27003 84116 30439 1-palmitoylplasmenylethanolamine* 50085 61273 121985 159243 81429 74252 63330 175912 68381 60832 92394 118001 50626 55732 1-stearoylglycerophosphoethanolamine 264960 399300 846050 998558 443656 224372 330490 940944 301017 368502 401579 775603 230174 149192 1-stearoylglycerophosphoinositol 32590 72437 68602 57628 76773 121780 115369 68461 55028 99498 79324 52203 69363 54995 10-heptadecenoate (17:1n7) 379107 299131 495339 443610 491538 804026 963017 455293 423503 506726 250928 313820 513314 544243 10-nonadecenoate (19:1n9) 139043 107099 138485 149849 162807 280598 258866 134908 89188 182127 92828 92112 134436 147897 10-undecenoate (11:1n1) 8606 18944 17644 25706 22614 20506 12161 14870 26588 20922 13941 11610 17294 12,13-hydroxyoctadec-9(Z)-enoate 47975 46705 45187 47938 67405 32108 69034 53560 50821 51430 23211 26756 23745 33867 12-HEPE 251753 442563 796710 771182 192136 486993 972331 905297 1545934 1427482 873518 839073 414432 473737 12-HETE 907001 831275 2384279 2662675 976129 2065897 3277216 3373324 3089545 2350946 3298088 2409789 1275423 1406550 13-HODE + 9-HODE 155701 225944 211020 202269 91282 675218 632071 284495 223299 249399 205190 153474 241004 247096 15-methylpalmitate (isobar with 2-methylpalmitate) 237268 211331 270652 299143 299406 402694 302473 282541 165722 278498 226404 263507 202235 258379 17-methylstearate 31509 40289 79229 55679 39088 64530 61086 53097 42194 56943 40512 58023 53801 69861 2'-deoxyuridine 15961 25329 22877 27066 23606 18072 19277 13983 16739 19052 20312 16587 10697 9144 2-arachidonoylglycerophosphoethanolamine* 145916 122306 113733 122518 112006 176541 250617 131893 156492 141296 143320 114872 224736 146162 2-hydroxy-3-methylvalerate 55203 56484 47799 57447 54973 50886 56531 19903 34156 37073 21767 27504 19357 12191 2-hydroxypalmitate 69174 61474 101200 151718 141526 84899 135555 49318 111201 67286 82515 77845 57329 68417 2-hydroxystearate 46871 42758 49997 71604 51367 89386 81338 39144 46255 42068 45456 36402 45147 33219 2-linoleoylglycerophosphoethanolamine* 86167 66665 96263 92685 78414 98826 119760 137709 54814 49480 64633 80262 138258 66006 2-oleoylglycerophosphoethanolamine* 33717 25951 40898 40335 43899 28812 23438 55580 34270 31045 29048 30438 36784 21011 2-palmitoylglycerophosphoethanolamine* 72907 61447 130611 129632 72328 35775 52353 137351 68152 59642 69399 94346 39705 29604 3-(4-hydroxyphenyl)lactate 123888 155057 144943 153646 120763 76909 107621 192664 85253 65694 155224 166148 49832 57578 3-hydroxydecanoate 10709 11332 15122 13937 21128 6842 23331 14290 24752 29317 8965 11440 6702 9709 3-indoxyl sulfate 1164190 836183 938264 851085 872785 1140204 1341647 950662 451432 537975 592204 632416 768874 694213 3-methyl-2-oxobutyrate 89757 101148 89536 84856 116814 68667 104491 78795 104521 115750 80731 103496 60810 67104 3-methyl-2-oxovalerate 195714 210586 176597 159756 223375 142651 221694 151876 241759 214137 230664 295625 121309 159170 3-methylhistidine 12170 7718 4814 4177 7520 7731 8847 9418 8531 7928 6249 5433 5366 3-phenylpropionate (hydrocinnamate) 52476 36349 38052 38663 80830 43507 21408 117849 21812 15935 16675 18904 47731 39979 4-hydroxyphenylpyruvate 31810 107309 82084 38415 63469 6495 55108 15065 19369 92428 110781 8404 12996 4-methyl-2-oxopentanoate 146226 149812 134362 123177 199167 115180 152074 130480 191117 145015 181892 230372 115437 116229 4-vinylphenol sulfate 31315 24295 30212 36383 43710 245014 240757 6615 7646 4346 9589 8976 163005 60637 5-oxoproline 138407 148461 122920 124031 135595 296962 286548 168770 156265 150016 165370 144156 318638 241341 7-alpha-hydroxy-3-oxo-4-cholestenoate (7-Hoca) 75987 86827 75123 91910 83922 78774 44826 94734 54287 38881 98084 90421 62828 63586 8-hydroxyoctanoate 39484 35191 30391 43956 59513 29005 30673 34991 54755 49780 29304 35026 29245 26321 adrenate (22:4n6) 1234629 975954 1751654 1117246 1014165 1147264 1720864 1194453 1026515 1490344 762901 1859119 921076 895822 alpha-hydroxyisocaproate 16933 22856 15715 22745 16756 16308 8690 15513 18108 18545 16632 23202 12790 10374 alpha-muricholate 9443 8769 4214 4737 22026 4641 19786 3984 anserine 27458 16706 12973 19220 19662 11988 15851 23418 17845 19780 30318 15290 15913 11785 arachidonate (20:4n6) 2064855 1941622 1704855 2170283 1657529 6383238 7901680 2180888 2430053 2300206 2045777 1823302 4730350 4268724 azelate (nonanedioate) 5711376 5714867 4510599 5306987 7840534 4200267 4634066 4297356 7093313 6757929 4302513 5345191 4905409 3973226 beta-estradiol 3-sulfate 26808 26725 22522 19979 28807 11005 6259 4041 9689 13175 beta-hydroxyisovalerate 21038 28754 30446 26293 21584 19683 25014 8749 23524 18123 17895 22917 16554 8052 beta-muricholate 186093 128861 72282 82318 188611 87655 55702 267484 32496 61209 87735 204088 45619 115458 bilirubin (E,E)* 15681 9108 18294 12632 38088 7433 7893 10373 7483 7442 4564 caprate (10:0) 959374 712844 622061 528073 874489 503125 508441 706105 1132618 1103135 658890 567929 545057 429914 caproate (6:0) 68871 68467 47313 54346 89090 47254 60029 51615 83977 87046 47238 54530 55604 38174 caprylate (8:0) 649528 466108 351739 320223 556565 286842 314245 419544 699288 738449 468536 367626 326133 261637 catechol sulfate 617548 198604 672905 629607 635233 283440 257174 704967 97357 76879 188418 137701 313034 256345 cholate 78668 363059 108528 122530 182290 33290 536893 17949 16539 113555 709852 134333 120570 cinnamoylglycine 111935 93540 88349 63908 123277 51932 51361 153804 72485 34867 34691 77954 95603 80117 cis-urocanate 37253 9142 4806 7192 10946 16702 18864 9327 6106 8809 11121 12754 24073 23553 daidzein 15611 61831 63020 68171 46461 17272 6026 57335 38330 46292 14233 6894 deoxycholate 278816 128273 62260 26049 268300 59406 125303 38770 21844 56756 31937 113697 46033 86371 dihomo-linoleate (20:2n6) 503311 550171 578984 575753 533650 1129635 1230537 608670 431824 717818 392723 391830 618785 582875 dihomo-linolenate (20:3n3 or n6) 568424 751778 620062 584422 681038 1528731 2210529 644361 638745 856062 610519 498177 1391211 1154625 docosadienoate (22:2n6) 20971 30038 32134 33233 33544 42792 48563 36961 23178 30284 22426 20389 37509 27808 docosahexaenoate (DHA; 22:6n3) 3430084 3982019 3561847 4427534 3795074 7802799 11564488 3015068 5433374 5483910 3656695 3791230 6096242 5833058 docosapentaenoate (n3 DPA; 22:5n3) 1252615 1601466 1109236 1220625 1145846 2165232 4116113 947971 2174689 2259858 1167689 926215 1789516 1600606 docosapentaenoate (n6 DPA; 22:5n6) 189230 201606 125397 147236 180174 368337 514196 167633 157141 249322 156152 105846 350531 238073 dodecanedioate 106980 102108 79574 110691 132771 66530 79237 92514 140021 121156 85582 99217 81030 67778 eicosapentaenoate (EPA; 20:5n3) 1265815 1286342 1086261 1251892 919275 2750607 3529633 1008858 1893893 1816107 1012153 874803 2543625 1953621 eicosenoate (20:1n9 or 11) 937157 1510488 1463042 1271032 1566898 2687231 2489957 1397225 674840 1363152 959946 1159409 1854431 1678349 equol sulfate 1162310 1197078 1636213 852525 2458598 1036608 1039126 1766774 491035 618978 602525 1137939 867258 742723 flavin adenine dinucleotide (FAD) 8432 7533 7915 12710 9074 8984 6069 9374 7751 9580 9898 8342 5183 7156 glycocholate 4187 22214 7363 5500 5650 10165 5006 6250 heptanoate (7:0) 65007 66073 48747 53335 84872 47317 46526 45577 81328 85578 48202 48476 46154 33297 hexadecanedioate 32125 36509 33199 38751 39603 23102 34518 36995 38072 33341 31381 30436 15775 13749 hexanoylglycine 92835 54936 121752 110245 116759 37925 179023 110801 400698 285306 143382 130843 44010 95237 hippurate 274549 199787 215106 221521 282925 191625 102672 508957 98216 76733 162922 179498 287977 235491 histidine 78320 110832 70783 77134 116077 82089 79255 147903 161339 146342 140555 144123 129757 123882 indolepropionate 14740 32196 19401 29392 41250 29097 17240 21694 15132 7931 12245 18693 11131 10568 inosine 6459 3188 73319 278404 8381 2622 6122 5862 17675 3283 isovalerate 9437 23892 9729 16027 15872 18803 18230 11329 9668 13836 15900 11978 11775 kynurenate 17588 17270 18830 32269 39228 8033 8204 19929 10088 12601 34411 37168 5495 10428 laurate (12:0) 6202211 4652859 3234592 2937248 5384976 3075292 3063791 4745019 7011980 6692001 4970388 4075975 3747756 2598796 linoleate (18:2n6) 21956662 21089910 23115776 27645198 26439362 33363874 45978368 22392406 23806488 24233904 16144134 17628466 21662266 24212228 linolenate [alpha or gamma; (18:3n3 or 6)] 3791072 3130159 3994959 4134430 3943586 4746735 7587260 3452388 4921198 4652476 2034579 2107065 2055223 2855120 margarate (17:0) 606661 471564 619113 616096 620024 1289373 841440 765093 385429 568141 500748 435819 549068 636567 mead acid (20:3n9) 76501 77631 68134 82085 65155 177072 104541 87053 87509 67428 81071 204217 183837 myristate (14:0) 4271632 3214506 3665066 4196734 4377528 3534841 5335365 4212102 3909160 5537197 2583372 3194735 2718469 2866094 myristoleate (14:1n5) 306099 132827 223885 325800 341571 213052 681345 192505 275843 488885 96265 167465 108349 186343 N-acetylalanine 19799 22188 20329 18333 20325 15084 18396 11977 15713 15674 12170 20043 7025 9713 N-acetylglutamine 34271 42333 41315 43303 44818 21469 28894 40598 41065 29420 49190 49930 21174 17266 N-acetylisoleucine 29514 18555 16861 35311 31609 18519 8841 46659 15340 43199 37152 20245 12899 N-acetylleucine 69732 106042 63406 72196 63594 39924 49180 135785 73954 50456 106421 126845 39564 27772 N-acetylmethionine 33775 87960 53382 50971 47031 18255 14733 102152 40832 34744 92210 96987 24840 16350 N-acetylphenylalanine 120274 146303 114682 122893 108443 64902 85552 112843 98843 63943 91068 105923 59032 43024 N-acetylthreonine 22280 30554 16658 32458 28575 27144 16383 29546 11308 16113 28048 32997 12029 18319 N-acetyltryptophan 142667 142290 106339 135975 107713 64323 86247 114009 106983 72749 106253 122940 45128 48148 N-acetyltyrosine 13909 51176 36837 30895 28642 15135 24761 25104 26941 13979 28335 37853 10396 10203 N-formylmethionine 14511 24281 22206 15833 23406 15158 12741 33397 19436 19854 31748 33227 22541 15397 nonadecanoate (19:0) 85209 138862 229240 157577 135051 333046 233502 255992 122368 173130 135404 190632 230434 235148 octadecanedioate 20413 39710 20948 29649 43396 24338 31608 25286 19121 21616 20908 23680 13890 20290 p-cresol sulfate 1179521 355939 515163 80970 612922 37602 38663 95052 31987 27918 141424 152212 16528 13030 palmitate (16:0) 23120328 17333620 28991654 31304112 19642676 31188108 43527308 31910278 24820132 24782864 17571778 23492250 24547670 25090308 palmitoleate (16:1n7) 5554581 3458228 5408836 6083272 6806272 6239498 13495080 4837054 7543248 7634383 2133298 3077801 4525068 4853958 pantothenate 194844 215627 182781 158437 191377 150969 182010 202082 164229 162376 216473 196286 129230 110173 pelargonate (9:0) 1049013 1211733 909092 886894 1255402 883479 955458 754660 1362770 1499837 771188 780390 847963 677686 phenol sulfate 607161 378463 412889 384220 604455 470144 608596 409222 144798 305697 308595 251041 305320 242036 phenylacetylglycine 93222 164249 45145 56526 50274 45452 85753 82639 111939 116043 155344 117726 112595 98673 phenyllactate (PLA) 14772 14600 18105 17953 14143 12967 15881 20020 10376 12174 14230 17376 6225 phenylpropionylglycine 49737 47184 47517 30761 64924 17819 12615 167738 28758 13307 32972 63417 28333 22143 pseudouridine 71014 64126 66458 64052 73822 66629 88595 53264 75879 71447 75723 55654 53142 47913 pyridoxate 45375 31665 32204 38220 41030 32956 37304 39829 42733 27708 31625 27839 19458 17020 sebacate (decanedioate) 498294 495033 367861 502127 693679 410246 429524 401514 689940 612140 382688 453427 522985 410963 stearate (18:0) 12797497 10715363 12977252 16423621 12063849 21240276 20092832 13976914 12178323 13698133 12259579 11331623 16112903 15393820 stearidonate (18:4n3) 234589 184341 196838 200858 178643 303734 562609 246098 299829 272707 96145 104778 158573 155677 suberate (octanedioate) 209902 232670 192117 236718 292216 254545 229164 223362 288617 254094 221231 249127 266756 205912 tauro-beta-muricholate 436917 2626958 1386953 2391106 898379 1421721 406910 682448 54573 87364 324610 465560 231400 205116 taurochenodeoxycholate 26652 191358 103321 98768 58234 35849 50974 51370 4837 12383 18757 63389 18499 26376 taurocholate 577936 3149013 1780171 1719061 997882 1951638 1125413 547049 67786 103272 297220 700640 407597 447485 taurodeoxycholate 309153 573717 364607 149635 228642 209645 462290 70191 29310 44941 41709 283033 63668 125113 tauroursodeoxycholate 49798 125317 75765 93082 45596 66443 118573 28132 10810 12117 15630 31523 26025 36073 tetradecanedioate 46601 40261 31346 48836 54515 31691 38211 45168 57074 51112 36635 42402 30526 24905 thymidine 56272 109512 98452 97839 96422 71311 85787 52321 90602 92861 87729 87037 37039 27780 undecanedioate 830231 841565 661595 839302 1084924 587781 607346 674030 1040912 939017 656207 801692 632237 593995 undecanoate (11:0) 118314 125956 112651 101688 129784 91036 101943 103802 141716 139739 89399 96010 94294 74645 urate 472624 413843 471068 517122 525821 371451 334503 707315 445247 404035 631170 636229 323649 270272 uridine 76744 61384 97932 124902 100855 72352 65933 54608 54610 70457 74805 109270 38193 39680 valerate 15753 17872 9762 17240 20071 10611 13111 21736 19047 20516 14502 10611 11671 10615 MS_METABOLITE_DATA_END #METABOLITES METABOLITES_START metabolite_name RI MASS PUBCHEM KEGG HMDB 1-arachidonoylglycerophosphoethanolamine* 5731 500.3 HMDB11517 1-arachidonoylglycerophosphoinositol* 5479 619.4 1-linoleoylglycerophosphoethanolamine* 5725 476.3 HMDB11507 1-linoleoylglycerophosphoinositol* 5487 595.3 1-oleoylglycerophosphoethanolamine 5928 478.3 9547071 HMDB11506 1-palmitoylglycerophosphoethanolamine 5940 452.3 9547069 HMDB11503 1-palmitoylglycerophosphoinositol* 5573 571.3 1-palmitoylplasmenylethanolamine* 6153 436.4 1-stearoylglycerophosphoethanolamine 6200 480.4 9547068 HMDB11130 1-stearoylglycerophosphoinositol 5800 599.4 10-heptadecenoate (17:1n7) 5558 267.3 5312435 10-nonadecenoate (19:1n9) 5775 295.4 5312513 10-undecenoate (11:1n1) 5086 183.3 12,13-hydroxyoctadec-9(Z)-enoate 5137 313.4 10236635 C14829 HMBD04705 12-HEPE 5236 317.3 10041593 HMDB10202 12-HETE 5295 319.3 HMDB06111 13-HODE + 9-HODE 5247 295.2 15-methylpalmitate (isobar with 2-methylpalmitate) 5698 269.4 17-methylstearate 5987 297.4 3083779 2'-deoxyuridine 1608 227.1 13712 C00526 HMDB00012 2-arachidonoylglycerophosphoethanolamine* 5674 500.3 2-hydroxy-3-methylvalerate 1787 131.1 164623 HMDB00317 2-hydroxypalmitate 5508 271.3 92836 2-hydroxystearate 5705 299.4 69417 C03045 2-linoleoylglycerophosphoethanolamine* 5650 476.4 2-oleoylglycerophosphoethanolamine* 5848 478.3 2-palmitoylglycerophosphoethanolamine* 5790 452.3 3-(4-hydroxyphenyl)lactate 1395 181.1 9378 C03672 HMDB00755 3-hydroxydecanoate 4681 187.2 26612 HMDB02203 3-indoxyl sulfate 2258 212 10258 HMDB00682 3-methyl-2-oxobutyrate 1489 115.1 49 C00141 HMDB00019 3-methyl-2-oxovalerate 2106 129.2 47 C00671 HMDB03736 3-methylhistidine 911 168.1 649,696,971,061 C01152 HMDB00479 3-phenylpropionate (hydrocinnamate) 2830 149.1 C05629 HMDB00764 4-hydroxyphenylpyruvate 1716 179.1 979 C01179 HMDB00707 4-methyl-2-oxopentanoate 2200 129.2 70 C00233 HMDB00695 4-vinylphenol sulfate 3323 199.1 6426766 C05627 HMDB04072 5-oxoproline 744 128.2 7405 C01879 HMDB00267 7-alpha-hydroxy-3-oxo-4-cholestenoate (7-Hoca) 5268 429.4 3081085 C17337 HMDB12458 8-hydroxyoctanoate 2323 159.1 69820 HMDB00711 adrenate (22:4n6) 5684 331.3 5282844 C16527 HMDB02226 alpha-hydroxyisocaproate 1854 131.2 83697 C03264 HMDB00746 alpha-muricholate 4763 407.4 3083761 C17647 HMDB00506 anserine 1126 239.2 6,992,114,112,072 C01262 HMDB00194 arachidonate (20:4n6) 5525 303.4 444899 C00219 HMDB01043 azelate (nonanedioate) 1322 187.2 2266 C08261 HMDB00784 beta-estradiol 3-sulfate 4405 351.2 66416 C08357 HMDB10358 beta-hydroxyisovalerate 1043 117.1 69362 HMDB00754 beta-muricholate 4787 407.4 3083762 C17726 HMDB00415 bilirubin (E,E)* 4242 583.2 5315454 caprate (10:0) 5092 171.2 2969 C01571 HMDB00511 caproate (6:0) 2766 115.2 8892 C01585 HMDB00535 caprylate (8:0) 4367 143.2 379 C06423 HMDB00482 catechol sulfate 1928 188.9 3083879 C00090 cholate 5148 407.4 C00695 HMDB00619 cinnamoylglycine 3139 204.1 709625 cis-urocanate 1187 137.1 1549103 daidzein 3541 253.1 5281708 C10208 HMDB03312 deoxycholate 5268 391.4 440355 C04483 HMDB00626 dihomo-linoleate (20:2n6) 5722 307.3 6439848 C16525 dihomo-linolenate (20:3n3 or n6) 5600 305.4 5312529 C03242 HMDB02925 docosadienoate (22:2n6) 6017 335.4 5282807 C16533 docosahexaenoate (DHA; 22:6n3) 5518 327.3 445580 C06429 HMDB02183 docosapentaenoate (n3 DPA; 22:5n3) 5574 329.4 C16513 HMDB01976 docosapentaenoate (n6 DPA; 22:5n6) 5625 329.4 6441454 C06429 HMDB13123 dodecanedioate 2990 229.2 12736 C02678 HMDB00623 eicosapentaenoate (EPA; 20:5n3) 5442 301.3 446284 C06428 HMDB01999 eicosenoate (20:1n9 or 11) 5955 309.4 HMDB02231 equol sulfate 3625 321.2 flavin adenine dinucleotide (FAD) 2413 784.1 643975 C00016 HMDB01248 glycocholate 5104 464.4 10140 C01921 HMDB00138 heptanoate (7:0) 3695 129.2 8094 C17714 HMDB00666 hexadecanedioate 4650 285.2 10459 HMDB00672 hexanoylglycine 2918 172.1 99463 HMDB00701 hippurate 2136 178.1 464 C01586 HMDB00714 histidine 757 154.1 7,733,651,426 C00135 HMDB00177 indolepropionate 2795 188.2 3744 HMDB02302 inosine 1600 267.2 isovalerate 1623 101.2 10430 C08262 HMDB00718 kynurenate 2243 188.1 3845 C01717 HMDB00715 laurate (12:0) 5288 199.3 3893 C02679 HMDB00638 linoleate (18:2n6) 5533 279.3 5280450 C01595 HMDB00673 linolenate [alpha or gamma; (18:3n3 or 6)] 5450 277.3 C06427 HMDB01388 margarate (17:0) 5733 269.3 10465 HMDB02259 mead acid (20:3n9) 5642 305.4 5312531 HMDB10378 myristate (14:0) 5439 227.3 11005 C06424 HMDB00806 myristoleate (14:1n5) 5338 225.3 5281119 C08322 HMDB02000 N-acetylalanine 882 130.1 88064 C02847 HMDB00766 N-acetylglutamine 783 187.1 182230 C02716 HMDB06029 N-acetylisoleucine 2279 172.2 2802421 N-acetylleucine 2385 172.1 70912 C02710 HMDB11756 N-acetylmethionine 1805 190.1 448580 C02712 HMDB11745 N-acetylphenylalanine 2590 206.2 74839 C03519 HMDB00512 N-acetylthreonine 846 160.1 4651717 C01118 N-acetyltryptophan 2650 245.2 700653 C03137 N-acetyltyrosine 1677 222.2 68310 HMDB00866 N-formylmethionine 1541 176.1 439750 C03145 HMDB01015 nonadecanoate (19:0) 6073 297.3 12591 C16535 HMDB00772 octadecanedioate 5033 313.3 70095 HMDB00782 p-cresol sulfate 2896 187.1 4615422 C01468 palmitate (16:0) 5619 255.3 985 C00249 HMDB00220 palmitoleate (16:1n7) 5477 253.3 445638 C08362 HMDB03229 pantothenate 1486 218.2 6613 C00864 HMDB00210 pelargonate (9:0) 4847 157.2 5461016 C01601 HMDB00847 phenol sulfate 2150 173.1 74426 C02180 phenylacetylglycine 2377 192.1 68144 C05598 HMDB00821 phenyllactate (PLA) 2237 165.1 3848 C05607 HMDB00779 phenylpropionylglycine 2981 206.1 152323 HMDB00860 pseudouridine 1104 243.1 C02067 HMDB00767 pyridoxate 2210 182.1 6723 C00847 HMDB00017 sebacate (decanedioate) 1778 201.2 5192 C08277 HMDB00792 stearate (18:0) 5886 283.4 5281 C01530 HMDB00827 stearidonate (18:4n3) 5381 275.3 5312508 C16300 HMDB06547 suberate (octanedioate) 831 173.1 10457 C08278 HMDB00893 tauro-beta-muricholate 4763 514.4 168408 HMDB00932 taurochenodeoxycholate 5218 498.3 387316 C05465 HMDB00951 taurocholate 5122 514.3 C05122 HMDB00036 taurodeoxycholate 5243 498.3 2733768 C05463 HMDB00896 tauroursodeoxycholate 5002.6 498.4 HMDB00874 tetradecanedioate 3970 257.2 13185 HMDB00872 thymidine 1935 284.8 5789 C00214 HMDB00273 undecanedioate 2376 215.1 15816 HMDB00888 undecanoate (11:0) 5207 185.2 8180 HMDB00947 urate 769 167.1 C00366 HMDB00289 uridine 1430 243.1 6029 C00299 HMDB00296 valerate 1774 101.2 7991 C00803 HMDB00892 METABOLITES_END #END