#METABOLOMICS WORKBENCH kapitsinou_20210703_202324_mwtab.txt DATATRACK_ID:2739 STUDY_ID:ST001866 ANALYSIS_ID:AN003027 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 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 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-arachidonoylglycerophosphocholine* 748779 831736 1362205 1734656 931384 1516496 1455492 1084453 976084 878191 626550 884393 1432232 1467464 1-arachidoylglycerophosphocholine 88503 264424 115259 184809 251472 106620 77244 113030 84065 100823 148110 182713 1-docosahexaenoylglycerophosphocholine* 832591 1132311 1825230 2040891 1215794 2797471 2899908 1240924 1363664 1487665 909878 1211677 2250561 2304119 1-eicosadienoylglycerophosphocholine* 168238 201637 421675 154748 109800 92862 117593 154100 207934 1-eicosatrienoylglycerophosphocholine* 308341 308646 547944 606631 277382 1172150 887182 403929 411667 437021 346477 441749 773784 562480 1-heptadecanoylglycerophosphocholine 115944 105830 316406 450761 118657 658746 414465 251174 176559 146792 169826 92241 289391 229735 1-linoleoylglycerophosphocholine 2973004 3192762 5112608 4974607 3273347 5335267 4851675 3591927 2995316 3354845 2617112 3707283 4634259 3791664 1-myristoylglycerophosphocholine 122065 83531 152608 217639 136166 195898 211936 126646 137043 118445 55268 71145 143105 103493 1-oleoylglycerophosphocholine 1296052 1175746 2765764 2853171 1362693 3162954 2872002 1653266 1481375 2110201 1447144 1873705 2269282 1828015 1-palmitoleoylglycerophosphocholine* 342473 300658 472402 578319 315001 437077 631851 495011 378979 421978 186276 398454 478140 380443 1-palmitoylglycerophosphocholine 2820095 3980558 5130449 5467792 3329121 6332100 5477497 4274277 3342753 3325523 3664578 4194083 3548931 4119896 1-pentadecanoylglycerophosphocholine* 27261 34093 25673 55769 60293 34860 18801 24575 42953 38839 1-stearoylglycerophosphocholine 3954581 3665309 5610692 5355524 3464760 7757220 8251261 4982959 4557361 4428699 3918121 4262330 5218931 4858100 2'-deoxycytidine 43431 60124 57169 60868 79333 63128 62867 34683 59707 49883 47063 66517 39042 36486 2-aminoadipate 106472 151244 114803 121430 122159 86691 83505 172159 153191 112178 122737 169391 73516 103104 2-arachidonoylglycerophosphocholine* 367516 278924 471215 543935 389433 479271 321977 425303 331009 231931 285806 348073 233246 253227 2-docosahexaenoylglycerophosphocholine* 767619 609477 1203525 1476040 779690 1029863 908066 1059570 722686 834957 551612 1009495 703902 2-docosahexaenoylglycerophosphoethanolamine* 483514 285410 460668 416407 255767 433906 407188 530676 354454 211620 382628 309513 390647 379283 2-linoleoylglycerophosphocholine* 753334 738005 1236716 1296798 825890 985596 814880 1147871 598508 577240 657088 722868 770022 609195 2-methylbutyroylcarnitine 52203 65227 63203 52217 74919 26544 41193 126325 53236 70140 114052 113445 49995 46247 2-oleoylglycerophosphocholine* 224039 204891 294994 448921 223332 352073 371518 271407 239795 252272 168779 293389 199119 180191 2-palmitoylglycerophosphocholine* 877350 916522 1449776 1631773 779648 2021884 2234974 939627 1168147 1165401 919413 1269927 1367724 1277948 2-stearoylglycerophosphocholine* 443514 278731 691592 703564 242200 1517686 1234781 543176 516722 459778 392027 297442 612812 676496 3-dehydrocarnitine* 373001 312613 344880 367085 358239 402393 379853 459373 404995 409360 421754 353617 409667 345171 3-ureidopropionate 133739 215153 133517 185416 258169 94003 164668 291858 94295 130774 247822 240839 106391 92086 4-acetamidobutanoate 20535 13269 17326 18155 20209 20452 21230 18850 10900 6316 18249 18342 21196 12938 4-guanidinobutanoate 16049 44269 44591 26363 29230 20448 97253 11372 54029 36436 17129 5-methylthioadenosine (MTA) 34039 27924 32530 34171 19741 15646 12224 33955 16767 18024 34624 28079 14504 7302 acetylcarnitine 4441866 2717623 2886479 3060120 3123322 1951476 3341921 3761090 5078341 4062253 3948546 3040152 2053251 2036949 adenosine 14072 17512 289972 330488 237290 11356 12721 11408 20372 19488 adenosine 5'-monophosphate (AMP) 282210 421670 92304 arginine 200360 353466 319625 300291 288882 188308 80168 308742 259932 266229 402303 300010 110322 128860 betaine 879418 768278 692261 744676 908665 690250 494952 778441 743511 631759 994082 666076 647311 531903 biliverdin 129238 57473 66777 103760 129190 85424 74273 70995 55629 74731 26359 61245 95603 108239 bradykinin, des-arg(9) 125254 butyrylcarnitine 356441 351777 487219 513782 436027 143972 279929 1550002 427937 485354 741078 678972 232877 180391 butyrylglycine 73749 17715 52840 55972 45219 15544 42582 230743 161185 63646 70351 62830 13904 31369 C-glycosyltryptophan* 37600 33762 35303 37582 39393 23852 30114 45538 43641 36071 51628 37977 22265 24591 carnitine 1380477 1222435 1190869 1194524 1248433 1179816 890930 1297257 1083369 1236393 1427826 1435897 1264754 1086418 choline 589905 606755 505775 477934 465085 938745 956705 635479 727072 632049 679123 578863 907256 769831 citrulline 274200 454229 290853 353924 319298 292407 261983 465917 349148 354270 389424 458467 394474 309457 corticosterone 117571 287170 426206 408511 222154 109849 342049 206634 452913 314552 340411 578603 254286 403348 creatine 1829171 1647392 1494751 1380075 1624953 999544 1103871 1919607 1713108 1675450 2128853 1775003 1103864 1069171 creatinine 67509 71619 83266 63422 60632 90428 140907 72966 49861 111869 77715 111690 61751 46204 cysteine-glutathione disulfide 816563 726465 789062 946018 673001 30566 1307793 791234 559238 1226342 1191133 11712 18043 cytidine 164651 156199 156590 165704 181112 180061 175694 190715 245479 197060 222526 211945 156095 135363 deoxycarnitine 114558 92186 79967 99388 95516 78981 59394 149667 136496 106333 137936 101155 88432 83492 dimethylarginine (SDMA + ADMA) 277185 188981 347537 228868 228003 194702 305272 148372 227395 389881 180378 307800 175932 216460 ergothioneine 291016 268168 210966 242991 184955 126951 92136 294010 261154 273557 281094 263159 104379 100193 gamma-glutamylalanine 138609 241245 211818 208621 232194 46933 61833 203615 101640 152721 302690 285803 34172 29937 gamma-glutamylglutamate 45791 39835 36031 42221 48334 28555 38360 46962 30368 45508 45495 60677 30726 31469 gamma-glutamylglutamine 159862 211486 322479 309057 340480 46633 121632 273088 175292 268734 285794 303271 28225 32687 gamma-glutamylisoleucine* 99309 120398 84128 111718 109557 61987 90506 110264 91784 96739 130009 116251 54906 47441 gamma-glutamylleucine 304435 486963 391730 380415 429546 267807 342411 422420 301030 319816 525924 477082 246964 182585 gamma-glutamylmethionine 34445 181119 135030 87706 172081 9140 7872 90356 25944 69288 156431 183527 4712 16667 gamma-glutamylphenylalanine 195489 332326 298430 292557 333586 169324 201260 245351 134997 169864 301703 317872 132814 104440 gamma-glutamylthreonine* 55953 82365 87112 88103 89317 33088 40875 100578 36601 58094 98667 111478 37049 25733 gamma-glutamyltryptophan 43136 78646 80085 77046 91389 38450 53756 51518 37712 56714 69244 81394 24605 36267 gamma-glutamyltyrosine 90785 267917 260659 223285 229475 96531 135919 254951 135555 137443 254868 250011 68149 75600 gamma-glutamylvaline 114564 185451 136878 176150 168716 103720 146169 148816 132481 154288 236632 181132 84705 76017 glutamine 813652 801422 721369 824515 940415 674490 651439 1084173 915442 893203 1017777 876370 840970 822024 glutaroyl carnitine 22257 17440 16465 20852 24625 16074 19421 33757 29900 24643 43737 25873 12059 12439 glutathione, oxidized (GSSG) 1809656 2255130 1996527 2384484 1560667 14481 5027 2028493 1816671 1648336 2675594 1905504 10836 10342 glycerophosphorylcholine (GPC) 97153 124777 170496 178281 102994 547930 502703 155618 167580 185232 170435 167331 454804 453219 glycylvaline 29392 15832 8793 11741 57359 67368 41596 46392 52056 45291 26144 53375 70544 heme 7298975 5527752 5196483 7047486 3861834 4516180 3519094 5556350 7374705 7674934 4126025 4309043 5410656 4534062 heptaethylene glycol 574702 320242 181775 214022 413829 156369 156619 324388 575357 529525 476683 233486 244118 161659 hexaethylene glycol 441953 256406 160403 165318 372478 133104 137227 247073 459595 403642 366876 191043 168576 150793 hexanoylcarnitine 105600 69799 124919 123738 129185 38123 130980 446434 121921 168766 148073 116837 37498 59988 homocitrulline 66465 50064 72285 62288 54719 88462 108259 80474 37492 46023 58004 67225 63820 64345 homostachydrine* 259841 307614 337807 291755 352273 317069 226523 386600 189892 151169 376658 282261 216495 171736 imidazole propionate 11237 28545 11240 12418 14067 25655 17869 16350 16695 29874 17710 15398 indoleacetate 48764 40229 51354 80789 60474 46700 31440 57566 25656 32862 32473 58748 18727 18746 isobutyrylcarnitine 139111 160334 168105 216547 170645 63045 76054 412668 136864 109008 272808 292034 98452 78267 isoleucine 6829046 8340873 5294569 5654210 6580966 6320721 7068688 8480981 7830302 6031710 8225052 8903664 5474194 4375002 isovalerylcarnitine 62521 141973 95913 77034 93802 55297 85850 164772 90398 89358 158753 149355 98471 70147 isovalerylglycine 68516 78967 71376 57090 52682 31623 51859 103324 95607 64561 97771 117820 53660 28385 kynurenine 176178 197331 185920 267948 285801 157711 165918 105750 123341 135929 152600 131208 83364 89285 leucine 9657165 10783539 7413447 7615425 8686133 8236212 9107491 13408218 12065784 8462201 13424513 14017389 9878673 6789651 levulinate (4-oxovalerate) 56181 67706 33403 42139 66213 55610 49246 29835 69927 67922 34040 30061 33990 28393 methionine 2394539 4613589 2784698 1834195 2849019 3163254 1715359 4175701 1836169 1974509 5087806 4441560 2766743 1723708 methyl-beta-glucopyranoside 1959319 1563048 2194260 2310818 2247011 1699769 1298829 1805400 1806109 2057378 2055446 1742133 1360753 1281478 methylglutaroylcarnitine 42651 23249 27073 19577 18214 15453 30623 28445 24227 38956 37460 43545 11152 13445 N-acetyl-aspartyl-glutamate (NAAG) 50754 21985 20367 18399 15043 18647 35531 48711 22907 31273 29954 13549 N-acetyl-beta-alanine 57858 46700 52302 56847 76181 51794 69535 40728 55289 36218 32029 44351 42620 31268 N-acetylornithine 340502 342366 351507 257713 285956 356464 361221 426585 357877 385565 465373 424877 399522 338573 N1-methyladenosine 45419 46431 44064 47629 55289 38392 42069 43195 69288 55227 47840 50264 30108 25871 N1-methylguanosine 30429 14735 24218 21935 18034 21061 38936 14725 11003 15708 17055 15875 13387 N4-acetylcytidine 28974 29467 21197 36355 36178 18107 30036 24446 19122 19414 16540 12026 N6-carbamoylthreonyladenosine 26996 20105 21216 32823 23746 30086 32254 19716 22992 22319 26301 19885 16317 13093 nicotinamide 394200 213196 251380 289229 227074 267258 237169 393075 501690 252754 319113 324930 285678 187462 octaethylene glycol 507617 368213 223334 236680 486091 145893 120767 305551 636824 492675 468080 319355 190905 193230 octanoylcarnitine 96857 78471 91629 100803 91618 50567 60044 95747 99344 129743 76040 77896 32832 47363 ophthalmate 54377 86379 76232 118484 87438 32631 46553 58080 84384 97953 193381 80786 33153 26211 palmitoylcarnitine 428459 214406 235523 345714 247571 224194 646478 304736 355727 336547 198674 247233 249255 263459 pentaethylene glycol 402127 251186 152936 168858 351335 122830 116549 243931 385377 339802 310997 159802 175535 141723 phenylalanine 7913724 11536084 8676500 8988864 9506602 8560433 9083302 11019897 9618837 8100780 11193949 10973146 8964172 7417442 pipecolate 367285 405805 381165 393724 360076 367970 369368 473410 344241 445572 599504 574719 369342 247376 pro-hydroxy-pro 198452 199102 178688 291012 205732 180619 311271 266655 320190 246274 300917 323391 209641 192570 proline 931444 1569348 1159410 1159640 1138063 1231407 983813 1751420 874151 961237 1851925 2057324 1264168 945818 propionylcarnitine 479701 568595 631010 568929 594364 274010 244757 1022435 421152 499147 845999 749255 377759 346969 riboflavin (Vitamin B2) 50251 56164 43963 58202 64189 39269 59419 44116 37998 36948 34206 46240 30512 21850 S-adenosylhomocysteine (SAH) 15629 18035 25458 23471 17422 8374 8766 26618 9558 12650 20910 38113 13981 7581 serotonin (5HT) 764520 225938 1595967 1563303 1219685 992608 795196 1165493 906093 1010591 1392505 1508509 683858 715205 spermidine 155868 241623 171581 197174 204115 119692 112688 105621 132510 125892 143153 119100 108805 89752 sphinganine 111145 41420 52853 72083 66142 135612 172654 33652 70141 37335 47686 51291 66139 sphingosine 131447 95652 110510 115813 64672 326709 358922 122849 90548 96461 42240 64923 214517 241953 stachydrine 640457 768059 893231 747990 849069 730454 506071 1115825 374849 303873 869362 798161 525551 357440 succinylcarnitine 47615 39309 25854 25571 33270 19324 14879 33383 40769 23817 27894 26521 21732 19526 taurine 113085 66499 103180 107202 83196 100419 116569 145551 151844 123505 122168 127174 99726 127650 TDTEDKGEFLSEGGGV* 7241961 739348 8307566 10257848 2535122 7362546 7998165 4105139 8069388 7255864 8012116 6408058 5695208 4149960 TDTEDKGEFLSEGGGVR* 846841 2009345 96580 443426 5164939 160012 160149 174839 117241 252523 24139 8414 tetraethylene glycol 237232 131030 99786 115211 199108 153613 93393 141492 187673 224439 163116 168905 170454 112390 threonine 134776 243108 99335 168779 180440 140666 100812 273109 174760 207418 311649 293781 215010 183146 tigloylglycine 17968 18780 12365 36699 46531 22778 19094 41571 trans-urocanate 74137 86243 68570 87343 86927 142214 186513 50011 79802 39910 62411 68402 264816 292902 triethyleneglycol 178754 132419 104721 108434 179748 86991 93001 114768 138863 180849 120151 99396 116558 118729 trigonelline (N'-methylnicotinate) 119652 148830 161272 131057 131389 152331 83721 199423 60797 51645 142709 134222 131506 81974 tryptophan 10248054 15876323 10679213 11494191 12009040 11607541 10772715 9283818 10871883 12563372 13268244 14072076 10385009 10365543 tyrosine 3329390 8566435 5298628 4945771 5220956 3955207 4111086 5185822 3076253 3673040 6791395 6845597 3719480 3065088 valerylcarnitine 22954 18246 34033 49269 34596 12503 16919 166730 16345 22650 62542 63242 9210 7483 valerylglycine 46755 31768 36111 33446 32924 15391 24584 137952 50315 38533 57790 53321 22562 28189 valine 6270019 9117785 5345699 5709205 6520635 5858772 6110177 8502922 7618755 6224579 8728732 9196776 6526250 5208150 xanthosine 45882 49192 56329 105247 39282 27656 20282 111135 26114 16355 77138 93721 37026 22080 MS_METABOLITE_DATA_END #METABOLITES METABOLITES_START metabolite_name RI MASS PUBCHEM KEGG HMDB 1-arachidonoylglycerophosphocholine* 5554 544.3 C05208 1-arachidoylglycerophosphocholine 6100 552.4 HMDB10390 1-docosahexaenoylglycerophosphocholine* 5518 568.4 1-eicosadienoylglycerophosphocholine* 5696 548.3 1-eicosatrienoylglycerophosphocholine* 5600 546.4 1-heptadecanoylglycerophosphocholine 5750 510.4 HMDB12108 1-linoleoylglycerophosphocholine 5574 520.4 11988421 C04100 1-myristoylglycerophosphocholine 5481 468.3 460604 HMDB10379 1-oleoylglycerophosphocholine 5700 522.4 16081932 1-palmitoleoylglycerophosphocholine* 5524 494.3 1-palmitoylglycerophosphocholine 5671 496.4 86554 1-pentadecanoylglycerophosphocholine* 5563 482.3 1-stearoylglycerophosphocholine 5844 524.4 497299 2'-deoxycytidine 1256 228 13711 C00881 HMDB00014 2-aminoadipate 794 162.1 469 C00956 HMDB00510 2-arachidonoylglycerophosphocholine* 5524 544.3 2-docosahexaenoylglycerophosphocholine* 5507 568.3 2-docosahexaenoylglycerophosphoethanolamine* 5512 526.2 2-linoleoylglycerophosphocholine* 5544 520.4 2-methylbutyroylcarnitine 2439 246.1 6426901 HMDB00378 2-oleoylglycerophosphocholine* 5640 522.4 2-palmitoylglycerophosphocholine* 5604 496.3 2-stearoylglycerophosphocholine* 5780 524.4 10208382 3-dehydrocarnitine* 1020 160.2 6991982 C02636 HMDB12154 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 acetylcarnitine 1203 204.2 7045767 C02571 HMDB00201 adenosine 1650 268.1 60961 C00212 HMDB00050 adenosine 5'-monophosphate (AMP) 1210 348.1 15938965 C00020 HMDB00045 arginine 650 175.2 5,246,487,232 C00062 HMDB00517 betaine 721 118.2 247 HMDB00043 biliverdin 4936 583.3 C00500 HMDB01008 bradykinin, des-arg(9) 3516 453 105044 C00306 HMDB04246 butyrylcarnitine 2007 232.2 213144 butyrylglycine 2077 146.1 88412 HMDB00808 C-glycosyltryptophan* 1912 367.1 carnitine 702 162.2 10917 choline 674 104.2 170746 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 (SDMA + ADMA) 812 203.2 123831 C03626 HMDB01539,HMDB03334 ergothioneine 847 230.2 3032311 C05570 HMDB03045 gamma-glutamylalanine 1108 219 440103 gamma-glutamylglutamate 1036 277.1 92865 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-glutamylthreonine* 977 249.1 gamma-glutamyltryptophan 3033 334.2 3038501 gamma-glutamyltyrosine 2073 311.2 94340 gamma-glutamylvaline 2040 247.2 HMDB11172 glutamine 684 147.2 69,920,865,961 C00064 HMDB00641 glutaroyl carnitine 1565 276.1 HMDB13130 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 heptaethylene glycol 2836 327.2 79718 hexaethylene glycol 2651 283.2 17472 hexanoylcarnitine 3174 260.2 6426853 C01585 HMDB00705 homocitrulline 832 190.1 650,726,991,977 C02427 HMDB00679 homostachydrine* 1199 158.2 441447 C08283 imidazole propionate 1011.7 141.1 70630 HMDB02271 indoleacetate 3760 176.1 802 C00954 HMDB00197 isobutyrylcarnitine 1941 232.2 isoleucine 1614 132.1 791 C00407 HMDB00172 isovalerylcarnitine 2533 246.2 6426851 HMDB00688 isovalerylglycine 2665 160.1 546304 HMDB00678 kynurenine 1902 209.1 1,611,666,971,029 C00328 HMDB00684 leucine 1674 132.2 70,457,986,106 C00123 HMDB00687 levulinate (4-oxovalerate) 1867 117 11579 HMDB00720 methionine 1252 150.1 69,920,876,137 C00073 HMDB00696 methyl-beta-glucopyranoside 1094.3 212.1 2108 methylglutaroylcarnitine 1900 290.1 128145 HMDB00552 N-acetyl-aspartyl-glutamate (NAAG) 1563 305 5255 C12270 HMDB01067 N-acetyl-beta-alanine 1460 132.1 76406 C01073 N-acetylornithine 875 175.2 6,992,102,439,232 C00437 HMDB03357 N1-methyladenosine 1356 282.1 5460178 C02494 HMDB03331 N1-methylguanosine 1850 298.1 96373 HMDB01563 N4-acetylcytidine 2030 286.1 107461 HMDB05923 N6-carbamoylthreonyladenosine 2656 413 nicotinamide 1267 123.1 936 C00153 HMDB01406 octaethylene glycol 3054 371.3 78798 octanoylcarnitine 4100 288.3 123701 ophthalmate 1457 290.1 9817431 HMDB05765 palmitoylcarnitine 5179 400.4 461 pentaethylene glycol 2471 239.2 62551 phenylalanine 2056 166.1 69,256,656,140 C00079 HMDB00159 pipecolate 1120 130.1 849 C00408 HMDB00070 pro-hydroxy-pro 960 229.2 11673055 HMDB06695 proline 796 116.1 1,457,426,971,047 C00148 HMDB00162 propionylcarnitine 1589 218.2 107738 C03017 HMDB00824 riboflavin (Vitamin B2) 3111 377.2 493570 C00255 HMDB00244 S-adenosylhomocysteine (SAH) 1480 385.1 C00021 HMDB00939 serotonin (5HT) 1660 177.1 5202 C00780 HMDB00259 spermidine 533 146.2 1102 C00315 HMDB01257 sphinganine 5175 302.3 3126 C00836 HMDB00269 sphingosine 5197 300.2 5353955 C00319 HMDB00252 stachydrine 860 144.1 115244 C10172 HMDB04827 succinylcarnitine 1401 262.1 taurine 687 126.1 11,234,068,592 C00245 HMDB00251 TDTEDKGEFLSEGGGV* 3301 821.1 TDTEDKGEFLSEGGGVR* 2880 600 tetraethylene glycol 2192 195.1 8200 threonine 713 120.1 69,710,196,288 C00188 HMDB00167 tigloylglycine 2523 158.1 6441567 HMDB00959 trans-urocanate 1119 139.1 736715 C00785 HMDB00301 triethyleneglycol 1824 168.1 trigonelline (N'-methylnicotinate) 757 138.1 5570 HMDB00875 tryptophan 2445 205.1 69,235,166,305 C00078 HMDB00929 tyrosine 1516 182.1 60,576,942,100 C00082 HMDB00158 valerylcarnitine 2584 246.2 6426903 HMDB13128 valerylglycine 2824 160.1 4737557 HMDB00927 valine 1040 118.1 69,710,186,287 C00183 HMDB00883 xanthosine 1785 285 64959 C01762 HMDB00299 METABOLITES_END #END