#METABOLOMICS WORKBENCH joh18358_20240719_105628 DATATRACK_ID:5027 STUDY_ID:ST003335 ANALYSIS_ID:AN005465 PROJECT_ID:PR002074 VERSION 1 CREATED_ON July 20, 2024, 7:15 am #PROJECT PR:PROJECT_TITLE Biological stress metabolomics in Duchenne muscular dystrophy rodent model PR:PROJECT_TYPE Biological Stress Discovery Targeted Metabolomics PR:PROJECT_SUMMARY Our goal is to identify stress-relevant metabolomic alterations in PR:PROJECT_SUMMARY dystrophin-deficient organisms following physiological stress exposure. Here we PR:PROJECT_SUMMARY performed a targeted mass spectrometry-based plasma metabolomics screen through PR:PROJECT_SUMMARY Metabolon that focused on biological stress pathways in healthy and PR:PROJECT_SUMMARY dystrophin-deficient mdx mice exposed to mild scruff stress. One-third of the PR:PROJECT_SUMMARY stress-relevant metabolites interrogated displayed significant elevation or PR:PROJECT_SUMMARY depletion in mdx plasma after scruff stress and were restored to WT by skeletal PR:PROJECT_SUMMARY muscle-specific dystrophin expression. The metabolic pathways of mdx mice PR:PROJECT_SUMMARY altered by scruff stress are associated with regulation of the PR:PROJECT_SUMMARY hypothalamic-pituitary-adrenal axis, locomotor tone, neurocognitive function, PR:PROJECT_SUMMARY redox metabolism, cellular bioenergetics, and protein catabolism. Our data PR:PROJECT_SUMMARY suggest that a mild stress triggers an exaggerated, multi-system metabolic PR:PROJECT_SUMMARY response in mdx mice. PR:INSTITUTE University of Minnesota PR:DEPARTMENT Biochemistry, Molecular Biology, and Biophysics PR:LABORATORY James Ervasti PR:LAST_NAME Johnson PR:FIRST_NAME Erynn PR:ADDRESS 420 Washington Ave SE PR:EMAIL joh18358@umn.edu PR:PHONE 4024054007 PR:FUNDING_SOURCE 5T32AR007612-21; 5T32AR007612-22; 5T32AG029796-13; 5T32AG029796-14; PR:FUNDING_SOURCE 5R01AR042423-27; 5R01AR049899-18 PR:CONTRIBUTORS Erynn E. Johnson; James M. Ervasti #STUDY ST:STUDY_TITLE Biological stress metabolomics in Duchenne muscular dystrophy rodent model ST:STUDY_TYPE Biological Stress Discovery Targeted Metabolomics ST:STUDY_SUMMARY Duchenne muscular dystrophy is a severe neuromuscular wasting disease that is ST:STUDY_SUMMARY caused by a primary defect in dystrophin protein and involves organism-wide ST:STUDY_SUMMARY comorbidities such as cardiomyopathy, metabolic and mitochondrial dysfunction, ST:STUDY_SUMMARY and non-progressive cognitive impairments. Physiological stress exposure in the ST:STUDY_SUMMARY mdx mouse model of Duchenne muscular dystrophy results in phenotypic ST:STUDY_SUMMARY abnormalities that include locomotor inactivity, hypotension, and increased ST:STUDY_SUMMARY morbidity. Severe and lethal stress susceptibility in mdx mice corresponds to ST:STUDY_SUMMARY metabolic dysfunction in several coordinated metabolic pathways within ST:STUDY_SUMMARY dystrophin-deficient skeletal muscle, as well as prolonged elevation in mdx ST:STUDY_SUMMARY plasma corticosterone levels that extends beyond the WT stress response. Here we ST:STUDY_SUMMARY performed a targeted mass spectrometry-based plasma metabolomics screen focused ST:STUDY_SUMMARY on biological stress pathways in healthy and dystrophin-deficient mdx mice ST:STUDY_SUMMARY exposed to mild scruff stress. One-third of the stress-relevant metabolites ST:STUDY_SUMMARY interrogated displayed significant elevation or depletion in mdx plasma after ST:STUDY_SUMMARY scruff stress and were restored to WT by skeletal muscle-specific dystrophin ST:STUDY_SUMMARY expression. The metabolic pathways of mdx mice altered by scruff stress are ST:STUDY_SUMMARY associated with regulation of the hypothalamic-pituitary-adrenal axis, locomotor ST:STUDY_SUMMARY tone, neurocognitive function, redox metabolism, cellular bioenergetics, and ST:STUDY_SUMMARY protein catabolism. Our data suggest that a mild stress triggers an exaggerated, ST:STUDY_SUMMARY multi-system metabolic response in mdx mice. ST:INSTITUTE University of Minnesota ST:DEPARTMENT Biochemistry, Molecular Biology, and Biophysics ST:LABORATORY James Ervasti ST:LAST_NAME Johnson ST:FIRST_NAME Erynn ST:ADDRESS 420 Washington Ave SE ST:EMAIL joh18358@umn.edu ST:PHONE 4024054007 ST:NUM_GROUPS 6 ST:TOTAL_SUBJECTS 48 ST:NUM_MALES 48 #SUBJECT SU:SUBJECT_TYPE Mammal SU:SUBJECT_SPECIES Mus musculus SU:TAXONOMY_ID 10090 SU:GENOTYPE_STRAIN C57BL6/J; C57BL10/J; C57BL/10ScSn-Dmdmdx/J SU:AGE_OR_AGE_RANGE 120-150 days SU:WEIGHT_OR_WEIGHT_RANGE 25-35g SU:HEIGHT_OR_HEIGHT_RANGE N/A SU:GENDER Male SU:ANIMAL_ANIMAL_SUPPLIER Jackson Laboratories SU:ANIMAL_HOUSING Research Animal Resources campus facilities SU:ANIMAL_LIGHT_CYCLE 12h light/dark cycle SU:ANIMAL_FEED Standard chow SU:ANIMAL_WATER Water bottle SU:ANIMAL_INCLUSION_CRITERIA Age; gender #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 - UNMN-01552 GENOTYPE:WT | TREATMENT:no stress | Sample source:mouse plasma SUBJECT_SAMPLE_FACTORS - UNMN-01553 GENOTYPE:WT | TREATMENT:no stress | Sample source:mouse plasma SUBJECT_SAMPLE_FACTORS - UNMN-01554 GENOTYPE:WT | TREATMENT:no stress | Sample source:mouse plasma SUBJECT_SAMPLE_FACTORS - UNMN-01555 GENOTYPE:WT | TREATMENT:no stress | Sample source:mouse plasma SUBJECT_SAMPLE_FACTORS - UNMN-01556 GENOTYPE:MDX | TREATMENT:no stress | Sample source:mouse plasma SUBJECT_SAMPLE_FACTORS - UNMN-01557 GENOTYPE:MDX | TREATMENT:no stress | Sample source:mouse plasma SUBJECT_SAMPLE_FACTORS - UNMN-01558 GENOTYPE:MDX | TREATMENT:no stress | Sample source:mouse plasma SUBJECT_SAMPLE_FACTORS - UNMN-01559 GENOTYPE:MDX | TREATMENT:no stress | Sample source:mouse plasma SUBJECT_SAMPLE_FACTORS - UNMN-01560 GENOTYPE:MTBD | TREATMENT:no stress | Sample source:mouse plasma SUBJECT_SAMPLE_FACTORS - UNMN-01561 GENOTYPE:MTBD | TREATMENT:no stress | Sample source:mouse plasma SUBJECT_SAMPLE_FACTORS - UNMN-01562 GENOTYPE:MTBD | TREATMENT:no stress | Sample source:mouse plasma SUBJECT_SAMPLE_FACTORS - UNMN-01563 GENOTYPE:MTBD | TREATMENT:no stress | Sample source:mouse plasma SUBJECT_SAMPLE_FACTORS - UNMN-01564 GENOTYPE:MTBD | TREATMENT:no stress | Sample source:mouse plasma SUBJECT_SAMPLE_FACTORS - UNMN-01565 GENOTYPE:WT | TREATMENT:stress | Sample source:mouse plasma SUBJECT_SAMPLE_FACTORS - UNMN-01566 GENOTYPE:WT | TREATMENT:stress | Sample source:mouse plasma SUBJECT_SAMPLE_FACTORS - UNMN-01567 GENOTYPE:WT | TREATMENT:stress | Sample source:mouse plasma SUBJECT_SAMPLE_FACTORS - UNMN-01568 GENOTYPE:WT | TREATMENT:stress | Sample source:mouse plasma SUBJECT_SAMPLE_FACTORS - UNMN-01569 GENOTYPE:MDX | TREATMENT:stress | Sample source:mouse plasma SUBJECT_SAMPLE_FACTORS - UNMN-01570 GENOTYPE:MDX | TREATMENT:stress | Sample source:mouse plasma SUBJECT_SAMPLE_FACTORS - UNMN-01571 GENOTYPE:MDX | TREATMENT:stress | Sample source:mouse plasma SUBJECT_SAMPLE_FACTORS - UNMN-01572 GENOTYPE:MDX | TREATMENT:stress | Sample source:mouse plasma SUBJECT_SAMPLE_FACTORS - UNMN-01573 GENOTYPE:MTBD | TREATMENT:stress | Sample source:mouse plasma SUBJECT_SAMPLE_FACTORS - UNMN-01574 GENOTYPE:MTBD | TREATMENT:stress | Sample source:mouse plasma SUBJECT_SAMPLE_FACTORS - UNMN-01575 GENOTYPE:MTBD | TREATMENT:stress | Sample source:mouse plasma SUBJECT_SAMPLE_FACTORS - UNMN-01576 GENOTYPE:WT | TREATMENT:no stress | Sample source:mouse plasma SUBJECT_SAMPLE_FACTORS - UNMN-01577 GENOTYPE:WT | TREATMENT:no stress | Sample source:mouse plasma SUBJECT_SAMPLE_FACTORS - UNMN-01578 GENOTYPE:WT | TREATMENT:no stress | Sample source:mouse plasma SUBJECT_SAMPLE_FACTORS - UNMN-01579 GENOTYPE:WT | TREATMENT:no stress | Sample source:mouse plasma SUBJECT_SAMPLE_FACTORS - UNMN-01580 GENOTYPE:MDX | TREATMENT:no stress | Sample source:mouse plasma SUBJECT_SAMPLE_FACTORS - UNMN-01581 GENOTYPE:MDX | TREATMENT:no stress | Sample source:mouse plasma SUBJECT_SAMPLE_FACTORS - UNMN-01582 GENOTYPE:MDX | TREATMENT:no stress | Sample source:mouse plasma SUBJECT_SAMPLE_FACTORS - UNMN-01583 GENOTYPE:MDX | TREATMENT:no stress | Sample source:mouse plasma SUBJECT_SAMPLE_FACTORS - UNMN-01584 GENOTYPE:MTBD | TREATMENT:no stress | Sample source:mouse plasma SUBJECT_SAMPLE_FACTORS - UNMN-01585 GENOTYPE:MTBD | TREATMENT:no stress | Sample source:mouse plasma SUBJECT_SAMPLE_FACTORS - UNMN-01586 GENOTYPE:MTBD | TREATMENT:no stress | Sample source:mouse plasma SUBJECT_SAMPLE_FACTORS - UNMN-01587 GENOTYPE:MTBD | TREATMENT:no stress | Sample source:mouse plasma SUBJECT_SAMPLE_FACTORS - UNMN-01588 GENOTYPE:WT | TREATMENT:stress | Sample source:mouse plasma SUBJECT_SAMPLE_FACTORS - UNMN-01589 GENOTYPE:WT | TREATMENT:stress | Sample source:mouse plasma SUBJECT_SAMPLE_FACTORS - UNMN-01590 GENOTYPE:WT | TREATMENT:stress | Sample source:mouse plasma SUBJECT_SAMPLE_FACTORS - UNMN-01591 GENOTYPE:WT | TREATMENT:stress | Sample source:mouse plasma SUBJECT_SAMPLE_FACTORS - UNMN-01592 GENOTYPE:WT | TREATMENT:stress | Sample source:mouse plasma SUBJECT_SAMPLE_FACTORS - UNMN-01593 GENOTYPE:MDX | TREATMENT:stress | Sample source:mouse plasma SUBJECT_SAMPLE_FACTORS - UNMN-01594 GENOTYPE:MDX | TREATMENT:stress | Sample source:mouse plasma SUBJECT_SAMPLE_FACTORS - UNMN-01595 GENOTYPE:MDX | TREATMENT:stress | Sample source:mouse plasma SUBJECT_SAMPLE_FACTORS - UNMN-01596 GENOTYPE:MDX | TREATMENT:stress | Sample source:mouse plasma SUBJECT_SAMPLE_FACTORS - UNMN-01597 GENOTYPE:MTBD | TREATMENT:stress | Sample source:mouse plasma SUBJECT_SAMPLE_FACTORS - UNMN-01598 GENOTYPE:MTBD | TREATMENT:stress | Sample source:mouse plasma SUBJECT_SAMPLE_FACTORS - UNMN-01599 GENOTYPE:MTBD | TREATMENT:stress | Sample source:mouse plasma #COLLECTION CO:COLLECTION_SUMMARY Blood was collected after euthanasia via cardiac puncture and plasma was CO:COLLECTION_SUMMARY extracted and stored at -80 degrees Celsius until sample submission to CO:COLLECTION_SUMMARY Metabolon. CO:SAMPLE_TYPE Blood (plasma) CO:COLLECTION_METHOD Blood was collected after euthanasia via cardiac puncture and was rotated CO:COLLECTION_METHOD end-over-end in EDTA-coated tubes for 15 minutes at room temperature. Samples CO:COLLECTION_METHOD were centrifuged for 10 minutes at 2,000xg at 4 degrees Celsius, then plasma CO:COLLECTION_METHOD supernatant was collected and stored at -80 degrees Celsius until sample CO:COLLECTION_METHOD submission to Metabolon. CO:COLLECTION_LOCATION -80 degree freezer CO:COLLECTION_FREQUENCY Single collection CO:COLLECTION_DURATION 30 minutes CO:VOLUMEORAMOUNT_COLLECTED 200 microliters CO:STORAGE_CONDITIONS -80℃ CO:COLLECTION_VIALS EDTA-coated centrifuge tubes CO:STORAGE_VIALS Centrifuge tubes CO:COLLECTION_TUBE_TEMP 20-25 degrees Celsius CO:ADDITIVES EDTA #TREATMENT TR:TREATMENT_SUMMARY Mice in the "no stress" group were euthanized and blood samples were collected TR:TREATMENT_SUMMARY following euthanasia. Mice in the "stress" group were monitored in open-field TR:TREATMENT_SUMMARY activity cages to measure total locomotion distance for 30 minutes, then were TR:TREATMENT_SUMMARY briefly handled by a standard scruff method for 30 seconds, followed by an TR:TREATMENT_SUMMARY additional 30 minute activity cage monitoring session and euthanasia/sample TR:TREATMENT_SUMMARY collection. TR:TREATMENT Scruff handling stress TR:TREATMENT_COMPOUND N/A TR:TREATMENT_ROUTE N/A TR:TREATMENT_DOSE N/A TR:TREATMENT_DOSEVOLUME N/A TR:TREATMENT_DOSEDURATION N/A TR:TREATMENT_VEHICLE N/A TR:ANIMAL_VET_TREATMENTS N/A TR:ANIMAL_ANESTHESIA N/A TR:ANIMAL_ACCLIMATION_DURATION N/A TR:ANIMAL_FASTING N/A TR:ANIMAL_ENDP_EUTHANASIA Tribromoethanol (Avertin) TR:ANIMAL_ENDP_TISSUE_COLL_LIST Blood TR:ANIMAL_ENDP_TISSUE_PROC_METHOD Cardiac Puncture TR:ANIMAL_ENDP_CLINICAL_SIGNS N/A #SAMPLEPREP SP:SAMPLEPREP_SUMMARY Plasma samples were pipetted in 200 microliter quantities into barcoded sample SP:SAMPLEPREP_SUMMARY tubes and submitted to Metabolon for additional sample preparation and analysis. SP:SAMPLEPREP_SUMMARY Sample preparation details are proprietary information held by Metabolon. SP:PROCESSING_METHOD N/A SP:PROCESSING_STORAGE_CONDITIONS On ice SP:EXTRACTION_METHOD N/A SP:EXTRACT_CONCENTRATION_DILUTION N/A SP:EXTRACT_ENRICHMENT N/A SP:EXTRACT_CLEANUP N/A SP:SAMPLE_RESUSPENSION N/A SP:SAMPLE_DERIVATIZATION N/A SP:SAMPLE_SPIKING N/A SP:SUBCELLULAR_LOCATION N/A #CHROMATOGRAPHY CH:CHROMATOGRAPHY_SUMMARY Low pH Lipophilic (LC/MS Pos late) CH:CHROMATOGRAPHY_TYPE Reversed phase CH:INSTRUMENT_NAME Waters Acquity CH:COLUMN_NAME Waters Acquity BEH C18 (100 x 2mm, 1.7um) CH:SOLVENT_A 100% water; 0.1% formic acid; 0.05% PFPA, pH ~2.5 CH:SOLVENT_B 50% methanol/50% acetonitrile; 0.1% formic acid; 0.05% PFPA, pH ~2.5 CH:FLOW_GRADIENT Linear gradient from 40% B to 99.5% B over 1.0 minute, hold 99.5% B for 2.4 CH:FLOW_GRADIENT minutes. CH:FLOW_RATE 0.60 mL/min CH:COLUMN_TEMPERATURE 40-50 #ANALYSIS AN:ANALYSIS_TYPE MS #MS MS:INSTRUMENT_NAME Thermo Q Exactive Orbitrap MS:INSTRUMENT_TYPE Orbitrap MS:MS_TYPE Other MS:ION_MODE POSITIVE MS:MS_COMMENTS Metabolon (LC/MS Pos late) #MS_METABOLITE_DATA MS_METABOLITE_DATA:UNITS Peak Area MS_METABOLITE_DATA_START Samples UNMN-01552 UNMN-01553 UNMN-01554 UNMN-01555 UNMN-01556 UNMN-01557 UNMN-01558 UNMN-01559 UNMN-01560 UNMN-01561 UNMN-01562 UNMN-01563 UNMN-01564 UNMN-01565 UNMN-01566 UNMN-01567 UNMN-01568 UNMN-01569 UNMN-01570 UNMN-01571 UNMN-01572 UNMN-01573 UNMN-01574 UNMN-01575 UNMN-01576 UNMN-01577 UNMN-01578 UNMN-01579 UNMN-01580 UNMN-01581 UNMN-01582 UNMN-01583 UNMN-01584 UNMN-01585 UNMN-01586 UNMN-01587 UNMN-01588 UNMN-01589 UNMN-01590 UNMN-01591 UNMN-01592 UNMN-01593 UNMN-01594 UNMN-01595 UNMN-01596 UNMN-01597 UNMN-01598 UNMN-01599 Factors GENOTYPE:WT | TREATMENT:no stress | Sample source:mouse plasma GENOTYPE:WT | TREATMENT:no stress | Sample source:mouse plasma GENOTYPE:WT | TREATMENT:no stress | Sample source:mouse plasma GENOTYPE:WT | TREATMENT:no stress | Sample source:mouse plasma GENOTYPE:MDX | TREATMENT:no stress | Sample source:mouse plasma GENOTYPE:MDX | TREATMENT:no stress | Sample source:mouse plasma GENOTYPE:MDX | TREATMENT:no stress | Sample source:mouse plasma GENOTYPE:MDX | TREATMENT:no stress | Sample source:mouse plasma GENOTYPE:MTBD | TREATMENT:no stress | Sample source:mouse plasma GENOTYPE:MTBD | TREATMENT:no stress | Sample source:mouse plasma GENOTYPE:MTBD | TREATMENT:no stress | Sample source:mouse plasma GENOTYPE:MTBD | TREATMENT:no stress | Sample source:mouse plasma GENOTYPE:MTBD | TREATMENT:no stress | Sample source:mouse plasma GENOTYPE:WT | TREATMENT:stress | Sample source:mouse plasma GENOTYPE:WT | TREATMENT:stress | Sample source:mouse plasma GENOTYPE:WT | TREATMENT:stress | Sample source:mouse plasma GENOTYPE:WT | TREATMENT:stress | Sample source:mouse plasma GENOTYPE:MDX | TREATMENT:stress | Sample source:mouse plasma GENOTYPE:MDX | TREATMENT:stress | Sample source:mouse plasma GENOTYPE:MDX | TREATMENT:stress | Sample source:mouse plasma GENOTYPE:MDX | TREATMENT:stress | Sample source:mouse plasma GENOTYPE:MTBD | TREATMENT:stress | Sample source:mouse plasma GENOTYPE:MTBD | TREATMENT:stress | Sample source:mouse plasma GENOTYPE:MTBD | TREATMENT:stress | Sample source:mouse plasma GENOTYPE:WT | TREATMENT:no stress | Sample source:mouse plasma GENOTYPE:WT | TREATMENT:no stress | Sample source:mouse plasma GENOTYPE:WT | TREATMENT:no stress | Sample source:mouse plasma GENOTYPE:WT | TREATMENT:no stress | Sample source:mouse plasma GENOTYPE:MDX | TREATMENT:no stress | Sample source:mouse plasma GENOTYPE:MDX | TREATMENT:no stress | Sample source:mouse plasma GENOTYPE:MDX | TREATMENT:no stress | Sample source:mouse plasma GENOTYPE:MDX | TREATMENT:no stress | Sample source:mouse plasma GENOTYPE:MTBD | TREATMENT:no stress | Sample source:mouse plasma GENOTYPE:MTBD | TREATMENT:no stress | Sample source:mouse plasma GENOTYPE:MTBD | TREATMENT:no stress | Sample source:mouse plasma GENOTYPE:MTBD | TREATMENT:no stress | Sample source:mouse plasma GENOTYPE:WT | TREATMENT:stress | Sample source:mouse plasma GENOTYPE:WT | TREATMENT:stress | Sample source:mouse plasma GENOTYPE:WT | TREATMENT:stress | Sample source:mouse plasma GENOTYPE:WT | TREATMENT:stress | Sample source:mouse plasma GENOTYPE:WT | TREATMENT:stress | Sample source:mouse plasma GENOTYPE:MDX | TREATMENT:stress | Sample source:mouse plasma GENOTYPE:MDX | TREATMENT:stress | Sample source:mouse plasma GENOTYPE:MDX | TREATMENT:stress | Sample source:mouse plasma GENOTYPE:MDX | TREATMENT:stress | Sample source:mouse plasma GENOTYPE:MTBD | TREATMENT:stress | Sample source:mouse plasma GENOTYPE:MTBD | TREATMENT:stress | Sample source:mouse plasma GENOTYPE:MTBD | TREATMENT:stress | Sample source:mouse plasma biliverdin 1082979 1801860 2980326 522223 5363076 4819547 6766001 4056095 5763942 4322014 2688469 1035425 3372515 4033795 1092693 2535855 11254082 9214698 8381081 3045479 6507383 1963635 5894282 2236951 1660435 2739179 3199444 10889134 4869696 7290637 10346302 4633343 5231599 6756579 691898 2213937 1094219 4022458 6082190 12045030 2612226 7682206 7518083 832844 1832889 sphingosine 7298678 9394172 5370124 5283545 9710956 11715808 8052925 5806694 5638397 4953104 5606514 7207631 10033528 4119672 7804894 5315287 3483174 7332114 5041820 5256584 4520178 10642194 2890772 7496113 4742048 8105332 8958347 8113540 9060858 7366497 10977870 4484231 7121822 6752873 10728693 4123254 7739644 5574806 11956106 4557000 8175040 7078320 5287663 6002472 6282576 5723532 5680786 5463033 sphinganine 2754669 3818028 2515706 2084224 1889896 2536248 2604926 1611320 1995040 2269942 2205420 2919829 3629189 1585884 3374214 2092798 1428643 2568242 2148803 1930329 1942856 4935329 1605390 2964708 1511002 2920014 2827102 3280890 2618295 1594816 3425026 2259290 2508814 2342067 4927243 1613875 4752005 2371133 5506523 2578499 3687438 2978638 2229433 1727520 2598675 2216894 2131348 2288975 retinol (vitamin A) 7316675 2789011 26710717 6224663 15878783 16151977 241791 10821405 14492592 13519455 10246298 9873357 7844367 12913989 14879327 6246005 30389604 23338847 17330013 12392741 32018845 14308489 37796467 21043008 4287759 10245181 7805512 8169080 21281200 16747451 22531677 23213475 12370861 7220149 102588 16427627 4215319 3912183 6698449 10031967 21713964 18477708 32296911 27714267 11988486 1468299 2627511 spermine 742916 883819 193202 249922 371710 955685 314252 264666 150783 221646 210957 234998 173489 134233 91094 227349 321051 278974 296219 430452 298793 352809 209850 215578 190016 340049 161860 232345 294820 270229 137489 139653 181336 952853 81583 117716 486023 308514 262514 439182 539605 362138 1177129 570217 228589 369660 513675 bilirubin (Z,Z) 7373738 4438715 13674360 1778718 1769929 27638084 22797127 3885349 3194861 527022 21113772 22631114 21395755 12082443 alpha-tocopherol 3980171 105864672 807216 33607704 20042495 29432456 17670082 20865915 12507287 9251630 3250094 14839233 38203078 917410 93634869 51282343 58596651 46692484 100261780 34987647 110463854 87643342 1615213 2400231 5140744 6132177 42874046 9265492 71337914 61030280 8994870 8013706 517376 42014867 1408021 976375 507911 14740036 78829439 87518431 130985277 92566919 3862778 heme 278309394 191593486 22914520 136168373 132523689 172397843 2898851 104710161 149326901 135765582 126391167 151596676 197631877 112826333 80646794 155509774 39749417 131386005 94732088 117442352 14786528 126510012 6587513 76630767 170980917 156844562 132856904 92804063 139935549 183082355 43394130 40420755 146787392 139575656 2808649 90554039 179502723 130221436 171353514 2162881 169647697 74033050 81466754 14481393 38951325 143781978 113401202 61977417 sphinganine-1-phosphate 3967820 2866831 2837771 1856046 2888790 2736698 2546764 3102131 3590229 4110287 2795174 3086574 3343318 2593078 2881355 2411537 4744768 2206751 2479841 2081026 3089752 2839203 4166156 3654681 2428412 2904544 3048460 2713418 2635506 2753047 3391169 4125065 2786269 3301011 2496519 3034757 2746308 2233082 3163762 1723789 3052602 2582618 3651808 2805017 3371873 3401711 3002054 3983177 12-HETE 13311120 22305496 11153742 21609246 20228720 24547500 8260905 12403363 17899071 4850825 18936751 16279662 18799807 10158555 27175059 21612746 8131171 37338019 34294712 25307457 2736373 28519759 5518744 20793660 7601530 20971039 19323615 27049225 17362911 9163705 31635249 13954240 35002341 15829980 11700796 7698438 23627252 21806012 41314846 7341287 28424610 33284051 38913858 8130599 8901028 20548764 27367062 14196618 gamma-tocopherol/beta-tocopherol 598469 1012654 808445 846968 1014340 417845 363401 547414 209340 752900 594039 1012213 516537 1063201 361363 1273285 606356 1165682 703575 266725 429541 649272 1035108 1929505 1042136 1417418 2088930 568984 491953 784850 128694 660898 1417716 838909 1276335 1240612 337417 MS_METABOLITE_DATA_END #METABOLITES METABOLITES_START metabolite_name KEGG CHEMSPIDER CAS HMDB PUBCHEM INCHIKEY SMILES SUPER_PATHWAY SUB_PATHWAY biliverdin C00500 10628548 55482-27-4,55482-27-4 HMDB0001008 5280353 QBUVFDKTZJNUPP-YBRAVLHJSA-N CC1=C(/C=C(N2)/C(C=C)=C(C)C2=O)NC(/C=C3C(CCC(O)=O)=C(C)C(/C=C(N4)C(C)=C(C=C)C4=O)=N)=C1CCC(O)=O Injury & Circulation Heme metabolism sphingosine C00319 4510275 123-78-4 HMDB0000252 5280335 WWUZIQQURGPMPG-CCEZHUSRSA-N CCCCCCCCCCCCC/C=C/C(C(CO)N)O Stress Signaling Molecule Sphingosine sphinganine C00836 3014 3102-56-5 HMDB0000269 3126 OTKJDMGTUTTYMP-UHFFFAOYSA-N CCCCCCCCCCCCCCCC(C(CO)N)O Stress Signaling Molecule Sphingosine retinol (vitamin A) C00473 393012 68-26-8 HMDB0000305 445354 FPIPGXGPPPQFEQ-OVSJKPMPSA-N C/C(/C=C/C(C(C)(CCC1)C)=C1C)=CC=CC(C)=CCO Vitamins Vitamin A spermine C00750 1072 71-44-3 HMDB0001256 1103 PFNFFQXMRSDOHW-UHFFFAOYSA-N NCCCNCCCCNCCCN Protein Catabolism & Decay Nitrogen metabolism & Polyamine bilirubin (Z,Z) C00486 4444055 635-65-4 HMDB0000054 5280352 BPYKTIZUTYGOLE-KDUUSRDASA-N CC(C(N)=O)=C(C=C)C1=C/C2=C(C)C(CCC(O)=O)=C(CC3=C(CCC(O)=O)C(C)=C(/C=C4NC(C(C=C)=C/4C)=O)N3)N2 Injury & Circulation Heme metabolism alpha-tocopherol C02477 14265 10191-41-0,59-02-9 HMDB0001893 86472 GVJHHUAWPYXKBD-IEOSBIPESA-N CC1=C2C(O[C@@](CCC[C@H](C)CCC[C@H](C)CCC[C@H](C)C)(C)CC2)=C(C)C(C)=C1O Vitamins Vitamin E heme C00032 14875-96-8 HMDB0003178 26945 GGIDWJQWCUJYRY-UHFFFAOYSA-K CC1=C(CCC(O)=O)C(/C=C(C(CCC([O-])=O)=C/2C)[N-]C2=C/C3=N/C(C(C=C)=C3C)=C)=N/C1=CC(N([Fe+2])C4=C5C)=C5C=C Injury & Circulation Heme metabolism sphinganine-1-phosphate 505 19794-97-9 HMDB0001383 520 YHEDRJPUIRMZMP-UHFFFAOYSA-N OP(O)(OCC(C(CCCCCCCCCCCCCCC)O)N)=O Stress Signaling Molecule Sphingosine 12-HETE C14777 21509475 71030-37-0,73837-14-6 HMDB0006111 5283155 ZNHVWPKMFKADKW-VXBMJZGYSA-N OC(CCC/C=CCC=C/C=C/C(C/C=CCCCCC)O)=O Inflammation & Immunity Lipid Mediator - Oxylipins gamma-tocopherol/beta-tocopherol C02483,C14152 HMDB0001492,HMDB0006335 QUEDXNHFTDJVIY-DQCZWYHMSA-N CC1=C(C(CC2)=CC(O)=C1C)O[C@@]2(CCC[C@@H](CCC[C@@H](CCCC(C)C)C)C)C Vitamins Vitamin E METABOLITES_END #END