#METABOLOMICS WORKBENCH joh18358_20240719_105628 DATATRACK_ID:5027 STUDY_ID:ST003335 ANALYSIS_ID:AN005467 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 HILIC (LC/MS Polar Neg) CH:CHROMATOGRAPHY_TYPE HILIC CH:INSTRUMENT_NAME Waters Acquity CH:COLUMN_NAME Waters Acquity BEH Amide (150 x 2.1mm, 1.7um) CH:SOLVENT_A 15% water/5% methanol/80% acetonitrile; 10 mM ammonium formate, (effective pH CH:SOLVENT_A 10.16 with NH4OH) CH:SOLVENT_B 50% water/50% acetonitrile; 10 mM ammonium formate, (effective pH 10.60 with CH:SOLVENT_B NH4OH) CH:FLOW_GRADIENT Linear gradient from 5% B to 50% B in 3.5 minutes, then linear gradient from 50% CH:FLOW_GRADIENT B to 95% B in 2 minutes. CH:FLOW_RATE 0.50 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 NEGATIVE MS:MS_COMMENTS Metabolon (LC/MS Polar) #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 3-hydroxybutyrate (BHBA) 52774470 78747839 109260980 8496502 7986039 4562859 9733841 8756935 19907575 9931185 28374721 11566527 8369873 76816646 92232717 48067558 36468943 13612993 43419210 14998030 27017769 38807293 46305097 19163709 324216402 131806215 178298062 472966788 117008107 66770212 59990950 82349969 320408437 37689919 58715260 81116269 422348136 1116568604 484068223 904932644 831884251 178364293 203549893 244251976 196294400 735247932 95702956 98914347 cystine 261758 124063 475415 665578 3061096 1328127 560636 1902219 206034 342638 239174 218210 569988 360345 286363 487055 493860 643756 411593 710138 957521 330766 717764 339146 564774 3875354 3040168 2502086 10697775 12932072 17681028 5839083 3566106 6847592 2462721 5097419 1523539 1454640 1585478 2899639 2549841 2711229 4197474 3457743 2998971 2281067 2290095 1151504 hypotaurine 507388 477335 187562 201001 461195 485530 407408 553361 414074 277332 418462 357444 517152 319956 330587 339395 367411 601046 517235 550052 857748 512243 560284 469397 8411243 2372265 2706631 1267518 3804409 3465535 2877564 1703329 3099791 2958974 4060127 2902932 2546512 2302058 2388747 2277285 1799906 3819761 2689725 3887151 3235597 2868621 3412136 4172188 2-aminoadipate 879842 271522 271157 438557 473574 459594 327517 340686 314993 298369 272031 370807 372663 541071 319412 335175 452994 366568 347028 338078 687868 286001 410855 436008 2931172 2094814 1145627 3495444 2661059 2547077 1905949 2405732 1682052 1737050 1641735 2460241 1590692 2106420 2007280 1621070 3503857 2223369 1739495 3455780 2963377 1559200 1745587 1997551 lactate 833126572 901235823 610309605 403627228 945825083 1195240875 1165781645 654474225 734375117 1214604709 947788771 1111272212 830258598 526559410 886250831 518073247 1533988969 1164181540 731540925 634188817 1776422245 1023385296 1681301222 1681499339 4730870967 5779706891 4941557014 3526587032 11008342827 7078586335 7688731636 5873331827 5226702102 4242561619 6356692817 4827314648 4216931563 3699731355 5102837303 3168750289 5347851851 11412178957 5451811692 14634035385 11909857583 4369007727 5098357519 5125216892 glucose 476311077 542173766 713794857 431701160 367057733 432782560 736358038 569843739 539731272 567577627 456705630 460318233 445052245 653488898 667893164 551722806 771109239 894368155 814603571 871320646 796239679 616643977 864968138 571540800 1707744114 2760511604 2324473771 2128532910 2471152784 1781218556 2039881858 2270006612 2253495982 1797436897 1973824357 2411388118 3163250462 2383827957 2439283722 2413057977 2887158910 3544160587 3901486393 3615017603 3667845104 2600918064 2090262253 2559593639 alpha-ketobutyrate 121887 320431 139663 586742 115156 112733 210394 182150 319307 135764 328411 190089 209502 176401 1556379 938668 1111604 1307752 4968408 704861 368366 669918 1283505 1154519 1476161 1615038 2195629 2789794 1847782 2117971 1983118 1778747 1780894 1563740 609626 2869067 urate 16084624 13417256 16752183 3737982 17046427 16949822 4431071 23113663 15871905 22350019 20600195 19155329 11806352 18023142 31451908 12684127 24944158 52219481 42838183 32719625 52407825 28256112 60477342 23470684 85324978 91868282 93498074 79663323 156776265 101466201 115204406 125128686 98271230 90396953 100269573 97116849 99899789 91473541 93988449 70414222 142333593 258925954 148378726 258161440 231423556 125068669 93110535 98084038 sphingosine 1-phosphate 388839 310735 265754 219080 475004 478925 366374 366930 352009 404112 365482 324544 357957 342700 297518 283720 306731 342047 383716 312336 351466 306541 348524 285788 2207187 2477219 2732212 2539803 2758764 3142636 2933735 2956676 2408707 2691505 2731483 3115742 2200960 1794832 2201156 2041300 2526957 2460665 2665550 2441945 2256910 2608503 2584007 2683627 3-methyl-2-oxobutyrate 7556765 7979313 11020902 3760274 8855542 8747610 5648686 5888116 8329212 12139996 6579245 10415745 5809351 8032357 10620020 15013693 16500003 19707368 12502844 12061522 16264175 10784733 19841992 16756530 41645208 43650236 43150608 36551318 67487898 45233876 53135465 37941100 35851278 33274565 50170034 59576059 38057725 38225052 54166709 37027184 37740255 54763128 55816753 83636456 98076620 36710393 38696460 38177978 ascorbic acid 2-sulfate 31558 29016 25437 26324 152813 105267 77424 87468 34172 34881 29262 57474 24288 51801 49749 25034 54770 124517 69118 92073 88696 48240 73256 46988 313203 300872 380592 545220 829126 960144 1101390 314535 416847 376470 431105 552725 346478 379963 359193 268089 696178 302646 353813 372402 312131 379516 314123 265728 MS_METABOLITE_DATA_END #METABOLITES METABOLITES_START metabolite_name KEGG CHEMSPIDER CAS HMDB PUBCHEM INCHIKEY SMILES SUPER_PATHWAY SUB_PATHWAY 3-hydroxybutyrate (BHBA) C03197,C01089 428 625-72-9 HMDB0000442,HMDB0000011,HMDB0000357 441,94318,92135 WHBMMWSBFZVSSR-UHFFFAOYSA-N CC(O)CC(O)=O Metabolism & Glycemic Stress Ketogenesis cystine C00491 575 56-89-3 HMDB0000192 67678 LEVWYRKDKASIDU-UHFFFAOYSA-N NC(C(O)=O)CSSCC(N)C(O)=O Oxidative Stress Cysteine/Glutathione-related hypotaurine C00519 96959 300-84-5 HMDB0000965 107812 VVIUBCNYACGLLV-UHFFFAOYSA-N NCCS(O)=O Oxidative Stress Cysteine/Glutathione-related 2-aminoadipate C00956 456 1118-90-7,542-32-5 HMDB0000510 92136 OYIFNHCXNCRBQI-UHFFFAOYSA-N OC(CCCC(N)C(O)=O)=O Inflammation & Immunity Amino Acid-related Mediator lactate C00186 592 79-33-4 HMDB0000190 612 JVTAAEKCZFNVCJ-UHFFFAOYSA-N CC(O)C(O)=O Metabolism & Glycemic Stress Glucose Regulation glucose C00031 71358 50-99-7 HMDB0000122 5793 WQZGKKKJIJFFOK-DVKNGEFBSA-N O[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O Metabolism & Glycemic Stress Glucose Regulation alpha-ketobutyrate C00109 2829426 600-18-0 HMDB0000005 58 TYEYBOSBBBHJIV-UHFFFAOYSA-N OC(C(CC)=O)=O Metabolism & Glycemic Stress Glucose Regulation urate C00366 120K5305,69-93-2 HMDB0000289 1175 LEHOTFFKMJEONL-UHFFFAOYSA-N O=C1NC(NC(NC2=O)=O)=C2N1 Oxidative Stress Nucleotide-related mediator sphingosine 1-phosphate C06124 4446673 26993-30-6 HMDB0000277 5283560 DUYSYHSSBDVJSM-KRWOKUGFSA-N OP([O-])(OC[C@@]([H])([C@](O)(/C=C/CCCCCCCCCCCCC)[H])[NH3+])=O Stress Signaling Molecule Sphingosine 3-methyl-2-oxobutyrate C00141 48 3715-29-5 HMDB0000019 49 QHKABHOOEWYVLI-UHFFFAOYSA-N OC(C(C(C)C)=O)=O Protein Catabolism & Decay BCAA catabolism ascorbic acid 2-sulfate 77998 52174-99-9 HMDB0060649 54676864 SKKZOYBAANIUOV-ZAFYKAAXSA-N O[C@@H](CO)[C@@](C1=O)([H])OC(O)=C1OS(O)(=O)=O Vitamins Vitamin C METABOLITES_END #END