#METABOLOMICS WORKBENCH juliehaines_20241125_124620 DATATRACK_ID:5395 STUDY_ID:ST003603 ANALYSIS_ID:AN005920 PROJECT_ID:PR002231 VERSION 1 CREATED_ON December 5, 2024, 7:15 pm #PROJECT PR:PROJECT_TITLE Macrophages recycle phagocytosed bacteria to fuel immunometabolic responses PR:PROJECT_SUMMARY Macrophages specialize in phagocytosis, a cellular process that eliminates PR:PROJECT_SUMMARY extracellular matter, including microbes, through internalization and PR:PROJECT_SUMMARY degradation. Despite the critical role of phagocytosis during bacterial PR:PROJECT_SUMMARY infection, the fate of phagocytosed microbial cargo and its impact on host cell PR:PROJECT_SUMMARY is poorly understood. Here, we reveal that ingested bacteria constitute an PR:PROJECT_SUMMARY alternative nutrient source that skews immunometabolic host responses. Tracing PR:PROJECT_SUMMARY stable isotope-labelled bacteria, we found that phagolysosomal degradation of PR:PROJECT_SUMMARY bacteria provides carbon atoms and amino acids that are recycled into various PR:PROJECT_SUMMARY metabolic pathways, including glutathione and itaconate biosynthesis, and PR:PROJECT_SUMMARY satisfy macrophage bioenergetic needs. Metabolic recycling of PR:PROJECT_SUMMARY microbially-derived nutrients is regulated by the nutrient sensing mTORC1 and PR:PROJECT_SUMMARY intricately tied to microbial viability. Dead bacteria, as opposed to live ones, PR:PROJECT_SUMMARY are enriched in cyclic- adenosine monophosphate (AMP), sustain the cellular AMP PR:PROJECT_SUMMARY pool and subsequently activate AMP protein kinase (AMPK) to inhibit mTORC1. PR:PROJECT_SUMMARY Consequently, killed bacteria strongly fuel metabolic recycling and support PR:PROJECT_SUMMARY macrophage survival, but elicit decreased reactive oxygen species (ROS) PR:PROJECT_SUMMARY production and a reduced IL-1β secretion compared to viable bacteria. These PR:PROJECT_SUMMARY results reveal a novel insight into the fate of engulfed microbes and highlights PR:PROJECT_SUMMARY a microbial viability-associated metabolite that triggers host metabolic and PR:PROJECT_SUMMARY immune responses. Our findings hold promise for shaping immunometabolic PR:PROJECT_SUMMARY intervention in various immune-related pathologies. PR:INSTITUTE University of Colorado Anschutz Medical Campus PR:LABORATORY Lab of Angelo D'Alessandro in collaboration with lab of Johan Garaude (INSERM, PR:LABORATORY Fr) PR:LAST_NAME Haines PR:FIRST_NAME Julie PR:ADDRESS 12801 E 17th Ave, Room 1303, Aurora, Colorado, 80045, USA PR:EMAIL julie.haines@cuanschutz.edu PR:PHONE 3037243339 #STUDY ST:STUDY_TITLE Comparison of metabolic responses in murine bone marrow derived macrophages upon ST:STUDY_TITLE LPS treatment versus following the engulfment of live or dead E coli. ST:STUDY_SUMMARY Global metabolomics and 13C-tracing analysis of murine bone marrow derived ST:STUDY_SUMMARY macrophages exposed to live or heat-killed uniformly 13C-labelled E. coli in a ST:STUDY_SUMMARY trans-well system for 6h or 18h. Global metabolomics was performed in parallel ST:STUDY_SUMMARY on murine BMDMs treated with 500 ng/ml LPS for 18h. ST:INSTITUTE University of Colorado Anschutz Medical Campus ST:LAST_NAME Haines ST:FIRST_NAME Julie ST:ADDRESS 12801 E 17th Ave, Room 1303, Aurora, Colorado, 80045, USA ST:EMAIL julie.haines@cuanschutz.edu ST:PHONE 3037243339 #SUBJECT SU:SUBJECT_TYPE Cultured cells SU:SUBJECT_SPECIES Mus musculus SU:GENDER Not applicable #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 - 156 Sample source:murine macrophage cells | Timepoint (h):18 | LPS treatment (ng/ml):0 | E coli viability:NA | Multiplicity of infection:NA RAW_FILE_NAME(Raw file name)=F2-23-01 SUBJECT_SAMPLE_FACTORS - 157 Sample source:murine macrophage cells | Timepoint (h):18 | LPS treatment (ng/ml):0 | E coli viability:NA | Multiplicity of infection:NA RAW_FILE_NAME(Raw file name)=F2-23-02 SUBJECT_SAMPLE_FACTORS - 158 Sample source:murine macrophage cells | Timepoint (h):18 | LPS treatment (ng/ml):0 | E coli viability:NA | Multiplicity of infection:NA RAW_FILE_NAME(Raw file name)=F2-23-03 SUBJECT_SAMPLE_FACTORS - 159 Sample source:murine macrophage cells | Timepoint (h):18 | LPS treatment (ng/ml):0 | E coli viability:live | Multiplicity of infection:25 RAW_FILE_NAME(Raw file name)=F2-23-04 SUBJECT_SAMPLE_FACTORS - 160 Sample source:murine macrophage cells | Timepoint (h):18 | LPS treatment (ng/ml):0 | E coli viability:live | Multiplicity of infection:25 RAW_FILE_NAME(Raw file name)=F2-23-05 SUBJECT_SAMPLE_FACTORS - 161 Sample source:murine macrophage cells | Timepoint (h):18 | LPS treatment (ng/ml):0 | E coli viability:live | Multiplicity of infection:25 RAW_FILE_NAME(Raw file name)=F2-23-06 SUBJECT_SAMPLE_FACTORS - 162 Sample source:murine macrophage cells | Timepoint (h):18 | LPS treatment (ng/ml):0 | E coli viability:dead | Multiplicity of infection:25 RAW_FILE_NAME(Raw file name)=F2-23-07 SUBJECT_SAMPLE_FACTORS - 163 Sample source:murine macrophage cells | Timepoint (h):18 | LPS treatment (ng/ml):0 | E coli viability:dead | Multiplicity of infection:25 RAW_FILE_NAME(Raw file name)=F2-23-08 SUBJECT_SAMPLE_FACTORS - 164 Sample source:murine macrophage cells | Timepoint (h):18 | LPS treatment (ng/ml):0 | E coli viability:dead | Multiplicity of infection:25 RAW_FILE_NAME(Raw file name)=F2-23-09 SUBJECT_SAMPLE_FACTORS - 165 Sample source:murine macrophage cells | Timepoint (h):18 | LPS treatment (ng/ml):500 | E coli viability:NA | Multiplicity of infection:NA RAW_FILE_NAME(Raw file name)=F2-23-10 SUBJECT_SAMPLE_FACTORS - 166 Sample source:murine macrophage cells | Timepoint (h):18 | LPS treatment (ng/ml):500 | E coli viability:NA | Multiplicity of infection:NA RAW_FILE_NAME(Raw file name)=F2-23-11 SUBJECT_SAMPLE_FACTORS - 167 Sample source:murine macrophage cells | Timepoint (h):18 | LPS treatment (ng/ml):500 | E coli viability:NA | Multiplicity of infection:NA RAW_FILE_NAME(Raw file name)=F2-23-12 SUBJECT_SAMPLE_FACTORS - 174 Sample source:murine macrophage cells | Timepoint (h):18 | LPS treatment (ng/ml):0 | E coli viability:NA | Multiplicity of infection:NA RAW_FILE_NAME(Raw file name)=F2-23-19 SUBJECT_SAMPLE_FACTORS - 175 Sample source:murine macrophage cells | Timepoint (h):18 | LPS treatment (ng/ml):0 | E coli viability:NA | Multiplicity of infection:NA RAW_FILE_NAME(Raw file name)=F2-23-20 SUBJECT_SAMPLE_FACTORS - 176 Sample source:murine macrophage cells | Timepoint (h):18 | LPS treatment (ng/ml):0 | E coli viability:NA | Multiplicity of infection:NA RAW_FILE_NAME(Raw file name)=F2-23-21 SUBJECT_SAMPLE_FACTORS - 177 Sample source:murine macrophage cells | Timepoint (h):18 | LPS treatment (ng/ml):0 | E coli viability:NA | Multiplicity of infection:NA RAW_FILE_NAME(Raw file name)=F2-23-22 SUBJECT_SAMPLE_FACTORS - 178 Sample source:murine macrophage cells | Timepoint (h):18 | LPS treatment (ng/ml):0 | E coli viability:NA | Multiplicity of infection:NA RAW_FILE_NAME(Raw file name)=F2-23-23 SUBJECT_SAMPLE_FACTORS - 179 Sample source:murine macrophage cells | Timepoint (h):18 | LPS treatment (ng/ml):0 | E coli viability:NA | Multiplicity of infection:NA RAW_FILE_NAME(Raw file name)=F2-23-24 SUBJECT_SAMPLE_FACTORS - 180 Sample source:murine macrophage cells | Timepoint (h):6 | LPS treatment (ng/ml):0 | E coli viability:dead | Multiplicity of infection:50 RAW_FILE_NAME(Raw file name)=F2-23-25 SUBJECT_SAMPLE_FACTORS - 181 Sample source:murine macrophage cells | Timepoint (h):6 | LPS treatment (ng/ml):0 | E coli viability:dead | Multiplicity of infection:50 RAW_FILE_NAME(Raw file name)=F2-23-26 SUBJECT_SAMPLE_FACTORS - 182 Sample source:murine macrophage cells | Timepoint (h):6 | LPS treatment (ng/ml):0 | E coli viability:dead | Multiplicity of infection:50 RAW_FILE_NAME(Raw file name)=F2-23-27 SUBJECT_SAMPLE_FACTORS - 183 Sample source:murine macrophage cells | Timepoint (h):6 | LPS treatment (ng/ml):0 | E coli viability:NA | Multiplicity of infection:NA RAW_FILE_NAME(Raw file name)=F2-23-28 SUBJECT_SAMPLE_FACTORS - 184 Sample source:murine macrophage cells | Timepoint (h):6 | LPS treatment (ng/ml):0 | E coli viability:NA | Multiplicity of infection:NA RAW_FILE_NAME(Raw file name)=F2-23-29 SUBJECT_SAMPLE_FACTORS - 185 Sample source:murine macrophage cells | Timepoint (h):6 | LPS treatment (ng/ml):0 | E coli viability:NA | Multiplicity of infection:NA RAW_FILE_NAME(Raw file name)=F2-23-30 SUBJECT_SAMPLE_FACTORS - 186 Sample source:murine macrophage cells | Timepoint (h):18 | LPS treatment (ng/ml):0 | E coli viability:dead | Multiplicity of infection:50 RAW_FILE_NAME(Raw file name)=F2-23-31 SUBJECT_SAMPLE_FACTORS - 187 Sample source:murine macrophage cells | Timepoint (h):18 | LPS treatment (ng/ml):0 | E coli viability:dead | Multiplicity of infection:50 RAW_FILE_NAME(Raw file name)=F2-23-32 SUBJECT_SAMPLE_FACTORS - 188 Sample source:murine macrophage cells | Timepoint (h):18 | LPS treatment (ng/ml):0 | E coli viability:dead | Multiplicity of infection:50 RAW_FILE_NAME(Raw file name)=F2-23-33 #COLLECTION CO:COLLECTION_SUMMARY BMDMs were seeded at 2.5E6 cell/well in a non-tissue treated 6-well plate (2 CO:COLLECTION_SUMMARY wells per condition) the day before the experiment. To harvest, BMDMs were CO:COLLECTION_SUMMARY washed with cold PBS and harvested with 5 mM EDTA in PBS, frozen as dry cell CO:COLLECTION_SUMMARY pellet, and stored at -80˚C until processing. CO:SAMPLE_TYPE Macrophages #TREATMENT TR:TREATMENT_SUMMARY Preparation of macrophages: Murine bone marrow-derived macrophages (BMDMs) were TR:TREATMENT_SUMMARY generated as described previously, in RPMI 1640 supplemented with M-CSF (30% TR:TREATMENT_SUMMARY mycoplasma-free L929 cell supernatant, NCBI Biosample accession # SAMN00155972) TR:TREATMENT_SUMMARY and 10% FBS, plus 100 µg/ml penicillin, 100 µg/ml streptomycin, 10 mM HEPES, 1 TR:TREATMENT_SUMMARY nM sodium pyruvate and 50 µM 2-mercaptoethanol (all from Gibco). BMDMs were TR:TREATMENT_SUMMARY used on day 5 to 7 after seeding. Period of differentiation of the cells, TR:TREATMENT_SUMMARY concentration of cells when replating and time-lapse between replating and TR:TREATMENT_SUMMARY stimulation with bacteria were important parameters to maintain metabolic TR:TREATMENT_SUMMARY backgrounds homogenous between experiments. Preparation of viable and killed TR:TREATMENT_SUMMARY U-[13C]Bacteria: ThyA- E. coli were grown overnight with shaking in LB TR:TREATMENT_SUMMARY supplemented with thymidine (500 µg/ml) and trimethoprim (50 µg/ml), diluted TR:TREATMENT_SUMMARY 1/40, and grown until log-phase [optical density at 600 nm (OD600) of 0.8-1.2]. TR:TREATMENT_SUMMARY Bacteria were washed with phosphate buffer saline (PBS) to remove LB salts TR:TREATMENT_SUMMARY before addition to cells. For labeling of bacteria, 10 µl of an overnight TR:TREATMENT_SUMMARY cultured of thyA- E. coli was added to 20 ml of a filtered M9 minimal medium TR:TREATMENT_SUMMARY salts (Life Technologies) supplemented with 1 mM thiamine, 1 mM MgSO4, 0.1 M TR:TREATMENT_SUMMARY CaCl2, 500 µg/ml thymidine, 50 µg/ml trimethoprim, and 0.5% U-[13C6] glucose TR:TREATMENT_SUMMARY (Campro Scientific). Bacteria were grown for 72h, washed with PBS and subjected TR:TREATMENT_SUMMARY to heat-killing by re-suspension in PBS and subsequently incubation at 60˚C for TR:TREATMENT_SUMMARY 60-90 min. For antibiotic killing, bacteria were incubated for 6h to 12h with TR:TREATMENT_SUMMARY Streptomycin or Gentamycin (50 µg/ml). Bacteria were kept at 4˚C until use. TR:TREATMENT_SUMMARY Efficient killing was confirmed by overnight plating on LB-agar plates. TR:TREATMENT_SUMMARY Treatment of macrophages: 2E6 BMDMs were plated 12-16h prior to stimulation in TR:TREATMENT_SUMMARY 6-well plate and insert of a trans-well system (Falcon). Cells in wells were TR:TREATMENT_SUMMARY stimulated with live or killed labelled-E. coli at MOI 50 or with 500 ng/mL LPS. TR:TREATMENT_SUMMARY Cells in inserts were left untreated. Plates were centrifuged at 2000 rpm for TR:TREATMENT_SUMMARY 5min. BMDMs were incubated for 5 min and washed with PBS to remove non-ingested TR:TREATMENT_SUMMARY bacteria and further incubated for 6h or 18h. #SAMPLEPREP SP:SAMPLEPREP_SUMMARY Metabolites from frozen pellets were extracted at 4e6 cells per mL using ice SP:SAMPLEPREP_SUMMARY cold 5:3:2 methanol:acetonitrile:water (v/v/v) with vigorous vortexing at 4 SP:SAMPLEPREP_SUMMARY degrees C followed by centrifugation as described for 10 min at 18,000 g. SP:SAMPLEPREP_SUMMARY Supernatants were maintained at 4°C until analysis that same day. SP:PROCESSING_STORAGE_CONDITIONS 4℃ SP:EXTRACT_STORAGE -80℃ #CHROMATOGRAPHY CH:CHROMATOGRAPHY_SUMMARY Positive C18 CH:CHROMATOGRAPHY_TYPE Reversed phase CH:INSTRUMENT_NAME Thermo Vanquish CH:COLUMN_NAME Phenomenex Kinetex C18 (150 x 2.1mm,1.7um) CH:SOLVENT_A 100% water; 0.1% formic acid CH:SOLVENT_B 100% acetonitrile; 0.1% formic acid CH:FLOW_GRADIENT 0-0.5 min 5% B, 0.5-1.1 min 5-95% B, 1.1-2.75 min hold at 95% B, 2.75-3 min CH:FLOW_GRADIENT 95-5% B, 3-5 min hold at 5% B CH:FLOW_RATE 450 uL/min CH:COLUMN_TEMPERATURE 45 CH:SAMPLE_INJECTION 6 uL #ANALYSIS AN:ANALYSIS_TYPE MS #MS MS:INSTRUMENT_NAME Thermo Q Exactive Orbitrap MS:INSTRUMENT_TYPE Orbitrap MS:MS_TYPE ESI MS:ION_MODE POSITIVE MS:MS_COMMENTS Resolution 70,000, scan range 65-900 m/z, maximum injection time 200 ms, MS:MS_COMMENTS microscans 2, automatic gain control (AGC) 3 x 10^6 ions, source voltage 4.0 kV, MS:MS_COMMENTS capillary temperature 320 C, and sheath gas 45, auxiliary gas 15, and sweep gas MS:MS_COMMENTS 0 (all nitrogen). Data converted to mzXML using RawConverter. Metabolites were MS:MS_COMMENTS annotated and integrated using Maven in conjunction with the KEGG database. #MS_METABOLITE_DATA MS_METABOLITE_DATA:UNITS peak area MS_METABOLITE_DATA_START Samples 156 157 158 159 160 161 162 163 164 165 166 167 174 175 176 177 178 179 180 181 182 183 184 185 186 187 188 Factors Sample source:murine macrophage cells | Timepoint (h):18 | LPS treatment (ng/ml):0 | E coli viability:NA | Multiplicity of infection:NA Sample source:murine macrophage cells | Timepoint (h):18 | LPS treatment (ng/ml):0 | E coli viability:NA | Multiplicity of infection:NA Sample source:murine macrophage cells | Timepoint (h):18 | LPS treatment (ng/ml):0 | E coli viability:NA | Multiplicity of infection:NA Sample source:murine macrophage cells | Timepoint (h):18 | LPS treatment (ng/ml):0 | E coli viability:live | Multiplicity of infection:25 Sample source:murine macrophage cells | Timepoint (h):18 | LPS treatment (ng/ml):0 | E coli viability:live | Multiplicity of infection:25 Sample source:murine macrophage cells | Timepoint (h):18 | LPS treatment (ng/ml):0 | E coli viability:live | Multiplicity of infection:25 Sample source:murine macrophage cells | Timepoint (h):18 | LPS treatment (ng/ml):0 | E coli viability:dead | Multiplicity of infection:25 Sample source:murine macrophage cells | Timepoint (h):18 | LPS treatment (ng/ml):0 | E coli viability:dead | Multiplicity of infection:25 Sample source:murine macrophage cells | Timepoint (h):18 | LPS treatment (ng/ml):0 | E coli viability:dead | Multiplicity of infection:25 Sample source:murine macrophage cells | Timepoint (h):18 | LPS treatment (ng/ml):500 | E coli viability:NA | Multiplicity of infection:NA Sample source:murine macrophage cells | Timepoint (h):18 | LPS treatment (ng/ml):500 | E coli viability:NA | Multiplicity of infection:NA Sample source:murine macrophage cells | Timepoint (h):18 | LPS treatment (ng/ml):500 | E coli viability:NA | Multiplicity of infection:NA Sample source:murine macrophage cells | Timepoint (h):18 | LPS treatment (ng/ml):0 | E coli viability:NA | Multiplicity of infection:NA Sample source:murine macrophage cells | Timepoint (h):18 | LPS treatment (ng/ml):0 | E coli viability:NA | Multiplicity of infection:NA Sample source:murine macrophage cells | Timepoint (h):18 | LPS treatment (ng/ml):0 | E coli viability:NA | Multiplicity of infection:NA Sample source:murine macrophage cells | Timepoint (h):18 | LPS treatment (ng/ml):0 | E coli viability:NA | Multiplicity of infection:NA Sample source:murine macrophage cells | Timepoint (h):18 | LPS treatment (ng/ml):0 | E coli viability:NA | Multiplicity of infection:NA Sample source:murine macrophage cells | Timepoint (h):18 | LPS treatment (ng/ml):0 | E coli viability:NA | Multiplicity of infection:NA Sample source:murine macrophage cells | Timepoint (h):6 | LPS treatment (ng/ml):0 | E coli viability:dead | Multiplicity of infection:50 Sample source:murine macrophage cells | Timepoint (h):6 | LPS treatment (ng/ml):0 | E coli viability:dead | Multiplicity of infection:50 Sample source:murine macrophage cells | Timepoint (h):6 | LPS treatment (ng/ml):0 | E coli viability:dead | Multiplicity of infection:50 Sample source:murine macrophage cells | Timepoint (h):6 | LPS treatment (ng/ml):0 | E coli viability:NA | Multiplicity of infection:NA Sample source:murine macrophage cells | Timepoint (h):6 | LPS treatment (ng/ml):0 | E coli viability:NA | Multiplicity of infection:NA Sample source:murine macrophage cells | Timepoint (h):6 | LPS treatment (ng/ml):0 | E coli viability:NA | Multiplicity of infection:NA Sample source:murine macrophage cells | Timepoint (h):18 | LPS treatment (ng/ml):0 | E coli viability:dead | Multiplicity of infection:50 Sample source:murine macrophage cells | Timepoint (h):18 | LPS treatment (ng/ml):0 | E coli viability:dead | Multiplicity of infection:50 Sample source:murine macrophage cells | Timepoint (h):18 | LPS treatment (ng/ml):0 | E coli viability:dead | Multiplicity of infection:50 L-alanine 1831550 2531756 2134534 1784593 1305773 1694913 2198777 2205878 2021611 1849654 2127338 2020564 1644809 2557674 2909276 1387059 1586627 1793346 1540157 1740649 2500886 1410618 1779945 1552930 1133839 1217591 1186338 L-arginine 3712675 4533998 4106087 2381237 2224698 2242980 3705266 3342320 2928002 3403688 3481230 3663627 2473974 2008624 2399709 6734912 7257614 6714254 4999220 3853674 5849364 6911498 6043536 7450098 1962536 2289554 1464178 L-asparagine 451954 562777 530546 274562 201849 284189 648683 577611 473120 438750 549152 568146 264336 349945 435624 385900 543497 450389 398983 330036 630584 389775 469045 356191 205462 202585 167371 L-aspartate 111526 144207 158104 431586 316495 435681 257394 271707 286464 137129 154392 230914 115772 122722 163734 100200 110728 146984 180089 174385 175242 88795 115920 117168 92399 75559 78828 L-cysteine 575806 675547 649508 909939 764959 884083 1438076 1039131 1133157 1114167 1086173 1187639 614961 738512 824903 539131 705931 710986 1178892 1255725 1334549 707097 708697 796393 1078364 1120056 861239 L-glutamate 2366937 2885009 2733637 3980571 2630367 3545128 3069887 3554819 3205923 2406194 2639161 3573047 2874336 3088831 3426221 602270 769675 972534 2272897 2297346 2094186 562696 680071 837388 2232183 2360316 1812026 L-glutamine 1656562 1934876 1765781 1086934 760758 1140803 1631820 1476845 1195934 1147649 1246367 1562575 499766 698747 845815 1078033 1703447 1512660 972068 790203 1302130 1065814 1628130 1189071 500489 500546 372770 glycine 883190 873601 954988 797998 732980 792884 798406 794617 833785 756517 780278 993400 674583 736534 745365 664239 705373 783886 618389 834085 792653 855291 819712 786849 755032 725509 747043 L-histidine 761921 886994 907296 832888 713329 790370 1229496 997940 895753 928771 1206013 1214887 603504 599698 748483 840971 1176895 1044056 758683 745313 1050285 792388 989918 968761 533572 618255 483509 L-leucine/isoleucine 17965490 18461130 18042060 13070160 10667610 14814250 16243330 21810210 17168460 17163680 18320640 20914130 8466744 6920490 9417359 20938320 33146510 25204630 14243320 13846920 15347800 24404810 22947680 30543550 8612758 8086470 7468814 L-lysine 2884788 3390229 3323563 2760512 2159050 2966347 5376172 3647130 3545148 2862360 3680781 3513277 2289986 1943027 3203485 3847165 6022592 5162794 3501472 3314758 4295684 4375605 4265088 4365903 2253825 2766997 2008157 L-methionine 5471258 6091408 5213618 4259148 3623253 4790913 8244048 6012166 5007568 6701430 5722124 7190672 2559650 2831414 3336927 5851430 7871930 6689784 5017372 4412324 5462876 7328550 6525888 7041542 2117158 2462285 1770030 L-phenylalanine 3289197 3304059 3196414 2715313 2226347 2737381 3648200 3498067 3642826 3200289 4445156 3158487 1419364 1695634 2001930 2314304 3538475 2997035 3310964 2852864 3706670 2286240 3619867 2937313 1581272 1417507 1329779 L-proline 5181733 4222108 5057992 3796312 4124065 4502710 6564622 5118388 4966726 6012674 5337648 6979954 1936442 2759124 2983043 2180267 2976725 3019031 3251439 3143492 4225782 2827177 2760829 2594881 2378116 2337360 2249555 L-threonine 1114548 996766 1199143 884384 762177 977238 1338212 1169647 975848 1003777 1214308 1341152 606376 605970 719890 886562 1151090 1031911 915628 788967 1035501 844215 991619 1177082 670382 671782 495079 L-tryptophan 1545208 1592463 1771313 1558589 1174248 1308080 2525683 2359454 2225300 2319776 2761223 2673443 1055447 1177620 1128898 1551088 2534596 1942630 1493216 1612132 1815944 1745615 1750669 2609497 1475075 1266602 1294564 L-tyrosine 2905454 3076057 2584682 2710040 2221690 2876959 5301800 3852328 3366797 4203516 4208274 5260820 1808014 2058139 2377670 2822624 3603069 3366908 3030443 2773508 3547437 3289454 3066916 3344409 1742099 1643580 1630133 L-valine 7062388 7761234 6641846 6624988 5362171 7117524 12901840 10891050 8970269 10132640 8522211 11062790 3653057 4237354 4604074 7185794 8821477 8756590 6927804 6371746 6465662 8133676 7846188 8623399 4672074 4540172 4139413 dAMP 14539 0 12741 13450 7532 6156 17718 11534 9480 17596 13157 8711 10476 14010 15426 2831 0 0 116827 111800 82899 0 0 0 52860 43261 44598 Adenosine 189264 249545 193718 240683 184217 180693 179954 159823 190798 186524 162998 385934 330664 340703 425655 182316 145265 167917 340393 353594 359588 175189 131348 85565 216265 229638 170330 Guanosine 17840 25673 15515 37542 20629 26430 19388 32844 19778 16845 8246 22703 16727 10220 27069 1819 0 0 11921 15402 13314 0 2778 0 5473 10710 4410 Guanine 235736 273644 232846 194535 144673 202031 352188 277538 233268 299874 246197 333012 99027 132519 136797 265514 363215 315078 209882 223021 267842 330253 289717 311931 83841 108830 77965 CMP 84449 102442 105144 176930 153854 139541 182474 161775 200481 255775 237255 230149 178409 215499 245865 43237 57186 76140 158982 202791 196058 47992 39222 58964 123812 156272 102414 Cytidine 124091 109693 132937 43401 24883 36824 137237 116365 79299 460200 413127 578016 148636 156445 195736 22358 35317 24013 104237 106407 102595 32305 18645 33004 153426 164940 124440 Cytosine 190638 173894 190356 58064 45937 56794 121049 103333 81775 476498 381371 432593 193248 233133 264206 62507 77244 75297 103082 118471 110140 53245 34044 41449 151679 166278 122805 Thymidine 8065 13912 22261 5495 6508 4725 19280 17747 20349 14217 19249 26740 13745 17193 15765 27263 47120 30912 6912 7358 12506 40281 35630 32997 16819 4957 3520 Uracil 58136 80116 58752 179491 133052 177622 168965 220143 134307 86048 79431 90226 71877 76842 98058 17133 31678 20509 106600 82860 98282 24183 10776 21704 53149 56957 41395 Hypoxanthine 10143580 9926051 9689031 12571340 9967527 13420130 15060890 14261950 12646170 14892930 10667070 16141340 8200626 9186749 11757800 1492227 2454408 2118323 6443886 8977242 6740742 1915594 1547918 2087512 7202742 5919364 5418220 Allantoate 29425 38762 48892 72544 68217 38673 64209 54557 63259 38147 67166 55335 66696 60218 59084 28386 65797 44772 35595 51288 61215 24178 32390 42396 73249 75349 61666 5-Hydroxyisourate 34965 61087 36839 32436 23756 40904 58140 43594 60511 31067 46802 49804 20253 23876 45700 15663 26975 33213 21975 30843 41221 15628 27929 27883 20175 11239 14637 Pyridoxal 83453 92655 65226 90927 85625 104492 139882 100587 114401 83643 104199 114489 54125 94915 83083 19898 19014 17685 66529 63215 47672 20105 13003 13427 82342 71964 54001 Nicotinamide 1803212 1961238 1971376 1011314 826386 1019352 1905736 1613287 1558760 3661002 2993661 3856473 2600108 2992401 2185002 986115 1044505 1097670 2631220 4112382 1773691 1469581 1078769 1633953 2253214 1817566 1582528 Glutathione disulfide 0 14122 2888 74342 43320 44743 42956 49186 49636 14674 34233 21885 9105 12846 16366 0 0 0 0 0 0 0 0 0 16797 20633 18192 5-Oxoproline 1169142 1492765 1298745 1275470 864741 910624 1235993 1105935 887323 983530 1219682 1372376 856505 924373 1083298 721304 1061469 1043713 926718 755192 1005371 668737 1038730 747953 696935 682235 419687 Cys-Gly 58333 73419 58384 77228 61147 69200 93201 104540 93081 68617 65244 67488 86818 98343 104406 37493 58649 37260 83698 89867 71518 56143 40075 54724 45830 53008 48848 gamma-L-Glutamyl-L-cysteine 54000 92193 49618 118848 112239 120572 134713 136981 111485 104005 128846 129064 194649 261608 240669 44104 75867 46842 97316 100992 85788 33541 32572 49174 338559 323817 320624 gamma-Glutamyl-Se-methylselenocysteine 5613 5100 10979 23332 22063 21830 33854 20865 16733 13541 23869 24576 14690 21636 20485 4498 19054 17151 14554 10506 22536 15108 8878 9289 20436 33834 28693 gamma-L-Glutamyl-D-alanine 101726 102822 135601 294312 282102 260713 181103 230572 169835 147881 85821 88508 60067 61716 76591 169520 287292 249334 121522 112583 134800 264518 242643 209163 55779 44788 53755 gamma-Glutamyl-gamma-aminobutyrate 143054 176985 162494 127195 122809 135003 202001 176333 147215 110776 133226 123560 69937 87686 97647 327410 416214 323773 141434 119958 134065 424115 338300 362356 54436 70233 62542 gamma-L-Glutamylputrescine 171339 197006 279638 99633 173570 181095 109889 148137 109504 121165 85567 65226 78111 40565 93235 502630 866475 779721 202561 246215 200705 689397 690509 624158 56193 104171 31927 (5-L-Glutamyl)-L-glutamine 42592 41183 46366 27768 26595 34902 45623 35626 39149 47224 27327 29095 14715 14301 20656 55766 93635 79287 26244 31613 31533 96056 84572 63616 5909 11319 8659 L-Homocysteine 2959 7516 5566 6627 3090 6576 10559 4642 9790 12803 16586 12256 2016 11786 7500 10841 10537 6964 16488 11035 11986 6678 4804 4794 4783 10402 4550 Dimethylglycine 140645 153000 163569 1315431 991960 1227116 490085 798976 630938 144579 110130 176204 102833 125619 131156 122006 152907 177718 997829 888901 760301 175025 142630 143004 414123 407636 363702 S-Adenosyl-L-methionine 6749 8336 3496 34621 34537 39960 66869 41310 61275 27311 35890 38966 10694 10093 12415 0 2218 1408 25657 25379 30968 5612 6290 11315 27357 51128 54712 5-10-Methenyltetrahydrofolate 1537 3924 2672 6181 3194 3310 8270 5916 12254 5884 2236 2148 2544 2813 4074 0 0 0 0 0 3202 0 0 0 0 0 0 Ornithine 123216 140161 126418 200826 224546 157817 316721 171629 185900 129311 217017 185880 241244 166999 258063 123215 176139 158349 156711 164922 219716 86329 115128 173176 254849 230979 205591 L-Citrulline 756248 734005 843115 2075913 1483846 1948954 2287663 2011067 1728345 1134586 1329680 1731715 600723 665796 789762 375973 500548 441491 619354 594086 636643 225246 288906 311115 1288229 1272874 1123545 Cadaverine 6172 6265 4297 180747 175995 183504 264591 302554 337927 5617 0 0 8324 4041 4759 2136 5711 4454 108818 162485 121167 32629 20668 31262 219239 209137 232808 Spermidine 3124949 4450402 2316723 3491060 3510298 2937174 3285434 3202179 3380866 3032537 3414691 3196719 1318452 2694813 3145795 1103299 1391178 1816704 1868900 1339993 1705759 490130 558392 775982 489817 1350849 1777269 Spermine 207074 401598 136294 33208 32911 32274 33703 67808 45824 46935 72392 66436 55783 99891 122161 69621 76056 79104 25552 23533 37718 17288 28509 23020 5930 15910 46664 Carnosine 47621 71395 88861 38002 46645 57727 51624 59737 31584 51510 42264 42200 25063 26275 41110 140860 200440 151986 70139 57016 68820 157289 149938 124256 34407 33173 34513 Creatine 12698200 8694647 11233480 21782460 17357660 19655580 17215920 17798000 20529250 20809680 14711670 24664630 10214240 12115480 14622310 2187420 2398040 3938614 9871661 13253350 10016380 3718889 3247273 3473200 10381210 11627540 11589470 Creatinine 243110 206073 258469 260524 229961 283765 254865 314973 336722 356088 304507 571943 188804 165506 193405 231386 159612 226824 261197 324903 203063 270029 277225 436832 264900 236264 253018 4-Acetamidobutanoate 29443 25655 32343 37837 29149 38469 40070 29217 35802 30120 34927 31281 17294 16778 18778 15594 21268 19073 10599 20319 21731 20264 20645 24510 19988 17880 25723 N-Acetyl-L-citrulline 87113 61771 106549 52785 54315 67622 76682 80800 56337 106404 41648 39186 23635 25489 35003 143680 277628 195255 65832 77127 90547 292418 274100 203470 25657 28588 18308 N-Acetylornithine 633424 719677 789031 492226 484818 570641 590600 706342 415431 603386 304993 379054 196667 173170 252251 1149500 1759928 1145456 529618 465053 466895 1742311 1447394 1461327 163659 175948 137268 Guanidinoacetate 56541 51546 64589 45502 33050 45236 48352 70969 46957 37021 31441 44664 61683 59429 70812 17076 21640 30275 54851 55520 53910 27825 28311 28411 18285 24653 9862 trans-4-Hydroxy-L-proline 90365 153967 86106 168524 134647 87089 190359 154948 151687 105320 218362 138174 206645 211531 166157 127300 154196 131788 216714 214276 169435 90656 84644 150552 174936 220941 247060 Pantetheine 13566 8999 13018 4657 5486 11779 18689 4115 5232 11151 0 0 4011 0 5989 12274 19476 14514 11738 24708 14781 17865 12132 20006 3678 4911 0 Hypotaurine 256696 365760 283435 379082 251475 299075 261360 312122 308215 319415 311641 249176 549741 664358 790241 55131 72540 93774 470973 312720 391054 58501 57375 79311 422287 314141 266496 L-Methionine S-oxide 92071 236980 134952 198782 278048 145973 278066 360650 488541 184434 280929 266120 209424 247069 229951 218386 278029 264328 225887 191941 281697 211223 208819 304770 140614 196340 234007 3-Methyldioxyindole 22204 29279 21601 30476 20776 23074 39984 38673 32861 30294 46449 29064 19639 23611 26894 29136 39969 26296 28209 27786 28180 22543 30944 35128 28761 21470 24728 Indole 16359 18343 22225 13525 14558 17039 31773 22392 14069 11425 31780 17288 11858 15466 14389 16117 27214 17613 16498 21573 15947 21387 8784 27135 17413 22237 10003 Indole-3-acetate 21074 44965 30069 2597 2628 5017 6485 7100 7069 26964 33746 20250 271725 243788 223749 148051 100378 155955 120226 64068 79070 139037 175128 366733 188469 184544 188414 Indolepyruvate 45629 47068 32402 32194 32212 45060 90199 57365 52760 54983 63291 76466 27614 28740 35766 40493 48879 42404 45912 41892 51314 26068 28547 47448 34367 31807 28125 Indoxyl 12064 16332 16856 13404 19692 15058 18880 21406 9519 10060 19240 8560 9711 4462 6154 22399 36142 24826 14168 8522 13140 18202 21269 24248 7123 9178 7070 6-Hydroxykynurenic acid 10392 15562 2974 32507 20488 43874 29484 38930 48029 34514 24331 36034 10128 10233 12361 0 0 2249 25007 33288 23229 19800 10274 24339 48451 46288 38274 N-formyl kynurenine 29058 37415 25022 11736 23097 26688 26667 26364 18967 28967 21236 11453 34248 26130 30657 82940 140345 75025 27050 27377 35677 143106 110731 99847 19395 29003 25162 Anthranilate 20444 20265 18562 24069 22715 16803 24220 18628 12821 16914 22393 13437 18606 17906 16489 20913 16806 21032 20303 22694 17376 25407 24810 48446 22442 17864 20769 g-Oxalo-crotonate 336590 331789 306382 303865 332885 375590 506925 392631 427489 411450 375261 502765 285440 321249 347052 52486 76876 77823 199185 234367 172268 72817 60481 85201 264871 225816 217533 2-Aminomuconate 5373 5491 0 1785 0 0 0 0 0 2000 5013 1747 36922 32466 25899 18631 14715 15397 11225 8376 9408 22538 22004 59557 21854 19629 23922 Dopamine 28162 47543 23581 23782 20823 27664 54146 46158 40544 29004 33829 30526 26301 13757 15969 39182 87703 58850 24905 24659 27343 48329 27484 65107 31806 14810 18110 Acetylcholine 496483 394237 516621 289972 285218 353105 267058 250840 314338 377735 200196 419091 245238 341602 465600 52160 46122 78869 297134 461904 242542 86153 78897 81527 116080 121007 120486 Choline 3675584 6973370 4705388 7709828 7833162 9213929 9414175 9620406 9849692 6182728 5700618 6776718 9337971 11089560 12528060 1677376 3556285 3650601 5129706 5559614 4435132 2206361 2098467 3475138 9320605 9714636 9673253 acetyl-carnitine (acyl-C2) 1012558 901696 747130 952741 716884 876336 1326158 1143048 1126729 1662300 1317126 2055833 1792907 2012985 2055922 288025 351173 393548 1311266 1521443 994338 503481 396682 546013 1033890 1267941 1033911 propionyl-carnitine (acyl-C3) 72798 88032 68116 47734 34333 45127 117120 74420 79529 143187 136423 193736 98010 113467 145773 35411 46943 43846 121767 138487 114806 51240 45199 65269 27613 35990 32704 acyl-C4-OH (Hydroxybutyrylcarnitine) 48626 62200 33133 82998 56713 85007 79303 91015 72138 65242 60195 72719 106452 116571 110608 20209 21768 25765 98146 101755 70894 37376 28286 34475 38635 43139 42647 acyl-C5-OH (hydroxyisovalerylcarnitine) 9045 11201 9259 15800 12074 11390 15989 17494 16347 9266 9424 18362 20075 14564 21280 12053 10698 11566 19922 24156 16206 19066 12163 12697 8666 10160 11745 Putrescine 11442 89 122615 148126 120575 1235144 1107653 959389 400999 372556 442644 221026 669264 714150 233007 185710 278064 56932 75463 85514 526838 587276 531247 113100 91758 139441 339606 Alanine 13C2 0 0 0 0 0 0 0 0 0 0 0 0 0 0 10401 3007 4375 4066 1127 3967 4470 3451 7143 4636 0 0 0 Alanine 13C3 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 41613 57204 88947 5275 2219 4242 9368 12680 8227 Arginine 13C5 0 0 0 0 0 0 0 0 0 0 0 0 2405 1304 3011 91040 107129 87302 43250 27265 34592 106016 128774 88036 2390 2961 2361 Arginine 13C6 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 152482 122628 132528 6914 4020 0 13237 20247 8643 Asparagine 13C4 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 23579 35104 40888 0 0 0 4577 3453 8663 Aspartate 13C4 0 0 0 0 0 0 0 0 0 0 0 0 0 1126 0 0 0 0 15490 15904 18579 0 0 0 2392 0 1189 Cysteine 13C3 0 0 0 0 0 0 0 0 0 0 0 0 1974134 1889913 2318287 417086 524779 720204 2183151 1975449 2095794 351809 331808 506278 1759308 2167921 1838530 Glutamate 13C1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 18388 0 0 1337 26592 20871 31593 1101 0 5636 12613 7023 9036 Glutamate 13C2 0 0 0 0 0 0 0 0 0 0 0 0 13996 20063 11022 3143 785 1271 57327 63161 60772 1416 1605 5439 24213 33380 23505 Glutamate 13C3 0 0 0 0 0 0 0 0 0 0 0 0 3992 0 0 7714 8947 5617 66344 73830 56880 4941 12417 5004 16454 22031 21365 Glutamate 13C4 0 0 0 0 0 0 0 0 0 0 0 0 6171 2800 5202 57113 108213 46624 28288 26442 26116 61730 77810 71588 2786 11255 3778 Glutamate 13C5 0 0 0 0 0 0 0 0 0 0 0 0 3117 5266 3381 6588 4294 9974 94429 102550 88179 10745 9054 3237 25968 26291 29926 Glutamine 13C1 0 0 0 0 0 0 0 0 0 0 0 0 2934 14524 13591 3290 8481 1964 0 13012 0 14523 0 9611 0 2910 8015 Glutamine 13C3 0 0 0 0 0 0 0 0 0 0 0 0 1416 2781 6141 13439 42718 27445 11844 3861 8034 17379 24910 9825 0 1381 1347 Glutamine 13C5 0 0 0 0 0 0 0 0 0 0 0 0 3297 0 2369 55388 96216 64820 29443 28872 47020 64140 64895 56268 2088 4913 7598 Histidine 13C1 0 0 0 0 0 0 0 0 0 0 0 0 0 1965 0 0 0 0 5167 0 6236 4234 608 13885 1163 0 0 Histidine 13C5 0 0 0 0 0 0 0 0 0 0 0 0 65240 67302 85266 474837 792125 511547 168022 195041 189876 910473 752390 545071 60710 60946 52775 Histidine 13C6 0 0 0 0 0 0 0 0 0 0 0 0 3333 2569 8407 35388 65836 36600 47813 45021 49584 49160 54129 38878 4679 3716 3714 Leucine/isoleucine 13C1 0 0 0 0 0 0 0 0 0 0 0 0 24257 4887 0 32792 9870 38344 19515 5954 49030 36213 3020 7018 17919 10925 0 Leucine/isoleucine 13C3 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1348 0 3960 19720 13255 13238 7666 2880 6245 0 3513 3381 Leucine/isoleucine 13C4 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 74084 77219 60255 4937 2828 4161 7429 6156 10593 Leucine/isoleucine 13C5 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 52649 53475 26797 0 0 2627 5775 3255 7398 Leucine/isoleucine 13C6 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 380307 368845 338256 30666 31664 57178 77185 53057 55083 Lysine 13C1 0 0 0 0 0 0 0 0 0 0 0 0 0 7239 32674 2252 34747 20055 0 26621 21458 5978 37239 31365 8587 0 10767 Lysine 13C6 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 3633 0 0 190273 145808 162656 0 2629 3571 20398 27575 24606 Methionine 13C1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 16469 6449 0 18682 5977 0 4881 9090 9586 5567 5834 Methionine 13C2 0 0 0 0 0 0 0 0 0 0 0 0 5633 2784 583 5173 3978 8808 2549 5181 2516 3643 0 9649 0 0 0 Methionine 13C5 0 0 0 0 0 0 0 0 0 0 0 0 13640 4251 21912 3738 0 5018 67977 68768 63005 8957 3458 7939 70390 59767 34424 Phenylalanine 13C3 0 0 0 0 0 0 0 0 0 0 0 0 261948 260195 408716 375595 547098 484038 459700 409990 509246 417539 477103 409492 294404 351478 290664 Phenylalanine 13C4 0 0 0 0 0 0 0 0 0 0 0 0 14835 41075 29283 54580 54941 36252 31339 39263 23463 69942 52707 61562 36609 41050 45521 Phenylalanine 13C6 0 0 0 0 0 0 0 0 0 0 0 0 7597 4015 6180 43389 49736 34888 14534 9519 16990 39428 65619 21834 4716 2276 2691 Phenylalanine 13C7 0 0 0 0 0 0 0 0 0 0 0 0 0 2761 0 10962 20089 4853 5541 2873 2409 11843 10534 2432 0 0 0 Phenylalanine 13C9 0 0 0 0 0 0 0 0 0 0 0 0 2473974 2008624 2399709 6734912 7257614 6714254 4999220 3853674 5849364 6911498 6043536 7450098 1962536 2289554 1464178 Proline 13C1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1958 11874 4233 0 2616 13272 4977 1301 635 0 0 5520 7470 Proline 13C2 0 0 0 0 0 0 0 0 0 0 0 0 6753 0 1367 42247 90895 39241 20481 21717 24285 53789 34156 48057 616 0 0 Proline 13C4 0 0 0 0 0 0 0 0 0 0 0 0 0 4244 0 2457 0 0 37169 50818 38081 0 0 0 3170 3111 5242 Proline 13C5 0 0 0 0 0 0 0 0 0 0 0 0 1127 0 2080 2129 5117 2548 333494 278787 331857 9594 7909 16362 67236 67482 66409 Threonine 13C2 0 0 0 0 0 0 0 0 0 0 0 0 19847 15122 19426 17999 24533 17637 26468 25440 23091 24679 22967 24752 38008 44562 48259 Threonine 13C4 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 5938 8602 1675 25213 23683 18414 6681 4312 3567 5205 3361 1467 Tryptophan 13C11 0 0 0 0 0 0 0 0 0 0 0 0 10243 14230 11247 8517 12670 13546 52311 64578 34471 13749 2891 10755 15078 12246 21391 Tyrosine 13C9 0 0 0 0 0 0 0 0 0 0 0 0 0 2699 0 33579 39580 56219 62085 58903 58842 78525 56590 49181 32143 36721 23785 Valine 13C1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 18362 32122 17702 8011 19243 34532 19406 3106 12304 0 302 0 Valine 13C2 0 0 0 0 0 0 0 0 0 0 0 0 0 0 3213 6811 7246 6212 12999 8703 7469 6655 9206 10492 3750 1915 11310 Valine 13C3 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1360 0 20725 30070 15847 0 0 0 0 2551 0 Valine 13C4 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 4167 0 0 16224 17735 9133 0 0 0 3075 0 0 Valine 13C5 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 357820 331013 294247 16282 14029 26744 37959 49778 60135 Spermidine 13C1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 984 2055 0 3697 15240 3164 7316 0 0 988 1340 0 579 Spermidine 13C3 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 12700 5266 6071 0 0 0 0 6549 6076 Spermidine 13C4 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 27332 15622 23510 2263 1592 0 6640 24141 31304 Spermidine 13C5 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 23056 24097 18767 0 0 1905 0 8975 15337 Spermidine 13C6 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 22309 15083 18188 0 0 1251 1462 8278 8290 Spermidine 13C7 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 119346 95970 82932 6317 3071 13874 21281 40682 63296 Glutathione 13C1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 39964 58662 15182 0 0 13766 5624 181404 8491 Glutathione 13C2 0 0 0 0 0 0 0 0 0 0 0 0 11247 27910 11569 0 2176 2915 1249985 1129351 940081 14123 12002 24471 363111 545112 383988 Glutathione 13C3 0 0 0 0 0 0 0 0 0 0 0 0 16578 21032 15885 1128 0 0 372612 415638 269777 3156 3604 3589 108493 126540 107131 Glutathione 13C4 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 136313 143638 89724 0 0 0 23327 27087 22335 Glutathione 13C5 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1622 389602 330177 280666 2937 2402 0 76623 106201 74544 Glutathione 13C6 0 0 0 0 0 0 0 0 0 0 0 0 8642 13735 10337 0 0 0 52551 55368 28000 2599 0 0 9010 3642 9080 Glutathione 13C7 0 0 0 0 0 0 0 0 0 0 0 0 1911 0 0 1976 1357 1564 163723 148150 113962 4802 2772 1896 11737 0 1960 Glutathione 13C8 0 0 0 0 0 0 0 0 0 0 0 0 0 1486 0 0 0 0 21730 22228 12308 1957 1817 0 0 0 1174 Glutathione 13C10 0 0 0 0 0 0 0 0 0 0 0 0 25046 33835 48225 10366 5200 19570 31017 48228 36520 8751 5598 13943 20527 17366 21346 Hypoxanthine 13C1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 45027 0 14989 0 22751 35291 29159 0 0 0 10727 31278 19721 Hypoxanthine 13C3 0 0 0 0 0 0 0 0 0 0 0 0 15069 17561 15133 12323 24484 20160 73311 88024 63676 18922 9525 5002 76398 65429 51034 Hypoxanthine 13C4 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1723 0 238670 264133 228146 12479 9795 3498 211781 167843 189341 Hypoxanthine 13C5 0 0 0 0 0 0 0 0 0 0 0 0 3142 6898 6360 6062 5066 8194 1675156 2311611 1525507 71208 58657 63108 1498456 1593230 1179250 Xanthine 0 0 0 0 0 0 0 0 0 0 0 0 532849 662627 756870 111286 144791 150723 529550 422279 497806 69711 77257 113612 246363 330822 230445 Xanthine 13C4 0 0 0 0 0 0 0 0 0 0 0 0 0 1115 0 2154 0 0 17147 18222 13976 0 0 0 2669 5600 5928 Xanthine 13C5 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 129580 133367 109918 0 1692 0 45029 65590 41497 Glutathione disulfide 13C2 0 0 0 0 0 0 0 0 0 0 0 0 34576 51795 46072 8305 7107 6766 15505 30189 32403 6738 4624 8285 23359 26248 15143 Glutathione disulfide 13C3 0 0 0 0 0 0 0 0 0 0 0 0 8375 12415 9480 1375 1917 2191 2587 3684 4013 0 1873 0 0 2939 5406 Glutathione disulfide 13C11 0 0 0 0 0 0 0 0 0 0 0 0 10649 14026 23426 0 0 3138 14803 12456 12066 0 1547 0 20639 31900 0 5-Oxoproline 13C4 0 0 0 0 0 0 0 0 0 0 0 0 8811 11826 20515 18255 21378 23387 14620 22847 21702 17117 15507 18941 5238 9264 9016 S-Adenosyl-L-homocysteine 0 0 0 0 0 0 0 0 0 0 0 0 7530 16170 11360 3330 2037 5404 29442 12906 18051 4823 7767 10967 11365 16171 17258 S-Adenosyl-L-methionine 13C15 0 0 0 0 0 0 0 0 0 0 0 0 2755 8909 6895 2931 2169 2793 6602 6472 8258 0 1769 0 42058 41637 19036 Ornithine 13C3 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 50052 35394 27629 0 0 0 7333 5337 8617 Citrulline 13C6 0 0 0 0 0 0 0 0 0 0 0 0 0 1483 1381 4925 4087 11745 17022 21544 26595 7288 5860 8134 7482 9650 4305 Putrescine 13C2 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 44061 55443 41076 5360 2090 2165 4368 5096 5185 Putrescine 13C4 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 59853 78586 46161 11183 7820 17272 35317 53120 42847 MS_METABOLITE_DATA_END #METABOLITES METABOLITES_START metabolite_name KEGG ID m/z RT L-alanine C00041 90.0557 0.654 L-arginine C00062 175.1191 0.637 L-asparagine C00152 133.0609 0.653 L-aspartate C00049 134.0449 0.673 L-cysteine C00097 122.0274 0.676 L-glutamate C00025 148.0605 0.665 L-glutamine C00064 147.0765 0.656 glycine C00037 76.0402 0.657 L-histidine C00135 156.0770 0.625 L-leucine/isoleucine C00123 132.1022 0.723 L-lysine C00047 147.1130 0.615 L-methionine C00073 150.0585 0.704 L-phenylalanine C00079 166.0862 0.829 L-proline C00148 116.0711 0.683 L-threonine C00188 120.0659 0.662 L-tryptophan C00078 205.0975 1.746 L-tyrosine C00082 182.0812 0.710 L-valine C00183 118.0867 0.692 dAMP C00360 332.0764 0.696 Adenosine C00212 268.1037 0.692 Guanosine C00387 284.0993 0.694 Guanine C00242 152.0547 0.699 CMP C00055 324.0590 0.678 Cytidine C00475 244.0930 0.688 Cytosine C00380 112.0510 0.692 Thymidine C00214 243.0961 0.656 Uracil C00106 113.0352 0.705 Hypoxanthine C00262 137.0459 0.709 Allantoate C00499 177.0610 0.624 5-Hydroxyisourate C11821 185.0321 0.654 Pyridoxal C00250 168.0655 0.698 Nicotinamide C00153 123.0556 0.755 Glutathione disulfide C00127 613.1596 0.696 5-Oxoproline C01879 130.0501 0.661 Cys-Gly C01419 179.0487 0.693 gamma-L-Glutamyl-L-cysteine C00669 251.0700 0.695 gamma-Glutamyl-Se-methylselenocysteine C05695 313.0340 0.626 gamma-L-Glutamyl-D-alanine C03738 219.0977 0.685 gamma-Glutamyl-gamma-aminobutyrate C15767 233.1133 0.697 gamma-L-Glutamylputrescine C15699 218.1503 0.611 (5-L-Glutamyl)-L-glutamine C05283 276.1190 0.678 L-Homocysteine C00155 136.0428 0.695 Dimethylglycine C01026 104.0713 0.680 S-Adenosyl-L-methionine C00019 399.1445 0.644 5-10-Methenyltetrahydrofolate C00445 457.1665 0.678 Ornithine C01602 133.0975 0.618 L-Citrulline C00327 176.1032 0.666 Cadaverine C01672 103.1235 0.605 Spermidine C00315 146.1652 0.596 Spermine C00750 203.2233 0.601 Carnosine C00386 227.1138 0.618 Creatine C00300 132.0771 0.676 Creatinine C00791 114.0667 0.670 4-Acetamidobutanoate C02946 146.0812 0.628 N-Acetyl-L-citrulline C15532 218.1134 0.674 N-Acetylornithine C00437 175.1078 0.694 Guanidinoacetate C00581 118.0615 0.663 trans-4-Hydroxy-L-proline C01157 132.0657 0.689 Pantetheine C00831 279.1339 0.696 Hypotaurine C00519 110.0275 0.659 L-Methionine S-oxide C02989 166.0534 0.833 3-Methyldioxyindole C05834 146.0603 1.748 Indole C00463 118.0655 1.775 Indole-3-acetate C00954 176.0707 1.931 Indolepyruvate C00331 204.0634 0.696 Indoxyl C05658 134.0585 0.630 6-Hydroxykynurenic acid C08480 206.0483 0.700 N-formyl kynurenine C02700 237.0903 0.685 Anthranilate C00108 138.0550 1.798 g-Oxalo-crotonate C03453 159.0279 0.700 2-Aminomuconate C02220 161.0461 1.952 Dopamine C03758 154.0852 0.704 Acetylcholine C01996 146.1177 0.679 Choline C00114 104.1075 0.660 acetyl-carnitine (acyl-C2) C02571 204.1231 0.697 propionyl-carnitine (acyl-C3) C03017 218.1387 0.696 acyl-C4-OH (Hydroxybutyrylcarnitine) HMDB13127 248.1494 0.697 acyl-C5-OH (hydroxyisovalerylcarnitine) ac107 262.1652 0.697 Putrescine C00134 89.10808 0.6055565 Alanine 13C2 C00041 92.06019 0.6557526 Alanine 13C3 C00041 93.0658 0.6561615 Arginine 13C5 C00062 180.1373 0.7243406 Arginine 13C6 C00062 181.1391 0.6345847 Asparagine 13C4 C00152 137.0749 0.6460111 Aspartate 13C4 C00049 138.058 0.6500429 Cysteine 13C3 C00097 125.0382 0.5942517 Glutamate 13C1 C00025 149.064 0.6650531 Glutamate 13C2 C00025 150.066 0.6596343 Glutamate 13C3 C00025 151.0719 0.6527643 Glutamate 13C4 C00025 152.0746 0.6960438 Glutamate 13C5 C00025 153.0773 0.712122 Glutamine 13C1 C00064 148.0799 0.6544532 Glutamine 13C3 C00064 150.0881 0.6276932 Glutamine 13C5 C00064 152.0927 0.6255616 Histidine 13C1 C00135 157.0809 0.6203719 Histidine 13C5 C00135 161.0931 0.6782344 Histidine 13C6 C00135 162.0959 0.6674704 Leucine/isoleucine 13C1 C00123 133.1055 0.7541156 Leucine/isoleucine 13C3 C00123 135.1103 0.740293 Leucine/isoleucine 13C4 C00123 136.1155 0.7188146 Leucine/isoleucine 13C5 C00123 137.1187 0.6950837 Leucine/isoleucine 13C6 C00123 138.1221 0.7028044 Lysine 13C1 C00047 148.1159 0.613589 Lysine 13C6 C00047 153.1333 0.6381131 Methionine 13C1 C00073 151.0618 0.701107 Methionine 13C2 C00073 152.0639 0.6926749 Methionine 13C5 C00073 155.0737 0.6623482 Phenylalanine 13C3 C00079 169.0953 0.6196371 Phenylalanine 13C4 C00079 170.0967 0.6951391 Phenylalanine 13C6 C00079 172.106 0.6582414 Phenylalanine 13C7 C00079 173.11 0.6526856 Phenylalanine 13C9 C00079 175.119 0.6333836 Proline 13C1 C00148 117.0744 0.6816895 Proline 13C2 C00148 118.0772 0.6426013 Proline 13C4 C00148 120.0843 0.7054959 Proline 13C5 C00148 121.0871 0.6868165 Threonine 13C2 C00188 122.0717 0.6628635 Threonine 13C4 C00188 124.0798 0.6406446 Tryptophan 13C11 C00078 216.1369 1.758987 Tyrosine 13C9 C00082 191.1122 0.6556907 Valine 13C1 C00183 119.09 0.6897496 Valine 13C2 C00183 120.091 0.6909844 Valine 13C3 C00183 121.0962 0.6905708 Valine 13C4 C00183 122.0996 0.6965842 Valine 13C5 C00183 123.1034 0.6936687 Spermidine 13C1 C00315 147.1687 0.5936 Spermidine 13C3 C00315 149.1755 0.603653 Spermidine 13C4 C00315 150.1787 0.5902986 Spermidine 13C5 C00315 151.1821 0.5855203 Spermidine 13C6 C00315 152.1854 0.5886295 Spermidine 13C7 C00315 153.1887 0.5890613 Glutathione 13C1 C00051 309.0944 0.6943896 Glutathione 13C2 C00051 310.0964 0.6939707 Glutathione 13C3 C00051 311.1005 0.7022544 Glutathione 13C4 C00051 312.1047 0.6995961 Glutathione 13C5 C00051 313.1086 0.6919687 Glutathione 13C6 C00051 314.1105 0.6906038 Glutathione 13C7 C00051 315.1169 0.8896617 Glutathione 13C8 C00051 316.1203 0.6900546 Glutathione 13C10 C00051 318.1201 0.6966136 Hypoxanthine 13C1 C00262 138.0493 0.7240098 Hypoxanthine 13C3 C00262 140.0544 0.6991011 Hypoxanthine 13C4 C00262 141.0592 0.6976484 Hypoxanthine 13C5 C00262 142.0621 0.7284386 Xanthine C00385 153.0405 0.6964892 Xanthine 13C4 C00385 157.0543 0.735945 Xanthine 13C5 C00385 158.0574 0.7628536 Glutathione disulfide 13C2 C00127 615.1605 0.6878536 Glutathione disulfide 13C3 C00127 616.1657 0.6880906 Glutathione disulfide 13C11 C00127 624.2006 0.6524737 5-Oxoproline 13C4 C01879 134.0639 0.6673805 S-Adenosyl-L-homocysteine C00021 385.1261 0.7211223 S-Adenosyl-L-methionine 13C15 C00019 414.2015 0.6622297 Ornithine 13C3 C01602 136.1063 0.6317766 Citrulline 13C6 C00327 182.1249 0.6437608 Putrescine 13C2 C00134 91.11414 0.6884627 Putrescine 13C4 C00134 93.12153 0.6070402 METABOLITES_END #END