#METABOLOMICS WORKBENCH juliehaines_20241125_132154 DATATRACK_ID:5397 STUDY_ID:ST003605 ANALYSIS_ID:AN005923 PROJECT_ID:PR002231 VERSION 1 CREATED_ON December 5, 2024, 7:25 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 Global metabolomics and tracing of E coli-derived metabolites following ST:STUDY_TITLE engulfment of heat-killed bacteria by wild type or RagAGTP-deficient bone marrow ST:STUDY_TITLE derived macrophages. ST:STUDY_SUMMARY Global metabolomics and 13C-tracing analysis of wild type or RagA-deficient bone ST:STUDY_SUMMARY marrow derived macrophages exposed to heat-killed uniformly 13C-labelled E. coli ST:STUDY_SUMMARY in a trans-well system for 6h or 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 - CT 389 n°1 genotype:WT | treatment:none | time (h):18 | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=F97-01- SUBJECT_SAMPLE_FACTORS - CT 389 n°2 genotype:WT | treatment:none | time (h):18 | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=F97-02- SUBJECT_SAMPLE_FACTORS - CT 389 n°3 genotype:WT | treatment:none | time (h):18 | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=F97-03- SUBJECT_SAMPLE_FACTORS - CT 390 n°1 genotype:WT | treatment:none | time (h):18 | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=F97-04- SUBJECT_SAMPLE_FACTORS - CT 390 n°2 genotype:WT | treatment:none | time (h):18 | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=F97-05- SUBJECT_SAMPLE_FACTORS - CT 390 n°3 genotype:WT | treatment:none | time (h):18 | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=F97-06- SUBJECT_SAMPLE_FACTORS - Dead 6h 389 n°1 genotype:WT | treatment:dead bacteria | time (h):6 | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=F97-07- SUBJECT_SAMPLE_FACTORS - Dead 6h 389 n°2 genotype:WT | treatment:dead bacteria | time (h):6 | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=F97-08- SUBJECT_SAMPLE_FACTORS - Dead 6h 389 n°3 genotype:WT | treatment:dead bacteria | time (h):6 | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=F97-09- SUBJECT_SAMPLE_FACTORS - Dead 6h 390 n°1 genotype:WT | treatment:dead bacteria | time (h):6 | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=F97-10- SUBJECT_SAMPLE_FACTORS - Dead 6h 390 n°2 genotype:WT | treatment:dead bacteria | time (h):6 | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=F97-11- SUBJECT_SAMPLE_FACTORS - Dead 6h 390 n°3 genotype:WT | treatment:dead bacteria | time (h):6 | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=F97-12- SUBJECT_SAMPLE_FACTORS - Dead 18h 389 n°1 genotype:WT | treatment:dead bacteria | time (h):18 | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=F97-13- SUBJECT_SAMPLE_FACTORS - Dead 18h 389 n°2 genotype:WT | treatment:dead bacteria | time (h):18 | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=F97-14- SUBJECT_SAMPLE_FACTORS - Dead 18h 389 n°3 genotype:WT | treatment:dead bacteria | time (h):18 | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=F97-15- SUBJECT_SAMPLE_FACTORS - Dead 18h 390 n°1 genotype:WT | treatment:dead bacteria | time (h):18 | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=F97-16- SUBJECT_SAMPLE_FACTORS - Dead 18h 390 n°2 genotype:WT | treatment:dead bacteria | time (h):18 | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=F97-17- SUBJECT_SAMPLE_FACTORS - Dead 18h 390 n°3 genotype:WT | treatment:dead bacteria | time (h):18 | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=F97-18- SUBJECT_SAMPLE_FACTORS - CT 477 n°1 genotype:Cre RagA KO | treatment:none | time (h):18 | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=F97-19- SUBJECT_SAMPLE_FACTORS - CT 477 n°2 genotype:Cre RagA KO | treatment:none | time (h):18 | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=F97-20- SUBJECT_SAMPLE_FACTORS - CT 477 n°3 genotype:Cre RagA KO | treatment:none | time (h):18 | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=F97-21- SUBJECT_SAMPLE_FACTORS - CT 479 n°1 genotype:Cre RagA KO | treatment:none | time (h):18 | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=F97-22- SUBJECT_SAMPLE_FACTORS - CT 479 n°2 genotype:Cre RagA KO | treatment:none | time (h):18 | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=F97-23- SUBJECT_SAMPLE_FACTORS - CT 479 n°3 genotype:Cre RagA KO | treatment:none | time (h):18 | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=F97-24- SUBJECT_SAMPLE_FACTORS - Dead 6h 477 n°1 genotype:Cre RagA KO | treatment:dead bacteria | time (h):6 | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=F97-25- SUBJECT_SAMPLE_FACTORS - Dead 6h 477 n°2 genotype:Cre RagA KO | treatment:dead bacteria | time (h):6 | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=F97-26- SUBJECT_SAMPLE_FACTORS - Dead 6h 477 n°3 genotype:Cre RagA KO | treatment:dead bacteria | time (h):6 | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=F97-27- SUBJECT_SAMPLE_FACTORS - Dead 6h 479 n°1 genotype:Cre RagA KO | treatment:dead bacteria | time (h):6 | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=F97-28- SUBJECT_SAMPLE_FACTORS - Dead 6h 479 n°2 genotype:Cre RagA KO | treatment:dead bacteria | time (h):6 | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=F97-29- SUBJECT_SAMPLE_FACTORS - Dead 6h 479 n°3 genotype:Cre RagA KO | treatment:dead bacteria | time (h):6 | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=F97-30- SUBJECT_SAMPLE_FACTORS - Dead 18h 477 n°1 genotype:Cre RagA KO | treatment:dead bacteria | time (h):18 | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=F97-31- SUBJECT_SAMPLE_FACTORS - Dead 18h 477 n°2 genotype:Cre RagA KO | treatment:dead bacteria | time (h):18 | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=F97-32- SUBJECT_SAMPLE_FACTORS - Dead 18h 477 n°3 genotype:Cre RagA KO | treatment:dead bacteria | time (h):18 | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=F97-33- SUBJECT_SAMPLE_FACTORS - Dead 18h 479 n°1 genotype:Cre RagA KO | treatment:dead bacteria | time (h):18 | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=F97-34- SUBJECT_SAMPLE_FACTORS - Dead 18h 479 n°2 genotype:Cre RagA KO | treatment:dead bacteria | time (h):18 | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=F97-35- SUBJECT_SAMPLE_FACTORS - Dead 18h 479 n°3 genotype:Cre RagA KO | treatment:dead bacteria | time (h):18 | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=F97-36- #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). For TR:TREATMENT_SUMMARY Tg.hUbC-cre-ERT2+/T::Rragaf/f and RagAGTP/delta mice, tamoxifen was added to the TR:TREATMENT_SUMMARY culture on day 2 or 3 to a final concentration of 1 µg/ml in order to induce TR:TREATMENT_SUMMARY CRE expression. BMDMs were used on day 5 to 7 after seeding. Period of TR:TREATMENT_SUMMARY differentiation of the cells, concentration of cells when replating and TR:TREATMENT_SUMMARY time-lapse between replating and stimulation with bacteria were important TR:TREATMENT_SUMMARY parameters to maintain metabolic backgrounds homogenous between experiments. TR:TREATMENT_SUMMARY Preparation of viable and killed U-[13C]Bacteria: ThyA- E. coli were grown TR:TREATMENT_SUMMARY overnight with shaking in LB supplemented with thymidine (500 µg/ml) and TR:TREATMENT_SUMMARY trimethoprim (50 µg/ml), diluted 1/40, and grown until log-phase [optical TR:TREATMENT_SUMMARY density at 600 nm (OD600) of 0.8-1.2]. Bacteria were washed with phosphate TR:TREATMENT_SUMMARY buffer saline (PBS) to remove LB salts before addition to cells. For labeling of TR:TREATMENT_SUMMARY bacteria, 10 µl of an overnight cultured of thyA- E. coli was added to 20 ml of TR:TREATMENT_SUMMARY a filtered M9 minimal medium salts (Life Technologies) supplemented with 1 mM TR:TREATMENT_SUMMARY thiamine, 1 mM MgSO4, 0.1 M CaCl2, 500 µg/ml thymidine, 50 µg/ml trimethoprim, TR:TREATMENT_SUMMARY and 0.5% U-[13C6] glucose (Campro Scientific). Bacteria were grown for 72h, TR:TREATMENT_SUMMARY washed with PBS and subjected to heat-killing by re-suspension in PBS and TR:TREATMENT_SUMMARY subsequently incubation at 60˚C for 60-90 min. For antibiotic killing, bacteria TR:TREATMENT_SUMMARY were incubated for 6h to 12h with Streptomycin or Gentamycin (50 µg/ml). TR:TREATMENT_SUMMARY Bacteria were kept at 4˚C until use. Efficient killing was confirmed by TR:TREATMENT_SUMMARY overnight plating on LB-agar plates. Treatment of macrophages: 2E6 BMDMs were TR:TREATMENT_SUMMARY plated 12-16h prior stimulation in non-tissue cultured treated 6-well plate (BD TR:TREATMENT_SUMMARY Falcons). Cells were then stimulated with live or killed labelled-E. coli at MOI TR:TREATMENT_SUMMARY 50, centrifuged at 2000 rpm for 5min. BMDMs were incubated for 5 min and washed TR:TREATMENT_SUMMARY with PBS to remove non-ingested 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 Negative 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 95% water/5% acetonitrile; 1 mM ammonium acetate CH:SOLVENT_B 95% acetonitrile/5% water; 1 mM ammonium acetate CH:FLOW_GRADIENT 0-0.5 min 0% B, 0.5-1.1 min 0-100% B, 1.1-2.75 min hold at 100% B, 2.75-3 min CH:FLOW_GRADIENT 100-0% B, 3-5 min hold at 0% 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 NEGATIVE 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 CT 389 n°1 CT 389 n°2 CT 389 n°3 CT 390 n°1 CT 390 n°2 CT 390 n°3 Dead 6h 389 n°1 Dead 6h 389 n°2 Dead 6h 389 n°3 Dead 6h 390 n°1 Dead 6h 390 n°2 Dead 6h 390 n°3 Dead 18h 389 n°1 Dead 18h 389 n°2 Dead 18h 389 n°3 Dead 18h 390 n°1 Dead 18h 390 n°2 Dead 18h 390 n°3 CT 477 n°1 CT 477 n°2 CT 477 n°3 CT 479 n°1 CT 479 n°2 CT 479 n°3 Dead 6h 477 n°1 Dead 6h 477 n°2 Dead 6h 477 n°3 Dead 6h 479 n°1 Dead 6h 479 n°2 Dead 6h 479 n°3 Dead 18h 477 n°1 Dead 18h 477 n°2 Dead 18h 477 n°3 Dead 18h 479 n°1 Dead 18h 479 n°2 Dead 18h 479 n°3 Factors genotype:WT | treatment:none | time (h):18 | Sample source:murine bone marrow derived macrophages genotype:WT | treatment:none | time (h):18 | Sample source:murine bone marrow derived macrophages genotype:WT | treatment:none | time (h):18 | Sample source:murine bone marrow derived macrophages genotype:WT | treatment:none | time (h):18 | Sample source:murine bone marrow derived macrophages genotype:WT | treatment:none | time (h):18 | Sample source:murine bone marrow derived macrophages genotype:WT | treatment:none | time (h):18 | Sample source:murine bone marrow derived macrophages genotype:WT | treatment:dead bacteria | time (h):6 | Sample source:murine bone marrow derived macrophages genotype:WT | treatment:dead bacteria | time (h):6 | Sample source:murine bone marrow derived macrophages genotype:WT | treatment:dead bacteria | time (h):6 | Sample source:murine bone marrow derived macrophages genotype:WT | treatment:dead bacteria | time (h):6 | Sample source:murine bone marrow derived macrophages genotype:WT | treatment:dead bacteria | time (h):6 | Sample source:murine bone marrow derived macrophages genotype:WT | treatment:dead bacteria | time (h):6 | Sample source:murine bone marrow derived macrophages genotype:WT | treatment:dead bacteria | time (h):18 | Sample source:murine bone marrow derived macrophages genotype:WT | treatment:dead bacteria | time (h):18 | Sample source:murine bone marrow derived macrophages genotype:WT | treatment:dead bacteria | time (h):18 | Sample source:murine bone marrow derived macrophages genotype:WT | treatment:dead bacteria | time (h):18 | Sample source:murine bone marrow derived macrophages genotype:WT | treatment:dead bacteria | time (h):18 | Sample source:murine bone marrow derived macrophages genotype:WT | treatment:dead bacteria | time (h):18 | Sample source:murine bone marrow derived macrophages genotype:Cre RagA KO | treatment:none | time (h):18 | Sample source:murine bone marrow derived macrophages genotype:Cre RagA KO | treatment:none | time (h):18 | Sample source:murine bone marrow derived macrophages genotype:Cre RagA KO | treatment:none | time (h):18 | Sample source:murine bone marrow derived macrophages genotype:Cre RagA KO | treatment:none | time (h):18 | Sample source:murine bone marrow derived macrophages genotype:Cre RagA KO | treatment:none | time (h):18 | Sample source:murine bone marrow derived macrophages genotype:Cre RagA KO | treatment:none | time (h):18 | Sample source:murine bone marrow derived macrophages genotype:Cre RagA KO | treatment:dead bacteria | time (h):6 | Sample source:murine bone marrow derived macrophages genotype:Cre RagA KO | treatment:dead bacteria | time (h):6 | Sample source:murine bone marrow derived macrophages genotype:Cre RagA KO | treatment:dead bacteria | time (h):6 | Sample source:murine bone marrow derived macrophages genotype:Cre RagA KO | treatment:dead bacteria | time (h):6 | Sample source:murine bone marrow derived macrophages genotype:Cre RagA KO | treatment:dead bacteria | time (h):6 | Sample source:murine bone marrow derived macrophages genotype:Cre RagA KO | treatment:dead bacteria | time (h):6 | Sample source:murine bone marrow derived macrophages genotype:Cre RagA KO | treatment:dead bacteria | time (h):18 | Sample source:murine bone marrow derived macrophages genotype:Cre RagA KO | treatment:dead bacteria | time (h):18 | Sample source:murine bone marrow derived macrophages genotype:Cre RagA KO | treatment:dead bacteria | time (h):18 | Sample source:murine bone marrow derived macrophages genotype:Cre RagA KO | treatment:dead bacteria | time (h):18 | Sample source:murine bone marrow derived macrophages genotype:Cre RagA KO | treatment:dead bacteria | time (h):18 | Sample source:murine bone marrow derived macrophages genotype:Cre RagA KO | treatment:dead bacteria | time (h):18 | Sample source:murine bone marrow derived macrophages L-asparagine 343255.4 204515 169712.2 150520.4 176096.8 136587.9 183058.6 279770.4 235146.2 286037.3 359100 333098.8 215372.6 136509.3 114792.6 84669.48 85550.5 110039.1 194165.2 129263.5 143478.8 246941.6 218756.8 304332 325132.8 285971.5 237244.5 222886.3 332855.1 284173.5 122019.6 161464.6 171378.6 129862.9 99468.91 149035.7 ADP 149295.9 130463.2 169805.8 225418.6 331259.8 399253.2 175330.5 203488.4 154266.1 203549.6 133949.6 194042.7 288743.3 211094.9 205737.9 161991.3 254141.5 286414.8 227732.5 200551.4 241631.2 185707.8 205568.8 191912.8 127073.8 188858.5 164937.6 269381.5 220730.5 138608.8 151485.6 179838.6 165995.7 129032.5 183677.4 109733.3 AMP 2364392 2033941 2789558 2732333 2994781 4242724 3195228 4194261 3988442 4029419 3179192 3243420 3130569 2499429 2021174 1194515 1404294 2003170 5915894 4892438 5461116 6988046 4502038 5351724 4251804 6443912 5511854 3867017 4654406 3616432 2359079 2120225 2572618 3429357 2522500 2597194 Adenosine 19956.89 24655.12 35535.8 54186.86 30604.2 32756.98 36991.65 29486.76 39502.06 38679.4 23278.38 34570.9 24003.69 27848.16 28843.97 23259.69 24425.38 20360.99 67612.13 134247.2 101781 144934.2 168646.4 274285 32594.45 30373.15 37466.17 30565.99 38819.73 43486.46 48344.29 63815.05 58075.11 107794.7 34009.66 68996.91 Adenine 125808 157236.1 168843 217254.6 176428.9 128882.1 178920 170342.3 184720.2 183308.7 139846.4 173433.1 104566.6 136276.5 147892 125650.3 171324.2 132580.9 387961.3 572270 461640.8 532152.6 735767.2 937009.9 190754.9 226462.9 186037.8 166107.2 220083.6 201323.1 180751.9 238979.6 286697.6 508761.1 197574.6 273622 GDP 33782.12 47167.59 35482.85 43423.71 64995.98 87636.55 72354.73 70127.87 50362.74 49917.68 38946.23 41518.55 81359.98 52806.54 51424.85 34669.97 51571.51 54756.5 57448.81 36833.05 48646.66 35022.24 56746.08 23026.47 24525.62 59860.21 56817.51 71956.17 48266.93 54800.11 26976.71 37373.77 29129.55 22670.6 33856.82 19702.89 GMP 230903.1 358039 466943.7 450957 356585.6 369092.8 717068.2 597360.1 1032766 748975.2 1069428 799842.2 211901.8 240363.1 219894 104955.4 154395.5 165427.5 605188.1 455065.5 448030.3 656199.9 660776.9 1108403 982861.2 974837.6 904850.2 377035.8 400616.7 506831.7 251173.6 297230.8 340355.2 407973.2 174636.9 352837.4 Cytidine 44398.37 60527.68 62961.22 67363.44 49769.08 86253.88 175189.6 185785.6 293430.6 255451.6 294898.4 219114 117024.3 156253.9 126995.5 75905.95 123435.2 95917.43 83547.14 110294.9 121534.7 97708.26 110689 151810.2 196874.6 262585.3 301560.2 212839.8 241221.7 237280.5 164168.3 227473.5 173481.3 121697.2 117213.3 181963.4 dTMP 34320.2 33876.75 51328.66 37495.96 54757.19 54544.69 57660.08 75605.25 56732.97 58907.61 56223.72 52694.04 44189.95 0 73667.8 57596.29 59730.96 54772.55 32827.87 23985.73 16004.62 44929.83 43477.34 18894.89 59440.43 41851.24 38313.67 51502.38 63917.32 39555.86 22374.4 43988.7 0 56173.9 54740.18 36684.28 UMP 412461.1 409627.5 519727.4 652886.2 553645.1 467802.2 752140.5 591352.7 888613.3 762382.9 864229.7 876318.3 328845.7 242575.5 248505.3 163626.1 117104.7 183643.4 772068.6 656268.7 558314.2 826454.8 711218.3 1353985 754925.1 1008547 701754.8 460887.4 594505.1 460548 266086.5 235866.6 306641.1 341473.8 196603.2 296143 IDP 631856.1 552499.8 403810.9 733247.6 1097983 803978.2 870073.3 1089992 774638.7 1045557 690993.8 900195 834870.8 501538.1 425437.8 600179.2 723080.5 876688 593914.4 546156.1 635326.9 358297 606869.5 557146.6 632040.6 669914.8 605824 897751.2 830851.3 621806.5 335622.5 459496.4 431316.2 644692.5 731105.5 424783.6 IMP 90263.62 78858.27 107759.5 94552.43 126998 133712.7 33365.88 38345.64 66849.49 29880.65 69825.52 31102.26 102240.5 86498.44 79640.18 57544.67 50328.88 60987.44 114232.7 69932.19 86478.18 93730.98 56258.33 137885.9 85014.99 80003.41 56063.8 55974.39 38883.65 38159.58 86755.95 57739.18 102932.2 106557.4 55514.76 85700.05 Inosine 1135096 1625408 2140721 1546761 1034820 1190068 908923.8 721513.3 1008128 1081496 1515603 1019555 529888 435371 335098.6 571731.9 311363.6 441358.3 567602.8 902608 798430.2 974463.9 1337694 3128502 545977.6 601096.1 747007.8 363037.5 386973.2 667316.8 552947.4 664770.8 549929.7 538443.1 213346.2 784568.8 Hypoxanthine 1036856 1124288 1279922 931504.2 737601.3 997132.2 615101.1 578561.6 675106.9 753218.3 1009136 893749 828542.8 482060 411229.4 639000.4 439250.2 511482.2 375006.9 526937.2 463598.9 560969.2 775438.1 1684558 699820.7 595358.9 656180.7 408975.1 435198.8 684569.6 528587.2 580561.5 552726.9 482352 266637.8 693662.7 Xanthine 318392.1 286155.1 355234.9 295889.9 237995.4 284735.2 195616.1 192289.8 205656.5 262570.3 307420.9 312166 141507.3 93674.27 58854.91 110639 69666.34 96727.76 153280.3 185771.1 183590.5 228329.7 257318.6 564940.2 162876.9 163294.2 143509 124568.4 153295.2 177832.3 69495.63 70243.7 76313.4 69750.93 42540 88213.88 Urate 33441.6 42446.19 54391.84 54981.22 85175.59 169435.5 82893.52 113504.6 72160.21 107794 85376.45 94189.31 63645.31 40272.04 30383.89 30252.23 23837.92 48332.86 79810.81 36748.54 37958.14 81174.23 47934.04 64898.91 80155.69 118960.3 56189.86 62693.8 87148.01 70140.15 30411.63 29605.21 41765.89 41557.82 23362.01 26636.65 UDP-glucose 109761.8 92680.84 83649.06 97889.38 124505.9 76087.76 92743.26 114281.2 112636.5 112647.8 125780.9 132222.5 95401.38 70636.28 73161.72 57131.09 52489.16 69649.56 158072.4 152345.4 143894.2 133284.6 178112.2 195120.4 101896.6 152910.5 142221.7 121463.9 155284.2 179184.5 75964.56 53217.3 62700.85 47560.16 35149.07 40192.75 ADP-D-ribose 210333.4 176311.7 117190.4 111756.2 151840.4 125719.5 65193.01 103535.1 86278.01 122400.5 98574.15 149996.3 110714.3 100542.4 68029.79 31002.85 48946.9 84002.01 124654.9 120691.1 116346.5 136396.8 175394.7 325830.7 124826.9 146150 115024.2 131417.3 68652.04 109578.2 43499.22 49187.5 39207.36 32790.75 29768.84 37808.79 Phosphate 53862970 64346930 58408720 61632690 71847930 63936180 90208360 89035190 78212500 77717260 59900930 73205630 86679500 69532280 61241680 74592740 63369150 63305760 66617250 72542420 76761870 72729800 72188450 74360860 71538890 60390210 67470150 74303750 85295340 75913050 47795240 61244670 56469490 58781890 71650180 52837550 Diphosphate 3613239 3523241 3404801 5092806 5033914 4974320 7072966 6310834 5604592 5249706 5970762 5198036 6476780 4264858 4615712 4611034 4323934 5434764 5277580 4685166 4076204 4210646 5543800 6634638 6438658 7046460 4640218 6448906 7175676 5630448 4501670 3916553 4371810 6028362 5220242 3823310 D-Glucose 333480.1 335367 374641.2 288317.6 348133.3 413949.6 462473.4 506745 475008.1 523719 584808.6 551249.6 448486.8 291179.2 348110.5 376239.8 260737.3 319051.3 489385.5 286489.6 380480.5 504937.7 440515.8 583434.6 470331.4 361917 359290.3 519651.4 453383.9 466637.1 251251.3 295485.7 333723.7 245672.7 236535.1 236688.5 D-Glucose 6-phosphate 664552.8 549729.7 367421.3 261742.3 335370.8 238778.9 212062.9 238063.1 205869.5 294374.1 225668.2 327548.9 1304116 641923.2 425019.2 357750.2 278386 496318.8 195384.9 117418.8 189900.4 228096.1 236496 299465.8 232049.5 179374.9 143113.6 196368.6 152923.2 135318.6 306374.3 224263.2 167734 179694.9 143911.5 188861.7 D-Fructose 1-6-bisphosphate 14328.42 27641.46 24515.81 34624.68 31418.24 37084.89 47828.5 51837.05 54629.92 46338.94 42664.13 67546.91 164822.7 120652.5 179370.6 191694 250941 156486.8 24732.4 22741.36 11796.9 28878.76 21648.83 24799.59 17986.44 18060.21 28363.15 23319.77 24515.09 28653.29 44262.23 35829.65 28576.77 48505.54 36652.85 29074.54 D-Glyceraldehyde 3-phosphate/Glycerone phosphate 481222.6 542038.7 461465.8 354088 473539.2 528433.8 524894.4 503847.4 520799.4 620065.1 502497.4 354683.7 413920.7 682168.8 533822.1 491586.3 582014 405088.1 434125.7 564505.2 591541.4 558330.6 391995.5 467112.7 499961 657158.6 430175.5 420708.3 465070.9 516426.8 494098.1 785682.8 1098450 567436.8 586045.3 417954.4 2/3-Phospho-D-glycerate 172136.3 235433.4 264595.4 162307.6 237219.7 225035.1 566520.1 591768.1 496809.5 494328.8 583684.2 626020.6 421444.8 291487.8 292793.9 229785.2 236112.8 394099.9 182609.9 95174.06 139498.7 203221.1 315887.6 310505.4 469952 420560.2 373928 443248 404553 462372.2 334409.2 262094.2 372746.3 184673.6 120643.8 200636.5 Pyruvate 242891 228569.6 207641.7 265363.8 208215.1 240208.5 220563.8 0 277172.4 238843.5 237501.8 191841.8 234101.6 225130.1 220540 176542.3 210324.5 191043.1 203546.8 220108.2 217261 252069.3 231258.4 380469.3 186875.8 184815 206405.5 192844.2 218184.1 230610 195690 221317.7 223943.3 193954 190750.9 198395.1 Lactate 3198489 1755950 1581932 1495963 1693332 2108166 1335145 1390056 1650268 1448914 1570606 1470804 3043192 3346109 2329660 2272861 2433274 1663739 4535172 907491.2 1004926 938449.9 1320739 1704573 1453620 1219188 1420001 887484.5 1901500 1093657 1107467 1021803 4584878 1119971 746963.2 1879370 Maltose 98407.52 25040.61 36858.92 130232.8 93895.38 19926.39 23678.99 26093.17 34856.07 17373.49 18812.09 20107.73 18489.48 163543.4 77683.79 62801.73 41692.43 23608.33 28859.71 62494.22 97740.66 20328.19 88450.43 70575.38 53579.89 45908.16 37986.79 38129.59 144098 76715.29 20794.07 17704.13 83284.95 47992.99 12882.69 119330.4 Mannitol 37057.66 28538.86 25601.17 24865.98 19822.73 24153.54 40666.86 37922.75 37437.62 49297.07 59023.05 56333.79 35385.23 21203.59 17285.79 20131.98 17527.72 21247.67 155932.9 19989.2 30890.96 34113.53 50593.98 80019.34 74639.14 65020.21 119122.2 52304.46 58815.25 52608.09 25230.85 21436.85 30848.35 43459.89 15624.08 29004.6 Citrate 195197.6 262186.8 201714.9 214111.1 243232.3 161086.9 375086.9 360237.3 412694.1 336472.1 426969.5 381172.2 962440.7 641395.4 531688.4 432855.1 274628.1 438302.8 507900.2 447983.4 511080.9 460345.1 446290.5 906792.8 711340.5 916780.7 427778.8 600703.8 707402.2 592608.3 675928.8 489305.8 635544.6 979269 450784.8 527008.4 2-Oxoglutarate 310777.3 322223.5 383284.9 531693.4 561599.6 894486.8 118223.5 116449.8 171560.4 93083.18 91250.19 120118.2 143313.3 171889.4 318672.1 177691.3 261445.7 164245.9 191249.8 214287.9 304829.1 243216.8 173700.2 189233.9 41471.98 76938.35 97238.48 61865.82 65192.31 84585.48 41674.78 48305.7 74792.4 105614 85281.73 52628.2 Succinate 1337084 244373.5 257898.8 325654.8 243034.8 428778.5 702858.6 579900.9 725259.2 717716.8 589585.2 843249.8 469304.7 362160.8 335494 276654.8 238016.1 270167.4 379076.4 307082 394567.2 329335.3 307591.7 696803.8 607438.4 785512 762958.5 472439.9 438600.8 573662.9 576804.8 692047.3 870667.1 864956.5 637374.4 745315.8 Fumarate 81363.86 77006.98 28815.97 51815.79 36867.96 31846.58 113367.1 102306.2 126374.4 104631.7 123167.4 152585.8 61270.37 54066.8 58167 36555.64 52980.96 83804.43 34377.44 41610.25 60559.27 54624.93 46944.81 77913.32 107058.2 138091.2 151956.3 87045.13 80493.26 112139.8 54252.25 59245.41 63815.33 93203.28 62974.21 69840.46 Malate 1139425 813304.9 564891.9 636766.5 779035.3 559124.3 1636855 1485086 1762825 1772033 1559435 1676316 1225566 983138.3 945703.8 764854.8 719007.2 828796.5 867876.2 597476.6 838704.3 793147.3 794628.8 1281779 1691855 1837903 1699415 1436135 1438071 1360949 942572.7 1075156 1350836 1281360 950240 835155.2 Oxaloacetate 77110.27 100649 77441.03 85606.56 79223.53 79809.12 119267 125359.7 105032.8 103485.8 105355.2 89914.02 96800.91 98372.96 103064.5 112249.8 79139.24 86695.48 77658.68 95803.05 95807.88 99098.71 80721.59 84044.57 98638.27 80959.38 108579 119986.9 109018.9 103311.8 98829.81 92155.73 100309.6 70458.7 78199.05 54565.33 Itaconate 9618497 8520883 9928495 12909470 9586434 13584060 7903790 8827365 9454661 8853940 7920296 10003740 14573200 11729550 12630920 9676975 8745105 8544597 5410324 4603872 5918262 5197030 4775636 8314496 5444906 6933886 6598174 4480382 5285184 4720510 5134228 7252860 8002262 9565703 7540354 7593348 2-Hydroxyglutarate/Citramalate 551306.4 447428.6 386354 508968.2 453771.6 642958.8 167036.9 195397.9 218822.3 195314 145284.6 171026.8 342206.8 255489 276434.4 201826.8 206650.5 218594.1 153361.4 123012 168960.5 149301.2 139108.7 293256.9 105093.9 128190.8 133121 113913.1 78271.07 86992.17 81384.24 104214.1 133471.1 132412.2 103975.7 83504.59 Sedoheptulose 1-phosphate 33996.06 30739.73 39302.35 30585.79 30559.97 19066.51 28311.07 17819.36 30904.5 36699.37 41067.57 47123.86 87593.63 63139.31 87879.06 61795.3 57614.57 68714.37 21215.66 12280.7 17542.42 8849.296 22226.2 56922.58 19406.28 32763.4 18121.9 27401.55 14537.88 14779.56 25632.21 22826.53 28884.42 35566.74 12111.98 24585.27 alpha-D-Ribose 1-phosphate 727202.2 875371 870264.2 790130.3 730919.1 624399.8 556983.1 667530.7 682397.4 709760 1038552 908298.1 767276.2 544186.4 526746.8 583877.4 355642.6 486003.7 378359 400591.1 374808.5 599273.8 593832.6 1212199 731272 653947.6 543425.6 478500.4 453339.9 671418.2 542385 483536.3 455343.9 389486 288991.2 543580.8 Glutathione 1871580 2576307 2691891 2999825 3247705 3551787 5370608 5734080 7602770 6058180 7284210 6325700 3255945 3639024 3357651 2706844 2665794 3318897 7663962 6686874 6883558 7526230 6715472 9086263 9969145 12057230 8884139 5271396 7677956 7517558 5134698 4772406 5258104 6978284 5011331 6638230 Ascorbate 1650230 2027790 1789960 2575174 2655597 2750826 1714920 1769441 2446272 1349377 1828218 1975678 996956.8 822287.8 1319178 1292308 1291893 1181740 1712244 1615760 2040331 1514514 1801644 1659385 845648.5 1065420 1504284 972334.4 1041236 1241956 427959.9 590877.1 735219.8 907661.3 649109.8 578333.5 Dehydroascorbate 8058.172 8823.417 9762.335 6586.141 7633.827 7418.043 3920.951 4897.209 5976.016 6939.043 9078.936 6481.552 2686.677 3095.147 945.2585 2511.852 0 1703.537 3261.413 7581.201 3736.303 5718.563 11859.75 13234.55 1713.395 4406.611 4557.576 4507.631 5379.994 6383.349 2408.045 2325.426 0 4669.661 2714.372 2249.496 gamma-Glutamyl-gamma-aminobutyrate 33045.24 31486.18 21724.94 30640.63 39192.41 35688.1 90348.32 79535.41 94898.84 99210.66 114575.6 93267.66 39575.61 31686.46 22317.78 27111.42 23466.71 28787.28 81436.49 63796.33 71023.41 90000.94 81780.95 101028 131325.7 107790.1 91350.98 122645.4 105260.3 127219.7 33318.55 25702.35 34273.12 33972.92 29774.3 36231.89 N-Acetylneuraminate 1798931 2114724 2199584 2364412 2700673 2906353 4870448 3836010 6417166 4401928 6143594 4070334 4090277 3446103 4063807 2859053 2866328 2684275 707957.3 590320.6 618933.3 721637.5 595387.4 865105.8 1707082 1675140 1848970 1302228 1364338 1405670 674220.4 717638.7 826379.4 976985.9 725342.3 788397.8 N-Glycoloyl-neuraminate 171993.3 165143.2 201052.2 197833.8 239044.1 237459.1 291703 190652 298921.1 267137.6 318189 249653.6 214573.7 152660.9 187584.5 147163.3 134079.8 163471.4 50369.09 36177.91 50831.24 54308.43 52894.72 73941.74 112322.5 122502 99105.99 94337.66 97573.16 86966.61 24530.36 48266.58 42915.96 59280.21 44364.81 38050.23 UDP-N-acetyl-D-glucosamine 117452.7 117531.5 84178.47 121899.3 177792.5 128096.5 154821.5 151640.9 172659.2 144176.7 160443.7 189129.1 123217.8 126100.9 161248.8 93441.76 106815.8 117288.9 174185.2 134361.6 139154.9 124262.4 193497.5 174586.9 127364.8 219656 185463.6 136244.9 194199.1 216557.1 108395.3 111897.8 148042.5 109497.1 82513.7 111505.3 CMP-N-acetylneuraminate 67392.57 71106.84 78273.64 79985.98 93671.88 98661.52 102362 129010 178608.5 130277.4 156094.7 174016.8 93241.29 85513.91 99765.41 59721.89 80322.81 71710.38 60760.33 80569.66 74147.7 61591.05 67887.77 74236.83 76622.1 130377.5 106299.5 59466.19 91012.37 103593 39640.61 41950.5 40178.36 45797.37 36629.5 26605.36 Carnosine 6114.374 8047.919 9498.636 8598.477 11693.3 9337.523 13912.34 14664.7 15852.61 18552.83 25739.83 27771.93 10914.08 7592.747 4658.483 7063.309 5082.008 4216.163 15902.37 9197.517 12940.61 15895.7 14623.11 18423.9 20478.87 26147.33 18239.33 22045.92 23285.02 26829.94 5515.18 5206.049 5859.723 6153.978 2458.558 9758.349 Phosphocreatine 78514.84 61988.41 54515.49 58431.29 80247.66 59990.5 87588.94 132282.5 107034 87578.74 59474.54 80081.27 101032.2 90107.95 78712.37 65154.67 83458.34 84542.96 959184 739368.8 924574.6 958042.5 879611.3 880296.5 797288.8 1111014 1347512 997491.2 1075640 1370349 519592 728321.6 689477.9 921611.3 647834.9 662928.8 Taurine 12343960 12720390 15553950 15375060 13849820 19850550 6985024 7482466 11713810 9182123 9164093 9782021 9063978 8594299 11991960 6565192 7712840 6999576 15462790 19804920 23577570 27024010 15900750 24979800 13372520 15270130 22413420 12491460 12621160 12334820 11324800 16008810 14098990 19582050 11440750 14324180 Hypotaurine 99544.24 134881.3 177361.9 205196.5 212917.9 190355 102912.7 100585.2 151523.8 125909.3 101562.9 126275 131721.9 102932.6 142641.5 101137.8 97679.75 117428.1 317733.4 283174.4 304282.8 479466.9 231097.6 347998.1 345804.6 414779.7 369318.1 192386 194975.1 213983.6 187646.3 168781.8 193189.1 371524.8 196393.8 286058.1 N-formyl kynurenine 456009.7 413028.2 466489.2 440427.6 377214.2 603529.2 784963.8 1125874 1266662 1131631 1192031 1077685 1366379 919977.5 1280080 688804.7 879940.4 696112.8 201240.9 293031 431879.2 561139.6 320971.9 568698.6 387143 503319.5 640704.2 566570.2 616838.3 528277.9 284692.1 437823.2 486123.8 395858.2 289923 359149.3 Serotonin 23702.08 13774.57 13742.8 11471.62 14982.95 9992.006 21421.67 34593.47 50800.48 30933.95 38616.45 36310.97 58321.74 53241.02 52459.7 48071.39 58288.82 46890.22 11459.3 11071.35 17924.75 16907.63 12277.32 22119.48 51947.54 52520.01 41857.78 49650.67 45770.36 50512.84 89259.34 99209.77 118618.5 86082.45 71061.73 96086.31 Glycerol 3-phosphate 69412.22 56895.4 76954.36 83989.43 72705.28 85388.41 133816.4 162742.9 111352.9 172676.8 133486.2 182934.2 236057.2 184879 166521.1 124284.9 105886.4 130889.8 53836.44 46925.91 44033.54 64573.06 88079.45 135867.3 225286.8 171320.5 86004.38 93800.72 146453.9 132604.5 77741.55 70441.12 87206.87 84431.2 67015.73 56616.81 sn-glycero-3-Phosphoethanolamine 219612.1 164523.6 221737.3 205852.6 204928.8 197526.8 542679.4 595637.5 787492.7 569537.8 622292.9 611885.2 632096.1 520064.9 722533.5 377632.5 582904.3 483029.1 101623.5 105499.4 118279.6 115769.7 102955.1 176329.8 278520.3 256844.4 269226.7 185876.4 260664.5 271287.5 364229 375568.7 446392.3 574951.2 361356.5 451952.6 Hexanoic acid (caproate) 908184.2 579595.9 502658.7 551814.6 415456.3 597583.9 486876.9 517057 557059.5 556887.1 653884.9 604951.3 634336.9 692096.6 559748.1 552377.9 598872.4 512317 542890.8 715163.7 623527.2 666727 614102.2 630673.8 421890.3 444191.9 558993.7 595159.9 523704.1 583834.9 702038.3 622145.7 637165.2 400157.8 485548.3 537126.4 Heptanoic acid 886390 793731.8 779840.5 577628.1 417213.3 705903.2 717145.1 698420.4 636192.6 696024.3 719880.6 772234.1 862142.7 581914.7 839983.5 716507.2 645908.8 640548.9 471642.3 696275.1 709811.2 638261 710965.5 900801.2 559785.2 660171.1 630487.8 541302.4 563767.8 777958.5 674700.3 749105.1 732734.8 548868.8 618197 556538.7 Nonanoic acid (pelargonate) 5176028 3564459 3928914 2580949 2367082 4345312 3310433 2491737 3949281 4375080 4932836 4506794 4278096 3698010 3838926 2436716 4157916 3173094 2082596 2912865 3674416 2591447 2673286 4723755 3066787 2273886 5436038 5131676 5102958 4423700 3384696 3835116 3304197 1691651 3491110 2409037 Decanoic acid (caprate) 1006297 1882112 1120044 1387986 874760.1 1108089 1037898 1138316 1558532 1915975 1295022 1230820 1639550 1317173 1538074 1012082 851284.6 980723.8 1140258 747822.2 2083038 876446 1195074 1335760 1193605 788351.7 1440551 1252970 1000279 1766704 1489567 1493430 1743993 670665.7 1135248 999759.2 Dodecanoic acid 774110.8 693284.8 363711.3 833631.3 690548.7 763624.2 726932.3 358158.5 722968.7 699187.8 378125.8 506908.4 566271.7 726366 413029.2 648657.8 395269.1 507175.3 432450.2 609883.5 611703.9 594599.8 450907.8 511328.7 484954.8 431713.8 691846.7 629992.9 611294.1 499792.3 718699.3 412993.9 719533.1 368145.5 512598.6 624209 Tetradecanoic acid 1581668 1338529 693687 1185451 739666 1104979 654557.9 972531.5 958446.1 869795 1190984 1211143 1430218 811680 948224.9 949287.7 790099.5 917469.7 894948.7 1360668 969083 750803.1 895820 1238987 717419.2 846594.2 892545.2 1013688 641556.8 579056.4 1179427 982069.4 1469824 762044.2 774203.1 853046.8 Hexadecanoic acid 13131040 15401190 12480000 15764260 6190136 11624240 15128410 11517940 10604860 14001820 12002940 10857500 9828144 16347750 11220110 10683160 19601770 8219686 11501040 11851850 10600200 9891696 14770020 7990256 11745680 10949240 13890020 13044330 12784670 9510471 12533040 19378580 15500950 10952920 12324810 7656544 Octadecanoic acid 3647309 4401431 2860826 5096422 2952101 4827086 2671060 5173944 3836566 4008082 7492752 3146547 4604000 3627972 4267604 3245941 3019570 3352541 3312730 6711110 5136498 2923362 5971582 2986013 2131204 2615088 3187550 6213440 3449635 2063113 2562873 1959467 4211010 2706283 3323128 3486545 Tetradecenoic acid 45371.13 50837.73 29274.77 27737.3 32007.82 33736.16 38897.47 33576.32 40377.47 75534.19 37615.96 39076.57 29886.41 43852.39 30896.31 43053.85 20490.97 32914.81 33232.02 43115.27 34431.66 46535.35 50514.07 34253.14 40298.91 30547.32 46958.07 38005.77 36197.11 33457.77 43236.75 39732.33 96056.12 27109.7 41802.27 42861.8 Hexadecenoic acid 185283.1 172686.1 128738.8 176290.2 145515.9 130649.5 224411.5 238515.6 216046.7 258218.3 171234.6 257285.9 221219.4 282870.7 218287.9 203448.4 239643.8 190348.1 177145.8 162893.6 123851.3 178952.2 128540.2 223855.2 198752.6 174972.4 163485.5 352807.4 217074.6 169972.1 171720.4 215066.5 767139.8 174206.4 161119.4 212354.6 Octadecenoic acid 3021691 1012025 582899.6 989611.4 842395.4 802892.8 770706.7 1111867 1203032 891846.2 974371.3 1539455 671923.8 1050035 811820.6 737659.8 909863 673297.2 392690.8 530162.8 639767.2 1054576 670333.8 1201247 1037944 908052.7 679645.3 1012719 1648755 808030.2 1178566 741985 1049270 526779.9 610473.9 993574.1 Linoleate 637593.8 141300.8 114507.3 126462.4 89239.47 108294.1 114203.5 132982.6 155077.9 154658.4 124462.2 244938.1 200668.5 211580.9 147626.8 121737.1 100787.5 134388.3 78058.16 147239.7 100625.6 183406.5 182848.6 160144.4 250079.6 201450.2 148761.4 133638.4 212688 205962.5 153269.4 157811.3 255889.8 112384.3 105696.7 125534.4 Eicosatetraenoic acid 629565.1 872734 522463.8 572926.6 764797 726373.2 321933.5 464238.8 245883.5 697373.8 925284.6 936485.1 763574.8 431637.2 515812.7 343784.8 327252.1 514250.1 374872.1 663847.8 371899 311366.9 273103.5 557604.8 516674.2 613127.5 517491.1 505957.8 461988.6 315026.3 560035.3 522904.8 594906.3 258492.1 246078.9 413614.6 Docosahexaenoic acid 194534.8 188452.9 164459.1 132239 136287.8 198191.1 199757 155260.7 140932.8 182578 504623.8 221197 522101.1 252373.7 153469.2 128896.9 112555.5 183341.3 149003.2 143682.7 254511.4 361277.3 485799.4 363852.6 282124.4 358487.7 225009.8 215807.7 193059.8 425738.4 312698.4 203990 216600.5 140148.1 180510.1 158994.7 Dodecanedioic acid 292047.7 247237.8 292910.5 225347.5 244630 262075.2 235112.3 282960.8 276546.7 232840.4 281306.9 306246.8 238897.3 344168.4 238021.7 214964.4 233058.5 251617.5 421150.7 294923.2 228459 242888.1 299951.2 289030.8 261637.3 338437.4 285346.7 266721.2 270015 271762.1 235893.9 262838.4 420342.2 468399.6 291745.9 280782.2 (8Z-11Z-14Z)-Icosatrienoic acid 103316.1 82347.77 106460.6 79327.91 40640.31 91111.69 44050.82 61111.88 75239.76 113791.6 139512.8 201208.2 138105.1 84171.97 42886.67 53538.89 54057.06 102856.5 23107.8 39427.14 53954.74 53299.43 45467.61 87026.62 111541.8 59341.71 121334.4 87400.4 76190.12 100164.9 51927.86 73917.87 72916.31 44835.59 28221.99 40789.8 (5Z-8Z-11Z-14Z-17Z)-Icosapentaenoic acid 356993.5 178096.2 81109.66 126921.1 114196.7 121663.7 48519.26 38518.94 45278.2 73026.63 85291.2 104605.3 88386.19 94191.16 87909.77 62660.4 58522.36 55519.74 133897.2 84424.88 98178.95 104909.4 96510.41 179094.3 102468.2 102179.6 86459.16 47963.44 63970.05 56634.95 68048.88 94060.81 102710.8 37231.47 36789.79 53301.69 (7Z-10Z-13Z-16Z-19Z)-Docosa-7-10-13-16-19-pentaenoic acid 314865.2 318085.2 251835.1 274082.8 269366.5 369014.6 122526 253473.2 215390.5 236297.6 410468.4 342255.1 550025 157887.2 184280.8 142373.2 129166.3 237442.9 139040.2 316895.8 202204.8 232620.4 258114.1 375759 233368.7 256156.6 247402.4 316776.6 144097 218072.9 175913.9 224230.9 281766.3 120491 89794.91 154642.6 6-Aminohexanoate 1715525 1604523 1123010 907487.2 807175.7 1077699 1678895 1968865 1307478 2223395 2611097 3284827 1585862 773924.3 763233 812918.8 861421.4 794306.8 1445541 1168748 1431872 1866691 2352396 4368812 3109200 2605675 2376685 2370034 2140953 3108368 1242093 1104862 1261040 926514.5 707704 1234678 L-4-Hydroxyglutamate semialdehyde 2727686 2152592 2426773 2760887 2629079 3220330 2280570 1837143 2747632 2457285 3029433 2785088 3498587 2589363 3151156 2386216 2683916 2550354 2666973 2127408 2208188 2762772 2043225 4256646 2647733 2324916 2558513 1629725 2017814 1839002 2502622 2872905 3633795 3668326 2625895 3230354 N-Acetylmethionine 46703.09 35305.46 38711.04 30670.95 28054.98 25888.05 57343.22 58507.18 50349.53 73961.7 100092.5 107168.6 48634.44 25473.96 14345.83 19044.03 10492.87 26357.45 23345.65 23748.77 21562.02 35985.96 37073.33 82298.04 95078.79 67694.86 44225.49 54480.23 78388.94 65842.88 26570.96 27794.69 21318.78 27971.52 11723.5 28474.84 3-Methyl-2-oxobutanoic acid 330223 314839.6 266355 264529.3 251790.1 304947.6 264720.2 307519.8 277914.2 281779.3 280534.6 300210.4 284574.1 275628.5 281048.2 238507.9 274983.2 257091.5 238401.6 303353.1 293434.2 282756.3 281900.4 279518.1 246931.4 235369.6 263191 314038.1 282726 295495.3 253251.1 277438.7 311666.2 234260.1 229507.8 245722.6 2-Oxoglutarate 13C54 43791.73 36582.99 31911.32 43055.19 41013.46 40290.93 67693.54 38730.86 33655.07 34438.68 33258.99 39944.98 35611.29 44023.89 45623.06 38660.14 53150.02 46613.11 34274.41 44662.92 41784.42 33475.29 42370.21 43079.82 34355.86 34736.86 32681.68 26715.08 48602.93 36957.27 40559.93 37188.11 36782.14 35039.9 43566.43 31923.86 Malate 13C4 857.5552 1127.837 0 1727.679 1105.743 832.196 114794.4 94817.27 105941.5 90328.48 91193.21 95027.66 35276.32 20991.1 38105.18 13463.45 45010.72 24480.22 797.4271 1217.896 858.1455 1051.445 953.7525 0 107054.8 111152.4 102119.5 71006.87 76195.01 74251.2 28636.48 33598.41 49047.39 49944.49 29568.21 30155.18 ADP 13C10 0 0 0 0 0 0 89503.53 105880.6 88019.55 108270.2 60127.78 88765.57 62405.63 50136.34 61568.93 58023.58 76079.82 78781.52 1739.437 0 0 0 0 1627.749 67450.76 90938.76 99881.07 130090.8 91811.16 61520.18 38566.94 49150.12 44360.28 34163.69 60350.51 25527.05 amp 13c10 0 0 0 0 0 0 1888885 2201572 2282683 2116826 1830442 1794690 692522.9 616775.9 655024.8 302108.6 504827.7 544256.3 0 0 0 0 0 0 2217528 2998453 2832756 1824750 2027937 1619590 585072.9 530123.8 703088.3 935181.8 662719.2 695228 Adenosine 13C10 0 0 0 0 0 0 16435.84 10685.02 18291.67 15543.81 14480.67 16859.01 2178.414 5960.054 9224.819 3143.047 7306.092 2178.322 0 0 0 0 0 0 13917.89 13519.94 17746.11 10436.69 17888.65 18622.29 9767.034 15482.25 14413.91 33063.91 9107.074 18606.04 Adenine 13C5 0 1435.177 0 0 0 0 69160.04 57633.03 66829.44 92476.65 62751.26 74326.31 18601.86 43116.86 57776.64 25556.23 53687.84 24555.97 0 0 0 942.0662 0 0 71934.37 76816.26 91584.55 64497.39 64525.07 81012.91 59686.73 81663.88 97526.91 207959.8 56023.56 100820.2 Hexose phosphate 13C6 4148.086 6315.68 3240.134 1454.721 4278.268 3758.577 1222.974 1938.715 1254.742 2098.594 2511.071 6283.398 0 0 0 0 0 0 6303.389 0 8775.343 7365.621 2678.689 19244.27 6685.474 6405.121 6068.103 6170.764 2908.477 2479.645 3644.339 5488.421 5806.456 0 1938.006 6762.805 Fructose bisphosphate 13C6 465691.2 632851.6 490090.3 594576.2 332497.4 588215.5 443029 583116.7 542816.8 712272.3 603926.4 531092.3 700400.4 1084192 547854.2 487515.9 525195.1 346611.7 336506.3 859757.3 613544.6 591508.7 946513.5 647948.6 392853.9 311700.8 613139.2 875603.8 973166.6 636241.6 649027.9 672939.1 648390.4 341187.5 300990.4 384883.2 Glyceraldehyde 3-phosphate 13C3 56646.31 24979.94 68985.69 73723.12 112113.2 33423 95102.46 96966.81 54203.18 33695.09 24173.94 35534.17 23967.41 28118.22 37928.96 105644.1 68976.7 125700.4 85731.84 59200.82 30337.22 51668.57 48625.46 31589.2 88938.94 109908.7 50453.89 35363.95 107019 45203.88 49761.3 19843.53 28035.47 92313.51 108219.7 81513.68 Phosphoenolpyruvate 13C3 2276.706 0 0 0 0 2586.564 706.8394 0 0 0 2531.62 5356.614 0 0 0 3626.183 0 0 0 0 0 0 0 0 2598.869 3370.93 0 0 1271.17 5427.357 0 0 0 673.1962 0 0 Sedoheptulose 1-phosphate 13C7 21239.14 20372.22 16602.86 19734.83 20985.13 13463.83 24456.69 37446.5 25622.95 30872.38 14818.1 19544.12 18118.52 18881.13 12635.75 20218.05 19432.53 16648.26 18706.58 14417.19 23004.65 13825.84 16402.22 14537.03 14505.72 19448.51 12768.93 19213.63 25210.94 28628.62 17287.84 15462.86 20467.99 19655.95 19503.49 22614.11 alpha-D-Ribose 1-phosphate 13C5 14343.86 14085.15 8443.59 10538.98 7263.777 7218.012 277669 301662.7 368286.2 362158 528916.9 477968.5 140201.1 119121.6 151475.3 142085.5 100560.4 116807.9 3680.343 5714.249 7474.382 13327.2 12744.42 7941.458 341751.2 287914.4 243231.7 210732.1 191306.2 293026.5 114572.7 139657.3 93894.52 98134.74 84686.22 136607.2 MS_METABOLITE_DATA_END #METABOLITES METABOLITES_START metabolite_name KEGG ID m/z r.t. L-asparagine C00152 131.0447 0.6347307 ADP C00008 426.0214 0.5565055 AMP C00020 346.0549 0.6203812 Adenosine C00212 266.0884 0.6793672 Adenine C00147 134.0458 0.684282 GDP C00035 442.0158 0.5343559 GMP C00144 362.0502 0.5732692 Cytidine C00475 242.079 0.6054067 dTMP C00364 321.0443 0.6345292 UMP C00105 323.0277 0.576729 IDP C00104 427.0062 0.5391139 IMP C00130 347.0392 0.5841831 Inosine C00294 267.0731 0.6761956 Hypoxanthine C00262 135.0297 0.6737581 Xanthine C00385 151.0246 0.676612 Urate C00366 167.0199 0.6102934 UDP-glucose C00029 565.0465 0.5236291 ADP-D-ribose C01882 558.0627 0.5512616 Phosphate C00009 96.96783 0.5737666 Diphosphate C00013 176.9344 0.5713288 D-Glucose C00031 179.055 0.64906 D-Glucose 6-phosphate C00092 259.0217 0.5521499 D-Fructose 1-6-bisphosphate C00354 338.9879 0.520139 D-Glyceraldehyde 3-phosphate/Glycerone phosphate C00118 168.9881 1.723363 2/3-Phospho-D-glycerate C00631 184.9843 0.535852 Pyruvate C00022 87.00703 0.6272945 Lactate C01432 89.02266 0.5969104 Maltose C00208 341.1082 0.663746 Mannitol C00392 181.0697 0.6648573 Citrate C00158 191.0184 0.5600852 2-Oxoglutarate C00026 145.0137 0.5532773 Succinate C00042 117.0176 0.5513467 Fumarate C00122 115.0021 0.5518985 Malate C00149 133.0126 0.5478894 Oxaloacetate C00036 131.0001 0.5800335 Itaconate C00490 129.0176 0.5605657 2-Hydroxyglutarate/Citramalate C02630 147.0285 0.5531359 Sedoheptulose 1-phosphate C06222 289.0324 0.5538169 alpha-D-Ribose 1-phosphate C00620 229.0108 0.5578731 Glutathione C00051 306.0761 0.5944909 Ascorbate C00072 175.0239 0.5509972 Dehydroascorbate C05422 173.0073 0.6784714 gamma-Glutamyl-gamma-aminobutyrate C15767 231.0978 0.5773529 N-Acetylneuraminate C00270 308.0979 0.5835356 N-Glycoloyl-neuraminate C03410 324.0927 0.5716186 UDP-N-acetyl-D-glucosamine C00043 606.0731 0.5258907 CMP-N-acetylneuraminate C00128 613.1385 0.5247538 Carnosine C00386 225.0982 0.6743999 Phosphocreatine C02305 210.0274 0.5280861 Taurine C00245 124.0058 0.6424347 Hypotaurine C00519 108.0107 0.6484862 N-formyl kynurenine C02700 235.074 0.6501437 Serotonin C00780 175.0904 0.6472222 Glycerol 3-phosphate C00093 171.005 0.5605046 sn-glycero-3-Phosphoethanolamine C01233 214.0475 0.632448 Hexanoic acid (caproate) C01585 115.0748 1.747154 Heptanoic acid C17714 129.0905 1.817635 Nonanoic acid (pelargonate) C01601 157.122 2.10041 Decanoic acid (caprate) C01571 171.1376 2.175749 Dodecanoic acid C02679 199.1691 2.341185 Tetradecanoic acid C06424 227.2008 2.58191 Hexadecanoic acid C00249 255.2323 2.951555 Octadecanoic acid C01530 283.2636 3.490514 Tetradecenoic acid C08322 225.1851 2.384604 Hexadecenoic acid C08362 253.2167 2.629765 Octadecenoic acid C00712 281.248 2.987842 Linoleate C01595 279.2323 2.666849 Eicosatetraenoic acid C00219 303.2323 2.56829 Docosahexaenoic acid C06429 327.2323 2.476799 Dodecanedioic acid C02678 229.1437 1.7356 (8Z-11Z-14Z)-Icosatrienoic acid C03242 305.248 2.738789 (5Z-8Z-11Z-14Z-17Z)-Icosapentaenoic acid C06428 301.2167 2.488116 (7Z-10Z-13Z-16Z-19Z)-Docosa-7-10-13-16-19-pentaenoic acid C16513 329.248 2.590683 6-Aminohexanoate C02378 130.0858 0.6855373 L-4-Hydroxyglutamate semialdehyde C05938 146.0443 0.5729986 N-Acetylmethionine C02712 190.0531 0.6744297 3-Methyl-2-oxobutanoic acid C00141 115.0385 0.6319067 2-Oxoglutarate 13C54 C00026 150.0293 0.5745239 Malate 13C4 C00149 137.0259 0.558234 ADP 13C10 C00020 436.0544 0.5499731 amp 13c10 C00008 356.0887 0.6161906 Adenosine 13C10 C00212 276.1224 0.6794081 Adenine 13C5 C00047 139.0626 0.679635 Hexose phosphate 13C6 C02965 265.045 0.6280133 Fructose bisphosphate 13C6 C00354 345.0139 0.7866501 Glyceraldehyde 3-phosphate 13C3 C00118 172.0005 0.5416526 Phosphoenolpyruvate 13C3 C00074 169.9843 0.5693247 Sedoheptulose 1-phosphate 13C7 C06222 296.0524 0.6340825 alpha-D-Ribose 1-phosphate 13C5 C00620 234.0278 0.5663581 METABOLITES_END #END