#METABOLOMICS WORKBENCH juliehaines_20241125_183122 DATATRACK_ID:5399 STUDY_ID:ST003606 ANALYSIS_ID:AN005925 PROJECT_ID:PR002231 VERSION 1 CREATED_ON December 5, 2024, 7:44 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 live or heat-killed bacteria by bone marrow derived macrophages ST:STUDY_TITLE expressing constitutively active mutants of Kras or Hras ST:STUDY_SUMMARY We sought to identify possible mechanisms governing the recycling of microbially ST:STUDY_SUMMARY derived nutrients produced by the degradation of killed E coli in macrophages. ST:STUDY_SUMMARY Recent studies have demonstrated that extracellular protein utilization supports ST:STUDY_SUMMARY the cellular metabolism of cancer cells expressing activated Ras pathways. Here ST:STUDY_SUMMARY we tested the involvement of Kras and Hras pathway in metabolic recycling of ST:STUDY_SUMMARY microbial nutrients upon phagocytosis by macrophages using global and ST:STUDY_SUMMARY 13C-tracing metabolomics in bone marrow derived macrophages exposed to ST:STUDY_SUMMARY 13C-labeled E coli. 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 - 1-89-5- time (h):6 | E coli treatment:live | genotype:WT | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=1-89-5- SUBJECT_SAMPLE_FACTORS - 1-89-6- time (h):6 | E coli treatment:live | genotype:WT | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=1-89-6- SUBJECT_SAMPLE_FACTORS - 1-89-7- time (h):6 | E coli treatment:live | genotype:WT | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=1-89-7- SUBJECT_SAMPLE_FACTORS - 1-89-8- time (h):6 | E coli treatment:live | genotype:WT | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=1-89-8- SUBJECT_SAMPLE_FACTORS - 1-89-9- time (h):6 | E coli treatment:dead | genotype:WT | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=1-89-9- SUBJECT_SAMPLE_FACTORS - 1-89-10- time (h):6 | E coli treatment:dead | genotype:WT | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=1-89-10- SUBJECT_SAMPLE_FACTORS - 1-89-11- time (h):6 | E coli treatment:dead | genotype:WT | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=1-89-11- SUBJECT_SAMPLE_FACTORS - 1-89-12- time (h):6 | E coli treatment:dead | genotype:WT | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=1-89-12- SUBJECT_SAMPLE_FACTORS - 1-89-13- time (h):18 | E coli treatment:live | genotype:WT | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=1-89-13- SUBJECT_SAMPLE_FACTORS - 1-89-14- time (h):18 | E coli treatment:live | genotype:WT | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=1-89-14- SUBJECT_SAMPLE_FACTORS - 1-89-15- time (h):18 | E coli treatment:live | genotype:WT | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=1-89-15- SUBJECT_SAMPLE_FACTORS - 1-89-16- time (h):18 | E coli treatment:live | genotype:WT | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=1-89-16- SUBJECT_SAMPLE_FACTORS - 1-89-17- time (h):18 | E coli treatment:dead | genotype:WT | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=1-89-17- SUBJECT_SAMPLE_FACTORS - 1-89-18- time (h):18 | E coli treatment:dead | genotype:WT | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=1-89-18- SUBJECT_SAMPLE_FACTORS - 1-89-19- time (h):18 | E coli treatment:dead | genotype:WT | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=1-89-19- SUBJECT_SAMPLE_FACTORS - 1-89-20- time (h):18 | E coli treatment:dead | genotype:WT | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=1-89-20- SUBJECT_SAMPLE_FACTORS - 1-89-21- time (h):18 | E coli treatment:none | genotype:WT | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=1-89-21- SUBJECT_SAMPLE_FACTORS - 1-89-22- time (h):18 | E coli treatment:none | genotype:WT | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=1-89-22- SUBJECT_SAMPLE_FACTORS - 1-89-23- time (h):18 | E coli treatment:none | genotype:WT | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=1-89-23- SUBJECT_SAMPLE_FACTORS - 1-89-24- time (h):6 | E coli treatment:live | genotype:WT | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=1-89-24- SUBJECT_SAMPLE_FACTORS - 1-89-25- time (h):6 | E coli treatment:live | genotype:WT | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=1-89-25- SUBJECT_SAMPLE_FACTORS - 1-89-26- time (h):6 | E coli treatment:live | genotype:WT | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=1-89-26- SUBJECT_SAMPLE_FACTORS - 1-89-27- time (h):6 | E coli treatment:dead | genotype:WT | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=1-89-27- SUBJECT_SAMPLE_FACTORS - 1-89-28- time (h):6 | E coli treatment:dead | genotype:WT | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=1-89-28- SUBJECT_SAMPLE_FACTORS - 1-89-29- time (h):6 | E coli treatment:dead | genotype:WT | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=1-89-29- SUBJECT_SAMPLE_FACTORS - 1-89-30- time (h):18 | E coli treatment:live | genotype:WT | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=1-89-30- SUBJECT_SAMPLE_FACTORS - 1-89-31- time (h):18 | E coli treatment:live | genotype:WT | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=1-89-31- SUBJECT_SAMPLE_FACTORS - 1-89-32- time (h):18 | E coli treatment:live | genotype:WT | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=1-89-32- SUBJECT_SAMPLE_FACTORS - 1-89-33- time (h):18 | E coli treatment:dead | genotype:WT | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=1-89-33- SUBJECT_SAMPLE_FACTORS - 1-89-34- time (h):18 | E coli treatment:dead | genotype:WT | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=1-89-34- SUBJECT_SAMPLE_FACTORS - 1-89-35- time (h):18 | E coli treatment:dead | genotype:WT | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=1-89-35- SUBJECT_SAMPLE_FACTORS - 1-89-36- time (h):18 | E coli treatment:none | genotype:HRAS +/+ | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=1-89-36- SUBJECT_SAMPLE_FACTORS - 1-89-37- time (h):18 | E coli treatment:none | genotype:HRAS +/+ | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=1-89-37- SUBJECT_SAMPLE_FACTORS - 1-89-38- time (h):18 | E coli treatment:none | genotype:HRAS +/+ | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=1-89-38- SUBJECT_SAMPLE_FACTORS - 1-89-39- time (h):6 | E coli treatment:live | genotype:HRAS +/+ | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=1-89-39- SUBJECT_SAMPLE_FACTORS - 1-89-40- time (h):6 | E coli treatment:live | genotype:HRAS +/+ | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=1-89-40- SUBJECT_SAMPLE_FACTORS - 1-89-41- time (h):6 | E coli treatment:live | genotype:HRAS +/+ | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=1-89-41- SUBJECT_SAMPLE_FACTORS - 1-89-42- time (h):6 | E coli treatment:dead | genotype:HRAS +/+ | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=1-89-42- SUBJECT_SAMPLE_FACTORS - 1-89-43- time (h):6 | E coli treatment:dead | genotype:HRAS +/+ | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=1-89-43- SUBJECT_SAMPLE_FACTORS - 1-89-44- time (h):6 | E coli treatment:dead | genotype:HRAS +/+ | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=1-89-44- SUBJECT_SAMPLE_FACTORS - 1-89-45- time (h):18 | E coli treatment:live | genotype:HRAS +/+ | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=1-89-45- SUBJECT_SAMPLE_FACTORS - 1-89-46- time (h):18 | E coli treatment:live | genotype:HRAS +/+ | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=1-89-46- SUBJECT_SAMPLE_FACTORS - 1-89-47- time (h):18 | E coli treatment:live | genotype:HRAS +/+ | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=1-89-47- SUBJECT_SAMPLE_FACTORS - 1-89-48- time (h):18 | E coli treatment:dead | genotype:HRAS +/+ | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=1-89-48- SUBJECT_SAMPLE_FACTORS - 1-89-49- time (h):18 | E coli treatment:dead | genotype:HRAS +/+ | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=1-89-49- SUBJECT_SAMPLE_FACTORS - 1-89-50- time (h):18 | E coli treatment:dead | genotype:HRAS +/+ | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=1-89-50- SUBJECT_SAMPLE_FACTORS - 1-89-51- time (h):18 | E coli treatment:none | genotype:Cre KRAS +/+ | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=1-89-51- SUBJECT_SAMPLE_FACTORS - 1-89-52- time (h):18 | E coli treatment:none | genotype:Cre KRAS +/+ | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=1-89-52- SUBJECT_SAMPLE_FACTORS - 1-89-53- time (h):18 | E coli treatment:none | genotype:Cre KRAS +/+ | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=1-89-53- SUBJECT_SAMPLE_FACTORS - 1-89-54- time (h):6 | E coli treatment:live | genotype:Cre KRAS +/+ | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=1-89-54- SUBJECT_SAMPLE_FACTORS - 1-89-55- time (h):6 | E coli treatment:live | genotype:Cre KRAS +/+ | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=1-89-55- SUBJECT_SAMPLE_FACTORS - 1-89-56- time (h):6 | E coli treatment:live | genotype:Cre KRAS +/+ | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=1-89-56- SUBJECT_SAMPLE_FACTORS - 1-89-57- time (h):6 | E coli treatment:dead | genotype:Cre KRAS +/+ | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=1-89-57- SUBJECT_SAMPLE_FACTORS - 1-89-58- time (h):6 | E coli treatment:dead | genotype:Cre KRAS +/+ | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=1-89-58- SUBJECT_SAMPLE_FACTORS - 1-89-59- time (h):6 | E coli treatment:dead | genotype:Cre KRAS +/+ | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=1-89-59- SUBJECT_SAMPLE_FACTORS - 1-89-60- time (h):18 | E coli treatment:live | genotype:Cre KRAS +/+ | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=1-89-60- SUBJECT_SAMPLE_FACTORS - 1-89-61- time (h):18 | E coli treatment:live | genotype:Cre KRAS +/+ | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=1-89-61- SUBJECT_SAMPLE_FACTORS - 1-89-62- time (h):18 | E coli treatment:live | genotype:Cre KRAS +/+ | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=1-89-62- SUBJECT_SAMPLE_FACTORS - 1-89-63- time (h):18 | E coli treatment:dead | genotype:Cre KRAS +/+ | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=1-89-63- SUBJECT_SAMPLE_FACTORS - 1-89-64- time (h):18 | E coli treatment:dead | genotype:Cre KRAS +/+ | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=1-89-64- SUBJECT_SAMPLE_FACTORS - 1-89-65- time (h):18 | E coli treatment:dead | genotype:Cre KRAS +/+ | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=1-89-65- SUBJECT_SAMPLE_FACTORS - 1-89-66- time (h):18 | E coli treatment:none | genotype:Cre | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=1-89-66- SUBJECT_SAMPLE_FACTORS - 1-89-67- time (h):18 | E coli treatment:none | genotype:Cre | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=1-89-67- SUBJECT_SAMPLE_FACTORS - 1-89-68- time (h):18 | E coli treatment:none | genotype:Cre | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=1-89-68- SUBJECT_SAMPLE_FACTORS - 1-89-69- time (h):6 | E coli treatment:live | genotype:Cre | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=1-89-69- SUBJECT_SAMPLE_FACTORS - 1-89-70- time (h):6 | E coli treatment:live | genotype:Cre | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=1-89-70- SUBJECT_SAMPLE_FACTORS - 1-89-71- time (h):6 | E coli treatment:live | genotype:Cre | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=1-89-71- SUBJECT_SAMPLE_FACTORS - 1-89-72- time (h):6 | E coli treatment:dead | genotype:Cre | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=1-89-72- SUBJECT_SAMPLE_FACTORS - 1-89-73- time (h):6 | E coli treatment:dead | genotype:Cre | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=1-89-73- SUBJECT_SAMPLE_FACTORS - 1-89-74- time (h):6 | E coli treatment:dead | genotype:Cre | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=1-89-74- SUBJECT_SAMPLE_FACTORS - 1-89-75- time (h):18 | E coli treatment:live | genotype:Cre | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=1-89-75- SUBJECT_SAMPLE_FACTORS - 1-89-76- time (h):18 | E coli treatment:live | genotype:Cre | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=1-89-76- SUBJECT_SAMPLE_FACTORS - 1-89-77- time (h):18 | E coli treatment:live | genotype:Cre | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=1-89-77- SUBJECT_SAMPLE_FACTORS - 1-89-78- time (h):18 | E coli treatment:dead | genotype:Cre | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=1-89-78- SUBJECT_SAMPLE_FACTORS - 1-89-79- time (h):18 | E coli treatment:dead | genotype:Cre | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=1-89-79- SUBJECT_SAMPLE_FACTORS - 1-89-80- time (h):18 | E coli treatment:dead | genotype:Cre | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=1-89-80- #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 Tg.hUbC-cre-8 ERT2+/T::Kras+/G12V mice were originally generated in the TR:TREATMENT_SUMMARY laboratory of M. Barbacid and provided by D. Santamaria. HrasG12S mice were TR:TREATMENT_SUMMARY originally generated at the Institut Clinique de la Souris (ICS) and provided by TR:TREATMENT_SUMMARY R. Rossignol. All transgenic mice were on a C57BL/6N background. We used 8- to TR:TREATMENT_SUMMARY 10-week-old male or female animals for all experiments and did not observe any TR:TREATMENT_SUMMARY gender bias. Preparation of macrophages: Murine bone marrow-derived macrophages TR:TREATMENT_SUMMARY (BMDMs) were generated as described previously, in RPMI 1640 supplemented with TR:TREATMENT_SUMMARY M-CSF (30% mycoplasma-free L929 cell supernatant, NCBI Biosample accession # TR:TREATMENT_SUMMARY SAMN00155972) and 10% FBS, plus 100 µg/ml penicillin, 100 µg/ml streptomycin, TR:TREATMENT_SUMMARY 10 mM HEPES, 1 nM sodium pyruvate and 50 µM 2-mercaptoethanol (all from Gibco). TR:TREATMENT_SUMMARY For Tg.hUbC-cre-ERT2+/T::Rragaf/f and Tg.hUbC-cre-ERT2+/T::Kras+/G12V mice, TR:TREATMENT_SUMMARY tamoxifen was added to the culture on day 2 or 3 to a final concentration of 1 TR:TREATMENT_SUMMARY µg/ml in order to induce CRE expression. BMDMs were used on day 5 to 7 after TR:TREATMENT_SUMMARY seeding. Period of differentiation of the cells, concentration of cells when TR:TREATMENT_SUMMARY replating and time-lapse between replating and stimulation with bacteria were TR:TREATMENT_SUMMARY important parameters to maintain metabolic backgrounds homogenous between TR:TREATMENT_SUMMARY experiments. Preparation of viable and killed U-[13C]Bacteria: ThyA- E. coli TR:TREATMENT_SUMMARY were grown overnight with shaking in LB supplemented with thymidine (500 µg/ml) TR:TREATMENT_SUMMARY and 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 1-89-5- 1-89-6- 1-89-7- 1-89-8- 1-89-9- 1-89-10- 1-89-11- 1-89-12- 1-89-13- 1-89-14- 1-89-15- 1-89-16- 1-89-17- 1-89-18- 1-89-19- 1-89-20- 1-89-21- 1-89-22- 1-89-23- 1-89-24- 1-89-25- 1-89-26- 1-89-27- 1-89-28- 1-89-29- 1-89-30- 1-89-31- 1-89-32- 1-89-33- 1-89-34- 1-89-35- 1-89-36- 1-89-37- 1-89-38- 1-89-39- 1-89-40- 1-89-41- 1-89-42- 1-89-43- 1-89-44- 1-89-45- 1-89-46- 1-89-47- 1-89-48- 1-89-49- 1-89-50- 1-89-51- 1-89-52- 1-89-53- 1-89-54- 1-89-55- 1-89-56- 1-89-57- 1-89-58- 1-89-59- 1-89-60- 1-89-61- 1-89-62- 1-89-63- 1-89-64- 1-89-65- 1-89-66- 1-89-67- 1-89-68- 1-89-69- 1-89-70- 1-89-71- 1-89-72- 1-89-73- 1-89-74- 1-89-75- 1-89-76- 1-89-77- 1-89-78- 1-89-79- 1-89-80- Factors time (h):6 | E coli treatment:live | genotype:WT | Sample source:murine bone marrow derived macrophages time (h):6 | E coli treatment:live | genotype:WT | Sample source:murine bone marrow derived macrophages time (h):6 | E coli treatment:live | genotype:WT | Sample source:murine bone marrow derived macrophages time (h):6 | E coli treatment:live | genotype:WT | Sample source:murine bone marrow derived macrophages time (h):6 | E coli treatment:dead | genotype:WT | Sample source:murine bone marrow derived macrophages time (h):6 | E coli treatment:dead | genotype:WT | Sample source:murine bone marrow derived macrophages time (h):6 | E coli treatment:dead | genotype:WT | Sample source:murine bone marrow derived macrophages time (h):6 | E coli treatment:dead | genotype:WT | Sample source:murine bone marrow derived macrophages time (h):18 | E coli treatment:live | genotype:WT | Sample source:murine bone marrow derived macrophages time (h):18 | E coli treatment:live | genotype:WT | Sample source:murine bone marrow derived macrophages time (h):18 | E coli treatment:live | genotype:WT | Sample source:murine bone marrow derived macrophages time (h):18 | E coli treatment:live | genotype:WT | Sample source:murine bone marrow derived macrophages time (h):18 | E coli treatment:dead | genotype:WT | Sample source:murine bone marrow derived macrophages time (h):18 | E coli treatment:dead | genotype:WT | Sample source:murine bone marrow derived macrophages time (h):18 | E coli treatment:dead | genotype:WT | Sample source:murine bone marrow derived macrophages time (h):18 | E coli treatment:dead | genotype:WT | Sample source:murine bone marrow derived macrophages time (h):18 | E coli treatment:none | genotype:WT | Sample source:murine bone marrow derived macrophages time (h):18 | E coli treatment:none | genotype:WT | Sample source:murine bone marrow derived macrophages time (h):18 | E coli treatment:none | genotype:WT | Sample source:murine bone marrow derived macrophages time (h):6 | E coli treatment:live | genotype:WT | Sample source:murine bone marrow derived macrophages time (h):6 | E coli treatment:live | genotype:WT | Sample source:murine bone marrow derived macrophages time (h):6 | E coli treatment:live | genotype:WT | Sample source:murine bone marrow derived macrophages time (h):6 | E coli treatment:dead | genotype:WT | Sample source:murine bone marrow derived macrophages time (h):6 | E coli treatment:dead | genotype:WT | Sample source:murine bone marrow derived macrophages time (h):6 | E coli treatment:dead | genotype:WT | Sample source:murine bone marrow derived macrophages time (h):18 | E coli treatment:live | genotype:WT | Sample source:murine bone marrow derived macrophages time (h):18 | E coli treatment:live | genotype:WT | Sample source:murine bone marrow derived macrophages time (h):18 | E coli treatment:live | genotype:WT | Sample source:murine bone marrow derived macrophages time (h):18 | E coli treatment:dead | genotype:WT | Sample source:murine bone marrow derived macrophages time (h):18 | E coli treatment:dead | genotype:WT | Sample source:murine bone marrow derived macrophages time (h):18 | E coli treatment:dead | genotype:WT | Sample source:murine bone marrow derived macrophages time (h):18 | E coli treatment:none | genotype:HRAS +/+ | Sample source:murine bone marrow derived macrophages time (h):18 | E coli treatment:none | genotype:HRAS +/+ | Sample source:murine bone marrow derived macrophages time (h):18 | E coli treatment:none | genotype:HRAS +/+ | Sample source:murine bone marrow derived macrophages time (h):6 | E coli treatment:live | genotype:HRAS +/+ | Sample source:murine bone marrow derived macrophages time (h):6 | E coli treatment:live | genotype:HRAS +/+ | Sample source:murine bone marrow derived macrophages time (h):6 | E coli treatment:live | genotype:HRAS +/+ | Sample source:murine bone marrow derived macrophages time (h):6 | E coli treatment:dead | genotype:HRAS +/+ | Sample source:murine bone marrow derived macrophages time (h):6 | E coli treatment:dead | genotype:HRAS +/+ | Sample source:murine bone marrow derived macrophages time (h):6 | E coli treatment:dead | genotype:HRAS +/+ | Sample source:murine bone marrow derived macrophages time (h):18 | E coli treatment:live | genotype:HRAS +/+ | Sample source:murine bone marrow derived macrophages time (h):18 | E coli treatment:live | genotype:HRAS +/+ | Sample source:murine bone marrow derived macrophages time (h):18 | E coli treatment:live | genotype:HRAS +/+ | Sample source:murine bone marrow derived macrophages time (h):18 | E coli treatment:dead | genotype:HRAS +/+ | Sample source:murine bone marrow derived macrophages time (h):18 | E coli treatment:dead | genotype:HRAS +/+ | Sample source:murine bone marrow derived macrophages time (h):18 | E coli treatment:dead | genotype:HRAS +/+ | Sample source:murine bone marrow derived macrophages time (h):18 | E coli treatment:none | genotype:Cre KRAS +/+ | Sample source:murine bone marrow derived macrophages time (h):18 | E coli treatment:none | genotype:Cre KRAS +/+ | Sample source:murine bone marrow derived macrophages time (h):18 | E coli treatment:none | genotype:Cre KRAS +/+ | Sample source:murine bone marrow derived macrophages time (h):6 | E coli treatment:live | genotype:Cre KRAS +/+ | Sample source:murine bone marrow derived macrophages time (h):6 | E coli treatment:live | genotype:Cre KRAS +/+ | Sample source:murine bone marrow derived macrophages time (h):6 | E coli treatment:live | genotype:Cre KRAS +/+ | Sample source:murine bone marrow derived macrophages time (h):6 | E coli treatment:dead | genotype:Cre KRAS +/+ | Sample source:murine bone marrow derived macrophages time (h):6 | E coli treatment:dead | genotype:Cre KRAS +/+ | Sample source:murine bone marrow derived macrophages time (h):6 | E coli treatment:dead | genotype:Cre KRAS +/+ | Sample source:murine bone marrow derived macrophages time (h):18 | E coli treatment:live | genotype:Cre KRAS +/+ | Sample source:murine bone marrow derived macrophages time (h):18 | E coli treatment:live | genotype:Cre KRAS +/+ | Sample source:murine bone marrow derived macrophages time (h):18 | E coli treatment:live | genotype:Cre KRAS +/+ | Sample source:murine bone marrow derived macrophages time (h):18 | E coli treatment:dead | genotype:Cre KRAS +/+ | Sample source:murine bone marrow derived macrophages time (h):18 | E coli treatment:dead | genotype:Cre KRAS +/+ | Sample source:murine bone marrow derived macrophages time (h):18 | E coli treatment:dead | genotype:Cre KRAS +/+ | Sample source:murine bone marrow derived macrophages time (h):18 | E coli treatment:none | genotype:Cre | Sample source:murine bone marrow derived macrophages time (h):18 | E coli treatment:none | genotype:Cre | Sample source:murine bone marrow derived macrophages time (h):18 | E coli treatment:none | genotype:Cre | Sample source:murine bone marrow derived macrophages time (h):6 | E coli treatment:live | genotype:Cre | Sample source:murine bone marrow derived macrophages time (h):6 | E coli treatment:live | genotype:Cre | Sample source:murine bone marrow derived macrophages time (h):6 | E coli treatment:live | genotype:Cre | Sample source:murine bone marrow derived macrophages time (h):6 | E coli treatment:dead | genotype:Cre | Sample source:murine bone marrow derived macrophages time (h):6 | E coli treatment:dead | genotype:Cre | Sample source:murine bone marrow derived macrophages time (h):6 | E coli treatment:dead | genotype:Cre | Sample source:murine bone marrow derived macrophages time (h):18 | E coli treatment:live | genotype:Cre | Sample source:murine bone marrow derived macrophages time (h):18 | E coli treatment:live | genotype:Cre | Sample source:murine bone marrow derived macrophages time (h):18 | E coli treatment:live | genotype:Cre | Sample source:murine bone marrow derived macrophages time (h):18 | E coli treatment:dead | genotype:Cre | Sample source:murine bone marrow derived macrophages time (h):18 | E coli treatment:dead | genotype:Cre | Sample source:murine bone marrow derived macrophages time (h):18 | E coli treatment:dead | genotype:Cre | Sample source:murine bone marrow derived macrophages itaconate 13C5 25876.9 26060.53 28019.62 28377.19 79169.77 54534.56 30903.44 89197.09 9666.121 11009.25 7732.033 14422.46 6500.754 10917.6 7468.118 6469.654 3609.223 9525.948 4574.466 29521 27053.08 40222.2 37837.41 43555.59 39567.29 8896 4080.652 11395.1 10190.71 11989.91 12451.45 2840.37 7241.227 5746.888 29301.48 23046.58 27242.69 33763.95 32892.36 36446.93 7762.809 10183.18 10160.76 9589.867 13972.6 7002.001 5827.664 7514.277 4539.969 50519.02 65184.36 34124.44 39303.07 35497.1 50740.3 16676.46 16529.9 27173.99 23793.82 18668.6 11205.4 8855.122 8273.511 5889.448 34297.8 34786.35 33138.57 30370.66 32868.33 36733.04 8530.173 13567.07 20120.83 13072.82 12128.88 14412.97 fumarate 13C4 5007.832 12038.4 9485.813 8207.895 16430.62 6929.975 3355.666 7767.461 11106.21 9840.882 7239.84 5942.253 2911.553 2722.392 5051.137 5201.92 0 0 0 1624.419 1759.121 532.5543 2043.836 5340.998 0 248.5757 0 2417.625 0 0 2793.026 0 0 0 2520.867 1839.844 0 2318.841 0 0 326.8771 0 0 0 0 0 0 0 0 4610.786 2299.512 2568.28 2503.76 3253.795 3460.172 0 2661.903 0 0 284.0047 0 0 0 0 2682.761 5009.999 1826.901 8604.167 5497.271 2699.451 0 1148.401 0 0 0 0 malate 13C4 154913.8 143934.8 224522.4 167908.8 143931.5 119730.1 106830.4 132328.9 152609.4 190544.8 153359.3 151508.6 69101.95 36670.67 53636.44 69408.49 0 0 0 38149.6 53359.64 33780.78 51364.33 50806.14 50866.91 25099.36 23464.97 16938.06 31516.53 26768.35 39078.12 941.7524 0 0 25054.26 30724.29 39790.87 66539.6 65880.45 42903.95 16182.5 10568.76 18478.15 16224.19 10858.68 12145.04 0 0 0 49713.82 59204.46 62840.89 64966.07 81198.55 59928.17 20959.33 21663.46 30684.66 19844.11 14903.36 29806.39 0 0 0 73652.74 77499.24 70357.89 117625.2 99510.32 76912.42 29208.09 26083.17 21436.38 21466.4 19890.95 22075.96 AMP 292169 157264 90230 107201 359097 193445 244883 335919 204425 74366 55796 112066 295662 386319 290883 356083 1294114 1107441 1118122 382710 151338 310974 275633 271527 529358 342570 129179 260851 356788 311317 313554 397302 614932 591450 220484 260641 226798 332116 191424 359258 219455 277694 155570 214875 304959 258546 2291407 1889918 1837695 513677 1031662 585171 543482 402673 910761 851910 1088223 844023 1225260 1302778 1093486 899507 1236331 1290224 880981 942164 848431 1066044 345756 930156 861286 1159641 1150544 1085158 1102847 799927 dAMP 5626 3226 15765 4221 8596 11692 10433 3180 4818 17728 10871 5277 0 3593 3988 9514 0 0 0 8477 24230 9793 11171 9660 8766 3681 3064 1133 2237 4650 0 0 0 0 8294 7058 9442 5368 7864 33773 0 1970 0 4807 0 1555 0 0 0 6929 10600 7927 11668 31399 10456 5779 5549 8414 12125 9471 4970 0 0 0 11161 8085 5793 15775 32613 16672 7175 4282 5219 5278 7188 8521 GMP 32373 25804 42225 30863 41749 29259 23582 39691 17690 29862 12637 18113 30979 37415 54899 55162 102801 69889 73090 76039 116645 125605 47351 111745 67095 42764 42597 39460 25162 40964 34066 69766 61307 72281 56265 69263 78639 47991 40781 25852 24828 22346 24381 25994 30518 26518 265915 208164 249926 67448 76146 61476 68181 91479 60688 84110 100911 137517 162743 164829 118802 175103 202110 207971 89071 115239 70732 73008 69095 65537 73778 92778 78265 72466 60996 90644 CMP 35426 31628 51519 49071 38426 37509 23681 33741 6353 23126 8045 7096 13723 19694 16288 14338 53882 48281 46984 53809 70485 67646 37758 48536 41639 24620 28763 28223 26456 28721 17555 32419 32099 42489 46614 57018 45385 57393 32721 27972 18104 25015 22792 21184 26156 25710 91663 98319 90843 54769 59969 41302 48239 53775 51465 50325 62599 65805 83976 79759 75597 81699 91669 67315 64669 64971 49337 65395 54088 54713 45287 61422 34842 62771 48208 65278 Cytidine 110091 92532 47376 77515 108547 123470 139509 108676 211255 113900 102621 164059 252187 269648 303629 314282 102802 64712 68272 87263 18306 60909 78559 100140 105736 142035 66987 136814 203856 199902 185432 47738 59606 59945 54528 40625 46714 100015 57267 228338 134683 151205 137836 167758 155911 180768 259695 193664 219210 182293 212724 150898 170844 101471 220837 450045 466285 426011 537293 532307 532397 164511 212395 143767 178792 188149 181093 212045 53703 190452 405866 369814 501438 416767 449827 379354 UMP 59338 32878 70578 56784 56117 85389 37715 84852 46086 63947 25804 20305 41493 57157 78455 81231 236007 164010 158677 107656 139676 142740 78369 163181 97078 51002 46378 37296 58834 81418 60666 152683 131681 172966 78845 59357 66933 104849 67491 61774 34052 41921 26120 45016 56344 47192 449514 386655 598589 124980 181066 123470 153356 218733 153799 142827 193612 241319 305216 261593 205360 365315 431184 317714 196255 228340 151820 219433 191320 185040 166778 174932 142943 213098 202089 239689 IMP 29422 31084 44203 40491 32239 35993 32681 46573 14855 21915 19005 15405 49302 46234 45152 43904 148912 82248 112994 42156 55184 68393 61139 71090 66702 22346 13495 11676 37508 41155 44331 37689 93110 116717 35575 29334 45289 98943 71449 61986 9748 14819 12345 28111 25036 21309 187390 172347 171171 39569 27308 49439 43994 41049 25543 49578 69507 74218 80498 116373 112299 177249 210818 210490 51078 48091 37234 42289 41004 47758 140410 126899 109179 76789 76695 81160 Inosine 10679 7277 9113 7819 9787 26065 12529 16520 5449 22517 10998 10446 8247 8892 19710 19382 48733 33974 37993 26309 36026 15399 19868 58903 20106 13194 9663 6633 11485 11618 10291 85227 41431 31322 11480 16862 14603 18362 12144 35990 6725 4854 4526 6981 8083 13909 184193 106301 137282 35863 22677 28897 29574 53852 24246 30894 33287 47951 71177 31044 27191 267919 174833 124794 19083 38118 24742 38104 17095 20233 26706 53291 38382 34695 22550 46051 Hypoxanthine 47812 31090 48485 39258 45450 66639 38864 62622 25506 56920 27083 32335 52860 54539 74263 81705 156874 99133 123501 104277 122816 69723 67442 137977 74538 61743 47375 36345 51263 56128 44282 180164 122068 97757 57331 80514 63569 59249 45110 1666953 41952 36245 26721 34568 29695 52977 414886 281934 329040 143868 87617 154110 116420 187863 85797 120826 122895 152908 211947 126126 147552 494225 381013 321912 85520 129699 103499 154262 100975 95183 124692 193204 157729 134204 110972 150597 5-6-Dihydrothymine 48108 26543 17034 21200 29002 26694 51815 34096 40589 22570 21622 32794 84744 79004 66732 67324 143174 113804 91849 36533 18963 26179 36785 49180 59013 66209 27610 54655 78684 74690 66614 82232 80131 84189 34536 50640 37148 57934 39076 90667 52191 51246 49662 70383 71395 74739 114868 76575 78704 42215 30064 44862 52541 36571 58648 88904 92829 83845 119416 116565 130336 78952 90729 89555 46739 45799 34301 77735 33435 67950 83507 102186 101727 127534 104922 97567 4-Pyridoxate 33831 36458 16734 44932 0 5411 4836 7567 3432 0 3715 0 6586 7274 8237 2146 4001 5185 2876 90792 112266 145476 6764 5833 5060 12670 4346 11163 9021 9922 3584 1932 2220 5626 99510 121297 49579 10915 0 223319 18781 11524 15425 8194 2944 7128 4507 5943 3760 13566 5612 21490 4593 3769 8226 7988 14457 8997 12461 10765 14982 13410 12735 8992 13836 7408 10774 6601 5464 2965 9310 15355 8602 13820 15619 13032 UDP-glucose 31599 19706 22091 25549 31084 21951 41972 19857 12915 12068 8350 10225 18059 21542 16698 22947 50112 38027 39058 46972 45283 43737 17456 28058 25244 22074 13108 19511 20143 25126 18026 18859 33129 30933 36308 49441 36974 25787 28093 31191 23591 22029 16962 20081 18247 16912 64859 39207 61480 46772 69041 41648 54219 76968 49543 36521 36039 33704 42443 49107 40617 45997 67551 58317 82315 103415 82858 85367 93062 91145 48282 53977 51464 50619 40993 43882 ADP-D-ribose 3431 4893 10554 3511 0 8353 8086 5579 2025 12245 6264 3035 2829 3168 13682 7604 56554 41576 35600 59994 52259 50092 24469 32947 32809 35878 36884 25346 7406 16327 6924 61241 38108 47890 46720 34594 35346 28259 17770 19628 29085 30231 24807 17609 19763 25015 73362 66858 63118 56913 45821 46110 33532 63078 40058 47449 67114 74909 93199 57568 62834 50923 71940 69303 45714 49020 33612 50141 37520 43949 55955 63999 52675 54272 35412 37025 Phosphate 48016930 38539330 59213530 51314870 54588520 41823070 58189300 39801300 45680340 63430000 52107360 55903040 50735100 44327400 53043580 54062090 35564500 26841380 42900800 45835970 63660430 46011950 51745790 46043960 51877880 43175200 58501390 35254170 36380040 30028380 34677630 25495730 29715720 37812320 44171680 47270330 56996960 44325100 56695820 37868640 40219660 39601620 40523410 34269790 36497630 37969260 47881330 40596010 50154410 43365680 50064280 49006740 50049040 62594110 38902920 38252720 43671900 40219690 49565130 45208480 38055780 40130160 39487440 52544580 47581060 51365840 48512390 53529430 73365000 54687090 46938880 40276260 54936680 37191800 39495960 44256410 Diphosphate 1490427 1006114 2705346 1578417 2043209 1245100 2837567 1009974 1501133 2850433 2109607 1901379 1798580 1383434 1947383 1967425 1008993 719188 1131548 1355993 3501695 1325858 1581366 1688734 1909358 1240578 2320083 951398 878203 573415 778653 476461 594316 956455 1216345 1608010 2319530 1207809 2092530 1535888 1016120 1046618 1073962 802173 906663 1062137 1914070 1351500 2045822 1387417 1772600 1872695 1741946 3211733 1004850 907300 1369108 1379060 1805311 1788803 1055351 1152535 1201202 1797538 1790073 2310591 1992435 2243097 3947775 1954208 1582508 1191557 2348030 1093862 1098938 1533156 D-Glucose 194406 172890 150471 126906 172691 102231 261409 177750 167512 111519 113434 152008 168823 143360 137078 130285 259939 169382 157570 163180 122551 118728 195669 145955 127299 239490 124052 109832 207025 132522 138665 116665 100658 103747 162504 162336 203320 171790 166500 166958 173952 120416 128399 136785 151017 151233 157789 127670 134636 233051 154980 271366 254573 166360 118550 178547 171110 171285 213387 193369 204791 139807 117751 105785 208673 177760 137840 321501 187659 169050 219733 187595 215683 174107 126106 123550 2/3-Phospho-D-glycerate 35689 20306 70810 37840 17880 19810 21013 6944 20535 27791 15184 13935 22516 27624 29560 31738 14201 7862 6310 96443 167693 106034 15158 24216 6981 35250 50972 26887 11145 11154 11158 1692 0 1292 84485 83727 102224 14788 20236 4430 18040 28498 17214 13162 5677 20117 14842 5624 16932 55029 42131 47182 47640 71220 21854 42362 43478 48978 60714 65662 43445 29251 14289 18072 58195 63502 39433 69622 99183 61948 58387 37982 61975 24897 34538 46543 Pyruvate 201581 125574 137046 137585 294338 314608 326228 234559 138203 145446 121794 115511 223435 222478 271449 389456 290665 294654 289412 140417 137493 140248 229102 315046 325012 196238 173755 160057 222703 228708 174937 195191 247594 206994 101476 115512 125225 273165 284394 1022881 166880 172012 150154 168616 135128 185595 346793 256186 280040 72712 98396 181958 160398 265874 139331 162475 182492 211805 271606 225570 223542 103921 157291 117668 93897 115753 81203 220402 202803 211567 140254 158584 191190 178813 181389 163161 Lactate 1965214 1057595 1604622 1178798 1286823 1879413 1598000 1759028 1341610 1767882 1018195 1554531 1691682 1601710 1879444 2007116 1379932 840304 1474586 832885 719289 788975 740611 762689 660810 1076876 1191032 1078348 1214506 1853669 1420028 465842 532573 478099 554760 1084153 559591 1562833 864671 21278610 1181005 856575 923531 1254146 921945 1091054 889885 690680 1102044 701623 1712612 2224031 910316 935259 1296225 1956521 2200492 2315085 2525648 2555314 3728993 1094839 1602083 1178946 1261985 1718534 1013938 1608354 2352783 1193185 2650319 2291799 2805452 2323007 2448756 2317760 Maltose 21270 7543 6517 7495 3106 15199 3201 7294 8052 3324 0 2581 3334 3044 0 10602 12855 3699 22136 50793 20065 25687 4883 4249 3821 11858 5413 24359 4549 14302 18606 5115 10077 17574 64309 52425 26307 3811 8781 23714 61199 8624 10979 10055 12348 9943 0 1629 6384 6164 13810 126023 1897 2201 17143 8558 17047 10452 3817 5857 26424 2083 13188 7580 8810 12130 5779 2100 2955 1619 5687 8788 10812 3956 1225 10637 Mannitol 9248 4917 20308 11933 21908 19310 25484 79375 23399 34840 38216 48593 19745 19079 15851 46758 13197 3294 4108 6150 6293 4311 18328 12686 11019 6900 8232 6596 13805 22498 26805 3081 3795 3262 4483 4957 7234 9900 17089 376453 12593 13228 11692 17644 20060 17872 10932 14411 15978 7293 22148 10664 15255 14412 9627 24629 23308 28164 27570 34351 26839 6946 3233 8670 11063 16629 6456 16357 16953 13713 31784 13469 70479 21525 25982 35964 D-Arabitol 98668 89019 108586 107710 127320 96999 73953 159807 35943 41703 38512 34003 47103 61415 71268 82171 5299 7417 9796 74976 52937 81255 99421 110652 111859 12329 24268 21301 46135 55250 48859 3697 3369 2764 66261 60704 60283 102685 78725 77506 17731 21159 12235 28898 35428 40622 7469 5185 5164 115686 127475 123797 84359 85024 109189 33047 41616 54846 55182 60540 45106 3050 4123 8093 121165 107404 93893 114143 70038 114204 58361 55980 60370 49287 50402 45086 Citrate 34737 29969 153837 78900 39268 33739 56892 12609 13918 51103 41900 42698 30782 28021 40096 63231 86729 45306 72156 185402 356780 177925 51173 42645 29056 25327 86439 28753 35141 33333 15393 20174 27449 30106 199122 108652 225290 49306 66569 52082 13672 52703 33830 25324 12780 45429 103821 67131 137900 34824 62557 45320 58909 127936 11829 43674 24630 61276 51975 55649 32595 69067 27507 75158 102156 91644 54410 126726 200027 112104 97280 37368 115427 45503 93873 112081 2-Oxoglutarate 60862 40910 79894 46019 119993 136001 187157 119732 110873 167655 132825 162312 154534 192679 221324 284132 492950 456743 408520 123485 186739 136278 249036 327375 406746 133994 117236 130895 256176 269303 139620 385490 514050 481128 82344 95240 81349 222168 221518 257077 124503 219262 119092 231987 223019 277002 22189 15979 30625 22558 41999 56748 56656 115253 87114 131988 212631 225730 254472 220727 187534 12721 13879 17992 56070 53371 47727 143080 148472 156481 140067 137055 184942 181609 200775 170028 2-Oxoglutaramate 18261 9508 379 430 3463 422 14921 22932 10783 380 1472 389 28092 13775 20268 5961 392 328 1304 599 409 0 2334 408 7616 17788 450 14825 6172 309 9818 6110 10740 11282 1745 12634 8273 0 354 70786 24301 382 4532 2868 19235 342 5645 7632 2509 3868 8813 12846 779 335 12633 1833 8281 352 13277 9150 7044 430 10648 6891 1359 6563 12719 363 0 3108 1984 8769 11300 7896 439 771 Succinate 154473 96982 102920 85453 65253 41317 89930 121226 64436 52807 40175 57411 63230 68558 72273 54752 133587 136900 121316 409980 416647 430769 87606 126048 163311 257739 166320 211840 114100 111609 95138 126583 216395 167167 392008 515956 361323 105633 95566 387749 266580 215840 219987 95177 177796 103922 591361 451666 543388 188501 352871 444232 161482 211286 221905 159111 229348 177987 310669 304414 182480 221166 277552 257290 213127 197756 188728 225251 235866 212016 136730 226088 182855 246059 214582 176144 Fumarate 101198 87998 128922 98420 102526 90889 114339 81634 174021 255358 169650 179809 161230 124886 153651 174955 89115 67352 63477 85816 122408 93997 57923 64758 55288 156304 130228 91558 78217 77024 111046 30965 36212 34100 80057 73352 82722 76909 68218 282287 100576 119040 113630 50215 42386 63466 123667 117370 151110 66522 89312 58482 99345 126744 77820 106016 105745 101177 150095 143774 141357 107077 107684 111236 89263 99627 82514 155568 145367 115839 88940 113799 115058 132105 126226 110627 Malate 1606899 1506188 2260851 1447723 1517140 1522153 1785385 1250443 2852777 4244918 2843028 2509371 2598216 2044294 2200262 2891430 1108851 904111 1047968 1348020 1947255 1228231 751420 937932 853493 2134016 1890908 1334186 1266466 1224562 1858656 403930 393659 466484 1082674 950069 1083432 1120018 1030732 937827 1546572 1911093 1710221 727906 714740 819065 1711221 1292423 1982685 935382 1299430 1062721 1445485 2041787 1197717 1618615 1460966 1726959 2065209 2274082 2084031 1587529 1405514 1438545 1335928 1437773 1225064 2518872 2143586 2078624 1688190 1809678 2002844 1948783 1971482 1879515 2-Hydroxyglutarate/Citramalate 70818 52061 48447 39957 108672 73065 151155 190099 79594 83655 46813 55635 201596 218254 246493 224616 417317 378122 346238 87549 117017 86786 97884 174612 209385 123505 80499 138547 222741 185905 164680 257988 396117 351973 55533 78015 57899 97140 82084 216798 96472 105980 66912 147765 222692 154102 189634 142237 189142 74090 149933 140301 95012 142604 181822 240865 367013 297164 439998 407345 347063 97843 102013 103513 99240 109973 93554 154850 138709 155848 186534 287173 256021 273590 207876 224570 Itaconate 522284 354858 544246 374144 1321867 1255733 1377887 1109788 1126406 2194496 1158666 1165988 2121558 2232244 2408271 3056898 2672459 2006701 2447913 889787 1560547 954131 1472980 1736023 1792699 2021193 1961904 1665733 2708994 2775860 2449752 1444781 1734500 1733066 531350 618116 706332 1345783 1667859 1350913 1677388 1727478 1381510 2105125 2677596 2983467 5388043 4245190 6303020 1645010 2217333 1626958 2101908 2835634 2085180 3525997 4730605 4308574 6940813 6752398 5131736 2707452 2916385 3066907 2190959 2911664 2332401 3002308 3583940 2984154 3610627 4201232 4612258 4466340 4510715 5015714 D-Glucono-1-5-lactone 6-phosphate 4952 9525 19638 16072 15557 15643 9597 5540 10934 21158 23324 18905 11231 7073 8485 11141 18093 9358 15438 18201 28297 20126 15419 19482 13439 6079 25655 8193 7890 14772 6640 10903 6927 7647 20624 5489 17505 16978 24551 9571 4626 17225 14309 10606 6126 16669 11792 9505 15544 7043 15182 9506 18104 26444 4978 14317 9110 19354 12101 12112 10437 11470 8171 13862 19971 14643 13228 21071 30890 19298 16791 12296 7983 12873 12135 18021 Sedoheptulose 1-phosphate 15519 12667 18756 22621 3888 11466 8542 12442 30460 54949 34960 29662 28935 45180 39510 55138 20908 8082 11110 28672 30231 31452 9600 6758 6643 13368 26362 12567 26200 38081 30308 8979 11903 7421 26133 28255 17625 9515 4108 4166 18123 21523 14231 19275 27028 30379 16250 13342 20815 13208 6681 11778 11828 14254 13564 51891 67029 66175 93651 88962 89715 22844 32746 22411 17893 12030 5842 17714 11509 13257 58735 72182 75484 74877 72002 72736 alpha-D-Ribose 1-phosphate 109319 64687 123671 109467 57438 115456 62490 77088 67760 132027 69659 78411 101603 99533 129285 136549 176609 135384 134528 146097 208299 186751 96614 190733 96514 108972 117377 84829 119635 137687 89006 187445 115016 142302 127236 123209 100113 112516 74210 68212 78656 65821 61174 76191 72441 115756 388673 324534 437772 232509 158082 167459 215647 291203 156020 236412 216273 269121 322838 283158 216786 477216 403549 334033 226189 239599 180160 257252 178943 195878 261236 294741 257018 274573 211012 316304 Glutathione 835637 863340 1912504 1557700 2367432 3052218 1734670 1402585 1316969 2410248 1807766 1453162 1716247 1990947 2018456 3749744 4415594 2832643 3427771 3165239 4338326 4026957 2191276 2223368 1697363 1078373 2156904 1252305 1775048 2494024 1387893 1706860 1237265 1705614 2773795 1949983 2865847 1662968 1649073 976067 1000903 1824792 1418880 1582573 1288202 2156764 6865438 5614632 8511487 1866829 2662006 1764446 2730965 3945591 1938151 3089621 3143599 4805984 5446520 6161204 4450692 4912426 3873718 4532210 3098682 3178939 2277379 3948333 3908830 3901357 3859712 2751560 3716173 3196124 5027566 5401530 Glutathione disulfide 2222 2491 3080 0 2835 0 4885 12233 3058 3672 0 2311 6033 9761 4590 3462 2953 9843 2787 2246 8278 5517 2065 0 0 3237 5248 3577 8584 3061 9360 4984 17124 9957 3199 4958 0 0 1647 0 3324 2166 6236 4154 5893 0 21360 22899 7912 1380 4997 0 0 0 10328 3648 9988 5909 15245 15228 19434 3909 33124 14583 0 0 6201 1996 0 1899 7834 19896 13677 26536 6183 7800 S-Glutathionyl-L-cysteine 18390 26624 15752 12399 25817 13160 26543 30023 12256 13481 8810 9941 23879 40801 38130 37418 22433 50976 29204 29450 17448 16095 8830 18590 22979 34150 23117 22452 41762 27484 38925 18351 29412 26602 20144 26844 25913 7285 4408 22890 23317 13074 18527 26648 29083 26772 78285 66110 26619 27215 33564 26169 7015 11469 31326 30825 56571 19967 101132 89623 85517 13562 58785 45275 28340 37166 35559 11044 17124 23746 46455 67375 47946 76758 37363 24932 Ascorbate 100102 89052 195128 114062 497007 540706 633030 321270 145896 254319 210140 216772 351216 385933 476288 661419 553052 419795 420122 165395 224499 179012 442094 519177 592333 146590 172608 118071 353759 408953 199886 318079 451941 346511 100637 79119 129905 469609 550289 425020 95888 200158 110044 309932 206686 357024 12507 14900 22275 88609 112345 114162 279936 443406 219574 205256 249592 320174 353177 308094 264043 26422 18416 17250 163973 130872 98808 420128 350615 334820 191304 224366 259355 240188 332068 309762 Dehydroascorbate 4998 1927 329 2785 1513 2014 1545 2865 1993 0 0 3485 1069 2496 1794 432 2181 2896 2976 5883 30200 15127 1637 3269 1888 1576 0 2624 1490 3874 706 1680 1669 2007 6520 5138 1522 1902 644 166238 3741 1265 815 1146 787 331 6032 4193 4062 1477 5465 3074 0 0 2635 2285 3458 0 3823 2499 3996 5436 5441 5167 1048 1045 4815 3683 3384 2745 2881 4106 3416 2784 4037 6746 Dimethylglycine 238257 200492 81940 97902 379633 173914 287283 428083 219040 88887 129600 207722 207587 249911 257492 237229 155691 168479 150271 209146 83968 170761 193476 334610 314415 110423 49518 131459 252861 198428 194109 114515 126019 146515 178888 152187 150049 252301 158464 171187 133022 106836 93831 138740 158637 158144 154201 169249 222672 324431 368209 263485 163789 115751 350899 183243 223829 184733 238423 243071 212433 158161 173909 124085 295219 321635 341428 239585 98631 231580 258005 409054 309508 227069 205158 146407 3-Phosphonooxypyruvate 7978 12828 1683 5881 10299 4619 13686 10597 9853 3262 7385 8547 12135 11354 7807 10622 9674 11109 9292 10309 1197 6724 8300 8893 10445 9009 5667 10048 5428 8595 14382 11819 11656 8074 10143 8923 9248 7788 5063 11739 12785 6072 8060 9982 13332 10335 14584 10863 9549 11216 11360 9895 13036 7511 10795 13482 13282 9881 17533 18821 16621 4449 13636 10942 10735 12701 9887 10179 4339 9626 12537 15850 11268 14506 13466 9396 Argininosuccinate 8494 9911 14800 4842 4467 13597 9487 7145 34000 39659 32130 29504 24490 20721 22651 26946 3082 6763 2355 8934 15208 16401 3588 7372 5364 11573 18699 15279 15495 9657 19953 0 2340 2112 11208 17937 14391 10642 8858 11096 11896 14077 17274 6783 4127 8421 2614 5664 3728 2677 7101 2627 5284 7769 3716 19712 15942 23617 37361 37107 33336 2397 6701 5856 9847 9525 6986 19995 4362 19227 31599 33050 38947 46946 37817 34487 N-Acetylneuraminate 239026 225837 272586 240263 604116 651532 453690 635395 166657 168263 125936 165069 143086 199490 195706 221399 839273 740183 639838 694566 615004 616747 921536 1256219 1019641 291301 211441 267107 531178 470156 470244 565337 646916 749363 568598 577735 521299 1450036 1208585 661238 300823 301200 215219 552915 615297 633987 1148420 1304704 1232545 697837 1130392 766664 1104345 1279318 1373206 471791 730309 680659 1160772 1339217 1186443 1100729 1257708 1030384 788600 927815 819568 1363546 1111784 1239298 566653 629443 464831 966261 964937 691200 N-Glycoloyl-neuraminate 32896 25296 26617 27354 64052 54856 58766 65393 23441 26182 10024 20621 22878 25160 30224 28688 72947 80698 52284 55971 30995 48846 76400 101112 93843 27645 24421 27726 57549 44430 39612 54449 81006 76735 45554 41517 50642 115392 104335 64439 22045 26057 24399 55469 75318 67038 87620 99193 98157 50880 72431 54111 73139 92433 85029 44510 58065 51012 92114 92393 78818 91028 123427 106119 87570 78015 74142 129918 81444 112116 49323 72787 55422 86109 91868 61891 alpha-D-Glucosamine 1-phosphate 5392 7061 5762 8230 4144 4939 3914 6014 8096 15446 8212 8418 13993 16239 13870 20534 13080 12283 10066 18450 26153 16059 6526 8551 7363 11635 15256 7247 16964 13971 13849 4552 8184 10264 27807 22796 27933 15438 16148 14024 14737 11024 9968 16136 18860 17639 24034 24606 23529 14702 12543 11529 8550 6101 12588 35338 29211 29318 45924 47066 48300 26503 17782 19796 16453 11044 13361 12069 12482 13833 29474 35532 24701 25367 29536 22556 1-4-beta-D-Xylan 14145 12087 16581 12391 32453 44777 38602 36374 19569 33917 23628 26694 46917 58249 62368 76660 219184 132259 180821 30821 62616 31096 56751 66796 67056 38136 40644 35775 76750 64372 49879 89401 111622 130827 22713 29170 23554 46087 66332 43473 32272 35924 24190 58944 58910 60352 226705 180700 269945 23700 39485 34790 44126 54372 33637 57318 83857 67146 120651 130312 85725 83344 86403 74733 27938 38411 39529 45792 53482 61518 52473 60752 70266 84084 73892 84232 UDP-N-acetyl-D-glucosamine 26229 20081 30839 20617 21287 9728 15268 18703 12262 10169 10073 13034 15680 13500 16430 19079 62460 58987 56357 71212 71834 69377 30344 43283 34444 25678 24333 27770 20083 24005 17748 28075 50613 39273 57010 63513 62382 25827 33098 37878 21018 27298 19496 21201 22149 19972 99752 82379 84908 39350 64264 30702 36709 50474 38673 30065 40214 29627 51050 51339 45590 70025 77120 80911 62455 65611 66534 70068 72243 74365 34550 42650 40473 48704 41573 50127 trans-4-Hydroxy-L-proline 99811 74752 33763 40326 85985 72096 91792 177990 95207 42183 45480 78791 136204 162896 174097 115296 119934 148315 97144 71900 34704 52809 66509 76174 100997 100757 34217 93725 120563 99600 152099 93974 269349 169940 59889 63765 46197 90707 59561 448685 91469 61686 64214 79096 149326 66313 162401 138006 122986 90598 110221 89131 88288 65310 133523 141870 126808 145968 216085 208295 201239 106307 150368 100637 103062 108041 91864 124860 52935 107879 155465 198126 144720 226730 129478 137276 5-Aminopentanoate 49755 30326 36937 29885 34328 32245 37270 42626 40282 29916 36650 28841 35106 38636 32393 29082 49280 50164 48381 63988 59756 58147 52344 78616 60140 70286 45247 40601 54436 59377 52805 59278 49430 48000 63159 70368 60112 71353 53395 6897646 91694 43121 28760 55583 52612 54593 124137 96366 70771 92700 59872 226413 86620 83775 77269 91058 91232 73276 126726 130230 130264 184404 124278 131859 71702 84198 63980 85221 83537 72764 83698 117226 83812 104321 70085 66597 Taurine 2011309 1585128 1039280 1208599 4370191 4281270 3813837 4061940 3834843 2910029 2195884 3394375 5163738 6051314 5355644 6647028 11230720 8562832 7873582 1716327 829309 1589316 2554073 3907612 3693239 3153955 1538463 2678548 5067102 4546904 4793624 6639562 7216338 7863038 874595 794616 815793 2581470 1962203 3290202 2593659 2748268 2210460 3408814 3502470 4367572 15955640 12654590 14508910 2243099 3703885 2564174 3364486 2902947 4619140 6694272 7742524 7862214 10245800 10113210 11249930 12482230 14631780 12735440 3928020 3942327 3283488 5138658 2024816 5432817 7364566 9854741 9605008 11104640 9312276 8761576 Hypotaurine 10721 7758 3672 7048 26215 25125 19332 20618 22063 15446 11135 22731 25200 33699 31928 35735 83190 56355 46075 12978 5212 10403 21656 29735 25697 17610 6345 21079 35679 37099 30213 45363 40485 43115 7532 5707 7880 23027 18401 12732 19296 22621 17454 23567 23614 30755 132751 106934 111008 13516 18315 15316 21824 20733 26711 53118 53574 62019 76509 70482 77099 93997 87616 78595 31638 24874 21411 41647 18589 45341 73009 75703 76369 85140 66878 90989 3-Sulfino-L-alanine 75670 77808 13358 32474 78201 40500 82848 113461 73295 44851 34924 49303 112024 136521 128886 106636 97274 136344 107230 82314 19182 32561 56338 89946 97089 119269 24663 101590 150214 93486 166816 86703 99769 113728 84661 95981 60736 93292 53490 84791 92889 65015 63229 107809 150099 102755 138465 136138 52186 135432 132559 118509 67210 46503 136147 124592 213766 89262 217205 206286 224817 70256 148297 106442 138611 147674 173738 91062 33346 98396 128809 211135 143987 209315 113271 54292 L-Cysteate 126159 85512 0 5163 78547 1496 91545 195709 78361 0 4157 25465 152391 189449 188053 66312 33428 156817 68002 63076 2433 15265 23115 68119 113618 164238 2212 160038 133711 51461 256023 86570 174809 147580 43517 126302 51720 29164 21234 136488 148642 25260 52878 105756 275114 62687 163033 125177 21446 174956 128301 167668 20855 13982 217894 99726 236705 29097 291753 223859 295502 14725 204704 117940 99394 155652 234154 46420 2445 54510 84709 309931 144056 401099 44522 16833 Glycerol 3-phosphate 35570 35272 43385 40599 47550 75964 49504 42347 43815 73380 47669 47632 50432 65343 56924 75741 62585 45227 39744 58767 71432 54198 50349 55744 41572 29842 51606 33034 73702 74498 61259 28518 22190 29939 57793 44701 54037 79790 85809 61780 52664 45733 23701 60859 52518 66066 31775 42502 36884 55776 47984 66877 61437 71608 30446 92121 93040 107375 130911 122692 132342 57646 49604 42323 68182 69070 57542 91436 103124 99003 129691 128667 121999 114994 120431 130855 Ethanolamine phosphate 259793 224662 304746 261710 771169 910098 644101 690029 643508 903495 744259 822266 746358 932380 901156 1324998 1403867 1340576 1221871 382267 484827 469746 795759 904753 785365 633342 652108 604833 904813 960474 777927 754159 796181 950888 278763 227764 289124 744453 775626 610282 499261 699824 453982 743634 722549 960789 2785291 2465052 2919470 490746 995695 571561 913516 1210615 855383 1450168 1679798 1908689 2572795 2583701 2400089 1890664 1891320 1951278 877875 1022599 789718 1494399 1306241 1395018 1718934 1677862 1780892 1701299 2103903 1957884 sn-glycero-3-Phosphoethanolamine 239947 210093 168644 203279 350226 375224 348455 297933 506406 409527 330569 410733 465585 624489 540684 644295 216579 166072 156760 164279 98382 162785 180506 194216 217242 298330 205093 252542 374881 372571 304021 121612 124729 126197 116197 108566 137677 205803 141634 190389 270958 337081 255208 337538 336665 344427 471714 370390 406748 280195 390425 264949 294874 251169 414195 791486 873403 880357 1044262 1009702 1099244 287342 359915 253424 340876 346100 323136 414447 201570 446610 686948 849776 881310 807408 751440 753074 Hexanoic acid (caproate) 389536 385850 248059 241424 418562 175528 313484 398227 315313 193569 233033 263094 394859 330268 340291 408682 318664 383852 367507 301047 182353 191617 278853 318278 331526 335118 267003 361496 364262 323803 440637 348351 430888 341348 281386 268901 328632 297631 287413 396125 424325 317345 338340 306020 310590 329319 409388 326444 244351 387290 383689 517884 262602 341676 325323 358083 380658 282367 354824 312412 391591 295776 397646 319834 262393 310960 290090 242987 187241 281573 319595 310888 323070 320047 265675 229678 Heptanoic acid 419768 419641 312204 259119 406564 258170 376494 408804 366415 278030 295273 294989 432250 365219 402236 454443 354273 340079 397872 407673 207948 269692 301120 306836 377951 395213 276201 425826 418077 388151 415456 369337 378627 361632 339917 371710 368452 335390 373377 459075 409517 343542 370332 384906 389056 382682 432610 375390 296998 400299 432001 393038 313280 308698 396551 411117 436260 300360 387262 396459 407669 367789 432075 410124 323024 347721 371210 297632 232486 310670 329802 376291 395280 338317 292836 259659 Octanoic acid (caprylate) 909602 855142 574246 486847 848487 440991 879604 885380 691620 467354 638616 713370 1000377 880523 893923 885090 774570 885952 765231 666482 346879 571328 591985 750783 757714 905328 469858 889333 830611 760703 918041 712266 960734 711919 789898 859763 749123 782545 608005 1066191 932000 487528 845703 737185 874953 750264 912252 819455 534471 949131 843766 1130854 615828 495023 839798 794017 874671 603494 814640 740348 835687 571263 868323 808176 689576 687669 676810 666999 466676 758256 623978 876395 752698 914187 487515 531171 Nonanoic acid (pelargonate) 2034594 2262903 1650610 1378222 2843862 1319808 2378788 2133368 1910218 1389056 2024882 2008616 3335024 1919710 3009350 2486898 2216425 2035286 2372549 1956798 1050725 1733419 1846586 2143808 2288471 3017764 1513937 2888388 2185212 2341156 2395671 2279129 2029628 2350646 2088298 2975420 1954765 2195771 1949025 2764490 2446267 1729167 2430258 2451363 2246209 2539754 2798193 2227026 1732211 2509524 2842280 2352575 2426539 1521914 2570470 2112513 2844123 1480223 2161249 1992076 2878410 1638030 2755776 2922422 1917222 2917829 2149838 1861976 1278522 1959540 1778487 2891349 1682179 2326557 1549126 1707056 Dodecanoic acid 1285738 1225450 851862 676681 1077798 636310 1205703 1139120 1014141 701023 879667 896462 1060500 791750 1220504 907177 1056291 945694 1005682 914904 668621 722074 1093206 902938 1012026 975008 881471 1179806 1359344 963949 888085 1100591 922540 906110 977404 1054434 1016706 967006 994861 1860027 1764792 902091 1322651 960229 1162921 1152164 1160990 940821 790983 1187837 1228137 3478990 1019584 855064 1223697 899155 1016289 737200 1130702 1110504 947927 806564 1171823 908050 863870 1168310 946982 898754 806163 972742 825044 1026693 1171670 1091141 795028 1002895 Tetradecanoic acid 1506498 1482173 1084628 1129878 1698279 1023497 1341482 1400776 1682602 1161210 1277599 1513101 1480276 1395301 1272419 1484001 1349334 1397185 1121696 1482731 1123035 1284257 1356605 1393042 1435162 1624287 1213543 1473197 1584753 1382728 1224954 1468733 1434771 1395985 1332504 1536232 1642713 1458460 1298952 3035744 5442970 1376280 1631353 1275775 1468611 1644079 1569565 1614138 1239892 1455155 1901540 12869560 1625018 1367163 1471584 1557862 1680270 1147612 2066984 1422165 1674085 1432558 1553752 1174815 1520362 1867694 1683583 1166398 1229656 1601988 1286935 1610715 1399360 1531974 1270231 1493739 Hexadecanoic acid 14959120 15406920 10435290 8787023 10243430 8016312 13807470 15114760 11575130 8158374 8578429 10848380 14439840 13098460 14434250 12750860 11526250 12432760 12116920 12651560 9875368 9797123 10930970 9514168 14200460 15545920 11883810 15202580 15760550 13956560 14383170 10729200 16728730 13075630 13697790 15097290 12205910 10979000 12786880 37494330 24541080 12519880 14099670 13123360 13093070 12956410 15465280 15461320 11808840 14717900 17875370 29164830 11952920 12032050 14065070 14834520 14154120 9862751 13860000 13277790 18144690 14029720 13578040 12863590 11727020 15127350 15812600 12133280 8953872 12102620 10667480 16226950 13739970 14822950 13130370 11854620 Octadecanoic acid (stearic acid) 5811820 6174544 9636773 9599912 6248424 9133453 6026158 5587554 5070810 9735901 7687882 5338512 5232494 5005064 5503600 5110338 4995053 5214589 4973122 5444500 13567730 10709410 7135250 6009138 5368994 6163550 10790940 6125636 6624694 5193257 6750800 5736468 5920748 5245510 6534082 7140012 5630232 5400368 7074368 14355450 7413184 4830967 5521620 6160802 6082372 5250240 6523854 5947242 7685276 6185184 6823128 8712632 5250544 5887660 5617336 7762634 6677850 5802978 5861964 6845234 6250810 6334204 6742408 5636902 5448940 7243112 5882426 4018971 9865566 4703224 5218196 7275496 7200252 6010350 5009798 10106970 Tetradecenoic acid 60063 40473 31103 31742 36145 32857 36984 46768 35109 29601 23085 36008 35320 33787 31772 42652 38881 34216 33233 55149 39782 41229 25486 40449 31154 40548 38133 37057 59737 46282 35291 36766 35955 37486 44355 42349 35509 40527 63847 212198 1011457 31535 41660 35805 31921 36776 43281 42013 32766 38524 74680 2094234 54886 27819 48590 32627 41387 33833 96740 36837 42225 36928 48731 37732 34010 36752 50668 43364 31531 40713 33945 36214 58003 33322 34359 57407 Hexadecenoic acid 356960 190732 174987 172419 189924 155614 185547 287832 195816 190419 185391 124769 211313 192100 205549 273376 240508 203890 247785 367465 338796 326968 322295 351020 350252 359088 288824 289371 430131 256034 273018 199675 183171 220362 269356 314356 315517 269744 452294 1488746 10376750 309548 286110 285105 283267 241074 396529 403229 305671 417095 550283 15546050 421980 343276 287764 353409 380443 324692 736442 474261 437249 469412 433646 396052 316874 473328 366227 321489 294916 307225 269935 361688 434085 363349 340242 370882 Octadecenoic acid (oleic acid) 1378487 1196322 920974 838634 860517 619962 887967 1473989 880541 772792 821225 649083 880502 949094 1062100 927635 1304313 1339184 1608777 2476726 1913350 2152466 2265422 2564600 2403623 2020992 1625672 1849141 1990113 1845385 1775568 997153 1261602 1447215 2312868 2377039 2360101 1557814 2026957 13321700 7490126 1481598 1396007 1336772 1571490 1737231 2816772 2471694 2041676 2734987 5401796 20397420 2095491 1734433 1850198 2008576 2274145 2134195 2804623 2450078 3095353 2327508 3186105 2282424 2195979 2475519 2389271 1742879 1643947 1997603 1511917 1927399 2192241 2160677 1973783 1533483 Linoleate 138270 104522 120056 94771 119684 100215 104116 160334 107533 106499 144481 91245 211348 115020 144074 138850 156379 143061 168083 186584 222254 209609 175972 203974 217040 171565 142302 143067 177769 181593 171533 115262 120007 128673 188513 194807 209396 195519 194564 3227673 956990 138905 141959 149035 141472 209418 283746 257963 254565 222596 1143064 5641854 224665 180688 180232 220825 248523 184364 360878 298114 326256 349104 372200 337064 224286 281736 252523 188336 209515 175311 210709 253591 220218 260940 222534 265018 Octadecatrienoic acid (linolenic acid) 9974 6460 3341 5602 8729 4596 7559 8180 3634 5916 10347 3497 10187 6977 6078 10158 9890 4566 6318 8243 8937 9740 6352 6177 9762 7968 8255 8598 7518 6421 6742 5452 5494 8946 8428 7724 5924 8564 7244 319340 50924 8086 6962 5617 4751 7863 10030 11113 10978 8603 39764 806720 4846 8285 7963 7027 8709 6469 18346 3209 14475 11001 14299 11107 5309 8831 12311 8524 8211 6583 6050 7061 9558 6341 7898 9590 Eicosatetraenoic acid 704213 753864 771433 729137 497174 412246 424564 617199 398206 639242 324344 325760 380024 401706 505268 511091 752734 693457 771823 1096244 1286634 1168477 819093 978215 662961 752034 830543 713164 694637 717457 547768 702540 729292 657362 970376 954868 961826 545144 534104 692769 750741 508776 621248 351317 407388 520581 1016418 1262320 838635 746853 593180 962715 538148 572976 358620 836890 643063 565781 942301 658520 580269 1680932 1607994 1177231 607398 807879 554101 395989 502940 461214 613942 782477 538966 746671 562632 747440 Eicosapentaenoic acid 143792 127082 133762 132938 78211 81245 82938 117429 74658 112639 57237 53100 79320 73062 113299 108892 269469 193489 252247 278256 323532 326096 188294 213760 183681 202094 208731 196636 176530 156410 164387 172141 156378 190986 245267 201338 185474 175901 132465 171212 136339 103962 113951 91264 80980 136217 416617 350019 367693 142752 156098 182237 87417 94703 65405 226576 168721 214820 270586 200611 219025 592223 553081 418563 109218 124080 100262 108076 88913 91250 135937 213498 159152 185360 163212 200968 Docosahexaenoic acid 252574 191307 211724 189720 151499 151959 164101 254905 144377 226723 164652 141096 169733 164896 216034 247445 405669 298265 365561 451807 539799 445818 354763 418906 345787 317499 367900 299160 298539 303880 282901 259314 328008 326363 337189 399467 389331 315886 282737 385153 274682 267412 273542 202410 198614 267196 1057274 904228 782278 498501 471678 444927 431203 397566 280519 467381 565421 480157 755348 688036 539475 1205532 1383967 1012226 413904 520074 386310 362504 369104 360494 432281 522359 618035 611350 485071 656591 (8Z-11Z-14Z)-Icosatrienoic acid 119168 88570 90254 94180 71463 75011 81820 114868 67951 81685 60589 58887 68907 72988 82887 85510 166050 122906 160038 242715 205590 225410 191351 260310 192797 182490 143438 150709 163958 120987 122299 121490 125448 132018 196273 197489 167494 142090 144874 196692 163872 122062 100483 83462 100087 104291 240928 205150 161841 142973 134885 316838 116837 114042 104963 147820 124042 113354 165250 153438 141578 301123 338606 233439 130371 158965 134161 98096 95756 98979 122932 158539 129210 143082 117307 134855 (5Z-8Z-11Z-14Z-17Z)-Icosapentaenoic acid 143792 127082 133762 132938 78211 81245 82938 117429 74658 112639 57237 53100 79320 73062 113299 108892 269469 193489 252247 278256 323532 326096 188294 213760 183681 202094 208731 196636 176530 156410 164387 172141 156378 190986 245267 201338 185474 175901 132465 171212 136339 103962 113951 91264 80980 136217 416617 350019 367693 142752 156098 182237 87417 94703 65405 226576 168721 214820 270586 200611 219025 592223 553081 418563 109218 124080 100262 108076 88913 91250 135937 213498 159152 185360 163212 200968 (7Z-10Z-13Z-16Z-19Z)-Docosa-7-10-13-16-19-pentaenoic acid 377973 322366 355003 301745 232493 225500 260668 405112 245835 262218 213691 208935 218891 211995 365930 303594 592217 505169 578425 795760 785938 680909 522372 560076 491748 486712 445159 441602 497675 422281 343737 461672 384148 470581 526756 586466 544628 496441 440784 513079 468092 405446 314969 290726 300595 411873 1580845 1016862 1073264 641185 494739 672053 438762 507935 369845 586385 611355 562532 884215 734949 792997 1830167 1755684 1411265 495531 612300 514709 362469 371496 445811 494222 711118 544026 723042 607681 700157 MS_METABOLITE_DATA_END #METABOLITES METABOLITES_START metabolite_name KEGG ID m/z r.t. itaconate 13C5 C00490 134.0349 0.5997645 fumarate 13C4 C00122 119.0159 0.5716002 malate 13C4 C00149 137.0264 0.5881515 AMP C00020 346.0553 0.64 dAMP C00360 330.0634 0.63 GMP C00144 362.0504 0.61 CMP C00055 322.0447 0.60 Cytidine C00475 242.0789 0.64 UMP C00105 323.0278 0.60 IMP C00130 347.0392 0.61 Inosine C00294 267.0734 0.97 Hypoxanthine C00262 135.0300 0.87 5-6-Dihydrothymine C00906 127.0498 0.64 4-Pyridoxate C00847 182.0427 0.67 UDP-glucose C00029 565.0469 0.57 ADP-D-ribose C01882 558.0632 0.59 Phosphate C00009 96.9680 0.60 Diphosphate C00013 176.9346 0.60 D-Glucose C00031 179.0550 0.65 2/3-Phospho-D-glycerate C00631 184.9849 0.60 Pyruvate C00022 87.0072 0.61 Lactate C01432 89.0229 0.61 Maltose C00208 341.1093 0.66 Mannitol C00392 181.0705 0.65 D-Arabitol C01904 151.0610 0.61 Citrate C00158 191.0187 0.59 2-Oxoglutarate C00026 145.0129 0.58 2-Oxoglutaramate C00940 144.0291 0.62 Succinate C00042 117.0178 0.57 Fumarate C00122 115.0022 0.59 Malate C00149 133.0129 0.59 2-Hydroxyglutarate/Citramalate C02630 147.0286 0.59 Itaconate C00490 129.0179 0.6 D-Glucono-1-5-lactone 6-phosphate C01236 257.0074 0.56 Sedoheptulose 1-phosphate C06222 289.0334 0.60 alpha-D-Ribose 1-phosphate C00620 229.0114 0.59 Glutathione C00051 306.0768 0.62 Glutathione disulfide C00127 611.1445 0.59 S-Glutathionyl-L-cysteine C05526 425.0803 0.60 Ascorbate C00072 175.0234 0.58 Dehydroascorbate C05422 173.0093 0.60 Dimethylglycine C01026 102.0546 0.63 3-Phosphonooxypyruvate C03232 182.9669 0.75 Argininosuccinate C03406 289.1151 0.59 N-Acetylneuraminate C00270 308.0981 0.60 N-Glycoloyl-neuraminate C03410 324.0935 0.60 alpha-D-Glucosamine 1-phosphate C06156 258.0380 0.59 1-4-beta-D-Xylan C02352 131.0335 0.59 UDP-N-acetyl-D-glucosamine C00043 606.0740 0.56 trans-4-Hydroxy-L-proline C01157 130.0497 0.64 5-Aminopentanoate C00431 116.0703 0.68 Taurine C00245 124.0059 0.64 Hypotaurine C00519 108.0109 0.65 3-Sulfino-L-alanine C00606 152.0010 0.61 L-Cysteate C00506 167.9961 0.60 Glycerol 3-phosphate C00093 171.0053 0.59 Ethanolamine phosphate C00346 140.0107 0.62 sn-glycero-3-Phosphoethanolamine C01233 214.0479 0.63 Hexanoic acid (caproate) C01585 115.0751 1.80 Heptanoic acid C17714 129.0908 1.92 Octanoic acid (caprylate) C06423 143.1065 2.02 Nonanoic acid (pelargonate) C01601 157.1221 2.09 Dodecanoic acid C02679 199.1697 2.33 Tetradecanoic acid C06424 227.2011 2.57 Hexadecanoic acid C00249 255.2325 2.94 Octadecanoic acid (stearic acid) C01530 283.2638 3.48 Tetradecenoic acid C08322 225.1855 2.38 Hexadecenoic acid C08362 253.2168 2.62 Octadecenoic acid (oleic acid) C00712 281.2481 2.98 Linoleate C01595 279.2325 2.66 Octadecatrienoic acid (linolenic acid) C06427 277.2168 2.47 Eicosatetraenoic acid C00219 303.2326 2.56 Eicosapentaenoic acid C06428 301.2168 2.40 Docosahexaenoic acid C06429 327.2327 2.47 (8Z-11Z-14Z)-Icosatrienoic acid C03242 305.2481 2.74 (5Z-8Z-11Z-14Z-17Z)-Icosapentaenoic acid C06428 301.2168 2.40 (7Z-10Z-13Z-16Z-19Z)-Docosa-7-10-13-16-19-pentaenoic acid C16513 329.2481 2.59 METABOLITES_END #END