#METABOLOMICS WORKBENCH juliehaines_20241125_131224 DATATRACK_ID:5396 STUDY_ID:ST003604 ANALYSIS_ID:AN005921 PROJECT_ID:PR002231 VERSION 1 CREATED_ON December 5, 2024, 7:19 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 Investigation of global metabolites and E coli-derived metabolites following ST:STUDY_TITLE engulfment of dead bacteria by wild type or RagAGTP-expressing bone marrow ST:STUDY_TITLE derived macrophages. ST:STUDY_SUMMARY Global metabolomics and 13C-tracing analysis of wild type or RagAGTP-expressing ST:STUDY_SUMMARY bone marrow derived macrophages exposed to heat-killed uniformly 13C-labelled E. ST:STUDY_SUMMARY coli 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 WT 1 time (h):0 | Dead E coli treatment:no | inhibitor:none | Sample source:murine bone marrow derived macrophages | genotype:WT RAW_FILE_NAME(raw file name)=F2-64-01- SUBJECT_SAMPLE_FACTORS - CT WT 2 time (h):0 | Dead E coli treatment:no | inhibitor:none | Sample source:murine bone marrow derived macrophages | genotype:WT RAW_FILE_NAME(raw file name)=F2-64-02- SUBJECT_SAMPLE_FACTORS - CT WT 3 time (h):0 | Dead E coli treatment:no | inhibitor:none | Sample source:murine bone marrow derived macrophages | genotype:WT RAW_FILE_NAME(raw file name)=F2-64-03- SUBJECT_SAMPLE_FACTORS - CT WT 4 time (h):0 | Dead E coli treatment:no | inhibitor:none | Sample source:murine bone marrow derived macrophages | genotype:WT RAW_FILE_NAME(raw file name)=F2-64-04- SUBJECT_SAMPLE_FACTORS - WT 1 6h time (h):6 | Dead E coli treatment:yes | inhibitor:none | Sample source:murine bone marrow derived macrophages | genotype:WT RAW_FILE_NAME(raw file name)=F2-64-05- SUBJECT_SAMPLE_FACTORS - WT 2 6h time (h):6 | Dead E coli treatment:yes | inhibitor:none | Sample source:murine bone marrow derived macrophages | genotype:WT RAW_FILE_NAME(raw file name)=F2-64-06- SUBJECT_SAMPLE_FACTORS - WT 3 6h time (h):6 | Dead E coli treatment:yes | inhibitor:none | Sample source:murine bone marrow derived macrophages | genotype:WT RAW_FILE_NAME(raw file name)=F2-64-07- SUBJECT_SAMPLE_FACTORS - WT 4 6h time (h):6 | Dead E coli treatment:yes | inhibitor:none | Sample source:murine bone marrow derived macrophages | genotype:WT RAW_FILE_NAME(raw file name)=F2-64-08- SUBJECT_SAMPLE_FACTORS - WT 1 18h time (h):18 | Dead E coli treatment:yes | inhibitor:none | Sample source:murine bone marrow derived macrophages | genotype:WT RAW_FILE_NAME(raw file name)=F2-64-09- SUBJECT_SAMPLE_FACTORS - WT 2 18h time (h):18 | Dead E coli treatment:yes | inhibitor:none | Sample source:murine bone marrow derived macrophages | genotype:WT RAW_FILE_NAME(raw file name)=F2-64-10- SUBJECT_SAMPLE_FACTORS - WT3 18h time (h):18 | Dead E coli treatment:yes | inhibitor:none | Sample source:murine bone marrow derived macrophages | genotype:WT RAW_FILE_NAME(raw file name)=F2-64-11- SUBJECT_SAMPLE_FACTORS - WT 4 18h time (h):18 | Dead E coli treatment:yes | inhibitor:none | Sample source:murine bone marrow derived macrophages | genotype:WT RAW_FILE_NAME(raw file name)=F2-64-12- SUBJECT_SAMPLE_FACTORS - CT RagA GTP 1 time (h):0 | Dead E coli treatment:no | inhibitor:none | Sample source:murine bone marrow derived macrophages | genotype:RagA GTP mutant RAW_FILE_NAME(raw file name)=F2-64-13- SUBJECT_SAMPLE_FACTORS - CT RagA GTP 2 time (h):0 | Dead E coli treatment:no | inhibitor:none | Sample source:murine bone marrow derived macrophages | genotype:RagA GTP mutant RAW_FILE_NAME(raw file name)=F2-64-14- SUBJECT_SAMPLE_FACTORS - CT RagA GTP 3 time (h):0 | Dead E coli treatment:no | inhibitor:none | Sample source:murine bone marrow derived macrophages | genotype:RagA GTP mutant RAW_FILE_NAME(raw file name)=F2-64-15- SUBJECT_SAMPLE_FACTORS - CT RagA GTP 4 time (h):0 | Dead E coli treatment:no | inhibitor:none | Sample source:murine bone marrow derived macrophages | genotype:RagA GTP mutant RAW_FILE_NAME(raw file name)=F2-64-16- SUBJECT_SAMPLE_FACTORS - RagA GTP 1 6h time (h):6 | Dead E coli treatment:yes | inhibitor:none | Sample source:murine bone marrow derived macrophages | genotype:RagA GTP mutant RAW_FILE_NAME(raw file name)=F2-64-17- SUBJECT_SAMPLE_FACTORS - RagA GTP 2 6h time (h):6 | Dead E coli treatment:yes | inhibitor:none | Sample source:murine bone marrow derived macrophages | genotype:RagA GTP mutant RAW_FILE_NAME(raw file name)=F2-64-18- SUBJECT_SAMPLE_FACTORS - RagA GTP 3 6h time (h):6 | Dead E coli treatment:yes | inhibitor:none | Sample source:murine bone marrow derived macrophages | genotype:RagA GTP mutant RAW_FILE_NAME(raw file name)=F2-64-19- SUBJECT_SAMPLE_FACTORS - RagA GTP 4 6h time (h):6 | Dead E coli treatment:yes | inhibitor:none | Sample source:murine bone marrow derived macrophages | genotype:RagA GTP mutant RAW_FILE_NAME(raw file name)=F2-64-20- SUBJECT_SAMPLE_FACTORS - RagA GTP 1 18h time (h):18 | Dead E coli treatment:yes | inhibitor:none | Sample source:murine bone marrow derived macrophages | genotype:RagA GTP mutant RAW_FILE_NAME(raw file name)=F2-64-21- SUBJECT_SAMPLE_FACTORS - RagA GTP 2 18h time (h):18 | Dead E coli treatment:yes | inhibitor:none | Sample source:murine bone marrow derived macrophages | genotype:RagA GTP mutant RAW_FILE_NAME(raw file name)=F2-64-22- SUBJECT_SAMPLE_FACTORS - RagA GTP 3 18h time (h):18 | Dead E coli treatment:yes | inhibitor:none | Sample source:murine bone marrow derived macrophages | genotype:RagA GTP mutant RAW_FILE_NAME(raw file name)=F2-64-23- SUBJECT_SAMPLE_FACTORS - RagA GTP 4 18h time (h):18 | Dead E coli treatment:yes | inhibitor:none | Sample source:murine bone marrow derived macrophages | genotype:RagA GTP mutant RAW_FILE_NAME(raw file name)=F2-64-24- SUBJECT_SAMPLE_FACTORS - CT WT 1 + Conca time (h):0 | Dead E coli treatment:no | inhibitor:none | Sample source:murine bone marrow derived macrophages | genotype:WT RAW_FILE_NAME(raw file name)=F2-64-25- SUBJECT_SAMPLE_FACTORS - CT WT 2 + Conca time (h):0 | Dead E coli treatment:no | inhibitor:none | Sample source:murine bone marrow derived macrophages | genotype:WT RAW_FILE_NAME(raw file name)=F2-64-26- SUBJECT_SAMPLE_FACTORS - CT WT 3 + Conca time (h):0 | Dead E coli treatment:no | inhibitor:none | Sample source:murine bone marrow derived macrophages | genotype:WT RAW_FILE_NAME(raw file name)=F2-64-27- SUBJECT_SAMPLE_FACTORS - CT WT 4 + Conca time (h):0 | Dead E coli treatment:no | inhibitor:none | Sample source:murine bone marrow derived macrophages | genotype:WT RAW_FILE_NAME(raw file name)=F2-64-28- SUBJECT_SAMPLE_FACTORS - WT 1 6h + Conca time (h):6 | Dead E coli treatment:yes | inhibitor:150 nM concanamycin A | Sample source:murine bone marrow derived macrophages | genotype:WT RAW_FILE_NAME(raw file name)=F2-64-29- SUBJECT_SAMPLE_FACTORS - WT 2 6h + Conca time (h):6 | Dead E coli treatment:yes | inhibitor:150 nM concanamycin A | Sample source:murine bone marrow derived macrophages | genotype:WT RAW_FILE_NAME(raw file name)=F2-64-30- SUBJECT_SAMPLE_FACTORS - WT 3 6h + Conca time (h):6 | Dead E coli treatment:yes | inhibitor:150 nM concanamycin A | Sample source:murine bone marrow derived macrophages | genotype:WT RAW_FILE_NAME(raw file name)=F2-64-31- SUBJECT_SAMPLE_FACTORS - WT 4 6h + Conca time (h):6 | Dead E coli treatment:yes | inhibitor:150 nM concanamycin A | Sample source:murine bone marrow derived macrophages | genotype:WT RAW_FILE_NAME(raw file name)=F2-64-32- SUBJECT_SAMPLE_FACTORS - WT 1 18h + Conca time (h):18 | Dead E coli treatment:yes | inhibitor:150 nM concanamycin A | Sample source:murine bone marrow derived macrophages | genotype:WT RAW_FILE_NAME(raw file name)=F2-64-33- SUBJECT_SAMPLE_FACTORS - WT 2 18h + Conca time (h):18 | Dead E coli treatment:yes | inhibitor:150 nM concanamycin A | Sample source:murine bone marrow derived macrophages | genotype:WT RAW_FILE_NAME(raw file name)=F2-64-34- SUBJECT_SAMPLE_FACTORS - WT3 18h + Conca time (h):18 | Dead E coli treatment:yes | inhibitor:150 nM concanamycin A | Sample source:murine bone marrow derived macrophages | genotype:WT RAW_FILE_NAME(raw file name)=F2-64-35- SUBJECT_SAMPLE_FACTORS - WT 4 18h + Conca time (h):18 | Dead E coli treatment:yes | inhibitor:150 nM concanamycin A | Sample source:murine bone marrow derived macrophages | genotype:WT RAW_FILE_NAME(raw file name)=F2-64-36- SUBJECT_SAMPLE_FACTORS - WT 1 6h + Bafilo time (h):6 | Dead E coli treatment:yes | inhibitor:50 nM bafilomycin A1 | Sample source:murine bone marrow derived macrophages | genotype:WT RAW_FILE_NAME(raw file name)=F2-64-37- SUBJECT_SAMPLE_FACTORS - WT 2 6h + Bafilo time (h):6 | Dead E coli treatment:yes | inhibitor:50 nM bafilomycin A1 | Sample source:murine bone marrow derived macrophages | genotype:WT RAW_FILE_NAME(raw file name)=F2-64-38- SUBJECT_SAMPLE_FACTORS - WT 3 6h + Bafilo time (h):6 | Dead E coli treatment:yes | inhibitor:50 nM bafilomycin A1 | Sample source:murine bone marrow derived macrophages | genotype:WT RAW_FILE_NAME(raw file name)=F2-64-39- SUBJECT_SAMPLE_FACTORS - WT 4 6h + Bafilo time (h):6 | Dead E coli treatment:yes | inhibitor:50 nM bafilomycin A1 | Sample source:murine bone marrow derived macrophages | genotype:WT RAW_FILE_NAME(raw file name)=F2-64-40- SUBJECT_SAMPLE_FACTORS - WT 1 18h + Bafilo time (h):18 | Dead E coli treatment:yes | inhibitor:50 nM bafilomycin A1 | Sample source:murine bone marrow derived macrophages | genotype:WT RAW_FILE_NAME(raw file name)=F2-64-41- SUBJECT_SAMPLE_FACTORS - WT 2 18h + Bafilo time (h):18 | Dead E coli treatment:yes | inhibitor:50 nM bafilomycin A1 | Sample source:murine bone marrow derived macrophages | genotype:WT RAW_FILE_NAME(raw file name)=F2-64-42- SUBJECT_SAMPLE_FACTORS - WT3 18h + Bafilo time (h):18 | Dead E coli treatment:yes | inhibitor:50 nM bafilomycin A1 | Sample source:murine bone marrow derived macrophages | genotype:WT RAW_FILE_NAME(raw file name)=F2-64-43- SUBJECT_SAMPLE_FACTORS - WT 4 18h + Bafilo time (h):18 | Dead E coli treatment:yes | inhibitor:50 nM bafilomycin A1 | Sample source:murine bone marrow derived macrophages | genotype:WT RAW_FILE_NAME(raw file name)=F2-64-44- #COLLECTION CO:COLLECTION_SUMMARY BMDMs were seeded at 2.5E6 cell/well in a non-tissue treated 6-well plate (2 CO:COLLECTION_SUMMARY wells per condition) the day before the experiment. To harvest, BMDMs were CO:COLLECTION_SUMMARY washed with cold PBS and harvested with 5 mM EDTA in PBS, frozen as dry cell CO:COLLECTION_SUMMARY pellet, and stored at -80˚C until processing. CO:SAMPLE_TYPE Macrophages #TREATMENT TR:TREATMENT_SUMMARY Preparation of macrophages: Murine bone marrow-derived macrophages (BMDMs) were TR:TREATMENT_SUMMARY generated as described previously, in RPMI 1640 supplemented with M-CSF (30% TR:TREATMENT_SUMMARY mycoplasma-free L929 cell supernatant, NCBI Biosample accession # SAMN00155972) TR:TREATMENT_SUMMARY and 10% FBS, plus 100 µg/ml penicillin, 100 µg/ml streptomycin, 10 mM HEPES, 1 TR:TREATMENT_SUMMARY nM sodium pyruvate and 50 µM 2-mercaptoethanol (all from Gibco). BMDMs were TR:TREATMENT_SUMMARY used on day 5 to 7 after seeding. Period of differentiation of the cells, TR:TREATMENT_SUMMARY concentration of cells when replating and time-lapse between replating and TR:TREATMENT_SUMMARY stimulation with bacteria were important parameters to maintain metabolic TR:TREATMENT_SUMMARY backgrounds homogenous between experiments. Preparation of viable and killed TR:TREATMENT_SUMMARY U-[13C]Bacteria: ThyA- E. coli were grown overnight with shaking in LB TR:TREATMENT_SUMMARY supplemented with thymidine (500 µg/ml) and trimethoprim (50 µg/ml), diluted TR:TREATMENT_SUMMARY 1/40, and grown until log-phase [optical density at 600 nm (OD600) of 0.8-1.2]. TR:TREATMENT_SUMMARY Bacteria were washed with phosphate buffer saline (PBS) to remove LB salts TR:TREATMENT_SUMMARY before addition to cells. For labeling of bacteria, 10 µl of an overnight TR:TREATMENT_SUMMARY cultured of thyA- E. coli was added to 20 ml of a filtered M9 minimal medium TR:TREATMENT_SUMMARY salts (Life Technologies) supplemented with 1 mM thiamine, 1 mM MgSO4, 0.1 M TR:TREATMENT_SUMMARY CaCl2, 500 µg/ml thymidine, 50 µg/ml trimethoprim, and 0.5% U-[13C6] glucose TR:TREATMENT_SUMMARY (Campro Scientific). Bacteria were grown for 72h, washed with PBS and subjected TR:TREATMENT_SUMMARY to heat-killing by re-suspension in PBS and subsequently incubation at 60˚C for TR:TREATMENT_SUMMARY 60-90 min. For antibiotic killing, bacteria were incubated for 6h to 12h with TR:TREATMENT_SUMMARY Streptomycin or Gentamycin (50 µg/ml). Bacteria were kept at 4˚C until use. TR:TREATMENT_SUMMARY Efficient killing was confirmed by overnight plating on LB-agar plates. TR:TREATMENT_SUMMARY Treatment of macrophages: 2E6 BMDMs were plated 12-16h prior stimulation in TR:TREATMENT_SUMMARY non-tissue cultured treated 6-well plate (BD Falcons). Cells were then TR:TREATMENT_SUMMARY stimulated with killed labelled-E. coli at MOI 50, centrifuged at 2000 rpm for TR:TREATMENT_SUMMARY 5min. BMDMs were incubated for 5 min and washed with PBS to remove non-ingested TR:TREATMENT_SUMMARY bacteria and further incubated for 6h or 18h. To inhibit lysosomal degradation, TR:TREATMENT_SUMMARY cells were treated with 50 nM Bafilomycin A1. To inhibit v-ATPase, cells were TR:TREATMENT_SUMMARY treated with 150 nM concanamycin A. All the above inhibitors were added to the TR:TREATMENT_SUMMARY cultured medium at least 2h before stimulation of the BMDMs. #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 WT 1 CT WT 2 CT WT 3 CT WT 4 WT 1 6h WT 2 6h WT 3 6h WT 4 6h WT 1 18h WT 2 18h WT3 18h WT 4 18h CT RagA GTP 1 CT RagA GTP 2 CT RagA GTP 3 CT RagA GTP 4 RagA GTP 1 6h RagA GTP 2 6h RagA GTP 3 6h RagA GTP 4 6h RagA GTP 1 18h RagA GTP 2 18h RagA GTP 3 18h RagA GTP 4 18h CT WT 1 + Conca CT WT 2 + Conca CT WT 3 + Conca CT WT 4 + Conca WT 1 6h + Conca WT 2 6h + Conca WT 3 6h + Conca WT 4 6h + Conca WT 1 18h + Conca WT 2 18h + Conca WT3 18h + Conca WT 4 18h + Conca WT 1 6h + Bafilo WT 2 6h + Bafilo WT 3 6h + Bafilo WT 4 6h + Bafilo WT 1 18h + Bafilo WT 2 18h + Bafilo WT3 18h + Bafilo WT 4 18h + Bafilo Factors time (h):0 | Dead E coli treatment:no | inhibitor:none | Sample source:murine bone marrow derived macrophages | genotype:WT time (h):0 | Dead E coli treatment:no | inhibitor:none | Sample source:murine bone marrow derived macrophages | genotype:WT time (h):0 | Dead E coli treatment:no | inhibitor:none | Sample source:murine bone marrow derived macrophages | genotype:WT time (h):0 | Dead E coli treatment:no | inhibitor:none | Sample source:murine bone marrow derived macrophages | genotype:WT time (h):6 | Dead E coli treatment:yes | inhibitor:none | Sample source:murine bone marrow derived macrophages | genotype:WT time (h):6 | Dead E coli treatment:yes | inhibitor:none | Sample source:murine bone marrow derived macrophages | genotype:WT time (h):6 | Dead E coli treatment:yes | inhibitor:none | Sample source:murine bone marrow derived macrophages | genotype:WT time (h):6 | Dead E coli treatment:yes | inhibitor:none | Sample source:murine bone marrow derived macrophages | genotype:WT time (h):18 | Dead E coli treatment:yes | inhibitor:none | Sample source:murine bone marrow derived macrophages | genotype:WT time (h):18 | Dead E coli treatment:yes | inhibitor:none | Sample source:murine bone marrow derived macrophages | genotype:WT time (h):18 | Dead E coli treatment:yes | inhibitor:none | Sample source:murine bone marrow derived macrophages | genotype:WT time (h):18 | Dead E coli treatment:yes | inhibitor:none | Sample source:murine bone marrow derived macrophages | genotype:WT time (h):0 | Dead E coli treatment:no | inhibitor:none | Sample source:murine bone marrow derived macrophages | genotype:RagA GTP mutant time (h):0 | Dead E coli treatment:no | inhibitor:none | Sample source:murine bone marrow derived macrophages | genotype:RagA GTP mutant time (h):0 | Dead E coli treatment:no | inhibitor:none | Sample source:murine bone marrow derived macrophages | genotype:RagA GTP mutant time (h):0 | Dead E coli treatment:no | inhibitor:none | Sample source:murine bone marrow derived macrophages | genotype:RagA GTP mutant time (h):6 | Dead E coli treatment:yes | inhibitor:none | Sample source:murine bone marrow derived macrophages | genotype:RagA GTP mutant time (h):6 | Dead E coli treatment:yes | inhibitor:none | Sample source:murine bone marrow derived macrophages | genotype:RagA GTP mutant time (h):6 | Dead E coli treatment:yes | inhibitor:none | Sample source:murine bone marrow derived macrophages | genotype:RagA GTP mutant time (h):6 | Dead E coli treatment:yes | inhibitor:none | Sample source:murine bone marrow derived macrophages | genotype:RagA GTP mutant time (h):18 | Dead E coli treatment:yes | inhibitor:none | Sample source:murine bone marrow derived macrophages | genotype:RagA GTP mutant time (h):18 | Dead E coli treatment:yes | inhibitor:none | Sample source:murine bone marrow derived macrophages | genotype:RagA GTP mutant time (h):18 | Dead E coli treatment:yes | inhibitor:none | Sample source:murine bone marrow derived macrophages | genotype:RagA GTP mutant time (h):18 | Dead E coli treatment:yes | inhibitor:none | Sample source:murine bone marrow derived macrophages | genotype:RagA GTP mutant time (h):0 | Dead E coli treatment:no | inhibitor:none | Sample source:murine bone marrow derived macrophages | genotype:WT time (h):0 | Dead E coli treatment:no | inhibitor:none | Sample source:murine bone marrow derived macrophages | genotype:WT time (h):0 | Dead E coli treatment:no | inhibitor:none | Sample source:murine bone marrow derived macrophages | genotype:WT time (h):0 | Dead E coli treatment:no | inhibitor:none | Sample source:murine bone marrow derived macrophages | genotype:WT time (h):6 | Dead E coli treatment:yes | inhibitor:150 nM concanamycin A | Sample source:murine bone marrow derived macrophages | genotype:WT time (h):6 | Dead E coli treatment:yes | inhibitor:150 nM concanamycin A | Sample source:murine bone marrow derived macrophages | genotype:WT time (h):6 | Dead E coli treatment:yes | inhibitor:150 nM concanamycin A | Sample source:murine bone marrow derived macrophages | genotype:WT time (h):6 | Dead E coli treatment:yes | inhibitor:150 nM concanamycin A | Sample source:murine bone marrow derived macrophages | genotype:WT time (h):18 | Dead E coli treatment:yes | inhibitor:150 nM concanamycin A | Sample source:murine bone marrow derived macrophages | genotype:WT time (h):18 | Dead E coli treatment:yes | inhibitor:150 nM concanamycin A | Sample source:murine bone marrow derived macrophages | genotype:WT time (h):18 | Dead E coli treatment:yes | inhibitor:150 nM concanamycin A | Sample source:murine bone marrow derived macrophages | genotype:WT time (h):18 | Dead E coli treatment:yes | inhibitor:150 nM concanamycin A | Sample source:murine bone marrow derived macrophages | genotype:WT time (h):6 | Dead E coli treatment:yes | inhibitor:50 nM bafilomycin A1 | Sample source:murine bone marrow derived macrophages | genotype:WT time (h):6 | Dead E coli treatment:yes | inhibitor:50 nM bafilomycin A1 | Sample source:murine bone marrow derived macrophages | genotype:WT time (h):6 | Dead E coli treatment:yes | inhibitor:50 nM bafilomycin A1 | Sample source:murine bone marrow derived macrophages | genotype:WT time (h):6 | Dead E coli treatment:yes | inhibitor:50 nM bafilomycin A1 | Sample source:murine bone marrow derived macrophages | genotype:WT time (h):18 | Dead E coli treatment:yes | inhibitor:50 nM bafilomycin A1 | Sample source:murine bone marrow derived macrophages | genotype:WT time (h):18 | Dead E coli treatment:yes | inhibitor:50 nM bafilomycin A1 | Sample source:murine bone marrow derived macrophages | genotype:WT time (h):18 | Dead E coli treatment:yes | inhibitor:50 nM bafilomycin A1 | Sample source:murine bone marrow derived macrophages | genotype:WT time (h):18 | Dead E coli treatment:yes | inhibitor:50 nM bafilomycin A1 | Sample source:murine bone marrow derived macrophages | genotype:WT ADP 173027 89930 257124 108722 119119 157152 128833 214691 102788 125024 101537 99024 213431 994765 155618 170544 312638 131916 157408 242364 131047 480459 124605 113091 152135 151363 401223 221487 91131 76785 83308 138298 47148 22425 46600 41578 64152 60526 139919 46352 25183 76366 40045 19419 Thymine 126505 116886 125864 106523 116484 119474 106886 109531 121249 117121 112476 121391 108269 124723 113875 120144 104062 125704 132549 142167 109965 118808 110326 116051 111328 109749 115467 112056 112735 117221 121514 119538 126980 131265 107720 118224 94711 117543 128856 89685 84260 102174 122202 96764 UMP 475460 1115567 525010 708156 647195 666958 857071 740519 1790516 3247893 1371884 2448934 1731609 1064913 1363374 586881 1630422 1424777 1079932 900163 384829 1433526 2157514 1528171 478821 695630 497655 341262 743882 563192 1046805 668184 1008232 504507 1552807 1673590 572632 466641 206364 485976 48746 41232 80833 73004 Uracil 131645 135920 128124 135990 131324 131034 105801 112318 913494 579173 380609 367574 129865 154565 146726 116595 144508 143682 132822 150134 170387 135225 253453 142583 150297 190679 157712 159924 113215 148813 192348 148058 549499 169738 333703 406101 139343 128189 143721 114583 103841 105836 128259 113653 IMP 124422 415971 281210 218412 550023 555418 1431365 460004 2806381 3794222 635863 1138606 420180 298325 279617 254818 516074 603411 248138 305595 1102659 2395590 992108 413116 968043 1047659 1621675 822024 925726 925194 1600971 1040674 2173272 563747 1405641 2704563 267559 245015 176311 162643 71840 127385 132396 109958 Xanthine 332022 427540 150192 277667 258316 153624 335803 205123 998517 778754 293609 348968 375938 114960 525535 168506 322960 436918 409384 221098 520456 353466 933158 529286 439331 338802 162695 389792 619312 458726 607943 517290 342118 283716 916269 717330 195201 156567 90922 191647 38378 26173 46371 47208 (S)(+)-Allantoin 8585 30863 13479 34923 31459 35287 27836 15437 74929 50232 32184 64173 67103 39955 27309 28956 32627 38092 61399 32126 79926 86564 105257 46004 20821 36909 33624 41060 23514 25635 26448 24969 31575 19275 47891 61641 31141 24320 10961 14993 8631 0 9303 17032 4-Pyridoxate 29412 15812 24886 15226 17668 29100 36413 30746 77325 36498 28343 34154 38700 49536 26762 8241 33180 34346 24205 15943 41827 82296 39984 26978 18952 19927 32482 29631 24560 30407 14179 20961 91023 20722 50622 59841 6939 4422 4239 10853 2775 5195 2934 0 UDP-glucose 43893 66982 31862 46703 41780 205489 73928 56419 120858 155625 83795 161237 80874 213617 61520 50426 72058 148045 68904 51023 14967 110765 85110 58692 29858 31710 135531 33992 34632 33751 49863 54329 227312 36961 76089 119253 26314 16336 25940 15233 3257 24652 6981 2552 ADP-D-ribose 26236 76994 19214 54424 13480 106000 27613 37693 148320 203049 83080 157983 49356 175109 51036 58477 75877 176953 76720 25429 41950 290156 187899 63768 25778 40461 81063 41128 23872 20842 15600 24579 88811 15880 33569 50202 68102 83484 1035 31994 16899 0 16080 32552 Phosphate 83096130 102633300 80212120 73986260 85810630 113710500 82116050 77971130 112702300 102376500 83941280 98696090 68202020 107586500 67836380 63518530 100129900 91813340 110891100 116762600 121566700 134921300 125321800 76294230 73324010 76057480 120667300 62287340 54837540 88338220 90246980 109958400 102948300 94682340 76495290 92362180 63762080 52190350 94864320 40788730 39057100 81836230 82370980 32152440 Diphosphate 7425742 8923775 8392875 6291590 6845140 9897087 6986560 9767499 9995218 8785342 7483702 8781736 6223358 9685115 5330504 5884276 10609800 9609435 11339800 13292970 14125110 13861660 11469450 7923074 7070094 7375506 11617840 6916526 7197986 7657048 8072334 11139390 8431041 7919354 8885483 8107310 5514268 5404854 9576415 5399044 5587126 6032006 7172984 2805620 D-Glucose 98166 146003 94083 96683 153688 204748 414831 91509 361421 268664 173280 213891 195014 220264 155598 122562 108614 179017 219598 83485 214496 355662 420218 201080 99302 123170 130300 111089 88559 113625 112088 183789 285812 187732 266384 293772 138743 128345 59718 174834 119717 89588 138448 114298 D-Glyceraldehyde 3-phosphate/Glycerone phosphate 149837 126873 102824 105425 163186 124507 144896 117820 1717889 1278074 722243 1000506 129416 65871 129944 177698 116385 134613 127991 123049 480027 915363 920539 696911 121455 140392 172991 143235 148631 159691 107050 204450 597786 667151 191627 186614 161700 132468 96456 107043 119856 65486 176653 141004 2/3-Phospho-D-glycerate 46697 39226 79844 73309 48393 49886 24878 104905 119332 45003 59434 51345 22449 230121 31761 32276 130055 56844 85203 40885 65780 250704 84406 60689 86587 46703 207563 107480 110520 64546 54184 99686 668744 115173 342656 200893 21146 21679 26898 34927 14849 54566 6338 10620 Pyruvate 255160 537071 308200 319816 316780 428172 475457 280793 411613 440670 329011 562231 646700 553394 503361 353614 245078 324321 275948 231254 262166 497304 334062 308363 325134 476038 625944 335025 583380 1054900 1416138 1206940 1272140 373077 841563 1117811 565518 543884 452244 346129 230910 450063 367969 323300 Lactate 3655764 5716780 9059275 6105200 7678022 11420490 19695080 11128980 18043680 12553280 8794324 16640340 8707529 6085296 3748963 2389690 10069620 6771470 4648012 4470064 9097008 12653920 14921160 8940355 11793190 12875240 20059260 12880110 9901261 10550660 23859420 20278040 30265860 10204580 40016800 45674360 5144964 3860460 2435799 3657735 2331063 2715668 2653222 3166649 Maltose 2168 1240 2951 2303 7010 16115 7143 4093 20730 1819 13550 7855 3619 3628 1340 12276 8117 4817 4149 4240 1689 9300 17592 15823 7825 7715 3056 11982 2284 9409 15406 10059 716305 13958 3320 14701 23208 7345 4102 3899 1056 7091 2599 13114 Mannitol 74427 121496 88712 63315 179174 16402770 8236192 357374 459572 354911 263608 296218 119104 193096 98131 11722700 779927 194708 203872 106936 319690 590566 562517 184127 90887 89864 148512 69784 49657 121661 148305 195001 258686 140218 188133 287695 74231 61164 47229 1806310 39936 346696 95192 88675 D-Ribose 12357 10277 14420 6382 19027 12817 113799 15494 35097 24054 28184 16168 24312 13772 18924 13027 17914 35302 13182 8658 36256 26567 36928 26025 30030 16260 18463 25362 21478 9987 26252 16469 36963 8597 18033 23419 17133 17876 12531 18214 21155 14273 11747 17358 D-Arabitol 12367 19479 13593 3896 870162 298328 643655 406709 93458 74482 84672 70082 26872 12321 26715 9469 199780 246379 181110 304555 57370 81229 76419 84359 18929 12825 26744 16463 1247341 1461161 1367966 904169 1166681 367728 974894 1124933 1076183 1413968 1038395 1059248 188112 172366 134220 242078 Citrate 240009 327807 512491 262211 131347 230852 239148 321665 3425978 2798234 1376011 1395084 555131 9036921 353971 261902 571004 453031 244268 382415 5666222 52742160 5711796 1531971 406044 510244 5990006 557177 205712 168356 301850 284856 5209008 212693 909870 501742 155433 159090 194807 187843 63045 810647 47016 44027 2-Oxoglutarate 650719 1383681 334082 771566 142473 545218 513689 190927 180546 209852 144265 323702 1039754 1357694 1304369 1245939 256510 540190 529108 485605 185252 260514 277313 79149 151860 228531 722242 172753 184675 638036 512752 568938 136819 51157 56124 189328 116808 71798 96614 108299 35709 141056 63533 34642 2-Oxoglutaramate 23711 17469 20615 26732 25661 18348 26881 33918 29233 34302 37535 39461 33305 11701 14309 20060 23753 27397 29107 30753 27968 23380 46907 27314 30469 26296 50579 27550 37056 41449 35081 45898 59265 27981 57256 68037 40673 35661 16653 24894 11132 23454 7824 13806 Succinate 1008218 1305231 502575 607266 602804 1023328 363131 303899 2343706 2710687 1037011 1523632 2200038 2333681 646505 550636 1203004 1700716 1848086 994507 3169497 3918908 2583199 1132930 912222 970289 659097 407309 551278 914173 628575 675038 1229153 603693 860957 1231380 436660 373932 406495 243594 89803 169570 206834 126979 Fumarate 143118 314501 90484 187714 334837 2494230 1983223 196906 149125 231333 313438 197914 251029 298451 143215 1426695 231716 448215 322656 120678 132948 166610 172926 120084 170900 236327 701390 193277 307989 543805 466123 460762 497836 222584 214896 520540 201976 160654 189776 202281 131599 250845 181213 140945 Malate 3718764 6550568 1214061 4294728 9156468 13704270 11372800 2627281 2527098 4131629 6399122 4013233 4760630 6306924 2288356 2729053 2549568 7764682 6128526 2871421 2103120 3294309 3382144 1453212 3003474 5613792 14419030 2469454 3787834 10811700 9872483 9091359 10377360 4623236 2364006 11410110 3771405 3196311 2397648 2532111 1436955 5063686 4034771 2321566 2-Hydroxyglutarate/Citramalate 435826 564026 381043 796475 359286 448366 610967 314549 627053 353040 469012 1082746 1184292 1002906 1325160 889578 554075 713377 669758 677812 460516 739740 534190 214632 374715 367811 1076003 410781 143468 336053 556130 623231 604059 143553 239945 904520 243573 193799 127816 79697 45122 171393 188693 101237 D-Glucono-1-5-lactone 6-phosphate 9450 11024 5139 4900 6907 12713 7457 5320 258412 117847 47770 34599 6904 16464 2390 3769 9628 6091 5809 4194 15932 29834 57894 29871 7484 3268 29525 4277 4328 3770 5140 9000 40966 29304 19967 26235 794 3425 4109 4366 3819 21071 3773 1901 D-Erythrose 4-phosphate 1470 5269 0 2403 3487 1308 0 0 109007 55583 26836 17579 0 0 8403 3501 0 0 0 3655 3922 10310 19114 12773 5560 8070 0 9492 1606 8860 6403 16537 22130 10411 14042 8469 4706 0 0 7417 1721 0 0 0 Sedoheptulose 1-phosphate 51768 84286 134929 112016 79087 76658 185278 109840 1115537 1042298 559816 622401 99212 39511 54497 34206 113654 60286 49111 44085 328427 458701 708322 506185 128162 100420 88836 97445 118253 84236 189643 116671 535234 433736 1034040 874688 56987 34241 39073 29551 73907 54817 101515 105517 alpha-D-Ribose 1-phosphate 1279453 1240904 926620 1279911 523158 607777 432820 565432 4563462 3253239 2084679 2335363 1014918 515822 824573 371922 1218385 1522557 1296055 571553 2217405 2425530 4141668 2536986 1001186 709479 321344 618095 533207 525161 585813 523547 1387268 1088141 1420742 1233138 436527 272724 138225 314376 74731 54806 120279 122662 Ascorbate 113395 488761 140781 180837 56491 451683 173280 101263 68580 78435 81548 389788 118613 486038 433054 267066 92434 239082 66312 81164 18740 76478 43639 31988 67241 78083 854089 133021 70863 106653 80992 47175 44216 7403 26943 75561 4482 6073 6129 3577 3300 9770 3068 2506 Dehydroascorbate 30754 31271 43496 24074 0 16423 0 149916 120322 116692 54956 60731 40662 221074 28103 0 90186 48537 55392 26380 167744 962535 232356 59398 32977 39140 140909 80308 146133 48682 0 0 100461 51600 59131 25607 0 0 105333 73552 100291 9459 0 0 gamma-L-Glutamyl-L-cysteine 75041 77260 57999 59044 85676 79148 104329 62870 80786 62035 69419 86281 141672 95214 166485 62322 92234 135123 128245 47155 166925 96303 185640 83834 55143 69973 83043 93600 51642 49758 96016 96873 80666 13465 61034 73677 28370 23347 31507 19018 6347 6954 11529 16301 5-L-Glutamyl-taurine 12911 7833 6685 4613 9494 6119 6894 4856 9411 4821 8656 10191 19027 0 5601 5244 15388 8191 0 0 10804 9067 2588 4557 69353 63329 32558 61604 97346 93646 109140 98651 247774 112742 272800 360369 100608 104292 88873 83530 59079 76418 89969 85153 3-Phosphonooxypyruvate 179389 137142 205791 158245 176513 162807 189745 167642 188801 249225 192014 190908 362781 57978 223182 233186 205028 251288 197666 165693 278716 188948 225418 249880 274233 288692 178973 276352 267517 168171 177113 183913 233888 123723 329946 293065 185025 174946 147570 179153 119390 62348 118024 107687 N-Acetylneuraminate 3193026 3603140 3862868 2674601 3382590 3095758 3704185 2989449 5009575 4446500 2882637 2329937 2073909 1654118 4065824 1386817 1609242 2125612 1467411 1265268 2294866 1408119 2324978 1512418 702545 690488 718594 762611 667518 554542 1022896 591024 280326 125982 593112 287599 636845 710740 483710 441275 41340 34178 41465 50704 N-Glycoloyl-neuraminate 75394 89749 179212 121187 148205 112610 174068 160952 181267 149254 141642 133930 107710 57371 236520 96996 119095 107948 82102 118015 75601 65969 98316 83784 14716 43830 18359 36068 15490 19203 52103 32810 5439 0 26795 13318 78185 83480 57744 64166 12132 0 9969 10430 alpha-D-Glucosamine 1-phosphate 48964 57743 48795 68326 47559 55997 54744 73635 101205 84590 57538 78429 155000 67605 122984 62472 99154 112572 140279 62360 85439 48482 93257 110381 158703 154588 81076 150032 96868 73724 75684 90722 68721 44495 147662 158279 88619 78448 61493 61039 25130 13858 28873 22942 L-Arabinose 12357 10277 14420 6382 19027 12817 113799 15494 35097 24054 28184 16168 24312 13772 18924 13027 17914 35302 13182 8658 36256 26567 36928 26025 30030 16260 18463 25362 21478 9987 26252 16469 36963 8597 18033 23419 17133 17876 12531 18214 21155 14273 11747 17358 1-4-beta-D-Xylan 352954 707688 637607 869151 344152 538231 594222 724499 181610 247364 309174 591859 1025199 1063528 1249272 481689 850256 699820 1379436 699202 174592 284106 439685 128782 343938 525750 1141192 697485 195023 299560 539453 721918 200911 91162 197258 481273 330505 305724 366693 149159 116579 314279 391262 211505 UDP-N-acetyl-D-glucosamine 77705 147778 51386 77900 44766 200941 66753 63145 262490 279512 77484 196875 149497 285374 121105 94466 89667 210712 131685 70980 43189 220277 223364 77933 62645 67850 177855 63039 46687 58398 67470 96733 210496 37833 88776 165003 42975 34197 31789 25034 4567 19132 12952 6866 CMP-N-acetylneuraminate 48388 94310 37415 58268 35010 103193 41494 30646 107413 90906 39266 54493 56608 126008 44049 25710 26597 83209 36465 21887 44701 101236 43984 19874 19799 22928 81990 19450 6003 14196 20397 15818 34566 11466 19948 16121 4713 7978 8382 4586 0 4125 876 0 beta-L-Arabinose 1-phosphate 1279453 1240904 926620 1279911 523158 607777 432820 565432 4563462 3253239 2084679 2335363 1014918 515822 824573 371922 1218385 1522557 1296055 571553 2217405 2425530 4141668 2536986 1001186 709479 321344 618095 533207 525161 585813 523547 1387268 1088141 1420742 1233138 436527 272724 138225 314376 74731 54806 120279 122662 trans-4-Hydroxy-L-proline 152431 203217 168718 189840 176095 236491 235232 169133 397121 394946 235099 358497 402246 254967 290890 169911 251365 393397 287943 139014 409715 450934 453416 232026 223193 251214 190909 210755 195302 227985 276249 231866 411592 174828 345291 536800 194242 204823 104037 133465 62390 62219 98635 76645 Pantothenol 774 703 2795 460 7690 10273 9095 4300 6813 10635 7914 7302 8092 4736 3689 7760 7088 8979 19646 4797 10713 21272 19775 10020 10485 18847 5824 12183 19941 47653 44915 35707 59665 35947 49168 115152 13478 9143 10455 11326 2929 415 2287 1534 Taurine 19409090 20956430 16667620 24124520 12600260 13343870 19881710 12311380 18278090 23914100 25602370 23727480 41264320 23609790 29688840 28060450 13106440 29605410 15878630 9323505 24783250 22388190 19551160 17397100 29461950 34994790 18747530 30798000 21327700 19527410 21956850 15995790 23028670 13850840 30767900 38469600 23214600 26391420 9184785 17430680 11702080 8423839 13898990 15206120 3-Sulfino-L-alanine 7165 6544 18096 20349 6315 12892 14046 40591 31006 26682 20509 11973 10290 30075 13267 16139 61447 17739 19145 6437 12515 7300 26445 28123 25538 11378 5151 31081 31982 10905 22002 7579 38668 21191 28209 58179 18088 19598 16809 22202 5133 5707 18575 15083 L-Selenomethionine 24863 17827 24285 17038 17140 6053 11507 22974 7649 8505 5709 4532 20213 71937 3425 6475 16212 25215 8962 17956 5117 32607 9043 22832 6312 13937 30570 16394 7808 6092 2775 4565 26031 14466 9440 4952 4791 12175 13541 12232 13583 81870 15448 5073 L-Cysteate 107046 74784 90057 91327 101077 79692 78290 98222 71268 72390 91465 62862 94312 20508 74101 82466 73392 93902 75137 120529 92223 61944 71506 106456 105314 90754 66888 119943 93050 84392 86757 81969 63497 75450 94300 68182 88548 94316 101531 81816 106976 53298 99258 72439 Glycerol 3-phosphate 118865 99055 172420 182664 314011 245671 306276 399396 544693 402976 305612 422788 194981 112168 184523 157439 348424 290645 264000 232983 273417 313391 546570 394871 728387 605576 470411 714936 566941 487196 582098 507346 756019 370661 1106622 1265157 560171 626504 460585 437292 222939 242555 336842 306006 Ethanolamine phosphate 6062308 8434645 5240702 5727224 4707652 7191566 5548242 4677720 8966823 10336780 6883322 9243703 9123901 9171557 8523823 5077046 5975260 8315230 6781910 4384505 7594864 7026148 10603530 6798346 6051072 7079620 5078758 5784058 5628804 4142236 4970014 4165091 8592151 3560409 8939088 10539300 4129843 4793654 3496465 3748119 1744515 1097570 2054707 1564218 N-Methylethanolamine phosphate 29600 41635 38995 31352 34640 10880 42122 34142 94179 61565 104620 129254 123236 68139 67801 95489 42416 34190 29787 46838 130868 89674 59600 101470 43371 20045 26534 51250 37975 8157 36970 30285 124483 22416 142311 217237 34318 25521 35631 38084 6417 3870 11620 17137 Sphingosine 1-phosphate 3616 4851 5901 3662 7393 4228 2931 11883 19298 15782 5422 9225 10652 12012 8269 6315 8184 9776 8084 3964 14604 16573 9366 14067 8002 3447 6892 10267 8395 6779 6640 5837 16350 10777 19780 17621 4314 4916 3053 3306 2124 990 2578 0 sn-glycero-3-Phosphoethanolamine 456903 321341 281543 382430 376048 192499 181022 242667 1848682 2190685 1412687 1986774 1278577 748431 753583 407697 348320 554957 514246 251204 1728534 1715054 3136239 2204919 373312 370518 115821 344690 273595 195562 173079 197513 1714621 835350 2391528 2646619 169381 195585 54291 179454 129545 97611 173512 154214 Hexanoic acid (caproate) 179181 203018 213428 198187 203501 170474 195618 231864 239302 204111 221194 176436 176767 75943 256726 210390 116604 179536 211727 231997 210619 83325 239486 252411 205633 212358 116082 228344 246928 199408 259921 259660 140554 220617 231919 157125 214139 244806 244704 205571 235068 83330 243543 180620 Heptanoic acid 347516 495118 351488 441560 421553 416212 489918 292690 396428 448151 429422 475188 387605 545046 423916 368919 286631 378833 442956 374645 438042 487671 437280 335340 323422 407298 473940 373086 385769 435747 431770 402832 427383 451804 405714 481558 398202 425524 332620 311835 393277 557203 397014 462974 Octanoic acid (caprylic acid) 679924 1037807 791625 769815 1019483 848580 1089621 743238 1019695 817987 689656 1016329 900076 923379 1158238 858199 651884 841025 878929 845492 1051130 893238 827560 951744 769566 867489 983738 890177 906892 906499 935404 961941 903794 998191 920329 937812 849219 839770 744012 718831 782036 832680 1017239 1033367 Nonanoic acid (pelargonic acid) 2083911 2476543 1529978 2182551 2260097 2316979 2442271 1644032 2686745 2507544 2417613 2198018 1833829 2563912 2141502 2080583 1649800 2534674 2419524 1792944 2489216 2623914 2658600 1740382 2178196 2145639 2431706 1778004 1767194 2126763 2596730 2100587 2452011 2478824 2097847 2335153 2615849 2067161 2136698 1558041 2007734 1854586 2134703 2430312 Dodecanoic acid (lauric acid) 878902 1001191 960117 1050395 947864 1033217 1100472 811439 2939933 1156128 972030 1019102 1205008 1086745 1037705 1095585 765808 1216017 1062548 974697 1161455 1378335 1589023 1195347 1171034 1112237 1112666 827635 884215 837072 1057571 1125065 1273634 1104366 1254360 1144977 1074233 1143230 1031306 751492 1011231 932439 1000988 1185900 Tetradecanoic acid (myristic acid) 2300537 2261339 2230583 2371820 2642014 2536337 2669506 2330106 3299304 2403907 2586427 2885544 2803326 2855968 2368270 2554220 1984662 2974840 2619175 2596234 3014904 3738070 2760372 2927284 3126267 2725280 2582253 2649085 2593329 2924489 2742941 2522908 3667826 2842577 3142741 3146385 2356661 2468765 2174682 2098462 2109763 2273480 2377290 2604840 Hexadecanoic acid (palmitic acid) 26296350 28924030 21912090 26574090 24014550 24470260 25914920 23415400 32586690 26953260 27625570 25009740 30609720 24166930 29050470 28541070 22732680 25096220 27535190 26352310 24405700 30769140 25627980 24762410 27391070 26609290 24600680 26749990 23743260 19403440 29783540 27939930 31141930 24336380 29309490 28762470 26952720 26778060 22404670 24489920 21457850 23439450 25486330 24665750 Octadecanoic acid (stearic acid) 7443360 9038984 7447732 9163264 7479330 8745692 9415135 7145946 11386750 7094936 7881090 7872122 9860731 7654190 10218040 7612634 8097326 8656839 9944847 8143848 7387152 9497673 7610514 6113046 6767680 6677840 7802794 6954558 7841036 6916060 7868106 7149806 8120898 7110034 8118772 15172390 8728099 10070710 6905346 7628912 7666296 7350650 8043712 5572526 Tetradecenoic acid (myristoleic acid) 67186 87436 56930 70691 68863 80068 74962 63101 179831 119559 61393 108987 98913 81060 106168 89150 74101 84595 77282 80717 119183 187085 199711 81605 102600 97497 71584 84187 77234 73757 88402 82207 141176 84800 143918 117941 74567 59772 54614 43318 57030 66753 47141 63852 Hexadecenoic acid (Palmitoleic acid) 598288 430130 333310 456590 614106 611557 529114 635492 2686097 1636494 739119 918649 830927 766386 727988 383318 604286 1033048 1171765 537812 2737638 1873842 2116606 1052896 756860 689969 568243 595078 678581 696370 899093 731495 2144579 1139393 1945923 1627059 614962 487803 410268 424118 384855 513624 391658 473362 Octadecenoic acid (Oleic acid) 2652702 2990376 2061570 2761699 2910947 2310461 1990825 3001446 12084560 7614146 4236708 4339448 4813570 4737380 4732740 2182432 3237831 4557262 6901998 2161324 8589024 10163670 9984261 5067589 3155486 2781815 2481411 3178303 3211786 2226268 3330472 3477088 7653176 4613634 6378960 6138324 2108045 2215259 1836434 1870497 1499592 1326524 1514302 1229312 Linoleic acid ((9Z,12Z)-Octadecadienoic acid) 336353 319744 205828 282815 379340 294902 221474 311366 1383173 786646 491512 414712 500539 503852 511747 214044 317890 459180 604632 215094 1125338 865359 804553 498639 421008 371069 277087 297673 327261 386082 403324 325276 816826 345847 675296 476225 153289 182191 162107 182572 112863 123653 127234 122544 a-Linolenic acid (Octadecatrienoic acid) 11778 10876 6671 8008 16207 16306 7165 16474 91117 50503 20080 32060 21370 11079 13017 4351 24231 18872 22736 13257 82749 103097 63373 22259 13587 13185 13061 15191 11957 14825 18774 13414 34190 12484 38968 20566 10288 8851 4664 4254 4215 6071 5551 2051 Arachidonic acid (Eicosatetraenoic acid) 893274 1387554 1229729 708515 642212 763391 570919 441118 3610849 2254385 1568321 1148197 527403 540805 614928 293656 503240 868308 841468 235002 2847315 2281156 2543095 1395776 667786 788243 459572 333940 583392 774328 722193 262442 531906 470140 613254 391351 270742 222568 182176 282823 133504 168404 198472 165949 Docosahexaenoic acid 905254 955507 832790 750901 647952 570685 578084 569741 1892721 1138066 738966 666481 711405 723706 774285 480722 665732 987123 711367 281047 1625211 1431900 1467779 842936 830986 972238 815072 527000 714917 653384 992029 351039 533895 360507 778720 388541 255155 278683 170784 337265 130175 122257 171509 139604 Eicosapentaenoic acid 169287 301623 274424 163890 192964 197109 156353 104050 463075 255767 154436 175894 89939 138039 225298 85502 93767 171006 121192 42018 415872 365477 344911 124193 195257 303143 235366 117516 236126 209171 324608 97179 104479 137307 100557 74474 82505 94791 58186 87884 50829 44630 60164 44073 Dihomo-gamma-linolenic acid ((8Z-11Z-14Z)-Icosatrienoic acid) 258825 262821 245985 189334 215381 172789 136078 183258 918131 453795 248497 350518 152846 160936 229182 81623 169192 236757 227057 66033 726968 517400 611998 312827 190284 192897 135907 111960 159073 158822 179416 124880 136162 129847 199173 120295 54326 54569 47522 77588 38654 48216 42667 37686 Docosapentaenoic acid ((7Z-10Z-13Z-16Z-19Z)-Docosa-7-10-13-16-19-pentaenoic acid) 1045830 1199867 1092928 652761 642357 631158 536218 441080 1820414 1218972 788354 637725 564556 595130 685901 321275 509393 856785 680528 244885 1697530 1128963 1284528 717901 745725 930985 714295 445413 530126 588686 825286 332438 301726 280898 424762 247131 252945 271429 167365 292818 124969 155822 153566 127939 Citrate 13C1 2009 1260 6944 0 1892 1842 3342 607 0 13223 0 3173 0 0 0 0 9009 1663 1894 3031 0 0 5037 269 0 0 507 0 4481 2655 4041 0 30905 6256 0 9235 0 3163 4838 2434 2240 3526 510 0 Citrate 13C2 0 1190 5248 0 3940 10995 8969 15009 5515 16495 22701 10819 7202 70318 748 177 16936 18003 3303 16909 32230 242555 25513 18574 3107 928 40937 3202 6353 12614 1815 10834 174684 10350 21779 21564 5096 3224 10129 3230 3070 20681 0 177 Citrate 13C3 5725 5324 9428 3625 5120 507 4192 6078 0 2542 6142 0 582 3157 356 3055 1546 461 4409 5422 0 34822 1375 1260 5200 0 630 0 6527 1798 0 2051 113304 2073 5087 14324 0 2473 0 0 5166 2376 2318 4746 Citrate 13C4 3689 407 4955 0 4109 8606 3887 2628 12067 14754 7258 5896 0 3140 7754 4419 4504 0 1783 6564 16955 194561 20092 6291 4075 0 0 0 2440 6318 5588 5820 130718 1945 8443 10302 2317 5750 10821 14515 2859 5090 7679 4162 2-Oxoglutarate 13C5 33096 17575 34272 16087 40719 31121 37246 30576 34132 22180 16728 32366 18300 17495 24233 37098 27562 30188 19209 30805 25543 25888 21822 28924 18342 31134 37827 21955 29009 71788 29675 56979 28019 23977 14997 25572 22836 23979 18196 15653 17028 30291 31640 15457 Itaconate 13C3 3284567 4048452 2922071 3050610 4775965 3652464 4063003 3352663 4343010 2774174 2282238 1713855 6646360 5102162 5233636 5539938 2946751 4522268 4591702 3118659 6775080 4498320 4914206 4110691 6846146 7747286 5638784 6110114 6512954 5940458 6237310 4959866 6173462 2581163 4900724 6253122 6188028 7175782 4877156 4533531 2311378 2259630 3527785 3675258 Itaconate 13C4 125047 171218 138972 143450 331785 242690 258855 169030 209437 150548 121332 147214 251826 213607 228647 213912 158259 244989 256489 197043 287823 227908 240775 179622 285711 316064 214509 274481 284557 272178 337375 258468 294268 122867 223208 293796 281345 372552 237310 215421 106659 88421 152242 164991 Itaconate 13C5 60429 48905 62721 49800 130955 73068 88500 76389 66949 51237 69102 87957 55889 51206 55324 57359 65367 70934 91635 81958 61653 75637 55578 54486 34314 44046 45241 54773 54304 86153 74444 69467 53446 53016 52053 50632 75991 72535 63753 55405 47180 62272 69093 47647 Succinate 13C4 14244 44829 11094 28462 47546 49281 23069 12135 82405 36691 24393 25112 24772 51418 45708 9675 0 27182 18912 24163 62323 83485 69439 4798 21114 49693 50210 4759 7463 67627 37821 13101 84644 48192 29832 16240 42071 22563 26278 0 0 62215 21415 15726 Fumarate 13C4 0 0 315 3163 42982 15227 31789 3941 336 0 4848 0 368 0 0 0 3398 3532 0 3479 0 463 0 3591 0 0 0 3856 18229 45429 23850 20167 62024 13071 8257 45993 17173 15219 13910 18298 1919 8085 4007 3181 Malate 13C4 0 0 0 0 521046 334929 451934 59440 17253 14683 47302 23507 0 0 0 0 11854 116728 65592 61775 1156 4682 9302 13265 0 0 0 0 154069 625766 521378 420664 791232 233141 109830 511596 204689 159963 109879 147182 26309 154026 79658 46278 ADP 13C10 0 0 0 0 23540 13822 14083 22208 5496 2962 8825 11073 0 0 552 0 17177 8885 6753 19953 3665 7364 1976 6541 0 0 0 0 0 2327 1040 1696 0 0 0 0 3493 4654 12862 2076 408 0 0 0 AMP 13C10 0 0 345 0 362559 130502 216303 120570 91946 126632 195207 222991 0 0 0 0 75700 188507 99442 103414 129417 169601 108045 167052 0 0 0 0 23555 90541 52885 37190 8036 3231 14980 17688 117111 142100 41644 95167 2011 0 0 2452 Adenosine 13C5 0 5155 2452 0 6530 106032 77136 0 0 0 5868 9967 0 0 0 5918 3691 8208 3639 0 0 0 0 3823 0 0 0 0 0 5248 0 395 0 4047 7333 3931 3088 0 0 0 0 0 0 0 Adenine 13C5 1961 0 0 0 269794 106360 67336 70167 49927 56320 115332 109886 0 0 0 0 73623 240568 125231 49491 40754 27421 66294 89741 0 0 0 0 24604 59891 44766 34285 34227 18125 39843 42280 84384 43293 19357 36144 8171 0 15581 4936 Fructose bisphosphate 13C6 442534 1377674 879734 676382 551680 1459491 926194 622258 1023414 927555 763140 1207784 315809 1255731 516902 429702 630388 724372 1033345 806794 370341 1177931 903542 272060 327470 388218 1676221 447733 468010 1200125 762759 922722 1272412 1296245 193743 718723 510366 318475 369350 317374 719051 1073314 863443 285898 Phosphoglycerate 13C3 14183 10060 7532 7954 10545 22945 13688 10559 52877 47302 8501 23741 15842 47628 23040 3398 20583 43916 26201 12255 30082 99650 57192 26332 0 3801 27351 2912 3523 6047 3216 6315 31714 0 0 15257 1772 0 2262 0 0 2910 0 0 Sedoheptulose 1-phosphate 13C7 183161 187443 171642 156476 260016 193712 160086 168602 507206 425820 286890 305081 198316 227297 215492 147688 195815 336161 284748 127661 375116 453586 581302 348845 216221 213965 113637 237954 236357 147821 137416 148340 182290 105168 192069 170609 136897 162018 83219 198255 82828 45318 67799 30969 Ribose phosphate 13C5 4219 0 0 0 118672 64684 50497 75083 152064 135686 134423 166338 0 5075 0 4667 81515 118782 92999 61312 76070 112312 136929 142129 0 0 0 0 71921 120264 106170 89283 34350 19264 17020 29981 41586 32891 32946 34191 6847 0 668 6766 Glutathione 13C10 53930 30544 7290 47140 32255 15725 28796 0 295750 242023 175882 189111 112357 76751 45824 33365 0 53207 53641 5287 150556 304732 422227 208101 34602 38563 39560 29116 29255 30592 28599 23455 594482 339518 374637 670611 36490 33676 0 4393 17386 39268 38362 27488 MS_METABOLITE_DATA_END #METABOLITES METABOLITES_START metabolite_name KEGG ID m/z RT ADP C00008 426.0220 0.71 Thymine C00178 125.0342 0.59 UMP C00105 323.0285 0.59 Uracil C00106 111.0186 0.60 IMP C00130 347.0396 0.60 Xanthine C00385 151.0250 0.64 (S)(+)-Allantoin C02350 157.0357 0.65 4-Pyridoxate C00847 182.0428 0.64 UDP-glucose C00029 565.0475 0.55 ADP-D-ribose C01882 558.0637 0.60 Phosphate C00009 96.9681 0.59 Diphosphate C00013 176.9349 0.59 D-Glucose C00031 179.0554 0.63 D-Glyceraldehyde 3-phosphate/Glycerone phosphate C00118 168.9887 0.62 2/3-Phospho-D-glycerate C00631 184.9847 0.65 Pyruvate C00022 87.0073 0.60 Lactate C01432 89.0229 0.60 Maltose C00208 341.1089 0.66 Mannitol C00392 181.0709 0.64 D-Ribose C00121 149.0456 0.60 D-Arabitol C01904 151.0612 0.61 Citrate C00158 191.0187 0.67 2-Oxoglutarate C00026 145.0131 0.60 2-Oxoglutaramate C00940 144.0289 0.60 Succinate C00042 117.0179 0.58 Fumarate C00122 115.0023 0.61 Malate C00149 133.0128 0.61 2-Hydroxyglutarate/Citramalate C02630 147.0292 0.59 D-Glucono-1-5-lactone 6-phosphate C01236 257.0070 0.59 D-Erythrose 4-phosphate C00279 199.0007 0.59 Sedoheptulose 1-phosphate C06222 289.0331 0.58 alpha-D-Ribose 1-phosphate C00620 229.0114 0.59 Ascorbate C00072 175.0247 0.62 Dehydroascorbate C05422 173.0076 0.63 gamma-L-Glutamyl-L-cysteine C00669 249.0548 0.60 5-L-Glutamyl-taurine C05844 253.0496 0.59 3-Phosphonooxypyruvate C03232 182.9669 0.68 N-Acetylneuraminate C00270 308.0985 0.59 N-Glycoloyl-neuraminate C03410 324.0935 0.59 alpha-D-Glucosamine 1-phosphate C06156 258.0381 0.58 L-Arabinose C00259 149.0455 0.60 1-4-beta-D-Xylan C02352 131.0342 0.59 UDP-N-acetyl-D-glucosamine C00043 606.0742 0.55 CMP-N-acetylneuraminate C00128 613.1399 0.56 beta-L-Arabinose 1-phosphate C03906 229.0114 0.58 trans-4-Hydroxy-L-proline C01157 130.0497 0.61 Pantothenol C00864 218.1029 0.69 Taurine C00245 124.0060 0.62 3-Sulfino-L-alanine C00606 152.0014 0.62 L-Selenomethionine C05335 195.9913 0.65 L-Cysteate C00506 167.9961 0.66 Glycerol 3-phosphate C00093 171.0054 0.59 Ethanolamine phosphate C00346 140.0107 0.60 N-Methylethanolamine phosphate C01210 154.0262 0.60 Sphingosine 1-phosphate C06124 378.2400 3.02 sn-glycero-3-Phosphoethanolamine C01233 214.0478 0.61 Hexanoic acid (caproate) C01585 115.0751 0.65 Heptanoic acid C17714 129.0908 1.93 Octanoic acid (caprylic acid) C06423 143.1065 2.01 Nonanoic acid (pelargonic acid) C01601 157.1222 2.09 Dodecanoic acid (lauric acid) C02679 199.1696 2.34 Tetradecanoic acid (myristic acid) C06424 227.2012 2.59 Hexadecanoic acid (palmitic acid) C00249 255.2326 2.97 Octadecanoic acid (stearic acid) C01530 283.2640 3.55 Tetradecenoic acid (myristoleic acid) C08322 225.1855 2.39 Hexadecenoic acid (Palmitoleic acid) C08362 253.2170 2.64 Octadecenoic acid (Oleic acid) C00712 281.2483 3.02 Linoleic acid ((9Z,12Z)-Octadecadienoic acid) C01595 279.2328 2.69 a-Linolenic acid (Octadecatrienoic acid) C06427 277.2172 2.48 Arachidonic acid (Eicosatetraenoic acid) C00219 303.2328 2.59 Docosahexaenoic acid C06429 327.2330 2.49 Eicosapentaenoic acid C06428 301.2173 2.41 Dihomo-gamma-linolenic acid ((8Z-11Z-14Z)-Icosatrienoic acid) C03242 305.2487 2.77 Docosapentaenoic acid ((7Z-10Z-13Z-16Z-19Z)-Docosa-7-10-13-16-19-pentaenoic acid) C16513 329.2488 2.61 Citrate 13C1 C00158 192.0228 0.6631375 Citrate 13C2 C00158 193.025 0.6870168 Citrate 13C3 C00158 194.031 0.6464354 Citrate 13C4 C00158 195.0316 0.6651838 2-Oxoglutarate 13C5 C00026 150.0297 0.5951046 Itaconate 13C3 C00490 132.0289 0.58915 Itaconate 13C4 C00490 133.032 0.5835452 Itaconate 13C5 C00490 134.0349 0.5931454 Succinate 13C4 C00042 121.0301 0.6372334 Fumarate 13C4 C00122 119.016 0.611162 Malate 13C4 C00149 137.0263 0.6047935 ADP 13C10 C00008 436.0555 0.7278184 AMP 13C10 C00020 356.089 0.6101578 Adenosine 13C5 C00212 271.1049 0.6272187 Adenine 13C5 C00047 139.0628 0.6487604 Fructose bisphosphate 13C6 C00354 345.0125 0.6415796 Phosphoglycerate 13C3 C00631 187.9984 0.6424828 Sedoheptulose 1-phosphate 13C7 296.0535 0.6206983 Ribose phosphate 13C5 C00620 234.0281 0.5889141 Glutathione 13C10 C00051 316.1161 0.6185545 METABOLITES_END #END