#METABOLOMICS WORKBENCH juliehaines_20241125_183122 DATATRACK_ID:5399 STUDY_ID:ST003606 ANALYSIS_ID:AN005926 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 Positive C18 CH:CHROMATOGRAPHY_TYPE Reversed phase CH:INSTRUMENT_NAME Thermo Vanquish CH:COLUMN_NAME Phenomenex Kinetex C18 (150 x 2.1mm,1.7um) CH:SOLVENT_A 100% water; 0.1% formic acid CH:SOLVENT_B 100% acetonitrile; 0.1% formic acid CH:FLOW_GRADIENT 0-0.5 min 5% B, 0.5-1.1 min 5-95% B, 1.1-2.75 min hold at 95% B, 2.75-3 min CH:FLOW_GRADIENT 95-5% B, 3-5 min hold at 5% B CH:FLOW_RATE 450 uL/min CH:COLUMN_TEMPERATURE 45 CH:SAMPLE_INJECTION 6 uL #ANALYSIS AN:ANALYSIS_TYPE MS #MS MS:INSTRUMENT_NAME Thermo Q Exactive Orbitrap MS:INSTRUMENT_TYPE Orbitrap MS:MS_TYPE ESI MS:ION_MODE POSITIVE MS:MS_COMMENTS Resolution 70,000, scan range 65-900 m/z, maximum injection time 200 ms, MS:MS_COMMENTS microscans 2, automatic gain control (AGC) 3 x 10^6 ions, source voltage 4.0 kV, MS:MS_COMMENTS capillary temperature 320 C, and sheath gas 45, auxiliary gas 15, and sweep gas MS:MS_COMMENTS 0 (all nitrogen). Data converted to mzXML using RawConverter. Metabolites were MS:MS_COMMENTS annotated and integrated using Maven in conjunction with the KEGG database. #MS_METABOLITE_DATA MS_METABOLITE_DATA:UNITS peak area MS_METABOLITE_DATA_START Samples 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 spermidine 13C7 236447.7 233347.1 252458.1 188080.4 361264.2 320394.8 330727.8 403261.8 169815.3 199415.2 113152.5 167321.8 422022.5 425695.5 468409.5 414828.1 0 0 0 64749.31 51463.92 77570.24 696181.7 966845 834377.8 23747.29 16621.02 25745.79 995941.3 1026904 1030040 0 0 0 66487.66 68711.45 57946.55 781115.8 622935.2 678526.4 27200.05 34745.42 13055.77 1154432 1371016 1246690 0 4243.299 0 60209.45 43848.09 65383.43 156839.8 92232.66 325920.2 220160.8 125632.3 175446.4 620544 749557.1 657295.7 0 0 3167.933 64150.12 59360.89 67967.24 67528.44 32505.32 68471.41 98820.77 122426.2 97915.79 624867.2 347146.8 352267.5 Glutathione 13C10 20181.21 15148.68 11062.5 10580.97 0 3452.523 0 3342.978 0 0 0 0 0 0 0 0 0 0 0 87793.9 96421.85 72427.8 3537.569 3868.738 4041.579 2797.338 3314.53 2920.983 0 0 0 0 0 0 92313.06 96012.44 107134.9 0 3542.522 270101.5 0 2632.222 1603.959 0 0 0 0 0 0 122167.2 124817.4 127088 0 0 0 4847.414 4487.017 0 0 0 3883.577 0 0 0 149342.6 211950.7 149498.1 0 0 0 4480.949 10062.58 8969.481 0 0 4157.348 Alanine 508358 439649 418313 363502 381958 638693 389003 440862 517190 485142 407642 362982 521519 608150 550086 602073 969387 817573 655373 381227 317653 357301 588745 636762 486361 606692 406087 453754 781195 731058 588466 671558 529782 550973 344972 377892 309610 579195 526185 12976960 543999 484329 404343 504841 535055 496625 1101835 958403 1078639 493514 472661 642954 517691 583167 665110 723716 736218 770061 1282336 1037081 1195950 1040748 1156242 921405 514276 563969 524660 907892 647834 563441 947759 885749 894634 1230238 1153625 798902 Arginine 2006366 2108810 1661842 1630551 1185060 1465324 1513339 1158481 930384 735560 774902 801269 1398883 1411017 1348648 1241505 2219725 1755058 1319105 2691920 2167320 2396394 1904848 2283409 1685524 1078947 638839 588949 1883699 1737951 1429454 1559971 1583365 1453339 2923870 2729922 2772296 2599444 2123302 71024700 1233324 753490 578497 1350919 1235116 1310631 3340889 3044948 2456402 3097899 2973274 2448617 3745596 3294588 3144529 1689119 1828446 1807188 3311049 2977898 3067477 2689708 2941182 2927576 4128833 3667218 3214521 5679646 4063645 4911596 2397476 2409974 1963961 4185686 3061963 2946653 Asparagine 110883 81520 57986 56774 100366 119187 94760 175834 77166 76871 60480 67855 210622 240897 207997 209377 133212 110240 117838 127249 113213 105289 118082 114427 92959 137192 115200 143725 164375 169244 132521 107611 97637 93025 127981 77417 103895 153808 107129 1312470 137776 100622 57753 127807 137450 114718 147198 162244 162402 216361 195572 157503 101243 101626 114006 277861 220466 160606 253710 238636 243208 193077 178323 131727 194213 191122 172692 164097 123107 118647 240798 222738 173074 231002 231706 160071 Aspartate 186876 188441 192598 191504 201226 219336 151235 272685 175157 126873 115167 151560 107132 134133 136758 128960 467723 575063 391869 268974 202889 278446 267508 254980 178411 186677 117053 170399 148263 207659 241231 294813 332328 246628 210307 201854 173318 253977 204077 8721700 274282 178462 146429 126465 151091 144298 1407664 1596249 1614437 261976 357694 194266 230091 263434 370463 144134 149796 155607 227283 218316 229777 721054 964701 687042 275782 217211 247066 236864 178635 225070 130633 149827 117288 209657 209403 138596 Cysteine 673007 625554 482644 525525 891063 898170 691151 890990 693445 623677 512236 572972 993329 1236101 1170359 1136034 1210554 1335669 1405291 1022505 909369 844372 978268 1215550 1047313 878669 687938 971174 1538435 1564093 1518731 877364 955774 961467 894942 892646 667079 1195616 1099448 1035169 794958 955172 619403 1261774 1344527 1305507 1326412 1298326 983757 1388882 1262127 1139493 1189591 1043214 1124504 1413078 1490381 1319975 2115986 2025209 2099120 1002163 1116792 914787 1751627 1656497 1386829 1313681 1246975 1503806 1304916 1557588 1213139 1864804 1618605 1578441 Glutamate 1729408 1797970 1902878 1916879 2722929 3276634 2345131 2950923 2881472 2696696 2373446 2416453 3150326 4367892 4049085 5100201 7766488 7563958 5864130 3890053 3325234 4621458 3487947 4283628 4004834 2415358 1819670 2416494 4867982 4945724 4672024 5183366 6287670 5313794 3214290 3196975 2587766 3592077 3150860 8676380 2532317 2626309 1684644 3315917 4011745 3640761 6807698 6135104 6855324 2358292 3463994 2420674 3170123 3658083 4673860 4510290 5195834 5501882 7036632 6907902 7788448 6149854 7515128 5889138 3524487 2945030 2393533 3809376 3177192 4841208 4812748 5820298 4435046 7247638 6756216 5063718 Glutamine 280685 243277 257526 268825 150087 330373 263956 166519 351365 385810 234519 240503 601680 717577 513575 625571 1671836 1753651 1073595 366730 273967 290046 573854 352683 440876 641818 331866 420362 824560 886652 701357 1086752 858211 809817 315837 329906 269285 669663 509229 741269 475812 608322 388085 795909 890294 727981 931322 959853 1009900 351182 302523 289818 537082 504268 557083 859034 823714 1021601 1448694 1419156 1461759 1040437 916712 855058 463046 343960 284159 848373 625878 696658 956086 1114338 825408 1434028 1449621 1084836 Histidine 179303 104587 123196 90534 102407 117463 112671 119645 120557 90585 68748 90698 121453 123556 103320 109180 147279 108341 157189 267764 172963 233194 165477 205169 142693 173197 150289 130580 122533 189767 149055 139263 97406 145791 241086 290005 181050 192466 134429 2440934 388595 127968 120919 110861 123387 142665 238897 245894 166375 222929 153878 324546 201017 191554 208012 194306 239097 274541 256154 317137 414725 280636 326415 223925 257069 225056 196015 267731 158435 177398 203763 220080 224965 268745 201053 205118 Leucine 1136899 838959 712733 528065 710581 853409 1339322 916985 936614 606910 595444 755822 742323 820130 1011496 702864 1321744 1301795 1154646 1687639 1373061 1819506 2180064 3492679 1824779 1662909 727056 1116606 1295222 1298704 898158 2062866 1726479 2038946 2086102 1859089 1566850 2662787 1577308 110391900 1400027 876867 641367 1157482 1218732 1124328 4308035 3089827 2887083 2762709 1898697 4933150 3219809 2988381 2223876 1931160 1582880 1496362 2761366 2500096 1947757 5128682 3635160 3797447 2496874 2336434 1506642 2726007 1637993 1999656 2107412 1846013 1830672 2390198 1803354 1542121 Methionine 194221 110330 164838 127008 151076 212441 178107 141869 92285 109415 92825 92345 137253 135437 136084 137572 288583 249602 214427 505285 536364 524523 421281 834666 368157 219988 165600 125195 206832 179511 150939 662482 315596 340535 503746 524257 454807 637305 420292 12107240 214575 178345 164417 206781 149131 260210 1278530 929981 738977 554685 331092 442876 954566 777191 267881 308736 382929 320365 564496 339327 374374 1535616 1163960 1036715 531854 495950 293437 679083 427704 385157 301843 338766 298195 277413 278553 417511 Phenylalanine 154459 110071 124008 81756 130619 163122 192209 166506 87831 105925 78621 94593 114397 100818 136448 134080 220727 137626 187315 305679 262556 178158 258852 449241 240752 205234 129016 116165 146980 164821 120661 216632 198082 220349 234729 329104 291710 300206 256731 41892010 295504 130953 123914 2206 116559 208195 610952 415285 357843 355712 229292 771448 361299 426509 246289 239030 255877 235947 459594 257203 330275 798631 624091 667980 236254 378255 249414 465395 274124 227557 230069 239594 251134 223118 202347 228813 Proline 6286326 6177452 8577907 8789846 1588392 2204280 1596374 1573718 1441575 1769357 1243321 1421927 1578259 1628379 1500106 1828837 2073076 1561839 1432376 14475520 21418000 21104450 1627341 1708809 1388986 2272426 2429912 1915228 1704285 1761473 1501669 1099233 953166 1002168 18292400 18648490 14817800 1882909 1679222 68338880 3240971 2235521 2213505 1252033 1177292 1197671 2182835 1941674 1780337 2292447 1801619 3961927 2100335 1865006 1610328 2429968 2410996 2962466 3307309 3447692 3535789 2819918 2382506 2109387 2787368 2464390 2097046 2506982 2351330 2218924 3276160 3372727 2910666 3291723 2692554 3010573 Serine 94100 65209 63683 53641 50561 94604 77086 83415 75837 88697 53494 102665 47080 98716 71482 83588 128624 106125 158446 121966 80615 114244 134454 141318 71197 139682 104513 138930 117254 237916 171931 138729 95728 108757 95623 127844 67677 151637 110846 21049260 437098 84230 69446 129295 150992 125985 173466 198325 151522 108526 105590 200011 109139 101216 122356 169900 152571 194501 150544 192026 326371 303742 246125 210546 131862 107143 100705 163036 153069 75279 185811 139924 143396 201792 204007 168470 Threonine 90783 68710 84143 69948 70620 89954 65792 80362 72454 77998 66170 84605 76346 109019 89689 89387 130001 116499 112085 153754 112927 132307 134067 160213 105868 119590 88765 120764 130521 142872 140991 113175 126021 94943 162779 159378 157434 168213 151051 14994150 244856 104430 94935 135421 123666 138959 205804 197703 154153 140620 133076 175235 127347 127849 122687 185691 186452 182340 225195 228391 267556 256551 255814 230469 161592 143540 100988 144565 136961 140540 187060 181569 166015 190536 189017 172101 Tryptophan 297228 190109 221344 162462 172974 213587 249168 218087 220140 197204 187384 159428 176436 184941 233643 216377 253415 236227 278637 397893 311322 294934 282761 352656 263187 328327 236941 212736 271070 264267 222117 192964 139019 169527 408621 325913 405520 340726 290897 4880522 853793 177347 168751 234134 203054 259430 391461 443210 284638 380305 437975 918942 403367 393735 308897 488798 485766 510241 665087 622061 506955 563700 434664 502049 471141 494665 369263 533135 603334 354313 547594 506335 493408 434373 438240 469641 Tyrosine 325218 190624 205468 226568 195738 195030 228262 212527 140336 159379 121543 148079 145641 128320 146495 118420 305720 206136 207555 574978 618534 494183 250796 305795 231377 294020 279122 244466 228869 240740 201218 243142 192013 177884 504561 650206 658567 325134 286289 42541550 473424 233930 231960 216154 199900 223083 416332 396335 392630 430859 337604 1094722 422588 347592 335781 391474 271021 380320 429699 465626 448329 628053 556445 401164 390415 412805 325133 396185 352856 298469 351383 303817 319006 325567 262329 372076 Valine 2463055 2225982 2247370 2103877 2431446 1803949 1953535 3563990 2033119 1909058 1798547 2125591 1887492 2009917 2028268 1655142 2564583 2108083 1993684 3632793 3199941 3956651 2150870 2149507 2011586 1982119 2268630 1995782 2299088 2281719 2097794 2307070 2126260 1966402 3759562 3928609 3625918 2366485 2474779 108714800 2653298 2158930 2027838 2073474 2125960 2253461 3071817 2936575 2966222 2792068 2392422 6654146 2971517 2512338 2293674 3062925 2508447 3032204 3473011 3535224 3484604 3947889 3305233 2822778 2672285 2554399 2425896 2790112 2601860 2187333 2877768 2734637 2528173 3175225 3000243 3368039 Adenosine 2226677 1060914 1883711 1763569 1366143 4915786 2363061 2242038 918759 4408648 3050288 2375221 557050 801796 2818135 1413344 10172640 5133792 3710672 2895754 3374846 2660519 2663790 7539484 2943214 1800838 1422262 1431283 1856789 2071245 1244521 5657368 6254502 6645154 1456533 1262169 1415476 3082838 1987392 1258818 723342 813106 572806 1028254 780719 3925168 6316914 5418214 5295000 1541097 876932 723584 2147993 1705695 1981329 3247235 1059723 5150592 3983854 2394928 1568964 4655442 3505906 1610956 841532 1039165 625585 967800 610598 558823 973283 1585999 1197608 2192660 1267756 5441058 Adenine 1480139 802200 1540600 1450240 906844 2780976 983857 1281443 473296 1639111 1083985 848641 202626 270554 699660 425815 1881524 1231613 803174 2668284 4030811 2908872 1359842 2968982 1283677 1465637 1856926 1290113 533429 688869 373088 1116743 1186113 1274720 1759272 1222595 1197391 1367654 970441 1004184 952021 1125026 866107 357018 286326 1015627 1295401 1343200 1335851 1726908 1120587 916296 1303450 1007795 982349 1129513 768275 2634835 961836 616243 535383 1173462 914276 483032 1178631 1157938 849250 798900 706420 540413 752671 900672 708101 749663 508426 1211421 Xanthine 223328 237541 135417 167548 208483 175496 193807 200345 140452 132820 126069 140723 220633 183581 243418 248424 249550 197556 255449 196375 200927 215110 216451 149973 124879 191912 186978 154505 226775 230792 267301 206219 252314 272174 252622 250268 224582 182194 193583 17205800 252459 212259 230205 222591 214349 289317 382099 300576 241792 170961 313884 340939 205699 199437 324737 311971 301174 301631 287097 378420 355387 290436 334949 322512 286435 266870 284073 180982 222655 285191 283026 251251 318538 327943 295426 285004 Allantoate 116502 67036 91627 62508 60112 48840 58912 69365 82953 95714 59886 88394 66069 48326 47048 54842 31137 33552 80989 32654 15410 31089 23305 23587 18272 131063 87645 81709 41134 77896 80475 13190 24232 29472 40910 49562 24822 29805 25206 5132588 329881 66936 58975 46774 40007 38430 17695 27793 30949 24497 11573 78955 13069 13050 58641 88652 83893 83168 53082 59478 124577 79089 76429 58721 45068 79960 49755 30690 72883 18665 143136 102445 92516 58235 52827 52156 5-Hydroxyisourate 3990 6375 0 4634 0 4286 8034 6303 6651 11613 6181 8831 12594 26949 14439 28459 60821 57163 44748 8091 4875 6161 31562 10966 13089 18064 11112 14601 38107 44573 35836 20054 21321 21588 10603 5143 6730 17997 7154 34074 9249 23124 13018 18670 33192 25336 49329 39123 33416 8647 13439 3839 14998 14643 21748 47779 51402 47501 81139 92219 107288 35008 28885 19449 17653 7496 15692 32115 28729 30288 48661 55285 32722 66854 68787 58204 Nicotinamide 2402153 1666934 2342408 2078571 2466940 2141778 1811741 2672993 1555508 1769718 1331988 1268556 2714701 3281713 3064407 3539503 7292390 4605368 5786526 7200090 9180709 5420750 4548278 6048148 4864636 5375324 5170930 4508990 3644023 3828759 3865993 6145748 5313300 4835606 4180253 5573858 4314338 3685796 3311393 6154146 5367625 4821958 4370770 4011836 3822975 5203918 15178240 11120800 10824010 10412740 8860741 8897141 7399554 9082453 5820794 9099619 12953830 11289980 14063010 10118910 12143530 11223140 10865030 9471986 5980018 7484050 6971250 8334270 6545774 6612318 6614518 11236720 8388584 7480788 9368785 8414073 NAD+ 163063 134340 155950 138854 161951 100048 109284 143894 11764 19071 13480 16940 19789 34066 11880 26723 128740 166228 123021 394277 374625 413686 35072 23728 42613 46785 57613 79674 10922 9998 16161 45423 128964 97537 423473 421023 367240 45594 81257 63279 75745 70624 94126 21527 11539 35034 162475 157256 159162 136807 247637 185895 69833 79611 99004 37698 89912 41679 42510 83535 78207 50606 115508 128184 289708 257719 265749 158982 148003 218712 80549 89894 101020 72661 70927 63508 5-Oxoproline 577821 605481 602444 629476 851194 993770 784226 906360 831164 888006 715513 814782 1150869 1654708 1375060 1763924 2808796 2823400 2167404 1225003 1004980 1359767 1230444 1317915 1236458 1026034 684416 847290 1728934 1719976 1673132 1814186 2224587 1933706 1028368 904629 829176 1292348 1198318 61181930 1259284 962963 677480 1325332 1530250 1534774 2215239 2305430 2446932 775676 1071166 840164 1188805 1317771 1502533 1720066 1724893 1791665 2697235 2798115 2893953 2279952 2618879 2018615 1177533 990444 820942 1478289 1070345 1694730 1869344 1946707 1702305 2823558 2520723 2006583 Cys-Gly 73100 40184 48598 40299 110329 81988 104704 102786 61941 53595 44498 56720 92608 131287 115787 112872 194815 156832 138439 137327 155682 127168 65676 91692 88098 83489 56079 87997 118236 98213 111526 86677 118713 103449 112118 126129 125566 64543 39211 108241 87397 79248 60633 78236 96375 51068 297725 259668 263605 123739 158886 94221 122722 108943 165483 166416 159723 169973 277335 263321 283556 184579 225869 192134 116733 154443 116593 149232 108621 159109 162405 191420 173548 223543 187200 176098 gamma-L-Glutamyl-L-cysteine 136023 93222 90526 80718 90211 90145 89941 101196 128780 118588 98934 117415 167431 236160 228095 258962 140341 163955 132334 232030 186722 166674 77901 112600 107950 157008 111073 153722 176955 120589 144244 75374 83378 88694 218911 177365 225663 89354 63484 127178 117866 148128 141090 120970 156683 122478 159665 142596 135926 186408 210483 130694 94796 77461 115448 150622 194981 170280 248225 355655 258784 120627 130065 114265 167629 236897 200282 126500 95014 119528 176536 201169 177705 217348 188898 197579 gamma-Glutamyl-Se-methylselenocysteine 62247 29728 31321 12875 26963 2238 17790 21619 35863 40889 16843 32102 19328 27463 7079 20002 6476 4104 19209 6062 5196 3542 4453 11831 0 47356 11919 27972 11689 27514 18333 0 4133 9782 13693 13696 2598 2345 0 1748194 111406 15792 16732 14084 11409 21105 2236 3497 3014 6773 0 49354 0 0 9838 35632 38653 25027 11377 16903 61831 20590 34445 38674 15489 14042 0 8047 45027 6601 47925 38258 52037 29504 7358 15678 gamma-L-Glutamyl-D-alanine 41080 48457 42995 49189 110871 107906 97296 133505 45997 50185 39406 47360 46958 63633 62204 70353 52016 61960 56376 86151 81488 78232 83628 113665 80006 49432 48857 53690 31594 39009 33764 58260 63011 46400 84718 81172 84611 104656 96424 365976 63692 53611 48637 46909 32866 51013 110111 102333 99051 80460 88563 79861 115875 117256 92004 38591 44724 43041 52468 84619 69299 134002 127213 97404 100866 92040 82647 134485 93790 115235 57787 59337 56760 63326 43579 58224 gamma-Glutamyl-gamma-aminobutyrate 34494 24273 22502 24737 51883 51636 49143 42738 24131 33338 29901 30002 49294 55963 54211 50979 104308 86608 78762 122336 135208 107170 137726 206905 166000 48704 43368 38787 37611 63077 48607 106054 97470 116448 137959 149571 153423 165877 191441 503184 55868 47670 33817 72247 76226 74558 250613 236160 168869 162330 170241 140062 249943 261446 131770 89974 71731 91689 155960 114123 148102 212173 213462 185804 145940 185152 131673 273747 229035 219298 103972 105484 83101 119825 113022 134057 gamma-L-Glutamylputrescine 38301 28464 19540 24505 32470 66811 56924 37213 11239 24219 26925 31398 11312 26194 34679 45140 58234 77202 76584 114933 68939 97108 140941 287596 136187 41334 26789 27034 41559 43995 26776 133167 85862 113699 88090 147618 89896 227878 170216 280520 40685 39142 13137 44293 37244 84836 210771 155464 165852 123376 108444 110138 177125 188099 187287 81864 79584 82946 85430 110190 58628 236577 238555 195485 136259 112052 112894 201273 147396 157732 58140 69070 38804 75211 67339 94202 (5-L-Glutamyl)-L-glutamine 3447 4784 3503 2379 6083 12797 5125 6128 5550 6842 0 6202 3931 8356 9415 10328 26945 18173 23156 17672 14230 15455 24475 45208 27560 2881 7284 10382 10350 9011 11309 22095 13067 15666 17397 20108 25023 30391 35304 48825 5047 4444 5537 16150 13855 19771 57863 46046 36173 26348 33069 17903 34651 41128 30388 12933 18826 17740 30131 34769 26430 36550 40509 30082 30658 34441 30306 47669 29598 33673 18405 13048 14443 19308 20800 19402 L-Homocysteine 35220 48751 124301 132787 74594 88951 31646 21927 70372 107029 100485 85895 26071 11581 29395 78469 144180 68739 91233 114581 83521 76844 89040 91386 35874 30639 196862 43910 66748 132546 35920 70899 24053 27608 112370 29744 60998 101953 119122 34822 36678 149494 40275 82285 21830 132121 52933 51417 99452 33552 71501 19580 77547 97871 23875 124962 32276 133556 30546 33642 34524 132495 28301 58130 97010 61622 30758 93698 88615 104056 85794 19183 38411 16307 107291 89773 S-Adenosyl-L-methionine 28877 30418 18378 40843 28422 29819 19472 35166 19685 17644 7099 8576 36320 40168 30474 58292 80363 92566 86899 94911 56173 110295 56835 70678 69207 46536 32600 46776 40991 39928 66489 62983 66607 52092 80336 79206 59142 32867 16761 44726 65796 58327 53670 48602 16011 40784 38657 49091 51837 28115 29634 28097 16180 18160 38632 75630 43395 53643 89929 82675 68823 20214 31967 44346 47080 48541 36112 29815 14041 38520 54544 61335 41972 52918 70353 66050 Ornithine 240467 150563 190069 107672 145397 83235 118810 140183 169552 142474 103396 175841 96870 105114 82402 106450 82230 56362 130907 73701 57842 80324 59357 47369 41074 166092 130947 148935 84553 176923 145390 46395 39281 58056 16085 103082 62561 48058 49968 17819850 681215 98626 123211 121091 80601 76698 58151 65626 59652 64634 81418 203976 44926 48549 106857 208038 203373 114039 119753 91305 279997 149238 158830 131033 98881 124960 84465 102958 131837 42765 299619 200178 229643 88542 117010 152981 L-Citrulline 271082 301886 283350 316825 318632 292043 211217 343419 941182 1020268 702767 904744 652503 987612 626100 894889 329997 320449 306118 421184 367262 385547 353031 345124 303407 930890 713320 862604 677656 861678 804720 218147 255246 228595 312865 342113 290200 259893 254484 1373636 976397 784013 660160 678496 821493 819480 259368 205296 253879 241961 225108 276493 178847 160288 184645 1348385 1304358 1240536 1359446 1774370 1692818 487190 405563 277122 272209 259452 322006 336597 311247 364442 1984750 1814305 1515327 1709245 1818000 1424331 Cadaverine 148374 172082 100676 119851 143851 152573 100700 140287 149628 164624 141038 138995 152879 163216 148864 212594 0 0 0 168592 176700 176073 112069 112441 99993 127053 118750 143511 288448 259158 276444 0 0 0 192957 169810 143068 127049 139464 158771 154287 119380 62779 177485 220671 239273 0 0 0 340291 362945 346599 166501 210872 197479 284319 412428 376928 327229 491576 868585 0 9754 0 480475 449561 372998 130895 158679 168819 253383 284839 232363 228788 304288 268661 Putrescine 783790 847945 568696 628717 810363 832583 685309 1020207 582215 489047 470451 510859 310420 329214 371989 525851 145239 161464 169866 926940 1054980 852301 244842 343246 284454 849279 832466 966805 238709 243264 520523 99921 136231 139755 897277 976382 821492 289192 285828 591593 1035314 997396 571505 161672 210266 209033 174501 130575 149103 1011706 1019164 1162940 239157 249362 310238 945915 1123548 1058761 418994 501960 714624 129475 168558 119305 1254891 1002602 1214162 255615 217907 250699 849177 1064603 840126 259788 299092 225478 Spermidine 2308320 2052937 2534708 1843322 6217382 6404774 7121226 7625316 4148358 4116787 2521349 3875683 9518732 8642555 10015310 9983163 10567540 11979750 13035630 2137306 1564984 1793969 4948491 6803046 5676998 2450150 1715751 2333764 6592518 6333696 6245700 10786200 11116870 12552850 1664915 1831033 1894900 5491732 4574874 4895365 2641461 3803081 1765687 7435786 8172868 6857412 8412033 9912513 9415252 617766 326731 943741 1347493 893915 2488205 7309594 4953803 5665142 9067004 10279100 9087917 10384140 10848690 9919669 616912 478650 707916 614260 288856 709270 3389116 3240437 3225305 8449359 5342132 5312024 Spermine 7545 13161 18895 20188 86985 163291 174570 111834 22349 45741 21428 36427 106593 246893 273481 60099 162693 760828 249047 3880 21249 4586 49030 65925 42068 7800 13284 3482 30651 45105 47923 2053819 1290431 1364806 3618 10811 9581 84856 25442 27353 2737 18547 7350 145902 168111 33049 54959 90692 62566 3021 2713 2007 6182 4885 6903 6326 13980 13457 16008 23695 29112 54757 134985 137990 3839 4514 1834 7032 4929 6896 4885 2266 10651 100807 19823 12601 Creatine 1384108 1317502 2123108 1873791 5498024 7359738 3868668 5038356 3633823 5532514 2740458 2818781 4667148 6163130 5419536 6541566 10347300 7584952 7543598 2059755 3621591 2584013 3798457 4122941 3890423 3085737 3175044 2741514 5583672 5180808 4243898 5744994 6107776 6634166 1040834 824020 830674 2782950 3292522 4303944 2414790 3070684 2046605 3964623 3996755 4241754 9694841 8744740 10971550 1857291 2930719 6394228 3997534 4394958 3684921 5926342 5410618 6809074 8773380 7501522 7694282 11047670 9756316 7966270 4205188 3533470 2678192 4959002 5786914 5689164 6822192 7559882 6844336 8335048 8213082 10785040 Creatinine 41943 21378 51183 19854 59813 71271 49828 584611 54273 62815 37813 50474 39529 66265 47832 58694 84565 54387 64502 27835 41669 37543 37832 40682 34831 51797 39559 38476 56796 61946 55260 39597 51264 43650 18141 19207 15596 40281 40897 6120550 170844 46587 52546 50874 35475 54318 51410 50443 64876 30025 35673 67741 58146 53075 47907 64368 62356 65427 67228 71255 81151 68268 71574 69392 49358 47113 31144 58025 49455 56863 75785 53680 66192 62351 62040 85271 4-Acetamidobutanoate 23223 16555 25540 22739 32650 36776 15415 36598 23889 26269 27607 30885 34176 37426 32095 29257 54297 48367 37447 28917 29833 15397 24127 28834 28061 19031 23053 23932 37462 29791 19262 37716 55752 34997 18946 22624 28080 25119 27547 49766 21919 28450 22336 29628 26421 25921 29023 25834 32175 20065 43852 179742 9639 32378 17212 33402 29978 26300 32891 31922 34580 25837 15615 23655 24648 19060 21129 19793 26649 21746 33331 36347 12912 30738 35133 31928 N-Acetyl-L-citrulline 44270 15082 17494 4269 38986 44498 18209 41755 0 4060 1918 2491 7383 4703 5748 3677 18007 17636 17641 34076 39653 28222 42702 100493 41410 8065 6002 5907 5661 7798 4289 42951 25246 36297 30811 31952 32664 69144 54878 78512 6590 3776 2703 19351 16371 20266 41144 43966 41207 31347 21333 32002 57054 61927 34954 7193 12085 4113 24921 18975 7903 86967 59519 45184 36282 33837 25656 56293 50344 38392 14422 9486 12078 12285 14665 18997 N-Acetylornithine 28628 15535 30229 21402 30467 49860 40649 39887 22657 33864 30506 34332 18490 27614 39295 26095 96304 77687 70385 100695 146051 98575 194493 330913 175285 46164 48028 39757 46699 46190 43201 225401 114405 142751 128327 160993 148813 242987 250981 6575592 60362 41065 35093 66126 66341 74330 286610 237406 203589 187918 134343 154401 307131 234092 163638 63537 68789 88289 102063 103246 103724 383018 312033 241272 164968 177202 128411 265364 213622 221526 65636 80040 57875 87787 82196 100211 Guanidinoacetate 69290 72097 87715 101862 230400 241201 151653 266077 83226 74835 66105 68902 62430 83900 86870 105055 190167 204489 150725 98736 97982 81986 179000 170265 130280 25865 34012 30105 47965 75181 55588 136024 155766 147740 59854 50761 70732 160902 158788 185830 30869 30471 27751 59176 67055 65453 161225 160084 148287 47552 64209 56627 53684 87441 81983 52865 75497 58023 75229 75536 84792 232498 223360 251803 145925 131320 125716 170082 177761 187401 103855 123654 100735 131592 170388 101285 L-Methionine S-oxide 83814 45862 28851 22556 17130 38516 75740 64544 19780 38081 19628 18187 52693 56512 68427 17578 36445 26218 23163 24763 140666 27749 42182 37302 129183 96014 33951 77883 26449 16180 67900 34259 114956 105971 30868 160576 54218 39852 50607 1319043 64069 23972 28565 25510 77464 32708 218894 47952 56674 145199 19136 118993 57550 68655 118990 34014 83316 40429 125596 108504 108828 68333 234607 164674 40048 47792 121207 51929 57462 34608 35330 117474 90355 126973 33327 45092 Indole-3-acetate 219550 151510 120925 142011 235792 164397 316094 154425 105235 72556 99110 76735 148817 120432 156120 132735 632228 391983 335052 84932 74994 45010 182774 136734 148259 142535 75810 69240 156441 98061 105822 190723 156448 194513 71172 111827 125641 239950 188049 204823 56289 66417 39906 64774 67935 63501 176367 167464 201036 142894 132422 110401 241864 201400 115424 172623 172405 112621 224238 201078 134458 184998 162537 215072 169720 149854 112698 399832 259806 220164 207139 196891 303407 138612 142654 121074 Indolepyruvate 18628 7031 3035 5181 11241 8255 14304 10713 6791 2913 6099 5633 8396 0 3941 3466 11058 9398 11387 34886 26680 22415 11853 18248 10969 18195 14477 9676 9810 7308 8420 13682 5554 6745 32210 32687 39782 15610 7864 1185804 22046 10801 10079 5361 6364 8143 19551 17906 7984 15015 5907 63940 23222 13509 15290 15071 19360 17585 22494 27025 17657 30013 27661 21513 14500 15897 13667 25011 24634 8795 21429 22568 15651 14988 11986 10665 kynurenine 5034 3582 14748 5273 15145 68319 17764 14379 4407 40517 6766 24274 5215 17587 4901 33406 33654 32606 31914 6733 10979 6268 22929 27584 15712 3678 5035 3694 11931 18280 2829 27424 11377 21566 8947 4105 3585 14875 13095 96632 6833 5539 10834 24084 10394 29399 22981 20364 40798 3499 4854 12420 5560 6914 2600 41169 9151 26311 17616 22491 27085 52841 29874 27566 8847 5914 3153 11479 3629 8322 6017 4640 7659 7124 19794 36505 N-formyl kynurenine 3164 5313 4978 2239 10690 17027 13808 13658 10181 3588 21778 28060 6496 9240 7579 19598 36220 24271 33758 27247 29163 28639 49848 113398 44719 7410 0 8636 15268 43187 9216 56439 28932 32678 35607 34666 40184 67004 62872 102550 2918 53804 17150 20815 20344 60360 80941 61862 35315 35290 33338 33478 80076 75065 33569 17684 6301 33118 36925 32568 13936 57839 53543 56068 51176 57212 40853 58720 50488 57397 14137 16121 19796 20372 25827 35451 Anthranilate 40846 29157 42785 65362 45854 60490 40595 36337 33252 47486 38590 41862 31746 38978 39934 34131 101111 56379 61882 62277 83555 86253 62692 68999 46295 34537 39629 37456 37844 56339 45738 44466 40877 43356 78626 84475 69320 43118 79669 286701 41078 40030 45139 40273 37350 48874 60753 73149 66148 61641 64336 230107 72495 71337 64237 46744 39587 60609 47595 55349 66410 73245 67132 63018 61874 56190 52678 89645 68224 69869 47584 48077 47384 63683 54485 56504 Picolinic acid 454970 310067 389161 328024 229325 170527 185107 198608 134537 127055 139982 129902 142773 115916 122254 141288 107502 106265 112495 968957 935769 516271 172576 183904 171530 388181 428634 286307 145190 146886 139027 109763 99849 104670 536642 897579 681033 141736 161707 185030 398972 322139 395791 136951 120715 152115 125994 115893 122413 504527 402464 521145 110160 160354 126036 175002 221938 230236 181521 129260 158566 114885 119553 113077 315431 459517 435480 187615 168989 160319 202780 224559 216112 141807 161311 150433 g-Oxalo-crotonate 152939 70682 134047 108866 126255 184612 155534 168874 88936 163007 92787 102351 198362 150625 210275 226583 456027 253879 399874 229227 368671 215603 185016 313259 207455 177641 147452 106706 156527 145062 154647 409401 299053 326451 135109 201806 166575 173213 113938 3043374 131541 100571 85815 92065 79177 150943 1072739 735472 1063690 333101 285208 426854 352648 447993 207393 318354 378610 480226 515596 398455 325297 1454268 1050379 1012172 238802 392861 258969 384668 276227 274696 360498 480302 528280 326199 326075 498540 Acetylcholine 136610 115462 155241 127492 403883 381192 314526 355984 230322 274498 213703 219963 196176 209670 205925 223345 480154 407549 392186 297721 373322 304166 630662 592569 499148 173392 202949 218454 298257 229408 232755 214906 300804 328243 227596 218279 255942 606887 791761 475938 155508 187709 125169 222575 200393 271877 673531 747870 764875 269140 377599 1001812 413403 501734 366921 383523 391149 621886 600988 586891 612124 825085 694150 654131 409531 424171 307113 550953 462207 522648 375517 466138 409465 385429 485942 557157 acetyl-carnitine 334306 195085 214439 182189 945692 813228 802922 704610 109666 120780 90233 112843 175663 208827 196712 214383 586296 374534 354048 224504 315896 188756 679873 703766 785957 124618 113096 104958 252696 195682 240949 151118 181020 225264 139719 177961 205386 655178 645473 546807 134395 89321 71105 176699 167430 193365 380950 305994 390494 325036 495798 2958909 818474 853865 638002 230057 221581 245844 466720 364400 436032 458759 439672 361845 552070 679525 600922 1495503 1328118 1393394 332983 330127 335013 401431 374413 455041 propionyl-carnitine 32853 23758 45496 49251 183333 86581 117083 232566 11363 12967 19103 19513 11003 31497 30291 36213 154900 137016 160718 85574 108863 75913 120646 224564 208850 32589 33669 47581 32670 36131 24461 80724 86058 107994 48196 66145 76282 109983 162323 245612 54641 34191 29831 45371 51358 51362 326119 247557 297443 171635 319313 264500 314780 387336 449151 89875 97513 97720 168555 166874 92269 214810 282370 186312 279273 318118 328141 297519 258912 424775 55186 70180 92545 73469 75896 77518 butanoyl-l-carnitine 34005 32625 34914 33870 30205 44358 38746 38448 22944 31876 41832 31284 32871 40291 28014 31790 32752 29747 37790 30415 38044 29793 33532 21955 33204 35634 41420 41199 31612 34864 36495 35143 31357 33571 43846 37681 30746 53303 30777 138861 32410 47370 30367 15925 31901 45856 27063 34206 39904 37086 45693 36779 33142 35736 32922 35297 34063 32951 36089 28670 40071 45588 34655 30422 35922 33225 35238 33975 52668 43302 37558 30537 32882 31445 33925 35188 MS_METABOLITE_DATA_END #METABOLITES METABOLITES_START metabolite_name KEGG ID m/z r.t. spermidine 13C7 C00750 153.1885 0.5673313 Glutathione 13C10 C00051 318.1241 0.7073272 Alanine C00041 90.0557 0.64 Arginine C00062 175.1191 0.62 Asparagine C00152 133.0606 0.64 Aspartate C00049 134.0449 0.65 Cysteine C00097 122.0274 0.66 Glutamate C00025 148.0605 0.65 Glutamine C00064 147.0763 0.64 Histidine C00135 156.0769 0.61 Leucine C00123 132.1021 0.75 Methionine C00073 150.0578 0.79 Phenylalanine C00079 166.0860 1.44 Proline C00148 116.0710 0.67 Serine C00065 106.0504 0.64 Threonine C00188 120.0658 0.65 Tryptophan C00078 205.0970 1.72 Tyrosine C00082 182.0810 0.69 Valine C00183 118.0866 0.67 Adenosine C00212 268.1035 0.69 Adenine C00147 136.0618 0.69 Xanthine C00385 153.0400 0.62 Allantoate C00499 177.0609 0.61 5-Hydroxyisourate C11821 185.0314 0.64 Nicotinamide C00153 123.0556 0.85 NAD+ C00003 664.1152 0.67 5-Oxoproline C01879 130.0499 0.65 Cys-Gly C01419 179.0485 0.69 gamma-L-Glutamyl-L-cysteine C00669 251.0692 0.74 gamma-Glutamyl-Se-methylselenocysteine C05695 313.0323 0.62 gamma-L-Glutamyl-D-alanine C03738 219.0975 0.67 gamma-Glutamyl-gamma-aminobutyrate C15767 233.1131 0.69 gamma-L-Glutamylputrescine C15699 218.1497 0.60 (5-L-Glutamyl)-L-glutamine C05283 276.1188 0.67 L-Homocysteine C00155 136.0409 1.74 S-Adenosyl-L-methionine C00019 399.1443 0.61 Ornithine C01602 133.0973 0.61 L-Citrulline C00327 176.1029 0.65 Cadaverine C01672 103.1234 0.59 Putrescine C00134 89.1080 0.59 Spermidine C00315 146.1651 0.57 Spermine C00750 203.2228 0.55 Creatine C00300 132.0770 0.66 Creatinine C00791 114.0665 0.66 4-Acetamidobutanoate C02946 146.0811 0.69 N-Acetyl-L-citrulline C15532 218.1134 0.67 N-Acetylornithine C00437 175.1077 0.68 Guanidinoacetate C00581 118.0615 0.65 L-Methionine S-oxide C02989 166.0530 0.68 Indole-3-acetate C00954 176.0704 1.91 Indolepyruvate C00331 204.0631 0.69 kynurenine C00328 209.0900 0.58 N-formyl kynurenine C02700 237.0897 0.67 Anthranilate C00108 138.0548 0.67 Picolinic acid C10164 124.0395 0.88 g-Oxalo-crotonate C03453 159.0276 0.88 Acetylcholine C01996 146.1176 0.67 acetyl-carnitine C02571 204.1230 0.69 propionyl-carnitine C03017 218.1386 0.69 butanoyl-l-carnitine C02862 232.1542 1.76 METABOLITES_END #END