#METABOLOMICS WORKBENCH juliehaines_20241125_132154 DATATRACK_ID:5397 STUDY_ID:ST003605 ANALYSIS_ID:AN005924 PROJECT_ID:PR002231 VERSION 1 CREATED_ON December 5, 2024, 7:25 pm #PROJECT PR:PROJECT_TITLE Macrophages recycle phagocytosed bacteria to fuel immunometabolic responses PR:PROJECT_SUMMARY Macrophages specialize in phagocytosis, a cellular process that eliminates PR:PROJECT_SUMMARY extracellular matter, including microbes, through internalization and PR:PROJECT_SUMMARY degradation. Despite the critical role of phagocytosis during bacterial PR:PROJECT_SUMMARY infection, the fate of phagocytosed microbial cargo and its impact on host cell PR:PROJECT_SUMMARY is poorly understood. Here, we reveal that ingested bacteria constitute an PR:PROJECT_SUMMARY alternative nutrient source that skews immunometabolic host responses. Tracing PR:PROJECT_SUMMARY stable isotope-labelled bacteria, we found that phagolysosomal degradation of PR:PROJECT_SUMMARY bacteria provides carbon atoms and amino acids that are recycled into various PR:PROJECT_SUMMARY metabolic pathways, including glutathione and itaconate biosynthesis, and PR:PROJECT_SUMMARY satisfy macrophage bioenergetic needs. Metabolic recycling of PR:PROJECT_SUMMARY microbially-derived nutrients is regulated by the nutrient sensing mTORC1 and PR:PROJECT_SUMMARY intricately tied to microbial viability. Dead bacteria, as opposed to live ones, PR:PROJECT_SUMMARY are enriched in cyclic- adenosine monophosphate (AMP), sustain the cellular AMP PR:PROJECT_SUMMARY pool and subsequently activate AMP protein kinase (AMPK) to inhibit mTORC1. PR:PROJECT_SUMMARY Consequently, killed bacteria strongly fuel metabolic recycling and support PR:PROJECT_SUMMARY macrophage survival, but elicit decreased reactive oxygen species (ROS) PR:PROJECT_SUMMARY production and a reduced IL-1β secretion compared to viable bacteria. These PR:PROJECT_SUMMARY results reveal a novel insight into the fate of engulfed microbes and highlights PR:PROJECT_SUMMARY a microbial viability-associated metabolite that triggers host metabolic and PR:PROJECT_SUMMARY immune responses. Our findings hold promise for shaping immunometabolic PR:PROJECT_SUMMARY intervention in various immune-related pathologies. PR:INSTITUTE University of Colorado Anschutz Medical Campus PR:LABORATORY Lab of Angelo D'Alessandro in collaboration with lab of Johan Garaude (INSERM, PR:LABORATORY Fr) PR:LAST_NAME Haines PR:FIRST_NAME Julie PR:ADDRESS 12801 E 17th Ave, Room 1303, Aurora, Colorado, 80045, USA PR:EMAIL julie.haines@cuanschutz.edu PR:PHONE 3037243339 #STUDY ST:STUDY_TITLE Global metabolomics and tracing of E coli-derived metabolites following ST:STUDY_TITLE engulfment of heat-killed bacteria by wild type or RagAGTP-deficient bone marrow ST:STUDY_TITLE derived macrophages. ST:STUDY_SUMMARY Global metabolomics and 13C-tracing analysis of wild type or RagA-deficient bone ST:STUDY_SUMMARY marrow derived macrophages exposed to heat-killed uniformly 13C-labelled E. coli ST:STUDY_SUMMARY in a trans-well system for 6h or 18h. ST:INSTITUTE University of Colorado Anschutz Medical Campus ST:LAST_NAME Haines ST:FIRST_NAME Julie ST:ADDRESS 12801 E 17th Ave, Room 1303, Aurora, Colorado, 80045, USA ST:EMAIL julie.haines@cuanschutz.edu ST:PHONE 3037243339 #SUBJECT SU:SUBJECT_TYPE Cultured cells SU:SUBJECT_SPECIES Mus musculus SU:GENDER Not applicable #SUBJECT_SAMPLE_FACTORS: SUBJECT(optional)[tab]SAMPLE[tab]FACTORS(NAME:VALUE pairs separated by |)[tab]Raw file names and additional sample data SUBJECT_SAMPLE_FACTORS - CT 389 n°1 genotype:WT | treatment:none | time (h):18 | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=F97-01- SUBJECT_SAMPLE_FACTORS - CT 389 n°2 genotype:WT | treatment:none | time (h):18 | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=F97-02- SUBJECT_SAMPLE_FACTORS - CT 389 n°3 genotype:WT | treatment:none | time (h):18 | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=F97-03- SUBJECT_SAMPLE_FACTORS - CT 390 n°1 genotype:WT | treatment:none | time (h):18 | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=F97-04- SUBJECT_SAMPLE_FACTORS - CT 390 n°2 genotype:WT | treatment:none | time (h):18 | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=F97-05- SUBJECT_SAMPLE_FACTORS - CT 390 n°3 genotype:WT | treatment:none | time (h):18 | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=F97-06- SUBJECT_SAMPLE_FACTORS - Dead 6h 389 n°1 genotype:WT | treatment:dead bacteria | time (h):6 | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=F97-07- SUBJECT_SAMPLE_FACTORS - Dead 6h 389 n°2 genotype:WT | treatment:dead bacteria | time (h):6 | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=F97-08- SUBJECT_SAMPLE_FACTORS - Dead 6h 389 n°3 genotype:WT | treatment:dead bacteria | time (h):6 | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=F97-09- SUBJECT_SAMPLE_FACTORS - Dead 6h 390 n°1 genotype:WT | treatment:dead bacteria | time (h):6 | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=F97-10- SUBJECT_SAMPLE_FACTORS - Dead 6h 390 n°2 genotype:WT | treatment:dead bacteria | time (h):6 | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=F97-11- SUBJECT_SAMPLE_FACTORS - Dead 6h 390 n°3 genotype:WT | treatment:dead bacteria | time (h):6 | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=F97-12- SUBJECT_SAMPLE_FACTORS - Dead 18h 389 n°1 genotype:WT | treatment:dead bacteria | time (h):18 | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=F97-13- SUBJECT_SAMPLE_FACTORS - Dead 18h 389 n°2 genotype:WT | treatment:dead bacteria | time (h):18 | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=F97-14- SUBJECT_SAMPLE_FACTORS - Dead 18h 389 n°3 genotype:WT | treatment:dead bacteria | time (h):18 | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=F97-15- SUBJECT_SAMPLE_FACTORS - Dead 18h 390 n°1 genotype:WT | treatment:dead bacteria | time (h):18 | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=F97-16- SUBJECT_SAMPLE_FACTORS - Dead 18h 390 n°2 genotype:WT | treatment:dead bacteria | time (h):18 | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=F97-17- SUBJECT_SAMPLE_FACTORS - Dead 18h 390 n°3 genotype:WT | treatment:dead bacteria | time (h):18 | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=F97-18- SUBJECT_SAMPLE_FACTORS - CT 477 n°1 genotype:Cre RagA KO | treatment:none | time (h):18 | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=F97-19- SUBJECT_SAMPLE_FACTORS - CT 477 n°2 genotype:Cre RagA KO | treatment:none | time (h):18 | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=F97-20- SUBJECT_SAMPLE_FACTORS - CT 477 n°3 genotype:Cre RagA KO | treatment:none | time (h):18 | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=F97-21- SUBJECT_SAMPLE_FACTORS - CT 479 n°1 genotype:Cre RagA KO | treatment:none | time (h):18 | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=F97-22- SUBJECT_SAMPLE_FACTORS - CT 479 n°2 genotype:Cre RagA KO | treatment:none | time (h):18 | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=F97-23- SUBJECT_SAMPLE_FACTORS - CT 479 n°3 genotype:Cre RagA KO | treatment:none | time (h):18 | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=F97-24- SUBJECT_SAMPLE_FACTORS - Dead 6h 477 n°1 genotype:Cre RagA KO | treatment:dead bacteria | time (h):6 | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=F97-25- SUBJECT_SAMPLE_FACTORS - Dead 6h 477 n°2 genotype:Cre RagA KO | treatment:dead bacteria | time (h):6 | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=F97-26- SUBJECT_SAMPLE_FACTORS - Dead 6h 477 n°3 genotype:Cre RagA KO | treatment:dead bacteria | time (h):6 | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=F97-27- SUBJECT_SAMPLE_FACTORS - Dead 6h 479 n°1 genotype:Cre RagA KO | treatment:dead bacteria | time (h):6 | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=F97-28- SUBJECT_SAMPLE_FACTORS - Dead 6h 479 n°2 genotype:Cre RagA KO | treatment:dead bacteria | time (h):6 | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=F97-29- SUBJECT_SAMPLE_FACTORS - Dead 6h 479 n°3 genotype:Cre RagA KO | treatment:dead bacteria | time (h):6 | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=F97-30- SUBJECT_SAMPLE_FACTORS - Dead 18h 477 n°1 genotype:Cre RagA KO | treatment:dead bacteria | time (h):18 | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=F97-31- SUBJECT_SAMPLE_FACTORS - Dead 18h 477 n°2 genotype:Cre RagA KO | treatment:dead bacteria | time (h):18 | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=F97-32- SUBJECT_SAMPLE_FACTORS - Dead 18h 477 n°3 genotype:Cre RagA KO | treatment:dead bacteria | time (h):18 | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=F97-33- SUBJECT_SAMPLE_FACTORS - Dead 18h 479 n°1 genotype:Cre RagA KO | treatment:dead bacteria | time (h):18 | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=F97-34- SUBJECT_SAMPLE_FACTORS - Dead 18h 479 n°2 genotype:Cre RagA KO | treatment:dead bacteria | time (h):18 | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=F97-35- SUBJECT_SAMPLE_FACTORS - Dead 18h 479 n°3 genotype:Cre RagA KO | treatment:dead bacteria | time (h):18 | Sample source:murine bone marrow derived macrophages RAW_FILE_NAME(raw file name)=F97-36- #COLLECTION CO:COLLECTION_SUMMARY BMDMs were seeded at 2.5E6 cell/well in a non-tissue treated 6-well plate (2 CO:COLLECTION_SUMMARY wells per condition) the day before the experiment. To harvest, BMDMs were CO:COLLECTION_SUMMARY washed with cold PBS and harvested with 5 mM EDTA in PBS, frozen as dry cell CO:COLLECTION_SUMMARY pellet, and stored at -80˚C until processing. CO:SAMPLE_TYPE Macrophages #TREATMENT TR:TREATMENT_SUMMARY Preparation of macrophages: Murine bone marrow-derived macrophages (BMDMs) were TR:TREATMENT_SUMMARY generated as described previously, in RPMI 1640 supplemented with M-CSF (30% TR:TREATMENT_SUMMARY mycoplasma-free L929 cell supernatant, NCBI Biosample accession # SAMN00155972) TR:TREATMENT_SUMMARY and 10% FBS, plus 100 µg/ml penicillin, 100 µg/ml streptomycin, 10 mM HEPES, 1 TR:TREATMENT_SUMMARY nM sodium pyruvate and 50 µM 2-mercaptoethanol (all from Gibco). For TR:TREATMENT_SUMMARY Tg.hUbC-cre-ERT2+/T::Rragaf/f and RagAGTP/delta mice, tamoxifen was added to the TR:TREATMENT_SUMMARY culture on day 2 or 3 to a final concentration of 1 µg/ml in order to induce TR:TREATMENT_SUMMARY CRE expression. BMDMs were used on day 5 to 7 after seeding. Period of TR:TREATMENT_SUMMARY differentiation of the cells, concentration of cells when replating and TR:TREATMENT_SUMMARY time-lapse between replating and stimulation with bacteria were important TR:TREATMENT_SUMMARY parameters to maintain metabolic backgrounds homogenous between experiments. TR:TREATMENT_SUMMARY Preparation of viable and killed U-[13C]Bacteria: ThyA- E. coli were grown TR:TREATMENT_SUMMARY overnight with shaking in LB supplemented with thymidine (500 µg/ml) and TR:TREATMENT_SUMMARY trimethoprim (50 µg/ml), diluted 1/40, and grown until log-phase [optical TR:TREATMENT_SUMMARY density at 600 nm (OD600) of 0.8-1.2]. Bacteria were washed with phosphate TR:TREATMENT_SUMMARY buffer saline (PBS) to remove LB salts before addition to cells. For labeling of TR:TREATMENT_SUMMARY bacteria, 10 µl of an overnight cultured of thyA- E. coli was added to 20 ml of TR:TREATMENT_SUMMARY a filtered M9 minimal medium salts (Life Technologies) supplemented with 1 mM TR:TREATMENT_SUMMARY thiamine, 1 mM MgSO4, 0.1 M CaCl2, 500 µg/ml thymidine, 50 µg/ml trimethoprim, TR:TREATMENT_SUMMARY and 0.5% U-[13C6] glucose (Campro Scientific). Bacteria were grown for 72h, TR:TREATMENT_SUMMARY washed with PBS and subjected to heat-killing by re-suspension in PBS and TR:TREATMENT_SUMMARY subsequently incubation at 60˚C for 60-90 min. For antibiotic killing, bacteria TR:TREATMENT_SUMMARY were incubated for 6h to 12h with Streptomycin or Gentamycin (50 µg/ml). TR:TREATMENT_SUMMARY Bacteria were kept at 4˚C until use. Efficient killing was confirmed by TR:TREATMENT_SUMMARY overnight plating on LB-agar plates. Treatment of macrophages: 2E6 BMDMs were TR:TREATMENT_SUMMARY plated 12-16h prior stimulation in non-tissue cultured treated 6-well plate (BD TR:TREATMENT_SUMMARY Falcons). Cells were then stimulated with live or killed labelled-E. coli at MOI TR:TREATMENT_SUMMARY 50, centrifuged at 2000 rpm for 5min. BMDMs were incubated for 5 min and washed TR:TREATMENT_SUMMARY with PBS to remove non-ingested bacteria and further incubated for 6h or 18h. #SAMPLEPREP SP:SAMPLEPREP_SUMMARY Metabolites from frozen pellets were extracted at 4e6 cells per mL using ice SP:SAMPLEPREP_SUMMARY cold 5:3:2 methanol:acetonitrile:water (v/v/v) with vigorous vortexing at 4 SP:SAMPLEPREP_SUMMARY degrees C followed by centrifugation as described for 10 min at 18,000 g. SP:SAMPLEPREP_SUMMARY Supernatants were maintained at 4°C until analysis that same day. SP:PROCESSING_STORAGE_CONDITIONS 4℃ SP:EXTRACT_STORAGE -80℃ #CHROMATOGRAPHY CH:CHROMATOGRAPHY_SUMMARY 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 CT 389 n°1 CT 389 n°2 CT 389 n°3 CT 390 n°1 CT 390 n°2 CT 390 n°3 Dead 6h 389 n°1 Dead 6h 389 n°2 Dead 6h 389 n°3 Dead 6h 390 n°1 Dead 6h 390 n°2 Dead 6h 390 n°3 Dead 18h 389 n°1 Dead 18h 389 n°2 Dead 18h 389 n°3 Dead 18h 390 n°1 Dead 18h 390 n°2 Dead 18h 390 n°3 CT 477 n°1 CT 477 n°2 CT 477 n°3 CT 479 n°1 CT 479 n°2 CT 479 n°3 Dead 6h 477 n°1 Dead 6h 477 n°2 Dead 6h 477 n°3 Dead 6h 479 n°1 Dead 6h 479 n°2 Dead 6h 479 n°3 Dead 18h 477 n°1 Dead 18h 477 n°2 Dead 18h 477 n°3 Dead 18h 479 n°1 Dead 18h 479 n°2 Dead 18h 479 n°3 Factors genotype:WT | treatment:none | time (h):18 | Sample source:murine bone marrow derived macrophages genotype:WT | treatment:none | time (h):18 | Sample source:murine bone marrow derived macrophages genotype:WT | treatment:none | time (h):18 | Sample source:murine bone marrow derived macrophages genotype:WT | treatment:none | time (h):18 | Sample source:murine bone marrow derived macrophages genotype:WT | treatment:none | time (h):18 | Sample source:murine bone marrow derived macrophages genotype:WT | treatment:none | time (h):18 | Sample source:murine bone marrow derived macrophages genotype:WT | treatment:dead bacteria | time (h):6 | Sample source:murine bone marrow derived macrophages genotype:WT | treatment:dead bacteria | time (h):6 | Sample source:murine bone marrow derived macrophages genotype:WT | treatment:dead bacteria | time (h):6 | Sample source:murine bone marrow derived macrophages genotype:WT | treatment:dead bacteria | time (h):6 | Sample source:murine bone marrow derived macrophages genotype:WT | treatment:dead bacteria | time (h):6 | Sample source:murine bone marrow derived macrophages genotype:WT | treatment:dead bacteria | time (h):6 | Sample source:murine bone marrow derived macrophages genotype:WT | treatment:dead bacteria | time (h):18 | Sample source:murine bone marrow derived macrophages genotype:WT | treatment:dead bacteria | time (h):18 | Sample source:murine bone marrow derived macrophages genotype:WT | treatment:dead bacteria | time (h):18 | Sample source:murine bone marrow derived macrophages genotype:WT | treatment:dead bacteria | time (h):18 | Sample source:murine bone marrow derived macrophages genotype:WT | treatment:dead bacteria | time (h):18 | Sample source:murine bone marrow derived macrophages genotype:WT | treatment:dead bacteria | time (h):18 | Sample source:murine bone marrow derived macrophages genotype:Cre RagA KO | treatment:none | time (h):18 | Sample source:murine bone marrow derived macrophages genotype:Cre RagA KO | treatment:none | time (h):18 | Sample source:murine bone marrow derived macrophages genotype:Cre RagA KO | treatment:none | time (h):18 | Sample source:murine bone marrow derived macrophages genotype:Cre RagA KO | treatment:none | time (h):18 | Sample source:murine bone marrow derived macrophages genotype:Cre RagA KO | treatment:none | time (h):18 | Sample source:murine bone marrow derived macrophages genotype:Cre RagA KO | treatment:none | time (h):18 | Sample source:murine bone marrow derived macrophages genotype:Cre RagA KO | treatment:dead bacteria | time (h):6 | Sample source:murine bone marrow derived macrophages genotype:Cre RagA KO | treatment:dead bacteria | time (h):6 | Sample source:murine bone marrow derived macrophages genotype:Cre RagA KO | treatment:dead bacteria | time (h):6 | Sample source:murine bone marrow derived macrophages genotype:Cre RagA KO | treatment:dead bacteria | time (h):6 | Sample source:murine bone marrow derived macrophages genotype:Cre RagA KO | treatment:dead bacteria | time (h):6 | Sample source:murine bone marrow derived macrophages genotype:Cre RagA KO | treatment:dead bacteria | time (h):6 | Sample source:murine bone marrow derived macrophages genotype:Cre RagA KO | treatment:dead bacteria | time (h):18 | Sample source:murine bone marrow derived macrophages genotype:Cre RagA KO | treatment:dead bacteria | time (h):18 | Sample source:murine bone marrow derived macrophages genotype:Cre RagA KO | treatment:dead bacteria | time (h):18 | Sample source:murine bone marrow derived macrophages genotype:Cre RagA KO | treatment:dead bacteria | time (h):18 | Sample source:murine bone marrow derived macrophages genotype:Cre RagA KO | treatment:dead bacteria | time (h):18 | Sample source:murine bone marrow derived macrophages genotype:Cre RagA KO | treatment:dead bacteria | time (h):18 | Sample source:murine bone marrow derived macrophages L-alanine 2398671 2173583 1740760 1459862 1485360 1409885 1659682 1813988 1998247 2256048 2850081 2933972 2028519 1985614 1682037 1114767 1306945 1489618 2121478 2048795 2107169 2756726 2961572 3785302 3597853 3492602 3588736 2364161 2814285 3525299 2137276 2520140 2627262 2718826 2064210 2794349 L-arginine 1195578 1182562 1029681 795083.7 913833 957318.7 2005812 1857038 2007912 2644985 2727224 3136553 1684793 1465523 1498254 1144778 1105402 1535598 1183194 1070290 1116262 1334112 1485054 2030137 2915120 3078306 2977834 2493320 2898357 2751480 799903.2 866443.8 1109256 768187.5 739416.3 1003182 L-aspartate 194002.1 415952.7 203997.3 209233.3 177841.5 188972.6 300334.1 297906 404959.4 399137.9 499363.7 462530 326746.8 382480.7 368135 200067.6 357839.6 315970.3 807136.9 478862.8 430575 565440.7 762063.8 565877 433108.8 518201.2 658479 401932 437975.2 400805.5 754419.8 976562.8 1119288 1050138 767066.1 1179805 L-cysteine 253681.8 771177.2 650961.9 574525.5 649471.1 546235 1095408 1192671 1341488 1468716 1609277 1806968 1207996 1404131 1149318 794455 1042428 927146 1462514 1692794 1512256 1830570 1834438 2791121 3593929 3581141 3386326 2617298 3152841 3061841 3036355 3184495 3111014 2885497 2189247 2940241 L-glutamate 4161669 4090040 4549416 4718842 3566207 5561046 2885564 2525886 4053637 3580544 4381366 4798976 4070867 4942212 5670046 3276009 3910816 3602627 3261949 3230294 3584400 4313218 3748032 6207302 3630016 3720387 3739651 2404043 2801686 2994040 4832447 4813452 5711306 6330770 3620131 6532482 L-glutamine 1452878 1210902 908085.8 706335.4 733243.5 710235.2 1080624 1281306 1285934 1555099 2349282 2378966 1035573 1005631 781378.7 543660.7 537858.8 637900.1 866867.2 847465.1 946297 1367588 1408960 2538376 2090698 1727139 1755154 1383705 1517371 1938522 760626.2 759910 675494.8 566285.3 475182.5 861580.2 glycine 1905627 1852184 2248279 2331890 2831450 1936760 2404640 2312005 2070273 1989389 1938904 2025759 1864301 1848942 1939167 2421563 1959524 2746658 2860695 2199000 1819342 2135365 1992130 1761648 2609841 2643961 2009628 1891214 2250598 1988851 1963378 1850180 1926140 3098867 2700334 2350609 L-histidine 319736.1 294497.9 239102.8 189160.1 194130.5 195818.2 304732.3 274628.4 273981.8 311458.4 393683.6 409384.8 349083.7 320977.2 244120.6 190730.6 226936.1 228786.2 473636.9 255513.1 207682.2 338159.7 459162.5 447612 497153.8 514689.4 530171.8 316281.3 406714.8 428588.9 258392.7 296920 480859.8 248810.2 193822.1 341312.5 L-leucine 6161102 4464078 3226318 3322843 3418075 2188938 4918278 6111194 5107370 7065480 9586917 9254781 5515188 3545830 2736336 2539981 2113749 2891504 5936270 4445844 4303530 5829546 7201280 9177925 10890550 8623368 6225850 8017798 8041542 9091331 3751576 4751492 4153370 3565811 2899749 4284054 L-lysine 891312.2 962019.2 807949.3 725408.9 675242.6 820109.2 1592083 1682510 1770336 2245487 3142747 2856509 1686983 1277666 1254720 778930.1 937026 1117404 1327557 1228847 1186140 1502656 1577110 2377854 2643916 2649324 2616011 2352549 2356555 2899299 1129409 1135457 1013489 849036.4 843984.1 1266817 L-methionine 1098334 631847.7 513994.6 410841.3 469675.1 280199.8 588532.8 896026.3 738183.8 1296247 1732565 1975502 624172.8 398212.7 225374.9 185470.3 137466.7 256645.9 700410.9 573716 492254.9 914679.5 959123.7 1736637 1944948 1654878 1175306 1246897 1624878 1817196 491782.7 536681.3 450400.5 314027.8 216444.6 522866.8 L-phenylalanine 756180.5 655742 468737.6 379330 414332.8 385517 626413.7 645965.2 621079.4 882233.3 999081.7 1158437 587660.5 359318.9 306762.2 261054.3 257966.4 353813.4 584855 536940.1 470359.9 748792.7 801019.7 1263964 1230575 1076918 840303 826535.4 839023.6 1076136 539245.1 530068.2 420482.5 376443.9 315479.2 519012.3 L-proline 1467157 1196397 951810.8 837059.5 1083530 1104218 1268598 1127925 1323692 1369018 1927525 1849266 1559781 1628605 1396632 1284531 1425308 1402410 1477709 991466.2 912929.6 1371498 1573445 2135804 2120335 2147525 1803620 1298993 1690828 1652087 1233322 1522100 1891933 1629570 931842.2 1765229 L-serine 674819.4 816584.2 415233.7 359719.2 296272.4 201155.6 359111.4 379048.8 438223.6 505248.1 742292.2 796488.7 343248.1 477263.1 243976.8 196387 220197.8 358835.7 949991.5 420038.3 303100.2 553913.2 1061603 899120.7 894941.3 742062.2 844772.6 497978.4 679928 664271.7 409416.6 504352.5 677779.2 343801.9 195388 502601 L-threonine 1539815 1291150 807436.7 683611.9 643709.4 795961.5 1064699 1142589 1150658 1505614 1675844 1991150 1579589 1520454 1225128 680324.7 819227.2 867238.5 1205077 845475.9 821610.8 1058742 1614508 2004297 2177910 1986572 1955452 1476718 1565594 1853231 1226109 1375330 1381148 1096869 792690 1417274 L-tryptophan 913471.5 896401.8 537812 438023.5 419763 669011.4 801713 945505 827619.3 1346092 1477993 1561554 1249321 942297.6 637552.8 361620.5 450200.9 496196.2 620686.8 600149.9 639529.2 860527.9 961144.8 1498221 1635543 1098165 988347.3 1040951 1126119 1267133 625542.8 678931.2 734183.8 526572.4 402731.8 555855.9 L-tyrosine 998379.6 607523.4 591514.4 471261 469282.7 377276.9 640408.8 870264.5 665941.6 882448.1 1116397 1198791 742628.2 540085.3 367805.7 376504.7 308262.2 438945.8 765351.2 523597 526772.7 814917.7 984674.6 1291452 1583135 1180033 879102.7 958837.5 1166593 1101754 583544.4 615102.2 677026.7 468790.6 373575.8 571103.3 L-valine 2086255 1457019 1419269 1156150 1229921 1052940 1812387 2208693 2057652 2512069 2842586 3317498 3235198 2887155 2325201 2115406 1926854 2441998 2084531 1376400 1301088 2070393 2089592 2899414 3516206 3495721 2694133 2361205 2682870 2963526 2889716 3232465 3498613 3785257 2978266 3368469 CMP 142197.5 156122.8 166316.5 189504.2 156805.7 209681.2 148484.5 174680 248420.6 181645.5 239850.6 225259.6 133072.3 130525.4 139635.3 81980.88 114218.5 96180.66 163969.7 177314.8 206340 204847.9 192797.8 263787.2 137923.8 177140.6 191056.8 125467.1 117367.9 142569.3 69110.64 63895.93 88571.27 69849 54826.45 59608.97 Cytosine 41319.34 41016.84 57268.21 40138.81 44259.57 49506.98 32670.48 29026.72 41449.29 49844.36 52813.21 50472.2 57843.93 45102.42 51242.54 39841.75 36425.79 45497.75 43998 34355.54 32392.05 44348.23 41974.96 83219.48 25507.54 32664.44 27074.79 23490.8 21950.1 24504.45 27700.35 30451.42 33708.92 33311.95 11080.76 29591.8 Allantoate 4865.258 44207.09 5817.681 6577.542 6912.131 7470.177 6469.931 4646.169 4196.925 4531.952 15135.11 11781.2 38996.91 37321.28 34457.53 14266.32 31704.88 19914.16 73353.22 14568.45 6488.243 22434.02 65366.31 12855.84 7789.139 14968 33490.14 17515.02 35055.95 13796.94 24958.59 35632.46 32345.58 25674.67 4360.626 31780.27 Nicotinamide 1891307 1502382 1564624 1437766 1605087 1081318 2182438 2065540 2218530 1992160 2165640 2536646 1964272 1966009 1514163 1142274 1270761 1950890 1775573 1344541 1325497 2278252 2034071 3531893 2092369 3030155 2139914 1458636 1974599 1929009 1083746 1024033 1127106 1185564 823024.7 1283886 5-Oxoproline 816514.8 718369.8 716427.9 691625 597782.6 795201.5 556180.3 532697.4 736871 784937.9 956514.4 1017410 753812.2 817911.9 893183.9 463804 557350.7 667675.8 724579.7 558687.2 663235.4 781377.5 653110 1327100 807711.2 733949.3 690014.2 514328.6 569122.9 676260.7 714960 726840.2 853607.9 875049.1 555228.5 968416 S-Glutathionyl-L-cysteine 39683.83 34192.34 58307.11 50977.78 23626.15 66734.38 30775.92 22881.32 72833.76 32245.63 54924.04 61262.48 35242.46 57375.33 62968.48 16867.79 69823.16 42496.39 40411.81 33464.97 65647.07 46254.45 31753.19 64536.36 71932.77 64619.86 89113.62 34996.6 27432.94 55104.18 97467.5 118155.1 96101.63 149689.6 80110.63 117923.9 gamma-L-Glutamyl-D-alanine 93083.4 92025.06 84934.8 101492.2 135306.4 87853.88 162473.4 159542.1 172787.2 202226.6 247622.3 223190.8 74615.35 85326.65 67913.8 52257.28 59757 49606.72 184920.7 168272 152782.2 241431.5 216547.4 259297.8 257747.7 260778.3 223292.2 197365.3 257640.6 259020.8 86162.85 106561.9 104373.7 96167.79 70741.15 103027.6 gamma-L-Glutamylputrescine 76092.46 82537.73 74512.41 91983.84 85821.33 80966.07 158872.3 199459.6 190287.9 223542.6 272515.7 275590.5 87837.71 63380.36 47107.21 35490.36 42023.29 62315.23 190153.2 165719.6 173164.3 161184.6 169773.5 227724.1 221492.9 290705.1 244390.6 261054.4 284213.1 335002.9 72268.31 63784.67 61213.05 44038.98 71365.85 78491.81 (5-L-Glutamyl)-L-glutamine 28939.12 23873.41 21094.5 26326.24 26407.19 17595.44 56604.91 47784.92 48844.98 76373.27 94411.1 85043.62 26860.46 23536.71 18534.44 14382.28 15680.06 13596.46 48906.89 44629.7 59341.1 62210.69 79628.46 98431.71 110203.7 101428.8 102079.3 71456.74 96746.21 83924.87 30946.57 30697.74 34300.16 16891.86 16731.94 22344.76 Dimethylglycine 380055.8 385091.5 425000.2 386421.8 328955.8 432196.4 2119072 2127165 2805433 2165659 2706426 2881355 978893.7 1173490 2057316 684512.6 1891310 862105.3 251914.1 196647.9 198965.7 304032.2 281068.2 323065.7 1718297 1861834 2226579 1117222 1189557 1365464 575112.8 675402.3 698355.8 982086.4 777063.8 856086.3 Ornithine 47037.67 214926.8 79961.32 70580.2 56168.64 63164.32 63093.2 52379.66 74514.7 50911.34 143806.6 78045.73 157083.3 198539.7 138254.2 89005.35 158007.2 122423.2 346648.7 80794.38 54731.32 114066.4 309423.2 96998.77 79105.45 89357.04 195627.8 80155.52 131203 84908.18 119422.3 201191 192546.2 136027.3 92073.84 148481.6 L-Citrulline 1169926 1027066 818098.6 755791.6 753612 838634.2 1411734 1620378 2097140 1956345 2012699 2130077 3567513 4133386 4660226 2340693 3798549 2957664 735636.8 660671.3 706839.5 858491.3 1078353 1374025 2755409 2688717 2917942 2198586 2290553 2395473 6291874 5937124 5925170 5422318 3910878 6510102 Putrescine 123768.1 257792.2 311600.5 423296.4 375640.2 406433.5 840427 693081.9 882564.2 708465.4 788714.2 715030.2 511321 554947.4 472641.8 434427 513962.9 452619.4 333918.8 375471.7 369696.2 428235 318836.6 517935.1 731753.7 1061586 840187.2 672925.2 701665.2 652743.9 335323.4 382494.8 397652.6 556771.3 488287.1 468805.4 Spermidine 2280341 4844378 4764452 4697520 4107552 5184064 2592121 2571390 2484553 2343286 2675044 2293618 3248595 2372368 1261902 1524189 750212.2 1368863 1894349 2975052 2945080 2269282 3341616 4695308 1765446 1732349 1468407 1576267 965036.7 1343120 890089.3 910681.4 477446.3 1107827 1591544 1782513 Spermine 97715.3 187339.5 144315.8 109381.1 127340.8 141579.7 41483.39 42868.39 38716.03 33804.54 47260.64 35050.64 27269.87 23497.36 17138.14 20058.19 10631.38 22740.4 47581.25 63972.58 79868.66 52663.11 91658.27 107724.9 26833.96 30001.79 16540.61 30087.04 15144.48 23563.45 21246.66 22914.92 1801.179 55959.81 34941.91 44579.08 Creatine 6575522 7085000 8598295 10615050 9071029 12183680 6459616 6836312 11001700 8133024 7763558 8612190 7893506 8319774 8775037 4794080 6616492 5474176 39820400 55230580 52887460 51309630 41514940 86507810 43243920 52425930 54777610 24637300 29546440 31766570 36511600 41939360 44136210 53024900 26864210 43364860 Creatinine 61523.71 82478.54 60198.07 59860.89 51978.02 54088.84 44350.89 42747.05 54778.22 63620.86 48378.6 50002.08 60739.16 68393.57 62363.33 41900.24 38379.04 52905.07 122987.2 135388.2 111356.6 143340.9 149344 156766.3 131881.6 118946.3 124382.1 86493.94 111648.5 118654.3 94067.48 94326.53 145179.7 149820.4 78081.31 118583.1 N-Acetyl-L-citrulline 129319.5 145945.2 79021.84 100075.7 110378.4 97426.1 171178.4 181362.9 169362.6 295335.2 388074.5 419585.2 71559.02 57786.63 37500.52 37743.51 30047.68 44844.39 156382.3 144995.6 139480.3 191018 233876.7 264814.2 274931.2 264785.5 237959.8 212438.8 254143 274185.9 65764.84 76425.32 67435.59 41045.58 45385.93 78333.3 N-Acetylornithine 215058.8 158006.6 112934.1 135136.7 181496.4 100635.1 258045 341898.2 256863 457277.9 459562.8 482119 138992 134904.3 71135.59 87429.96 74072.3 91266.62 276809.1 215848.8 192485.8 324444 328216.7 341654.9 432538.4 450109 352717.7 481144 587764.8 641667.3 102623.1 139140.7 123436.6 109868 90797.79 125665 Guanidinoacetate 124080.2 125047.3 130097.9 155997 124513.1 212403.7 209974.4 227432.3 296081.2 267443.3 255772.6 282405.2 188479.4 192697.9 202477.9 106623.5 172945.6 150847.5 29717.87 40141.71 41130.16 48501.74 47952.47 68784.32 84342.64 95386.62 90318.96 83917.52 89860.09 103877.5 54157.26 68542.34 63354.33 77454.09 63657.25 74419.93 trans-4-Hydroxy-L-proline 276764.8 286967.2 352613.6 323704.2 294471.5 362477.8 262467.3 333376.5 264294 254376.4 258451 267750.3 202260.5 186798.4 232509.5 179989 193573.3 171712 162566 125061.2 127843.2 149283.8 151615.8 139967.7 217103.2 226433.5 222449.9 189352.6 214247.1 176970.2 238355.8 116038.9 126859.5 153145.1 148652.5 298847.7 L-Methionine S-oxide 361725.2 354556.2 269674.7 274369.5 296067.2 205187.2 353265.4 451680 319339.2 418973.6 413881.1 455305 400194.2 240688.5 190623.6 217700.9 152171.5 290099.7 314953.7 253188 250176.5 283945.5 321906.8 342751.8 458217.1 442662.2 275923.5 410644.3 438633.6 346472.3 224164.6 248333.9 222744.9 221880.3 220228.8 219464 Indolepyruvate 33414.32 24506.4 15503.24 15893.85 9737.083 12512.07 16877.36 29792.33 15175.73 20836.52 29839.38 33794.22 26026.41 18576.5 10294.75 7922.716 6609.01 11592.79 8220.618 14831.21 20657.23 26577.43 31079.81 33887.39 28117.08 25131.52 16916.26 32862 22646.14 30150.2 17641.09 20984.57 22197.94 11179.95 10924.38 13188.62 Picolinic acid 1021208 1102289 1326690 1321464 1053068 1651146 1608667 1451048 2284274 2386919 2386647 2273586 2221742 1745751 1792858 983038.2 1149882 1118535 957009.2 1394261 1744281 1519933 1624659 2469965 1603866 1707970 0 1816406 1600621 1908539 1175755 1644674 1729737 1077139 1064629 1217624 L-Adrenaline 63880.14 70335.47 45427.04 40726.83 42551.25 95335.88 64591.39 90023.23 106364.6 93099.13 88819.48 103725.3 19304.32 34160.45 30101.82 13490.13 11619.63 22290.96 96509.81 66983.48 95540.34 100022.4 109935.6 177208.1 159698 117915.5 133179.2 147609.2 127691.5 170712.2 55302.55 54185.29 59503.57 49554.22 31061.7 65206.31 Ethanolamine phosphate 1888420 2193059 2794306 2406106 1865447 2780080 1543168 1637274 2658535 1829696 2367393 2622205 2376121 2730366 2984208 1658657 2091592 2004140 2030712 2089075 2421868 2353063 1808653 2926513 1940240 2330683 2768756 1168523 1323939 1526730 2720643 3034747 2967326 3034197 1973201 2959007 L-Carnitine 231855.1 285673.2 272480.8 242269.1 223901.2 450928.3 538889.4 553084.6 663466.7 686788.4 676870.7 719974.1 155227.9 161550.5 131930.6 86019.9 94317.94 117336.9 548846.4 394940.8 477173.5 682317.8 624272.8 956074.7 1097370 1004003 907726.3 815987.3 947650.1 1106505 387299.9 338398.6 458588.4 405138.4 232021.3 426208.9 acyl-C3 (propionyl-carnitine) 86249.95 83123.16 106884 112239.6 87368.66 102666.8 503430.1 789469.7 777623.8 639501.3 579320.3 672892.4 93471.62 95333.81 74755.03 64687.07 52215.23 100159.4 373764.7 230338.1 340762.3 379670.5 287778.7 370325.8 493079.9 547114.5 528456.4 448819.3 577005.8 486805.1 95898.25 104506.6 110056.7 165132.9 128762.7 119857.4 acyl-C5 (isovalerylcarnitine) 44581.35 38295.08 28008.14 38948.64 35991.54 44155.2 49717.23 42483.58 64271.57 56241.61 33882.68 64418.58 43356.84 45113.89 43904.46 34502.1 43218.75 34123.55 40969.74 40187.91 51701.92 43461.75 47145.49 39287.98 53889.81 35877.77 57603.03 38689.74 45343.02 26235.53 34520.45 45946.67 56819.52 33247.3 36419.4 42952.67 acyl-C6 (hexanoyl-l-carnitine) 29938.43 9913.372 17848.94 11840.41 35645.56 21660.06 32477.03 30145.47 25078.15 15566.13 22262.65 24781.54 26254.12 11135.41 26999.1 22817.03 14608.08 17315.17 13655.64 12025.79 34178.19 26329.12 26051.5 26399.59 25041.22 18859.78 33013.43 27632.6 20720.27 43630.35 16943.41 21861.44 23815.29 18789.67 19414.88 26027.59 acyl-C8 (L-octanoylcarnitine 9337.595 10393.46 5195.958 13613.79 12063.62 10083.27 9652.214 10584.99 17389.31 7776.632 8514.505 5129.974 16882.66 4668.239 5730.565 21997.17 9676.235 14052.65 13781.93 14127.42 8293.251 15289.67 5838.229 22042.86 18912.15 9070.146 6161.389 11759.37 17518.98 14362.8 5814.756 6279.039 15148.14 7008.414 7270.76 9091.365 Triacanthine 187771.1 165456 209450.3 196987.8 184805.2 156371 627797.8 824535.5 750277.8 842063.5 697740.2 722290.5 442416.2 380142.3 306245.3 293265.2 202764.2 277803.1 642810.5 430136.2 450321.9 499493.4 363811.7 429618.3 1081001 1155170 759205.2 725488.7 913194.8 764409.8 400051.2 452779.2 462630.6 671534.5 401583 444278.5 N5-Methyl-L-glutamine 279274.4 228748.4 163773.2 192802.2 256003.8 169839.4 308039.3 316010.6 372881.8 466224.2 587651.9 592889.4 108097.1 158368.6 96612.04 97134.56 99627.6 98680.79 360921.8 371163.1 318771.6 442509.4 447138.1 606359.5 622483.2 581714.6 481756.4 442261 536754.7 468749.3 173969.8 202862.2 164896.2 139632 116442.7 167973 6-Lactoyl-5-6-7-8-tetrahydropterin 2648096 2548929 2813203 2921385 2944891 3249755 6773614 6812690 7219850 7139686 7104438 7715500 6990230 8292954 7762470 4421226 6181396 5945844 2141199 1973146 1947799 2941817 2494457 2880124 3344605 3478575 3473140 3310978 3549266 3914561 2601760 2875507 2579285 3362124 2299217 3291908 Methylenediurea 69825.15 70240.08 93456.24 115154.3 81713.99 130337.8 66026.86 69796.21 117420 85578.3 74882.38 98949.68 83821.11 76654.11 91202.32 56719.36 70437.12 67994.4 420678 575030.3 578400.2 558051.2 430808.8 887399.8 450421.9 581858.1 599834.7 272798.6 304366.2 343904.8 396513.3 461207.3 457470.8 542692.3 288109.5 478662.7 2-Deoxy-alpha-D-glucoside 1644752 1723354 2300226 2268223 2009986 2513943 2978976 2543282 3874056 3913584 3938370 3627866 3485609 2797242 2927020 1721065 2303399 2060121 1875974 2471296 2582184 2594714 2345943 3699362 2811831 3318877 4077891 3078841 2702581 3062355 1943617 2684750 2734966 2123246 2002239 2123990 N-Carbamyl-L-glutamate 69697.32 64337.55 57181.2 64738.66 43180.87 66656.59 114495.4 143208.8 148056.7 181430.5 177449.8 202107.2 110482.6 124757 124474.7 70777.52 87346.45 85911.38 54369.53 64045.16 59174.89 81099.41 67121.62 94608.54 86683.38 108223.4 107518 103550 91203.02 99725.09 52324.5 62021.54 57057.23 53814.23 49173.54 57600.25 2-Oxo-7-methylthioheptanoic acid 84804.44 90307.71 89666.21 64740.47 57502.89 72739.3 161849.9 159833.1 192914.2 226717.3 242345.8 287421.8 195373.1 147883 106922.4 88743.15 93914.91 110532.4 100266.6 110954.4 88394.85 113004.7 136023.2 234314.2 279980.2 232448.8 244621.1 190623.6 221694.4 247287.9 108285.1 132253.5 120870.8 85380 72374.48 129281.8 Alanine 13C3 0 0 0 0 0 0 139690.8 147853.3 160528.3 113001.7 179025.1 184812.8 40410.52 63562.36 67707.7 23566.13 57922.75 37058.25 0 0 0 0 0 0 220821.3 181902 240236 106809.4 137410.5 148867 71904.77 95802.49 94332.55 95364.12 59809.44 92313.15 L-Arginine 13C6 67721.8 0 0 0 0 0 56485.68 63065.71 45625.1 47627.86 44314.12 50654.75 5848.206 5828.361 11486.82 5590.696 7903.043 3422.167 0 0 0 0 0 0 50281.81 51448.78 52587.88 35738.75 50003.98 26024.71 0 4898.221 0 3640.337 2883.908 4431.715 Asparagine 13C4 0 0 0 0 0 0 41097.86 33258.38 40164.57 30826.05 43531.5 57845.05 0 6732.566 18616.39 5302.225 8883.07 0 0 0 0 0 0 0 54369.05 49171.39 47647.03 26826.42 21834.78 29449.65 13331.6 11928.76 6747.305 0 9449.934 7089.915 L-Aspartate 13C4 1886.577 0 0 0 1737.323 7054.549 25659.54 18352.32 30102.91 19493.14 23253.56 28348.17 6740.928 4848.655 6681.889 5372.826 5391.52 10710.64 0 3539.405 4683.904 1975.711 3964.652 1667.587 40792.19 30690.12 35958.43 29168.51 28025.8 16477.82 20291.29 34262.61 36226.5 32274.58 21216.01 41609.93 Cysteine 13C3 1245561 1289561 1368928 1506335 1190574 1879669 1817653 1589528 2544875 2803859 2660278 2606133 2544246 2047096 1907317 1116084 1363882 1246497 1080552 1612775 1864267 1659478 1840365 2762559 1750127 2005900 2644716 2129410 1778616 2204161 1299988 1905000 1984176 1162624 1178448 1378237 Glutamate 13C5 7351.896 6974.705 9248.304 16621.34 13149.76 7343.426 217554.2 166603.6 280733.4 185416 227794.2 257583 164270.5 201809.3 332052.7 149059.2 297100.1 164941 11745.45 4196.528 4460.854 9413.671 5738.003 6516.069 169548.9 171158.8 206994.3 147747.4 160920.5 161113 129555.2 151991.3 168284.8 222498.3 133116.4 204954 Histidine 13C6 14015.18 12446.29 10591.44 7700.758 19764.99 10855.26 19975.06 19935.14 19473.56 34840.86 39995.98 39078.9 2617.863 8277.543 3700.171 2349.546 3369.001 5312.082 12995.99 30470.77 18716.16 16924.51 30269.99 36579.09 44904.86 40648.4 31125.35 31053.07 29456.13 36231.71 16247.1 9100.671 2109.958 5057.185 6613.315 4868.895 Leucine/isoleucine 13C6 0 0 0 0 0 0 170275.9 214011.7 170613.6 180664.9 169918.7 191746.1 40916.81 35425.22 41418.04 17214.62 43709.21 25058.91 0 0 0 0 0 0 324961.8 308063.9 272235.5 298671.4 256164.2 244364 37730.18 51685.82 48374.52 31767.18 36740.29 33582.66 Lysine 13C6 3832.287 0 0 0 0 0 86945.38 77809.17 82492.43 69109.05 93857.23 92203.16 10177.98 17237.88 8848.812 7138.746 24792.76 0 0 0 0 0 0 0 87763.62 94495.48 95822.62 69632.4 62435.14 72105 6916.48 10581.67 10632.5 5153.424 1980.56 9675.673 L-Methionine 13C5 0 0 0 0 0 1906.796 8520.128 14884.03 13225.62 17585.32 22908.01 27055.05 3028.922 3190.417 2257.222 21732.33 17733.59 5612.758 6250.624 0 0 5340.104 0 0 34163.3 38377.34 31436.92 25308.2 30009.19 30752.46 12205.75 0 3431.642 8044.725 23193.93 32129.78 L-Phenylalanine 13C9 1195578 1182562 1029681 795083.7 913833 957318.7 2005812 1857038 2007912 2644985 2727224 3136553 1684793 1465523 1498254 1144778 1105402 1535598 1183194 1070290 1116262 1334112 1485054 2030137 2915120 3078306 2977834 2493320 2898357 2751480 799903.2 866443.8 1109256 768187.5 739416.3 1003182 Proline 13C5 2762.589 3666.811 0 2139.061 2743.053 3023.423 161812.1 148389.4 157899.9 129412.4 177509.7 165743.4 28310.92 42083.24 52418.01 32065.08 82906.94 33708.02 0 0 2175.929 2244.355 2648.628 2170.217 210875.4 224021.7 204866.5 126040.6 146984.6 131639.2 40520.86 53846 73451.24 53905.29 35573.59 48417.29 Serine 13C3 0 0 0 0 0 0 31577.25 26282.28 33038.42 27046.08 36343.8 44520.72 7673.658 0 5336.849 0 4426.507 0 0 0 0 0 0 0 36364.25 34614.55 36603.69 16667.44 29092.03 20737.68 9662.726 12788.34 6893.226 0 2966.117 5642.127 L-Threonine 13C4 0 0 0 0 0 0 73403.51 53857.66 55270.92 58116.63 61515 75190.38 8397.482 13474.43 22265.86 0 14302.52 5565.654 0 2562.894 0 2171.813 1832.484 0 81963.02 88048.82 89096.43 46836.78 50145.1 71781.78 13159.47 10862.99 17603.17 8996.952 13333.23 19462.74 L-Tryptophan 13C11 0 0 2795.752 0 0 1212.783 34059.6 46379.26 46447.95 45598.86 44449.76 42915.68 12219.79 9775.286 16756.32 0 8719.164 0 0 0 0 3575.343 7195.274 3648.378 63142.96 39450.19 59294.74 42879.79 51736.9 47682.03 4442.372 2686.707 3280.331 0 0 6856.408 Tyrosine 13C9 0 0 1323.248 0 0 0 23847.98 27716.29 28689.42 26110.48 34460.27 31142.95 8444.769 24549.13 17897.04 7876.349 5362.729 16310.54 0 0 0 2719.524 1499.776 3819.296 71274.12 48731.52 52644.14 40517.17 58077.61 39129.03 6838.208 10731.76 6355.645 10211.81 3770.865 6238.498 L-Valine 13C5 0 0 0 0 0 0 144839.2 208769.1 155443.9 164380.1 149900.7 171608.5 45879.65 43154.14 47509.89 28827.77 46678.5 33511.69 0 0 0 0 0 0 264127.1 220406.8 185920.2 184936.9 196239 179636.5 38427.85 48820.36 58149.14 61951.27 45541.78 49688.06 Spermidine 13C7 0 0 0 0 3403.164 0 275394.8 267361.1 278267.9 211474.4 281843.7 218564.6 240547.5 189873.7 94033.12 140264.2 60741.5 108146.1 0 3785.621 0 0 0 0 232724.3 200539.9 201138 186263.1 95972.35 154227.1 78632.52 85294.88 43847.68 111445.8 170332.3 193959.8 Hypoxanthine 13C5 13331.87 16299.45 13821.14 15678.92 15678.92 15678.92 15678.92 15678.92 15678.92 15678.92 15678.92 1901229 773386.6 701094.8 797883.1 976422.9 681444.3 764627 18355.06 17508.55 15060.89 16985.23 15189.4 9100.702 1398433 1041060 875053.2 635971.4 603150.8 1030521 765838.8 889123.2 769553.7 850921.2 522518.5 1072134 Xanthine 13C5 1825.057 1734.512 7830.219 2986.707 2750.223 4478.534 46287.81 62188.32 69924.62 64832.7 108708.2 97882.57 32438.69 24694.19 15723.97 26436.27 14012.57 19654.5 4496.448 3966.101 1559.869 0 3983.791 1648.856 52935.06 40893.49 30063.66 42518.68 36109.14 51371.43 12472.09 16852.61 12880.68 9114.66 8790.146 17238.15 Citrulline 13C6 0 0 0 0 0 0 0 0 0 0 0 73925.16 14590.13 18125.4 39578.66 12655.77 55024.24 23994.3 0 2224.487 0 0 0 0 116812 96047.78 121555.4 100237.6 92811.4 72625.97 40503.49 41816.5 45424.93 44075.64 30790.43 44396.57 Cadaverine 13C5 0 0 0 0 0 0 24989.15 10812.76 11413.51 19495.29 15239.07 18131.8 6572.647 13388.23 10281.2 8131.686 28396.97 13034.3 0 0 0 0 0 0 28739.62 36394.38 26088.59 23146.68 22800.51 23072.18 15621.64 16536.52 12191.56 9510.283 17277.87 33736.74 Putrescine 13C4 0 0 0 0 0 0 0 0 0 0 0 232151 186951.2 214978.4 182424.5 239903.9 184764.4 218237.1 0 0 0 0 0 0 292583.2 463966.5 352624.4 267761 289769.8 276338.9 233018.6 238496.2 240925.8 382032.1 296988.3 279236.6 MS_METABOLITE_DATA_END #METABOLITES METABOLITES_START metabolite_name KEGG ID m/z r.t. L-alanine C00041 90.05567 0.642512 L-arginine C00062 175.119 0.625237 L-aspartate C00049 134.0449 0.6451106 L-cysteine C00097 122.0273 0.6568359 L-glutamate C00025 148.0605 0.6485493 L-glutamine C00064 147.0764 0.6433787 glycine C00037 76.04012 0.6738933 L-histidine C00135 156.0769 0.6100052 L-leucine C00123 132.1021 0.685496 L-lysine C00047 147.1129 0.5993748 L-methionine C00073 150.0585 0.6797932 L-phenylalanine C00079 166.0864 0.7254986 L-proline C00148 116.071 0.6659439 L-serine C00065 106.0503 0.6405067 L-threonine C00188 120.0659 0.6460626 L-tryptophan C00078 205.0974 1.716904 L-tyrosine C00082 182.0812 0.6776466 L-valine C00183 118.0866 0.6730147 CMP C00055 324.059 0.660597 Cytosine C00380 112.0509 0.6788441 Allantoate C00499 177.061 0.611945 Nicotinamide C00153 123.0556 0.758368 5-Oxoproline C01879 130.05 0.6592079 S-Glutathionyl-L-cysteine C05526 427.0899 0.6465999 gamma-L-Glutamyl-D-alanine C03738 219.0976 0.6591579 gamma-L-Glutamylputrescine C15699 218.1501 0.5944437 (5-L-Glutamyl)-L-glutamine C05283 276.1191 0.6568426 Dimethylglycine C01026 104.0712 0.6494853 Ornithine C01602 133.0973 0.5991414 L-Citrulline C00327 176.1031 0.6468733 Putrescine C00134 89.10802 0.605892 Spermidine C00315 146.1652 0.5985987 Spermine C00750 203.2233 0.6048154 Creatine C00300 132.0769 0.6585813 Creatinine C00791 114.0666 0.6540974 N-Acetyl-L-citrulline C15532 218.1135 0.655669 N-Acetylornithine C00437 175.1079 0.6774729 Guanidinoacetate C00581 118.0615 0.6467685 trans-4-Hydroxy-L-proline C01157 132.0657 0.6670581 L-Methionine S-oxide C02989 166.0533 0.6747 Indolepyruvate C00331 204.0633 0.6780344 Picolinic acid C10164 124.039 0.5873675 L-Adrenaline C00788 184.0953 0.6503147 Ethanolamine phosphate C00346 142.0264 0.6492864 L-Carnitine C00318 162.1124 0.6499674 acyl-C3 (propionyl-carnitine) C03017 218.1387 0.6836 acyl-C5 (isovalerylcarnitine) C20826 246.17 1.754408 acyl-C6 (hexanoyl-l-carnitine) HMDB00756 260.1856 1.794817 acyl-C8 (L-octanoylcarnitine HMDB00791 288.2168 1.845904 Triacanthine C08435 204.1231 0.6828259 N5-Methyl-L-glutamine C03153 161.0922 0.6603435 6-Lactoyl-5-6-7-8-tetrahydropterin C04244 240.1093 0.6466594 Methylenediurea C06381 133.0735 0.6633319 2-Deoxy-alpha-D-glucoside C03573 164.067 0.5849646 N-Carbamyl-L-glutamate C05829 191.0664 0.6449022 2-Oxo-7-methylthioheptanoic acid C17220 191.0765 0.6090014 Alanine 13C3 C00041 93.0657 0.6434884 L-Arginine 13C6 C00062 181.1391 0.62498 Asparagine 13C4 C00152 137.0742 0.6422032 L-Aspartate 13C4 C00049 138.0581 0.6438946 Cysteine 13C3 C00097 125.038 0.5863734 Glutamate 13C5 C00025 153.0771 0.6730269 Histidine 13C6 C00135 162.0967 0.6727316 Leucine/isoleucine 13C6 C00123 138.1221 0.6828344 Lysine 13C6 C00047 153.1327 0.6032408 L-Methionine 13C5 C00073 155.0744 0.6666916 L-Phenylalanine 13C9 C00079 175.119 0.6286651 Proline 13C5 C00148 121.0872 0.6912161 Serine 13C3 C00065 109.0604 0.6415526 L-Threonine 13C4 C00188 124.0794 0.6419193 L-Tryptophan 13C11 C00078 216.1333 1.700353 Tyrosine 13C9 C00093 191.1116 0.7061304 L-Valine 13C5 C00183 123.1033 0.677107 Spermidine 13C7 C00315 153.1887 0.6015 Hypoxanthine 13C5 C00262 142.0616 0.7137239 Xanthine 13C5 C00385 158.0568 0.7342514 Citrulline 13C6 C00327 182.1238 0.652813 Cadaverine 13C5 C01672 108.1402 0.6014631 Putrescine 13C4 C00134 93.12141 0.6083794 METABOLITES_END #END