#METABOLOMICS WORKBENCH jsto1886_20230720_133749 DATATRACK_ID:4176 STUDY_ID:ST002846 ANALYSIS_ID:AN004664 PROJECT_ID:PR001781 VERSION 1 CREATED_ON September 7, 2023, 1:09 pm #PROJECT PR:PROJECT_TITLE Apolipoprotein E suppresses hyperlipidemia-driven hematopoiesis & inflammation PR:PROJECT_TITLE by controlling mitochondrial metabolism PR:PROJECT_SUMMARY Apolipoprotein E (ApoE) is recognized for its pleiotropic properties that PR:PROJECT_SUMMARY suppress inflammation. We report that ApoE serves as a metabolic rheostat that PR:PROJECT_SUMMARY regulates microRNA-control of glycolytic and mitochondrial activity in myeloid PR:PROJECT_SUMMARY cells and hematopoietic stem & progenitor cells (HSPCs). ApoE expression in PR:PROJECT_SUMMARY myeloid cells increases microRNA-146a, which reduces NF-κB-driven GLUT1 PR:PROJECT_SUMMARY expression and glycolytic activity. In contrast, ApoE expression reduces PR:PROJECT_SUMMARY microRNA-142a, which increases CPT1A expression, fatty acid oxidation, and PR:PROJECT_SUMMARY oxidative phosphorylation. Improved mitochondrial metabolism by ApoE expression PR:PROJECT_SUMMARY causes an enrichment of TCA cycle metabolites and NAD+ in macrophages. The study PR:PROJECT_SUMMARY of mice with conditional ApoE expression supports the capacity for ApoE to PR:PROJECT_SUMMARY foster microRNA-controlled immunometabolism. Modulation of microRNA-146a & -142a PR:PROJECT_SUMMARY in the hematopoietic system of hyperlipidemic mice using RNA mimics & PR:PROJECT_SUMMARY antagonists, respectively, improves mitochondrial metabolism, which suppresses PR:PROJECT_SUMMARY inflammation and hematopoiesis. Our findings unveil an RNA regulatory network, PR:PROJECT_SUMMARY controlled by ApoE, which exerts metabolic control over hematopoiesis and PR:PROJECT_SUMMARY inflammation in hyperlipidemia. PR:INSTITUTE Northwestern University PR:DEPARTMENT Pulmonary and Critical Care PR:LABORATORY Chandel Laboratory PR:LAST_NAME Stoolman PR:FIRST_NAME Joshua PR:ADDRESS 303 E Superior Street, Chicago, IL, 60611 PR:EMAIL joshua.stoolman@northwestern.edu PR:PHONE 7343559440 #STUDY ST:STUDY_TITLE Apolipoprotein E suppresses hyperlipidemia-driven hematopoiesis & inflammation ST:STUDY_TITLE by controlling mitochondrial metabolism ST:STUDY_SUMMARY Apolipoprotein E (ApoE) is recognized for its pleiotropic properties that ST:STUDY_SUMMARY suppress inflammation. We report that ApoE serves as a metabolic rheostat that ST:STUDY_SUMMARY regulates microRNA-control of glycolytic and mitochondrial activity in myeloid ST:STUDY_SUMMARY cells and hematopoietic stem & progenitor cells (HSPCs). ApoE expression in ST:STUDY_SUMMARY myeloid cells increases microRNA-146a, which reduces NF-κB-driven GLUT1 ST:STUDY_SUMMARY expression and glycolytic activity. In contrast, ApoE expression reduces ST:STUDY_SUMMARY microRNA-142a, which increases CPT1A expression, fatty acid oxidation, and ST:STUDY_SUMMARY oxidative phosphorylation. Improved mitochondrial metabolism by ApoE expression ST:STUDY_SUMMARY causes an enrichment of TCA cycle metabolites and NAD+ in macrophages. The study ST:STUDY_SUMMARY of mice with conditional ApoE expression supports the capacity for ApoE to ST:STUDY_SUMMARY foster microRNA-controlled immunometabolism. Modulation of microRNA-146a & -142a ST:STUDY_SUMMARY in the hematopoietic system of hyperlipidemic mice using RNA mimics & ST:STUDY_SUMMARY antagonists, respectively, improves mitochondrial metabolism, which suppresses ST:STUDY_SUMMARY inflammation and hematopoiesis. Our findings unveil an RNA regulatory network, ST:STUDY_SUMMARY controlled by ApoE, which exerts metabolic control over hematopoiesis and ST:STUDY_SUMMARY inflammation in hyperlipidemia. ST:INSTITUTE Northwestern University ST:LAST_NAME Stoolman ST:FIRST_NAME Joshua ST:ADDRESS 303 E Superior Street, Chicago, IL 60611 ST:EMAIL joshua.stoolman@northwestern.edu ST:PHONE 7343559440 #SUBJECT SU:SUBJECT_TYPE Mammal SU:SUBJECT_SPECIES Mus musculus SU:TAXONOMY_ID 10090 #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 genotype:wild-type | treatment:no treatment RAW_FILE_NAME=Nav-Jos-20210423-01 SUBJECT_SAMPLE_FACTORS - 2 genotype:wild-type | treatment:no treatment RAW_FILE_NAME=Nav-Jos-20210423-02 SUBJECT_SAMPLE_FACTORS - 3 genotype:wild-type | treatment:no treatment RAW_FILE_NAME=Nav-Jos-20210423-03 SUBJECT_SAMPLE_FACTORS - 4 genotype:wild-type | treatment:no treatment RAW_FILE_NAME=Nav-Jos-20210423-04 SUBJECT_SAMPLE_FACTORS - 5 genotype:wild-type | treatment:IL-4 RAW_FILE_NAME=Nav-Jos-20210423-05 SUBJECT_SAMPLE_FACTORS - 6 genotype:wild-type | treatment:IL-4 RAW_FILE_NAME=Nav-Jos-20210423-06 SUBJECT_SAMPLE_FACTORS - 7 genotype:wild-type | treatment:IL-4 RAW_FILE_NAME=Nav-Jos-20210423-07 SUBJECT_SAMPLE_FACTORS - 8 genotype:wild-type | treatment:IL-4 RAW_FILE_NAME=Nav-Jos-20210423-08 SUBJECT_SAMPLE_FACTORS - 17 genotype:ApoE-KO | treatment:no treatment RAW_FILE_NAME=Nav-Jos-20210423-17 SUBJECT_SAMPLE_FACTORS - 18 genotype:ApoE-KO | treatment:no treatment RAW_FILE_NAME=Nav-Jos-20210423-18 SUBJECT_SAMPLE_FACTORS - 19 genotype:ApoE-KO | treatment:no treatment RAW_FILE_NAME=Nav-Jos-20210423-19 SUBJECT_SAMPLE_FACTORS - 20 genotype:ApoE-KO | treatment:no treatment RAW_FILE_NAME=Nav-Jos-20210423-20 #COLLECTION CO:COLLECTION_SUMMARY BMDMs were seeded in a 6-well cell culture plate at a density of 50,000/well, CO:COLLECTION_SUMMARY and incubated in complete media at 37C & 5% CO2 overnight. Cells were gently CO:COLLECTION_SUMMARY washed 4x with DPBS before freezing at -80C. For metabolite extraction, cells CO:COLLECTION_SUMMARY were extracted with 1 mL HPLC-grade methanol/water 80:20. Cell lysates were CO:COLLECTION_SUMMARY centrifuged at 18,000 x g for 10 min. Supernatants were collected for downstream CO:COLLECTION_SUMMARY metabolomic analysis. The samples were evaporated using a stream of nitrogen. CO:COLLECTION_SUMMARY Subsequently metabolites were reconstituted in 50% acetonitrile in HPLC-grade CO:COLLECTION_SUMMARY water,vortexed and centrifuged to remove any debris. Samples were analyzed by CO:COLLECTION_SUMMARY Ultra-High-Performance Liquid Chromatography and High-Resolution Mass CO:COLLECTION_SUMMARY Spectrometry and Tandem Mass Spectrometry (UHPLC-MS/MS). Specifically, the CO:COLLECTION_SUMMARY system consisted of a Thermo Q-Exactive in line with an electrospray source and CO:COLLECTION_SUMMARY an Ultimate3000 (Thermo Fisher, USA) series HPLC consisting of a binary pump, CO:COLLECTION_SUMMARY degasser, and auto-sampler outfitted with an Xbridge Amide column (Waters; CO:COLLECTION_SUMMARY dimensions of 4.6mm × 100mm and a 3.5μm particle size). Mobile phase A CO:COLLECTION_SUMMARY contained 95% (vol/vol) water, 5% (vol/vol) acetonitrile, 10mM ammonium CO:COLLECTION_SUMMARY hydroxide, 10mM ammonium acetate, pH = 9.0; and mobile phase B was 100% CO:COLLECTION_SUMMARY Acetonitrile. The gradient was as follows: 0 min, 15% A; 2.5 min, 30% A; 7 min, CO:COLLECTION_SUMMARY 43% A; 16 min, 62% A; 16.1-18 min, 75% A; 18-25 min, 15% A with a flow rate of CO:COLLECTION_SUMMARY 400μL/min. The capillary of the ESI source was set to 275°C, with sheath gas CO:COLLECTION_SUMMARY at 45 arbitrary units, auxiliary gas at 5 arbitrary units, and the spray voltage CO:COLLECTION_SUMMARY at 4.0kV. In positive/negative polarity switching mode, an m/z scan automatic CO:COLLECTION_SUMMARY gain control (AGC) target was set at 1x106 and the maximum injection time was CO:COLLECTION_SUMMARY 200 ms. The top 5 precursor ions were subsequently fragmented, in a CO:COLLECTION_SUMMARY data-dependent manner, using the higher energy collisional dissociation (HCD) CO:COLLECTION_SUMMARY cell set to 30% normalized collision energy in MS2 at a resolution power of CO:COLLECTION_SUMMARY 17,500. CO:SAMPLE_TYPE Macrophages CO:STORAGE_CONDITIONS -80℃ #TREATMENT TR:TREATMENT_SUMMARY Briefly, bone marrow cells were flushed from the tibia and femurs of 6- to TR:TREATMENT_SUMMARY 12-week-old male Apoe-/-, Apoe+/-, or wildtype mice on C57BL/6J background. TR:TREATMENT_SUMMARY Cells were cultured in complete media containing DMEM (Corning, USA) TR:TREATMENT_SUMMARY supplemented with 10% fetal bovine serum (GIBCO, USA), 1% GlutaMax (GIBCO, USA), TR:TREATMENT_SUMMARY and 1% penicillin-streptomycin (GIBCO, USA) and differentiated with 25 ng/ml TR:TREATMENT_SUMMARY mouse M-CSF (Peprotech, USA) for 6 days in 37C and 5% CO2. BMDM were then seeded TR:TREATMENT_SUMMARY into 12-well culture plates (Corning, USA) at a concentration of 3 x 10^5. TR:TREATMENT_SUMMARY Stimulation was done with 20 ng/mL IL-4 for 16 hours prior to collection. #SAMPLEPREP SP:SAMPLEPREP_SUMMARY Following incubation/ stimulation cells were washed with 2mL ice-cold 0/9% NaCl. SP:SAMPLEPREP_SUMMARY Following plate wash, plates were placed on dry ice 100uL 80:20 methanol/water SP:SAMPLEPREP_SUMMARY solution in dry ice. Plates were scraped on dry ice and lysates were transferred SP:SAMPLEPREP_SUMMARY to eppendorf tubes and centrifuged at 21,000xg for 10 min. Supernatants were SP:SAMPLEPREP_SUMMARY transferred to fresh tubes and kept at -80dC until analysis. #CHROMATOGRAPHY CH:CHROMATOGRAPHY_SUMMARY Samples were analyzed by high-performance LC (HPLC) and high-resolution MS and CH:CHROMATOGRAPHY_SUMMARY MS/MS (HPLC-MS/MS). The system consists of Thermo Q Exactive with an CH:CHROMATOGRAPHY_SUMMARY electrospray source and an UltiMate3000 (Thermo Fisher Scientific) series HPLC CH:CHROMATOGRAPHY_SUMMARY consisting of a binary pump, degasser, and autosampler outfitted with an XBridge CH:CHROMATOGRAPHY_SUMMARY Amide column (Waters; dimensions of 4.6 mm by 100 mm and a 3.5-μm particle CH:CHROMATOGRAPHY_SUMMARY size). Mobile phase A contained water and acetonitrile (95/5, v/v), 10 mM CH:CHROMATOGRAPHY_SUMMARY ammonium hydroxide and 10 mM ammonium acetate (pH 9.0). Mobile phase B was 100% CH:CHROMATOGRAPHY_SUMMARY acetonitrile. The gradient was set to 0 min, 15% A; 2.5 min, 30% A; 7 min, 43% CH:CHROMATOGRAPHY_SUMMARY A; 16 min, 62% A; 16.1–18 min, 75% A; 18–25 min, 15% A, with a flow rate of CH:CHROMATOGRAPHY_SUMMARY 400 μl min–1. CH:CHROMATOGRAPHY_TYPE HILIC CH:INSTRUMENT_NAME Thermo Fisher UltiMate 3000 CH:COLUMN_NAME Waters XBridge Amide (100 x 4.6mm, 3.5um) CH:SOLVENT_A 95% water/5% acetonitrile; 10 mM ammonium hydroxide; 10 mM ammonium acetate (pH CH:SOLVENT_A 9.0) CH:SOLVENT_B 100% acetonitrile CH:FLOW_GRADIENT 0 min, 15% A; 2.5 min, 30% A; 7 min, 43% A; 16 min, 62% A; 16.1 to 18 min, 75% CH:FLOW_GRADIENT A; and 18 to 25 min, 15% A CH:FLOW_RATE 400 μl/min CH:COLUMN_TEMPERATURE 275 #ANALYSIS AN:ANALYSIS_TYPE MS #MS MS:INSTRUMENT_NAME Thermo Q Exactive Plus Orbitrap MS:INSTRUMENT_TYPE Orbitrap MS:MS_TYPE ESI MS:ION_MODE UNSPECIFIED MS:MS_COMMENTS A 15μl aliquot of the sample was used for high-resolution HPLC-tandem mass MS:MS_COMMENTS spectrometry. High-resolution HPLC-tandem mass spectrometry was performed on a MS:MS_COMMENTS Q-Exactive (ThermoFisher Scientific) in line with an electrospray source and an MS:MS_COMMENTS UltiMate 3000 (ThermoFisher Scientific) series HPLC consisting of a binary pump, MS:MS_COMMENTS degasser and autosampler outfitted with a XBridge Amide column (Waters; 4.6 mm MS:MS_COMMENTS × 100 mm dimension and a 3.5 μm particle size). The capillary of the MS:MS_COMMENTS electrospray ionization source was set to 275 °C, with sheath gas at 45 MS:MS_COMMENTS arbitrary units, auxiliary gas at 5 arbitrary units and the spray voltage at 4.0 MS:MS_COMMENTS kV. A mass/charge ratio scan ranging from 70 to 850 was used in MS:MS_COMMENTS positive/negative polarity switching mode. MS1 data were collected at a MS:MS_COMMENTS resolution The automatic gain control (AGC) target was set at 1 × 106, with a MS:MS_COMMENTS maximum injection time of 200 ms. The top five precursor ions were fragmented MS:MS_COMMENTS using the higher-energy collisional dissociation cell with normalized collision MS:MS_COMMENTS energy of 30% in MS2 at a resolution of 17,500. Data were acquired with Xcalibur MS:MS_COMMENTS software (v.4.1; ThermoFisher Scientific). Analysis was performed using MS:MS_COMMENTS MeatboAnalyst (v5.0) with peak area normalized to total ion count for each MS:MS_COMMENTS sample. #MS_METABOLITE_DATA MS_METABOLITE_DATA:UNITS Peak area MS_METABOLITE_DATA_START Samples 1 2 3 4 5 6 7 8 17 18 19 20 Factors genotype:wild-type | treatment:no treatment genotype:wild-type | treatment:no treatment genotype:wild-type | treatment:no treatment genotype:wild-type | treatment:no treatment genotype:wild-type | treatment:IL-4 genotype:wild-type | treatment:IL-4 genotype:wild-type | treatment:IL-4 genotype:wild-type | treatment:IL-4 genotype:ApoE-KO | treatment:no treatment genotype:ApoE-KO | treatment:no treatment genotype:ApoE-KO | treatment:no treatment genotype:ApoE-KO | treatment:no treatment (S)-4-hydroxymandelonitrile 1269325.845 1843675.605 1450533.054 586437.7325 2399396.597 1957623.081 1524374.281 1361895.183 631491.9904 600842.506 717381.7018 1112970.523 1,3-bisphospho-D-glycerate 0 29680.83635 45474.95767 10859.80957 0 0 19468.10112 0 20774.74975 0 19485.11074 0 1-methylnicotinamide+ 15992201.79 8819394.041 3958120.7 24370980.88 4954145.22 15838733.35 13901678.15 5269296.558 16586929.39 13027792.23 14388712.98 8431610.49 1-phenylethylamine 690329.3879 844911.9922 762096.8706 856677.9228 1226124.602 1273986.601 988894.1051 1145627.434 551547.4954 1065135.519 978230.0356 1101934.691 2- / 3-phosphoglycerate 2059849.809 2434090.22 1690346.989 2010215.895 6702122.979 6181934.278 7355115.485 5048109.81 1161150.275 1525177.901 1260534.421 1969328.998 2-(Formamido)-N1-(5-phospho-D-ribosyl)acetamidine 14659.79596 0 0 0 0 0 0 0 0 11056.48285 16879.35088 19148.75318 2,3-bisphospho-D-glycerate 10314.38826 0 0 0 10541.06303 0 0 0 0 0 0 0 2-aminobutanoate / 2-aminoisobutanoate 0 0 0 0 0 0 0 0 0 0 0 0 2-HG 955804.4027 725512.0293 1072044.484 1464297.153 2435608.436 3108472.331 1678018.451 1889369.005 894295.4809 888686.597 1049034.303 1203292.125 2-hydroxybutanoic acid 5710096.688 2624744.41 2633887.972 5855345.616 3517491.182 2943756.258 3342414.627 3173581.432 4048241.768 2445119.934 4005698.116 2569747.311 2-keto-isovaleric acid 3830045.619 11285502.5 9190746.64 2329100.316 0 5613504.358 4243766.699 3826080.985 0 0 3233004.437 12233278.34 2-ketovaleric acid 1678562.376 0 0 0 2413435.73 0 0 0 0 0 0 3569601.153 2-oxoadipic acid 0 0 0 0 0 0 0 0 0 0 0 0 2-oxobutanoic acid 0 0 0 0 0 0 0 0 0 0 0 0 3- / 4 -hydroxybutanoic acid 31991711.09 23765630.45 20246024.01 33840228.12 15019586.18 38515113.82 35436075.63 30310759.69 23746923.36 38473767.47 45751469.36 52378910.61 3- / 4-hydroxyphenylacetic acid / vanillin / 11169702.83 25209163.14 16092577.55 10213421.46 11459328.85 14818566.11 18634588.33 8937799.282 8139765.464 8841094.774 11412552.25 12190890.86 3- / 7-methylguanine 440304.1812 792867.57 663316.2128 391103.994 928817.5214 947932.229 632756.4171 563639.5578 223347.2853 209791.4548 380353.0473 691336.8804 3,4-dihydroxymandelic acid 0 0 0 0 0 0 0 0 0 0 0 0 3,4-dihydroxyphenylpropanoate 0 0 0 0 0 0 0 0 0 0 0 0 3-aminoisobutanoate 352038.0245 404929.2971 325711.7079 478055.5953 340851.8975 596762.6671 559566.7322 493059.0152 616302.3051 746776.4979 634130.5456 697899.2774 3-hydroxy-anthranilic acid 0 0 0 0 0 0 0 0 0 0 0 0 3-hydroxykynurenine 0 263889.7847 0 42695.91515 323936.2885 0 0 91279.85115 0 98152.47611 19610.15084 128227.465 3-hydroxypropanoic acid 0 0 0 0 0 0 0 0 0 0 0 0 3-methoxytyramine 0 0 0 0 0 0 0 0 0 0 0 0 3-phosphohydroxypyruvic acid 0 0 0 0 0 0 0 0 0 0 0 0 3-phospho-serine 3459342.608 2920803.525 3071687.433 3014232.555 7449983.93 12090730.1 8818677.705 5860367.655 2203252.146 797681.7905 2353007.138 830774.4345 3-ureidopropionic acid 0 0 0 0 0 0 0 0 0 0 0 0 4-hydroxyphenylpyruvic acid 84736.60426 54609.86643 37035.02598 35383.53609 278128.1731 0 24662.75527 54821.43289 46632.5626 0 39232.56008 0 4-hydroxyproline / 5-aminolevulinate / N-acetyl-b-alanine 0 0 0 0 410595.0378 465559.1541 641882.2938 160325.5756 0 0 0 0 4-phosphopantothenate 7677.562502 0 0 17825.75894 0 5571.456469 0 0 0 0 29474.1647 0 4-trimethylammoniobutanoate+ 11113321.11 12803138.14 11682181.42 9734202.226 21743698.76 21608316.02 18162835.54 18027258.8 6550535.637 7203117.441 7796714.61 7978330.696 5,6-dihydroxyindole 0 3905329.828 0 0 0 0 0 0 0 0 0 0 5-methylcytosine 1082161.322 1188058.806 889265.3166 998330.3709 961840.1391 1016840.128 874013.055 731679.327 728332.4929 589700.0567 1009298.847 826401.1698 5-methyl-THF 0 0 0 0 0 0 0 0 0 0 0 0 5'-methylthioadenosine 82112972.73 139378595.1 61904693.38 70808266.43 244783003 260547060.8 255468322.5 189390118.9 39597186.32 32936541.24 35320679.49 31974487.06 6-aminocaproic acid 0 0 0 0 0 0 0 0 0 0 0 0 6-methylnicotinamide 0 0 0 131293.404 0 0 0 0 111215.2306 0 267690.6513 183788.2523 6-O-methylguanine 0 10075.631 6945.916336 0 0 0 0 0 0 0 0 0 6-phosphogluconic acid 110882.2134 97405.76801 124928.3951 104235.7429 360921.6579 305702.4531 314982.2294 417270.4442 81754.29882 95470.93363 328575.1476 164072.4283 6-phosphoglucono-D-lactone 18523.6274 19453.81808 19190.32241 17106.98151 15318.12233 0 0 0 11844.58217 8793.5079 0 20300.17632 acetoacetic acid 0 0 0 0 0 0 0 0 0 0 0 0 acetylcholine+ 4191716.138 5474158.602 5566726.402 3812208.666 10878909.92 9830603.965 10893149.24 9628225.318 4863310.975 4378563.199 5202870.139 6099429.049 acetyl-CoA 35655.11889 21265.86891 0 36858.26949 0 0 0 0 50276.85043 0 0 0 aconitic acid 371799.2728 94871.33705 0 71346.17467 0 672638.2098 365191.9775 153308.9303 99709.28014 0 0 0 adenine 8794347.379 10514285.59 5362642.529 4255958.207 16165852.22 15693325.36 15306901.24 10954994.28 3312274.468 2038930.428 2794347.969 2807096.744 adenosine 2175289.897 1676083.895 2586175.876 1864814.322 1406997.219 3245918.257 2827289.871 2265548.896 1854904.422 1086919.808 1785104.424 1067169.087 adenylosuccinate 78304.72365 107378.8721 63426.47923 71856.72361 33632.4926 62744.14731 22604.95936 39099.21945 12149.88089 0 45291.4481 0 ADP / dGDP 50885292.48 48139908.43 31281759.49 47571247.61 73746122.4 93031737.43 93197345.03 76097277.09 31293330.11 15301405.74 22423913.43 15839532.11 ADP-D-glucose 0 0 0 0 0 0 0 0 0 0 0 0 agmatine 416984.1759 886508.807 768678.8519 571295.8591 276181.251 197308.584 141892.276 100635.2044 290997.9325 234059.1329 498996.3984 815958.3406 AICA ribonucleotide 0 0 0 0 635363.8533 682839.1423 847799.5391 502302.5553 0 0 0 0 a-KG 0 0 172706.9931 0 226189.7522 180696.4199 492632.0089 154444.7252 0 0 0 242824.6174 alanine 97803548.44 162189787.1 106447540.8 84714994.46 266663201.4 278585318.1 180141833.1 170230832.9 74584942.48 43306510.02 111534151.3 143695555.8 alanine methyl ester 13742279.59 12033246.75 11027050.89 2905112.8 11743416.32 18153365.23 15500395.68 11146508.23 11747996.15 8134161.624 12880418.79 9152435.826 allantoin 13236877.17 21110991.71 17755684.52 10420894.81 23484215.93 23964321.13 16296282.49 14583368.27 8665045.311 7542158.742 12882422.51 21934048.29 AMP / dGMP 12269482.29 10556180.1 11787439.6 10414896.9 17036662.34 21534559.99 17526086.26 16713140.21 7383346.96 5803917.625 8614318.366 6114871.847 anandamide 99567.85004 272718.1964 137937.9644 81377.02413 243569.96 812019.192 157656.164 0 244640.6746 465257.4132 0 258574.5523 arginine 1943390123 3347696064 2501534493 1730171380 1702414340 1486471470 834455872 850730208.6 1086665134 967845322.3 1849511054 3063506293 ascorbic acid 0 0 0 0 0 0 0 0 0 0 0 0 asparagine 1038991.632 2840541.565 1533015.462 1089498.433 2914067.518 3271002.278 1887925.085 1786883.501 682951.2231 869435.3675 1782499.319 1963828.442 aspartic acid 353509258.2 312407229.9 229369854.6 330250810.5 305820601.7 646882472.5 632384016 460945718.3 225454670 210605837.7 236806431 208627063.2 ATP / dGTP 214955816.7 237609398.8 100069494 196750255.4 271394475.8 315974289.9 270795867.8 282103737.8 108286994.3 68792437.16 81686403.14 53733018.38 b-alanine 18522035.51 7048971.704 35363851.59 1224516.2 83630932.97 55178125.94 101570678.9 76189265.21 12259019.48 2856493.888 286077.5461 3313991.873 betaine 2373366720 4444621589 3010874226 1619524659 2307303911 5888066334 5002485548 4832603149 1511986696 1389237382 1588492422 1866228014 butyric acid 3316102.956 2956974.84 1426003.034 2543825.105 1112047.535 2671959.101 2115914.586 1668749.1 0 2540907.507 3036738.426 3726920.038 butyric acid(iso) 157270.4235 0 0 213986.1668 0 85341.07693 0 69169.98886 668366.5215 653279.1523 979486.9752 1616072.999 carbamoyl phosphate 0 0 0 0 0 0 0 0 0 0 0 0 carnitine+ 24560072.96 32097247.97 26630558.61 21491289.37 55629614.48 49935125.15 44885794.42 46097696.27 19007258.23 18658399.69 18281052.28 22303916.81 CDP 2638887.267 2827855.738 1487290.242 2406138.347 5568037.85 5107988.516 5398324.029 5046837.32 1760059.466 1301091.937 1252084.974 840940.7489 CDP-choline 5150563.641 5693053.77 4627224.67 4825187.555 2635900.98 3353332.241 2740303.33 2655230.094 2688243.277 1141668.705 2801108.931 1537905.499 cGMP 0 0 0 0 0 0 0 0 0 0 0 0 choline+ 2359317185 3330614097 2962732551 2017514878 3817266409 3293207000 2907704288 2824611108 1743742549 1880008651 2033312820 2922478430 citraconic acid 30459842.44 54683230.3 16887988.47 17443062.29 16023027.23 37378760.37 14190606.1 12386828.15 11437126.89 16527814.51 16035707.5 26427047.65 citramalic acid 42240871.26 28130824.24 22156789.73 27158213.07 34204283.58 47611820 27736395.35 27082757.43 23121752.75 13946703.57 31907331.33 23218030.95 citrate / citrate(iso) 401092789.5 402348055.4 181695929.4 267189028.4 921828100.4 1873570031 984216201.9 795299617.5 102258038.6 67302933.62 127808733 115723036.7 citrulline 0 31398.82366 0 0 0 0 0 0 0 0 0 0 CMP 10583481.52 10916548.61 11158115.44 10971169.44 12460176.77 13183916.43 10100705.45 10608630.23 7109652.134 6482785.993 9246468.166 9020358.268 cortisol 38383.95057 47659.08573 0 25054.72499 18845.8788 83929.289 83642.0682 37919.43837 27209.53982 126055.5538 0 18993.5789 creatine 20575184.03 26492002.22 24354053.94 17934871.69 128649031.7 142443443.7 117718415.8 102390069.8 17034426.83 10548238.8 16341496.25 12882335.36 creatinine 168573588.5 266375781.5 228637189.5 116518828.9 434771701.8 412286600.3 335902680 295526249.7 109928792.1 108920877.2 137068452.2 233979411.6 CTP 11820973.81 11931020.6 6685198.504 10373960.09 21717000.71 27733537.65 23593582.02 21772803.61 5200390.372 3456536.844 3627949.644 2131968.011 cystathionine 1024305.011 1566416.293 1339996.273 935863.4785 4590596.548 4457789.131 3623903.365 3209153.22 575123.5507 522613.8018 944190.4266 1247533.66 cysteine 0 0 0 0 0 0 103660.482 0 0 0 0 0 cysteine-S-sulfate 0 0 0 66623.18664 0 0 0 0 0 0 0 66473.0215 cystine 3259454.432 2233823.362 9861122.482 8159827.02 754273.3632 1262935.129 227651.6522 239200.5092 5717195.62 1886509.018 11114018.39 16576269.8 cytidine 1992342.54 2868307.833 1750692.123 3173369.802 757387.7687 1239252.691 522909.7034 453638.2509 5335587.569 2330882.344 5551945.647 4284485.891 cytosine 5357650.919 6074019.851 5497665.501 4577108.447 4282566.11 4065386.396 3451609.748 3399716.425 3463464.666 2524821.376 3134848.668 4071084.038 dADP 0 0 0 0 0 0 20079.51476 0 0 0 0 0 dAMP 16444.90096 50912.4786 0 34051.74547 0 16308.6234 31408.69168 40063.68592 0 0 0 0 D-arabinono-1,4-lactone 0 0 0 178430.1547 0 0 0 0 94371.90243 129600.6015 130891.8747 90855.08172 dATP 0 0 0 0 13845.20448 31164.86562 38286.49096 11244.7737 0 0 0 0 dCDP 32357.13307 27084.30514 0 9131.39736 373270.6001 245468.0795 374520.5686 173377.0414 0 8978.697537 0 0 dCMP 694639.1342 676144.9944 738176.7485 700974.3465 2224055.408 2584690.931 1966804.277 1796244.648 333379.0891 276249.0889 569415.2779 382753.9979 dCTP 548294.3065 616524.4367 360098.9035 506990.4567 2174647.631 2557925.638 2039586.041 1858267.429 217741.3673 124187.1842 136807.056 118146.2363 dehydroascorbic acid 0 0 0 0 0 0 0 20461.32628 0 0 19343.29234 0 deoxyguanosine 0 0 0 0 0 0 0 0 0 0 0 0 deoxyinosine 142975.9328 109562.3506 162573.9495 128748.7461 0 21457.51096 0 0 15541.19921 10994.97115 27267.3955 0 deoxyuridine 538571.7855 1293936.245 836783.3511 339891.6754 1487684.835 1632472.337 905883.8583 899156.0301 422088.786 286920.7457 523400.9709 1133664.007 D-erythrose-4-phosphate 0 0 0 0 0 0 0 0 0 0 0 0 D-galactonic acid / D-gluconic acid 2970778.017 3558201.417 1919273.937 1810408.813 7098732.53 8554056.136 5165483.269 4556323.735 599690.4761 770737.2574 1531696.594 1340303.625 D-galactosamine/glucosamine-1-phosphate 0 0 0 0 0 0 0 0 0 0 0 0 D-galactosamine/glucosamine-6-phosphate 10749.7412 8346.965312 7396.242209 13536.91786 78070.70198 17825.99054 10238.93002 59505.68488 7420.787088 7745.108341 6809.99906 47977.40829 dihydroorotate 35702.20678 0 0 0 0 0 0 0 0 0 20375.18396 65763.42728 dimethylglycine 1969621.426 2210455.044 1811341.695 1592276.225 5435748.813 9408410.504 4466514.634 7708030.468 0 0 0 0 DL-DOPA 0 0 0 0 0 0 0 0 0 0 0 0 DOPAC 25329.12039 10922.79504 6682.684152 6596.294992 79167.96288 0 5029.986253 6410.022287 27324.20882 19783.17917 16385.66543 22442.65811 DOPAL 255372.7457 273862.716 243435.6774 362414.9693 179932.8391 264356.8817 417886.2838 387733.4445 369987.299 258800.1009 375325.1711 523820.3467 dopamine 201930.7922 532475.3263 391962.0863 326467.5061 620946.2447 554987.8214 412163.788 559343.145 484324.6428 686975.5739 462405.6072 508807.7311 dopamine quinone 6491119.351 23468709.02 0 0 0 5540638.462 4476763.442 3374651.648 0 0 0 0 DOPEG 507839.9268 864842.6104 638922.8267 274519.3432 627535.8831 387568.9761 461657.0371 1035151.03 735441.5414 578323.9495 797314.0819 926430.1224 DOPET 375128.3161 312920.2192 347047.016 247339.5015 119960.6876 86405.53523 141703.5808 28309.4904 33293.52994 261042.4395 201825.5519 404387.5724 D-ribose-1/5-phosphate / D-ribulose 5-phosphate 412047.5351 480354.1827 410980.3029 239647.1347 1294342.493 1790587.307 1505226.505 1208112.837 113149.3085 99411.99397 116541.5999 333060.3423 D-sedoheptulose-7-phosphate 428864.5037 717762.4198 432624.3529 443335.1963 2183853.37 1459715.746 1502445.141 1993075.347 90111.52858 464224.8082 191693.3039 1031095.834 dTMP 0 0 0 0 0 0 0 0 0 0 0 0 dTTP 0 0 0 0 202523.0003 187642.292 163097.4013 114007.5585 9542.246905 0 0 0 dUMP 0 0 0 0 0 0 0 0 0 0 0 0 dUTP 0 0 0 0 0 0 0 0 0 0 0 0 epinephrine 133810.7013 204633.2965 205243.1539 92650.02413 49332.67726 75562.86858 51144.60763 85817.91164 198925.6614 99184.91002 132552.0221 55893.96661 ethyl acetate 8402002.363 12782459.39 9709363.735 7184957.808 9717563.544 8466893.314 8317354.671 9800269.777 6306530.658 6706263.424 7932399.371 7007871.51 F-1,6/2,6-DP 6261444.531 6392895.11 4446565.795 5047958.556 14863861.99 14881340.43 15104557.18 12809331.73 3443889.658 3083562.422 3579695.911 4383558.07 F1P 77381.99275 38361.20307 19146.89456 27169.44859 39133.90857 20186.28871 26737.38314 0 0 0 21902.47643 0 F6P / G1P / G6P 4974038.238 5352534.239 5027218.443 4272076.815 14998074.91 12433244.82 10287231.11 11846159.83 2521380.306 4932462.224 3751430.579 9764167.491 FAD 71081.06329 0 0 0 0 0 0 0 0 0 0 0 FMN 0 0 0 0 0 0 0 0 0 0 0 0 folic acid 2411637.604 3639021.701 3489102.659 2232487.805 3751330.455 3802138.884 2056011.484 2051280.488 1684821.035 1738669.352 2988778.095 5287225.546 fructose / mannose 102986083.5 139961948.8 130094690.6 84429307.61 83208453.36 170488862.4 101900557.6 90541735.06 86978077.26 64175715.7 135977198.7 219385190.6 fumaric acid 0 366912.898 237266.2084 0 935219.2607 1345224.93 1349866.564 495973.492 119590.0785 119134.4514 159806.3154 136937.5926 GABA 2575824.802 2417053.778 2417973.094 1544532.309 10167995.46 6798214.437 9127683.164 8025522.935 2559752.827 1172360.77 1738035.765 1039425.195 galactosamine / glucosamine 342436.0105 456291.2116 472319.8964 648533.6642 356940.6677 177848.2026 78781.67946 32842.64558 1072545.289 588701.3923 1427532.722 1973156.09 galactose / glucose 417641283.4 573832012.1 553667951.2 531842182 514072282.9 592211540.3 327409959.5 292050619.8 385471975.4 440135103.9 731554866.3 1115263159 GalNAC/GlcNAC/ManNAC 4195944.922 4476383.245 3185034.053 3751067.995 1859067.009 1393725.238 1081946.52 823382.5303 3118563.407 2859514.235 3569300.154 3501978.488 GAP / DHAP 711937.2331 766127.8731 713192.3675 716147.9752 3563248.247 5137474.556 3641687.268 2631402.304 456918.47 393061.8742 455250.919 766227.8441 GDP 6240323.237 4569105.791 2528786.482 4699040.973 5352745.285 6522054.219 6401858.583 5286604.892 3076619.397 1996553.555 2059596.007 1544268.741 GDP-L-fucose 973889.4646 909375.7056 679144.347 624707.8941 1407935.91 1884254.109 1301118.863 1142842.029 492274.5903 491560.5924 681910.9049 661993.556 glucono-lactone 1816704.014 932755.234 980604.2573 104560.5621 1075125.82 1386845.401 717104.9884 1331061.22 1584641.428 1315035.627 2429477.441 2730709.714 glutaconic acid 3207810.826 1739637.21 1012012.239 2285121.3 2569945.585 1765941.064 1321635.663 1429232.385 2104435.616 1846077.95 2187639.157 1915860.195 glutamine 85723762.98 126010742 123386711 75956469.91 180592220.6 190282052.7 118172773.2 116296730.5 65003666.05 56018905.72 95599665.99 156434287.9 glutaminic acid 120093407.3 127629468.8 115600426.5 114561211.5 291466899.5 312967206.7 270778214.6 243002502.4 85037062.01 65736334.96 102729210.1 94329994.33 glutathione 1340809.153 1102407.494 575097.017 940105.6519 1894016.947 2014413.095 4467062.31 2996665.851 679125.5332 495460.0659 548838.164 320219.075 glutathione disulfide 126871593.1 148639423.2 123121193.7 124875391 221998467.1 204185404.8 199427292.4 184435245.1 79943903.27 74873593.65 100868518.1 90747715.21 glyceraldehyde 0 0 88189710.5 199023192 69322736.17 0 0 0 109837809.8 181478103.8 269154897.2 416226720.3 glyceric acid 1076672.448 652828.514 529425.7759 7669183.639 224727.0163 2272258.891 2110260.227 707972.2069 7853777.683 6845741.845 7664709.582 11062069.44 glycerol 2/3-phosphate 13301187.78 17342862.25 13301166.54 12219496.94 42227116.75 39680390.47 36094568.88 33535143.3 8858471.87 10058386.7 10519305.2 13384192.97 glycine 9443030.374 13706637.58 9488294.198 9438111.122 22311942.4 20759976.83 16143930.71 16236129.47 8407655.026 8029213.661 9619110.716 15820349.24 glycylglycine 0 0 0 0 0 0 0 0 0 0 0 0 GMP 2968989.638 2387210.2 2018561.571 2043603.787 2927737.817 3089856.636 2656382.961 2818031.804 1235764.592 972634.0672 1430598.946 1088738.95 GTP 14763296.43 15009680.13 4449445.109 13919271.6 16227570.19 24787482.45 19168766.92 18494313.74 6099778.135 3110806.716 3358806.281 2324119.882 guanidine 2080061.364 1794239.417 2162389.974 3482317.021 0 1569225.346 816495.3868 747769.9754 3446650.592 9504204.974 3299090.689 1974117.978 guanidinoacetate 0 0 0 0 2084969.851 2852178.782 2015040.104 1814219.669 0 0 0 0 guanine 459514.0502 604678.647 1139613.627 342277.1365 252607.7105 358905.6529 138670.3835 120912.7102 158272.4398 121542.7714 230234.9428 278666.7789 guanosine 727953.3741 519753.7742 282716.2116 587948.503 15765.57676 305336.488 159991.5434 172407.2263 429772.0578 166288.9494 395130.5211 207771.4371 gulonic-lactone 8708198.305 5978990.145 4816898.597 6391093.356 3584042.357 4997736.656 4547764.908 4240501.91 6316179.282 3822995.051 8068385.529 8407013.68 histamine 0 0 0 0 0 0 0 0 0 0 0 0 histidine 68164336.37 71517309.36 54369176.38 61595269.29 63856663.95 78157476.69 64199101.36 58848904.09 53526417.6 41169393.95 54143241.91 59805357.48 homocysteine 0 0 0 29175.39776 0 0 0 0 28743.23868 0 115484.4168 213699.5629 homoserine / theronine 47546796.95 81373653.32 67836062.8 40115789.04 107593185.4 105738293.1 61452891.01 58007152.9 33338349.5 30069017.47 53240511.06 94093880.98 homovanillic acid 10946.42936 33491.91747 0 0 31381.16306 0 0 9891.227351 0 0 40666.70596 0 hydroxyphenyllactic acid 2202228.35 1862182.547 2081130.102 1193081.589 4139414.26 3144825.619 3278100.236 2927700.028 658466.6614 651535.8427 1095881.051 1820637.547 hypoxanthine 8828841.512 15988153.58 13102115.32 6460379.548 2750252.264 3482977.663 2531557.182 2181132.458 6327781.44 5232837.21 8679641.878 14122538.93 IDA 740210.3618 361286.1388 410028.806 422371.0234 566261.1586 453965.9354 704108.7304 975050.9345 471426.0295 232790.3275 129081.1288 1518829.854 IDP 0 26294.235 0 0 0 0 0 0 0 0 0 0 imidazole-4-acetate 45742.13513 0 0 0 0 158425.9813 0 0 26577.93341 11799.01269 24195.99676 0 IMP 2850279.502 2402862.987 2093715.676 2393272.427 1950423.838 3163857.969 2371148.887 1754007.248 1609889.501 361535.7593 1662258.919 406030.409 inosine 77524.45016 0 33034.71091 17168.74403 35649.55786 37485.69295 0 16006.83606 23118.31305 0 14014.32444 0 isonictinic acid 124478.5365 0 0 154965.5388 0 0 0 0 222186.0837 266112.1334 137266.448 242863.3408 itaconic acid 190581.7797 1954328.17 142439.6365 1045617.599 2636140.591 109891.8764 96709.61767 1377397.682 720417.0833 621060.9002 1134200.759 962799.955 kynurenic acid 85251.35218 73486.90282 188111.9709 13670.73404 85108.58731 67321.16473 14585.50808 30994.43421 10328.01203 0 32440.59542 76680.7631 kynurenine 403135.5517 790729.8783 1276276.331 225295.4743 1380669.306 1192795.436 872611.256 651032.6325 400169.8646 381581.4348 545845.7192 1003778.241 lactic acid 3612928087 3861938910 2993186598 2513376026 3326164128 5180208037 3741738864 3122662577 2042411518 2089143680 3096583176 4543047660 L-arginino-succinate 806273.6631 918863.8276 791494.8753 672849.2553 1580622.14 1700425.304 1367054.586 1087036.918 495032.6396 469954.648 607826.2947 736464.0592 L-cysteic acid 0 0 0 0 0 0 0 0 0 0 0 0 leucine / leucine(iso) 2309660710 2940806113 1953319968 2395789372 2169346204 4537592822 2909278016 1936670304 2506341992 1889132664 3379716068 5179634639 levulinic acid 5948786.588 5477821.275 6514770.861 7354397.518 5885779.159 9418540.179 7014798.678 6368367.408 5803920.755 7831511.008 5199933.636 3092581.763 L-NMMA 14788789.36 20043374.88 12989679.87 10053949.74 44577860.2 39952900.89 28875564.58 26071294.13 5748465.39 4530822.023 9345182.933 16202114.48 L-tyrosine methyl ester 9822.943086 353813.349 21901.38328 29745.65041 11539.38351 137170.4205 0 107004.713 24770.24728 154655.0969 18130.65757 0 lysine 963326171.3 1558528693 1409956376 852978123.8 3036349985 2767892482 1802847637 1783091023 527733176.6 525534809.2 991822936 1686984643 maleic acid 3255346.146 2164375.542 1933694.344 3104858.347 0 6362261.387 5557184.878 3460760.119 1678534.176 1514197.392 1991311.459 1647316.338 malic acid 33174183.42 27749589.9 23019051.58 34017697.21 0 76518423.69 72363923 38770013.41 0 0 21224037.55 16153336.62 malonyl-CoA 0 0 11326.74877 46635.65489 0 0 16774.78141 0 0 0 36170.18212 22181.78668 mesaconic acid 0 0 0 0 0 0 0 0 0 0 0 0 methionine 436108621.2 792211510.3 528120621 334418687.3 336926365.7 798399012.2 516504808.7 479088547.4 263402541.9 281120333.7 446427003.9 864767998.3 methyl acetoacetate 0 0 0 0 0 0 0 0 0 0 0 0 methylglyoxal 0 0 0 0 0 0 0 0 0 0 0 0 methylmalonic acid 362095721.4 311296143.7 283408145 104127833 329241332.5 163877311.4 171446286.9 224653537.9 97238910.88 161852327.2 151096666 228642378.3 mevalonic acid 13089927.97 9911122.52 5956490.698 11723301.84 5109671.524 11632662.03 11340333.28 8113955.27 12228686.59 7856881.154 14450220.28 13415924.49 N1/N8-acetylspermidine 0 0 0 37895.94267 0 289104.2725 38002.27847 35684.98482 40730.71188 55873.41055 0 31767.0183 N-acetylaspartic acid 1666776.046 2144057.651 2245947.939 1246355.411 1281957.741 592748.0762 984388.7157 1579242.815 816843.505 916105.513 1515119.974 718266.7009 N-acetylaspartylglutamic acid 45819.25797 36954.49453 112107.1263 49725.82731 52271.00217 297880.8772 171448.3889 254887.7118 0 0 16130.43104 26072.00527 N-acetyl-DL-alanine 56262219.48 77449122.12 61100849.08 43862643.27 66998298.44 80273705.33 75557614.34 76278671.59 32926058.4 50244222.89 52383466.37 66585991.46 N-acetyl-DL-serine 13708271.3 4997208.035 2570047.104 34839589 1674073.157 7758023.887 6996478.968 8030055.508 87657318.34 50312993.98 76247695.78 25699434.6 N-acetyl-dopamine 0 0 0 0 0 0 0 0 0 0 0 0 N-acetylglucosamine 1/6-phosphate 1078430.201 1499392.174 1094962.857 1097508.504 2181776.262 1920081.299 1885989.801 2053243.776 625947.915 993311.1734 925015.1861 1421845.334 N-acetyl-L-glutamic acid 0 0 0 0 0 0 43238.91902 0 0 0 0 0 NAD+ 46850505.22 50741025.1 38572313.94 42585396.38 93144330.14 108510807.4 91279911.88 93570915.11 32730190.63 25203249.62 33253584.16 28582933.08 NADH 0 0 0 0 0 0 0 0 0 0 0 0 NADP+ 5034650.192 4909078.419 3325793.694 4468253.103 9628037.052 10582100.57 7710315.504 6783604.12 2554820.636 1661526.813 2896863.87 2204069.855 NADPH 15130.04205 72421.18567 24728.48326 0 160884.1245 115049.0101 111538.0174 125815.8281 23627.51466 35796.13104 7755.430475 28347.12236 N-carbamoyl-L-aspartate 36172.3335 0 0 21343.48002 913234.9308 1545270.468 1118111.975 751585.9515 0 0 0 0 nebularine 143045.3793 109541.4282 162584.0351 128670.0226 0 21404.62165 0 0 15505.23264 10974.38094 27301.10412 0 nicotinamide 173045083.2 386129957 316543903.8 183962540 343253367.9 398787199.5 305476775.4 271024537.3 128984523.1 136193644.2 195654812.9 257529412.7 nicotinamide riboside+ 0 0 0 0 0 0 0 0 0 0 0 0 nicotinic acid 2202952.44 2717309.87 2744052.77 2146877.022 3668451.73 3830479.59 3659094.226 3029190.564 4635124.413 3125509.073 3978567.312 3033581.076 N-methyltryptamine 0 0 7687.576642 0 9332.980392 0 0 0 0 0 0 0 NMN 290572.1118 290391.497 232258.7867 184388.9608 549043.3742 737812.6145 553691.6145 446461.8026 191476.8621 63579.31319 172423.7058 57598.30377 norepinephrine 1095179.21 0 46946.82459 5570511.342 0 0 8015341.87 7019874.065 3695423.373 3930306.296 3582764.142 4446649.087 O-acetyl-L-serine 21026294.98 23041657.39 22196189.42 11097164.43 25057675.23 21145971.19 25704473.32 32797929.66 9265515.207 13539777.25 12992206.29 19680767.44 octopamine 1412628.914 1522342.743 1001478.227 1362988.954 1152230.695 1516409.789 1783133.125 1918630.072 1414971.08 1035464.077 919973.2715 1242121.935 ornithine 51465134.53 78533953.33 68089460.52 43574552.47 1399380283 1106051984 852874404 784620049.7 19502460.54 17494609.58 34266481.86 71246944.27 orotic acid 328235.5111 419400.1544 181037.8004 334674.3745 126764.0688 172852.2268 70225.48976 48096.80786 0 66974.76463 0 108819.753 orotidylic acid 30967.53204 12419.15661 0 12740.62545 0 0 0 0 0 0 0 0 oxalacetic acid 260524.1073 0 0 0 0 0 0 0 0 0 0 0 pantothenic acid 141233411.1 159872012.3 63303153.36 140115079 60891609.12 265458639.6 121925658.4 64287669.62 140750172.1 124532203.6 221258033.3 359981986.5 phenethylamine 0 0 0 0 0 0 0 0 0 0 0 0 phenylalanine 395059199 694583879.3 582387089.5 307918480.8 814603880.8 822879421.6 497447205.2 443550566.1 234087144.2 252452096.3 404547642.6 724520583.9 phenylephrine / synephrine 40065.6407 198383.2198 22266.12789 9912.452106 41007.24012 55656.55243 39324.62517 6067.317414 54003.32274 18499.80218 41467.37831 74441.08565 phosphocreatine 734852353.1 806149626.8 698005723.1 645748126.1 3200095407 3185862184 2811089947 2706014004 437431320.9 431764484.6 491793668.6 532815118.5 phosphoenolpyruvate 387733.7923 445968.1198 253547.3343 385886.1301 1489738.293 1231601.282 1385895.971 1251993.672 239398.3098 275974.752 237901.9027 454668.946 phosphorylcholine+ 593729616.8 645857606.8 555343062.5 486708408.1 2107356079 2183777004 1808898648 1696731174 368499330.9 311464615 428792554.9 379101588.4 picolinic acid 4954389.542 4889087.258 4309329.203 5725713.178 2931296.738 5302845.043 4116214.329 4920260.171 6702129.976 6549434.74 6683697.897 6562378.971 proline 88994537.3 41332724.45 22255018.66 86032143.99 6057142.027 90810231.12 81052031.98 49228555.7 129125740.8 75734323.07 103075242.3 106004548.1 propionic acid 0 0 0 0 0 0 0 0 10590060.33 0 8006454.494 0 PRPP 0 0 0 0 0 0 0 0 0 0 0 0 pseudouridine 2061547.218 2166037.18 836347.6309 1778067.579 103073.9904 3358849.858 1723596.058 1150342.863 1353748.062 1587441.221 2381153.015 4791147.957 putrescine 672281.1349 295192.5102 12372.16025 615593.851 0 460640.5487 528564.0216 210337.1435 476505.3117 366633.1996 246607.6682 146146.7506 pyridoxine 0 0 0 0 0 0 0 0 0 0 0 0 pyroglutamic acid 1888365808 0 0 1199813796 0 1780005152 1827143394 2038328964 2002967033 1777030852 2442320704 2809871216 pyrroline hydroxycarboxylic acid 22193481.08 35552738.18 30973313.66 19641620.55 45578688.97 51262270.54 32371991.75 30387592.19 15910701.21 13653648.85 23868658.26 40466237.7 pyruvic acid 125119879.9 226432268.2 188125864.5 151532970.2 234063295.7 269869229.7 180898987.8 178173485.7 113577307.8 100034787 213007835.2 432929828.8 quinolinic acid 42109.79051 0 30653.16269 11640.8308 0 105288.4296 0 0 0 25429.56818 0 19768.29763 S-adenosyl-L-homocysteine 0 0 0 0 0 0 0 0 0 0 0 0 S-adenosyl-L-methionine+ 6093078.54 9212455.658 4489277.202 4192735.832 34368029.39 39333395.84 27406194.82 23573970.73 3112554.929 2021579.904 2842330.134 2724277.773 S-adenosylmethioninamine+ 8941.370789 0 0 0 21150.17895 39871.82353 10022.17018 16510.32218 0 0 0 18499.54458 SAICAR 0 0 0 0 70735.30495 41345.81074 61063.29269 39381.4785 0 0 0 0 sarcosine 3766826.05 0 60934592.07 0 54055485.16 75747085.91 118213347.8 0 56971230.08 30495406.59 0 77874737 serine 10783924.87 20116703.05 14749390.97 9518469.527 22463207.92 22390112.41 13774998.83 13193113.92 6723374.593 6363555.881 12975438.66 20248326.14 serotonin 21374.96114 38159.93533 24295.19831 51193.04761 43842.37169 62220.84616 84555.09661 28635.13777 65207.94555 131850.7206 23176.38631 98309.77744 sorbitol / galactitol / L-iditol / manitol 248739596.3 265890361.1 223197130.5 272852504.5 258673094.1 316965559.6 224646843 210559465.6 173857386.7 199204373.1 279134357.1 532909685.7 spermidine 169471201.1 70389696.52 42277204.14 176966715.9 7158414.757 54229420.27 52246010.8 40595769.02 57484279.72 39270285.34 39291893.12 31361938.12 spermine 729507.7926 230049.0006 402669.3697 1044847.388 0 303096.2302 308860.9344 231611.0639 754223.0562 585523.8781 544019.3177 665426.3456 succinic acid 46709895.28 66372813.1 51502357.89 42682705.6 69249452.54 72258097.08 55793259.73 50194787.15 33092913.51 41743524.8 46984074.33 59434616.07 succinic semialdehyde 0 0 0 0 0 0 0 0 0 0 0 0 succinyl-CoA 39291.00437 13291.20943 25689.84378 22125.04212 84489.41478 29989.30573 55663.7274 35173.26192 11000.27032 0 0 0 taurine 2849031823 1817835934 982702049.8 3069220098 1685046274 4694373593 4315901908 3857341971 3015280863 2828878274 3210153879 2674397297 thiamine+ 0 0 0 0 0 0 0 0 0 0 0 0 thymidine 779270.3296 4764296.887 5407669.759 2708998.413 1489998.121 1269411.427 1031978.365 1040215.721 2440394.463 2642144.716 3133008.267 3970067.7 thymine 1059176.002 1071632.049 1463786.303 1741831.05 1908284.167 1393704.117 1754908.849 1968298.798 1816075.906 1387059.657 1341858.695 1844640.383 tryptamine 15952.59975 0 0 0 54021.76397 0 26276.32355 25480.31339 47250.51119 27487.91048 11176.92647 29722.60517 tryptophan 45480886.67 88112815.72 78981332.37 34986314.57 120764786.7 109656684.4 69102291.18 62081063.85 29726449.87 29786458.09 48977704.21 94341325.79 tyramine 1646034.507 910595.7173 967715.963 1069675.632 696878.848 1423089.691 1959517.496 846566.3399 410770.4173 661282.4691 891106.2409 1389793.611 tyrosine 544440108.3 568377437.2 310365510.9 488216663.2 124812029 876145301.2 606526275.9 455005757.9 411180180.6 377488774 600873841.8 936233689.5 UDP 2991598.608 3345467.647 2127625.583 2761636.353 7305371.048 9383435.527 6760213.319 6120360.209 2266128.092 1189597.227 1582595.655 1270454.743 UDP-D-glucose 7134227.082 10175714.52 4876044.222 5608751.753 11854290.43 18428471.13 16628741.69 14563711.09 5787976.608 3703599.647 5724217.852 4224874.048 UDP-N-acetyl-galactosamine/UDP-N-acetyl-glucosamine 10961150.01 11761041.85 9413201.691 9406358.423 19352047.69 22169218.51 17153365.3 17122995.49 7253520.886 6431710.922 10308273.16 10287800.59 UMP 14871848.64 13291056.31 15734105.9 13426658.42 43322923.71 47306272.8 31428729.14 28687384.45 7369459.059 7087994.021 14269047.14 13517225.72 uracil 12780400.12 19482996.47 20075919.06 9470272.356 23156483.31 25111848.47 16862920.82 16725651.14 8578680.711 8482993.694 14451357.81 22383267.78 urea 754477.6967 1984460.7 1096775.106 412632.2173 2739754.38 3512260.451 2008469.813 1186778.293 359331.001 365496.6451 608683.2714 1064863.46 uric acid 1834000.594 3273280.464 2748589.752 1701406.318 4558135.569 4911652.384 2443927.876 1980946.654 1372202.305 1370914.651 2609197.544 6593974.477 uridine 2119345.16 2442344.741 1888378.599 1719793.011 477451.0351 298967.1511 248272.764 304593.011 1328038.144 1176305.629 1843613.91 2324523.177 UTP 8452922.514 10875473.27 4068256.062 7394088.551 21123564.13 23460275.16 21562055.45 19160177.8 5464917.735 3196742.842 4711677.697 3543411.777 valine 629550466.3 289161861.7 292297805.8 632116703.1 222519056.1 1102706263 836707057.4 626678395.7 538796685.5 554718068.2 985403631.9 1495870143 xanthine 3222276.746 7193396.365 5389681.303 2135995.706 3669573.075 3533245.851 1416844.491 1419134.475 1865012.207 1738403.319 3728735.814 8757756.42 xanthosine 0 0 0 0 0 0 0 0 0 22002.12315 56526.82736 13375.31295 xanthurenic acid 0 0 0 0 0 0 0 0 0 0 0 7210.489384 XMP 65012.07878 74937.80411 0 70439.84906 206143.6383 176933.7408 63395.8973 256565.8742 48566.34427 0 53305.63115 12172.17961 y-glutamylcysteine 0 0 0 0 0 0 0 0 0 0 0 0 MS_METABOLITE_DATA_END #METABOLITES METABOLITES_START metabolite_name (S)-4-hydroxymandelonitrile 1,3-bisphospho-D-glycerate 1-methylnicotinamide+ 1-phenylethylamine 2- / 3-phosphoglycerate 2-(Formamido)-N1-(5-phospho-D-ribosyl)acetamidine 2,3-bisphospho-D-glycerate 2-aminobutanoate / 2-aminoisobutanoate 2-HG 2-hydroxybutanoic acid 2-keto-isovaleric acid 2-ketovaleric acid 2-oxoadipic acid 2-oxobutanoic acid 3- / 4 -hydroxybutanoic acid 3- / 4-hydroxyphenylacetic acid / vanillin / 3- / 7-methylguanine 3,4-dihydroxymandelic acid 3,4-dihydroxyphenylpropanoate 3-aminoisobutanoate 3-hydroxy-anthranilic acid 3-hydroxykynurenine 3-hydroxypropanoic acid 3-methoxytyramine 3-phosphohydroxypyruvic acid 3-phospho-serine 3-ureidopropionic acid 4-hydroxyphenylpyruvic acid 4-hydroxyproline / 5-aminolevulinate / N-acetyl-b-alanine 4-phosphopantothenate 4-trimethylammoniobutanoate+ 5,6-dihydroxyindole 5-methylcytosine 5-methyl-THF 5'-methylthioadenosine 6-aminocaproic acid 6-methylnicotinamide 6-O-methylguanine 6-phosphogluconic acid 6-phosphoglucono-D-lactone acetoacetic acid acetylcholine+ acetyl-CoA aconitic acid adenine adenosine adenylosuccinate ADP / dGDP ADP-D-glucose agmatine AICA ribonucleotide a-KG alanine alanine methyl ester allantoin AMP / dGMP anandamide arginine ascorbic acid asparagine aspartic acid ATP / dGTP b-alanine betaine butyric acid butyric acid(iso) carbamoyl phosphate carnitine+ CDP CDP-choline cGMP choline+ citraconic acid citramalic acid citrate / citrate(iso) citrulline CMP cortisol creatine creatinine CTP cystathionine cysteine cysteine-S-sulfate cystine cytidine cytosine dADP dAMP D-arabinono-1,4-lactone dATP dCDP dCMP dCTP dehydroascorbic acid deoxyguanosine deoxyinosine deoxyuridine D-erythrose-4-phosphate D-galactonic acid / D-gluconic acid D-galactosamine/glucosamine-1-phosphate D-galactosamine/glucosamine-6-phosphate dihydroorotate dimethylglycine DL-DOPA DOPAC DOPAL dopamine dopamine quinone DOPEG DOPET D-ribose-1/5-phosphate / D-ribulose 5-phosphate D-sedoheptulose-7-phosphate dTMP dTTP dUMP dUTP epinephrine ethyl acetate F-1,6/2,6-DP F1P F6P / G1P / G6P FAD FMN folic acid fructose / mannose fumaric acid GABA galactosamine / glucosamine galactose / glucose GalNAC/GlcNAC/ManNAC GAP / DHAP GDP GDP-L-fucose glucono-lactone glutaconic acid glutamine glutaminic acid glutathione glutathione disulfide glyceraldehyde glyceric acid glycerol 2/3-phosphate glycine glycylglycine GMP GTP guanidine guanidinoacetate guanine guanosine gulonic-lactone histamine histidine homocysteine homoserine / theronine homovanillic acid hydroxyphenyllactic acid hypoxanthine IDA IDP imidazole-4-acetate IMP inosine isonictinic acid itaconic acid kynurenic acid kynurenine lactic acid L-arginino-succinate L-cysteic acid leucine / leucine(iso) levulinic acid L-NMMA L-tyrosine methyl ester lysine maleic acid malic acid malonyl-CoA mesaconic acid methionine methyl acetoacetate methylglyoxal methylmalonic acid mevalonic acid N1/N8-acetylspermidine N-acetylaspartic acid N-acetylaspartylglutamic acid N-acetyl-DL-alanine N-acetyl-DL-serine N-acetyl-dopamine N-acetylglucosamine 1/6-phosphate N-acetyl-L-glutamic acid NAD+ NADH NADP+ NADPH N-carbamoyl-L-aspartate nebularine nicotinamide nicotinamide riboside+ nicotinic acid N-methyltryptamine NMN norepinephrine O-acetyl-L-serine octopamine ornithine orotic acid orotidylic acid oxalacetic acid pantothenic acid phenethylamine phenylalanine phenylephrine / synephrine phosphocreatine phosphoenolpyruvate phosphorylcholine+ picolinic acid proline propionic acid PRPP pseudouridine putrescine pyridoxine pyroglutamic acid pyrroline hydroxycarboxylic acid pyruvic acid quinolinic acid S-adenosyl-L-homocysteine S-adenosyl-L-methionine+ S-adenosylmethioninamine+ SAICAR sarcosine serine serotonin sorbitol / galactitol / L-iditol / manitol spermidine spermine succinic acid succinic semialdehyde succinyl-CoA taurine thiamine+ thymidine thymine tryptamine tryptophan tyramine tyrosine UDP UDP-D-glucose UDP-N-acetyl-galactosamine/UDP-N-acetyl-glucosamine UMP uracil urea uric acid uridine UTP valine xanthine xanthosine xanthurenic acid XMP y-glutamylcysteine METABOLITES_END #END