#METABOLOMICS WORKBENCH fpagano_20230718_094948 DATATRACK_ID:4171 STUDY_ID:ST002805 ANALYSIS_ID:AN004561 PROJECT_ID:PR001752 VERSION 1 CREATED_ON August 2, 2023, 12:34 pm #PROJECT PR:PROJECT_TITLE IL-1β-mediated adaptive re-programming of endogenous human cardiac fibroblasts PR:PROJECT_TITLE to cells with immune features during fibrotic remodeling PR:PROJECT_SUMMARY The source and roles of fibroblasts and CD4 helper T-cells during maladaptive PR:PROJECT_SUMMARY remodeling and myocardial fibrosis in pulmonary arterial hypertension (PAH) have PR:PROJECT_SUMMARY been long debated. We demonstrate, using single-cell mass cytometry, a PR:PROJECT_SUMMARY sub-population of endogenous human cardiac fibroblasts expressing increased PR:PROJECT_SUMMARY levels of CD4, a helper T-cell marker, in addition to myofibroblast markers PR:PROJECT_SUMMARY distributed in human fibrotic RV tissue, interstitial/perivascular lesions of PR:PROJECT_SUMMARY SUGEN/Hypoxia (SuHx) rats and fibroblasts labelled with pdgfrα CreERt2/+ in PR:PROJECT_SUMMARY R26R-tdTomato mice. Recombinant IL-1β increases IL-1R, CCR2 receptor PR:PROJECT_SUMMARY expression, modifies the secretome, and differentiates cardiac fibroblasts to PR:PROJECT_SUMMARY form CD68 positive cell clusters. IL-1β also activates stemness markers such as PR:PROJECT_SUMMARY NANOG and SOX2 and genes involved in de-differentiation, lymphoid cell function PR:PROJECT_SUMMARY and metabolic reprogramming. IL-1β induction of lineage traced primary mouse PR:PROJECT_SUMMARY cardiac fibroblasts causes these cells to lose their fibroblast identity and PR:PROJECT_SUMMARY acquire an immune phenotype. Our results identify IL-1β induced PR:PROJECT_SUMMARY immune-competency in human cardiac fibroblasts and suggest that fibroblast PR:PROJECT_SUMMARY secretome modulation may constitute a therapeutic approach to PAH and other PR:PROJECT_SUMMARY diseases typified by inflammation and fibrotic remodeling. PR:INSTITUTE Brown University PR:DEPARTMENT MPPB PR:LABORATORY Siamwala Lab PR:LAST_NAME Siamwala PR:FIRST_NAME Jamila PR:ADDRESS 830 Chalkstone Avenue, Building 35 PR:EMAIL jamila_siamwala@brown.edu PR:PHONE 6192136223 #STUDY ST:STUDY_TITLE IL-1β-mediated adaptive re-programming of endogenous human cardiac fibroblasts ST:STUDY_TITLE to cells with immune features during fibrotic remodeling ST:STUDY_SUMMARY The source and roles of fibroblasts and CD4 helper T-cells during maladaptive ST:STUDY_SUMMARY remodeling and myocardial fibrosis in pulmonary arterial hypertension (PAH) have ST:STUDY_SUMMARY been long debated. We demonstrate, using single-cell mass cytometry, a ST:STUDY_SUMMARY sub-population of endogenous human cardiac fibroblasts expressing increased ST:STUDY_SUMMARY levels of CD4, a helper T-cell marker, in addition to myofibroblast markers ST:STUDY_SUMMARY distributed in human fibrotic RV tissue, interstitial/perivascular lesions of ST:STUDY_SUMMARY SUGEN/Hypoxia (SuHx) rats and fibroblasts labelled with pdgfrα CreERt2/+ in ST:STUDY_SUMMARY R26R-tdTomato mice. Recombinant IL-1β increases IL-1R, CCR2 receptor ST:STUDY_SUMMARY expression, modifies the secretome, and differentiates cardiac fibroblasts to ST:STUDY_SUMMARY form CD68 positive cell clusters. IL-1β also activates stemness markers such as ST:STUDY_SUMMARY NANOG and SOX2 and genes involved in de-differentiation, lymphoid cell function ST:STUDY_SUMMARY and metabolic reprogramming. IL-1β induction of lineage traced primary mouse ST:STUDY_SUMMARY cardiac fibroblasts causes these cells to lose their fibroblast identity and ST:STUDY_SUMMARY acquire an immune phenotype. Our results identify IL-1β induced ST:STUDY_SUMMARY immune-competency in human cardiac fibroblasts and suggest that fibroblast ST:STUDY_SUMMARY secretome modulation may constitute a therapeutic approach to PAH and other ST:STUDY_SUMMARY diseases typified by inflammation and fibrotic remodeling. ST:INSTITUTE Brown University ST:DEPARTMENT Molecular Pharmacology, Physiology and Biotechnology ST:LABORATORY Siamwala Lab ST:LAST_NAME Siamwala ST:FIRST_NAME Jamila ST:ADDRESS 830 Chalkstone Avenue, Building 35 ST:EMAIL jamila_siamwala@brown.edu ST:PHONE 6192136223 #SUBJECT SU:SUBJECT_TYPE Cultured cells SU:SUBJECT_SPECIES Homo sapiens SU:TAXONOMY_ID 9606 SU:AGE_OR_AGE_RANGE 63 - 73 SU:GENDER Male and female #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 - 62122_c Sex:M | Treatment:Control Sample type=Human cardiac fibroblast cells; RAW_FILE_NAME=120319QJS1.wiff SUBJECT_SAMPLE_FACTORS - 1281202_c Sex:M | Treatment:Control Sample type=Human cardiac fibroblast cells; RAW_FILE_NAME=120319QJS2.wiff SUBJECT_SAMPLE_FACTORS - 534282_c Sex:F | Treatment:Control Sample type=Human cardiac fibroblast cells; RAW_FILE_NAME=120319QJS3.wiff SUBJECT_SAMPLE_FACTORS - 62122_t Sex:M | Treatment:IL-1B Sample type=Human cardiac fibroblast cells; RAW_FILE_NAME=120319QJS4.wiff SUBJECT_SAMPLE_FACTORS - 1281202_t Sex:M | Treatment:IL-1B Sample type=Human cardiac fibroblast cells; RAW_FILE_NAME=120319QJS5.wiff SUBJECT_SAMPLE_FACTORS - 534282_t Sex:F | Treatment:IL-1B Sample type=Human cardiac fibroblast cells; RAW_FILE_NAME=120319QJS6.wiff #COLLECTION CO:COLLECTION_SUMMARY Metabolomics of conditioned media was performed at the Beth Israel Deaconess CO:COLLECTION_SUMMARY Medical Center Mass Spectrometry Core according to published protocols (M. Yuan, CO:COLLECTION_SUMMARY S. B. Breitkopf, X. Yang, J. M. Asara, A positive/negative ion-switching, CO:COLLECTION_SUMMARY targeted mass spectrometry-based metabolomics platform for bodily fluids, cells, CO:COLLECTION_SUMMARY and fresh and fixed tissue. Nat Protoc 7, 872-881 (2012)). hVCF (2 x 106) were CO:COLLECTION_SUMMARY seeded and grown to confluence and treated with IL-1β (10 ng/ml) for 24h. CO:COLLECTION_SUMMARY Conditioned media (1ml) from the vehicle or IL-1β treated hVCF cells were used CO:COLLECTION_SUMMARY for the metabolomics analysis. CO:SAMPLE_TYPE Cultured fibroblasts #TREATMENT TR:TREATMENT_SUMMARY hVCF (2 x 106) were seeded and grown to confluence and treated with IL-1β (10 TR:TREATMENT_SUMMARY ng/ml) for 24h. Conditioned media (1ml) from the vehicle or IL-1β treated hVCF TR:TREATMENT_SUMMARY cells were used for the metabolomics analysis. #SAMPLEPREP SP:SAMPLEPREP_SUMMARY 500 μL of chilled -80°C 80% methanol was added to 15ml tubes containing 1ml of SP:SAMPLEPREP_SUMMARY conditioned media and evaporated using Speedvac to pellet the metabolites. SRM SP:SAMPLEPREP_SUMMARY with polarity switching with a QTRAP 5500 mass spectrometer (AB/SCIEX) was used SP:SAMPLEPREP_SUMMARY to assay 300 polar molecules, based on the previously published protocol. #CHROMATOGRAPHY CH:CHROMATOGRAPHY_TYPE HILIC CH:INSTRUMENT_NAME Shimadzu Prominence UFLC HPLC CH:COLUMN_NAME Waters XBridge Amide (100 x 4.6mm,3.5um) CH:SOLVENT_A 20 mM ammonium hydroxide/20 mM ammonium acetate (pH=9.0) in 95:5 CH:SOLVENT_A water:acetonitrile CH:SOLVENT_B HPLC grade acetonitrile CH:FLOW_GRADIENT Gradients were run with a Prominence UFLC HPLC (Shimadzu) starting from 85% CH:FLOW_GRADIENT buffer B (HPLC grade acetonitrile) to 42% B from 0-5 minutes; 42% B to 0% B from CH:FLOW_GRADIENT 5-16 minutes; 0% B was held from 16-24 minutes; 0% B to 85% B from 24-25 CH:FLOW_GRADIENT minutes; 85% B was held for 7 minutes to re-equilibrate the column. CH:FLOW_RATE 400uL/min CH:COLUMN_TEMPERATURE 475 CH:METHODS_FILENAME nprot_2012_024_v2.pdf #ANALYSIS AN:ANALYSIS_TYPE MS AN:ANALYSIS_PROTOCOL_FILE nprot_2012_024_v2.pdf #MS MS:INSTRUMENT_NAME ABI Sciex 6500 QTrap MS:INSTRUMENT_TYPE QTRAP MS:MS_TYPE Other MS:ION_MODE UNSPECIFIED MS:MS_COMMENTS Ion Mode Positive/Negative Switching: Metabolomics of conditioned media was MS:MS_COMMENTS performed at the Beth Israel Deaconess Medical Center Mass Spectrometry Core MS:MS_COMMENTS according to published protocols (M. Yuan, S. B. Breitkopf, X. Yang, J. M. MS:MS_COMMENTS Asara, A positive/negative ion-switching, targeted mass spectrometry-based MS:MS_COMMENTS metabolomics platform for bodily fluids, cells, and fresh and fixed tissue. Nat MS:MS_COMMENTS Protoc 7, 872-881 (2012)). hVCF (2 x 106) were seeded and grown to confluence MS:MS_COMMENTS and treated with IL-1β (10 ng/ml) for 24h. Conditioned media (1ml) from the MS:MS_COMMENTS vehicle or IL-1β treated hVCF cells were used for the metabolomics analysis. MS:MS_COMMENTS 500 μL of chilled -80°C 80% methanol was added to 15ml tubes containing 1ml of MS:MS_COMMENTS conditioned media and evaporated using Speedvac to pellet the metabolites. MS:MS_COMMENTS Samples were re-suspended using 20 mL HPLC grade water for mass spectrometry. MS:MS_COMMENTS 5-7 μL were injected and analyzed using a hybrid 6500 QTRAP triple quadrupole MS:MS_COMMENTS mass spectrometer (AB/SCIEX) coupled to a Prominence UFLC HPLC system (Shimadzu) MS:MS_COMMENTS via selected reaction monitoring (SRM) of a total of 283 endogenous water MS:MS_COMMENTS soluble metabolites for steady-state analyses of samples. Some metabolites were MS:MS_COMMENTS targeted in both positive and negative ion mode for a total of 304 SRM MS:MS_COMMENTS transitions using positive/negative ion polarity switching. ESI voltage was MS:MS_COMMENTS +4950V in positive ion mode and –4500V in negative ion mode. The dwell time MS:MS_COMMENTS was 3 ms per SRM transition and the total cycle time was 1.39 seconds. MS:MS_COMMENTS Approximately 10-14 data points were acquired per detected metabolite. Samples MS:MS_COMMENTS were delivered to the mass spectrometer via hydrophilic interaction MS:MS_COMMENTS chromatography (HILIC) using a 4.6 mm i.d x 10 cm Amide XBridge column (Waters) MS:MS_COMMENTS at 400 μL/min. Gradients were run with a Prominence UFLC HPLC (Shimadzu) MS:MS_COMMENTS starting from 85% buffer B (HPLC grade acetonitrile) to 42% B from 0-5 minutes; MS:MS_COMMENTS 42% B to 0% B from 5-16 minutes; 0% B was held from 16-24 minutes; 0% B to 85% B MS:MS_COMMENTS from 24-25 minutes; 85% B was held for 7 minutes to re-equilibrate the column. MS:MS_COMMENTS Buffer A was comprised of 20 mM ammonium hydroxide/20 mM ammonium acetate MS:MS_COMMENTS (pH=9.0) in 95:5 water:acetonitrile. Peak areas from the total ion current for MS:MS_COMMENTS each metabolite SRM transition were integrated using MultiQuant v3.0 software MS:MS_COMMENTS (AB/SCIEX) #MS_METABOLITE_DATA MS_METABOLITE_DATA:UNITS Q3 Peak Area (area under curve) MS_METABOLITE_DATA_START Samples 62122_c 1281202_c 534282_c 62122_t 1281202_t 534282_t Factors Sex:M | Treatment:Control Sex:M | Treatment:Control Sex:F | Treatment:Control Sex:M | Treatment:IL-1B Sex:M | Treatment:IL-1B Sex:F | Treatment:IL-1B 1-Methyl-Histidine 62421.04863 56011.57737 92018.25178 104642.0462 37576.33151 38900.13063 1-Methyladenosine 6735.478569 3304.400403 8249.980851 9842.184295 7387.284692 5025.969712 1,3-diphopshateglycerate 12798.52329 8132.178918 11698.36388 4456.909412 4957.432549 7904.69915 2-Aminooctanoic acid 4803.817247 8855.850251 13096.38278 12225.44434 7825.744618 8597.503669 2-dehydro-D-gluconate 25541.63674 21404.67235 18119.59466 17337.25752 14830.07313 26435.97041 2-deoxyglucose-6-phosphate 95635.78431 91987.89581 65142.01119 78534.23648 67128.78065 39249.43657 2-Hydroxy-2-methylbutanedioic acid 182388.9684 208942.4793 167598.4861 247821.5211 98909.99432 129494.9978 2-hydroxygluterate 546168.6423 440719.0491 523984.3575 427070.7483 427068.9629 499403.5025 2-Isopropylmalic acid 67570.60213 77186.31725 72808.32332 95264.82075 61779.02982 524067.0633 2-keto-isovalerate 460564.3872 355279.1512 284451.011 287121.4855 330449.1084 323522.127 2-ketohaxanoic acid 21009.38488 9204.90578 12420.13678 8325.297575 15602.50556 N/A 2-oxo-4-methylthiobutanoate 14556.38804 5704.960931 16780.52251 21906.84581 21596.29839 32814.20619 2-oxobutanoate 152997.5874 136358.8649 93485.7779 79773.99059 127597.9024 192107.267 2,3-dihydroxybenzoic acid 104250.7913 86045.13895 84184.06248 71482.09557 62568.67541 20371.0193 2,3-Diphosphoglyceric acid 3663.147139 4953.316617 N/A N/A N/A 4102.961071 3-hydroxybuterate 22153.72249 9098.419999 9111.579414 21704.20192 20036.35201 22988.70586 3-methylphenylacetic acid 8862.527879 21354.53875 7738.425205 21993.51417 21573.59759 4010.285601 3-phospho-serine 2481.564756 1655.424581 N/A 1655.258127 N/A 1655.424578 3-phosphoglycerate 14570.94733 12666.62164 8492.067921 8711.44152 17147.94896 13121.44378 3-S-methylthiopropionate 2477.632204 N/A N/A N/A N/A 7428.43208 4-aminobutyrate N/A N/A N/A 7368.117952 N/A N/A 4-phosphopantothenate 2513.401934 5023.981375 N/A 4189.487597 N/A 1676.297587 4-Pyridoxic acid 42399.21784 10329.84277 19819.74368 24255.44533 18666.63876 33660.6524 5-methoxytryptophan N/A 3302.694673 2479.383357 5780.697336 N/A 11560.21705 5-methyl-THF N/A N/A N/A N/A N/A N/A 5-phosphoribosyl-1-pyrophosphate N/A N/A N/A N/A 4955.325782 N/A 6-phospho-D-gluconate N/A 7435.318166 5771.126844 N/A 1652.642084 6608.118943 7-methylguanosine 14875.83057 16517.00732 9909.223236 20644.56786 4951.398371 15675.65091 7,8-dihydrofolate N/A N/A N/A N/A N/A N/A a-ketoglutarate 5589169.66 5475922.053 6309820.523 5510113.043 5473937.152 3725444.947 acadesine N/A N/A 5780.133117 N/A N/A N/A acetoacetate 97556.02426 106598.9211 70268.07056 81954.77303 144383.009 108584.1052 acetoacetyl-CoA-posi N/A N/A N/A N/A N/A N/A acetyl-CoA-posi N/A N/A N/A N/A N/A N/A Acetylcarnitine DL 49602.11903 45812.68699 32621.97701 33012.42776 9079.087953 36223.42405 Acetyllysine 9810.285328 13259.55595 5788.404409 29736.20189 6634.754626 12452.07389 acetylphosphate N/A 12089.55508 70930.81776 49631.32651 N/A N/A aconitate 123846.6044 125871.9413 86957.38455 152248.6898 112889.8855 87824.99397 adenine 415012.486 413768.0193 385602.6813 368883.6467 498190.1712 346924.7575 adenosine 13847.64091 9002.538396 4208.093068 3978.001357 2477.658771 3314.999414 adenosine 5-phosphosulfate N/A N/A N/A N/A N/A N/A Adenylosuccinate 164348.1074 94148.04132 86714.0138 75152.29672 113141.3356 124708.0176 ADP-D-glucose N/A N/A N/A 4119.500535 N/A N/A ADP-nega 9082.925489 N/A N/A N/A N/A N/A alanine 5376216.365 4792675.036 5516011.453 6026657.105 5343504.352 3018220.983 allantoate 7383.34914 N/A N/A 3267.047272 4033.695735 N/A allantoin 15094.24261 8599.371663 24858.69767 34176.99424 31231.27543 14533.04525 Aminoadipic acid 604824.4813 548636.3275 434156.2712 448858.2786 582850.4828 204322.0422 aminoimidazole carboxamide ribonucleotide N/A N/A N/A N/A N/A N/A AMP 4955.196625 N/A N/A N/A N/A N/A anthranilate 12180.37855 27099.10425 8625.976361 21644.80523 18907.27462 16853.3334 arginine 48281152.31 55992349.65 54212599.4 55145204.02 61742251.44 44744033.67 arginosuccinic acid 34534.89906 46599.14234 52731.02478 31999.147 39442.43017 40389.72602 Ascorbic acid 1807930.889 2621292.307 1700216.776 1282679.622 2733923.441 1126553.906 asparagine 6708305.553 7475690.076 7555886.699 7061255.258 6368976.461 4830244.977 aspartate 3632102.289 2514522.28 2346025.523 2735726.858 2800160.341 3429226.955 ATP-nega 3308.242861 N/A N/A N/A N/A N/A Atrolactic acid 27104.69156 32998.44097 53645.95693 66144.68461 57378.93184 69590.18706 betaine 1112611.704 1264289.339 833463.2414 786853.1903 994827.3528 1289283.084 betaine aldehyde 56523.98693 60199.47008 28445.7671 50821.46861 35778.86486 48221.69027 biotin 45557.44164 39478.97929 53895.60291 51944.89476 62553.12474 153402.0241 Carbamoyl phosphate 160827.1238 44466.99595 249669.9855 156783.6037 53654.57617 61915.67285 carnitine 131131.0149 114956.4441 140799.5667 268544.9949 77380.13095 147030.6731 CDP-choline N/A N/A N/A N/A N/A N/A CDP-ethanolamine N/A N/A N/A N/A N/A N/A CDP-nega 6940.860796 4658.190041 13756.44859 N/A 3188.341415 4351.815967 Cellobiose N/A N/A N/A N/A N/A N/A cholesterol 48719.89202 58653.81665 72356.77877 52002.60231 57140.00576 104893.9072 cholesteryl sulfate 27300.67541 23974.33344 25939.11637 42931.40108 7837.967252 10749.52555 Cholic acid 11380.49755 11537.06494 14048.18083 11448.36344 5748.158005 4123.935255 choline 354306186.1 378713211 388582462.2 362207184.6 352353973.1 44343.70561 Citraconic acid/itaconic acid 284203.0002 321360.4896 372703.107 361574.9581 57841.17238 40947.62868 citrate 7952726.355 7922470.885 6279267.424 5464704.778 4600506.99 1357042.798 citrate-isocitrate 17696956.89 15889105.57 16491831.46 3291829.668 10675586.32 2967477.244 citrulline 1310193.019 1634627.7 1318705.454 1445500.422 1620144.682 7091.121283 CMP N/A N/A N/A 4955.253146 N/A N/A coenzyme A-posi N/A N/A 2477.539124 3395.47303 4979.438331 5782.800016 creatine 343441.7848 314794.9553 601472.6241 596811.7259 217118.94 204978.4812 Creatinine 26223.2952 13045.5144 24171.59903 13358.37855 N/A 24074.53292 CTP-nega 8279.770003 N/A N/A N/A N/A N/A cyclic bis(3->5) dimeric GMP N/A N/A 5780.360931 N/A N/A N/A cyclic-AMP 118963.6673 73501.56363 56158.29408 59464.29478 54506.24365 28906.43396 cystathionine 13215.61862 21460.43936 10737.8601 6607.9362 N/A N/A cysteine 87724.96531 100424.2793 150684.3277 100309.6819 153462.441 103185.3969 cysteine sulfinate 4758.733259 5149.167668 5780.327377 12385.76457 1674.808259 4130.179466 Cystine 5916993.71 5333790.322 4882688.745 6197335.24 7056273.962 3180717.824 cytidine 67698.30312 29807.02964 31383.43944 11601.56596 11563.00213 9362.53389 cytosine 294766.8178 332516.5511 384978.2625 371027.6814 307767.2929 208105.2142 D-erythrose-4-phosphate 45890.25263 16236.49176 39452.16419 26321.29065 30259.17277 13169.2492 D-glucarate 3302.692472 N/A N/A 6657.457163 N/A 3288.759873 D-gluconate 129057.4437 146831.7787 118018.4035 112170.1204 119991.7197 115617.6011 D-glucono-?-lactone-6-phosphate 9490.373031 8853.830778 6603.387265 15296.20045 9224.547665 5774.494283 D-glucosamine-1-phosphate N/A N/A N/A N/A N/A 7432.943912 D-glucosamine-6-phosphate N/A 4955.293697 N/A N/A 4130.041219 N/A D-glyceraldehdye-3-phosphate N/A 5646.506868 3230.418967 5699.012107 5043.873438 5657.860011 D-sedoheptulose-1-7-phosphate 111686.5853 133826.4313 55760.12435 46153.79193 27527.67198 21497.24036 dAMP N/A N/A N/A N/A N/A N/A dATP-nega N/A N/A N/A N/A N/A N/A dCDP-nega N/A N/A N/A N/A N/A N/A dCMP N/A N/A N/A N/A N/A N/A dCTP-nega N/A N/A 3302.776368 N/A N/A 3302.66888 dehydroascorbic acid 3380.751959 4129.355608 15056.77122 9583.341854 17336.81298 41798.59573 deoxyadenosine 2477.919739 1652.721158 N/A N/A 8261.85431 4955.968524 Deoxycholic acid N/A N/A N/A N/A N/A N/A deoxyguanosine 6608.12703 3301.442963 10739.45739 5782.999987 4955.795928 10476.82273 deoxyinosine 4951.135641 N/A 3302.722943 N/A 4129.574607 12387.5905 deoxyribose-phosphate 4143.908616 3086.060591 N/A 8632.631527 5741.043677 N/A deoxyuridine N/A N/A N/A N/A N/A N/A dephospho-CoA-nega N/A 3302.758483 14038.34459 8258.135056 4955.331811 N/A dephospho-CoA-posi N/A N/A N/A N/A N/A N/A dGDP-nega 5780.56197 N/A 3302.652973 4955.24149 N/A N/A dGMP N/A N/A N/A 3286.227484 N/A 4931.48457 dGTP 9906.429002 4933.109102 4955.331812 N/A N/A N/A dihydroorotate 167772.836 103716.0427 76432.95541 83143.6603 95772.7899 220944.1316 dihydroxy-acetone-phosphate 2812.333789 6772.010443 16520.99522 7667.940457 N/A N/A Diiodothyronine N/A N/A N/A N/A N/A N/A dimethylglycine 60316746.82 59101953.42 61934729 60738105.96 51828019.75 15327.65193 DL-Pipecolic acid 8646306.384 8520730.993 7036982.168 8312761.728 6907667.681 4615290.651 dTDP-nega N/A N/A N/A 7432.708034 3302.756018 2406.978417 dTMP N/A N/A N/A N/A 4179.936341 N/A dTMP-nega 11506.89931 3302.577036 4442.683615 4903.418271 9094.853065 69142.67654 dTTP-nega N/A N/A N/A N/A N/A N/A dUMP-nega N/A N/A N/A N/A N/A 4955.051235 dUTP-nega N/A 2477.621132 N/A N/A N/A N/A ethanolamine N/A N/A N/A N/A N/A N/A FAD N/A N/A N/A N/A N/A N/A Flavone 13354.81049 26180.22216 21742.29753 18577.44221 13883.84998 21904.1716 FMN N/A N/A N/A N/A N/A N/A folate 18170.80994 14038.12519 13192.42434 37951.73669 18170.79443 16375.76463 fructose-1,6-bisphosphate 23895.353 32217.34199 17203.8486 33003.96361 28086.96951 17320.80555 fructose-6-phosphate 7436.491749 3299.18467 N/A 10717.80305 N/A 7340.297261 fumarate 312608.4705 499118.4494 446830.0121 286326.0363 331360.6229 334084.8293 GDP-nega N/A N/A N/A N/A N/A N/A Geranyl-PP N/A N/A N/A N/A N/A N/A glucono-?-lactone 6646.187994 6730.369892 8153.523708 N/A N/A 4074.155974 glucosamine 1170906.939 1231941.551 1304877.406 1283926.302 1130295.295 936043.7442 glucose-1-phosphate 40716.7511 29076.87114 31971.868 23480.21697 38108.29694 34635.6684 glucose-6-phosphate N/A 29839.55992 48683.64596 43268.89865 50702.22324 75831.64871 glutamate 11670105.02 8907952.606 8492957.013 10302545.41 8534705.424 6822163.321 glutamine 81909772.34 85045116.84 79322725.08 79499809.07 77212459.47 62708872.04 glutathione 18892.2318 22263.88515 16646.32891 28960.44221 5783.275151 33673.10797 glutathione disulfide-nega 34259.22544 30556.80689 45353.46195 44561.29779 35676.82031 27092.26334 glutathione disulfide-posi 8022.071112 12383.79506 15690.63199 N/A 10004.17035 14870.88305 glutathione-nega 27944.56984 29542.82956 21408.95397 38461.13328 12681.19848 21232.52373 glycerate 789506.8327 857938.5843 838792.8795 917999.7448 870971.1278 599139.1332 Glycerophosphocholine 6328670.929 3762037.586 6968524.614 6949826.635 3470972.984 4235435.039 glycine N/A N/A N/A N/A N/A N/A glycolate 130248.681 56119.97121 41484.59699 68935.91552 14915.11635 28157.11379 glyoxylate 10373.13751 13160.82606 21513.66221 15789.17231 17017.41113 7844.239263 GMP N/A N/A N/A N/A N/A N/A GTP-nega 1652.703594 2478.097204 N/A N/A N/A N/A Guanidoacetic acid 386481.352 427224.7241 356437.0385 339238.1298 369134.4422 205510.9003 guanine 11530.30798 12672.56448 7562.256701 15089.27614 9867.004621 8049.203423 guanosine N/A 4979.446351 5780.355676 4955.54544 4131.464542 3202.807866 guanosine 5-diphosphate,3-diphosphate N/A N/A N/A N/A 3305.249162 N/A hexose-phosphate 65177.49449 62689.21473 55014.23132 52026.83419 67555.94228 48800.44602 histidine 54838010.37 65949193.25 68655162.13 60295597.12 61440544.51 41364419.24 histidinol 3300.706599 N/A N/A N/A N/A N/A HMG-CoA_pos N/A N/A N/A N/A N/A N/A homocysteic acid 13213.50036 23100.11624 42977.80543 42092.0263 28130.31916 11563.21901 homocysteine 11560.4995 11852.63238 10729.64119 16520.79818 10735.43146 N/A homoserine 15534.94783 11561.44869 23946.83678 13046.60049 15053.04729 8234.51318 Hydroxyisocaproic acid 448959.4789 525091.5921 557341.8496 542266.9063 411530.9688 439304.5375 Hydroxyphenylacetic acid 76313.96226 84460.92502 115424.7103 118101.2973 111809.2527 5846.783964 hydroxyphenylpyruvate 811038.7633 838431.1505 842964.0606 856537.4784 788451.2134 754086.5982 hydroxyproline 10735.15078 20644.48083 32935.86369 42120.56499 22356.29015 10069.42567 hypoxanthine 6204.011082 3077.858854 5584.141616 N/A 4782.430966 14120.07763 IDP-nega N/A N/A N/A N/A N/A N/A Imidazoleacetic acid 462419.9582 580808.522 424189.0541 537608.1047 530891.1626 431270.1468 IMP N/A N/A N/A N/A N/A N/A indole 28485.13933 36140.04638 20456.06481 25795.72272 24668.12675 7711.877523 Indole-3-carboxylic acid 388280.4652 418719.7928 207557.4142 227705.3707 287464.334 123713.2058 Indoleacrylic acid 72544.39496 20704.97096 44954.29015 60230.05144 54589.99612 27489.63568 inosine 260990.237 275007.7523 322919.5451 340308.9854 360087.5316 227941.6171 isocitrate 9082.913226 7430.467973 9719.134014 9912.927396 13356.9391 14858.1451 itaconic acid 284203.0002 321360.4896 465825.1646 361574.9581 153785.0904 103490.5333 Kynurenic acid 1106074.351 1438798.053 3532844.599 4692716.574 7239863.121 36814.21626 Kynurenine N/A 9061.247892 6080.137493 13696.10003 11761.28333 4983.085784 L-arginino-succinate 29516.66359 35507.70681 25980.24872 40082.45848 38118.58424 27657.47072 lactate 30571864.48 40031079.21 60999692.96 76737252.34 53728895.4 36123279.18 leucine-isoleucine 96322955.23 99375981.69 94649799.77 91868397.16 92276919.39 64026954.61 lipoate N/A N/A N/A N/A N/A N/A lysine 4072828.128 4495908.533 3507946.649 3227249.493 3827512.507 2083613.645 malate 352210.9069 395973.4758 257529.0241 291034.1384 696330.4082 275529.2049 Maleic acid 392854.3832 408263.2397 235694.3562 328506.5598 384435.4651 346320.6698 malonyl-CoA-posi N/A N/A N/A N/A N/A N/A methionine 1238133.238 1371771.426 1068853.573 1053635.216 1100425.912 1101529.155 Methionine sulfoxide 61140.67479 110693.0518 90846.64936 102544.819 73503.12109 71847.57575 Methylcysteine 415012.486 413768.0193 385602.6813 368883.6467 498190.1712 346924.7575 Methylmalonic acid 424084.345 315479.3211 223267.2514 220965.0181 109243.5422 227515.9656 methylnicotinamide 4099.025986 8132.153677 6632.399192 4665.387 4268.585479 N/A myo-inositol 13073164.34 15371897.79 17178094.14 16616002.36 14657920.45 12818826.2 N-acetyl spermidine N/A 1660.764163 N/A 5635.205775 1652.679716 N/A N-acetyl spermine 8256.670462 13237.38317 13154.04142 24779.38561 22248.605 28801.25455 N-acetyl-glucosamine 5782.716321 N/A N/A N/A N/A 4965.082079 N-acetyl-glucosamine-1-phosphate 6568.831837 8252.514605 33031.95123 34687.07967 13213.98216 16735.32517 N-acetyl-glutamate 37847.94848 127163.8408 78042.28786 151642.0932 3247.574027 5342.668076 N-acetyl-glutamine 17814.97353 148997.4902 27460.17513 25720.89395 174280.6 7031.763118 N-Acetyl-L-alanine 136141.5302 100470.7819 203266.1872 124248.1709 66553.64276 29636.46039 N-acetyl-L-aspartic acid N/A N/A 4961.452182 2524.041432 N/A N/A N-acetyl-L-aspartylglutamic acid N/A N/A N/A N/A N/A N/A N-acetyl-L-ornithine 27584.07976 9348.335898 12638.08958 16603.13235 10107.88356 10520.86677 N-Acetylputrescine 13814.14492 17603.59979 N/A 20081.92435 13227.12947 15259.71607 N-carbamoyl-L-aspartate N/A N/A N/A N/A N/A N/A N-carbamoyl-L-aspartate-nega N/A 6576.625633 N/A 5795.271697 N/A N/A N6-Acetyl-L-lysine 9109.488604 10735.55302 11846.22776 5925.145861 N/A 4129.532499 NAD+_nega N/A N/A 3302.722379 N/A N/A N/A NAD+_posi N/A N/A N/A N/A N/A N/A NADH N/A N/A N/A N/A N/A N/A NADH-nega N/A N/A N/A N/A N/A N/A NADP+_nega N/A N/A N/A N/A N/A N/A NADP+_posi N/A N/A N/A N/A N/A N/A NADPH N/A N/A N/A N/A N/A N/A NADPH-nega N/A N/A N/A N/A N/A N/A Ng,NG-dimethyl-L-arginine 240840.8528 219682.3012 386928.3544 419305.3011 185824.2799 113138.4915 nicotinamide 105026864.1 93391219.17 115077653.8 110841573.9 99022364.51 71687786.52 Nicotinamide Riboside 5782.217173 7431.763442 9081.896585 3475.319125 13167.84167 17337.51331 Nicotinamide ribotide 4952.745377 4955.236128 6607.905106 3276.68683 N/A 7432.940255 nicotinate 351420.7543 217019.7072 346078.8663 375215.7665 212340.4689 161022.9 O-acetyl-L-serine 6550.416108 4958.676666 N/A N/A N/A N/A O8P-O1P 5780.396631 15694.95432 4951.297451 4516.597494 9113.695872 4955.331811 OBP 22298.75913 18991.92311 17074.37179 15699.66395 18989.37525 22290.18845 ornithine 166214.9415 146964.8821 137833.7791 165546.1832 122935.3645 36133.07666 orotate 84321.32697 64659.6467 66586.83403 54317.50297 328193.4223 25076.22481 orotidine-5-phosphate 18838.077 6083.362195 N/A 6598.210073 N/A 12687.15397 oxaloacetate 245135.3827 142468.6897 253911.8426 66221.72625 67478.09051 84330.21589 p-aminobenzoate 38184.55221 13150.91277 20607.01628 9812.234919 11130.01598 7490.366153 p-hydroxybenzoate 136689.4494 95381.07445 61117.73014 57537.00396 172812.2197 45292.8601 pantothenate 629203.1914 817156.6221 560182.961 655616.6896 864098.9474 945425.3776 phenylalanine 15397800.89 12917576.65 12208367.04 10986426.67 11808025.15 4483171.254 Phenyllactic acid 185875.6784 161798.1749 133745.3733 124705.7644 184150.8336 127996.4012 Phenylpropiolic acid 81060.05813 62430.88414 83651.82344 81049.32033 66956.57285 8575610.316 phenylpyruvate 6650.592604 16156.64509 15071.96123 24516.61972 5224.033899 11155.21822 phosphocreatine 294437.0331 308523.6941 356364.8297 336048.9981 349198.0361 473909.129 phosphoenolpyruvate N/A N/A 6706.238926 N/A N/A 4074.028514 Phosphorylcholine 71138.51828 47055.32015 74246.59071 71368.42672 28862.07386 85395.24629 prephenate N/A N/A N/A N/A N/A N/A proline 29600225.86 27728017.15 36151913.23 31068812.76 27527598.62 22255300.12 propionyl-CoA-posi N/A N/A N/A N/A N/A N/A purine 177706.7886 152203.9519 171926.4926 169427.6756 140596.6917 81322.99664 putrescine 26933.6037 N/A 15898.76496 17052.06904 2717.194758 21451.90502 Pyridoxamine 3306.849115 5780.35822 N/A N/A N/A 2425.524465 pyridoxine 1113363.87 1023785.602 1286712.831 945388.2027 992644.8749 566475.7624 Pyroglutamic acid 1001967.488 941238.2953 933404.6774 869084.5848 884789.0508 767085.26 Pyrophosphate 37296.60037 51989.04408 22255.10867 19552.45322 31715.51648 215686.156 pyruvate 89380.44334 131016.8577 67621.94724 82800.6439 83295.62807 37258.75667 quinolinate 97161.72734 15218.35097 126991.6748 16366.13331 10261.3722 117502.2646 retinoic acid N/A N/A N/A N/A N/A N/A riboflavin 61041.18212 80937.43629 55331.02524 57793.37294 45492.82978 39827.42581 ribose-phosphate 4194.372788 16507.65412 14274.06603 12544.44011 15559.70426 3144.716069 S-adenosyl-L-homocysteine-nega 7432.771959 10735.50112 26430.75746 5780.356483 7432.677579 N/A S-adenosyl-L-homoCysteine-posi 4955.145428 N/A N/A 7432.876526 4954.909902 N/A S-adenosyl-L-methioninamine N/A N/A 8330.103379 4970.234309 N/A 9085.482725 S-adenosyl-L-methionine N/A N/A N/A N/A N/A N/A S-methyl-5-thioadenosine 2513.135929 N/A 1720.90564 N/A 2512.93265 N/A S-ribosyl-L-homocysteine-nega N/A N/A N/A 2461.970579 N/A N/A S-ribosyl-L-homocysteine-posi 643909.2846 593055.8606 711274.4424 672382.0952 824669.2311 639994.6853 sarcosine 3778311.163 3535458.611 4387174.962 5139279.084 3446774.647 2594284.609 SBP 79617.85596 54460.29282 76233.10529 36860.97122 61159.85041 25966.32123 serine 21375858.57 19346196.59 19442751.91 24783482.49 18266691.25 12136592.53 shikimate 7365073.431 5341709.512 17471389.2 15943344.27 3328596.328 2818157.137 shikimate-3-phosphate N/A N/A N/A N/A N/A N/A sn-glycerol-3-phosphate 62141.33062 139285.3953 132077.7926 126449.2497 112425.9318 189835.4565 spermidine 87516.97482 102563.3815 107755.1118 123553.3096 163133.0068 146042.0198 spermine 2477.927164 3305.660073 N/A N/A 4066.096988 18968.95145 succinate 319042.6791 271085.2763 309757.4158 159226.7263 156577.4742 178893.0818 succinyl-CoA-posi N/A N/A N/A N/A N/A N/A taurine 27362.27833 34717.53483 27325.79735 29114.09128 29031.76123 33478.69026 Taurodeoxycholic acid 115628.8516 91675.8751 113971.4398 139571.9557 102409.5855 75155.68865 thiamine N/A N/A N/A N/A N/A N/A Thiamine pyrophosphate N/A N/A N/A 3302.620966 8310.074651 3302.546457 thiamine-phosphate N/A N/A N/A N/A N/A N/A threonine 24168768.63 26255855.54 25277924.92 23577291.12 25431058.56 14920455.42 thymidine N/A N/A N/A N/A N/A N/A thymine 6345.320416 6163.159393 N/A 4612.314097 13003.68581 42336.59023 trans, trans-farnesyl diphosphate N/A 3305.085244 4130.194428 N/A N/A N/A trehalose-6-Phosphate N/A N/A N/A N/A 2477.683817 N/A trehalose-sucrose N/A N/A N/A 13631.0601 N/A N/A tryptophan 9945704.264 9670168.475 7686529.355 8587927.116 8089000.14 3329656.224 tyrosine 1386593.828 1405594.403 1080197.567 1177799.763 1188971.203 907959.3131 UDP-D-glucose N/A N/A N/A N/A N/A N/A UDP-D-glucuronate N/A N/A N/A N/A 2477.701701 N/A UDP-N-acetyl-glucosamine N/A N/A N/A N/A N/A N/A UDP-nega N/A 4955.890555 N/A N/A N/A N/A UMP N/A 3280.438514 N/A N/A N/A 4130.331637 uracil 80876.87219 71215.50693 78651.23137 71683.92678 73570.259 69785.99241 Urea 139831.6398 146458.3001 174578.8692 76914.58102 182491.583 210903.6527 Uric acid N/A 2494.285294 2483.939511 3244.812389 8962.398274 12406.18615 uridine 11015.34358 5749.582932 21900.36293 10120.38097 9477.03373 7663.885003 UTP-nega 5778.904629 2477.534906 5823.532108 N/A N/A N/A valine 3008190.838 3116744.573 2162687.142 2680296.424 3462947.389 2359300.358 xanthine 44139.32474 62278.07759 100850.9698 85206.73429 37152.31388 25238.29434 xanthosine 4115.744966 13398.60135 13834.02571 18138.38777 4119.48295 12410.44437 xanthosine-5-phosphate N/A N/A N/A N/A N/A N/A Xanthurenic acid 23550.82407 466108.9736 404829.5551 430183.1652 20509.2397 486286.4934 MS_METABOLITE_DATA_END #METABOLITES METABOLITES_START metabolite_name formula KEGG ID HMDB PubChem ID 1-Methyl-Histidine C7H11N3O2 C01152 1-Methyladenosine C11H15N5O4 C02494 1,3-diphopshateglycerate C3H8O10P2 C00236 2-Aminooctanoic acid C8H17NO2 HMDB00991 2-dehydro-D-gluconate C6H10O7 C00629 2-deoxyglucose-6-phosphate C6H13O8P C06369 2-Hydroxy-2-methylbutanedioic acid C5H8O5 C02612 2-hydroxygluterate C5H8O5 C02630 2-Isopropylmalic acid C7H12O5 C02504 2-keto-isovalerate C5H8O3 C00141 2-ketohaxanoic acid C6H10O3 HMDB01864 2-oxo-4-methylthiobutanoate C5H8O3S C01180 2-oxobutanoate C4H6O3 C00109 2,3-dihydroxybenzoic acid C7H6O4 C00196 2,3-Diphosphoglyceric acid C3H8O10P2 C01159 3-hydroxybuterate C4H8O3 C01089 3-methylphenylacetic acid C9H10O2 HMDB02222 3-phospho-serine C3H8NO6P C01005 3-phosphoglycerate C3H7O7P C00197 3-S-methylthiopropionate C4H8O2S C08276 4-aminobutyrate C4H9NO2 C00334 4-phosphopantothenate C9H18NO8P C03492 4-Pyridoxic acid C8H9NO4 C00847 5-methoxytryptophan C12H14N2O3 HMDB02339 5-methyl-THF C20H25N7O6 C00440 5-phosphoribosyl-1-pyrophosphate C5H13O14P3 C00119 6-phospho-D-gluconate C6H13O10P C00345 7-methylguanosine C11H16N5O5 HMDB01107 7,8-dihydrofolate C19H21N7O6 C00415 a-ketoglutarate C5H6O5 C00026 acadesine C9H14N4O5 D02742 acetoacetate C4H6O3 C00164 acetoacetyl-CoA-posi C25H40N7O18P3S C00332 acetyl-CoA-posi C23H38N7O17P3S C00024 Acetylcarnitine DL C9H18NO4 C02571 Acetyllysine C8H16N2O3 C02727 acetylphosphate C2H5O5P C00227 aconitate C6H6O6 C00417 adenine C5H5N5 C00147 adenosine C10H13N5O4 C00212 adenosine 5-phosphosulfate C10H14N5O10PS C00224 Adenylosuccinate C14H18N5O11P C03794 ADP-D-glucose C16H25N5O15P2 C00498 ADP-nega C10H15N5O10P2 C00008 alanine C3H7NO2 C00041 allantoate C4H8N4O4 C00499 allantoin C4H6N4O3 C01551 Aminoadipic acid C6H11NO4 C00956 aminoimidazole carboxamide ribonucleotide C9H15N4O8P C04677 AMP C10H14N5O7P C00020 anthranilate C7H7NO2 C00108 arginine C6H14N4O2 C00062 arginosuccinic acid C10H18N4O6 C03406 Ascorbic acid C6H8O6 C00072 asparagine C4H8N2O3 C00152 aspartate C4H7NO4 C00049 ATP-nega C10H16N5O13P3 C00002 Atrolactic acid C9H10O3 HMDB00475 betaine C5H11NO2 C00719 betaine aldehyde C5H12NO C00576 biotin C10H16N2O3S C00120 Carbamoyl phosphate CH4NO5P C00169 carnitine C7H15NO3 C00318 CDP-choline C14H27N4O11P2 C00307 CDP-ethanolamine C11H20N4O11P2 C00570 CDP-nega C9H15N3O11P2 C00112 Cellobiose C12H22O11 C00185 cholesterol C27H46O C00187 cholesteryl sulfate C27H46O4S HMDB00653 Cholic acid C24H40O5 C00695 choline C5H14NO C00114 Citraconic acid/itaconic acid C5H6O4 C02226 citrate C6H8O7 C00158 citrate-isocitrate C6H8O7 C00158 citrulline C6H13N3O3 C00327 CMP C9H14N3O8P C00055 coenzyme A-posi C21H36N7O16P3S C00010 creatine C4H9N3O2 C00300 Creatinine C4H7N3O C00791 CTP-nega C9H16N3O14P3 C00063 cyclic bis(3->5) dimeric GMP C20H24N10O14P2 C16463 cyclic-AMP C10H12N5O6P C00575 cystathionine C7H14N2O4S C02291 cysteine C6H12N2O4S2 C00491 cysteine sulfinate C3H7NO4S C00606 Cystine C6H12N2O4S2 C00491 cytidine C9H13N3O5 C00475 cytosine C4H5N3O C00380 D-erythrose-4-phosphate C4H9O7P C00279 D-glucarate C6H10O8 C00818 D-gluconate C6H12O7 C00257 D-glucono-?-lactone-6-phosphate C6H11O9P C01236 D-glucosamine-1-phosphate C6H14NO8P C00352 D-glucosamine-6-phosphate C6H14NO8P C00352 D-glyceraldehdye-3-phosphate C3H7O6P C00118 D-sedoheptulose-1-7-phosphate C7H15O10P C05382 dAMP C10H14N5O6P C00360 dATP-nega C10H16N5O12P3 C00131 dCDP-nega C9H15N3O10P2 C00705 dCMP C9H14N3O7P C00239 dCTP-nega C9H16N3O13P3 C00458 dehydroascorbic acid C6H6O6 C05422 deoxyadenosine C10H13N5O3 C00559 Deoxycholic acid C26H43NO5 C04483 deoxyguanosine C10H13N5O4 C00330 deoxyinosine C10H12N4O4 C05512 deoxyribose-phosphate C5H11O7P C00673 deoxyuridine C9H12N2O5 C00526 dephospho-CoA-nega C21H35N7O13P2S C00882 dephospho-CoA-posi C21H35N7O13P2S C00882 dGDP-nega C10H15N5O10P2 C00361 dGMP C10H14N5O7P C00362 dGTP C10H16N5O13P3 C00286 dihydroorotate C5H6N2O4 C00337 dihydroxy-acetone-phosphate C3H7O6P C00111 Diiodothyronine C15H13I2NO4 HMDB00582 dimethylglycine C4H9NO2 C01026 DL-Pipecolic acid C6H11NO2 C00408 dTDP-nega C10H16N2O11P2 C00363 dTMP C10H15N2O8P C00364 dTMP-nega C10H15N2O8P C00364 dTTP-nega C10H17N2O14P3 C00459 dUMP-nega C9H13N2O8P C00365 dUTP-nega C9H15N2O14P3 C00460 ethanolamine C2H7NO C00189 FAD C27H33N9O15P2 C00016 Flavone C15H10O2 C15608 FMN C17H21N4O9P C00061 folate C19H19N7O6 C00504 fructose-1,6-bisphosphate C6H14O12P2 C05378 fructose-6-phosphate C6H13O9P C05345 fumarate C4H4O4 C00122 GDP-nega C10H15N5O11P2 C00035 Geranyl-PP C10H20O7P2 C00341 glucono-?-lactone C6H10O6 C00198 glucosamine C6H13NO5 C00329 glucose-1-phosphate C6H13O9P C00103 glucose-6-phosphate C6H13O9P C00668 glutamate C5H9NO4 C00025 glutamine C5H10N2O3 C00064 glutathione C10H17N3O6S C00051 glutathione disulfide-nega C20H32N6O12S2 C00127 glutathione disulfide-posi C20H32N6O12S2 C00127 glutathione-nega C10H17N3O6S C00051 glycerate C3H6O4 C00258 Glycerophosphocholine C8H21NO6P C00670 glycine C2H5NO2 C00037 glycolate C2H4O3 C00160 glyoxylate C2H2O3 C00048 GMP C10H14N5O8P C00144 GTP-nega C10H16N5O13P3 C00044 Guanidoacetic acid C3H7N3O2 C00581 guanine C5H5N5O C00242 guanosine C10H13N5O5 C00387 guanosine 5-diphosphate,3-diphosphate C10H11N5O17P4 C01228 hexose-phosphate C6H13O9P C05345 histidine C6H9N3O2 C00135 histidinol C6H11N3O C00860 HMG-CoA_pos C27H44N7O20P3S C00356 homocysteic acid C4H9NO5S C16511 homocysteine C4H9NO2S C00155 homoserine C4H9NO3 C00263 Hydroxyisocaproic acid C6H12O3 HMDB00746 Hydroxyphenylacetic acid C8H8O3 C05852 hydroxyphenylpyruvate C9H8O4 C01179 hydroxyproline C5H9NO3 C01157 hypoxanthine C5H4N4O C00262 IDP-nega C10H14N4O11P2 C00104 Imidazoleacetic acid C6H8N2O2 C02835 IMP C10H13N4O8P C00130 indole C8H7N C00463 Indole-3-carboxylic acid C9H7NO2 HMDB03320 Indoleacrylic acid C11H9NO2 HMDB00734 inosine C10H12N4O5 C00294 isocitrate C6H8O7 C00311 itaconic acid C5H6O4 HMDB0002092 Kynurenic acid C10H7NO3 C01717 Kynurenine C10H12N2O3 C00328 L-arginino-succinate C10H18N4O6 C03406 lactate C3H6O3 C00186 leucine-isoleucine C6H13NO2 C00123 lipoate C8H14O2S2 C00725 lysine C6H14N2O2 C00047 malate C4H6O5 C00149 Maleic acid C4H4O4 C01384 malonyl-CoA-posi C24H38N7O19P3S C00083 methionine C5H11NO2S C00073 Methionine sulfoxide C5H11NO3S HMDB02005 Methylcysteine C4H9NO2S HMDB0002108 Methylmalonic acid C4H6O4 C02170 methylnicotinamide C7H9N2O C02918 myo-inositol C6H12O6 C00137 N-acetyl spermidine C9H21N3O HMDB0001276 N-acetyl spermine C12H28N4O C02567 N-acetyl-glucosamine C8H15NO6 C00140 N-acetyl-glucosamine-1-phosphate C6H14NO8P C04256 N-acetyl-glutamate C7H11NO5 C00624 N-acetyl-glutamine C7H12N2O4 HMDB06029 N-Acetyl-L-alanine C5H9NO3 C01073 N-acetyl-L-aspartic acid C6H9NO5 C01042 N-acetyl-L-aspartylglutamic acid C11H16N2O8 C12270 N-acetyl-L-ornithine C7H14N2O3 C00437 N-Acetylputrescine C6H14N2O C02714 N-carbamoyl-L-aspartate C5H8N2O5 C00438 N-carbamoyl-L-aspartate-nega C5H8N2O5 C00438 N6-Acetyl-L-lysine C8H16N2O3 C02727 NAD+_nega C21H27N7O14P2 C00003 NAD+_posi C21H27N7O14P2 C00003 NADH C21H29N7O14P2 C00004 NADH-nega C21H29N7O14P2 C00004 NADP+_nega C21H28N7O17P3 C00006 NADP+_posi C21H28N7O17P3 C00006 NADPH C21H30N7O17P3 C00005 NADPH-nega C21H30N7O17P3 C00005 Ng,NG-dimethyl-L-arginine C8H18N4O2 C03626 nicotinamide C6H6N2O C00153 Nicotinamide Riboside C11H15N2O5 C03150 Nicotinamide ribotide C11H15N2O8P C00455 nicotinate C6H5NO2 C00253 O-acetyl-L-serine C5H9NO4 C00979 O8P-O1P C8H17O11P 90657269 OBP C5H11O8P 130470 ornithine C5H12N2O2 C00077 orotate C5H4N2O4 C00295 orotidine-5-phosphate C10H13N2O11P C01103 oxaloacetate C4H4O5 C00036 p-aminobenzoate C7H7NO2 C00568 p-hydroxybenzoate C7H6O3 C00156 pantothenate C9H17NO5 C00864 phenylalanine C9H11NO2 C00079 Phenyllactic acid C9H10O3 C01479 Phenylpropiolic acid C9H6O2 HMDB00563 phenylpyruvate C9H8O3 C00166 phosphocreatine C4H10N3O5P C02305 phosphoenolpyruvate C3H5O6P C00074 Phosphorylcholine C5H15NO4P C00588 prephenate C10H10O6 C00254 proline C5H9NO2 C00148 propionyl-CoA-posi C24H40N7O17P3S C00100 purine C5H4N4 C00465 putrescine C4H12N2 C00134 Pyridoxamine C8H12N2O2 C00534 pyridoxine C8H11NO3 C00314 Pyroglutamic acid C5H7NO3 C01879 Pyrophosphate P2H4O7 C00013 pyruvate C3H4O3 C00022 quinolinate C7H5NO4 C03722 retinoic acid C20H28O2 C00777 riboflavin C17H20N4O6 C00255 ribose-phosphate C5H11O8P C00117 S-adenosyl-L-homocysteine-nega C14H20N6O5S C00021 S-adenosyl-L-homoCysteine-posi C14H20N6O5S C00021 S-adenosyl-L-methioninamine C14H23N6O3S C01137 S-adenosyl-L-methionine C15H22N6O5S C00019 S-methyl-5-thioadenosine C11H15N5O3S C00170 S-ribosyl-L-homocysteine-nega C9H17NO6S C03539 S-ribosyl-L-homocysteine-posi C9H17NO6S C03539 sarcosine C3H7NO2 C00213 SBP C7H16O13P2 C00447 serine C3H7NO3 C00065 shikimate C7H10O5 C00493 shikimate-3-phosphate C7H11O8P C03175 sn-glycerol-3-phosphate C3H9O6P C00093 spermidine C7H19N3 C00315 spermine C10H26N4 C00750 succinate C4H6O4 C00042 succinyl-CoA-posi C25H40N7O19P3S C00091 taurine C2H7NO3S C00245 Taurodeoxycholic acid C26H45NO6S C05463 thiamine C12H16N4OS C00378 Thiamine pyrophosphate C12H19N4O7P2S C00068 thiamine-phosphate C12H17N4O4PS C01081 threonine C4H9NO3 C00188 thymidine C10H14N2O5 C00214 thymine C5H6N2O2 C00178 trans, trans-farnesyl diphosphate C15H28O7P2 C00448 trehalose-6-Phosphate C12H23O14P C00689 trehalose-sucrose C12H22O11 C00089 tryptophan C11H12N2O2 C00078 tyrosine C9H11NO3 C00082 UDP-D-glucose C15H24N2O17P2 C00029 UDP-D-glucuronate C15H22N2O18P2 C00167 UDP-N-acetyl-glucosamine C17H27N3O17P2 C00043 UDP-nega C9H14N2O12P2 C00015 UMP C9H13N2O9P C00105 uracil C4H4N2O2 C00106 Urea CH4N2O C00086 Uric acid C5H4N4O3 C00366 uridine C9H12N2O6 C00299 UTP-nega C9H15N2O15P3 C00075 valine C5H11NO2 C00183 xanthine C5H4N4O2 C00385 xanthosine C10H12N4O6 C01762 xanthosine-5-phosphate C10H13N4O9P C00655 Xanthurenic acid C10H7NO4 C02470 METABOLITES_END #END