#METABOLOMICS WORKBENCH chenweiyi_20210701_091947 DATATRACK_ID:2734 STUDY_ID:ST001856 ANALYSIS_ID:AN003008 PROJECT_ID:000000 VERSION 1 CREATED_ON July 6, 2021, 7:09 pm #PROJECT PR:PROJECT_TITLE Anti-anemia drug FG4592 retards the AKI to CKD transition by improving vascular PR:PROJECT_TITLE regeneration and anti-oxidative capability PR:PROJECT_SUMMARY Acute kidney injury (AKI) is a known risk factor for the development of chronic PR:PROJECT_SUMMARY kidney disease (CKD), with no satisfactory strategy to prevent the progression PR:PROJECT_SUMMARY of AKI to CKD. Damage to the renal vascular system and subsequent hypoxia are PR:PROJECT_SUMMARY common contributors to both AKI and CKD. Hypoxia inducible factor (HIF) is PR:PROJECT_SUMMARY reported to protect the kidney from acute ischemic damage and a novel HIF PR:PROJECT_SUMMARY stabilizer, FG4592 (Roxadustat), has become available in the clinic as an PR:PROJECT_SUMMARY anti-anemia drug. However, the role of FG4592 in the AKI-to-CKD transition PR:PROJECT_SUMMARY remains elusive. In the present study, we investigated the role of FG4592 in the PR:PROJECT_SUMMARY AKI-to-CKD transition induced by unilateral kidney ischemia-reperfusion (UIR). PR:PROJECT_SUMMARY The results showed that FG4592, given to mice 3 days after UIR, markedly PR:PROJECT_SUMMARY alleviated kidney fibrosis and enhanced renal vascular regeneration, possibly PR:PROJECT_SUMMARY via activating the HIF-1α/vascular endothelial growth factor A (VEGFA)/VEGF PR:PROJECT_SUMMARY receptor 1 (VEGFR1) signaling pathway and driving the expression of the PR:PROJECT_SUMMARY endogenous antioxidant superoxide dismutase 2 (SOD2). In accordance with the PR:PROJECT_SUMMARY improved renal vascular regeneration and redox balance, the metabolic disorders PR:PROJECT_SUMMARY of the UIR mice kidneys were also attenuated by treatment with FG4592. However, PR:PROJECT_SUMMARY the inflammatory response in the UIR kidneys was not affected significantly by PR:PROJECT_SUMMARY FG-4592. Importantly, in the kidneys of CKD patients, we also observed enhanced PR:PROJECT_SUMMARY HIF-1α expression which was positively correlated with the renal levels of PR:PROJECT_SUMMARY VEGFA and SOD2. Together, these findings demonstrated the therapeutic effect of PR:PROJECT_SUMMARY the anti-anemia drug FG-4592 in preventing the AKI-to-CKD transition related to PR:PROJECT_SUMMARY ischemia and the redox imbalance. PR:INSTITUTE Children's Hospital of Nanjing Medical University PR:LAST_NAME Weiyi PR:FIRST_NAME Chen PR:ADDRESS 72 Guangzhou Road, Nanjing 210008, P. R. of China PR:EMAIL chen.weiyi@qq.com PR:PHONE +862583117309 #STUDY ST:STUDY_TITLE The metabolomic resetting effect of FG4592 in AKI to CKD transition-day 21 ST:STUDY_SUMMARY C57BL/6 mice were anesthetized using isoflurane. UIR was induced by clamping the ST:STUDY_SUMMARY right renal pedicle for 45 minutes and then releasing it to allow reperfusion, ST:STUDY_SUMMARY leaving the left kidney intact. Sham treated mice served as controls. Each mouse ST:STUDY_SUMMARY was located supine on a thermostatic pad (37 °C) to maintain its body ST:STUDY_SUMMARY temperature throughout the whole process. After 3 days of recovery, the mice ST:STUDY_SUMMARY received a daily intraperitoneal (i.p.) injection of FG4592 (10 mg/kg) or ST:STUDY_SUMMARY vehicle for 7 consecutive days. After treatment, the mice were ST:STUDY_SUMMARY sacrificed.Non-target metabolomics analysis was carried out using the kidney ST:STUDY_SUMMARY tissues of mice sacrificed at day 10 after UIR. ST:INSTITUTE Children's Hospital of Nanjing Medical University ST:LAST_NAME Weiyi ST:FIRST_NAME Chen ST:ADDRESS 72 Guangzhou Road, Nanjing 210008, P. R. of China ST:EMAIL chen.weiyi@qq.com ST:PHONE +862583117309 #SUBJECT SU:SUBJECT_TYPE Mammal SU:SUBJECT_SPECIES Mus musculus SU:TAXONOMY_ID 10090 SU:GENOTYPE_STRAIN C57BL/6 SU:AGE_OR_AGE_RANGE 8 weeks SU:WEIGHT_OR_WEIGHT_RANGE 20-25 g SU:GENDER Male SU:ANIMAL_ANIMAL_SUPPLIER Model Animal Research Center of Nanjing University SU:ANIMAL_HOUSING Standard specific pathogen free (SPF) conditions SU:ANIMAL_LIGHT_CYCLE 12:12-h light/dark cycle SU:ANIMAL_FEED food freely SU:ANIMAL_WATER water freely #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 - a1 surgery:sham | day:10 | FG-4592(mg/kg):- SUBJECT_SAMPLE_FACTORS - a2 surgery:sham | day:10 | FG-4592(mg/kg):- SUBJECT_SAMPLE_FACTORS - a3 surgery:sham | day:10 | FG-4592(mg/kg):- SUBJECT_SAMPLE_FACTORS - a4 surgery:sham | day:10 | FG-4592(mg/kg):- SUBJECT_SAMPLE_FACTORS - a5 surgery:UIR | day:10 | FG-4592(mg/kg):- SUBJECT_SAMPLE_FACTORS - a6 surgery:UIR | day:10 | FG-4592(mg/kg):- SUBJECT_SAMPLE_FACTORS - a7 surgery:UIR | day:10 | FG-4592(mg/kg):- SUBJECT_SAMPLE_FACTORS - a8 surgery:UIR | day:10 | FG-4592(mg/kg):- SUBJECT_SAMPLE_FACTORS - a9 surgery:UIR | day:10 | FG-4592(mg/kg):10 SUBJECT_SAMPLE_FACTORS - a10 surgery:UIR | day:10 | FG-4592(mg/kg):10 SUBJECT_SAMPLE_FACTORS - a11 surgery:UIR | day:10 | FG-4592(mg/kg):10 SUBJECT_SAMPLE_FACTORS - a12 surgery:UIR | day:10 | FG-4592(mg/kg):10 #COLLECTION CO:COLLECTION_SUMMARY Non-target metabolomics analysis was carried out using the kidney tissues of CO:COLLECTION_SUMMARY mice sacrificed at day 10 after UIR. CO:SAMPLE_TYPE Kidney #TREATMENT TR:TREATMENT_SUMMARY C57BL/6 mice were anesthetized using isoflurane. UIR was induced by clamping the TR:TREATMENT_SUMMARY right renal pedicle for 45 minutes and then releasing it to allow reperfusion, TR:TREATMENT_SUMMARY leaving the left kidney intact. Sham treated mice served as controls. Each mouse TR:TREATMENT_SUMMARY was located supine on a thermostatic pad (37 °C) to maintain its body TR:TREATMENT_SUMMARY temperature throughout the whole process. After 3 days of recovery, the mice TR:TREATMENT_SUMMARY received a daily intraperitoneal (i.p.) injection of FG4592 (10 mg/kg) or TR:TREATMENT_SUMMARY vehicle for 7 consecutive days. After treatment, the mice were sacrificed. TR:TREATMENT_SUMMARY Non-target metabolomics analysis was carried out using the kidney tissues of TR:TREATMENT_SUMMARY mice sacrificed at day 10 after UIR. TR:TREATMENT_COMPOUND FG4592 TR:TREATMENT_DOSEVOLUME 10 mg/kg #SAMPLEPREP SP:SAMPLEPREP_SUMMARY 20 mg of each tissue sample were homogenized with 0.6 mL of 2 SP:SAMPLEPREP_SUMMARY chlorophenylalanine (4 ppm) containing methanol (−20 °C), centrifuged, and SP:SAMPLEPREP_SUMMARY filtered through a 0.22-μm membrane. #CHROMATOGRAPHY CH:CHROMATOGRAPHY_SUMMARY A 2 μL aliquot of the samples was injected into a Thermo Ultimate 3000 system CH:CHROMATOGRAPHY_SUMMARY equipped with an ACQUITY UPLC® HSS T3 column (150 × 2.1 mm, 1.8 μm, Waters, CH:CHROMATOGRAPHY_SUMMARY Milford, MA, USA) maintained at 40 °C. The mobile phase for positive mode CH:CHROMATOGRAPHY_SUMMARY analysis consists of 0.1% formic acid in water (phase C) and 0.1% formic acid in CH:CHROMATOGRAPHY_SUMMARY acetonitrile (phase D), while the mobile phase for negative mode analysis CH:CHROMATOGRAPHY_SUMMARY consists of 5 mM ammonium formate in water (phase A) and acetonitrile (phase B). CH:CHROMATOGRAPHY_SUMMARY Phase C and D, as well as phase A and B, were mixed and delivered at a flow rate CH:CHROMATOGRAPHY_SUMMARY of 0.25 mL/min with a gradient program as follows: 0~1 min; 2% B.D 1~9 min, CH:CHROMATOGRAPHY_SUMMARY 2%~50% B.D 9~12 min, 50%~98% B.D 12~13.5 min, 98% B.D 13.5~14 min, 98%~2% CH:CHROMATOGRAPHY_SUMMARY B.D 14~20 min, 2% D-positive model (14~17 min, 2% B-negative model). CH:CHROMATOGRAPHY_TYPE Reversed phase CH:INSTRUMENT_NAME Thermo Ultimate 3000 system CH:COLUMN_NAME ACQUITY UPLC® HSS T3 column #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 Proteowizard software (v3.0.8789) #MS_METABOLITE_DATA MS_METABOLITE_DATA:UNITS AUC MS_METABOLITE_DATA_START Samples a1 a2 a3 a4 a5 a6 a7 a8 a9 a10 a11 a12 Factors surgery:sham | day:10 | FG-4592(mg/kg):- surgery:sham | day:10 | FG-4592(mg/kg):- surgery:sham | day:10 | FG-4592(mg/kg):- surgery:sham | day:10 | FG-4592(mg/kg):- surgery:UIR | day:10 | FG-4592(mg/kg):- surgery:UIR | day:10 | FG-4592(mg/kg):- surgery:UIR | day:10 | FG-4592(mg/kg):- surgery:UIR | day:10 | FG-4592(mg/kg):- surgery:UIR | day:10 | FG-4592(mg/kg):10 surgery:UIR | day:10 | FG-4592(mg/kg):10 surgery:UIR | day:10 | FG-4592(mg/kg):10 surgery:UIR | day:10 | FG-4592(mg/kg):10 (R)-5,6-Dihydrothymine 2471276.048 2217114.336 15108313.14 11010489.07 6123663.477 25126016.44 13129837.99 43800087.4 79520118.66 32811480.45 44992027.2 55824317.19 (S)-2,3,4,5-tetrahydropyridine-2-carboxylate 9809185.445 10470565.63 43245638.21 32090954.91 142412161 34758337.6 203080879 83256888.16 16503250.68 160367272 151471012.7 43987481.35 12-Keto-tetrahydro-leukotriene B4 49995581.82 8073887.542 5807368.678 5276422.184 12810930.23 91614910.27 9724677.82 3047961.678 2810743.464 2201099.933 2323729.654 9347733.03 1-Aminocyclopropanecarboxylic acid 2675225482 3096618909 3047161369 3024370920 1794311918 1653398294 2050100708 2231119341 2373790890 2015129770 2138865646 2325384508 1-Methylhistamine 100190782 143974003 125875013.8 135959686.7 12602504.3 2357896.807 9927765.689 2538452.359 5988689.707 128614414.2 17263616.38 19384067.52 1-Methylhistidine 534398570.7 459771863 616742830.1 399967598.2 42917601.56 41074875.36 69143201.98 73965598.83 75988445.28 68090365.25 69706515.46 64524028.71 1-Pyrroline-2-carboxylic acid 139061536.2 326263316.9 434944360 323024954.4 116053341.2 72357222.64 68753019.6 67261130.69 81863468.3 123746386.4 41898896.02 56475627.56 1-Pyrroline-4-hydroxy-2-carboxylate 10829746.97 10240994.59 14098658.08 3297081.422 12076116.51 17725896.79 13768480.87 20433665.83 16560247.1 9745356.683 16924842.16 4028319.137 2-Aminophenol 66537154.93 84840899.63 69959065.96 76690811.11 77273483.99 281568307.9 342176943.1 325364684.8 297383110.4 296485535.9 307950261.6 152083104 2-Dehydropantoate 463714717.4 597008189.9 694240363.3 454840472.1 303478344.3 265822898.4 336899746.7 311635733.9 366031247.9 500785256.2 262119038.9 487186038.5 2-Ketobutyric acid 50925339.76 26160903.37 29167317.75 137567210.3 2963573.87 16114891.65 48464522.49 23125696.93 26304047.03 6103224.031 22474237.3 48618614.88 2-Naphthol 170.9372573 170.9372573 170.9372573 170.9372573 170.9372573 170.9372573 170.9372573 170.9372573 170.9372573 170.9372573 170.9372573 170.9372573 2-Phenylacetamide 1246312551 1293700701 1992747488 1463805134 99780106.25 847670038.5 467738417.1 361341728 531516282.4 744452805.4 382997655.7 197714591.7 3-Dehydrosphinganine 36758379.95 17540604.2 15912385.31 18915089.8 58411475.43 60053386.88 234158493.5 207143481.2 227303946.9 142058920.4 171980502.6 89172716.99 3-Sulfinylpyruvic acid 3268207.978 4232902.413 13447559.64 22307830.87 13385590.73 5083432.328 34057666.76 170.9372573 170.9372573 205917077.4 67371139.9 18451319.26 4,5-Dihydroorotic acid 444594378 170.9372573 170.9372573 170.9372573 170.9372573 170.9372573 170.9372573 170.9372573 170.9372573 170.9372573 170.9372573 170.9372573 5-(2-Hydroxyethyl)-4-methylthiazole 84784080.73 89751968.97 130558965.2 100213718.8 5056413.492 16615767.67 9208021.917 8542265.493 9557693.074 9359829.796 7760731.093 14418809.76 5,6-Dihydro-5-fluorouracil 2074416231 2578369235 3624970078 2174371736 1095394640 1035026091 1443459408 1469809890 1807914575 2122008860 1114422992 2272636880 5-Hydroxylysine 176732554.3 164416864.9 191831636.1 217750588.6 12940298.11 11539529.87 11010447.73 10726000.47 10945354.9 11813257.85 10881644.7 13446306.01 5-Methylthioadenosine 562116749.9 544774399 636052895.6 540002025.6 286286852.5 301059866.8 229637634.4 192115687 209218659.1 252135959.4 251908759.1 478091249.7 5-phosphonooxy-L-lysine 225469585.4 166473767.1 182188683.7 293894554.1 10158753.55 22423925.3 19051539.57 22127331.35 3764630.953 2825275.956 23517293.6 2070290.944 6-Amino-6-deoxyfutalosine 31544952.8 25305986.64 20117880.1 25168657.43 17729040.02 73881.15331 15175701.93 15639845.94 16820.83211 15503.84255 16528366.85 536633.3861 Acetylcholine 267410689.4 202591979.9 202244055.6 201673202.4 427822548.5 379945736.9 487777470.1 498615632.8 706867371.5 832191723 421860752.5 573491060.4 Acetylphosphate 290321472.5 316322082.8 310624988.5 317524746.1 64529647.92 135242114.3 84312165.13 107619038.2 67668560.98 322841535.5 84005672.69 162498569.5 Allocholic acid 30917023.9 18724919.2 14199889.93 24152488.4 12929951.06 14930933.48 28265011.83 37222802.22 26588947.85 32583859.76 23528145.01 21338763.14 alpha-Tocopherol 3864419.73 3549494.133 4382379.335 4388026.873 3876216.086 55050940.89 5738373.088 4516373.39 3808002.026 4944296.604 3032689.146 4925549.223 Aminoadipic acid 348252417.8 690110193.3 1409897287 1085719419 519056313.9 645891763 553899841.3 662724745.5 487302251.2 663714690.8 467837285.6 788518779.6 AMP 1658099.49 996124.0857 891001.5946 476191.744 30149341.14 25749694.45 17010547.27 14171421.29 17129489.23 34131307.18 21115847.42 60171573.7 Antibiotic JI-20A 94269010455 17006225249 12333825313 1521109582 10046088951 1335543519 39290415.84 749708033.8 247075242.4 96817805.68 40276571.7 41278953.48 Argininosuccinic acid 16945865.38 25050089.82 24361365.72 16841937.85 713063.8883 4276809.46 10136614.61 6170207.036 12477979.78 9775246.32 7113458.3 8169271.93 Aspartame 81311149.81 108910012.8 158707732.2 106566642.6 66732445.11 126341455.3 131494694.5 112921272.6 123330508.8 183306388.2 90074452.81 164563114.2 Betaine 33147694072 31323727624 34998948591 28116744975 13291817660 19685267703 22429380917 20015271921 27461506841 27794628525 22412553506 22148551389 Betaine aldehyde 2266873559 1998962389 2401755531 1856410044 281258079 740321518.9 926605913.6 1144398046 1059919314 913384947.3 823455595.3 957580295.6 Carnosine 21426175.26 33733553.82 32184413.33 27250251.79 2469383.306 3573101.23 4909568.775 3643974.037 1315681.464 4561080.038 5132649.563 4712646.535 Choline 771228464.3 996202364.8 514408124.3 777674272.4 1083220556 971866037.7 432607629 65985836.23 78559650.73 74247494.64 79030367.48 191825705.7 cis-4-Hydroxy-D-proline 643391240.7 656138354.5 692223250 702658246.2 1213053389 779630560.4 771903601.4 909147318.3 985474004.8 1084137756 795892082.6 1026410892 Citicoline 36665356.3 30413302.14 30149152.84 28974334.68 86342.31439 423412.5575 1026388.038 593891.4812 815393.9402 1380064.481 766943.7798 6839423.624 CMP 80266329.15 89424357.37 99457907.29 75390244.72 42105912.95 38827430.02 33605962.09 33766032.8 38280967.87 65615606.48 34256157.89 72328376.71 Corticosterone 60370227.27 62390373.23 61419880.26 80011836.37 36534165.98 19587317.83 22108335.37 20397989.69 6109782.891 26351150.1 15840150.78 33424649.18 Cortisol 13488359.29 11620317.03 11643705.85 12054094.59 47292.56193 14294.14877 56341.99681 19264.73228 9243590.235 136810.6582 8183975.178 12383.589 Creatine 15953889172 15332105639 17620527763 15999972675 14822530591 10023483872 15943836456 17949108874 15424366779 23316848434 13777582921 20585121086 Creatinine 997422374.6 1185193828 1523277252 1315902218 281978803.9 290200039.4 316237182.1 296164513.7 242416296.2 265286406.6 262743155.9 274820047.3 Cyclic GMP 44687846.76 37591401.23 871223288.9 802489373.8 175928239.7 241687420.3 992022335 392140319.7 189571351.1 167089335.7 28444107.59 171875826.9 Cytosine 111301630.8 116452806.2 113893374.6 99489471.25 907701009.8 271141660.4 456688131.6 195292730.9 232936254.4 710713475.6 217739501.5 488435356 D-4-Phosphopantothenate 3417555.22 3443716.813 1730125.076 2590568.181 9024629.489 141830.9788 707635.4691 1230868.261 641411.85 5638435.237 110236.5935 1314631.033 Dehypoxanthine futalosine 35371669.32 26169948.26 30561285.79 26005862.13 6698824.545 20780714.32 10273390.07 9244999.537 11673974.12 16704708.31 19266347.02 38107296.34 Deoxycholic acid 48611958.39 48120761.95 42826531.66 39943979.78 47436536.6 80261375.27 775213603.9 170.9372573 170.9372573 1132954908 461176687 376053044 Deoxycytidine 6956519.891 9316509.573 10368495.77 9768084.135 97402.48528 6239991.264 381485.7775 746693.4337 149073.149 486590.275 477084.9262 257738.6754 Deoxyuridine 226914993.2 112423096.5 376376158.8 126859632.7 113245880.1 246431195.8 170.9372573 170.9372573 170.9372573 170.9372573 1359073888 351133816 D-Fructose 35990832.07 53795782.22 51264611.26 42389516.96 164203266.4 20365217.46 20762476.26 10501048.84 18753551.02 5431607.979 6970401.895 11346850.18 D-Glucose 1-phosphate 352243676.7 250333001.4 240502733.5 279335479.5 218867773.3 210981888 230910355.1 192049242.4 172838978.7 199308133.1 168939569.3 240102161 Dodecanoic acid 340997483.1 377486562 268501318.3 268677275.3 274052954.8 563165587 451850007.4 275212059.2 381254669.8 381822849.1 375886396.6 592532837.7 D-Ribose 94930465.37 470002353.5 71781596.35 70356316.34 67793157.27 326367109.4 170.9372573 170.9372573 170.9372573 170.9372573 170.9372573 334353542.1 Ergocalciferol 3761565.74 1023659.87 1163599.504 1358962.943 1417042.101 777221.9365 372058.3372 328550.5144 470228.78 3282988.569 146069.8582 6598058.674 Ergothioneine 1740996896 1553030848 1894453446 1045807258 60739225.71 584016494.5 456517112.3 370853671.2 566671903.2 891102834.5 375567760.2 824634641.5 Erucic acid 170.9372573 170.9372573 170.9372573 170.9372573 170.9372573 170.9372573 170.9372573 170.9372573 170.9372573 170.9372573 170.9372573 170.9372573 gamma-Aminobutyric acid 170.9372573 170.9372573 170.9372573 170.9372573 170.9372573 170.9372573 170.9372573 170.9372573 170.9372573 170.9372573 170.9372573 170.9372573 gamma-Glutamylcysteine 7304034.789 9385692.253 9942431.106 6583790.303 80291.10821 13333.75012 64368.2417 63984.11633 13687.01952 48148.98506 47814.66361 86270.64881 gamma-L-Glutamyl-L-2-aminobutyrate 55159322.1 67611305.55 64469485.32 49579320.52 2499760.298 5402709.278 2520125.308 2170300.061 3164455.01 1080087.032 2433811.91 6014330.497 Gentamicin C1a 22921078.71 19648127.06 41272686.2 23531217.52 12528061.99 5046678.039 9925063.501 12649735.3 18437199.15 17371405 14749780.65 18191722.17 Gentisic acid 2640610835 1121776652 512817028.3 980111220 442468097.1 392459775.4 170.9372573 170.9372573 170.9372573 170.9372573 170.9372573 170.9372573 GMP 48994659.38 47141333.87 46834499.32 34626464.51 2087983.09 6618147.6 11164144.16 8014800.776 15481154.63 19473837.45 13337414.34 34821022.33 Guanine 545725542.9 600895050.6 778845144.7 646939012.6 135079628.7 123430304.8 150070011.4 80450865.6 91867369.24 95886923.32 84917925.66 245049851.4 Guanosine 364460311 382534317.6 494263544.7 428105874.7 90838611.31 93434955.79 81903718.79 62086621.13 68839823.84 72498806.63 65563399.7 172389662 Hippuric acid 803294671.8 525558284.7 801275662 733736763.6 30839632.76 65868288.23 42352337.06 3606404.053 3242296.66 2835011.21 33129916.83 61911939.74 Hydrogen phosphate 93373176.72 54685451.37 85326862.79 102860471.3 2387230.764 2338865.66 131422414.9 139374075.8 1178792.216 4425847.736 3656366.002 275607333.2 IMP 154952468.8 27315938.46 110407357.2 148834858.7 505351.8525 4265851.074 10389664.05 1586513.592 15596589.7 6043853.347 3969200.822 32488352.27 Indole 20427868.58 40689533.82 42534609.34 21550726.79 5231036.628 4075779.62 10212931.25 2593585.623 8116737.419 5094127.36 3832035.993 4372931.549 Indoleglycerol phosphate 62674891.68 88520024.01 65803684.82 81574632.47 114514797.2 37504864.92 67499466.92 77982563.99 38721292.27 59665717.21 82506347.53 70345171.9 Isocitric acid 135176241.1 27507652.71 19287452.99 27270862.29 10653364.74 3717701.771 8758187.389 6488144.182 11938111.87 1485984.539 6626844.184 2707835.08 Kynurenic acid 245058687 149688193.1 123717378.6 151016984.5 7689343.362 10534913.68 7279609.26 4892726.983 4260606.923 3569363.332 3394782.01 11069891.09 L-2,4-diaminobutyric acid 19259445.55 6222004.358 8236635.324 22591101.94 7985208.977 7909798.517 2229859.966 8241544.681 2862280.541 1033470.895 4837289.707 10855613.73 L-Arginine 2315853101 2762277044 3497595918 2429820664 112842642.5 866592419.7 908188930.8 790777779.6 1753418125 988449491.7 1511184366 1560835578 L-Asparagine 1636409008 1558565473 1116204624 1499318330 2226553554 2188985904 1919983400 1852255315 2312388161 1543271864 2028221655 1523771148 L-Carnitine 19625883377 20888729727 17821702747 17215437539 7975880691 13422065229 16207552019 17344541484 17572283057 19740992570 18159102108 17543952680 L-Cystine 46203946.39 51808609.25 64582885.96 59653394.67 5675054.586 13787707.2 14473246.56 20260030.27 13957442.78 16124034.93 11774380.67 16152153.47 L-Glutamine 692599152.6 788998066.4 934965774.5 741469779.1 186499535.7 613193464.2 552025843.5 524641260.5 617458332.9 707833011.9 564441228.6 523571896.4 L-Histidine 1151049302 1163920912 1210425716 898087340.2 565625973.8 543646380 517185884.9 314279002.1 475401622.6 450322603.3 500991003 651105252.9 Linoleic acid 81218773.84 35995045.83 142048364.5 159270053.5 46768037.91 46986197.38 55495267.04 82552087.33 54134545.82 79621829.46 25570016.43 87659123.56 L-Isoleucine 43948937.36 50877751.54 13810783.36 9077727.903 61385249.17 24013553.86 170.9372573 170.9372573 170.9372573 170.9372573 360024630.2 111080593.1 L-Leucine 95112949.35 109625620.5 151022541.3 294996787.5 51637719.48 56321940.94 935033118.1 2455620683 2525987560 1123718940 723399672.3 915013100.1 L-Lysine 3013898380 4541155338 4503880175 3936765493 2706245725 2066597467 1634463166 1305072591 1857758458 1795930726 1634411045 1840117858 L-Methionine 9172989728 11698322410 15193365454 6726324394 2584261005 1605975324 1886253708 1813611233 1508532037 2132901463 1520387111 2861316227 L-Phenylalanine 27499769386 37420623625 44301258426 33525578116 25589821277 21499997435 22593004789 21629698446 26313741886 33239169242 19472522857 36368494840 L-Proline 173825941.9 213272003.4 218005848.2 160049933.8 87298444.88 104510213.5 116429458.9 138808579.1 168983515 202961971.2 148567963.3 103750213.2 L-Rhamnofuranose 15272568.55 35787246.39 4976895.437 4201290.953 5243112.991 6086861.558 734837.9185 539547.9956 963999.6671 2448005.765 154526.4104 1967744.947 L-Serine 503497775.7 603180178.7 720507973.9 523660107.2 249632986.7 379776702.8 319515483.5 408355419.7 476823623.9 454060593.2 440012055.6 409355296.5 L-Threonine 5917894911 6845100962 7889184185 6764280623 4352914146 3533217828 4306471644 4460424628 5049284718 4243484870 4333094315 5156520777 L-Tryptophan 5561206901 6637616822 8604717197 5586257812 4142242663 3851364795 4386535794 4113293321 4779323169 6375361551 3573890333 6409750114 L-Tyrosine 15617112013 19920480738 26460397795 18878346975 10188893086 9689586089 170.9372573 170.9372573 170.9372573 170.9372573 170.9372573 170.9372573 L-Valine 3018139345 3704759309 4473077802 3153198729 2190276903 2409417563 691444757 586326272.8 719597927.1 1100039359 730877239.3 1959128078 Methyl beta-D-galactoside 462405559.8 170.9372573 170.9372573 170.9372573 170.9372573 170.9372573 170.9372573 170.9372573 170.9372573 170.9372573 170.9372573 170.9372573 myo-Inositol 1403502109 1294089773 618716885.4 200414430.2 1201714712 420531571.2 170.9372573 170.9372573 170.9372573 170.9372573 170.9372573 6279333956 N6-Acetyl-L-lysine 99805283.38 123108247.6 144575034.3 105468545.6 19985794 19112965.07 18660703.42 17000964.9 19351105.4 30380400.58 14851065.6 34607838.52 N-Acetyl-alpha-D-glucosamine 1-phosphate 74921998.17 140595930.2 170.9372573 170.9372573 170.9372573 170.9372573 134819330.2 71451709.77 62863486.73 107708644.9 46067283.49 74089378.23 Niacinamide 2685741545 2869613483 2103610259 2799076326 345801876 990099282.6 874037305.6 856521409.3 876064279 599889118.6 1030884681 519288231.4 Norepinephrine 191904811.7 212463035.6 184553716.1 158019750.1 130957061.2 69605068.63 137308639 164177834.6 208703278.6 185132857.2 206383118.7 251063432.7 Oleic acid 3.34381E+12 170.9372573 170.9372573 170.9372573 170.9372573 170.9372573 170.9372573 170.9372573 170.9372573 81913268333 62952097881 12986826058 O-Phosphoethanolamine 591154943.4 496935260.4 490616582.3 593442146.4 803068182 1061571304 1117747476 880969034 941038665.5 830768137.2 1249789529 759572795.8 Ornithine 174898039.8 288651434.9 378184428.2 259270413 635375302.7 193783552 234248488.1 224301594.5 205146343 327233945.2 151295656.6 208011537.3 Palmitic acid 59623732.27 127172028.8 170.9372573 170.9372573 106055661.9 13339774.46 35648342.88 73843633.17 34963222.15 63383335.28 36950569.42 25126021.66 Palmitoleic acid 10207827.37 2544732.736 2346567.603 6145489.975 2193741.539 2333457.345 4032031.026 4593785.411 4754126.786 4797779.397 7823292.774 8207699.063 Palmitoyl-L-carnitine 537083099.4 575967197.1 634305692.5 412368117.4 2286488128 913335589.3 1276943954 1168223970 1162424718 364436216.6 951384428.2 1424098881 p-Aminobenzoic acid 61255353.02 56945379.23 66151598.6 214269479.5 95991286.82 44163057.35 123450291.6 163181035.9 196521144.7 51429910.54 140380362.1 44116791.74 Pantothenic acid 1910913517 2096987236 2546489879 1660525861 206362399.7 657999796.4 535799590.7 459236569.4 583178140.5 813033197.2 454602771.5 969261145.2 Phenylacetylglycine 511556193.2 587690689.2 608329616.9 480442028.4 42205825.14 139384952.8 56731124.15 36057636.62 42131743.18 33159729.22 17546512.6 48799832.08 Phosphorylcholine 10093701045 11268133398 12009273851 11481837788 10123352682 15396770984 20843763183 18906041039 19075432916 28913228083 19538199693 23050399107 Phytosphingosine 21029183.13 30434503.34 21879549.61 27639769.48 97987637.55 80150031.55 168949856.8 182806472.3 153281716.2 105200397.4 303477448.7 175875069.7 Pipecolic acid 11551466374 13312092073 10432799308 12328929650 5398853401 5857804752 8448727966 9489805484 11425686590 10599163785 10599426765 11023441097 Prostaglandin F2a 9156114.659 8390709.114 11152518.22 17015226.97 54385190.82 158645889.9 56282239.81 36852761.45 32979738.54 51139321.59 20649241.69 29755652.06 Protoporphyrinogen IX 16325374447 14538869832 17888613266 20157421264 4637614199 1326224176 1373960450 1297143796 1449426982 1948212594 981431261.9 2659847780 Pyridoxamine 5-phosphate 86713458.49 99650408.31 145392615.1 188625312.7 1791258.258 170.9372573 1242235.677 1149122.082 636011.5159 410040.7135 1155841.707 535609.0081 Pyrimidodiazepine 48842244.02 59896120.31 81945902.58 52107055.07 28550742.4 6387046.926 6303981.09 6831774.854 5008098.199 9308086.565 6747178.395 10750688.53 Pyroglutamic acid 25626391.68 35215845.39 5368113.017 24425442.1 13454066.15 33602010.32 12679272.35 17188732.31 17625246.63 23860068.69 28560024.34 97457437.82 Pyrrolidonecarboxylic acid 170.9372573 170.9372573 170.9372573 170.9372573 170.9372573 170.9372573 170.9372573 170.9372573 170.9372573 170.9372573 774889017.7 117213784.4 Retinoyl b-glucuronide 129425374.5 98946447.3 96457036.76 102979118.6 25379085.89 21124275.37 11587423.05 6048709.099 6368962.121 8299849.775 6084519.381 12520918.58 Riboflavin 68981355.32 221384777.9 202403999.5 147317186.5 23090019.8 39128629.51 37163366.26 43077465.41 38890251.35 51389536.8 31792356.69 65805469.13 Saccharopine 57740251.64 72547539.59 114434670.9 61197461.19 17897843.85 356600719.2 37125590.14 38426844.5 47666682.84 48225449.72 33913627.22 63644462.68 S-Adenosylhomocysteine 83341492.15 80751732.46 99650945.69 84289837.93 3008744.921 9285027.187 170.9372573 170.9372573 170.9372573 170.9372573 170.9372573 170.9372573 S-Adenosylmethionine 313912676 653423919.5 1611797142 2466133724 797302919.9 402917870.8 1285702964 1923081776 1625706522 1507193723 1281620338 1457287622 Se-Methylselenocysteine 54039601.73 94634892.91 76144192.03 102932699 44847055.82 19196206.68 110431160.1 168880793.7 459435939.8 360734154.5 123327584.7 77624345.28 Sorbitol 204632437.3 225593074.9 193966157.6 228838646.8 909810044.1 281538044 286120031.3 324797675.8 286190849.8 302372657.5 266778464.1 215446841.7 Spermidine 879134974.9 660138171.5 492489855.3 240229807 585397206 195339176.2 1917654487 1075650055 2508469293 1390261958 1308627703 1393586437 Sphinganine 83682703.98 77496870.77 90200188.79 100869185.9 75717574.37 121592774.1 207791928.5 193281937 131171300.5 181265394.8 176106653.2 164321699.2 Sphingosine 355232157.5 802817940.9 698662630.8 1064985502 4381147044 1704602964 1890981753 1679623766 1692031622 960470070.8 2583093313 1415700831 Sucrose 5922221.834 15579996.45 10333483.14 83387026.87 23597444.1 11357070.89 20494060.31 31026715.82 5894027.221 34767596.98 18530299.02 29490050.06 Taurine 1780712075 1045932825 715596407.2 2044169269 358725062.3 170.9372573 170.9372573 170.9372573 170.9372573 170.9372573 170.9372573 170.9372573 Thiamine 238478436.2 188166142.1 204862369 221221871 10638777.64 41061971.2 49907786.61 40751074.52 61218961.94 31699505.45 44645203.45 50998201.17 Thiamine aldehyde 7009060.231 7202408.591 8980696.368 6845404.362 749753.1262 7569026.142 1926020.451 431708.9399 2203565.704 2776440.272 1865165.631 3427213.774 Thiamine monophosphate 121356274.5 118215809.7 142104782.2 144110428 2956146.214 41739471.14 33162616.44 33975324.81 29511902.75 25943146.38 29006007.9 38037698.46 Thymine 1249950.504 847085.4026 709169.4856 1620405.107 1640941.054 1141120.433 4775943.464 4666539.742 6395857.762 37192768.87 11739075.24 7758710.452 UMP 29373525.69 28582133.41 34008700.45 29737264.95 2882973.012 10891468.09 8897586.05 6270029.257 9154543.446 11288898.86 8069870.901 21403127.63 Uracil 4540397582 3434637090 5506250565 3789018354 1267619790 973067796.6 3484119928 4206013963 3538169605 4999096940 1358213153 4310766675 Uric acid 43158426.29 46413710.82 38132655.26 41631640.95 439965067 236263230.6 199994382.4 208641599 237434413.8 505550326.4 129228654.9 185913667 Uridine 74996673.09 82676995.18 118991836.5 88737370.04 44095038.96 27517037.09 18586700.84 12910110.14 12501234.4 27090347.28 10032924.87 24874283.37 Vanillylmandelic acid 88017867.21 88186563.17 106664437.5 123941135.9 87373988.6 103695795.7 107058461.8 106304989 100523866.7 106357664.4 174074726.6 184419976.4 MS_METABOLITE_DATA_END #METABOLITES METABOLITES_START metabolite_name KEGG mz rt pubchem (R)-5,6-Dihydrothymine C21028 128.0699884 379.753 676415 (S)-2,3,4,5-tetrahydropyridine-2-carboxylate C00450 128.070005 362.383 24771808 12-Keto-tetrahydro-leukotriene B4 C02165 336.3242663 824.917 5280492 1-Aminocyclopropanecarboxylic acid C01234 102.0556603 86.9667 535 1-Methylhistamine C05127 126.1026108 73.5933 3614 1-Methylhistidine C01152 170.0921134 81.35575 64969 1-Pyrroline-2-carboxylic acid C03564 114.0550968 91.6641 440046 1-Pyrroline-4-hydroxy-2-carboxylate C04282 130.0500177 303.467 440282 2-Aminophenol C01987 110.0600691 34.12605 5801 2-Dehydropantoate C00966 146.0597969 389.76 38 2-Ketobutyric acid C00109 102.0550391 288.692 58 2-Naphthol C11713 144.0652791 688.4185 8663 2-Phenylacetamide C02505 136.07576 178.053 7680 3-Dehydrosphinganine C02934 300.2884167 788.483 439853 3-Sulfinylpyruvic acid C05527 152.9948242 45.89235 110 4,5-Dihydroorotic acid C00337 158.9612035 179.031 439216 5-(2-Hydroxyethyl)-4-methylthiazole C04294 144.0476666 316.43 1136 5,6-Dihydro-5-fluorouracil C16630 133.0316659 144.3385 121997 5-Hydroxylysine C16741 163.1073942 74.5495 3032849 5-Methylthioadenosine C00170 298.0953333 377.527 439176 5-phosphonooxy-L-lysine C03366 243.0730941 81.9686 25163995 6-Amino-6-deoxyfutalosine C20773 413.1221835 325.1615 56927843 Acetylcholine C01996 146.1172995 93.6146 187 Acetylphosphate C00227 139.9820748 179.778 186 Allocholic acid C00695 408.3662657 838.9995 221493 alpha-Tocopherol C02477 430.2406698 524.126 14985 Aminoadipic acid C00956 162.0760486 95.4502 92136 AMP C00020 348.0684207 282.6095 6083 Antibiotic JI-20A C17704 482.3264073 739.222 512870 Argininosuccinic acid C03406 291.1282108 86.2388 16950 Aspartame C11045 295.1272032 416.2835 134601 Betaine C00719 118.0849853 88.6907 247 Betaine aldehyde C00576 102.091914 95.3988 249 Carnosine C00386 227.113488 81.3668 439224 Choline C00114 104.1061042 137.0045 305 cis-4-Hydroxy-D-proline C03440 132.0653589 86.3942 440014 Citicoline C00307 489.1114547 89.1003 13804 CMP C00055 324.0572137 96.4734 6131 Corticosterone C02140 347.2194149 706.2485 5753 Cortisol C00735 363.2140037 659.774 5754 Creatine C00300 132.0756528 93.1181 586 Creatinine C00791 114.0658419 89.3776 588 Cyclic GMP C00942 346.3302183 794.075 135398570 Cytosine C00380 112.0506693 97.44095 597 D-4-Phosphopantothenate C03492 299.0811173 313.372 41635 Dehypoxanthine futalosine C17010 296.0642731 86.1212 25137931 Deoxycholic acid C04483 393.2827764 790.3655 222528 Deoxycytidine C00881 227.1637163 749.419 13711 Deoxyuridine C00526 228.1954449 774.422 13712 D-Fructose C00095 181.0142837 690.1885 439163 D-Glucose 1-phosphate C00103 261.0361322 89.40155 65533 Dodecanoic acid C02679 199.9874057 34.1886 3893 D-Ribose C00121 151.0352467 127.678 5779 Ergocalciferol C05441 397.1990957 797.1855 5280793 Ergothioneine C05570 230.0943406 97.38925 3037043 Erucic acid C08316 338.3410702 770.879 5281116 gamma-Aminobutyric acid C00334 104.1061114 105.6955 119 gamma-Glutamylcysteine C00669 251.0685052 434.9015 123938 gamma-L-Glutamyl-L-2-aminobutyrate C21015 233.0910782 511.196 7014903 Gentamicin C1a C00908 432.278672 450.506 72396 Gentisic acid C00628 154.9896356 808.7755 3469 GMP C00144 364.0628949 141.963 135398631 Guanine C00242 152.0564932 295.017 135398634 Guanosine C00387 284.0980513 295.017 135398635 Hippuric acid C01586 180.0650433 456.675 464 Hydrogen phosphate C00009 98.98387021 153.97 1004 IMP C00130 349.0534732 149.858 135398640 Indole C00463 118.0651346 573.77 798 Indoleglycerol phosphate C03506 288.0734139 86.8329 444150 Isocitric acid C00311 192.0321603 139.238 1198 Kynurenic acid C01717 190.0497674 411.5515 3845 L-2,4-diaminobutyric acid C03283 118.0660629 584.913 134490 L-Arginine C00062 175.1187227 81.3894 6322 L-Asparagine C00152 133.0605947 83.103 6267 L-Carnitine C00318 162.1120076 87.27295 10917 L-Cystine C00491 241.1284285 81.52915 67678 L-Glutamine C00064 147.0762909 84.7034 5961 L-Histidine C00135 156.0768164 81.0159 6274 Linoleic acid C01595 280.2631022 838.187 5280450 L-Isoleucine C00407 132.1027952 347.051 6306 L-Leucine C00123 132.1019689 310.143 6106 L-Lysine C00047 147.112701 74.63245 5962 L-Methionine C00073 150.0582029 118.999 6137 L-Phenylalanine C00079 166.0837578 334.8235 71567 L-Proline C00148 116.0695572 94.67215 145742 L-Rhamnofuranose C02431 164.0707085 70.7517 11953811 L-Serine C00065 106.0495101 83.0688 5951 L-Threonine C00188 120.0647339 86.34545 6288 L-Tryptophan C00078 205.0966077 389.7295 6305 L-Tyrosine C00082 182.0803667 213.1785 6057 L-Valine C00183 118.0854839 139.762 6287 Methyl beta-D-galactoside C03619 176.971698 131.435 94214 myo-Inositol C00137 181.0140536 770.6025 892 N6-Acetyl-L-lysine C02727 189.1228471 97.4596 92832 N-Acetyl-alpha-D-glucosamine 1-phosphate C04501 284.0519193 93.9054 440364 Niacinamide C00153 123.0544798 97.8966 936 Norepinephrine C00547 169.9770116 33.9434 439260 Oleic acid C00712 282.2799153 769.886 445639 O-Phosphoethanolamine C00346 142.0259898 82.847 1015 Ornithine C00077 133.0970815 74.63245 6262 Palmitic acid C00249 256.2624713 724.5185 985 Palmitoleic acid C08362 255.2310763 838.125 445638 Palmitoyl-L-carnitine C02990 400.3401992 804.0185 NULL p-Aminobenzoic acid C00568 138.0546372 93.21095 978 Pantothenic acid C00864 220.1173406 351.889 6613 Phenylacetylglycine C05598 194.0803054 487.0485 68144 Phosphorylcholine C00588 184.0726495 84.557 1014 Phytosphingosine C12144 318.2984551 761.798 122121 Pipecolic acid C00408 130.0491734 86.9845 439227 Prostaglandin F2a C00639 337.2352045 691.6825 5280363 Protoporphyrinogen IX C01079 568.3345052 826.617 121893 Pyridoxamine 5-phosphate C00647 249.0627792 83.291 1053 Pyrimidodiazepine C02587 221.091613 287.5265 135398683 Pyroglutamic acid C01879 130.0502227 205.4365 7405 Pyrrolidonecarboxylic acid C02237 130.0487954 609.396 439685 Retinoyl b-glucuronide C11061 476.2739684 798.3975 5281877 Riboflavin C00255 377.1435091 441.034 493570 Saccharopine C00449 276.1175619 94.8208 160556 S-Adenosylhomocysteine C00021 385.1256251 97.6196 439155 S-Adenosylmethionine C00019 398.241845 790.351 34755 Se-Methylselenocysteine C05689 182.983879 302.99 147004 Sorbitol C00794 182.9861291 107.481 5780 Spermidine C00315 144.9819087 838 1102 Sphinganine C00836 302.3034456 762.4445 91486 Sphingosine C00319 300.288564 773.2745 5280335 Sucrose C00089 343.2956637 733.5765 5988 Taurine C00245 125.9862491 190.029 1123 Thiamine C00378 265.1110141 84.68885 1130 Thiamine aldehyde C05856 264.0809898 351.845 440815 Thiamine monophosphate C01081 345.0762476 85.386 1131 Thymine C00178 125.9865306 345.2995 1135 UMP C00105 325.0411857 138.581 6030 Uracil C00106 113.033695 204.073 1174 Uric acid C00366 169.0355688 98.089 1175 Uridine C00299 245.0761278 141.17 6029 Vanillylmandelic acid C05584 198.1849171 683.6175 1245 METABOLITES_END #END