#METABOLOMICS WORKBENCH WXIAOLAB_20230807_091801 DATATRACK_ID:4207 STUDY_ID:ST003454 ANALYSIS_ID:AN005675 PROJECT_ID:PR002128 VERSION 1 CREATED_ON September 4, 2024, 6:31 am #PROJECT PR:PROJECT_TITLE Aerobic activation of hypoxia-inducible factor 1alpha in vascular cells. PR:PROJECT_SUMMARY This project aims to delineate the possible mediators of aerobic activation of PR:PROJECT_SUMMARY HIF1alpha in normal primary cells and its biological consequences related to PR:PROJECT_SUMMARY pulmonary vascular pathobiology. PR:INSTITUTE Peking University PR:DEPARTMENT Department of Toxicology PR:LABORATORY WXIAO PR:LAST_NAME Xiao PR:FIRST_NAME Wusheng PR:ADDRESS 38 Xueyuan Rd, Haidian District, Beijing, Beijing, 100191, China PR:EMAIL wxiao@bjmu.edu.cn PR:PHONE +1-010-82801628 #STUDY ST:STUDY_TITLE Branched chain alpha-ketoacids impact pulmonary artery smooth muscle cell ST:STUDY_TITLE metabolism ST:STUDY_SUMMARY Hypoxia-inducible factor 1α (HIF1α) is a master regulator of biological ST:STUDY_SUMMARY processes in hypoxia. Yet, the mechanisms and biological consequences of aerobic ST:STUDY_SUMMARY HIF1α activation by intrinsic factors, particularly in normal (primary) cells, ST:STUDY_SUMMARY remain elusive. Here, we show that HIF1α signalling is activated in several ST:STUDY_SUMMARY human primary vascular cells in normoxia, and in vascular smooth muscle cells ST:STUDY_SUMMARY (VSMCs) of normal human lungs. Mechanistically, aerobic HIF1α activation is ST:STUDY_SUMMARY mediated by paracrine secretion of three branched chain α-ketoacids (BCKAs), ST:STUDY_SUMMARY which suppress PHD2 activity via direct inhibition and via LDHA-mediated ST:STUDY_SUMMARY generation of L-2-hydroxyglutarate. BCKA-mediated HIF1α signalling activation ST:STUDY_SUMMARY stimulated glycolytic activity and governed a phenotypic switch of pulmonary ST:STUDY_SUMMARY artery SMCs, which correlated with BCKA metabolic dysregulation and ST:STUDY_SUMMARY pathophenotypic changes in pulmonary arterial hypertension patients and male rat ST:STUDY_SUMMARY models. We thus identify BCKAs as novel signalling metabolites that aerobically ST:STUDY_SUMMARY activate HIF1α and that the BCKA-HIF1α pathway modulates VSMC function, an ST:STUDY_SUMMARY effect that may be relevant to pulmonary vascular pathobiology. ST:INSTITUTE Peking University ST:DEPARTMENT Department of Toxicology ST:LAST_NAME Xiao ST:FIRST_NAME Wusheng ST:ADDRESS 38 Xueyuan Rd, Haidian District, Beijing, Beijing, 100191, China ST:EMAIL wxiao@bjmu.edu.cn ST:PHONE +1-010-82801628 #SUBJECT SU:SUBJECT_TYPE Cultured cells SU:SUBJECT_SPECIES Homo sapiens SU:TAXONOMY_ID 9606 SU:GENDER Male and female #FACTORS #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 Ctrl 01 Treatment:control | Sample source:Vascular smooth muscle cells SUBJECT_SAMPLE_FACTORS 2 Ctrl 02 Treatment:control | Sample source:Vascular smooth muscle cells SUBJECT_SAMPLE_FACTORS 3 Ctrl 03 Treatment:control | Sample source:Vascular smooth muscle cells SUBJECT_SAMPLE_FACTORS 4 Ctrl 04 Treatment:control | Sample source:Vascular smooth muscle cells SUBJECT_SAMPLE_FACTORS 5 Ctrl 05 Treatment:control | Sample source:Vascular smooth muscle cells SUBJECT_SAMPLE_FACTORS 6 Ctrl 06 Treatment:control | Sample source:Vascular smooth muscle cells SUBJECT_SAMPLE_FACTORS 7 BCKAs 01 Treatment:BCKAs | Sample source:Vascular smooth muscle cells SUBJECT_SAMPLE_FACTORS 8 BCKAs 02 Treatment:BCKAs | Sample source:Vascular smooth muscle cells SUBJECT_SAMPLE_FACTORS 9 BCKAs 03 Treatment:BCKAs | Sample source:Vascular smooth muscle cells SUBJECT_SAMPLE_FACTORS 10 BCKAs 04 Treatment:BCKAs | Sample source:Vascular smooth muscle cells SUBJECT_SAMPLE_FACTORS 11 BCKAs 05 Treatment:BCKAs | Sample source:Vascular smooth muscle cells SUBJECT_SAMPLE_FACTORS 12 BCKAs 06 Treatment:BCKAs | Sample source:Vascular smooth muscle cells #COLLECTION CO:COLLECTION_SUMMARY intracellular metabolites were collected and stored at -80 degree before LC-MS CO:COLLECTION_SUMMARY analysis. CO:SAMPLE_TYPE Vascular smooth muscle cells CO:COLLECTION_METHOD -80 C precold 80% LC-MS grade methanol was used to collect cell metabolites by CO:COLLECTION_METHOD scraping and centrifugation CO:COLLECTION_LOCATION on dry ice CO:COLLECTION_DURATION 1 min CO:STORAGE_CONDITIONS -80℃ CO:COLLECTION_TUBE_TEMP -100 C CO:TISSUE_CELL_IDENTIFICATION Pulmonary artery smooth muscle cells #TREATMENT TR:TREATMENT_SUMMARY human pulmonary artery smooth muscle cells were treated with branched chain TR:TREATMENT_SUMMARY alpha-ketoacids at 50-100 micromolar concentration for 8 hours. TR:TREATMENT_COMPOUND branched chain alpha-ketoacids KIC, KIV, and KMV TR:TREATMENT_ROUTE addition to medium TR:TREATMENT_DOSE 50-100 uM TR:TREATMENT_DOSEDURATION 8 hours TR:TREATMENT_VEHICLE water TR:CELL_GROWTH_CONTAINER 75 cm flasks TR:CELL_GROWTH_CONFIG 1200 rpm TR:CELL_GROWTH_RATE 30-40 hours TR:CELL_MEDIA Complete vascular smooth muscle cell growth medium supplemented with growth TR:CELL_MEDIA factors and 5% FBS TR:CELL_ENVIR_COND 37 C and 5% CO2 TR:CELL_PCT_CONFLUENCE 70-80% TR:CELL_MEDIA_LASTCHANGED Every 48 hours #SAMPLEPREP SP:SAMPLEPREP_SUMMARY PASMCs were quickly washed with two volumes of ice-cold PBS, lysed for 15 min in SP:SAMPLEPREP_SUMMARY pre-chilled 80% liquid chromatography-mass spectrometry (LC-MS)-grade methanol, SP:SAMPLEPREP_SUMMARY and harvested by scraping on dry ice followed by centrifugation at maximal speed SP:SAMPLEPREP_SUMMARY for 30 min at 4°C. For medium samples, 50 μL of medium were incubated in 200 SP:SAMPLEPREP_SUMMARY μL of pre-cooled 100% LC-MS-grade methanol for 15 min on dry ice and then SP:SAMPLEPREP_SUMMARY centrifuged as cell samples did. The supernatants of cell and medium samples SP:SAMPLEPREP_SUMMARY were collected and evaporated to dryness on an Integrated SpeedVac System SP:SAMPLEPREP_SUMMARY (Thermo Fisher Scientific; Waltham, MA) at 42°C. The resulting pellets were SP:SAMPLEPREP_SUMMARY resuspended in 50 μL of LC-MS-grade water. Twenty microliters of sample were SP:SAMPLEPREP_SUMMARY loaded in an autosampler vial for analysis. SP:PROCESSING_STORAGE_CONDITIONS Described in summary SP:EXTRACT_STORAGE Described in summary #CHROMATOGRAPHY CH:CHROMATOGRAPHY_SUMMARY LC-MS analysis was performed on a Vanquish ultra-high performance liquid CH:CHROMATOGRAPHY_SUMMARY chromatography system coupled to a Q Exactive mass spectrometer (Thermo Fisher CH:CHROMATOGRAPHY_SUMMARY Scientific) that was equipped with an Ion Max source and HESI II probe. CH:CHROMATOGRAPHY_SUMMARY metabolites were separated using a ZIC-pHILIC stationary phase (150 mm × 2.1 mm CH:CHROMATOGRAPHY_SUMMARY × 3.5 mm; Merck) with a guard column. Mobile phase A contained 20 mM ammonium CH:CHROMATOGRAPHY_SUMMARY carbonate and 0.1% ammonium hydroxide. Mobile phase B was acetonitrile. The CH:CHROMATOGRAPHY_SUMMARY mobile phase flow rate was 100 μL/min and gradient (%B) was 0 min, 80%; 20 min, CH:CHROMATOGRAPHY_SUMMARY 20%; 20.5 min, 80%; 28 min, 80%; and 42 min, stop. The column effluent was CH:CHROMATOGRAPHY_SUMMARY introduced into the mass spectrometer with the following ionization source CH:CHROMATOGRAPHY_SUMMARY settings: sheath gas 40, auxiliary gas 15, sweep gas 1, spray voltage +3.0 or CH:CHROMATOGRAPHY_SUMMARY -3.1 kV, capillary temperature 275°C, S-lens RF level 40, and probe temperature CH:CHROMATOGRAPHY_SUMMARY 350°C. The mass spectrometer was operated in polarity-switching full scan mode CH:CHROMATOGRAPHY_SUMMARY from 70-1000 m/z. Resolution was set to 70,000, and the AGC target was 1×106 CH:CHROMATOGRAPHY_SUMMARY ions. Data were acquired and analyzed using TraceFinder 4.1 (Thermo) with peak CH:CHROMATOGRAPHY_SUMMARY identifications based on an in-house library of authentic metabolite standards CH:CHROMATOGRAPHY_SUMMARY previously analyzed utilizing this method. Missing values were imputed using CH:CHROMATOGRAPHY_SUMMARY random forest. Sample peak areas were normalized using probabilistic quotient CH:CHROMATOGRAPHY_SUMMARY normalization. CH:CHROMATOGRAPHY_TYPE HILIC CH:INSTRUMENT_NAME Thermo Vanquish CH:COLUMN_NAME Merck ZIC-pHILIC(150 mm × 2.1 mm,3.5um) CH:SOLVENT_A 100% water; 20 mM ammonium carbonate; 0.1% ammonium hydroxide CH:SOLVENT_B 100% acetonitrile CH:FLOW_GRADIENT gradient (%B) was 0 min, 80%; 20 min, 20%; 20.5 min, 80%; 28 min, 80%; and 42 CH:FLOW_GRADIENT min CH:FLOW_RATE 100 CH:COLUMN_TEMPERATURE 4 #ANALYSIS AN:ANALYSIS_TYPE MS #MS MS:INSTRUMENT_NAME Thermo Q Exactive Focus MS:INSTRUMENT_TYPE Triple quadrupole MS:MS_TYPE MALDI MS:ION_MODE UNSPECIFIED MS:MS_COMMENTS The mass spectrometer was operated in polarity-switching full scan mode from MS:MS_COMMENTS 70-1000 m/z. Resolution was set to 70,000, and the AGC target was 1×106 ions. MS:MS_COMMENTS Data were acquired and analyzed using TraceFinder 4.1 (Thermo) with peak MS:MS_COMMENTS identifications based on an in-house library of authentic metabolite standards MS:MS_COMMENTS previously analyzed utilizing this method. Missing values were imputed using MS:MS_COMMENTS random forest. Sample peak areas were normalized using probabilistic quotient MS:MS_COMMENTS normalization #MS_METABOLITE_DATA MS_METABOLITE_DATA:UNITS ion intensity MS_METABOLITE_DATA_START Samples Ctrl 01 Ctrl 02 Ctrl 03 Ctrl 04 Ctrl 05 Ctrl 06 BCKAs 01 BCKAs 02 BCKAs 03 BCKAs 04 BCKAs 05 BCKAs 06 Factors Treatment:control | Sample source:Vascular smooth muscle cells Treatment:control | Sample source:Vascular smooth muscle cells Treatment:control | Sample source:Vascular smooth muscle cells Treatment:control | Sample source:Vascular smooth muscle cells Treatment:control | Sample source:Vascular smooth muscle cells Treatment:control | Sample source:Vascular smooth muscle cells Treatment:BCKAs | Sample source:Vascular smooth muscle cells Treatment:BCKAs | Sample source:Vascular smooth muscle cells Treatment:BCKAs | Sample source:Vascular smooth muscle cells Treatment:BCKAs | Sample source:Vascular smooth muscle cells Treatment:BCKAs | Sample source:Vascular smooth muscle cells Treatment:BCKAs | Sample source:Vascular smooth muscle cells oleate 88800.91439 27588.56763 46970.7729 57382.37029 52003.21934 124947.7194 149826.3009 41193.96772 65319.67705 70776.65908 95568.87317 117274.3456 stearate 3644665.233 166715.9056 549801.0613 712879.8163 159039.3147 4470385.933 5630927.722 173248.0239 687784.9256 682789.4704 255805.0328 4415549.413 ketoleucine 3097502.459 1149790.763 2362236.996 1944796.635 2638198.265 2856260.821 17087227.11 5131546.946 10590865.76 8598213.225 9167572.666 10791707.98 methylthioadenosine 765290.6543 420742.1588 1680326.259 1445460.138 1470741.841 1433342.259 1204342.968 439798.801 1724347.345 1010007.497 1103048.427 995055.7576 niacinamide 35569614.71 13297765.09 30969056.15 25044390.77 28306387.94 21673481.59 40558515.3 14332479.64 29269815.42 23805745.56 20131497.96 25808080.14 pyridoxine 22261065.65 8376509.036 18267902.43 15313796.12 18879953.09 17038093.57 23636996.76 9125945.066 16937741.4 14526617.32 15706218.84 19389737.2 butyrylcarnitine 1457017.349 374974.569 1417166.532 1527520.422 1040041.176 791152.2991 1780008.742 597542.7053 1828042.873 1704418.442 1236559.998 1089694.868 2-hydroxybutyrate 28317.24469 7705.560383 18050.31864 17833.08728 20595.85194 19060.06654 29692.03554 13066.1763 23836.96938 18350.87815 23826.24703 22005.53387 pantothenate 68974900.45 27926751.56 61414738.72 63682406.04 75115445.69 61776514.84 76180042.44 33471139.31 64824604.34 61870316.64 65021336.79 68115198.4 pyruvate 988403.4038 262776.9387 431207.5433 321897.7353 572342.4784 405308.0639 1176487.383 229449.3812 517640.2871 414709.8773 490781.492 813078.7393 acetylalanine 197007.452 67499.15475 216689.7615 241852.9607 218796.4774 172537.8115 235469.1824 89120.97261 245991.5006 234849.4335 211720.7813 182446.9124 propionylcarnitine 2778406.711 765310.1297 1978148.245 2006382.331 1719768.419 1706159.436 3322659.836 1121859.349 2791733.095 2436641.68 2067806.227 2182734.997 creatinine 9479750.701 2869081.436 7337856.692 6546806.663 7543814.132 5887876.174 10697988.58 3403758.125 7209228.237 6323582.36 6026659.503 6763010.065 phenylalanine 37665163.24 16379462.05 40171983.54 35422956.66 39178741.68 30774379.59 51450078.43 26966836.06 49049887.1 45397577.37 44454882.87 44259989.51 hypoxanthine 802333.5188 300343.6114 665425.9366 634301.6086 754221.8015 469044.8663 1080411.086 1220672.545 820195.7498 843833.1231 788254.3786 786616.8211 lactate 12390514.83 4316131.253 14119910.33 12232850.02 11940102.12 9828899.687 15414624.74 5722662.641 13473895.99 12626597.6 11305383.54 12896866.03 glycerol 182653.9274 20516.04447 35378.75469 24233.13272 41920.87758 101473.0847 459246.9634 34502.8138 40556.86753 35485.96997 23729.99484 156472.8813 kynurenine 84183.04931 37207.99489 79512.93449 88194.21138 91495.73364 38778.64442 113952.9639 61190.49414 115108.8526 97549.86827 99165.10763 56147.57873 leucine 120860979.4 58474090.01 132129285.2 118698180.2 139535006 109205239.2 173287824.3 85721224.51 166778686.4 151781384.6 149172197.9 146498529.4 orotate 12004.40714 7539.286166 41625.00099 41353.15916 33654.93358 29355.85159 16292.57789 7066.433669 21771.14617 39730.95037 15584.3025 8422.451169 o-acetylcarnitine 18265812.45 6098227.055 18516105.36 17759130.36 16498201.33 11801663.16 18402218.85 5540154.143 16389637.83 14695922.54 12710954.46 10442854.71 acetylglutamine 35193.68664 17676.3343 49200.1701 47437.60787 54089.55635 51703.84538 53746.33157 24899.77895 53333.99676 55463.65647 52600.94119 47698.83047 betaine 5684131.907 2522475.291 5895395.051 5831564.355 6284631.476 5078782.393 6506068.775 2835248.053 6235815.538 5952360.889 5764788.726 5579057.105 tryptophan 1706529.25 837004.0579 1776107.297 1573872.696 2064411.64 1767758.95 2366271.153 1324646.707 2232017.504 2053516.637 2200964.679 2448479.192 xanthine 417068.4454 227889.9224 480287.7821 491351.3364 514798.1693 389911.0026 462304.6128 225620.913 490598.504 437563.0199 519755.0996 417150.6965 glycerate 50876.9964 25393.19987 68809.44625 52686.01633 62325.15258 55655.59786 69356.7298 35963.35547 75291.49103 63293.07474 64650.80754 60203.75059 valine 42279928.36 20213977.04 44715239.17 40603197.74 46219199.82 37655685.73 59632977.89 31042449.33 52662504.1 49130898.1 51474061.74 47518362.89 proline 181684370.1 79867409.44 233180223.9 230880837.2 225054613.7 177660578.7 241670755.6 114603744.1 263697818.3 238723207.5 230810092.4 193314269.2 acetylcholine 3977770.487 1545132.541 4602955.576 4677413.384 4063117.029 3286061.268 4960701.46 2025133.848 5095185.022 4576180.725 4442644.739 3487759.369 tyrosine 4435151.691 2257313.636 5171630.257 4552048.637 5100746.596 4189530.504 6251707.957 3557072.969 5897000.627 5362547.923 5685635.745 5151177.89 fructose 137747.7557 99181.02292 118143.2148 85329.68672 96688.18523 57996.27211 131631.0511 44351.71621 86136.93111 83761.67184 83366.24673 89039.25003 carnitine 9626537.432 3358882.903 10285413.58 10876857.58 9748346.121 9593224.017 12955281.4 4910657.877 11879639.45 11488633.15 10846984.07 10465712.14 methionine sulfoxide 427283.9682 179863.0896 490516.3208 462833.9393 459414.9115 217705.66 571327.7496 325399.2525 568418.9528 581248.1798 447186.6085 265509.7562 o-acetylserine 5163.040886 2301.682733 5009.315201 5163.040886 6005.133873 7336.031736 12534.66366 9230.60393 7268.028695 9230.60393 1577.250613 15542.47275 AMP 353258.7543 195981.8235 734839.672 692989.6684 532820.7383 490494.9784 468146.7756 289764.9696 644852.8705 710131.5899 780983.7282 340663.4464 sorbitol 2553867.509 190205.3867 512146.484 447670.0841 511220.9532 1969926.767 2908964.994 254266.8701 533985.5676 474882.2471 472698.2716 2369224.24 threonine 4892466.697 2333032.6 5058540.015 5196906.491 5409732.935 4345165.567 5276742.645 3509036.819 5764831.459 5160772.524 5413035.834 3934665.967 glycerophosphocholine 54671866.59 21067384.3 55870193.24 50016208.79 67899564.75 78505981.87 68818775.38 25873552.6 62683067.53 49170971.33 59122255.83 79097747.36 creatine 148915666.7 43945097.95 143826524.4 146481910.5 142682444.8 145353268.8 147174844.3 46534713.03 144438955.7 128145574.6 129344215.7 130589416.1 acetylglutamate 1132974.312 465595.1526 1167191.72 1168097.269 1160951.558 962182.9248 1010496.695 460798.6211 1205657.051 989433.6076 946716.6265 972886.4467 hydroxyproline 4577359.056 2234229.246 4773409.714 4698700.11 5650825.935 4515347.842 4502480.065 2376290.892 5082499.997 4423147.637 4841217.662 4204997.357 glutamine 291646672.8 128495754.8 277031223.7 279437135.8 316976074.2 258000590.5 303306796 172538446.4 284946295 284346238.1 307826208 250236541.1 GSH 70471506.02 31422487.48 71604185.94 82771391.11 88149894.87 70144738.17 59610564.29 31263063.51 68031513.72 70506704.4 65283258.1 51570666.82 alanine 3284101.79 1483432.731 3533689.202 3572363.786 3803462.554 4026867.256 3055157.278 2042811.018 3374826.646 3319975.782 3577022.8 3112206.981 histidine 34611304.86 14798286.72 33612188.5 31617300.58 37284416.94 29532758.43 39599909.44 19941815.67 43350796.77 36418538.94 38560724.12 34943121.91 acetylaspartate 5597370.796 1718333.237 3174889.754 3208439.142 3642809.873 2889993.268 4963978.193 2069278.746 3901347.013 3721936.636 3033176.739 3684324.064 glutamate 38804235.19 20722904.22 57579421.28 57386270.72 57840613.93 51582668.02 37709653.52 24859776.91 50916149.62 48603995.23 50212262.08 35237629.06 phosphocholine 217896469.8 93813667.55 188351239.7 198285580.2 222348970.5 151293316 211548832.6 109371147.7 214071974.9 206562535.2 204010555.7 177201310.7 aminoadipate 307422.2713 227991.5474 519288.1696 504941.5495 545721.6549 486029.9555 785698.0133 283492.6707 583412.1015 594647.499 623025.411 555706.9379 asparagine 2173505.665 1243631.215 3236895.901 3090063.186 3396606.789 2971312.591 2764589.9 1959604.304 3418871.581 3284234.745 3680798.852 2239216.377 carnosine 142718.8455 49138.41594 117303.2635 100374.0094 105889.9037 101614.6001 150729.0868 63996.44223 117420.7144 98204.82138 108328.0879 92243.76726 glycerol 3-phosphate 825221.1654 284229.9228 559492.0901 502516.1461 502090.1299 581110.1396 665920.7273 314036.617 690955.1674 527355.166 569151.9978 740970.9216 taurine 541790.3625 150453.9614 728915.9587 855001.7491 828431.636 372222.9139 590220.2409 170222.7052 668238.7213 742626.5206 835394.8384 327606.8574 beta-alanine 424660.7243 144810.8198 458354.2763 432907.5276 429764.4404 294547.3474 504285.1546 162667.6908 472923.5237 459535.418 486349.7625 417152.3099 aspartate 16009405.25 7527828.299 17838506.4 17995728.99 19960682.22 14276272.44 11184271.56 6119828.071 12866021 12758917.86 13180487.12 9740163.467 glycine 1714109.344 684599.5389 1912133.038 1840818.691 1812549.61 1520609.106 1826417.361 907830.7493 2451839.722 2002746.028 1944872.188 1580060.464 serine 2293887.68 1157843.894 2513981.773 2385083.477 2731453.428 2241565.704 2509160.414 1479959.386 2844618.821 2629620.288 2789535.704 2608329.237 citrulline 299102.1849 84647.03589 221165.4283 187589.1004 228621.6835 163048.44 335089.7575 94563.74518 241781.4545 217095.2006 205552.6073 239302.0984 DHAP 250477.194 137482.0396 131257.5702 105426.6326 148945.1778 51303.62351 111989.4079 69632.51105 147526.0439 115808.0465 182394.5019 523171.4675 guanidinoacetate 17401.25602 4728.19672 11770.01166 5188.467129 13234.24651 7866.312201 20937.45878 4313.24835 8957.940215 6569.971676 7243.363194 13601.40972 2-oxoglutarate 1701665.018 868912.5955 1667767.505 1660342.261 1533218.479 2058763.046 4411793.518 2028705.104 4152518.465 3535133.608 3592783.855 4117669.173 succinate 967649.7693 336345.4507 837255.6999 774789.5725 985925.1747 717759.2135 1253194.648 495063.8406 1143658.903 1079985.568 1124551.516 1019842.98 ATP 996049.4624 1472148.576 3525204.817 3320246.997 3115802.453 3003261.097 975157.8369 1880780.241 3955603.363 4194567.779 2204495.094 3343615.338 cystine 6352.38544 4795.063851 23163.14372 33863.57598 18952.96161 1555.186759 13120.08161 5299.526857 13363.35515 9030.074964 10253.95256 133.5337297 glyceraldehyde 3-phosphate 511434.2274 317741.1998 652368.1352 668566.4266 690353.9243 632772.555 462464.5936 296104.8358 630713.4176 514763.1342 566151.7785 523171.4675 fumarate 703728.2253 280434.8391 899093.1474 949516.5772 999073.8209 786218.5338 1214177.941 446465.3412 1365489.489 1218875.095 1247855.757 1067174.594 malate 14766574.43 5748247.368 18735208.08 19581211.39 20741488.44 16153699.82 23824449.12 9103899.136 27614941.74 24956700.36 24319727.62 21517628.47 glucuronate 59664.1009 27909.45598 54136.03827 52639.73179 68413.13645 52015.55493 63428.73318 31144.362 54167.43124 46422.34779 63309.66412 54212.57849 cystathionine 50355.34203 34146.02738 96414.8795 105618.4076 131921.0768 102920.9782 53263.82922 42941.05897 101145.989 91552.47591 112076.571 96981.18609 glucose 6-phosphate 265349.9882 48560.18157 149497.7975 159267.304 159477.2846 139806.8596 437332.5979 88740.5086 242779.1083 177822.8974 220841.6421 221532.6441 myo-inositol 576820.9808 493244.4125 860908.1811 822053.8589 1198874.525 701175.0428 634217.2993 552129.8601 882375.0529 742482.0315 1095386.729 741699.6892 phosphoenolpyruvate 43262.95286 32489.03811 97390.34073 98999.47346 77614.7044 87204.30664 41580.13021 73659.41857 104058.8311 139008.9442 76562.26512 113109.7667 glucaric acid 43345.8698 42217.65958 38454.12708 36995.88992 42217.65958 50074.75154 35965.69958 44933.25089 48920.04909 47453.42153 47393.83336 44933.25089 aconitate 2723565.653 844425.3915 2352470.343 2203300.079 2494164.495 2240559.593 3545534.563 1409760.776 3278600.509 2775794.477 3003477.367 3119158.433 choline 68165886.13 31486262.47 52674950.25 49476395.28 58494643.64 44999730.52 63932770.12 34031161.01 44920568.85 42708629.33 46376432.92 45748840.53 citrate 13406571.72 5713379.528 15582172.26 15013050.97 15542634.71 14522046.67 17496364.92 9090451.843 19673333.69 19233087.97 16785909.3 19132856.76 trimethyllysine 1259761.343 476589.3899 1110962.919 1139612.624 1139051.466 888978.6543 1473857.214 626097.7011 1285401.559 1213330.213 1102769.937 1039451.135 ornithine 387505.262 129514.9968 370095.8693 336084.0857 291085.0721 237744.8659 402843.5347 167865.504 356585.4462 372371.0993 297312.8614 251367.6332 lysine 14485856.01 4818399.224 11038634.92 8112264.376 10236655.34 7514559.4 16766879.61 5615249.296 9608273.565 8272088.402 7822286.874 10580265.66 palmitate 1862733.391 424851.5384 905995.0775 1566360.556 509332.9232 2325903.905 2728312.574 353044.3177 1198523.113 1520795.995 646537.1234 2313688.657 acetylmethionine 512877.6366 212837.0141 566752.9333 572597.8397 659078.9451 506692.8935 569263.2074 268719.7057 585487.6048 549529.6384 667759.7082 515802.4168 thymidine 10562.29183 4370.702929 14012.30991 10979.91416 16059.48438 11760.68625 19467.87998 7971.86096 12499.44183 17414.70236 11848.84551 12246.82352 pyridoxal 682938.6324 227577.0652 509750.1743 513798.6209 605600.1326 969399.8808 601152.7662 340912.529 591600.5093 550642.0826 699274.5916 1067215.454 uridine 35759.89291 15056.79449 35968.33032 39940.53084 46641.4814 119773.0963 43884.92049 55974.23887 44231.79447 41234.13326 38626.69816 55112.10335 deoxycytidine 2575.777349 1253.780423 3841.612197 3204.304007 3131.11202 2373.256373 4883.709302 2307.581012 5483.923528 5697.880942 5457.775469 4401.622705 inosine 12902.50323 8313.621533 19292.24414 24427.40788 26546.55303 167121.3936 23119.61814 56369.33284 18596.50195 37496.21649 25561.41002 69175.26287 methionine 14003523.58 6190576.367 14299034.69 12591530.52 15206728.62 11799844.96 18945588.24 9129612.551 17380532.22 16319889.65 15434476.59 15495671.33 cytidine 20773.95624 8010.738089 21837.44252 23805.06164 17836.53095 11689.03954 21682.06481 10361.78857 24338.37276 23062.67338 20956.45559 13954.1944 xanthosine 868.5963514 624.4589476 762.1675639 559.7455103 937.3051332 780.962893 915.6241314 457.6599982 1715.085346 800.5089825 705.4316919 672.0849342 ribitol 162174.5325 62934.80381 173699.2022 163277.2276 167658.2236 142715.0034 196470.7606 78841.87875 159788.7873 139396.1751 161317.247 134282.3577 1-methyladenosine 349333.8181 173573.2892 490094.3652 465270.463 394482.9603 316547.4583 469478.8228 281874.3725 582287.9159 502229.4802 458237.49 349871.6064 SAH 123629.623 147899.7797 430709.4204 525751.7628 408334.5081 568514.7554 207712.5124 160955.2844 383645.4231 368168.2248 318762.7879 253864.5016 dTMP 51.6829535 132.3398517 92.97288375 234.9351164 coenzyme A 15443.54752 23761.51115 79461.62889 81575.30836 62827.74357 75196.95619 14653.00658 32104.48995 67133.04919 87061.4158 31374.40694 73203.58737 urate 106827.8913 28638.65967 72621.66187 52130.13809 67716.01012 79159.15137 134023.4325 26105.74738 58196.22653 42274.1852 54411.94133 82407.08186 NAD 6763088.716 3291889.789 6676748.823 6518277.129 7566284.708 6417015.917 6373438.762 3831609.078 7031307.885 6446353.756 6636623.952 5917939.903 allantoin 401520.4986 204198.5158 547677.8312 566146.9319 543952.3767 386325.4817 448315.0367 319610.4999 515240.4903 531203.975 566517.8512 253079.4617 pseudouridine 239811.4519 104836.6296 294763.3185 301506.8155 239157.7718 240117.2118 222653.8338 120050.0046 324512.1913 270315.9461 247116.5423 237476.317 ADP 106741.8625 175408.3613 975043.2707 960088.3645 539645.8027 592817.5064 232682.0871 333910.2572 996619.4237 892863.1837 416676.0708 281885.9134 glucose 508917.1616 201334.4439 253474.6178 156140.2714 275235.7092 185828.3902 569099.6629 181376.2533 245589.4729 180312.7886 202927.1433 220462.4302 hypotaurine 27020.47813 1079.795579 83777.16697 78837.07834 48251.49585 16857.69766 24549.43343 3101.755322 40534.34241 62364.11264 36019.74297 9790.799721 citicoline 139436.5324 59305.48551 135307.2156 141519.249 181593.5414 179778.3282 163712.0561 87650.39897 162332.216 135428.6626 213372.9099 147843.1215 phosphocreatine 5754336.334 1876226.926 6081430.228 6298547.602 5003448.105 5777203.122 6351465.734 2596921.903 6400369.848 6028228.884 5329828.214 4718911.604 SAM 2957169.609 1638811.472 2937123.745 2571956.398 3450827.364 2314257.116 2805236.829 2250398.584 3269495.778 2761227.252 3824449.584 2045848.179 UDP-GlcNAc 3207850.378 1358171.178 4494756.589 4768453.148 3929272.17 3488877.845 3569317.963 1994189.732 4544912.601 4360170.323 4405842.114 2668350.803 UMP 26812.08427 19670.00497 68746.27291 82172.60001 46919.2706 67096.64992 40173.25158 16918.4051 70022.40558 44699.17668 46014.38602 49156.16279 2-hydroxyglutarate 1174934.225 563172.8397 1248079.905 1094606.47 1184851.164 1308617.319 1776257.069 980674.0691 2221513.413 1925522.847 2009369.123 1313.747534 IMP 4211.732758 2928.311877 9590.609135 6020.812798 5744.943003 5153.360731 4006.541348 2819.40036 6989.478714 6991.549651 4224.554128 3751.537374 o-phosphoethanolamine 179056.7991 292675.9034 82207.15469 95301.13967 168144.3762 467288.3682 179216.1493 322734.5618 120164.2531 68232.74498 179077.5694 443850.4988 ribose 5-phosphate 25699.4366 6827.582357 21198.23129 19526.1393 22528.51908 17758.96083 25955.23364 16607.456 23690.55544 23923.80952 28348.18434 22581.76772 CMP 13126.06462 14979.90647 19203.32919 15563.77215 5437.085414 13097.18229 14345.47598 CDP-ethanolamine 37090.78701 25475.28056 23749.32598 26405.89212 41943.23854 50421.45968 36986.32308 27000.31045 30737.20246 18563.42319 41340.54318 54403.39828 phosphoserine 153316.8289 271272.6593 277507.2562 260459.475 325504.8762 295776.6225 119165.275 204371.0457 225109.6615 186644.3172 220739.7885 176422.8227 sedoheptulose 7-phosphate 43168.22921 7094.778818 22370.2421 27614.63127 28466.16119 32154.55369 51910.51237 13045.81473 24560.06579 22672.40389 26364.84761 30129.08258 UDP 36638.37286 62261.62734 235872.1148 251035.1532 183461.2863 216119.3813 62174.87145 99038.73975 266657.0383 242006.676 109172.7881 143059.5057 argininosuccinate 59775.69927 21454.852 55687.51282 64703.29841 61059.52898 59410.69311 93145.76335 38151.36809 89715.0788 96818.49102 92989.4776 88976.84751 carbamoylaspartate 130612.6537 86648.69364 210947.5515 187752.9198 181081.5152 141022.6827 107648.6835 50186.58216 151818.3557 121287.4095 127079.9762 88192.32157 UDP-glucose 912545.4442 619238.4606 1302533.313 1437080.21 1365357.544 1260302.547 999598.9147 813838.987 1560408.525 1422540.458 1294379.136 1340774.324 3-phosphoglycerate 548317.8331 513968.3775 1239321.782 1584222.468 1128440.071 1186172.523 482896.6647 790183.0129 1319991.608 1511645.063 1021220.637 1182564.495 CDP 3798.227147 11607.66938 60335.90996 58740.95425 37605.8157 46071.5873 13399.62822 19126.77598 68741.32335 52906.26767 20537.68537 28292.12236 GMP 14565.02638 2987.065386 18896.21251 16095.33863 13031.1974 3151.327475 14428.7834 1718.602797 21010.74087 8255.106473 13638.32255 4006.682793 GSSG 1281401.206 560396.7767 999914.4197 1097957.044 1232514.383 899468.6197 1440885.854 534869.3978 1341652.264 958648.8414 1384626.89 973302.5962 GDP 7516.518661 16514.28491 64430.24593 61521.93146 31896.94899 38545.6265 11174.9548 25732.17817 86975.7954 70645.22116 19392.03479 25441.33403 CTP 51099.33037 76536.31298 191942.9102 170423.2384 131971.5793 142941.1871 52590.57481 111653.4972 241938.4619 264283.6976 113167.5468 198202.7626 thiamine 759229.7018 1191903.497 1361209.673 1301713.705 2890518.014 4275118.479 1369100.576 1380978.592 1479545.122 1226015.916 2643426.499 4797411.054 GDP-mannose 9880.245023 5799.954517 22776.69264 21759.14316 20014.11291 15803.52332 10797.28215 11947.45531 25015.27666 27120.58753 17885.56022 18553.23238 UDP-glucuronate 71607.22131 106370.7154 252824.4304 248475.4063 152961.4889 132768.7464 84124.64485 142058.8462 269597.9166 309283.6163 92000.27856 152021.7617 GTP 26579.94535 64459.58943 162198.9323 133589.5273 105602.8687 122150.7727 28307.3373 104249.816 221090.9781 254112.4212 82803.29526 168343.4426 3-hydroxybutyrate 47933.39138 9010.978802 31731.56568 29741.57272 42989.26738 33635.49049 36796.34712 18225.34123 40830.2004 35308.23621 32909.99098 31509.78601 arginine 22332504.84 17678353.35 17390058.59 14935168.9 18697457.4 15036577 25208446.01 10118022.65 18543978.47 16463902.73 17095068.48 17698324.33 FAD 345.294158 1037.564323 7111.772207 7813.196312 9787.391747 4611.018354 881.2402964 9015.807331 12163.46043 11723.45737 11546.97222 4237.231908 fructose 1,6-bisphosphate 633602.7049 876581.1304 952226.7377 741094.2247 1296509.221 1030787.373 GABA 703256.1169 215451.3917 748791.1754 841587.3665 701724.4876 672495.56 771109.8482 258370.2598 755676.2366 800938.2994 709345.3245 528055.1782 glucose 1-phosphate 36300.66225 12703.67494 34745.6783 38893.27607 35951.67741 34256.75789 54166.53876 21930.64989 42099.29118 41329.54809 44562.72582 33051.46005 isoleucine 61790234.01 27192806.21 63840849.73 56011959.23 65701623.7 52520659.85 86923727.53 39854320.75 76051453.91 74284997.97 69753427.04 146498529.4 NADH 8328.803347 33287.11624 182771.0109 113770.7152 194884.5754 299641.3311 16870.97804 27299.35992 157268.3587 150627.9957 60967.69695 237578.6971 NADP 19186.44938 21422.9889 42944.01009 48665.08913 53175.49515 63428.22243 20018.68997 25387.35237 53126.85871 54428.52069 48411.62523 46083.40378 NADPH 7829.813495 12236.00981 47266.38406 45222.30675 24600.19959 18802.69424 10349.83552 17224.69452 49585.02314 50072.53472 11727.44575 37111.38249 UTP 158554.4999 238390.36 573241.4867 548480.9195 459980.0639 429049.6365 157974.9522 336022.8147 674575.1024 724323.7833 338343.8799 560667.3817 MS_METABOLITE_DATA_END #METABOLITES METABOLITES_START metabolite_name Ctrl 01 Ctrl 02 Ctrl 03 Ctrl 04 Ctrl 05 Ctrl 06 BCKAs 01 BCKAs 02 BCKAs 03 BCKAs 04 BCKAs 05 BCKAs 06 oleate 88800.91439 27588.56763 46970.7729 57382.37029 52003.21934 124947.7194 149826.3009 41193.96772 65319.67705 70776.65908 95568.87317 117274.3456 stearate 3644665.233 166715.9056 549801.0613 712879.8163 159039.3147 4470385.933 5630927.722 173248.0239 687784.9256 682789.4704 255805.0328 4415549.413 ketoleucine 3097502.459 1149790.763 2362236.996 1944796.635 2638198.265 2856260.821 17087227.11 5131546.946 10590865.76 8598213.225 9167572.666 10791707.98 methylthioadenosine 765290.6543 420742.1588 1680326.259 1445460.138 1470741.841 1433342.259 1204342.968 439798.801 1724347.345 1010007.497 1103048.427 995055.7576 niacinamide 35569614.71 13297765.09 30969056.15 25044390.77 28306387.94 21673481.59 40558515.3 14332479.64 29269815.42 23805745.56 20131497.96 25808080.14 pyridoxine 22261065.65 8376509.036 18267902.43 15313796.12 18879953.09 17038093.57 23636996.76 9125945.066 16937741.4 14526617.32 15706218.84 19389737.2 butyrylcarnitine 1457017.349 374974.569 1417166.532 1527520.422 1040041.176 791152.2991 1780008.742 597542.7053 1828042.873 1704418.442 1236559.998 1089694.868 2-hydroxybutyrate 28317.24469 7705.560383 18050.31864 17833.08728 20595.85194 19060.06654 29692.03554 13066.1763 23836.96938 18350.87815 23826.24703 22005.53387 pantothenate 68974900.45 27926751.56 61414738.72 63682406.04 75115445.69 61776514.84 76180042.44 33471139.31 64824604.34 61870316.64 65021336.79 68115198.4 pyruvate 988403.4038 262776.9387 431207.5433 321897.7353 572342.4784 405308.0639 1176487.383 229449.3812 517640.2871 414709.8773 490781.492 813078.7393 acetylalanine 197007.452 67499.15475 216689.7615 241852.9607 218796.4774 172537.8115 235469.1824 89120.97261 245991.5006 234849.4335 211720.7813 182446.9124 propionylcarnitine 2778406.711 765310.1297 1978148.245 2006382.331 1719768.419 1706159.436 3322659.836 1121859.349 2791733.095 2436641.68 2067806.227 2182734.997 creatinine 9479750.701 2869081.436 7337856.692 6546806.663 7543814.132 5887876.174 10697988.58 3403758.125 7209228.237 6323582.36 6026659.503 6763010.065 phenylalanine 37665163.24 16379462.05 40171983.54 35422956.66 39178741.68 30774379.59 51450078.43 26966836.06 49049887.1 45397577.37 44454882.87 44259989.51 hypoxanthine 802333.5188 300343.6114 665425.9366 634301.6086 754221.8015 469044.8663 1080411.086 1220672.545 820195.7498 843833.1231 788254.3786 786616.8211 lactate 12390514.83 4316131.253 14119910.33 12232850.02 11940102.12 9828899.687 15414624.74 5722662.641 13473895.99 12626597.6 11305383.54 12896866.03 glycerol 182653.9274 20516.04447 35378.75469 24233.13272 41920.87758 101473.0847 459246.9634 34502.8138 40556.86753 35485.96997 23729.99484 156472.8813 kynurenine 84183.04931 37207.99489 79512.93449 88194.21138 91495.73364 38778.64442 113952.9639 61190.49414 115108.8526 97549.86827 99165.10763 56147.57873 leucine 120860979.4 58474090.01 132129285.2 118698180.2 139535006 109205239.2 173287824.3 85721224.51 166778686.4 151781384.6 149172197.9 146498529.4 orotate 12004.40714 7539.286166 41625.00099 41353.15916 33654.93358 29355.85159 16292.57789 7066.433669 21771.14617 39730.95037 15584.3025 8422.451169 o-acetylcarnitine 18265812.45 6098227.055 18516105.36 17759130.36 16498201.33 11801663.16 18402218.85 5540154.143 16389637.83 14695922.54 12710954.46 10442854.71 acetylglutamine 35193.68664 17676.3343 49200.1701 47437.60787 54089.55635 51703.84538 53746.33157 24899.77895 53333.99676 55463.65647 52600.94119 47698.83047 betaine 5684131.907 2522475.291 5895395.051 5831564.355 6284631.476 5078782.393 6506068.775 2835248.053 6235815.538 5952360.889 5764788.726 5579057.105 tryptophan 1706529.25 837004.0579 1776107.297 1573872.696 2064411.64 1767758.95 2366271.153 1324646.707 2232017.504 2053516.637 2200964.679 2448479.192 xanthine 417068.4454 227889.9224 480287.7821 491351.3364 514798.1693 389911.0026 462304.6128 225620.913 490598.504 437563.0199 519755.0996 417150.6965 glycerate 50876.9964 25393.19987 68809.44625 52686.01633 62325.15258 55655.59786 69356.7298 35963.35547 75291.49103 63293.07474 64650.80754 60203.75059 valine 42279928.36 20213977.04 44715239.17 40603197.74 46219199.82 37655685.73 59632977.89 31042449.33 52662504.1 49130898.1 51474061.74 47518362.89 proline 181684370.1 79867409.44 233180223.9 230880837.2 225054613.7 177660578.7 241670755.6 114603744.1 263697818.3 238723207.5 230810092.4 193314269.2 acetylcholine 3977770.487 1545132.541 4602955.576 4677413.384 4063117.029 3286061.268 4960701.46 2025133.848 5095185.022 4576180.725 4442644.739 3487759.369 tyrosine 4435151.691 2257313.636 5171630.257 4552048.637 5100746.596 4189530.504 6251707.957 3557072.969 5897000.627 5362547.923 5685635.745 5151177.89 fructose 137747.7557 99181.02292 118143.2148 85329.68672 96688.18523 57996.27211 131631.0511 44351.71621 86136.93111 83761.67184 83366.24673 89039.25003 carnitine 9626537.432 3358882.903 10285413.58 10876857.58 9748346.121 9593224.017 12955281.4 4910657.877 11879639.45 11488633.15 10846984.07 10465712.14 methionine sulfoxide 427283.9682 179863.0896 490516.3208 462833.9393 459414.9115 217705.66 571327.7496 325399.2525 568418.9528 581248.1798 447186.6085 265509.7562 o-acetylserine 5163.040886 2301.682733 5009.315201 5163.040886 6005.133873 7336.031736 12534.66366 9230.60393 7268.028695 9230.60393 1577.250613 15542.47275 AMP 353258.7543 195981.8235 734839.672 692989.6684 532820.7383 490494.9784 468146.7756 289764.9696 644852.8705 710131.5899 780983.7282 340663.4464 sorbitol 2553867.509 190205.3867 512146.484 447670.0841 511220.9532 1969926.767 2908964.994 254266.8701 533985.5676 474882.2471 472698.2716 2369224.24 threonine 4892466.697 2333032.6 5058540.015 5196906.491 5409732.935 4345165.567 5276742.645 3509036.819 5764831.459 5160772.524 5413035.834 3934665.967 glycerophosphocholine 54671866.59 21067384.3 55870193.24 50016208.79 67899564.75 78505981.87 68818775.38 25873552.6 62683067.53 49170971.33 59122255.83 79097747.36 creatine 148915666.7 43945097.95 143826524.4 146481910.5 142682444.8 145353268.8 147174844.3 46534713.03 144438955.7 128145574.6 129344215.7 130589416.1 acetylglutamate 1132974.312 465595.1526 1167191.72 1168097.269 1160951.558 962182.9248 1010496.695 460798.6211 1205657.051 989433.6076 946716.6265 972886.4467 hydroxyproline 4577359.056 2234229.246 4773409.714 4698700.11 5650825.935 4515347.842 4502480.065 2376290.892 5082499.997 4423147.637 4841217.662 4204997.357 glutamine 291646672.8 128495754.8 277031223.7 279437135.8 316976074.2 258000590.5 303306796 172538446.4 284946295 284346238.1 307826208 250236541.1 GSH 70471506.02 31422487.48 71604185.94 82771391.11 88149894.87 70144738.17 59610564.29 31263063.51 68031513.72 70506704.4 65283258.1 51570666.82 alanine 3284101.79 1483432.731 3533689.202 3572363.786 3803462.554 4026867.256 3055157.278 2042811.018 3374826.646 3319975.782 3577022.8 3112206.981 histidine 34611304.86 14798286.72 33612188.5 31617300.58 37284416.94 29532758.43 39599909.44 19941815.67 43350796.77 36418538.94 38560724.12 34943121.91 acetylaspartate 5597370.796 1718333.237 3174889.754 3208439.142 3642809.873 2889993.268 4963978.193 2069278.746 3901347.013 3721936.636 3033176.739 3684324.064 glutamate 38804235.19 20722904.22 57579421.28 57386270.72 57840613.93 51582668.02 37709653.52 24859776.91 50916149.62 48603995.23 50212262.08 35237629.06 phosphocholine 217896469.8 93813667.55 188351239.7 198285580.2 222348970.5 151293316 211548832.6 109371147.7 214071974.9 206562535.2 204010555.7 177201310.7 aminoadipate 307422.2713 227991.5474 519288.1696 504941.5495 545721.6549 486029.9555 785698.0133 283492.6707 583412.1015 594647.499 623025.411 555706.9379 asparagine 2173505.665 1243631.215 3236895.901 3090063.186 3396606.789 2971312.591 2764589.9 1959604.304 3418871.581 3284234.745 3680798.852 2239216.377 carnosine 142718.8455 49138.41594 117303.2635 100374.0094 105889.9037 101614.6001 150729.0868 63996.44223 117420.7144 98204.82138 108328.0879 92243.76726 glycerol 3-phosphate 825221.1654 284229.9228 559492.0901 502516.1461 502090.1299 581110.1396 665920.7273 314036.617 690955.1674 527355.166 569151.9978 740970.9216 taurine 541790.3625 150453.9614 728915.9587 855001.7491 828431.636 372222.9139 590220.2409 170222.7052 668238.7213 742626.5206 835394.8384 327606.8574 beta-alanine 424660.7243 144810.8198 458354.2763 432907.5276 429764.4404 294547.3474 504285.1546 162667.6908 472923.5237 459535.418 486349.7625 417152.3099 aspartate 16009405.25 7527828.299 17838506.4 17995728.99 19960682.22 14276272.44 11184271.56 6119828.071 12866021 12758917.86 13180487.12 9740163.467 glycine 1714109.344 684599.5389 1912133.038 1840818.691 1812549.61 1520609.106 1826417.361 907830.7493 2451839.722 2002746.028 1944872.188 1580060.464 serine 2293887.68 1157843.894 2513981.773 2385083.477 2731453.428 2241565.704 2509160.414 1479959.386 2844618.821 2629620.288 2789535.704 2608329.237 citrulline 299102.1849 84647.03589 221165.4283 187589.1004 228621.6835 163048.44 335089.7575 94563.74518 241781.4545 217095.2006 205552.6073 239302.0984 DHAP 250477.194 137482.0396 131257.5702 105426.6326 148945.1778 51303.62351 111989.4079 69632.51105 147526.0439 115808.0465 182394.5019 523171.4675 guanidinoacetate 17401.25602 4728.19672 11770.01166 5188.467129 13234.24651 7866.312201 20937.45878 4313.24835 8957.940215 6569.971676 7243.363194 13601.40972 2-oxoglutarate 1701665.018 868912.5955 1667767.505 1660342.261 1533218.479 2058763.046 4411793.518 2028705.104 4152518.465 3535133.608 3592783.855 4117669.173 succinate 967649.7693 336345.4507 837255.6999 774789.5725 985925.1747 717759.2135 1253194.648 495063.8406 1143658.903 1079985.568 1124551.516 1019842.98 ATP 996049.4624 1472148.576 3525204.817 3320246.997 3115802.453 3003261.097 975157.8369 1880780.241 3955603.363 4194567.779 2204495.094 3343615.338 cystine 6352.38544 4795.063851 23163.14372 33863.57598 18952.96161 1555.186759 13120.08161 5299.526857 13363.35515 9030.074964 10253.95256 133.5337297 glyceraldehyde 3-phosphate 511434.2274 317741.1998 652368.1352 668566.4266 690353.9243 632772.555 462464.5936 296104.8358 630713.4176 514763.1342 566151.7785 523171.4675 fumarate 703728.2253 280434.8391 899093.1474 949516.5772 999073.8209 786218.5338 1214177.941 446465.3412 1365489.489 1218875.095 1247855.757 1067174.594 malate 14766574.43 5748247.368 18735208.08 19581211.39 20741488.44 16153699.82 23824449.12 9103899.136 27614941.74 24956700.36 24319727.62 21517628.47 glucuronate 59664.1009 27909.45598 54136.03827 52639.73179 68413.13645 52015.55493 63428.73318 31144.362 54167.43124 46422.34779 63309.66412 54212.57849 cystathionine 50355.34203 34146.02738 96414.8795 105618.4076 131921.0768 102920.9782 53263.82922 42941.05897 101145.989 91552.47591 112076.571 96981.18609 glucose 6-phosphate 265349.9882 48560.18157 149497.7975 159267.304 159477.2846 139806.8596 437332.5979 88740.5086 242779.1083 177822.8974 220841.6421 221532.6441 myo-inositol 576820.9808 493244.4125 860908.1811 822053.8589 1198874.525 701175.0428 634217.2993 552129.8601 882375.0529 742482.0315 1095386.729 741699.6892 phosphoenolpyruvate 43262.95286 32489.03811 97390.34073 98999.47346 77614.7044 87204.30664 41580.13021 73659.41857 104058.8311 139008.9442 76562.26512 113109.7667 glucaric acid 43345.8698 42217.65958 38454.12708 36995.88992 42217.65958 50074.75154 35965.69958 44933.25089 48920.04909 47453.42153 47393.83336 44933.25089 aconitate 2723565.653 844425.3915 2352470.343 2203300.079 2494164.495 2240559.593 3545534.563 1409760.776 3278600.509 2775794.477 3003477.367 3119158.433 choline 68165886.13 31486262.47 52674950.25 49476395.28 58494643.64 44999730.52 63932770.12 34031161.01 44920568.85 42708629.33 46376432.92 45748840.53 citrate 13406571.72 5713379.528 15582172.26 15013050.97 15542634.71 14522046.67 17496364.92 9090451.843 19673333.69 19233087.97 16785909.3 19132856.76 trimethyllysine 1259761.343 476589.3899 1110962.919 1139612.624 1139051.466 888978.6543 1473857.214 626097.7011 1285401.559 1213330.213 1102769.937 1039451.135 ornithine 387505.262 129514.9968 370095.8693 336084.0857 291085.0721 237744.8659 402843.5347 167865.504 356585.4462 372371.0993 297312.8614 251367.6332 lysine 14485856.01 4818399.224 11038634.92 8112264.376 10236655.34 7514559.4 16766879.61 5615249.296 9608273.565 8272088.402 7822286.874 10580265.66 palmitate 1862733.391 424851.5384 905995.0775 1566360.556 509332.9232 2325903.905 2728312.574 353044.3177 1198523.113 1520795.995 646537.1234 2313688.657 acetylmethionine 512877.6366 212837.0141 566752.9333 572597.8397 659078.9451 506692.8935 569263.2074 268719.7057 585487.6048 549529.6384 667759.7082 515802.4168 thymidine 10562.29183 4370.702929 14012.30991 10979.91416 16059.48438 11760.68625 19467.87998 7971.86096 12499.44183 17414.70236 11848.84551 12246.82352 pyridoxal 682938.6324 227577.0652 509750.1743 513798.6209 605600.1326 969399.8808 601152.7662 340912.529 591600.5093 550642.0826 699274.5916 1067215.454 uridine 35759.89291 15056.79449 35968.33032 39940.53084 46641.4814 119773.0963 43884.92049 55974.23887 44231.79447 41234.13326 38626.69816 55112.10335 deoxycytidine 2575.777349 1253.780423 3841.612197 3204.304007 3131.11202 2373.256373 4883.709302 2307.581012 5483.923528 5697.880942 5457.775469 4401.622705 inosine 12902.50323 8313.621533 19292.24414 24427.40788 26546.55303 167121.3936 23119.61814 56369.33284 18596.50195 37496.21649 25561.41002 69175.26287 methionine 14003523.58 6190576.367 14299034.69 12591530.52 15206728.62 11799844.96 18945588.24 9129612.551 17380532.22 16319889.65 15434476.59 15495671.33 cytidine 20773.95624 8010.738089 21837.44252 23805.06164 17836.53095 11689.03954 21682.06481 10361.78857 24338.37276 23062.67338 20956.45559 13954.1944 xanthosine 868.5963514 624.4589476 762.1675639 559.7455103 937.3051332 780.962893 915.6241314 457.6599982 1715.085346 800.5089825 705.4316919 672.0849342 ribitol 162174.5325 62934.80381 173699.2022 163277.2276 167658.2236 142715.0034 196470.7606 78841.87875 159788.7873 139396.1751 161317.247 134282.3577 1-methyladenosine 349333.8181 173573.2892 490094.3652 465270.463 394482.9603 316547.4583 469478.8228 281874.3725 582287.9159 502229.4802 458237.49 349871.6064 SAH 123629.623 147899.7797 430709.4204 525751.7628 408334.5081 568514.7554 207712.5124 160955.2844 383645.4231 368168.2248 318762.7879 253864.5016 dTMP 51.6829535 132.3398517 92.97288375 234.9351164 coenzyme A 15443.54752 23761.51115 79461.62889 81575.30836 62827.74357 75196.95619 14653.00658 32104.48995 67133.04919 87061.4158 31374.40694 73203.58737 urate 106827.8913 28638.65967 72621.66187 52130.13809 67716.01012 79159.15137 134023.4325 26105.74738 58196.22653 42274.1852 54411.94133 82407.08186 NAD 6763088.716 3291889.789 6676748.823 6518277.129 7566284.708 6417015.917 6373438.762 3831609.078 7031307.885 6446353.756 6636623.952 5917939.903 allantoin 401520.4986 204198.5158 547677.8312 566146.9319 543952.3767 386325.4817 448315.0367 319610.4999 515240.4903 531203.975 566517.8512 253079.4617 pseudouridine 239811.4519 104836.6296 294763.3185 301506.8155 239157.7718 240117.2118 222653.8338 120050.0046 324512.1913 270315.9461 247116.5423 237476.317 ADP 106741.8625 175408.3613 975043.2707 960088.3645 539645.8027 592817.5064 232682.0871 333910.2572 996619.4237 892863.1837 416676.0708 281885.9134 glucose 508917.1616 201334.4439 253474.6178 156140.2714 275235.7092 185828.3902 569099.6629 181376.2533 245589.4729 180312.7886 202927.1433 220462.4302 hypotaurine 27020.47813 1079.795579 83777.16697 78837.07834 48251.49585 16857.69766 24549.43343 3101.755322 40534.34241 62364.11264 36019.74297 9790.799721 citicoline 139436.5324 59305.48551 135307.2156 141519.249 181593.5414 179778.3282 163712.0561 87650.39897 162332.216 135428.6626 213372.9099 147843.1215 phosphocreatine 5754336.334 1876226.926 6081430.228 6298547.602 5003448.105 5777203.122 6351465.734 2596921.903 6400369.848 6028228.884 5329828.214 4718911.604 SAM 2957169.609 1638811.472 2937123.745 2571956.398 3450827.364 2314257.116 2805236.829 2250398.584 3269495.778 2761227.252 3824449.584 2045848.179 UDP-GlcNAc 3207850.378 1358171.178 4494756.589 4768453.148 3929272.17 3488877.845 3569317.963 1994189.732 4544912.601 4360170.323 4405842.114 2668350.803 UMP 26812.08427 19670.00497 68746.27291 82172.60001 46919.2706 67096.64992 40173.25158 16918.4051 70022.40558 44699.17668 46014.38602 49156.16279 2-hydroxyglutarate 1174934.225 563172.8397 1248079.905 1094606.47 1184851.164 1308617.319 1776257.069 980674.0691 2221513.413 1925522.847 2009369.123 1313.747534 IMP 4211.732758 2928.311877 9590.609135 6020.812798 5744.943003 5153.360731 4006.541348 2819.40036 6989.478714 6991.549651 4224.554128 3751.537374 o-phosphoethanolamine 179056.7991 292675.9034 82207.15469 95301.13967 168144.3762 467288.3682 179216.1493 322734.5618 120164.2531 68232.74498 179077.5694 443850.4988 ribose 5-phosphate 25699.4366 6827.582357 21198.23129 19526.1393 22528.51908 17758.96083 25955.23364 16607.456 23690.55544 23923.80952 28348.18434 22581.76772 CMP 13126.06462 14979.90647 19203.32919 15563.77215 5437.085414 13097.18229 14345.47598 CDP-ethanolamine 37090.78701 25475.28056 23749.32598 26405.89212 41943.23854 50421.45968 36986.32308 27000.31045 30737.20246 18563.42319 41340.54318 54403.39828 phosphoserine 153316.8289 271272.6593 277507.2562 260459.475 325504.8762 295776.6225 119165.275 204371.0457 225109.6615 186644.3172 220739.7885 176422.8227 sedoheptulose 7-phosphate 43168.22921 7094.778818 22370.2421 27614.63127 28466.16119 32154.55369 51910.51237 13045.81473 24560.06579 22672.40389 26364.84761 30129.08258 UDP 36638.37286 62261.62734 235872.1148 251035.1532 183461.2863 216119.3813 62174.87145 99038.73975 266657.0383 242006.676 109172.7881 143059.5057 argininosuccinate 59775.69927 21454.852 55687.51282 64703.29841 61059.52898 59410.69311 93145.76335 38151.36809 89715.0788 96818.49102 92989.4776 88976.84751 carbamoylaspartate 130612.6537 86648.69364 210947.5515 187752.9198 181081.5152 141022.6827 107648.6835 50186.58216 151818.3557 121287.4095 127079.9762 88192.32157 UDP-glucose 912545.4442 619238.4606 1302533.313 1437080.21 1365357.544 1260302.547 999598.9147 813838.987 1560408.525 1422540.458 1294379.136 1340774.324 3-phosphoglycerate 548317.8331 513968.3775 1239321.782 1584222.468 1128440.071 1186172.523 482896.6647 790183.0129 1319991.608 1511645.063 1021220.637 1182564.495 CDP 3798.227147 11607.66938 60335.90996 58740.95425 37605.8157 46071.5873 13399.62822 19126.77598 68741.32335 52906.26767 20537.68537 28292.12236 GMP 14565.02638 2987.065386 18896.21251 16095.33863 13031.1974 3151.327475 14428.7834 1718.602797 21010.74087 8255.106473 13638.32255 4006.682793 GSSG 1281401.206 560396.7767 999914.4197 1097957.044 1232514.383 899468.6197 1440885.854 534869.3978 1341652.264 958648.8414 1384626.89 973302.5962 GDP 7516.518661 16514.28491 64430.24593 61521.93146 31896.94899 38545.6265 11174.9548 25732.17817 86975.7954 70645.22116 19392.03479 25441.33403 CTP 51099.33037 76536.31298 191942.9102 170423.2384 131971.5793 142941.1871 52590.57481 111653.4972 241938.4619 264283.6976 113167.5468 198202.7626 thiamine 759229.7018 1191903.497 1361209.673 1301713.705 2890518.014 4275118.479 1369100.576 1380978.592 1479545.122 1226015.916 2643426.499 4797411.054 GDP-mannose 9880.245023 5799.954517 22776.69264 21759.14316 20014.11291 15803.52332 10797.28215 11947.45531 25015.27666 27120.58753 17885.56022 18553.23238 UDP-glucuronate 71607.22131 106370.7154 252824.4304 248475.4063 152961.4889 132768.7464 84124.64485 142058.8462 269597.9166 309283.6163 92000.27856 152021.7617 GTP 26579.94535 64459.58943 162198.9323 133589.5273 105602.8687 122150.7727 28307.3373 104249.816 221090.9781 254112.4212 82803.29526 168343.4426 3-hydroxybutyrate 47933.39138 9010.978802 31731.56568 29741.57272 42989.26738 33635.49049 36796.34712 18225.34123 40830.2004 35308.23621 32909.99098 31509.78601 arginine 22332504.84 17678353.35 17390058.59 14935168.9 18697457.4 15036577 25208446.01 10118022.65 18543978.47 16463902.73 17095068.48 17698324.33 FAD 345.294158 1037.564323 7111.772207 7813.196312 9787.391747 4611.018354 881.2402964 9015.807331 12163.46043 11723.45737 11546.97222 4237.231908 fructose 1,6-bisphosphate 633602.7049 876581.1304 952226.7377 741094.2247 1296509.221 1030787.373 GABA 703256.1169 215451.3917 748791.1754 841587.3665 701724.4876 672495.56 771109.8482 258370.2598 755676.2366 800938.2994 709345.3245 528055.1782 glucose 1-phosphate 36300.66225 12703.67494 34745.6783 38893.27607 35951.67741 34256.75789 54166.53876 21930.64989 42099.29118 41329.54809 44562.72582 33051.46005 isoleucine 61790234.01 27192806.21 63840849.73 56011959.23 65701623.7 52520659.85 86923727.53 39854320.75 76051453.91 74284997.97 69753427.04 146498529.4 NADH 8328.803347 33287.11624 182771.0109 113770.7152 194884.5754 299641.3311 16870.97804 27299.35992 157268.3587 150627.9957 60967.69695 237578.6971 NADP 19186.44938 21422.9889 42944.01009 48665.08913 53175.49515 63428.22243 20018.68997 25387.35237 53126.85871 54428.52069 48411.62523 46083.40378 NADPH 7829.813495 12236.00981 47266.38406 45222.30675 24600.19959 18802.69424 10349.83552 17224.69452 49585.02314 50072.53472 11727.44575 37111.38249 UTP 158554.4999 238390.36 573241.4867 548480.9195 459980.0639 429049.6365 157974.9522 336022.8147 674575.1024 724323.7833 338343.8799 560667.3817 METABOLITES_END #END