#METABOLOMICS WORKBENCH ADSL1_20240920_053231 DATATRACK_ID:5211 STUDY_ID:ST003499 ANALYSIS_ID:AN005743 PROJECT_ID:PR002082 VERSION 1 CREATED_ON September 23, 2024, 1:02 am #PROJECT PR:PROJECT_TITLE ADSL deficiency drives mitochondrial dysfunction and ERK2 dysregulation in a PR:PROJECT_TITLE linear genotype to phenotype correlation PR:PROJECT_SUMMARY Adenylosuccinate lyase (ADSL) deficiency (ADSLd) is a rare autosomal recessive PR:PROJECT_SUMMARY defect of purine metabolism associated with a wide range of clinical PR:PROJECT_SUMMARY manifestations. Despite ADSL implication in purine synthesis, no additional PR:PROJECT_SUMMARY molecular alterations have been identified as a cause of ADSLd besides the PR:PROJECT_SUMMARY accumulation of toxic substrates. Here we uncover a novel association between PR:PROJECT_SUMMARY ADSLd and mitochondrial dysfunction, which is characterized by an increase in PR:PROJECT_SUMMARY fragmentation and reduction in respiration and ATP production. The extent of PR:PROJECT_SUMMARY this mitochondrial dysfunction is directly proportional to the pathological PR:PROJECT_SUMMARY manifestations of ADSLd, which are predominantly observed in tissues that rely PR:PROJECT_SUMMARY heavily on mitochondria. Our analysis also unveils a striking defect in PR:PROJECT_SUMMARY mitochondrial dynamics and transport, which are associated with the suppression PR:PROJECT_SUMMARY of ERK2 and AKT function. Remarkably, the mitochondrial phenotype can be rescued PR:PROJECT_SUMMARY in part by overexpression of a constitutive form of ERK2 or through the PR:PROJECT_SUMMARY administration of purine intermediates. This scenario provides an alternative PR:PROJECT_SUMMARY explanation of ADSLd onset, reorienting research towards developing innovative PR:PROJECT_SUMMARY therapeutic strategies based on the restoration of mitochondrial metabolism. PR:INSTITUTE Catholic University of the Sacred Heart PR:LAST_NAME Bordi PR:FIRST_NAME Matteo PR:ADDRESS Largo Francesco Vito 1, Rome, Italy, 00168, Italy PR:EMAIL matteo.bordi@unicatt.it PR:PHONE +390630155135/5258 #STUDY ST:STUDY_TITLE Metabolic analysis of ADSL deficiency patients' EBV-LCLs. ST:STUDY_SUMMARY Adenylosuccinate lyase (ADSL) deficiency (ADSLd) is a rare autosomal recessive ST:STUDY_SUMMARY defect of purine metabolism associated with a wide range of clinical ST:STUDY_SUMMARY manifestations. Despite ADSL implication in purine synthesis, no additional ST:STUDY_SUMMARY molecular alterations have been identified as a cause of ADSLd besides the ST:STUDY_SUMMARY accumulation of toxic substrates. Here we uncover a novel association between ST:STUDY_SUMMARY ADSLd and mitochondrial dysfunction, which is characterized by an increase in ST:STUDY_SUMMARY fragmentation and reduction in respiration and ATP production. The extent of ST:STUDY_SUMMARY this mitochondrial dysfunction is directly proportional to the pathological ST:STUDY_SUMMARY manifestations of ADSLd, which are predominantly observed in tissues that rely ST:STUDY_SUMMARY heavily on mitochondria. Our analysis also unveils a striking defect in ST:STUDY_SUMMARY mitochondrial dynamics and transport, which are associated with the suppression ST:STUDY_SUMMARY of ERK2 and AKT function. Remarkably, the mitochondrial phenotype can be rescued ST:STUDY_SUMMARY in part by overexpression of a constitutive form of ERK2 or through the ST:STUDY_SUMMARY administration of purine intermediates. This scenario provides an alternative ST:STUDY_SUMMARY explanation of ADSLd onset, reorienting research towards developing innovative ST:STUDY_SUMMARY therapeutic strategies based on the restoration of mitochondrial metabolism. ST:INSTITUTE Catholic University of the Sacred Heart ST:LAST_NAME Bordi ST:FIRST_NAME Matteo ST:ADDRESS Largo Francesco Vito 1, Rome, Italy, 00168, Italy ST:EMAIL matteo.bordi@unicatt.it ST:PHONE +390630155135/5258 ST:STUDY_COMMENTS This new submission is part of PR002082 #SUBJECT SU:SUBJECT_TYPE Cultured cells SU:SUBJECT_SPECIES Homo sapiens SU:TAXONOMY_ID 9606 #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 - BT03-001 Sample source:Blood | Phenotype:Control | Genotype:Wildtype | Age:13 yr | Sex:F RAW_FILE_NAME(Raw file name)=BT03-001.raw SUBJECT_SAMPLE_FACTORS - BT03-002 Sample source:Blood | Phenotype:Control | Genotype:Wildtype | Age:13 yr | Sex:F RAW_FILE_NAME(Raw file name)=BT03-002.raw SUBJECT_SAMPLE_FACTORS - BT03-003 Sample source:Blood | Phenotype:Control | Genotype:Wildtype | Age:13 yr | Sex:F RAW_FILE_NAME(Raw file name)=BT03-003.raw SUBJECT_SAMPLE_FACTORS - BT03-004 Sample source:Blood | Phenotype:Control | Genotype:Wildtype | Age:13 yr | Sex:F RAW_FILE_NAME(Raw file name)=BT03-004.raw SUBJECT_SAMPLE_FACTORS - BT03-005 Sample source:Blood | Phenotype:Control | Genotype:Wildtype | Age:13 yr | Sex:F RAW_FILE_NAME(Raw file name)=BT03-005.raw SUBJECT_SAMPLE_FACTORS - BT03-006 Sample source:Blood | Phenotype:Mild | Genotype:T450S/D332H | Age:- | Sex:M RAW_FILE_NAME(Raw file name)=BT03-006.raw SUBJECT_SAMPLE_FACTORS - BT03-007 Sample source:Blood | Phenotype:Mild | Genotype:T450S/D332H | Age:- | Sex:M RAW_FILE_NAME(Raw file name)=BT03-007.raw SUBJECT_SAMPLE_FACTORS - BT03-008 Sample source:Blood | Phenotype:Mild | Genotype:T450S/D332H | Age:- | Sex:M RAW_FILE_NAME(Raw file name)=BT03-008.raw SUBJECT_SAMPLE_FACTORS - BT03-009 Sample source:Blood | Phenotype:Mild | Genotype:T450S/D332H | Age:- | Sex:M RAW_FILE_NAME(Raw file name)=BT03-009.raw SUBJECT_SAMPLE_FACTORS - BT03-010 Sample source:Blood | Phenotype:Mild | Genotype:T450S/D332H | Age:- | Sex:M RAW_FILE_NAME(Raw file name)=BT03-010.raw SUBJECT_SAMPLE_FACTORS - BT03-011 Sample source:Blood | Phenotype:Mild | Genotype:R309H/c.1191+5G->C | Age:14 yr | Sex:F RAW_FILE_NAME(Raw file name)=BT03-011.raw SUBJECT_SAMPLE_FACTORS - BT03-012 Sample source:Blood | Phenotype:Mild | Genotype:R309H/c.1191+5G->C | Age:14 yr | Sex:F RAW_FILE_NAME(Raw file name)=BT03-012.raw SUBJECT_SAMPLE_FACTORS - BT03-013 Sample source:Blood | Phenotype:Mild | Genotype:R309H/c.1191+5G->C | Age:14 yr | Sex:F RAW_FILE_NAME(Raw file name)=BT03-013.raw SUBJECT_SAMPLE_FACTORS - BT03-014 Sample source:Blood | Phenotype:Mild | Genotype:R309H/c.1191+5G->C | Age:14 yr | Sex:F RAW_FILE_NAME(Raw file name)=BT03-014.raw SUBJECT_SAMPLE_FACTORS - BT03-015 Sample source:Blood | Phenotype:Mild | Genotype:R309H/c.1191+5G->C | Age:14 yr | Sex:F RAW_FILE_NAME(Raw file name)=BT03-015.raw #COLLECTION CO:COLLECTION_SUMMARY 1x106 cells were plated onto 35mm plates in RPMI media (5 replicates for each CO:COLLECTION_SUMMARY cell type). After two days, before extraction, cells were counted using CASY CO:COLLECTION_SUMMARY cell counter (Omni Life Sciences) using a separate counting plate. After that, CO:COLLECTION_SUMMARY cells were washed at room temperature with PBS twice and then kept in a cold CO:COLLECTION_SUMMARY bath with dry ice and methanol before adding the metabolite extraction solution. CO:SAMPLE_TYPE Blood (serum) #TREATMENT TR:TREATMENT_SUMMARY Cells were cultured in RPMI media supplemented with 10% FBS #SAMPLEPREP SP:SAMPLEPREP_SUMMARY Metabolite extraction solution (50% methanol, 30% acetonitrile, 20% ultrapure SP:SAMPLEPREP_SUMMARY water, 5 µM final concentration valine-d8) was added to each well after the SP:SAMPLEPREP_SUMMARY washes in PBS following the proportion of 1ml of extraction solution per million SP:SAMPLEPREP_SUMMARY cells. The extracts were scraped and mixed at 4°C for 15 min. After final SP:SAMPLEPREP_SUMMARY centrifugation at max speed for 15 min at 4°C, the supernatants were SP:SAMPLEPREP_SUMMARY transferred into LC-MS vials. #CHROMATOGRAPHY CH:CHROMATOGRAPHY_TYPE HILIC CH:INSTRUMENT_NAME Dionex Ultimate 3000 UHPLC CH:COLUMN_NAME SeQuant ZIC- pHILIC (150 x 2.1mm,5um) CH:SOLVENT_A 100% water; 20 mM ammonium carbonate; 0.05% ammonium hydroxide CH:SOLVENT_B 100% acetonitrile CH:FLOW_GRADIENT 0-2 min: 80% B; 2-17 min: linear gradient from 80% B to 20% B; 17-17.1 min: CH:FLOW_GRADIENT linear gradient from 20% B to 80% B; 17.1-23 min: hold at 80% B. CH:FLOW_RATE 0.200 mL/min CH:COLUMN_TEMPERATURE 40 #ANALYSIS AN:ANALYSIS_TYPE MS #MS MS:INSTRUMENT_NAME Thermo Q Exactive Orbitrap MS:INSTRUMENT_TYPE Orbitrap MS:MS_TYPE ESI MS:ION_MODE UNSPECIFIED MS:MS_COMMENTS Metabolites were measured with a Thermo Scientific Q Exactive Hybrid MS:MS_COMMENTS Quadrupole-Orbitrap Mass spectrometer (HRMS) coupled to a Dionex Ultimate 3000 MS:MS_COMMENTS UHPLC. The mass spectrometer was operated in full-scan, polarity-switching mode, MS:MS_COMMENTS with the spray voltage set to +4.5 kV/-3.5 kV, the heated capillary held at 320 MS:MS_COMMENTS °C, and the auxiliary gas heater held at 280 °C. The sheath gas flow was set MS:MS_COMMENTS to 55 units, the auxiliary gas flow was set to 15 units, and the sweep gas flow MS:MS_COMMENTS was set to 0 unit. HRMS data acquisition was performed in a range of m/z = MS:MS_COMMENTS 70–900, with the resolution set at 70,000, the AGC target at 1 × 106, and the MS:MS_COMMENTS maximum injection time (Max IT) at 120 ms. Metabolite identities were confirmed MS:MS_COMMENTS using two parameters: (1) precursor ion m/z was matched within 5 ppm of MS:MS_COMMENTS theoretical mass predicted by the chemical formula; (2) the retention time of MS:MS_COMMENTS metabolites was within 5% of the retention time of a purified standard run with MS:MS_COMMENTS the same chromatographic method. Chromatogram review and peak area integration MS:MS_COMMENTS were performed using the Thermo Fisher software Tracefinder 5.0 and the peak MS:MS_COMMENTS area for each detected metabolite was normalized against the total ion count MS:MS_COMMENTS (TIC) of that sample to correct any variations introduced from sample handling MS:MS_COMMENTS through instrument analysis. The normalized areas were used as variables for MS:MS_COMMENTS further statistical data analysis. #MS_METABOLITE_DATA MS_METABOLITE_DATA:UNITS peak area MS_METABOLITE_DATA_START Samples BT03-001 BT03-002 BT03-003 BT03-004 BT03-005 BT03-006 BT03-007 BT03-008 BT03-009 BT03-010 BT03-011 BT03-012 BT03-013 BT03-014 BT03-015 Factors Sample source:Blood | Phenotype:Control | Genotype:Wildtype | Age:13 yr | Sex:F Sample source:Blood | Phenotype:Control | Genotype:Wildtype | Age:13 yr | Sex:F Sample source:Blood | Phenotype:Control | Genotype:Wildtype | Age:13 yr | Sex:F Sample source:Blood | Phenotype:Control | Genotype:Wildtype | Age:13 yr | Sex:F Sample source:Blood | Phenotype:Control | Genotype:Wildtype | Age:13 yr | Sex:F Sample source:Blood | Phenotype:Mild | Genotype:T450S/D332H | Age:- | Sex:M Sample source:Blood | Phenotype:Mild | Genotype:T450S/D332H | Age:- | Sex:M Sample source:Blood | Phenotype:Mild | Genotype:T450S/D332H | Age:- | Sex:M Sample source:Blood | Phenotype:Mild | Genotype:T450S/D332H | Age:- | Sex:M Sample source:Blood | Phenotype:Mild | Genotype:T450S/D332H | Age:- | Sex:M Sample source:Blood | Phenotype:Mild | Genotype:R309H/c.1191+5G->C | Age:14 yr | Sex:F Sample source:Blood | Phenotype:Mild | Genotype:R309H/c.1191+5G->C | Age:14 yr | Sex:F Sample source:Blood | Phenotype:Mild | Genotype:R309H/c.1191+5G->C | Age:14 yr | Sex:F Sample source:Blood | Phenotype:Mild | Genotype:R309H/c.1191+5G->C | Age:14 yr | Sex:F Sample source:Blood | Phenotype:Mild | Genotype:R309H/c.1191+5G->C | Age:14 yr | Sex:F 2/3-phosphoglycerate 60799193.5 44998494.27 35827049.44 40235936.02 36381833.95 30181977.69 35692807.27 26542620.99 15565241.59 35705145.82 13920071.34 22315672.5 26191488.75 21446147.56 18846963.82 2-aminoadipic acid 4385518.836 3472865.657 4721314.77 3775124.938 2872279.723 5868323.294 4088884.327 4458489.61 3950044.234 5351805.637 3575835.24 3118513.344 2700736.887 3215680.613 3262442.81 2-hydroxyglutarate 130844444.4 91106211.87 95236492.97 108810482.6 114719745.7 65073377.48 61019206.05 61467997.35 58259247.92 71891121.39 80008747.7 83844644.69 82877062.07 76436656.62 79599758.79 2-ketoglutarate 162546707.3 134150758.1 137563212.5 131070038.3 123660603.4 27697602.83 24390779.54 23008102.48 27432871.74 41070816.39 47081287.73 35261383.05 36836367.27 65169316.39 58115304.13 4-guanidinobutanoate 158226223.4 119368120.6 129729898.6 126944632 135015486.3 192722792.8 176923196.3 198711978.4 175166330.9 205430741.1 303840490.8 305831685.7 294991877.6 261209174.6 283113981.4 acetylcarnitine 1850176160 1365247289 1532761381 1742900005 1451102353 4458009348 3845087570 4479524089 4316331624 4732582535 3390846208 3585724264 3441050275 3492712828 3614721685 acetylcholine 775274851.4 555983376.7 641348663.3 625218363.2 617401815.6 1109513243 989621514.7 1120994604 989253464.3 1252622073 730608449.9 672704223.4 650001452.4 592001105.1 662529357.9 acetyl-CoA 2381091.06 1914880.154 897936.232 1437808.563 1830252.573 1155880.706 1511250.242 1276085.758 1114826.771 1696773.519 2987452.673 1919606.663 2035016.668 2413560.401 1713366.411 adenosine 199018437.1 33703467.48 139409134.5 129510041.6 151527528.7 221863966 119273568.8 240251115.8 76409351.05 182836590.6 58651366.44 132246381 127849011.4 45873689.85 49986325.38 adenylosuccinate 258464.7852 114619.0734 103579.7876 86926.36773 27162.23054 1764280.186 1708108.375 1725827.867 1774087.773 2274471.111 37396.25519 162229.5275 81076.25769 332199.0485 169396.8329 ADP 234136357.3 181444497.3 194667053 197149681.8 196315119.3 166347876.7 158343657.6 158961715.9 177380855.5 208092567.3 123334184 137182344.4 136341633.7 161709417.9 142966406 ADP-ribose 2954138.344 1474120.797 1857230.832 1688081.007 1944999.591 3181250.464 2350766.005 3412943.871 1530857.451 3379754.743 2055105.981 2523670.258 2136376.864 1565735.417 1516115.433 alanine 285032606.4 217115861.8 240320998.8 223221283 248094454.5 180794867.6 162088583.7 175208962.8 152750759.7 186726613.3 500146267.7 451514470.2 439777012.4 385734193.5 454305977.1 aminobutyrate 250455600.5 322036027.6 211962752.7 207702961.3 213094496 179955153.9 170614323.5 177643730.2 167210757.4 190761633.5 105099658 100884003.5 98291353.25 100251198.3 96788321.05 AMP 297933355.2 49089529.02 139379880.8 148901748 236780581.5 145722399.6 100079679.5 154607557 51542762.82 206045569.3 85277040.22 167532582.6 170775641.4 64279404.92 75484391.91 arginine 2210740506 1610600932 1817857880 1713683300 1604556621 1671618838 1474008732 1419298091 1404764692 1636764680 1721132783 1677651680 1661385038 1773447805 1800265291 argininosuccinate 7197055.151 4917684.867 5500626.411 5424629.515 5521307.944 4038185.492 3518925.228 4118071.605 3124493.248 4542067.611 8419162.725 6987870.354 7172425.84 6829811.023 7102633.446 asparagine 391278003.5 295679930.6 323492901.9 300004420.3 317075974.7 241889479.9 202202638.2 234658389.2 201004221.4 233306442.6 261789385.7 240286228 238975448.9 213019276.1 239004091.6 aspartate 1561267549 1287083478 1305682231 848179875 1293701945 1277976097 1147690605 1215820390 1086027375 1246914989 885217678.5 812891237.2 811288440.8 748141214.9 844020811.7 aspartylglucosamine 1798339.514 971477.4406 1323665.937 1138564.301 1235123.201 1608814.612 1405746.922 1598077.254 1590951.987 1868696.764 1317289.339 1290582.501 1402505.914 1341119.516 1608110.742 ATP 199915533.9 290008906.6 206014451.1 211443943.1 162394319.6 127843183.6 134820287.6 111132845.1 194848024.4 184808216 103988720.5 88359461.68 90863854.85 166472378.4 145944382.9 beta-alanine 76205134.08 62257269.6 66731397.18 58669720.19 60829125.63 80627448.73 69325408.85 78855716.39 64165142.21 80953760.71 182143439.8 174964782.5 169307351.3 148655680.3 167935153 beta-citrylglutamic acid 7266989.245 5442766.208 5404627.04 6016099.238 5822815.538 6548947.748 5893567.414 6423979.554 6251249.546 7541135.132 15361735.56 15874901.72 14901548.34 14685933.4 15626637.71 betaine 3817164056 2638240987 3153380196 3053018559 3002973630 8295064232 7331027618 7973846207 6579024378 8962135949 2684102050 2586597412 2396664190 2096795406 2505372596 butyrylcarnitine 251004834.2 181149895.8 199776766.5 201000951.7 196415383.7 1103496307 956487653 1113067509 952069396.1 1253155040 496689491.2 466784677.8 482189316.9 428959138.7 464206614.7 cAMP 691016.1968 314031.8023 321644.5141 673480.7858 333140.0409 394769.8232 313583.0866 271135.736 163069.4264 448949.7483 452702.6201 693657.1527 850927.7352 417124.4073 519517.1652 carnitinamide 113354351.5 83926942.23 95766980.63 94670967.5 90103215.11 62440317.66 56276721.25 59487282.13 56846721.55 67183526.21 48533700.39 45907183.47 46210273.3 49413463.71 49181082.16 carnitine 2772028960 1857500342 2145113720 2361420341 2207396825 6953269916 6389869201 6863299224 5960130766 8124671686 6415900472 6019952040 5800507347 4988675626 5659204999 carnosine 10137543.09 7973324.968 6943869.381 6839447.505 6635631.359 4905690.907 4640832.342 4366910.991 4162863.369 5389565.301 4758933.965 4371841.393 4193795.484 4159090.857 4796673.172 CDP 16671090.21 14744439.94 13457439.66 14126971.12 13914649.44 9864604.352 9734040.279 8904135.699 10810658.65 13873331.91 6058755.975 7528495.6 7094102.9 8847210.105 7845560.11 CDP-ethanolamine 12538899.12 8409132.308 9779794.354 10244402.95 9711791.634 6621261.823 5594869.724 6891013.359 5627617.851 7609969.168 1894055.492 2189554.645 1965741.464 1669093.206 1881366.957 C-glycosyltryptophan 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 choline 3047187901 1919525063 2343554673 2803165456 2345229282 2290115846 1900084977 2164847739 1183935359 2237567982 1525531261 1562792763 1537922332 1040611617 1441447293 cis-aconitate 137822990.1 90809741.12 106635400 129241789.8 108443999.9 96063773.39 81940184.09 92282445.91 106845012.1 110222774.7 82943892.96 83520362.8 85187697.89 97416139.55 94070989.04 citicoline 24812940.13 12442793.45 14496380.61 15885585.55 17068137.75 7227575.76 5938627.186 7464561.865 6067868.931 7974330.424 5852036.716 8672848.689 9935543.879 5739936.297 5473846.265 citrate 968556278.2 1596135504 611245881.6 973345714.3 649071838.2 485850319.1 676891174.5 311432840.8 1066197406 767178810.6 215959912.2 358817159.2 344667855.4 430742622.5 351548121.4 citrulline 27483756.12 20460034.62 24411136.88 22159656.12 21241883.52 18001969.57 13739058.54 16852439.06 14703184.52 17059267.43 27554553.2 25984173.28 25595076.13 22415650.19 23147894.87 CMP 9688081.481 1920409.356 5106212.711 5023022.778 6554005.941 5352694.731 3193522.867 5751561.03 2288249.414 6494703.396 3344191.424 4058750.953 3931959.226 2927526.791 2820882.751 CMP-acetylneuraminic acid 5825086.099 4150102.01 4253948.226 4637910.386 4297135.231 3562164.932 3115161.677 3720233.06 3117552.638 3990376.588 3155883.472 3031498.925 2914747.914 3013142.874 2911236.398 creatine 8441854088 6211062539 6464762755 7575182015 7188871090 14166883221 13404580864 14190577882 12545038649 15674761988 6888317474 6719115571 6450211944 5505481583 6246979480 creatinine 1066640301 641527002.2 761156974.6 938860854 705742759.3 686554502.6 564684864.4 624627142.8 471060699.2 699824832 669827118.6 631721987.8 595791992.7 498537909.2 603925220.6 CTP 8972796.815 13972895.2 8849829.033 9142448.316 7201920.064 5266501.225 5758337.966 3807554.066 8360117.53 7555000.468 3087688.868 3088087.619 3249336.055 5783608.144 4945928.182 cyclic ADP-ribose 17934532.86 14891831.21 15513879.28 15765624.21 16442368.83 15166271.47 13849816.62 14217888.91 16329047.08 16761997.43 18918358.28 17437977.03 17235842.61 18184877.18 19676173.34 Cys-Gly 19760475.09 15014715.39 16710233.88 16182722.85 12730461.05 20216242.97 17733833.54 19687051.77 17895046.87 22059199.8 16397565.58 15851588.44 14928932.22 13877463.82 15994709.85 cystathionine 1325536.315 846592.4065 907228.8808 933818.2843 975829.4582 446780.537 292936.6097 413923.7464 397036.5102 427459.3429 550378.2941 468026.9104 433444.6268 458123.454 534720.7772 cysteic acid 305749.1407 172737.0202 166361.8557 64158.18649 193503.9058 309978.3683 209629.3841 235753.8351 127216.0935 229214.0451 109027.9989 111877.7598 103928.9967 130884.2133 121759.0412 cystine 2774244.647 890097.0111 898163.7481 586895.6847 1772609.415 599616.3137 51045.79749 156189.0788 69421.28591 228243.8877 474158.1113 522306.1469 332570.9424 345232.1286 257288.7854 cytidine 18932643.56 7310097.003 9778463.872 8888957.87 7366416.971 2927518.079 1860741.352 3058380.203 2914811.021 2909161.8 2715435.662 3149547.116 2668630.603 3916228.391 2914268.611 deoxycytidine 22749782.35 16895974.96 18862480.68 19981495.41 17920607.65 22973407.48 19782942.25 22202554.21 13630799.54 24339937.33 41690649.51 43143074.52 42652152.19 28721002.2 39952971.17 deoxyribose 5-phosphate 1400403.765 1031178.82 1050422.368 908359.7103 1152370.142 1433309.065 1101477.126 1122798.156 1537841.879 1436207.522 920952.5554 807664.6604 832569.8071 999706.6555 1118052.469 dihydroorotate 4331298.214 3179906.816 2758434.931 4748764.23 3547746.453 4279977.768 3984979.483 4721058.748 5873902.212 8220817.999 3762795.234 6986589.977 6399834.083 3901791.536 4470642.934 dihydroxyacetone phosphate 8107655.271 6202086.614 7120401.275 5651223.968 5009126.564 4199353.058 4676205.509 3438671.951 2324374.384 4246812.047 4624367.91 2826564.606 3032614.653 3833288.109 5400843.816 dimethylarginine 82279468.48 40735662.43 60068711.49 56635267.84 57468097.97 57348537.31 46014822.35 54226026.02 43649555.97 56509569.5 81747741.09 76958032.03 78839097.97 72166262.45 76649981.81 dimethyllysine 5281035.536 1746849.312 4089330.056 3402647.035 3679225.372 4666569.277 2838445.864 3853879.291 2019012.014 3331004.692 9272698.001 7384544.147 6337548.682 4556232.203 6962429.42 dTTP 1313291.297 2083851.357 1246580.253 1429999.701 828423.8168 870359.5222 811786.2638 732705.6876 1330963.638 1221539.558 927731.1432 787783.7335 826606.035 1375610.753 1291106.95 ethanolamine phosphate 94295768.63 63104902.55 73742683.23 71385482.29 71657407.75 59043700.62 49407593.98 54587681.69 47496275.36 62267264.57 6006835.729 6403330.754 6532873.821 5626269.209 6548763.586 FAD 1740044.079 1195614.209 1517989.871 1485708.857 1333461.826 1289616.14 916982.1 1076614.33 1001500.464 1525490.338 816530.2857 783238.9592 966883.0724 972974.9125 915119.3326 fructose 1,6-bisphosphate 12242258.99 14316675.4 10807258.11 9546318.474 10107247.19 9542348.748 10237014.99 6073311.632 7499515.238 9661175.183 6265143.708 6278809.164 6378470.46 5518766.802 7720953.504 fructose 6-Phosphate 13111347.23 8362874.778 10765277.49 11568449.31 10038075.4 5566540.595 4927501.618 5530893.219 3722892.433 7032056.465 8385585.339 6726174.956 7109949.568 5239590.178 8137307.205 fumarate 148248249.9 67262678.08 113347750.3 113909712.3 118328697.4 84534083.92 56758211.57 87390762.48 45687578.69 86923285.57 188853545.7 144697647.2 126221891.3 107722353.7 152764660.3 GDP 12065396.53 15207119.43 10751799.42 11712701.73 9742917.537 8552881.49 8999898.632 7173321.456 13506388.97 13759628.43 4740308.324 5348696.412 6109294.753 9590696.454 7461597.534 GDP-glucose 1782052.358 1230832.68 1514357.906 1385348.594 1447147.18 1162125.008 1155142.921 1097828.629 1079625.551 1490559.789 1579662.476 1456891.485 1481382.154 1700780.103 1721859.918 gluconate 335602566.5 250359680.1 255698458.5 254495989.7 258102747 142602973.7 125274562 128582910.5 125034502.6 156667532.7 309618492.7 304997977.5 303475528.9 266789352 289850841.1 glucose 6-phosphate 10405951.02 5772359.917 8571033.269 7143670.478 8289263.448 3997122.849 3050742.311 3564260.951 1784208.997 4258478.836 7577645.303 5456021.28 5527896.565 3319193.772 7941962.78 glucuronic acid 9744405.839 7695512.02 8526038.857 8590334.477 8203238.556 8298079.299 7170562.015 8089101.559 7237404.622 8887070.186 6041350.906 5632545.249 5787054.592 5359369.948 5578398.762 glutamate 4527309182 5758354560 3799050499 3722408980 3778450866 3237072276 3042847106 3169076795 3011175752 3312098112 1849699461 1772316000 1749943398 1755326931 1755028741 glutamine 12322766502 9864565780 10789803935 10238940560 10266064861 8850820331 7914189234 8880055543 7679566373 8661154712 7334264722 6978531701 6956192250 5891411443 6683202796 glutamylcysteine 2235605.515 1361590.203 1246239.147 1146919.473 1002259.06 1169933.762 1119871.811 1054694.837 832547.3106 1070693.586 1245882.641 1225063.122 1390502.227 847960.2465 1020113.457 glutamylproline 10276642.24 9246606.135 10282206.27 10186060.45 10420510.28 10127168.62 10258581.98 10917275.33 10818891.08 10880008.78 11077749.49 9735391.713 10032816.56 10478725.3 10151079.92 glutathione 1787554482 1241584686 1397295336 1438430486 1149412937 1730937810 1525011343 1649784590 1524864580 1907829022 1361655763 1322770120 1304599020 1225968153 1322331880 glyceraldehyde 3-phosphate 47423727.34 21323794.38 37069784.71 36270314.14 37162272.56 28050600.08 19165433.83 26186251.42 19668657.38 30881634.19 31084589.88 29208817.19 26452263.99 25227323.43 29124484.79 glycerol 3-phosphate 10705435.76 7630372.884 7444842.968 6821546.846 7013630.958 2262922.425 2062852.949 2662008.469 2472964.525 3423712.529 1964504.43 2827031.977 2599076.789 3155676.912 2226107.383 glycerophosphoethanolamine 46886677.42 34111719.9 39957992.89 33828029.68 35023272.91 8903360.627 7946629.752 8547300.516 5199139.373 10450761.37 16510077.34 14125210.4 13499820.57 8116535.005 12424073.42 glycerophosphoinositol 15427889.72 5851018.206 11278505.93 13415836.12 10968860.15 13420486.92 9453540.199 12934965.28 8622928.266 14067726.19 16006928.68 16481051.83 16180287.98 13799290.6 14867848.37 glycerophosphorylcholine 1708442269 1132835406 1344113389 1367352492 1290872651 271581709.6 230986832.9 242971552.7 142800548.9 275033153.8 562146567.4 476625100.7 484839710.5 255897197.3 427123450.5 glycerophosphoserine 710902.5249 478941.9425 475610.7548 537040.3933 512941.83 409618.5764 348605.2059 365951.8804 322750.6709 477325.0876 623690.0878 485317.2268 539071.2266 588862.8848 523611.1705 glycerylphosphorylcholine 1708442269 1132835406 1344113389 1367352492 1290872651 271581709.6 230986832.9 242971552.7 142800548.9 275033153.8 562146567.4 476625100.7 484839710.5 255897197.3 427123450.5 glycine 30454551.12 558907177.3 27313427.11 25324275.8 23433203.42 19692892.25 35579096.88 17027637.48 17880398.52 20743940.12 17038289.9 17938125.05 19294635.42 14542445.52 15999785.14 glycylglycine 2371103.274 1830064.919 1954852.46 1612076.592 1798684.99 2003462.427 4929216.281 1780872.16 2417941.089 1924174.312 1867471.369 1775260.475 1842915.549 1622244.218 1717177.753 GMP 13251620.96 4600545.461 7249933.912 6846934.752 10410550.49 8570465.128 7055495.771 10026304.16 5121650.489 12316491.59 4567957.479 7204594.851 6585307.047 4463207.261 4077007.665 GTP 6687033.464 11867883.68 6871592.053 7240750.952 5508102.61 4940808.89 5288133.019 3713188.323 9274150.901 7560209.052 3076995.122 2792792.475 3064319.729 5972979.379 5109387.198 guanidineacetic acid 52352692.97 43595909.79 46394793.49 43652418.32 43180962.55 194322599.5 191092651.1 193866612.3 165257740.9 190561034.1 63701802.65 61465985.39 60471855.52 49109211.62 60366509.87 guanine 6185597.618 1618586.323 3360329.251 2530002.872 2446408.73 1861849.275 1234942.833 1999917.389 632392.2866 1392050.532 117556.6655 282062.3313 475330.1484 582860.8148 126018.2513 guanosine 11486389.92 2569862.258 5914196.268 4359163.688 4188883.917 3787175.666 2032765.792 3441275.124 1145349.778 2687404.476 424899.9973 1151636.821 596820.2528 1148204.426 300117.8473 histidine 1027472387 819164370.8 807024144.4 739106462.8 796430756.6 616525178.6 558854345.2 576786138.7 531291472.9 628037667.1 814274056.8 786715125 798241954.8 706662295.6 751764978.1 homoarginine 9531236.645 6279903.149 7438343.306 7144065.852 6510968.447 7051150.624 5619104.663 5546595.427 5370295.995 6473207.19 7767358.334 7279776.005 7073795.025 7323650.272 7913791.089 hydantoin-5-propionic acid 1201925.869 738014.9631 853645.9254 768439.4036 899781.4723 940542.9798 903884.3261 696715.6212 773892.5856 802240.9015 715719.223 548423.5627 586750.4239 629858.9014 615595.9188 hydroxyphenyllactate 100183183.2 76244823.89 88207618.26 81752676.26 82855807.66 40380990.35 35484424.46 42539723.04 35289350.33 42011693.53 32564130.05 26759511.95 26102383.67 24589491.17 29222918.96 hydroxyproline 2014636615 1681284376 1908293191 1919955809 1975351912 1037505718 1000992467 973197300 880720178.8 899572300.6 1998381212 1572449836 1758326436 1411722630 1813477899 hydroxytrimethyllysine 7110567.001 1975033.657 5641405.555 5109085.689 5507095.255 3187613.253 2476264.97 2972546.077 1542136.397 3016657.119 5599128.597 4475230.021 3950912.787 3361116.826 4553121.973 hypotaurine 20224945.82 15316523.75 18396623.98 16216123.95 16976640.9 22784855.61 20194778.77 22096153.49 19164802.8 23889282.68 24841415.95 23650644.29 23522197.7 20368236.66 22846928.17 hypoxanthine 358388635 98220449.44 145456257.3 96482952.31 96464123.18 54404575.83 28401001.84 41718736.84 34679069.21 29987455.71 25859470.1 34062351.52 21013615.18 44793163.21 24369343.67 IMP 25308397.11 20544327.88 18841503.96 19769994.54 18395011.06 8386790.903 7201012.034 9054333.225 13893195.38 10272411.46 4177960.386 6324086.626 4935879.235 10778037.89 6192768.676 indole 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 inosine 46041508.74 13133713.55 28601038.86 18245068.47 20140859.37 11665814.15 5247342.244 8614216.722 3888567.013 7029612.537 5598953.961 5938128.494 4012302.766 5885564.322 3995855.623 inositol 511011326.5 435090673.1 502861794 512668358.4 472879066.8 477315867.6 420737874 463758157.4 413603860.3 476411403.2 590676431.7 542170565.7 540873212.4 477541665.3 527299333.2 isoleucine 1681943125 1061887619 1298790815 1204271697 1244511143 1044212209 890901532.3 929553011.8 808321185.9 1026771103 1243742635 1166095910 1115700207 977143727.2 1143341911 isovalerylcarnitine C5 78587315.72 55424973.63 66480681.64 67681572.59 60243087.58 128926155.1 112831183.8 131500000.6 110388480.1 138053356.3 104070733.2 85717088.82 85460275.02 82998681.01 92552827.15 ketoleucine+ketoisoleucine 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 ketovaline 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 kynurenine 3217087.053 2141210.313 2877405.866 2453359.7 2167532.13 6791993.488 5697691.825 6227880.815 5155049.448 7237638.079 4866969.235 4697543.899 4376127.188 3937437.289 4041108.151 lactate 2466623066 1487560178 1772877368 1547112145 1727802221 1369453214 1204897061 1357816731 533981152.7 1522712534 3322059239 3064937981 2889626889 1990585874 2897233207 leucine 1664268319 1025216748 1210401517 1185001986 1084665483 935247281.9 789763417.5 859206686.4 706122431.5 985864499 968018358.3 882221969.8 924926176.9 749693896.2 829349578.2 lysine 37325687.78 22642552.23 25038063.59 23438859.79 22658291.61 23520646.75 19880310.95 18660516.43 19537010.25 23074321.77 15772826.02 15673323.89 15330506.58 15968687.47 16759456.65 malate 2073421969 1000146065 1663489840 1653346668 1645496179 1168380913 844050196.6 1228492240 696843272.9 1259671670 2627156052 1929545402 1680384172 1671310477 2191625542 methionine 402743553.3 258237951.5 305424396.9 285403780 292834896.8 225654150.6 191745117.4 207302441.9 168399722.2 226915363.8 164361644.4 155885980.9 155098268.5 124039689.9 145754776 methionine sulfoxide 36524750.92 23891004.32 28862294.41 27062245.27 27544822.71 22434212.5 18488017.57 20719983.67 17344752.06 21949879.08 27964330.51 25481532 26286703.32 22551712.63 24878208.65 N-acetylarginine 3299677.486 2119090.932 2766742.652 2781170.744 2142911.912 1994945.642 1509258.776 1902014.456 1770792.038 2441976.439 3193278.026 3406109.876 2834747.61 2358186.235 2675920.369 N-acetylaspartate 148259127.5 115185680.1 119897354.9 142674535.1 124587695.5 199572426.5 169612207.2 192597638.5 166291937.7 212647530.6 168059503.3 155649084.7 150790587 137638730.4 154555814.1 N-acetylaspartylglutamate 748772.3068 148245.9195 509271.3629 392875.7143 553509.4192 1308884.787 858755.3831 1003133.34 784197.4828 1199428.567 2519886.659 1833837.814 1517590.66 1016348.459 1753874.588 N-acetylglutamate 62209361.38 94853811.65 55225395.55 56041895.85 55015885.41 61376191.91 60889663.19 62141920.03 58837443 66325270.14 65716773.71 63587450.79 61970006.2 56642034.76 62335154.45 N-acetylhexosamine phosphate 15312985.78 10649951.78 11583558.65 20006757.43 11578586.15 7560699.318 6646275.332 7343936.235 6650136.904 8294437.526 6711670.832 6814758.574 6238521.969 5795894.045 6407188.476 N-acetylhistidine 57554457.42 25539542.51 34267888.52 28222836.38 26589362.17 25892852.09 20980410.81 20136489.72 16065639.49 25386187.84 40243573.32 36937234.55 37409703.9 32330353.99 36529183.98 N-acetylneuramic acid 9065104.275 5509957.03 5951128.718 7627719.768 5620407.396 5415802.638 4241614.232 4745289.72 4218822.244 5440039.511 4629945.34 4917724.502 4638842.745 3845593.668 4391535.467 N-acetylornithine 55568203.29 40120799.66 45222165.38 42872026.84 42618568.89 36693372.2 30639372.94 34558258.35 31976880.74 37039242.12 47875672.61 45960946.98 45625800.62 42258353.34 45271470.86 N-acetylserine 452917864.9 335540437.2 375891285.3 347492897.3 360477053.8 556159515 470585744.3 542968307.2 468050433.9 592760918.4 518478804.7 484933047.4 476029815.5 442289352.4 483392042.8 NAD 145707599.4 123358170.9 123831555.6 127604010.7 126997982.9 116603898.4 106966785.3 104773671.3 128561862.2 130990926.2 141773318 135159875.6 133589891.2 140784167.1 146832689.8 NADH 3043221.071 5036126.792 1917937.928 2181448.602 1632082.317 6906881.666 8669655.918 8377104.175 4481539.329 6360490.46 3266588.233 3506745.383 2893688.076 4173220.113 2708263.812 NADP 2340464.755 1212674.246 1575040.934 1621704.393 2344880.644 1966881.815 1669285.914 1857694.239 1070443.096 2171913.257 1316466.12 1462648.825 1421495.796 832183.8242 1333400.478 NADPH 1961906.906 2805267.282 2166851.968 2360172.531 1723693.004 2175979.778 1885494.639 1950115.018 3806249.486 2492853.719 1657610.909 1292227.647 1131242.274 2696828.552 1965805.837 N-carbamoylaspartate 1893897.067 695406.5473 1634161.723 1828438.023 1470047.882 1897090.529 1678479.108 2178809.189 2512585.029 2746965.185 4944478.653 5421085.738 4879207.737 5035489.135 4614902.483 N-carbamoylglutamate 1645645.056 301435.0807 1422721.732 1432780.823 1284168.012 1810033.271 1343704.349 1358512.488 1435032.167 1604754.501 1043102.232 918894.3151 1012251.018 1140301.295 923995.8986 nicotinamide riboside 5436193.629 3797331.911 4291055.196 5025892.822 4135062.994 3338408.27 2920093.404 3374385.511 3017057.991 3692313.445 5301165.684 4946293.407 5189498.662 4816981.33 5057147.555 ophthalmic acid 4094666.021 3191232.859 3490803.498 3397175.973 3406629.328 2104915.865 1920147.16 2207909.172 2048406.297 2308860.186 1054752.39 881721.1301 714625.8465 826917.9383 1044177.946 ornithine 56057995.41 33594170.67 37616225.33 33066063.52 31200580.35 32680798.37 28025395.78 25158398.09 27190385.25 31456055.85 32461093.29 32376368.94 31948150.28 35910223.4 35935624.95 orotate 4307899.54 3282817.356 2635363.716 163426554.9 2791930.449 4984125.591 3787409.452 5635113.811 4816100.334 5463382.708 3703002.361 7545493.913 6945535.562 3550609.638 3703293.522 orotidine 61739064.38 40533572.76 50010812.5 49729735.87 51751302.86 66182282.79 53297601.35 66343801.75 52825344.84 68842599.24 69675079.03 64202777.36 60195813.79 57605390.18 66134740.65 oxidized glutathione 6278258.622 4870920.777 4918573.105 4795901.815 14201054.22 5852430.428 5050157.688 6211103.055 5676062.045 6873048.469 4793309.182 3672686.841 3848912.993 4084038.841 4217493.908 pantothenate 608105614.5 405120062.3 473204471.9 470225083.9 462274989.9 221784766.7 189064059.5 221377696.2 189207063.2 253423628 189091501.1 179581707.2 171422320.5 162831974.6 182089778.4 phenylalanine 602369780.5 364379096.6 436519138.6 423553123.8 409994663.5 352030898.4 295945179.1 322975940.5 258524147.5 357703898.1 305648528.9 295525256 292361230.2 246399273.7 268588591.7 phosphocholine 20617887226 15475335880 16483432256 17990218118 17168670838 18743142046 16352308722 18081113185 16731048576 20109458541 12105486587 11247332104 11773368470 10976742113 11685286079 phosphocreatine 39060592.81 31098141.86 33993053.91 31731617.25 30647399.99 12606775.21 10855757.78 11554421.97 11657593.04 13311424.1 13396004.2 11356875.61 11077555.65 12450271.63 12996655.22 phosphoenolpyruvate 7279852.151 6707273.431 6862711.093 6493207.296 4278284.102 3299095.783 5400925.902 3445014.515 5756401.704 4212952.578 2027935.561 2664789.612 3363911.061 11211199.35 4595666.206 phosphoethanolamine 61528598.19 46803911.64 47659210.87 45033883.75 46264858.16 36823209.79 32624824.3 34337400.9 32800948.05 41076735.06 3512691.722 3946478.653 3794783.795 3860168.408 3685840.398 phosphorylcholine 20522867390 15450798958 16411301106 17919510822 17093909992 18665312191 16311856240 17996314451 16690145826 20022756751 12063343639 11194986815 11725388738 10926712137 11649558936 proline 21808112903 16667220321 18347440427 17392304922 17423798023 16271219805 14300745283 16277403492 13085403653 16102693539 18469190409 16394572541 16027949167 14029168302 16711439114 propionylcarnitine 457313380.6 316884757.4 366037504.5 352535744.2 340734147.1 638202007.8 538337878.3 622081877.6 527924402.5 648498909.7 758664277.8 606683063.4 568082979 564348357.2 689289789.7 propionylcholine 48999484.46 35692501.7 40234588.6 117435196.2 38928645.48 121334760.4 109834676.8 122447375.6 109493280.1 139230205.1 127841570.5 121476908.7 116471188.6 107096162.5 117789483 pyroglutamic acid 4255053725 2906734087 3217011336 2909779872 2902617869 2840944934 2384591857 2581900293 2111609797 3043894006 3594752211 3378015453 3348948521 2870276365 3286697775 pyruvate 66713033.75 35870400.04 46362239.8 36483049.17 44368825.44 13331736.37 10000831.35 9969650.942 3388402.07 15930591.12 64219511.17 48806187.96 50722039.01 28772535.34 50971615.57 quinolinic acid 30690710.45 22623481.18 24026802.25 21866584.34 22843890.91 2207341.41 1992605.623 2016161.617 1817033.694 2255287.262 27708216.24 24696192.28 24122456.05 23916440.93 25615255.91 S-(2-succinyl)cysteine 715876.9971 721956.4576 315466.3014 518480.8977 422549.7772 214279.5012 163978.3202 206938.1678 224655.7254 442965.9178 522295.8784 494949.2225 524895.0894 578175.6054 444232.2657 S-(2-Succinyl)glutathione 642338.2886 473673.7437 495735.9347 469968.8344 472470.8238 544511.2497 386256.1804 453741.8259 388432.1989 540443.5208 807874.2359 751188.741 701319.095 726587.6405 767889.7629 saccharopine 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 S-adenosylhomocysteine 11592984.39 6897685.144 7933114.67 9016589.568 8509403.395 11664427.21 9505792.335 13709408.85 12323433.6 12576169.03 8459991.872 11114917.11 9457642.89 10401178.13 8439391.017 S-adenosylmethionine 155285793 128334608.8 112786605 116059120.5 107708126.2 89591477.1 79533251.28 74545912.29 99313168.57 118037683.5 67534975.34 74608741.17 80449204.24 104152943.7 92894482.18 SAICAR 0 0 0 0 0 2445340.409 2350865.094 2727258.705 2570080.099 3429134.919 0 0 0 0 0 sarcosine 4618924.333 5586212.64 3900368.544 3591286.087 3651057.03 4171441.499 4961806.335 2858027.39 2797116.085 3103718.043 4568220.525 4456746.949 4732401.122 3611174.045 3840869.018 sedoheptulose 7-phosphate 6079159.228 4162215.88 4697995.818 5027200.843 4960102.362 6000406.028 6198800.664 6325095.993 6163839.595 6945005.859 2567700.217 2055776.365 2017452.872 2069980.003 2403690.683 serine 62982591.05 51486260.54 55632750.33 48944185.95 49446959.73 28387831.94 25157756.92 26032511.22 22260323.18 27448841.19 8969193.239 9648254.448 10619435.37 7502100.759 8322329.758 S-lactoylglutathione 3014623.998 1857603.458 2014033.841 1827221.371 1690927.949 1979715.117 1806620.731 1731096.461 1598172.141 2170234.574 4505277.323 4414250.871 4035594.272 3417033.63 4024903.187 succinate 116510308.7 77996417.38 91084693.64 85315360.92 93119277.35 46045208.48 44023031.69 43051117.63 30153726.06 53159023.35 85532616.98 71979674.82 70112629.08 62075496.59 72760845.72 succinyladenosine 0 0 0 0 0 7403533.197 6680919.625 7371430.076 6923266.769 9570632.067 385842.13 554819.1409 586274.4903 472063.0313 710944.9734 succinylcarnitine 932565.2442 534617.6596 712045.0681 1180359.378 966799.7984 1715142.746 1414949.949 1973443.008 1479941.236 2106215.062 2370663.854 2269595.616 2188681.695 1934070.526 2244718.681 succinylglutathione 642338.2886 473673.7437 495735.9347 469968.8344 472470.8238 544511.2497 386256.1804 453741.8259 388432.1989 540443.5208 807874.2359 751188.741 701319.095 726587.6405 767889.7629 taurine 1607779076 1136638605 1323038046 1170491921 1229824652 1818001610 1588127359 1708801081 1429931158 1816006509 1769802643 1689440767 1659008542 1416081668 1629142731 thiamine 29870108.43 7039058.56 21681860.8 19619432.32 20833542.58 39017876.53 25520829.53 34663810.13 18469580.04 32993121.35 85417780.99 60531384.51 49084312.62 37271564.53 57057498.39 threonine 381916606.9 277704187 304373703.8 298630051.1 296797462.1 206536777 180572107.9 204009981.1 170237758.8 208484882.8 140463886.8 136838642.3 142011944.6 115326876.7 126691530 trimethyllysine 34666303.76 17575929.51 22945995.1 23507566.01 21972302.75 27515392.32 22196909.8 24539870.22 22075621.04 31140111.13 40570167.94 41129974.17 38940484.72 36265951.15 39360667.4 tryptamine 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 tryptophan 54155432.08 34314687.32 38141613.73 36261198.18 37968201.05 32039204.2 27558290.95 32295541.57 21344356.22 34486399.66 21170941.47 20511693.53 22389300.04 17675205.32 19648484.53 tyrosine 247687635.4 162986860.2 184614605.7 172694621.6 172431360.5 151882659.9 117052127.3 142308036.5 112064707 160173215.2 170013756.5 160573999 162191241.7 142232558.5 155637496.9 UDP 76256398.06 55557222.67 54519063.75 58649500.03 62073471.94 40409342.55 38844515.44 41127371.95 42126938.16 53840213.49 25796576.34 33762440.38 31582697.19 34873447.2 31690561.32 UDP-GlcNac 237367557.7 163258784.6 175978251.7 182994022.6 184037760.8 103904680.7 90020119.04 103922982.9 93664832.55 119036424.5 130765022.7 129046476.5 124965960 121408263.3 126766337.6 UDP-glucose 143958144.1 117828304.4 109474749.4 117140828.8 111463161.7 66049677.16 63871275.68 71345331.58 67516785.09 83192306.08 36422373.76 36080011.13 35341665.72 37057253.44 38637242.79 UDP-hexose 144095825.3 117828304.4 109511309.1 117159364.5 111469686.8 66075595.34 63871275.68 71353145.38 67516785.09 83192306.08 36422373.76 36080011.13 35341665.72 37057253.44 38637242.79 UMP 35773053.82 8193555.977 16733069.81 16678022.35 26315544.46 17951526.58 13146385.89 20375269.97 8640981.325 22914910.6 10484978.83 17141054.17 14866242.83 9432829.794 9454323.321 uric acid 26952928.3 17387781.05 20745500.22 34114696.05 20389015.89 19625424.58 16669455.68 18769251.14 14745850.77 21842685.36 28105178.14 27283911.9 26080078.73 22840088.05 26324765.24 uridine 18756872.14 7248665.873 10578814.6 8703349.092 6186801.289 3563036.642 1783861.294 4200795.683 2573253.682 3356842.579 1825492.745 3132996.824 2681622.759 2477661.482 1679387.561 UTP 49362519.98 63588688.7 48222242.22 49828539.63 39643354.33 25980201.95 27090512.39 21852817.86 38024072.87 37338379.88 20246546.04 17711664.24 17748860.49 30743917.31 28588783.22 valine 344109377.2 221875731.9 267069581.4 233869552.2 247849268.9 206099637.7 155504341.3 161878467.8 149967788.6 272489684.1 215559287.9 170162660.6 195988316.6 151375144.2 184256998.3 valine-d8 2309257657 2062899074 2331030780 2358167770 2257841149 2414160655 2144547322 2264761497 2347226053 2239247311 2389728504 2316647295 2317757228 2325470461 2387514145 xanthine 82818616.47 48719914.29 60302862.45 47589514.71 54173370.86 58007057.05 47071080.97 50883451.71 14855707.47 55526867.61 60291191.93 56589806.26 55761311.4 30027821.96 52661890.14 MS_METABOLITE_DATA_END #METABOLITES METABOLITES_START metabolite_name PubChem ID Kegg ID 2/3-phosphoglycerate 59/724 C00631/C00597 2-aminoadipic acid 92136 C00956 2-hydroxyglutarate 43 C02630 2-ketoglutarate 51 C00026 acetylcarnitine 439756 C02571 acetylcholine 187 C01996 adenosine 60961 C00212 ADP 6022 C00008 ADP-ribose 192 C00301 alanine 5950 C00041 AMP 6083 C00020 arginine 6322 C00062 argininosuccinate 16950 C03406 asparagine 6267 C00152 aspartate 5960 C00049 aspartylglucosamine 134129131 - ATP 5957 C00002 beta-alanine 239 C00099 beta-citrylglutamic acid 254741242 C20775 betaine 248 C00719 butyrylcarnitine 213144 - cAMP 6076 C00575 carnitinamide 5346 C02290 carnitine 10917 C00318 carnosine 439224 C00386 CDP 6132 C00112 choline 305 C00114 cis-aconitate 643757 C00417 citicoline 13805 C00307 citrate 311 C00158 citrulline 9750 C00327 CMP-acetylneuraminic acid 448209 C00128 creatine 586 C00300 creatinine 588 C00791 cyclic ADP-ribose 22062770 C13050 Cys-Gly 439498 C01419 cystathionine 439258 C02291 cytidine 6175 C00475 dihydroorotate 439216 C00337 dihydroxyacetone phosphate 668 C00111 dimethylarginine 123831 C03626 dimethyllysine 4478779 C05545 dTTP 64968 C00459 fructose 6-Phosphate 439160 C00085 fumarate 444972 C00122 GDP 8977 C00035 GDP-glucose 135398656 C00394 gluconate 10690 C00257 glucose 6-phosphate 5958 C00092 glucuronic acid 444791 C00191 glutamate 33032 C00025 glutamine 5961 C00064 glutamylproline 11218768 - glutathione 124886 C00051 glyceraldehyde 3-phosphate 439168 C00118 glycerol 3-phosphate 439162 C00093 glycerophosphoethanolamine 123874 C01233 glycerophosphoinositol 45480545 C01225 glycerylphosphorylcholine 439285 C00670 glycine 750 C00037 glycylglycine 11163 C02037 GMP 6804 C00144 GTP 135398633 C00044 guanine 764 C00242 guanosine 6802 C00387 histidine 6274 C00135 homoarginine 9085 C01924 hydroxyphenyllactate 9378 C03672 hydroxyproline 440015 C01015 hydroxytrimethyllysine - - hypotaurine 107812 C00519 hypoxanthine 790 C00262 IMP 8582 C00130 inosine 6021 C00294 isoleucine 6306 C00407 isovalerylcarnitine C5 - - ketoleucine+ketoisoleucine 70 C00233 ketovaline 49 C00141 kynurenine 161166 C00328 lactate 107689 C01432 leucine 6106 C00123 lysine 5962 C00047 malate 92824 C00497 methionine 6137 C00073 methionine sulfoxide 847 - N-acetylarginine 67427 - N-acetylaspartate 65065 C01042 N-acetylaspartylglutamate 188803 C12270 N-acetylglutamate 70914 C00624 N-acetylneuramic acid 445063 - N-acetylornithine 439232 C00437 N-acetylserine 65249 - NAD 5892 C00003 NADP 5885 C00006 NADPH 5884 C00005 N-carbamoylaspartate 93072 C00438 N-carbamoylglutamate 121396 - nicotinamide riboside 439924 C03150 ophthalmic acid 7018721 C21016 ornithine 6262 C00077 orotate 967 C00295 orotidine 92751 C01103 oxidized glutathione 65359 C00127 pantothenate 6613 C00864 phenylalanine 6140 C02057 phosphocholine 1014 C00588 phosphocreatine 587 C02305 proline 145742 C16435 propionylcarnitine 107738 C03017 propionylcholine 75612 - pyroglutamic acid 7405 C01879 pyruvate 1060 C00022 S-(2-succinyl)cysteine 25060473 - S-(2-Succinyl)glutathione - - S-adenosylhomocysteine 439155 C00021 S-adenosylmethionine 34756 C00019 sarcosine 1088 C00213 sedoheptulose 7-phosphate 616 C05382 serine 5951 C00065 succinate 1738118 C00042 succinyladenosine 20849086 - taurine 1123 C00245 thiamine 1130 C00378 threonine 6288 C00188 trimethyllysine 440121 - tryptophan 6305 C00078 tyrosine 6057 C01536 UDP-GlcNac 445675 C00043 UDP-glucose 8629 C00029 UMP 6030 C00105 uric acid 1175 C00366 uridine 6029 C00299 UTP 6133 C00075 valine 6287 C16436 valine-d8 90969676 - xanthine 1188 C00385 4-guanidinobutanoate 500 C01035 acetyl-CoA 444493 C00024 adenylosuccinate 447145 C03794 aminobutyrate 119 C00334 CDP-ethanolamine 123727 C00570 C-glycosyltryptophan 21775807 - CMP 6131 C00055 CTP 6176 C00063 cysteic acid 25701 C00506 cystine 67678 C00491 deoxycytidine 13711 C00881 deoxyribose 5-phosphate 45934311 - ethanolamine phosphate 1015 C00346 FAD 643975 C00016 fructose 1,6-bisphosphate 10267 C05378 glutamylcysteine 10171468 C00669 glycerophosphorylcholine 657272 D07349 glycerophosphoserine 3081457 C22237 guanidineacetic acid 763 C00581 hydantoin-5-propionic acid 782 C05565 indole 798 C00463 inositol 892 C00137 N-acetylhexosamine phosphate - - N-acetylhistidine 75619 C02997 NADH 439153 C00004 phosphoenolpyruvate 1005 C00074 phosphoethanolamine 1015 C00346 phosphorylcholine 7886 C00588 quinolinic acid 1066 C03722 saccharopine 160556 C00449 SAICAR 160666 C04823 S-lactoylglutathione 119450 C03451 succinylcarnitine 131802075 - succinylglutathione 439932 C03174 tryptamine 1150 C00398 UDP 6031 C00015 UDP-hexose 1166 - METABOLITES_END #END