#METABOLOMICS WORKBENCH riverup_20230405_193420 DATATRACK_ID:3845 STUDY_ID:ST002541 ANALYSIS_ID:AN004186 PROJECT_ID:PR001637 VERSION 1 CREATED_ON April 6, 2023, 11:09 am #PROJECT PR:PROJECT_TITLE The metabolomics analysis of Methionine restriction PR:PROJECT_TYPE targeted metabolomics data PR:PROJECT_SUMMARY Methionine restriction (MR) provides metabolic benefits in many organisms. PR:PROJECT_SUMMARY However, mechanisms underlying the MR-induced effect remain incompletely PR:PROJECT_SUMMARY understood. Here, we show in the budding yeast S. cerevisiae that MR relays a PR:PROJECT_SUMMARY signal of S-adenosylmethionine (SAM) deprivation to adapt bioenergetic PR:PROJECT_SUMMARY mitochondria to nitrogenic anabolism.In particular, decreases in cellular SAM PR:PROJECT_SUMMARY constrain lipoate metabolism and protein lipoylation required for the operation PR:PROJECT_SUMMARY of the tricarboxylic acid (TCA) cycle in the mitochondria, leading to incomplete PR:PROJECT_SUMMARY glucose oxidation with an exit of acetyl-CoA and -ketoglutarate from the TCA PR:PROJECT_SUMMARY cycle to the syntheses of amino acids, such as arginine and leucine. This PR:PROJECT_SUMMARY mitochondrial SAM-induced response, namely mitoSIR, promotes cell fitness PR:PROJECT_SUMMARY through the coordination of mitochondrial fuel metabolism with the nitrogenic PR:PROJECT_SUMMARY synthesis of amino acids. PR:INSTITUTE Life Sciences Institute, ZheJiang University PR:LAST_NAME Cunqi PR:FIRST_NAME Ye PR:ADDRESS 866 Yuhangtang Rd, Hangzhou 310058, P.R. China PR:EMAIL yecunqi@zju.edu.cn PR:PHONE 15267181160 #STUDY ST:STUDY_TITLE Methionine restriction constrains lipoylation and activates mitochondria for ST:STUDY_TITLE nitrogenic synthesis of amino acids (Part 1) ST:STUDY_SUMMARY Methionine restriction (MR) provides metabolic benefits in many organisms. ST:STUDY_SUMMARY However, mechanisms underlying the MR-induced effect remain incompletely ST:STUDY_SUMMARY understood. Here, we show in the budding yeast S. cerevisiae that MR relays a ST:STUDY_SUMMARY signal of S-adenosylmethionine (SAM) deprivation to adapt bioenergetic ST:STUDY_SUMMARY mitochondria to nitrogenic anabolism. In particular, decreases in cellular SAM ST:STUDY_SUMMARY constrain lipoate metabolism and protein lipoylation required for the operation ST:STUDY_SUMMARY of the tricarboxylic acid (TCA) cycle in the mitochondria, leading to incomplete ST:STUDY_SUMMARY glucose oxidation with an exit of acetyl-CoA and -ketoglutarate from the TCA ST:STUDY_SUMMARY cycle to the syntheses of amino acids, such as arginine and leucine. This ST:STUDY_SUMMARY mitochondrial SAM-induced response, namely mitoSIR, promotes cell fitness ST:STUDY_SUMMARY through the coordination of mitochondrial fuel metabolism with the nitrogenic ST:STUDY_SUMMARY synthesis of amino acids. ST:INSTITUTE Life Sciences Institute, ZheJiang University ST:LAST_NAME Cunqi ST:FIRST_NAME Ye ST:ADDRESS 866 Yuhangtang Rd, Hangzhou 310058, P.R. China ST:EMAIL yecunqi@zju.edu.cn ST:PHONE 15267181160 #SUBJECT SU:SUBJECT_TYPE Yeast SU:SUBJECT_SPECIES Saccharomyces cerevisiae SU:TAXONOMY_ID 4932 SU:GENOTYPE_STRAIN CEN.P.K #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 - met6KO_0h_1 Sample Type:0h RAW_FILE_NAME=met6KO_0h_1.wiff SUBJECT_SAMPLE_FACTORS - met6KO_0h_2 Sample Type:0h RAW_FILE_NAME=met6KO_0h_2.wiff SUBJECT_SAMPLE_FACTORS - met6KO_0h_3 Sample Type:0h RAW_FILE_NAME=met6KO_0h_3.wiff SUBJECT_SAMPLE_FACTORS - met6KO_2h_1 Sample Type:2h RAW_FILE_NAME=met6KO_2h_1.wiff SUBJECT_SAMPLE_FACTORS - met6KO_2h_2 Sample Type:2h RAW_FILE_NAME=met6KO_2h_2.wiff SUBJECT_SAMPLE_FACTORS - met6KO_2h_3 Sample Type:2h RAW_FILE_NAME=met6KO_2h_3.wiff SUBJECT_SAMPLE_FACTORS - met6KO_4h_1 Sample Type:4h RAW_FILE_NAME=met6KO_4h_1.wiff SUBJECT_SAMPLE_FACTORS - met6KO_4h_2 Sample Type:4h RAW_FILE_NAME=met6KO_4h_2.wiff SUBJECT_SAMPLE_FACTORS - met6KO_4h_3 Sample Type:4h RAW_FILE_NAME=met6KO_4h_3.wiff SUBJECT_SAMPLE_FACTORS - met6KO_6h_1 Sample Type:6h RAW_FILE_NAME=met6KO_6h_1.wiff SUBJECT_SAMPLE_FACTORS - met6KO_6h_2 Sample Type:6h RAW_FILE_NAME=met6KO_6h_2.wiff SUBJECT_SAMPLE_FACTORS - met6KO_6h_3 Sample Type:6h RAW_FILE_NAME=met6KO_6h_3.wiff SUBJECT_SAMPLE_FACTORS - met6KO_15h_1 Sample Type:15h RAW_FILE_NAME=met6KO_15h_1.wiff SUBJECT_SAMPLE_FACTORS - met6KO_15h_2 Sample Type:15h RAW_FILE_NAME=met6KO_15h_2.wiff SUBJECT_SAMPLE_FACTORS - met6KO_15h_3 Sample Type:15h RAW_FILE_NAME=met6KO_15h_3.wiff #COLLECTION CO:COLLECTION_SUMMARY Care was taken to quench cells quickly in -40℃ and maintain metabolites in CO:COLLECTION_SUMMARY acid to minimize oxidation CO:SAMPLE_TYPE Yeast cells #TREATMENT TR:TREATMENT_SUMMARY Mutant MET6KO cells were cultured in SD medium with the supplements of Met and TR:TREATMENT_SUMMARY growed to log phase, then cells were washed with normal SD medium and TR:TREATMENT_SUMMARY re-cultured in SD medium #SAMPLEPREP SP:SAMPLEPREP_SUMMARY Briefly, equal OD units of cells were rapidly quenched to stop metabolism by SP:SAMPLEPREP_SUMMARY addition into 4 volumes of quenching buffer containing 60% methanol and 10 mM SP:SAMPLEPREP_SUMMARY Tricine, pH 7.4 that was pre-cooled to -40°C. 5 min after holding at -40°C, SP:SAMPLEPREP_SUMMARY cells were spun at 5,000 g for 3 min at 0°C, washed with the same buffer, and SP:SAMPLEPREP_SUMMARY then resuspended in 1 mL extraction buffer containing 75% ethanol and 0.5 mM SP:SAMPLEPREP_SUMMARY Tricine, pH 7.4. Intracellular metabolites were extracted by incubating at 75°C SP:SAMPLEPREP_SUMMARY for 3 min, followed by chilling on ice for 5 min. Samples were spun at 20,000 g SP:SAMPLEPREP_SUMMARY for 1 min to pellet cell debris, and 0.9 mL of the supernatant was transferred SP:SAMPLEPREP_SUMMARY to a new tube. After a second spin at 20,000 g for 10 min, 0.8 mL of the SP:SAMPLEPREP_SUMMARY supernatant was transferred to a new tube. Metabolites in the extraction buffer SP:SAMPLEPREP_SUMMARY were dried using a vacuum concentrator system (Labconco) and stored at -80°C SP:SAMPLEPREP_SUMMARY until analysis. Dried metabolite extracts were resuspended in 60% acetonitrile SP:SAMPLEPREP_SUMMARY for injection. #CHROMATOGRAPHY CH:CHROMATOGRAPHY_SUMMARY Low pH polar CH:CHROMATOGRAPHY_TYPE HILIC CH:INSTRUMENT_NAME Shimadzu 20AD CH:COLUMN_NAME Merck SeQuant ZIC-pHILIC (150 x 2.1mm,5um) CH:SOLVENT_A 20 mM ammonium carbonate and 0.1% (v/v) ammonium hydroxide CH:SOLVENT_B acetonitrile CH:FLOW_GRADIENT 0.01 min 80% B, 20 min 20% B, 20.5 min 80% B, 34 min 80% B. CH:FLOW_RATE 0.15ml/min CH:COLUMN_TEMPERATURE 45 #ANALYSIS AN:ANALYSIS_TYPE MS #MS MS:INSTRUMENT_NAME ABI Sciex 6500+ MS:INSTRUMENT_TYPE QTRAP MS:MS_TYPE ESI MS:ION_MODE POSITIVE MS:MS_COMMENTS SCIEX OS #MS_METABOLITE_DATA MS_METABOLITE_DATA:UNITS Peak intensity MS_METABOLITE_DATA_START Samples met6KO_0h_1 met6KO_0h_2 met6KO_0h_3 met6KO_2h_1 met6KO_2h_2 met6KO_2h_3 met6KO_4h_1 met6KO_4h_2 met6KO_4h_3 met6KO_6h_1 met6KO_6h_2 met6KO_6h_3 met6KO_15h_1 met6KO_15h_2 met6KO_15h_3 Factors Sample Type:0h Sample Type:0h Sample Type:0h Sample Type:2h Sample Type:2h Sample Type:2h Sample Type:4h Sample Type:4h Sample Type:4h Sample Type:6h Sample Type:6h Sample Type:6h Sample Type:15h Sample Type:15h Sample Type:15h Urea 940986.3436 769611.7903 842261.4398 718109.7533 899621.9125 863348.7546 880729.1284 887198.6118 630411.5278 635595.5685 681972.15 793087.2237 1004964.974 859400.0124 808811.8004 Ethanolamine 41419.87897 93641.94105 57108.74191 41232.54481 112299.3596 111903.1814 132868.5871 260648.061 703840.8838 421327.1959 423218.222 82956.96875 1808354.639 1560356.386 1214869.208 Imidazole 83854.58409 70615.88886 87802.644 76472.90476 41146.91481 23853.88061 126038.0686 112574.2662 135466.6357 195054.4691 158544.7607 99610.54525 166696.1622 118237.1282 3039198.493 Glycine 39244.21653 33776.88712 31571.9719 39102.52561 28702.30232 38939.70043 35452.4511 32281.27242 40422.09532 30138.53743 32766.65106 33261.95516 35879.346 39225.9698 28247.89074 L-Alanine 956632.1516 2174848.456 2868374.626 960325.0417 1150442.786 3903602.289 13389626.88 22351591.66 30727769.27 28299322.05 27878207.01 3844375.233 29214946.96 21928348.69 22258604.69 Betaine aldehyde 244152058.9 177027005.6 300817001.9 208188638.2 217241835.9 324799595.5 229554858.1 244270163.4 229692666.3 186263743.4 181002595 304167123.9 317497870.5 310113540.7 241625319.1 Choline 3317150.567 8296350.888 2084853.41 4836491.404 3654449.353 4344764.82 2538602.502 5380786.709 42875422.65 4628607.778 1753462.403 1867362.619 12183953.46 6458091.295 9682907.683 Gamma-Aminobutyric acid 26171.96177 35472.43533 36895.95577 43807.38492 59739.54464 47242.25519 112864.7495 243160.8277 502103.9979 247847.5436 275967.3705 41308.80013 407628.2177 310022.4238 290775.835 Dimethylglycine 101159.5362 95550.8156 71254.3111 112172.2109 90791.75805 157642.0257 142953.1286 224871.355 166658.9512 312518.9481 325801.5117 109433.7388 736625.738 746070.4415 604296.4442 Serine 952224.6015 1996194.362 1841603.73 2015972.963 2200246.215 4465453.747 5012648.501 7381877.638 11567343.15 7349741.407 8830275.9 1971074.022 6271578.187 6849542.545 6528440.317 Cytosine 1072944.178 750030.417 1123147.933 1204583.288 837431.7861 484458.9229 999072.1394 1510442.224 1131615.792 2144625.447 1212842.986 560022.7367 730158.1981 1017927.636 721616.4508 Creatinine 375608.9844 1692319.768 404931.1375 712550.2096 784232.8963 653854.8255 317390.6941 829007.4337 4740648.71 610424.1131 482183.3784 537827.9191 789652.6183 645298.2072 1195122.537 L-Proline 5582870.113 14325150.33 11617836.33 10858571.99 13122305.13 35074727.88 124477834.6 158576883.4 241977530.2 231683793.4 178958666 14807968.76 296254583.8 280790796.8 238045883.3 Indole 39480.15191 74340.51011 72957.13317 132185.2835 143199.2753 400063.9467 740908.0804 881547.2784 1129810.524 918372.174 1086412.834 65855.69715 893443.3281 900879.2205 889721.566 Betaine 41355005.88 54431660.69 103430682.9 48757033.6 58340840.01 41746853.57 36455168.25 96431439.92 755099863.5 66046712.61 43602014.81 31525979.87 137805141.6 202768772.8 92261437.39 L-Valine 39140.77515 158515.3151 87763.62857 316228.9939 337917.9137 1248155.033 2972319.025 3788638.242 4896559.025 5016900.235 5517450.458 92990.18168 6580029.567 5514710.718 5532159.901 L-Threonine 1698833.618 4059408.111 4872451.976 3308171.013 3377492.378 8720692.11 18989435.57 24270588.15 31075161.91 31350617.01 34007310.16 5027611.601 46808270.86 37407059.17 38228009.35 L-Homoserine 80533.34135 155321.9047 276030.1466 54410.70444 49678.06505 125856.6843 197836.8176 313468.7032 278300.9337 358714.0333 395086.4386 239776.8547 310574.8862 265426.9216 220251.4212 Purine 70245.18373 194818.2319 84285.16546 163063.3367 97494.16317 427195.3752 936155.9332 1165687.544 2539279.778 1626945.609 1750412.258 118157.3091 1748107.542 1590414.735 1486375.351 L-Cysteine 10632.92265 3334.893879 5875.566689 8967.006271 7154.905346 13169.56135 6438.324402 8269.884683 6170.938019 10241.23811 11675.7184 8747.235588 8556.704026 6529.623371 5763.739843 Creatine 368093.2092 1533573.738 492587.274 608835.4536 1013698.004 641124.3499 510481.3737 780361.6044 3366759.158 587362.6984 484740.9793 581667.0979 1011186.951 714131.2376 963426.1524 Niacinamide 1458796.815 2490459.775 1284490.355 2210428.798 1671272.91 1283279.499 3652095.542 5336531.409 4213284.932 8128384.244 9636665.333 1294767.688 2983430.448 3066946.711 3907686.744 Imidazoleacetic acid 325985.2293 424383.4051 431591.7132 379864.6665 419382.2293 436114.3861 1365486.775 1864075.163 1832870.033 2336152.78 3514166.282 564762.4289 2899150.639 3060633.028 2245330.061 Thymine 84054.9913 72622.85007 59727.82943 96417.76563 51867.23219 40854.22799 74655.2409 100337.5674 94351.4492 158256.6446 165394.4837 119069.3283 63315.0518 126680.5531 141347.101 Pipecolic acid 20119500.36 56676294.83 71480926.47 131411039.9 131976702.4 389295864.1 633518274.1 820119581.6 754153338.9 861611605.1 912475515.6 81915795.08 821937982.7 783638841 697234262 N-Acetylputrescine 161119.7421 931319.6233 1165350.951 549132.6037 915417.671 1691432.011 3912082.525 8675576.682 7477254.332 5649224.256 8091068.876 1290675.506 26071616.94 25417351.88 24635516.01 Hydroxyproline 1834173.683 1728707.811 1576754.637 1734630.71 1647637.513 1794139.08 1674351.883 1769419.335 1664147.649 1754635.33 1967650.122 1591401.715 1849094.25 1875349.355 1803887.116 L-Leucine 4462792.831 22887513.39 8145995.922 14625930.36 14597239.65 55039869.66 89523802.75 121253084.4 271314253.7 187972768.6 232967807 9763379.138 352506892.2 314251582.6 295842627.6 Ornithine 3148453.236 5494366.403 4180290.471 5560072.535 6469784.285 9153524.181 17715748.78 24896686.34 24668707.28 26709518.44 27317727.3 5831203.624 47542625.99 43754909.64 36597546.79 L-Asparagine 224844.083 741084.3831 795897.5207 657592.7449 717256.7211 1893176.447 3783422.165 5103226.03 6701990.667 4732495.915 5518298.896 875650.3435 5227856.168 4479114.654 3884746.868 L-Aspartic acid 944595.0701 3057838.008 3253083.587 3944409.377 3764799.879 10843048.13 21000609.35 26275357.38 30858452.17 23874219.03 25067030.88 3346322.173 12750387 13521968.18 12032240.02 Adenine 64012974.14 92900288.1 80360886.3 25767661.01 24589226.52 32675487.91 19659426.5 33886809.01 105668983.7 22725999.39 26811501.58 86536364.2 10179513.46 10328506.95 16121831.25 Methylcysteine 210687.0205 830740.3336 630154.5936 1568345.208 1590359.9 4668032.499 8206744.579 9933953.48 12373838.04 11192002.2 10554090.62 697390.428 16418900.74 13348945.75 13729045.87 Homocysteine 4738.510555 11594.37346 20297.87672 12477.34206 19485.9705 71894.06734 125622.3417 200474.767 320997.7415 142759.7807 230246.7515 19029.20687 80503.01782 62293.25748 N/A 1-Methylnicotinamide 61369.43183 163968.6353 148829.1857 158374.4939 135426.7711 370990.1593 5050185.718 5807749.966 5489744.572 8609795.085 10927300.89 121943.2726 8028309.049 7084124.364 7574598.653 L-Histidinol 133393.6503 121657.3415 100545.0231 105749.2171 117235.8965 156813.7709 108480.3213 221591.2032 155062.5649 137153.8386 154759.0715 280808.5158 53569.76818 100583.6522 69046.6523 L-Lysine 296459.1399 590962.5956 550409.4555 864823.8177 1039581.049 1240729.796 4114613.245 5519631.575 6361841.586 5511057.49 6447175.283 717319.6311 6656584.269 6247617.223 5114118.421 L-Glutamine 3844414.724 10507458.49 15353473.65 46472214.96 45062429.62 138493166 219392252.8 277275424.5 273006947.5 306487212.9 340741405.9 18454791.29 317854105.2 301189190.4 267911231.4 O-Acetylserine 47428.28841 42606.81317 14703.85883 51547.35235 25597.82293 23825.24624 19260.91915 38529.82197 64201.93575 82364.04675 79248.45828 16480.33786 22990.92014 49032.18284 51307.31238 L-Glutamic acid 17430520.05 56946684.62 52594282.01 74904994.2 73040433.36 180259604.7 331025871.2 403275401.8 426551659 383273090.3 435509368.7 65493311.93 311868228.9 292776827.8 254400701.7 L-Methionine 29794634.6 50311725.94 89319867.1 404878.8386 518047.277 470543.027 578453.2503 797698.7933 7752656.286 1456181.074 1002655.687 111997571.9 1380820.314 1321176.475 1491510.505 Guanine 1867898.12 426415.8797 613646.7558 537903.631 530918.4135 572126.1348 7153970.232 8348005.191 5636790.688 5825308.794 6290580.235 468959.0381 2725479.946 2923801.831 2404665.811 L-Histidine 43645861.18 80388545.02 90649000.25 119801451.4 138738381 257839079.3 545316651.6 716332547.3 672934587.7 785958064.2 935186276.8 164420131.9 1087542206 1044870579 940021545.4 DL-2-Aminooctanoic acid 3443.861249 23182.6766 4427.395899 6852.864619 37513.89279 9510.854056 11736.59211 23117.28456 109317.7302 21049.86308 21715.0489 9341.551958 44009.12235 31298.89422 39771.26834 Carnitine 948448.8759 2593021.26 951548.8077 946584.4217 1317919.152 1259082.019 1961167.092 2809069.184 9363768.968 2254549.936 2412254.67 997487.5722 1874293.525 1901696.368 1983636.999 Methionine sulfoxide 4915192.621 10254624.49 25153841.34 253992.5025 355718.3623 433258.602 229759.9806 474842.3966 8135251.979 560438.2803 694338.8046 11925201.18 641289.9859 748293.4149 1039996.363 L-Phenylalanine 1338105.242 8412312.62 3585449.618 6274740.316 6132252.827 19713785.04 36280208.22 53552371.17 116900631.2 75726762.09 81447257.58 3971980.317 89126880.45 75043929.99 77326931.47 Pyridoxamine 9876.130864 21573.53848 31890.57436 9948.048969 49533.40346 22952.26929 10513.41653 29474.57784 65149.84658 21611.07879 46796.45289 56676.50269 22664.80112 21534.98655 77276.70302 Pyridoxine 851750.8106 376288.9577 373889.4098 158507.1085 136505.3534 230581.2341 166790.1716 405247.763 1448154.179 393364.6788 744083.4131 425372.7851 513473.9572 737227.5326 763257.0173 1-Methylhistidine 58665.336 88716.00892 150554.2696 5808.287809 13855.75486 34427.33913 62864.87572 61948.76958 84587.24523 51854.4819 79973.86828 102211.2561 67683.50462 36753.45606 50231.9982 N-Acetylornithine 2462632.847 7244160.089 6864879.424 3838965.58 3489725.553 9192083.428 10545264.81 13879321.41 11601719.07 12292791.18 13293483.03 7995969.97 18087403.63 14046476.31 13966923.91 L-Arginine 35704429.5 60052457.48 51520721.76 70429561.03 78236499.7 104736176.2 215970282.6 269211854.3 274956937.4 279105654.1 299651481.7 71508015.11 314353289 314458466.3 244366635.3 Citrulline 6958796.426 19435102.92 19386348.95 12190124.87 12412154.26 32421165.88 31962653.76 41439552.73 41770105.51 24634712.83 34456285.56 27842848.13 13086693.53 12374622.9 10356531.41 Ureidosuccinic acid 94218.30272 184902.0286 150707.327 82499.15457 78141.7022 138055.2148 193385.0488 209481.0045 379997.1 193631.4599 172961.6663 197283.8776 83566.06312 88094.30246 89547.86142 Glucosamine 1325098889 1148101199 1194451732 1223483109 1174059697 1309729204 1339037911 1347336187 1281331224 1300514304 1350553540 1238611046 1248343287 1385334641 1258823543 L-Tyrosine 230571.114 934922.4146 693082.0197 1725813.92 1739308.095 5295238.65 9641234.464 11046554.17 14430897.84 12945664.76 12078256.88 875150.069 18124687.71 15811692.95 14241915.11 Phosphorylcholine 93814.02145 356305.6606 160466.4583 144586.344 130981.0187 156172.7136 207826.9483 358645.5563 3797713.047 573221.6277 438815.8969 249857.5806 327168.0022 323950.3254 451366.5503 DL-O-Phosphoserine 11421.32361 16590.70961 11215.98707 21638.38505 12487.36806 18838.84257 10685.78014 11087.92273 10567.32504 10267.99785 11717.5377 10565.81181 4214.204863 9517.314214 3127.405217 N6-Acetyl-L-lysine 3101685.496 9769550.991 9996323.023 6933310.087 6776714.17 20620878.1 50071461.57 54316592.29 53418600.03 70974110.48 61618141.58 10948552.37 76103447.3 72940045.82 62818362.63 N-Alpha-acetyllysine 2381179.714 7398618.562 7627138.764 5766832.648 5592453.15 15582383.14 40567983.73 40115378.89 43027544.75 50048613.18 46841278.5 9307786.399 56326511.95 54222954.8 51415361.31 N-Acetylglutamine 2163728.555 5081285.525 4947273.428 4628651.815 4313267.387 9369215.454 8068053.853 9257510.503 11368212.5 12228973.69 13583934 4793218.394 14393488.01 13535805.31 15422826.39 N-Acetylglutamic acid 1393372.724 2650341.309 2493157.064 1034025.595 1152774.028 2007512.266 2390361.537 3199204.089 2619435.846 3143353.572 3329359.205 3402935.26 3227508.545 2452157.702 2161066.718 Asymmetric dimethylarginine 224852.7618 491565.7823 473581.4544 204611.3488 278902.782 621409.1378 1004382.551 1266639.212 1148628.985 1321877.719 1344762.763 336295.654 3168511.482 3023742.154 2974113.667 L-Acetylcarnitine 855262.0846 1827609.666 1758713.648 1411129.35 1237820.462 2595423.325 3748906.985 3824554.935 4436059.953 4545563.023 5188903.806 1976959.513 4983954.786 4017264.7 4363325.09 L-Tryptophan 248356.347 621928.1479 540462.8911 1039700.358 1143336.427 3152695.789 7269078.122 8063522.807 9159599.062 7809161.578 9421504.576 643061.5937 8404984.475 7456993.938 7728588.966 L-Kynurenine 18800.31783 65848.25183 98629.10591 83612.24604 73468.61738 284061.1644 600596.8716 652913.428 821520.476 838968.9251 933088.2799 112789.3436 681546.3451 660352.7495 627771.5555 N-Acetyl-D-glucosamine 82683.96848 144102.9382 135685.3512 131232.853 102067.6674 211623.37 308665.0856 334243.607 314902.1064 365630.2773 444425.6316 137720.4981 268918.4028 294227.1274 265450.1649 Flavone 56584.18435 96141.90981 138457.5816 139845.2321 110672.8676 89005.70727 102514.7411 108974.8333 117933.5052 177664.7386 177198.3584 79051.01653 99487.1668 120804.4673 77498.94935 L-Cystathionine 1920656.994 3898716.454 3723901.562 847681.7205 764353.4138 1154396.052 1750451.339 2064062.232 1966404.427 1811584.424 1814062.212 3787317.349 931190.3949 1001777.623 925414.002 5-Methoxytryptophan 36869.40669 23703.11489 25306.78577 17950.1795 10031.74794 15997.56537 11945.1484 45992.75166 12282.23005 14047.26644 34660.01321 23340.1529 15104.54142 16483.6591 5436.376113 L-Cystine 2203.283848 N/A N/A N/A 2955.668607 N/A N/A N/A N/A N/A N/A N/A N/A 2084.056766 N/A Cytidine 721106.9886 2161172.262 1507619.92 2464861.889 2350275.897 7411388.927 55415581.89 69149573.07 57243120.91 54595912.53 61016083.5 2089722.245 9147113.638 8921360.034 7516574.863 Biotin 478225.2695 552346.3661 990883.7334 971305.1218 722120.24 3050423.259 1388775.634 1462091.738 1535028.363 1073331.606 960297.3735 942653.8924 162573.5067 94633.16679 232564.2431 Deoxyadenosine 734993.4085 942757.6781 1266022.69 1214027.432 1177245.649 2668856.974 3888140.604 4625842.962 5756912.459 4676083.853 6807124.798 1260848.521 4667080.926 3855624.42 4363969.02 Glycerophosphocholine 54094004.39 106063759.9 38401162.9 22849901.72 25697218.74 23534024.73 27288465.09 30434726.89 193676092.6 32107698.69 23787536.76 41059180.81 30511723.35 23523329.42 25667094.57 AICA-riboside 220701.0279 472663.4489 313544.4915 132597.3292 158913.6136 276023.5061 411818.0598 421882.1949 299659.726 542402.3578 659976.3645 473827.8983 370795.7955 348654.1723 257110.5553 Glucosamine 6-phosphate N/A N/A N/A 3526.297731 1813.034494 N/A 4060.717523 3518.591041 N/A N/A 13246.99601 N/A 6896.280705 N/A N/A Glucosamine-1P 13209.27444 6567.075094 12796.06739 14025.72548 7707.502839 19885.89062 5364.092139 11994.97637 17861.70897 10925.99415 24369.61016 12065.98964 9824.780089 19283.30781 21431.49079 Thiamine 109627471 290622363.5 297886868.4 132367781.2 151953539.6 284536197.3 221581483.7 314853404.6 343723593.8 215473686.8 240937323.4 253229085.5 257388299.2 194427995.4 210863946.3 S-Ribosyl-L-homocysteine 6923.011052 5409.062961 10141.47975 16611.95596 14191.81194 59945.37384 6745.374674 14899.59121 5695.289811 11901.39276 9842.325118 5550.745418 10173.86701 3998.038806 15873.00661 Deoxyguanosine 48338.9948 140301.7998 84318.62743 164738.7036 168342.021 257745.7617 1023913.764 934944.6968 904777.1313 615457.0783 765365.3773 111918.6355 305684.7766 271780.2006 239470.9724 Adenosine 35543712.43 29743601.1 23951755.31 22081553.64 19109177.95 26099935.22 31923989.07 49019836.89 496858924.2 53289723.29 41166235.42 38355623.59 23666112.41 26342317.7 55017523.14 1-Methyladenosine 2484638.236 4401541.789 4187442.508 3946162.001 3855902.123 6774911.731 16930900.21 15898977.17 13557081.86 29849751.61 21437868.75 4516291.173 58548072.27 60679811.21 46557805.18 Guanosine 91528.28535 125305.2321 100731.173 116312.1677 130551.3046 251729.1373 4380536.872 3995018.245 3762577.475 3938430.775 4407056.561 90152.61143 1590389.827 1639084.058 1521263.048 Argininosuccinic acid 500569.0756 863439.447 742782.1191 688127.9397 658451.731 1335996.398 1917616.8 2121253.699 4015963.985 2870418.181 2090039.024 738426.2452 1414722.871 1242796.421 2047732.595 5'-Methylthioadenosine 1020671812 1598160726 1044623842 334794835.3 224795691.1 225073117.4 220198021.8 330369711.2 264759629 299726058.8 299029463.3 1133395761 64190226.41 66660546.88 80008537.29 7-Methylguanosine 22352.75655 26402.72406 27110.48578 60625.15172 71836.22235 99043.70851 973404.5822 914304.6087 680217.6249 1077709.989 1477608.841 50972.99575 763065.401 772300.0434 584834.29 dCMP 19080.60269 37003.37353 25211.3941 20521.03954 27008.10672 52449.82463 37546.98964 57144.50117 66689.67151 35778.10594 53425.43908 28989.68694 36684.2692 34664.45628 28262.92662 Glutathione 20784616.03 61724983.5 33085710.76 9404215.816 8794992.576 24558124.71 26688272.87 22694916.37 24848646.6 24614823.72 12015398.72 51139267.47 18502580.24 7739861.492 12252869.04 5-Thymidylic acid 39705.48009 40345.11597 62585.36288 48989.21877 47815.04574 92389.26832 44334.28803 59625.59331 25287.65777 37803.9086 30242.14873 72327.5918 78050.63338 77867.27395 49092.00115 Cytidine monophosphate 510848.8079 1016480.536 755971.3982 453548.2847 417115.6724 809456.1066 1650459.061 1439300.216 2493263.85 1637167.794 1726545.617 843580.9206 679204.9794 614696.898 709805.9319 Uridine 5'-monophosphate 400678.5427 620631.7081 596430.0677 277313.3962 289134.6805 461228.6746 764355.6263 977952.504 1023207.127 1030153.274 1166662.053 565322.4829 865295.4697 894578.1021 1004187.771 Deoxyadenosine monophosphate 4992080.487 6829090.672 6516888.048 6691471.237 5030059.787 6489447.042 6689264.339 9282317.542 4353503.563 6996586.016 7785883.79 3777439.986 7208019.516 5197589.109 4372231.292 Nicotinamide ribotide 1402468.459 2173632.221 1580946.974 1477441.13 1461436.103 2525991.89 4145444.447 5982555.748 5562759.585 5230876.206 5783875.192 1996679.57 4648029.987 4788888.644 4747577.044 AICAR 281322.7033 412587.2827 333641.6252 129575.3951 108798.8541 150989.6336 83126.52579 132312.5648 113097.5096 119574.2681 103319.4205 304079.7539 53050.8696 74862.13259 72364.09364 Thiamine monophosphate 120767.0241 138024.336 98013.17159 172089.9264 171209.4925 190769.5855 192640.2213 339712.4634 222391.137 218490.9679 220161.1894 115632.9792 207077.0941 172546.7207 168711.8434 dGMP 27916.62815 16430.92036 32234.56265 19083.82498 34875.09657 31586.87496 60978.73278 18651.30876 39309.52689 42273.63955 51156.54779 28239.09976 49165.97252 32412.61827 16355.37875 Adenosine monophosphate 47521533 81765987.78 73687010.41 37508564.07 33699281.33 64992883.29 65964377.19 91372313.46 69531916.87 86877234.66 82501229.14 90019517.58 43087373.57 36224179.35 41486575.52 IMP 2761991.006 4594323.556 4273901.801 2256154.881 2116654.021 4217913.068 3958933.198 5115382.461 4141782.05 5272955.037 4549129.874 5108926.847 2149373.938 1973550.598 2480615.594 S-Adenosylmethioninamine 476591.0577 2067407.006 2867596.529 411929.468 514681.9078 846212.7381 1714274.83 2006539.568 3884126.71 1183561.049 1364747.716 2128957.593 600019.9145 548993.5502 577945.9105 GMP 1190909.327 1926881.96 1564903.51 710537.7777 789642.5396 1231259.299 1633402.969 2135936.492 2001844.951 1476708.634 1466120.952 1498567.26 708798.8444 838320.3833 834442.4148 Xanthylic acid 3912.992738 8860.913157 9821.840966 692.1959447 644.5223516 2301.601009 4215.498434 2037.071421 N/A 2633.988459 5022.377456 4066.118332 5979.626056 3375.684921 2134.05167 Riboflavin 406044.0692 422369.0555 415816.9728 486117.0655 403367.1704 525966.2163 720059.3533 662234.5814 986634.8557 618249.0086 807656.0669 366079.1707 496365.9577 345810.6843 369976.834 S-Adenosylhomocysteine 4636747.785 9382751.27 7915924.373 2547344.264 2378539.835 4035734.857 7708906.006 8486688.595 8201557.294 10435483.04 10337369.52 8217478.026 6655172.641 4593839.648 5428169.382 S-Adenosylmethionine 200195119.7 277297444.6 201181277.4 75568066.1 78496298.67 118618720 68749345.45 100048294.2 76064554.24 60955671.13 59576116.15 253650964.8 26242643.83 24343509.55 24272033.68 Folic acid 106881.5769 182471.1882 180230.6795 121738.6788 196311.8826 198577.7423 98789.12297 139764.5124 200087.9766 86584.11365 154187.8779 187034.1172 155024.8076 153581.0434 126406.2424 Dihydrofolic acid 18409.91823 16792.4248 17930.13177 21894.28299 16901.59154 24090.61061 16435.28443 22901.31498 32100.67139 22256.54278 16707.85593 29566.47655 19174.53172 25570.89412 16432.33381 5-Methyltetrahydrofolic acid 14725.97248 23566.78788 30067.54769 22866.90276 25637.31061 30923.01836 17429.41017 25988.13036 18907.23604 25213.85438 12517.41435 10183.68318 28351.84117 9903.795003 22355.2489 3,5-Diiodothyronine 6183.319035 11567.99262 13627.94565 7876.865557 14565.75129 9018.412026 6200.38065 7052.590251 7879.404861 5659.319465 10763.35417 16641.94998 4087.377672 9003.593641 18926.6963 Oxidized glutathione 5659249.654 10310555.44 11866426 4801686.91 4660298.575 7623701.365 9028994.78 12661591.39 14385878.21 9572088.552 14462245.53 8703903.648 8228158.184 9230999.29 7175379.165 NAD 110819351.2 119416586.6 116312467.3 121779146.5 115454851.7 116472524.2 143782990.2 185571050.1 143188067.6 157168496.8 158058243.7 94986592.83 162881238.5 126126621.1 119144908.9 NADH 18948080.96 26108427.75 24830051.66 14699199.44 15241036.12 26439671.3 21751102.5 23586540.56 36276874.48 32348573.4 26813676.99 26867422.26 12260269.73 11043328.66 12924583.7 Dephospho-CoA 406198.7427 442977.9756 308099.4564 182548.1907 177128.2055 288346.3728 414294.5036 363012.3781 429051.7058 398736.0253 383580.8505 345508.9692 207167.57 106789.1706 136692.0776 NADP 3070011.633 4593596.698 3082015.584 4397261.812 4283383.153 4962275.958 4256898.962 5699285.734 4729796.225 2888427.426 2975643.741 2633293.934 3883336.375 3535544.132 2514129.321 NADPH 359103.5535 925606.7603 805290.3344 933747.2508 1042230.818 2158032.252 1503594.372 2007484.762 2322405.394 1365133.184 1531379.967 628228.2294 624933.2379 646413.1928 617608.2384 Coenzyme A 211492.0136 55915.31666 100961.6562 180288.3119 100042.582 251896.0953 248420.5357 307566.0622 246566.194 192166.7688 63551.66465 47553.5808 123627.108 150794.8106 97256.36303 FAD 5386346.073 5033825.708 4884227.488 5032046.037 4386078.914 5136774.473 5335007.868 5183560.634 5276055.883 4769155.416 5006258.415 4482754.765 4394867.616 4536532.696 3809427.432 Acetyl-CoA 5841993.168 5284400.606 4807952.842 5929647.873 5649566.03 5053031.235 4313608.986 5800134.671 6150996.48 4854255.898 3561083.768 4634409.292 3491278.854 2694623.813 3447849.839 Propionyl-CoA 118965.7204 103911.57 94331.86496 38990.79863 35051.07153 42959.98071 44030.40249 45496.7221 37262.31857 68779.80044 51100.22487 119962.7375 65505.74787 48161.46434 47944.74055 Acetoacetyl-CoA N/A 4065.584353 4554.585117 8844.612946 10045.38788 5503.88158 7414.434359 9089.021435 5499.065943 2862.788888 5011.868055 7653.933873 3587.780946 2400.026017 3336.034294 Malonyl-CoA 13038.58219 26650.0451 27621.10302 4105.422248 4685.93322 21533.03718 5360.040921 8131.824998 6672.62468 N/A N/A 4764.230635 1674.254232 N/A N/A Succinyl-CoA N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A Putrescine 1492556.876 1417420.977 1322363.471 1225729.013 746659.5518 1124848.317 888338.7791 892416.662 734403.4772 303552.8641 756427.5667 339785.3392 354854.973 458843.5017 339774.0743 Spermidine N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A Spermine N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A Sarcosine 152733.1016 381487.789 461166.0899 210336.8651 219708.9399 483284.1665 1573180.023 2613424.398 3362165.236 3179622.151 2910921.052 550014.645 3615183.712 2584365.136 2607115.606 13C-Proline1 73448.54079 42427.67281 53461.35484 46385.64413 58509.72406 82041.74645 58573.49988 58698.10591 60364.52951 60447.94323 79278.18697 53872.66459 72822.54555 84102.76471 48359.71756 13C-Alanine-1 N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A 13C-Serine-1 N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A 13C-Threonine-1 7257.900672 N/A 8842.060413 3716.898261 4610.199512 5318.001908 3106.774781 7104.909282 1617.280673 4364.658357 9089.56954 10771.50254 2590.961393 3861.115515 1602.369263 13C-Valine-1 4323.237494 N/A N/A N/A N/A N/A N/A 2363.872397 N/A N/A N/A N/A N/A N/A N/A 13C-Glycine-1 N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A 13C-Aspartate-1 1196.625518 7776.907223 16435.03465 17239.38963 7490.351932 27055.57701 6190.470306 23028.23975 8254.830014 8120.155946 16859.32344 8747.930781 8705.40919 17033.0535 13009.48539 13C-Arginine-1 8217.663751 3168.550045 10322.86654 16726.58745 5632.704229 4497.404071 14974.39431 8982.085041 3431.20198 2012.311836 9882.639032 3148.026968 11415.10793 4431.627677 4814.977427 13C-Cystine-1 1521.235778 2762.258259 5910.735783 2413.427932 4440.793301 4126.438339 7457.015611 25164.35841 13922.00066 11204.96476 21723.57758 4736.749368 2226.254065 2649.43695 5288.737968 13C-Glutamic acid-1 9567.435369 10761.35925 24157.05449 9089.164347 21774.67626 36868.99516 13394.38352 11959.26922 12914.66967 10762.49076 12196.89926 22003.66181 23918.53304 23524.14037 8419.91375 13C-Histidine-1 98663.89556 77968.89729 81518.96931 85289.66809 118886.5056 137901.1601 110720.7161 175309.7753 294164.7121 151628.1848 222354.9946 163115.7145 160933.9168 192038.7926 170124.1692 13C-Iso Leucine-1 N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A 13C-Lysine-1 613699.7233 809391.9851 621335.7505 1176893.669 1431330.338 951610.0267 478475.6465 777473.0998 212835.489 265772.4796 434213.1758 1269860.962 556737.3633 838729.0737 1132690.327 13C-Methionine-1 375117.9879 359807.3007 485425.4832 405763.0857 366675.5737 493352.9059 342595.9867 351360.5594 438065.4864 341888.3115 338517.9394 457271.8623 438300.9275 436881.6091 395812.64 13C-Phenylalanine-1 1174.358806 4448.019358 5367.679935 2615.672122 8090.80045 4446.295867 8344.776626 1421.717498 N/A 1246.586634 11197.98044 2587.235293 6955.714158 4224.405902 2031.941544 13C-Tyrosine 160766530.8 139860027.4 216868714.8 161503972.5 156171160.5 252267639.7 147963524.3 147665122.2 200259906 125354528.4 100530507.4 205386411.7 198987285.7 206912951.3 150302623.9 13C valine-1 N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A 13C tyrosine 2330870.608 2096050.723 3007649.278 2276440.715 2347165.793 3587171.916 2030429.826 2192562.852 2930854.029 1708711.353 1367341.348 2862867.024 2670988.612 2888074.372 2223426.147 13 C phenylalanine 2932.047809 2813.403196 N/A 2669.146932 N/A 5816.284758 8931.270682 3017.342756 6062.478189 8419.723433 6699.829053 4002.086655 3276.080908 3154.187409 4191.032124 13C lysine N/A N/A 2152.684432 N/A N/A N/A N/A N/A N/A N/A N/A 2630.906783 N/A N/A N/A MS_METABOLITE_DATA_END #METABOLITES METABOLITES_START metabolite_name Urea Ethanolamine Imidazole Glycine L-Alanine Betaine aldehyde Choline Gamma-Aminobutyric acid Dimethylglycine Serine Cytosine Creatinine L-Proline Indole Betaine L-Valine L-Threonine L-Homoserine Purine L-Cysteine Creatine Niacinamide Imidazoleacetic acid Thymine Pipecolic acid N-Acetylputrescine Hydroxyproline L-Leucine Ornithine L-Asparagine L-Aspartic acid Adenine Methylcysteine Homocysteine 1-Methylnicotinamide L-Histidinol L-Lysine L-Glutamine O-Acetylserine L-Glutamic acid L-Methionine Guanine L-Histidine DL-2-Aminooctanoic acid Carnitine Methionine sulfoxide L-Phenylalanine Pyridoxamine Pyridoxine 1-Methylhistidine N-Acetylornithine L-Arginine Citrulline Ureidosuccinic acid Glucosamine L-Tyrosine Phosphorylcholine DL-O-Phosphoserine N6-Acetyl-L-lysine N-Alpha-acetyllysine N-Acetylglutamine N-Acetylglutamic acid Asymmetric dimethylarginine L-Acetylcarnitine L-Tryptophan L-Kynurenine N-Acetyl-D-glucosamine Flavone L-Cystathionine 5-Methoxytryptophan L-Cystine Cytidine Biotin Deoxyadenosine Glycerophosphocholine AICA-riboside Glucosamine 6-phosphate Glucosamine-1P Thiamine S-Ribosyl-L-homocysteine Deoxyguanosine Adenosine 1-Methyladenosine Guanosine Argininosuccinic acid 5'-Methylthioadenosine 7-Methylguanosine dCMP Glutathione 5-Thymidylic acid Cytidine monophosphate Uridine 5'-monophosphate Deoxyadenosine monophosphate Nicotinamide ribotide AICAR Thiamine monophosphate dGMP Adenosine monophosphate IMP S-Adenosylmethioninamine GMP Xanthylic acid Riboflavin S-Adenosylhomocysteine S-Adenosylmethionine Folic acid Dihydrofolic acid 5-Methyltetrahydrofolic acid 3,5-Diiodothyronine Oxidized glutathione NAD NADH Dephospho-CoA NADP NADPH Coenzyme A FAD Acetyl-CoA Propionyl-CoA Acetoacetyl-CoA Malonyl-CoA Succinyl-CoA Putrescine Spermidine Spermine Sarcosine 13C-Proline1 13C-Alanine-1 13C-Serine-1 13C-Threonine-1 13C-Valine-1 13C-Glycine-1 13C-Aspartate-1 13C-Arginine-1 13C-Cystine-1 13C-Glutamic acid-1 13C-Histidine-1 13C-Iso Leucine-1 13C-Lysine-1 13C-Methionine-1 13C-Phenylalanine-1 13C-Tyrosine 13C valine-1 13C tyrosine 13 C phenylalanine 13C lysine METABOLITES_END #END