#METABOLOMICS WORKBENCH jgiafaglione_20230911_190913 DATATRACK_ID:4304 STUDY_ID:ST002856 ANALYSIS_ID:AN004678 PROJECT_ID:PR001788 VERSION 1 CREATED_ON September 12, 2023, 2:49 pm #PROJECT PR:PROJECT_TITLE MYC is a regulator of AR inhibition-induced metabolic requirements in prostate PR:PROJECT_TITLE cancer PR:PROJECT_SUMMARY Advanced prostate cancers are treated with therapies targeting the androgen PR:PROJECT_SUMMARY receptor (AR) signaling pathway. While many tumors initially respond to AR PR:PROJECT_SUMMARY inhibition, nearly all develop resistance. It is critical to understand how PR:PROJECT_SUMMARY prostate tumor cells respond to AR inhibition in order to exploit PR:PROJECT_SUMMARY therapy-induced phenotypes prior to the outgrowth of treatment-resistant PR:PROJECT_SUMMARY disease. Here, we comprehensively characterize the effect of AR blockade on PR:PROJECT_SUMMARY prostate cancer metabolism using transcriptomics, metabolomics and bioenergetics PR:PROJECT_SUMMARY approaches. The metabolic response to AR inhibition is defined by reduced PR:PROJECT_SUMMARY glycolysis, robust elongation of mitochondria, and increased reliance on PR:PROJECT_SUMMARY mitochondrial oxidative metabolism. We establish DRP1 activity and MYC signaling PR:PROJECT_SUMMARY as mediators of AR blockade-induced metabolic phenotypes. Rescuing DRP1 PR:PROJECT_SUMMARY phosphorylation after AR inhibition restores mitochondrial fission, while PR:PROJECT_SUMMARY rescuing MYC restores glycolytic activity and prevents sensitivity to complex I PR:PROJECT_SUMMARY inhibition. Our study provides new insight into the regulation of PR:PROJECT_SUMMARY treatment-induced metabolic phenotypes and vulnerabilities in prostate cancer. PR:INSTITUTE UCLA PR:LABORATORY Goldstein Lab PR:LAST_NAME Giafaglione PR:FIRST_NAME Jenna PR:ADDRESS 610 Charles E Young Dr S, Los Angeles, CA, 90024, USA PR:EMAIL jgiafaglione@g.ucla.edu PR:PHONE 408-728-3065 #STUDY ST:STUDY_TITLE Validation of on-target effect of IACS-010759 in vehicle- and ST:STUDY_TITLE Enzalutamide-treated 16D cells ST:STUDY_SUMMARY In this study, we sought to validate that 30nM IACS-010759, a complex I ST:STUDY_SUMMARY inhibitor, had an on-target effect in vehicle- and Enzalutamide-treated 16D ST:STUDY_SUMMARY prostate cancer cells. ST:INSTITUTE UCLA ST:LABORATORY Goldstein Lab ST:LAST_NAME Giafaglione ST:FIRST_NAME Jenna ST:ADDRESS 610 Charles E Young Dr S, Los Angeles, CA, 90024, USA ST:EMAIL jgiafaglione@g.ucla.edu ST:PHONE 408-728-3065 #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 - Naive-NT1 Treatment:Vehicle (DMSO) RAW_FILE_NAME=Naive-NT1 SUBJECT_SAMPLE_FACTORS - Naive-NT2 Treatment:Vehicle (DMSO) RAW_FILE_NAME=Naive-NT2 SUBJECT_SAMPLE_FACTORS - Naive-NT3 Treatment:Vehicle (DMSO) RAW_FILE_NAME=Naive-NT3 SUBJECT_SAMPLE_FACTORS - Naive-IACS-1 Treatment:30nM IACS-010759 RAW_FILE_NAME=Naive-IACS-1 SUBJECT_SAMPLE_FACTORS - Naive-IACS-2 Treatment:30nM IACS-010759 RAW_FILE_NAME=Naive-IACS-2 SUBJECT_SAMPLE_FACTORS - Naive-IACS-3 Treatment:30nM IACS-010759 RAW_FILE_NAME=Naive-IACS-3 SUBJECT_SAMPLE_FACTORS - LT Enza-NT1 Treatment:Vehicle (DMSO) RAW_FILE_NAME=LT Enza-NT1 SUBJECT_SAMPLE_FACTORS - LT Enza-NT2 Treatment:Vehicle (DMSO) RAW_FILE_NAME=LT Enza-NT2 SUBJECT_SAMPLE_FACTORS - LT Enza-NT3 Treatment:Vehicle (DMSO) RAW_FILE_NAME=LT Enza-NT3 SUBJECT_SAMPLE_FACTORS - LT Enza-IACS-1 Treatment:30nM IACS-010759 RAW_FILE_NAME=LT Enza-IACS-1 SUBJECT_SAMPLE_FACTORS - LT Enza-IACS-2 Treatment:30nM IACS-010759 RAW_FILE_NAME=LT Enza-IACS-2 SUBJECT_SAMPLE_FACTORS - LT Enza-IACS-3 Treatment:30nM IACS-010759 RAW_FILE_NAME=LT Enza-IACS-3 #COLLECTION CO:COLLECTION_SUMMARY Vehicle- and Enzalutamide-treated 16D cells were cultured with 30nM IACS-010759 CO:COLLECTION_SUMMARY for 24 hours CO:SAMPLE_TYPE Cultured cells #TREATMENT TR:TREATMENT_SUMMARY Vehicle- and Enzalutamide-treated 16D cells were cultured with 30nM IACS-010759 TR:TREATMENT_SUMMARY in U13C-glucose-containing media for 24 hours #SAMPLEPREP SP:SAMPLEPREP_SUMMARY Cell plates were placed on ice and quickly washed with ice-cold 0.9% (w/v) NaCl. SP:SAMPLEPREP_SUMMARY Cells were immediately treated with 500 μL of ice-cold MeOH and 200 μL water SP:SAMPLEPREP_SUMMARY containing 1 μg of the internal standard norvaline. Cells were then scraped and SP:SAMPLEPREP_SUMMARY placed in 1.5 mL centrifuge tubes kept on ice. Next, 500 μL of chloroform was SP:SAMPLEPREP_SUMMARY added, after which samples were vortexed for 1 minute and then spun at 10,000g SP:SAMPLEPREP_SUMMARY for 5 minutes at 4C. The aqueous layer was transferred to a GC/MS sample vial SP:SAMPLEPREP_SUMMARY and dried overnight using a refrigerated CentriVap. #CHROMATOGRAPHY CH:CHROMATOGRAPHY_TYPE GC CH:INSTRUMENT_NAME Agilent 7890A CH:COLUMN_NAME Agilent DB5-MS (30m x 0.25mm, 0.25um) CH:SOLVENT_A N/A (GC-MS) CH:SOLVENT_B N/A (GC-MS) CH:FLOW_GRADIENT N/A (GC-MS) CH:FLOW_RATE 1 ml/min CH:COLUMN_TEMPERATURE 23 #ANALYSIS AN:ANALYSIS_TYPE MS #MS MS:INSTRUMENT_NAME Agilent 5977B MS:INSTRUMENT_TYPE GC-TOF MS:MS_TYPE EI MS:ION_MODE POSITIVE MS:MS_COMMENTS Data was analyzed using Agilent MassHunter software. Stable isotope tracing data MS:MS_COMMENTS was corrected for natural abundance of heavy isotopes with FluxFix software MS:MS_COMMENTS using a reference set of unlabeled metabolite standards2. #MS_METABOLITE_DATA MS_METABOLITE_DATA:UNITS abundance MS_METABOLITE_DATA_START Samples LT Enza-IACS-1 LT Enza-IACS-2 LT Enza-IACS-3 LT Enza-NT1 LT Enza-NT2 LT Enza-NT3 Naive-IACS-1 Naive-IACS-2 Naive-IACS-3 Naive-NT1 Naive-NT2 Naive-NT3 Factors Treatment:30nM IACS-010759 Treatment:30nM IACS-010759 Treatment:30nM IACS-010759 Treatment:Vehicle (DMSO) Treatment:Vehicle (DMSO) Treatment:Vehicle (DMSO) Treatment:30nM IACS-010759 Treatment:30nM IACS-010759 Treatment:30nM IACS-010759 Treatment:Vehicle (DMSO) Treatment:Vehicle (DMSO) Treatment:Vehicle (DMSO) a-Ketoglutarate(M0) 99792 106227 27397 16501 45395 15677 109019 163257 236113 57764 65165 55183 a-Ketoglutarate(M1) 27012 29811 7399 6334 17293 6327 28521 42532 62072 18109 20578 17510 a-Ketoglutarate(M2) 17391 17326 4525 7450 20759 7297 14758 21905 31372 23562 26476 22126 a-Ketoglutarate(M3) 5004 4888 1290 2885 8369 2925 3355 4886 7049 8694 10250 8141 a-Ketoglutarate(M4) 2280 2057 468 1504 4474 1572 1149 1792 2942 5683 6280 4911 a-Ketoglutarate(M5) 887 497 236 584 1720 531 480 623 824 2195 2485 2036 a-Ketoglutarate(M6) 2260 206 158 197 1586 356 139 144 229 649 678 651 Alanine260(M0) 347992 304246 127124 215690 493745 300897 190886 248095 344244 474138 543040 475509 Alanine260(M1) 84950 74185 31090 52690 120919 73435 46972 61016 84438 120178 136954 119851 Alanine260(M2) 50668 47518 19364 26996 62778 37530 30655 38658 52604 71447 80192 70174 Alanine260(M3) 414036 409583 176339 107178 249742 150091 279888 368704 504625 474792 546152 460254 Alanine260(M4) 81616 80654 34541 20783 48753 29305 55029 72583 99197 93635 108125 91382 Asparagine(M0) 1009566 895924 239743 277551 846800 472191 596242 824483 1141523 770563 904853 735327 Asparagine(M1) 378186 333547 86528 101076 316461 174011 219235 306109 427761 285676 337770 272437 Asparagine(M2) 177273 155219 39939 47764 149812 82321 101807 141772 199196 134608 158848 128790 Asparagine(M3) 44832 39529 10173 11725 36870 19857 25054 35035 48983 32799 38387 31336 Asparagine(M4) 10765 9469 2490 2766 9068 4966 6114 8415 11697 7816 9151 7411 Asparagine(M5) 2090 1915 525 562 1958 918 1137 1494 2091 1446 1728 1541 Aspartate418(M0) 195550 197609 48245 82575 237275 143991 64890 87671 134395 232148 261238 210047 Aspartate418(M1) 71574 70933 16735 35205 102818 61929 23208 31407 47498 97421 109980 88244 Aspartate418(M2) 40702 36894 8752 25167 73247 43587 12642 15910 24828 82784 94530 75720 Aspartate418(M3) 25728 30826 6797 11771 34148 20208 10268 12245 18548 47855 53815 42252 Aspartate418(M4) 8355 9605 2104 4414 12837 7599 3250 3873 5863 19736 22345 17571 Aspartate418(M5) 2994 3760 778 1371 3891 2330 1376 1517 2254 6330 7250 5684 Citrate459(M0) 259696 194777 33887 199299 522614 341684 98254 132349 192898 505142 535640 449210 Citrate459(M1) 108572 74133 12946 97653 261469 170281 39001 50164 74062 236628 250774 208074 Citrate459(M2) 114201 55734 8366 124291 336339 219868 38206 40431 59647 467196 497097 405808 Citrate459(M3) 50502 22718 3402 60302 166903 107257 16912 17148 25433 225645 239952 194992 Citrate459(M4) 27676 10173 1488 35105 96256 62456 9020 8256 11972 162560 173046 138143 Citrate459(M5) 12763 4783 732 14958 42257 27081 4452 4149 5898 82315 87262 68759 Citrate459(M6) 4683 1913 276 5408 15157 9903 1892 1635 2177 33007 34714 26838 Citrate459(M7) 1729 1276 632 2255 5044 3333 1077 1170 1596 10841 11417 9104 Citrate591(M0) 48875 35782 6401 36480 99889 63921 17832 24072 34804 96233 101381 84538 Citrate591(M1) 25641 17953 3176 21972 59866 38570 9204 12002 17868 55266 58304 47913 Citrate591(M2) 24604 12854 2187 25551 71079 45349 8414 9053 13530 93010 99326 80898 Citrate591(M3) 12295 5536 776 14148 38540 24966 4140 4081 6400 50983 55183 44282 Citrate591(M4) 6647 2662 358 8080 22688 14291 2295 2009 2985 35429 38247 30190 Citrate591(M5) 3122 1102 212 3644 10424 6623 1052 1026 1436 18881 19719 15869 Citrate591(M6) 1251 414 78 1375 3924 2646 437 368 518 8188 8632 6775 Citrate591(M7) 429 171 18 549 1363 893 172 142 190 2901 3055 2409 Cysteine(M0) 23428 25676 1385 1318 6895 1373 6104 27600 28239 3847 6472 7644 Cysteine(M1) 8038 8917 477 519 2345 455 2143 9831 9880 1245 2004 2558 Cysteine(M2) 4830 5118 282 176 1385 197 1175 5726 5773 746 1204 1487 Cysteine(M3) 1628 1378 157 115 611 164 316 1565 1649 217 461 620 Cysteine(M4) 492 426 34 52 328 41 42 434 538 107 102 220 Fumarate(M0) 297423 345604 120547 45649 105267 64798 203366 282960 384063 182440 208741 172595 Fumarate(M1) 73693 84908 30144 15047 35614 21806 50078 69196 94011 55822 64273 52640 Fumarate(M2) 43235 46509 16624 12057 29714 18096 26973 36790 50178 55348 63541 50658 Fumarate(M3) 58852 60773 23936 5025 13648 8100 39397 56524 75943 29420 33113 26731 Fumarate(M4) 15426 21060 7391 2974 7867 5085 11059 13904 19153 13414 14313 11549 Fumarate(M5) 5292 7258 2435 627 1462 1062 3801 4966 7090 3167 3548 2610 GABA(M0) 27975 29870 7247 3731 15089 7153 17984 25165 40459 8093 17940 13949 GABA(M1) 6219 5876 1501 649 3228 1440 3872 5669 8598 1727 3997 2999 GABA(M2) 2640 2933 593 262 1498 566 1846 2531 3701 705 1453 1362 GABA(M3) 732 1124 376 1855 474 2344 2573 2328 2299 491 515 377 GABA(M4) 273 411 155 277 374 298 933 1225 1032 318 264 559 GABA(M5) 131 138 429 188 205 447 332 184 156 498 41 115 Glutamate432(M0) 2147649 2202498 718099 886558 2273429 1382455 1288339 1719802 2362496 1588360 1822097 1531879 Glutamate432(M1) 852865 848532 266843 438353 1149927 692062 488485 652815 905766 684174 790570 658296 Glutamate432(M2) 603646 543616 166578 490676 1308822 786124 283478 362904 505833 801539 924647 759431 Glutamate432(M3) 215559 180541 54028 230336 626680 373980 85226 104504 145835 361911 417552 337641 Glutamate432(M4) 96538 74831 21972 122981 338800 201539 33020 37250 51858 220095 253560 201624 Glutamate432(M5) 37146 28896 8683 46541 129374 77408 11295 12184 16707 93089 107918 84420 Glutamate432(M6) 10982 8629 2558 14235 39788 23753 3160 3432 4702 29840 34398 27046 Isoleucine274(M0) 161724 166539 52166 51963 153622 128328 100803 134061 210366 124092 169851 121935 Isoleucine274(M1) 42539 43741 13706 12019 40515 33754 26436 34983 55797 32529 44776 32173 Isoleucine274(M2) 15114 16711 5608 4943 15552 12603 9959 13368 21237 12428 17142 11773 Isoleucine274(M3) 2763 2974 870 833 2737 2204 1758 2428 3529 2139 2951 1901 Isoleucine274(M4) 705 537 933 52 1494 860 326 513 912 435 587 454 Isoleucine274(M5) 128 74 73 188 97 166 144 148 89 57 160 Isoleucine274(M6) 122 39 39 213 60 68 35 21 37 46 26 Isoleucine274(M7) 28 47 22 323 128 1206 Itaconate(M0) 1244 3973 808 11754 1111 964 1150 917 1041 1478 1282 648 Itaconate(M1) 249 1364 3849 3381 5684 4092 4893 4223 5014 5384 282 325 Itaconate(M2) 5506 3509 4229 4591 4839 4958 3857 4479 5665 656 5076 4099 Itaconate(M3) 3504 1893 2269 2328 2392 2393 1292 2255 3132 2189 2161 2469 Itaconate(M4) 578929 167230 359099 383383 361021 432142 178991 319433 475830 240941 328553 380785 Itaconate(M5) 152438 43195 93278 100113 94321 113133 46409 83437 124146 62380 85585 100581 Itaconate(M6) 42121 5066 3474 3764 4542 3050 5282 3861 35245 3923 4230 3968 KIC (M0) 18686 19489 5533 4787 13926 4635 24363 32599 51708 10221 9742 10955 KIC (M1) 2659 2965 1004 1056 1792 483 3397 4629 8141 1662 1263 1359 KIC (M2) 893 1309 428 293 724 328 1125 1538 2753 400 661 853 KIC (M3) 1640 1985 104 1403 2086 72 1790 105 282 75 1431 1566 KIC (M4) 329 23 60 40 490 11 133 463 299 255 56 362 KIC (M5) 1131 2051 63 622 1244 520 2066 831 870 1249 1540 807 KIC (M6) 2355 2720 2372 2360 3208 2018 2119 2127 1794 1812 2011 2182 KIC (M7) 379 79 53 63 43 409 522 435 443 73 24 KIV (M0) 807 969 614 600 589 766 907 737 1915 493 281 925 KMV(M0) 14310 16931 8918 6320 13204 6124 15747 21836 32382 10312 12261 11733 Lactate261(M0) 1196661 971763 439592 331918 1105297 948370 1097993 1719796 2143845 793387 800079 611706 Lactate261(M1) 277408 224940 100266 79000 257610 218026 254832 398785 501223 189498 190570 147506 Lactate261(M2) 174602 157367 66850 41195 124674 105463 192178 277244 362144 120748 123928 101477 Lactate261(M3) 1374233 1461494 618121 146085 274459 152882 2076662 2765173 3840234 770592 808819 723843 Lactate261(M4) 272848 292006 121707 28625 52385 28345 420230 562633 796239 151918 160304 143161 Leucine 274 (M0) 233755 244519 83763 83814 240761 201785 142420 188062 284248 170784 231946 173355 Leucine 274 (M1) 58850 61438 20620 20735 60338 50592 35086 47371 72048 42724 58289 43668 Leucine 274 (M2) 22889 23498 7866 8068 24561 19536 13738 18050 27428 16913 24238 17414 Leucine 274 (M3) 3720 3889 1336 1346 4164 3187 2214 3014 4646 2772 4167 3053 Leucine 274 (M4) 713 535 308 190 985 495 464 977 1239 704 1195 496 Leucine 274 (M5) 767 493 700 344 607 787 894 453 791 654 705 580 Leucine 274 (M6) 3285 4357 2755 3047 4567 2600 3601 4186 4598 2878 4335 3553 Malate(M0) 489598 558136 193726 48496 139821 80332 358903 477570 646897 301571 333139 277949 Malate(M1) 178287 201971 68283 22731 66644 37905 128550 172170 234019 129174 142516 118226 Malate(M2) 109575 118055 40435 19785 59139 34512 72826 96926 130322 124378 136184 110903 Malate(M3) 118795 136116 48078 10193 30694 17611 85973 114705 153074 71447 77712 62736 Malate(M4) 38174 43348 15218 4125 12591 7061 26740 35958 47579 30705 33435 26641 Malate(M5) 15753 18288 6520 1304 3936 2267 11468 15250 20152 10110 10969 8664 Methionine320(M0) 69564 67708 18714 22342 75146 52193 36913 50339 79600 47115 65481 50128 Methionine320(M1) 17792 17477 4799 5883 19560 13551 9649 12943 20731 12345 17000 13009 Methionine320(M2) 9981 10309 2750 3334 10771 7598 5469 7259 11512 6826 9441 7170 Methionine320(M3) 2155 2244 503 668 2230 1586 1244 1483 2514 1450 2103 1494 Methionine320(M4) 1050 1036 256 387 1268 877 891 1197 1866 1236 1843 1321 Methionine320(M5) 215 196 158 314 469 377 334 332 400 389 561 377 Methionine320(M6) 89 70 70 34 25 103 170 169 140 162 190 144 N-AcetylAspartate(M0) 1312318 1465725 469880 698030 1773597 1104964 203049 270212 388504 579161 628760 510252 N-AcetylAspartate(M1) 376624 399676 122563 214055 556580 358112 55119 69533 102612 186297 202245 160899 N-AcetylAspartate(M2) 227972 223009 60683 178112 461964 291904 44726 48022 74073 282207 292435 231835 N-AcetylAspartate(M3) 136234 146987 44002 61750 158462 101326 33844 41876 59157 103187 108891 83151 N-AcetylAspartate(M4) 36776 36982 10812 28767 73277 47630 10613 11604 17899 62130 66890 51047 N-AcetylAspartate(M5) 17284 18765 5723 9939 25307 16488 5757 6750 9607 25507 27374 20963 Norvaline 260(M0) 3974877 3962784 1827885 1703480 3679113 3189396 2534652 3159229 3991789 2660455 3217247 2659020 Norvaline 260(M1) 1092441 1090942 490306 450636 1007972 859518 681138 857863 1101177 717103 875987 715646 Norvaline 260(M2) 409565 410397 183977 171562 377992 325551 255240 321875 411512 267778 327993 267359 Norvaline 260(M3) 66754 67039 32200 29574 62204 53367 42607 52818 66920 44044 53443 43284 Norvaline 288(M0) 3265341 3270719 1477085 1342339 2996590 2601310 2036278 2563583 3277615 2135918 2607973 2132606 Norvaline 288(M1) 869910 870560 381062 345706 793735 683579 529887 672706 872733 557823 686216 555317 Norvaline 288(M2) 337419 336360 149980 135525 308021 264648 206069 260697 338043 216206 266058 216583 Norvaline 288(M3) 53065 52762 23816 21663 48394 41673 32647 41289 53551 34010 41445 34314 Ornithine474(M0) 5268 5218 713 573 3286 1330 3545 5660 9911 1115 2670 1964 Ornithine474(M1) 2207 2120 315 233 1289 472 1523 2306 4025 451 1000 801 Ornithine474(M2) 987 1007 151 101 588 239 577 1086 1791 246 496 417 Ornithine474(M3) 296 219 67 118 165 77 150 282 442 44 107 43 Ornithine474(M4) 59 47 35 72 18 16 45 63 125 10 13 20 Ornithine474(M5) 50 9 6 20 245 10 14 57 33 85 20 55 Ornithine474(M6) 683 465 163 28 320 184 9 329 203 16 34 24 Pyruvate(M0) 215579 206392 104245 124663 270083 151032 169389 220542 232331 235060 206784 178005 Pyruvate(M1) 22902 34190 21111 13567 42867 28332 17785 24570 37003 27181 33432 30336 Pyruvate(M2) 9067 11820 2891 9013 17306 8543 15333 12102 19293 20768 13292 12494 Pyruvate(M3) 82914 93994 31765 31924 49440 21493 139003 179940 265334 163389 141305 130490 Pyruvate(M4) 6822 6800 4552 2022 7206 794 10849 17939 21631 13136 11239 11401 Serine390(M0) 1323279 1307215 540211 582180 1350869 805170 850988 1090835 1425068 1038591 1160357 968192 Serine390(M1) 557195 553634 226446 231654 542200 321127 375476 483343 635340 454989 508105 419082 Serine390(M2) 312322 312737 126802 123011 289015 170704 221166 285704 375925 261392 292918 240036 Serine390(M3) 125924 110499 44418 60736 141510 83850 111519 139268 182578 254294 285846 232663 Serine390(M4) 37680 32626 12958 17678 41457 24514 34010 42282 55840 77665 87828 70969 Succinate(M0) 115272 1075985 59855 56283 131426 72058 90905 87326 118003 129255 130210 100195 Succinate(M1) 27882 260454 14084 15538 37248 20714 21454 20586 26771 33209 34919 26885 Succinate(M2) 14959 112383 6347 10138 25455 14760 9689 9506 12890 26674 29434 21770 Succinate(M3) 3367 17855 1155 3050 7800 4698 1913 1935 2577 9283 10123 7727 Succinate(M4) 1491 4180 680 1697 3695 2352 1055 1189 1368 4014 4746 3793 Succinate(M5) 412 662 248 345 932 630 263 267 216 932 1115 1100 Threonine404(M0) 115134 128562 28728 29033 109256 39902 68795 125115 149722 111856 118510 99986 Threonine404(M1) 40278 45002 10035 10167 38341 14117 23891 43292 52362 39666 41514 35129 Threonine404(M2) 20842 22999 5269 5266 19398 7243 12092 21085 25146 18468 20061 16676 Threonine404(M3) 5043 5513 1380 1073 4672 1764 3044 4901 6083 4292 4659 3943 Threonine404(M4) 1310 1580 290 243 1030 371 732 1280 1455 965 1233 930 Threonine404(M5) 289 236 91 52 207 130 141 237 204 272 179 172 Urea(M0) 543176 461669 465 531 1048292 273828 74405 422136 516481 346239 403927 257679 Urea(M1) 111405 32042 558 620 217563 56156 40523 86696 106745 71630 30523 53855 Valine288(M0) 91415 93209 33420 27370 82301 51486 56761 76732 114600 62324 78346 62725 Valine288(M1) 22477 23200 8199 6872 20577 12462 14013 18581 28361 15215 19250 15120 Valine288(M2) 9038 8882 3189 2751 7995 4994 5676 7468 11073 6212 7472 6058 Valine288(M3) 1480 1459 502 459 1324 821 875 1121 1667 965 1224 1062 Valine288(M4) 198 194 82 79 205 154 162 129 303 119 195 196 Valine288(M5) 525 558 404 434 585 451 550 464 571 455 547 493 Valine288(M6) 133 171 13 10 19 27 98 124 16 103 171 MS_METABOLITE_DATA_END #METABOLITES METABOLITES_START metabolite_name a-Ketoglutarate(M0) a-Ketoglutarate(M1) a-Ketoglutarate(M2) a-Ketoglutarate(M3) a-Ketoglutarate(M4) a-Ketoglutarate(M5) a-Ketoglutarate(M6) Alanine260(M0) Alanine260(M1) Alanine260(M2) Alanine260(M3) Alanine260(M4) Asparagine(M0) Asparagine(M1) Asparagine(M2) Asparagine(M3) Asparagine(M4) Asparagine(M5) Aspartate418(M0) Aspartate418(M1) Aspartate418(M2) Aspartate418(M3) Aspartate418(M4) Aspartate418(M5) Citrate459(M0) Citrate459(M1) Citrate459(M2) Citrate459(M3) Citrate459(M4) Citrate459(M5) Citrate459(M6) Citrate459(M7) Citrate591(M0) Citrate591(M1) Citrate591(M2) Citrate591(M3) Citrate591(M4) Citrate591(M5) Citrate591(M6) Citrate591(M7) Cysteine(M0) Cysteine(M1) Cysteine(M2) Cysteine(M3) Cysteine(M4) Fumarate(M0) Fumarate(M1) Fumarate(M2) Fumarate(M3) Fumarate(M4) Fumarate(M5) GABA(M0) GABA(M1) GABA(M2) GABA(M3) GABA(M4) GABA(M5) Glutamate432(M0) Glutamate432(M1) Glutamate432(M2) Glutamate432(M3) Glutamate432(M4) Glutamate432(M5) Glutamate432(M6) Isoleucine274(M0) Isoleucine274(M1) Isoleucine274(M2) Isoleucine274(M3) Isoleucine274(M4) Isoleucine274(M5) Isoleucine274(M6) Isoleucine274(M7) Itaconate(M0) Itaconate(M1) Itaconate(M2) Itaconate(M3) Itaconate(M4) Itaconate(M5) Itaconate(M6) KIC (M0) KIC (M1) KIC (M2) KIC (M3) KIC (M4) KIC (M5) KIC (M6) KIC (M7) KIV (M0) KMV(M0) Lactate261(M0) Lactate261(M1) Lactate261(M2) Lactate261(M3) Lactate261(M4) Leucine 274 (M0) Leucine 274 (M1) Leucine 274 (M2) Leucine 274 (M3) Leucine 274 (M4) Leucine 274 (M5) Leucine 274 (M6) Malate(M0) Malate(M1) Malate(M2) Malate(M3) Malate(M4) Malate(M5) Methionine320(M0) Methionine320(M1) Methionine320(M2) Methionine320(M3) Methionine320(M4) Methionine320(M5) Methionine320(M6) N-AcetylAspartate(M0) N-AcetylAspartate(M1) N-AcetylAspartate(M2) N-AcetylAspartate(M3) N-AcetylAspartate(M4) N-AcetylAspartate(M5) Norvaline 260(M0) Norvaline 260(M1) Norvaline 260(M2) Norvaline 260(M3) Norvaline 288(M0) Norvaline 288(M1) Norvaline 288(M2) Norvaline 288(M3) Ornithine474(M0) Ornithine474(M1) Ornithine474(M2) Ornithine474(M3) Ornithine474(M4) Ornithine474(M5) Ornithine474(M6) Pyruvate(M0) Pyruvate(M1) Pyruvate(M2) Pyruvate(M3) Pyruvate(M4) Serine390(M0) Serine390(M1) Serine390(M2) Serine390(M3) Serine390(M4) Succinate(M0) Succinate(M1) Succinate(M2) Succinate(M3) Succinate(M4) Succinate(M5) Threonine404(M0) Threonine404(M1) Threonine404(M2) Threonine404(M3) Threonine404(M4) Threonine404(M5) Urea(M0) Urea(M1) Valine288(M0) Valine288(M1) Valine288(M2) Valine288(M3) Valine288(M4) Valine288(M5) Valine288(M6) METABOLITES_END #END