#METABOLOMICS WORKBENCH RCulpHill_20210317_102457 DATATRACK_ID:2534 STUDY_ID:ST001730 ANALYSIS_ID:AN002816 PROJECT_ID:PR001108 VERSION 1 CREATED_ON March 24, 2021, 2:54 pm #PROJECT PR:PROJECT_TITLE Mitochondrial ATP fuels ABC transporter-mediated drug efflux in cancer PR:PROJECT_TITLE chemoresistance PR:PROJECT_SUMMARY Chemotherapy remains the standard of care for most cancers worldwide, however PR:PROJECT_SUMMARY development of chemoresistance due to the presence of the drug-effluxing ABC PR:PROJECT_SUMMARY transporters remains a significant problem. The development of safe and PR:PROJECT_SUMMARY effective means to overcome chemoresistance is critical for achieving durable PR:PROJECT_SUMMARY remissions in many cancer patients. We have investigated the energetic demands PR:PROJECT_SUMMARY of ABC transporters in the context of the metabolic adaptations of PR:PROJECT_SUMMARY chemoresistant cancer cells. Here we show that ABC transporters use PR:PROJECT_SUMMARY mitochondrial-derived ATP as a source of energy to efflux drugs out of cancer PR:PROJECT_SUMMARY cells. We further demonstrate that the loss of MCJ (DnaJC15), an endogenous PR:PROJECT_SUMMARY negative regulator of mitochondrial respiration, in chemoresistant cancer cells PR:PROJECT_SUMMARY boosts their ability to produce ATP from mitochondria and fuel ABC transporters. PR:PROJECT_SUMMARY We have developed novel MCJ mimetics that can attenuate mitochondrial PR:PROJECT_SUMMARY respiration and safely overcome chemoresistance in vitro and in vivo. PR:PROJECT_SUMMARY Administration of MCJ mimetics in combination with standard chemotherapeutic PR:PROJECT_SUMMARY drugs could therefore become an new strategy for treatment of multiple cancers. PR:INSTITUTE University of Colorado Denver PR:DEPARTMENT Biochemistry and Molecular Genetics PR:LABORATORY Angelo D'Alessandro PR:LAST_NAME Culp-Hill PR:FIRST_NAME Rachel PR:ADDRESS 12801 E 17th Ave L18-9403D, Aurora, Colorado, 80045, USA PR:EMAIL rachel.hill@cuanschutz.edu PR:PHONE 303-724-5798 #STUDY ST:STUDY_TITLE Mitochondrial ATP fuels ABC transporter-mediated drug efflux in cancer ST:STUDY_TITLE chemoresistance ST:STUDY_SUMMARY Chemotherapy remains the standard of care for most cancers worldwide, however ST:STUDY_SUMMARY development of chemoresistance due to the presence of the drug-effluxing ABC ST:STUDY_SUMMARY transporters remains a significant problem. The development of safe and ST:STUDY_SUMMARY effective means to overcome chemoresistance is critical for achieving durable ST:STUDY_SUMMARY remissions in many cancer patients. We have investigated the energetic demands ST:STUDY_SUMMARY of ABC transporters in the context of the metabolic adaptations of ST:STUDY_SUMMARY chemoresistant cancer cells. Here we show that ABC transporters use ST:STUDY_SUMMARY mitochondrial-derived ATP as a source of energy to efflux drugs out of cancer ST:STUDY_SUMMARY cells. We further demonstrate that the loss of MCJ (DnaJC15), an endogenous ST:STUDY_SUMMARY negative regulator of mitochondrial respiration, in chemoresistant cancer cells ST:STUDY_SUMMARY boosts their ability to produce ATP from mitochondria and fuel ABC transporters. ST:STUDY_SUMMARY We have developed novel MCJ mimetics that can attenuate mitochondrial ST:STUDY_SUMMARY respiration and safely overcome chemoresistance in vitro and in vivo. ST:STUDY_SUMMARY Administration of MCJ mimetics in combination with standard chemotherapeutic ST:STUDY_SUMMARY drugs could therefore become an new strategy for treatment of multiple cancers. ST:INSTITUTE University of Colorado Denver ST:DEPARTMENT Biochemistry and Molecular Genetics ST:LABORATORY Angelo D'Alessandro ST:LAST_NAME Culp-Hill ST:FIRST_NAME Rachel ST:ADDRESS 12801 E 17th Ave L18-9403D, Aurora, Colorado, 80045, USA ST:EMAIL rachel.hill@cuanschutz.edu ST:PHONE 303-724-5798 #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 - nci-adr-res-1 line:NCI-ADR-RES RAW_FILE_NAME=nci-adr-res-1 SUBJECT_SAMPLE_FACTORS - nci-adr-res-2 line:NCI-ADR-RES RAW_FILE_NAME=nci-adr-res-2 SUBJECT_SAMPLE_FACTORS - nci-adr-res-3 line:NCI-ADR-RES RAW_FILE_NAME=nci-adr-res-3 SUBJECT_SAMPLE_FACTORS - nci-adr-res-4 line:NCI-ADR-RES RAW_FILE_NAME=nci-adr-res-4 SUBJECT_SAMPLE_FACTORS - ovcar8-1 line:OVCAR8 RAW_FILE_NAME=ovcar8-1 SUBJECT_SAMPLE_FACTORS - ovcar8-2 line:OVCAR8 RAW_FILE_NAME=ovcar8-2 SUBJECT_SAMPLE_FACTORS - ovcar8-3 line:OVCAR8 RAW_FILE_NAME=ovcar8-3 SUBJECT_SAMPLE_FACTORS - ovcar8-4 line:OVCAR8 RAW_FILE_NAME=ovcar8-4 #COLLECTION CO:COLLECTION_SUMMARY NCI/ADR-RES (formerly MCF7/Adr) were previously described. NCI/ADR-RES cells CO:COLLECTION_SUMMARY were verified to be of ovarian origin by genotyping. OVCAR-8 cells provided by CO:COLLECTION_SUMMARY Dr. Ernst Lengyel at the University of Chicago. All cancer cell lines were CO:COLLECTION_SUMMARY maintained in RPMI 1640 (Sigma R8758) containing glucose (2 mg/ml) and glutamine CO:COLLECTION_SUMMARY (0.6 mg/ml) but no pyruvate and was supplemented with 5% Fetal calf serum. CO:SAMPLE_TYPE Cultured cells #TREATMENT TR:TREATMENT_SUMMARY N/A - compared cell lines only #SAMPLEPREP SP:SAMPLEPREP_SUMMARY All cancer cell lines were maintained in RPMI 1640 (Sigma R8758) containing SP:SAMPLEPREP_SUMMARY glucose (2 mg/ml) and glutamine (0.6 mg/ml) but no pyruvate and was supplemented SP:SAMPLEPREP_SUMMARY with 5% Fetal calf serum. Metabolic profile comparisons of OVCAR-8 and SP:SAMPLEPREP_SUMMARY NCI/ADR-RES cells were performed on equal cell numbers. Cells were cultured SP:SAMPLEPREP_SUMMARY under normal conditions, detached using trypsin-EDTA (0.05 %), counted, SP:SAMPLEPREP_SUMMARY normalized to 0.5 x 10e6 in each sample, and cell pellets were snap frozen in SP:SAMPLEPREP_SUMMARY liquid nitrogen prior to analysis. Briefly, 2 x 10e6 cells and 20μL cell media SP:SAMPLEPREP_SUMMARY were extracted in 1mL and 980μL cold lysis and extraction buffer (methanol : SP:SAMPLEPREP_SUMMARY acetonitrile : water, 5:3:2), respectively, and pellets were discarded. #CHROMATOGRAPHY CH:CHROMATOGRAPHY_SUMMARY Negative Mode 10 μL of water and methanol soluble fractions were run through a CH:CHROMATOGRAPHY_SUMMARY Kinetex C18 1.7 μm, 100 x 2.1 mm (Phenomenex) reversed phase column (Negative CH:CHROMATOGRAPHY_SUMMARY ion mode – phase A: 1 mM NH4Ac 95:5 water : acetonitrile; phase B: 1 mM NH4Ac CH:CHROMATOGRAPHY_SUMMARY 95:5 acetonitrile : water) via an ultra-high performance chromatographic system CH:CHROMATOGRAPHY_SUMMARY (UHPLC - Vanquish, Thermo Fisher). UHPLC was coupled in line with a CH:CHROMATOGRAPHY_SUMMARY high-resolution quadrupole Orbitrap instrument run in negative polarity mode CH:CHROMATOGRAPHY_SUMMARY (QExactive, Thermo Fisher) at 70,000 resolution (at 200 m/z). Gradients and CH:CHROMATOGRAPHY_SUMMARY other technical parameters and the variants employed herein have been CH:CHROMATOGRAPHY_SUMMARY extensively described. CH:CHROMATOGRAPHY_TYPE Reversed phase CH:INSTRUMENT_NAME Thermo Vanquish CH:COLUMN_NAME Phenomenex Kinetex C18 (150 x 2.1mm, 2.6 um) #ANALYSIS AN:ANALYSIS_TYPE MS #MS MS:INSTRUMENT_NAME Thermo Q Exactive Orbitrap MS:INSTRUMENT_TYPE Orbitrap MS:MS_TYPE ESI MS:ION_MODE NEGATIVE MS:MS_COMMENTS UHPLC was coupled in line with a high-resolution quadrupole Orbitrap instrument MS:MS_COMMENTS run in negative polarity mode (QExactive, Thermo Fisher) at 70,000 resolution MS:MS_COMMENTS (at 200 m/z). Gradients and other technical parameters and the variants employed MS:MS_COMMENTS herein have been extensively described. #MS_METABOLITE_DATA MS_METABOLITE_DATA:UNITS Relative Abundance MS_METABOLITE_DATA_START Samples nci-adr-res-1 nci-adr-res-2 nci-adr-res-3 nci-adr-res-4 ovcar8-1 ovcar8-2 ovcar8-3 ovcar8-4 Factors line:NCI-ADR-RES line:NCI-ADR-RES line:NCI-ADR-RES line:NCI-ADR-RES line:OVCAR8 line:OVCAR8 line:OVCAR8 line:OVCAR8 ADP 6555772 6065822 5627218 5020242 1195020 1324574 1603449 1271472 Adenosine 56869 52127 62706 51022 43165 56695 64920 38247 Adenine 4681998 4823433 5343932 4569250 1855910 1827785 2208756 1771566 Guanosine 93011 110978 96284 108844 275265 594398 568583 593627 CTP 483410 422287 439497 472869 447503 721665 773763 655819 CDP 1228105 1002104 1082754 1076646 676421 703983 878290 711149 CMP 783555 781840 733690 682620 146341 129752 180992 149787 Cytidine 2031748 1953112 2140788 2093888 939895 1151636 1315728 1539288 Thymidine 305951 301790 274266 308615 186431 237766 263818 248392 Thymine 128917 126405 110512 126769 131550 114834 127277 116693 UTP 1944783 1760894 1773049 1743530 319858 612303 696481 300259 UDP 5316928 4582916 4779398 4371268 665499 697815 935314 581638 UMP 3530433 3742542 3135419 2705698 120470 149615 164491 79945 Inosine 8702914 12161080 12305680 12606760 18267070 17095970 19968730 12410890 Hypoxanthine 31389380 38631060 43306020 45223620 54848180 51187890 57504770 48006220 5-Hydroxyisourate 6600634 6845890 6129292 6672658 13074440 11204840 11933680 11254750 5-6-Dihydrothymine 1827361 1917009 1719157 1691828 1844995 2011282 2043275 1913102 UDP-glucose 3036627 2653580 2983349 2710025 1842791 1852765 1906913 1591182 Diphosphate 13250200 14018560 14756440 14311440 18897040 19043040 17841270 16779580 D-Glucose 13245630 15120110 15483060 14798540 8514636 10892060 12217580 13205660 D-Glucose 6-phosphate 965733 879319 944493 931321 720689 728885 790393 910790 D-Fructose 1-6-bisphosphate 693229 598937 648081 624524 521029 510357 577103 565111 D-Glyceraldehyde 3-phosphate/Glycerone phosphate 79993 88314 88696 93905 73940 77792 105776 106402 2/3-Phospho-D-glycerate 331029 318597 334435 363356 464036 371523 357735 391849 Pyruvate 300991 297121 283715 339693 403531 370553 376885 328033 Lactate 19984170 20611440 22715860 27923880 30321490 28519180 27757210 28896200 Maltose 78961 101403 94227 112907 71082 81829 77783 64310 Mannitol 269193 293102 287456 302170 215641 186355 245363 226844 D-Arabitol 318789 364619 343100 351264 116018 127009 158137 125711 Citrate 6144180 6624204 6092672 6558234 3894526 4806244 5379170 4769874 2-Oxoglutarate 82373 82131 71494 72471 119781 134001 142412 140057 2-Oxoglutaramate 66009 46541 101089 95699 99312 67226 95442 83971 Succinate 5051718 4632874 4694440 4474824 3089888 2754352 3435312 3081745 Fumarate 1998416 2118175 2108554 2202846 2628653 2866999 2677834 2757380 Malate 13499630 15175080 14208560 16032200 21240740 22191530 21088750 21688840 2-Hydroxyglutarate/Citramalate 110985 102400 108831 102258 158238 154510 158279 122248 D-Erythrose 4-phosphate 61257 60428 63666 67497 66071 62218 74146 87996 Sedoheptulose 1-phosphate 368576 423839 387490 400416 280751 330259 343344 341265 alpha-D-Ribose 1-phosphate 1363503 1686475 1505766 1510734 1551482 1717348 1958548 1755789 5-Oxoproline 20035530 17614330 18651800 18941670 25838820 25910490 24729090 26230150 S-Glutathionyl-L-cysteine 185201 142348 120420 226713 206357 116059 169554 110912 Ascorbate 125971 127185 131568 149338 42464 52379 64334 48230 Dehydroascorbate 155108 127602 132534 126829 154124 158130 189749 152763 gamma-L-Glutamyl-L-cysteine 2664481 2003993 2886200 2974413 1912238 2137534 2557639 2001136 S-Adenosyl-L-homocysteine 152892 198011 216287 190078 196282 175034 208810 199425 Argininosuccinate 1094164 924501 1117527 968319 925862 1207270 1214132 1369926 N-Acetylneuraminate 343068 365403 322373 426927 198429 221959 296090 358237 UDP-N-acetyl-D-glucosamine 6029590 5346558 6077392 5820928 3837310 4199980 4219220 3707591 CMP-N-acetylneuraminate 232783 204329 238756 231446 209731 211454 228466 235212 Carnosine 56911 22379 34427 36965 46879 24824 30922 31410 Phosphocreatine 55262 53067 50912 61662 150166 176380 147416 218074 N-Succinyl-L-citrulline 62440 74634 53772 64203 248718 256257 213800 278537 trans-4-Hydroxy-L-proline 3968769 4120931 4091915 4000207 2916128 3157280 3139636 3249364 Pantothenol 795363 957834 1011441 821598 1716890 1727497 1891423 1763959 Thiocysteine 1428920 1391540 1225487 1267495 1564229 1527586 1384193 1371336 Glycerol 3-phosphate 648291 1167293 898106 867120 758139 908349 1084276 2394869 Ethanolamine phosphate 92122 104421 91673 109400 214155 231923 248290 232158 Sphingosine 1582643 763672 938619 674337 182864 1438968 1664510 2142818 Acetylcholine 1866771 1837308 1891551 1690812 2493443 2728297 2598340 2220422 CDP-choline 1359205 1775477 1530045 1290695 759828 788369 1004458 516172 Sphinganine 1-phosphate 38898 36111 26141 28369 19061 29280 32577 32854 Pentanoate (valerate) 41547 40632 44074 39879 40512 48844 58257 55990 Hexanoic acid (caproate) 309251 324207 309188 301193 320974 251949 293121 321228 Heptanoic acid 103910 117553 130471 123040 146563 118003 156584 152012 Octanoic acid (caprylic acid) 453196 436075 475466 388530 492294 491560 521353 522676 Nonanoic acid (pelargonic acid) 2374261 2023772 2314727 2343822 1072073 1440051 1642882 2049484 Decanoic acid (capric acid) 732115 763066 849987 836056 317197 429200 556691 629346 Dodecanoic acid (lauric acid) 420354 543508 601562 550855 186951 279165 351478 375580 Tetradecanoic acid (myristic acid) 3512301 5204536 6482808 4864078 1710970 2418621 3310937 3833415 Hexadecanoic acid (palmitic acid) 35878000 40728450 40741760 41372540 23986310 27066920 34670920 43710380 Octadecanoic acid (stearic acid) 34812070 35356450 35678140 36534390 29785500 32249330 32618460 34393620 Tetradecenoic acid (myristoleic acid) 240638 324979 284509 326227 98558 150071 182863 211641 Hexadecenoic acid (Palmitoleic acid) 2832538 4640954 4047791 3912873 1094956 1465419 2416690 3841405 Octadecenoic acid (Oleic acid) 28583670 42149870 29823460 33395290 17230680 19074610 28926970 38732080 Linoleic acid ((9Z,12Z)-Octadecadienoic acid) 14942380 19607390 19464280 16742240 8910852 10256900 17474980 28407360 a-Linolenic acid (Octadecatrienoic acid) 471631 838270 670931 659983 223316 305805 550998 801080 Arachidonic acid (Eicosatetraenoic acid) 4813734 8177662 6548844 5157922 3094451 3274047 6217032 5973594 Stearidonic acid ((6Z,9Z,12Z,15Z)-Octadecatetraenoic acid) 15522 19990 12504 15554 13221 20215 22300 40992 Docosahexaenoic acid 1751217 2226616 2251408 2210329 1220578 1397951 2603774 2788565 Adrenic acid (7,10,13,16-Docosatetraenoic acid) 1137044 1594413 1708128 1241052 2419052 2699333 4068651 4399400 Eicosapentaenoic acid 166244 192221 179515 176588 99993 145150 272189 227376 Dihomo-gamma-linolenic acid ((8Z-11Z-14Z)-Icosatrienoic acid) 947422 1395105 1377340 1164749 597151 660778 1171155 1312168 Docosapentaenoic acid ((7Z-10Z-13Z-16Z-19Z)-Docosa-7-10-13-16-19-pentaenoic acid) 424138 532120 685695 495403 857528 1002668 1462240 1829528 Undecanoic acid 132426 153822 149023 151567 79805 95469 109453 120105 Glycochenodeoxycholate 70859 57499 45494 38720 50977 54325 74067 88128 Taurodeoxycholate/taurochenodeoxycholate/tauroursodeoxycholate 47389 37791 32388 21326 31091 31650 44134 55465 13(S)-HODE 107867 135405 119713 119528 80201 86807 121109 138328 Prostaglandin A2 11712 10754 10006 13419 6351 10697 9442 12439 Prostaglandin D2/Thromboxane A2 (isobars) 409262 448929 386805 459663 237822 285883 316394 377429 Leukotriene A4 20781 23176 23301 26241 8977 14752 14216 11759 Cholesterol sulfate 141629 109692 133520 114677 175122 200736 211723 179199 2-Methyleneglutarate 102179 89312 44661 124152 48008 32528 106176 25342 Leucocyanidin 296101 278697 405583 485330 194437 214836 291223 253157 Methylenediurea 13162700 12867100 14631040 13925980 11085980 11168300 11585540 11679420 3-Oxalomalate 5070158 5135138 4264520 4040513 6775326 5579422 6304176 5982938 2-Deoxy-alpha-D-glucoside 3054921 3400782 3062493 2801976 797638 1296303 1525692 1427221 N-Acyl-D-mannosaminolactone 375385 350169 363687 454780 97181 156837 173277 224510 N6-Methyl-L-lysine 359806 359106 337377 388175 345086 405232 414818 377839 Shikimate 3-phosphate 126734 107116 115952 144625 116999 122350 130522 111505 D-glucono-1,5-lactone 36678 28181 43772 37391 30449 31846 37924 27425 Catechin 401136 520397 582781 595374 1872750 1364505 1470464 1388229 Riboflavin 37618 49781 28185 61165 66122 64288 70586 63026 Glucosinolate 235258 260780 237203 224656 124275 154713 177612 134227 D-Ribose 5-diphosphate 149743 140498 157250 141249 121498 138867 159724 233791 S-Acylglutathione 526977 478753 390774 485706 367528 452210 365857 425410 9-Oxononanoic acid 108794 121000 134732 134852 113444 121038 114911 90511 L-Noradrenaline 757413 764735 694149 702746 627277 580290 711411 531691 N-Acetylmethionine 1631244 1717060 1833503 1828822 744468 736437 941529 923388 2-Oxo-7-methylthioheptanoic acid 155660 192478 206230 302902 264813 214152 227702 277755 MS_METABOLITE_DATA_END #METABOLITES METABOLITES_START metabolite_name kegg mass rt ADP C00008 426.0222 0.67181 Adenosine C00212 268.1033 0.67937 Adenine C00147 136.0616 0.6750599 Guanosine C00387 284.0977 0.6756378 CTP C00063 481.9772 CDP C00112 402.0103 0.6030908 CMP C00055 324.0585 0.6803118 Cytidine C00475 242.0795 0.6416436 Thymidine C00214 243.1003 0.6752188 Thymine C00178 127.0499 0.6544333 UTP C00075 482.961 0.7489136 UDP C00015 402.9947 0.6141199 UMP C00105 323.0283 0.6546757 Inosine C00294 269.0872 0.678325 Hypoxanthine C00262 137.0457 0.6787575 5-Hydroxyisourate C11821 185.0319 0.6398596 5-6-Dihydrothymine C00906 129.0658 0.648505 UDP-glucose C00029 565.0475 0.603427 Diphosphate C00013 176.9349 0.6300375 D-Glucose C00031 179.0552 0.6673 D-Glucose 6-phosphate C02965 259.0223 0.6244945 D-Fructose 1-6-bisphosphate C00354 338.9886 0.6129044 D-Glyceraldehyde 3-phosphate/Glycerone phosphate C00118 168.9893 0.628085 2/3-Phospho-D-glycerate C00631 184.9852 1.735109 Pyruvate C00022 87.00725 0.6584475 Lactate C01432 89.02277 0.6785876 Maltose C00208 341.1087 0.6615025 Mannitol C00392 181.0704 0.6623849 D-Arabitol C01904 151.0602 0.66036 Citrate C00158 191.0187 0.6785351 2-Oxoglutarate C00026 145.0131 0.672705 2-Oxoglutaramate C00940 144.0291 0.6138319 Succinate C00042 117.0179 0.6801701 Fumarate C00122 115.0022 0.6705475 Malate C00149 133.0129 0.661405 2-Hydroxyglutarate/Citramalate C02630 147.0288 0.6695288 D-Erythrose 4-phosphate C00279 199.0005 0.6378711 Sedoheptulose 1-phosphate C06222 289.0328 0.6260999 alpha-D-Ribose 1-phosphate C00620 229.0114 0.6364051 5-Oxoproline C01879 130.0498 0.64991 S-Glutathionyl-L-cysteine C05526 427.0938 0.6503704 Ascorbate C00072 175.0238 0.66831 Dehydroascorbate C05422 173.0083 0.6714271 gamma-L-Glutamyl-L-cysteine C00669 251.069 0.6771369 S-Adenosyl-L-homocysteine C00021 385.1278 0.674227 Argininosuccinate C03406 291.1291 0.6448406 N-Acetylneuraminate C00270 310.1122 0.6623605 UDP-N-acetyl-D-glucosamine C00043 606.0743 0.6056216 CMP-N-acetylneuraminate C00128 613.1408 0.6128405 Carnosine C00386 227.1144 0.6135757 Phosphocreatine C02305 212.0424 0.662325 N-Succinyl-L-citrulline trans-4-Hydroxy-L-proline C01157 132.0655 0.6545975 Pantothenol C00864 218.1028 0.684045 Thiocysteine C01962 153.9977 0.9480731 Glycerol 3-phosphate C00093 171.0053 0.6299675 Ethanolamine phosphate C00346 142.0263 0.663135 Sphingosine C00319 300.2891 2.00264 Acetylcholine C01996 146.1174 0.6640199 CDP-choline C00307 489.1132 0.6459703 Sphinganine 1-phosphate C01120 380.2553 1.804202 Pentanoate (valerate) C00803 101.0593 1.73687 Hexanoic acid (caproate) C01585 115.0752 1.231544 Heptanoic acid C17714 129.0909 1.23364 Octanoic acid (caprylic acid) C06423 143.1064 2.066512 Nonanoic acid (pelargonic acid) C01601 157.1223 2.418412 Decanoic acid (capric acid) C01571 171.138 1.963073 Dodecanoic acid (lauric acid) C02679 199.1695 2.400162 Tetradecanoic acid (myristic acid) C06424 227.2012 2.674048 Hexadecanoic acid (palmitic acid) C00249 255.2327 3.083581 Octadecanoic acid (stearic acid) C01530 283.264 3.690377 Tetradecenoic acid (myristoleic acid) C08322 225.1853 2.489214 Hexadecenoic acid (Palmitoleic acid) C08362 253.2171 2.723397 Octadecenoic acid (Oleic acid) C00712 281.2484 3.131838 Linoleic acid ((9Z,12Z)-Octadecadienoic acid) C01595 279.2327 2.785384 a-Linolenic acid (Octadecatrienoic acid) C06427 277.2172 2.567058 Arachidonic acid (Eicosatetraenoic acid) C00219 303.2328 2.675434 Stearidonic acid ((6Z,9Z,12Z,15Z)-Octadecatetraenoic acid) C16300 275.2015 2.408585 Docosahexaenoic acid C06429 327.2329 2.569912 Adrenic acid (7,10,13,16-Docosatetraenoic acid) C16527 331.2642 2.968593 Eicosapentaenoic acid C06428 301.2173 2.483914 Dihomo-gamma-linolenic acid ((8Z-11Z-14Z)-Icosatrienoic acid) C03242 305.2485 2.86611 Docosapentaenoic acid ((7Z-10Z-13Z-16Z-19Z)-Docosa-7-10-13-16-19-pentaenoic acid) C16513 329.2486 2.696104 Undecanoic acid C17715 185.1538 2.254826 Glycochenodeoxycholate C05466 448.3065 2.013092 Taurodeoxycholate/taurochenodeoxycholate/tauroursodeoxycholate C05463 498.2894 1.887603 13(S)-HODE C14762 295.2276 2.227839 Prostaglandin A2 C05953 333.2029 1.728156 Prostaglandin D2/Thromboxane A2 (isobars) C00696 351.2205 2.25828 Leukotriene A4 C00909 317.2162 1.985211 Cholesterol sulfate C18043 465.3044 2.623917 2-Methyleneglutarate Leucocyanidin Methylenediurea 3-Oxalomalate 2-Deoxy-alpha-D-glucoside N-Acyl-D-mannosaminolactone N6-Methyl-L-lysine Shikimate 3-phosphate D-glucono-1,5-lactone Catechin Riboflavin Glucosinolate D-Ribose 5-diphosphate S-Acylglutathione 9-Oxononanoic acid L-Noradrenaline N-Acetylmethionine 2-Oxo-7-methylthioheptanoic acid METABOLITES_END #END