#METABOLOMICS WORKBENCH linuxmant_20230420_101902 DATATRACK_ID:3873 STUDY_ID:ST002585 ANALYSIS_ID:AN004257 PROJECT_ID:PR001665 VERSION 1 CREATED_ON April 26, 2023, 1:07 pm #PROJECT PR:PROJECT_TITLE Zinc treatment reverses and anti-Zn-regulated miRs suppress esophageal PR:PROJECT_TITLE carcinomas in vivo PR:PROJECT_SUMMARY We previously showed that replenishing Zn in Zn-deficient rats and supplementing PR:PROJECT_SUMMARY Zn in Zn-sufficient rats inhibit the development of esophageal squamous cell PR:PROJECT_SUMMARY carcinoma (ESCC) (1) and tongue squamous cell carcinoma (2). To determine if Zn PR:PROJECT_SUMMARY has anticancer activity in established ESCC, we performed a 33-day Zn treatment PR:PROJECT_SUMMARY study in 31 ESCC-bearing ZD male rats with 85% ESCC incidence (designated PR:PROJECT_SUMMARY Zn-untreated) that were generated in a 20-wk Zn deficiency-promoted, PR:PROJECT_SUMMARY N-nitrosomethylbenzylamine (NMBA)-induced ESCC experiment (3). The ESCC-bearing PR:PROJECT_SUMMARY Zn-untreated male rats demonstrated oncogenic miR-31 and -21 upregulation (3, 4) PR:PROJECT_SUMMARY and human ESCC-associated metabolic changes (3), with decreased levels of PR:PROJECT_SUMMARY glycolytic intermediates and increased levels of anabolic/biosynthetic PR:PROJECT_SUMMARY intermediates, changes pointing to a classic cancer cell remodeling of energy PR:PROJECT_SUMMARY and nucleoside metabolism (5). The 31 ESCC-bearing Zn-untreated rats were PR:PROJECT_SUMMARY randomized into two groups, viz Zn-untreated (n = 10) and Zn-treated (n = 21). PR:PROJECT_SUMMARY While Zn-untreated rats continued on ZD diet and deionized water, Zn-treated PR:PROJECT_SUMMARY rats were given deionized water supplemented with 25 ppm Zn as Zn gluconate (2) PR:PROJECT_SUMMARY and paired-fed a ZS diet to Zn-untreated rats. This study was concluded after 33 PR:PROJECT_SUMMARY days of Zn medication. We found that Zn therapy reduced ESCC incidence from 90 PR:PROJECT_SUMMARY to 43%, a drop of 47%. We then determined if Zn intervention, that reduced ESCC PR:PROJECT_SUMMARY incidence, would induce metabolic changes to reverse the ESCC-associated PR:PROJECT_SUMMARY metabolome (3). PR:INSTITUTE West Coast Metabolomics Center PR:LAST_NAME Pedrosa PR:FIRST_NAME Diego PR:ADDRESS 451 Health Science Dr, Davis, CA, 95616, USA PR:EMAIL dpedrosa@ucdavis.edu PR:PHONE (530) 752-8129 #STUDY ST:STUDY_TITLE Zinc treatment reverses and anti-Zn-regulated miRs suppress esophageal ST:STUDY_TITLE carcinomas in vivo ST:STUDY_SUMMARY Using gas chromatography time-of-flight mass spectrometry GC-TOF MS (3), we ST:STUDY_SUMMARY performed untargeted metabolomic profiling on esophageal mucosa of Zn-treated vs ST:STUDY_SUMMARY Zn-untreated rats (n = 10 rats per cohort). Thirty-eight significantly altered ST:STUDY_SUMMARY metabolites (24 down-, 14 up-regulated, P < 0.05) were identified in the ST:STUDY_SUMMARY Zn-treated vs Zn-untreated esophagus. Of the 24 down-regulated metabolites, 15 ST:STUDY_SUMMARY (63%) were involved in anabolic/biosynthetic pathways, including amino ST:STUDY_SUMMARY acid/pyrimidine/purine metabolism and polyamine biosynthesis. Putrescine ST:STUDY_SUMMARY (intermediate in polyamine biosynthesis), shown to be up 6.4-fold in ST:STUDY_SUMMARY ESCC-bearing ZD esophagus (3), was down-regulated -3.96-fold in Zn-treated ST:STUDY_SUMMARY esophagus. Ornithine decarboxylase (ODC) is the rate liming enzyme in the ST:STUDY_SUMMARY polyamine biosynthetic pathway to form putrescine, which is converted into ST:STUDY_SUMMARY spermidine and spermine. Polyamines are indispensable for cell ST:STUDY_SUMMARY proliferation/tumor growth, and depletion of polyamines inhibits tumor growth ST:STUDY_SUMMARY (6). Of the 14 metabolites that were significantly up-regulated in the ST:STUDY_SUMMARY Zn-treated esophagus, five (37%) were carbohydrates, including glucose, which is ST:STUDY_SUMMARY up-regulated 3.4-fold, pointing to a decreased uptake of glucose and a reversal ST:STUDY_SUMMARY of the Warburg effect after Zn treatment. Critical to cancer aerobic glycolysis ST:STUDY_SUMMARY is the metabolic enzyme hexokinase 2 (HK2) that catalyzes the first committed ST:STUDY_SUMMARY step in glucose metabolism where glucose is phosphorylated to form ST:STUDY_SUMMARY glucose-6-phosphate. HK2 overexpression accounts for the high glycolytic rate in ST:STUDY_SUMMARY cancer cells (7). In summary, Zn treatment that significantly reduced ESCC ST:STUDY_SUMMARY incidence reversed classic cancer cell metabolic phenotypes such as increased ST:STUDY_SUMMARY glycolysis and nucleoside intermediates, with decrease in putrescine, increase ST:STUDY_SUMMARY in glucose, accompanied by down-regulation of metabolite enzymes ODC and HK2. ST:INSTITUTE West Coast Metabolomics Center ST:LAST_NAME Pedrosa ST:FIRST_NAME Diego ST:ADDRESS 451 Health Science Dr, Davis, CA, 95616, USA ST:EMAIL dpedrosa@ucdavis.edu ST:PHONE (530) 752-8129 #SUBJECT SU:SUBJECT_TYPE Mammal SU:SUBJECT_SPECIES Rattus norvegicus SU:TAXONOMY_ID 10116 #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 - A1_001 treatment:Turmor bearing-untreated RAW_FILE_NAME=200408alvsa11_1 SUBJECT_SAMPLE_FACTORS - A2_002 treatment:Turmor bearing-untreated RAW_FILE_NAME=200408alvsa10_1 SUBJECT_SAMPLE_FACTORS - A3_003 treatment:Turmor bearing-untreated RAW_FILE_NAME=200408alvsa17_1 SUBJECT_SAMPLE_FACTORS - A4_004 treatment:Turmor bearing-untreated RAW_FILE_NAME=200408alvsa13_1 SUBJECT_SAMPLE_FACTORS - A5_005 treatment:Turmor bearing-untreated RAW_FILE_NAME=200408alvsa05_1 SUBJECT_SAMPLE_FACTORS - A6_006 treatment:Turmor bearing-untreated RAW_FILE_NAME=200408alvsa03_1 SUBJECT_SAMPLE_FACTORS - A7_007 treatment:Turmor bearing-untreated RAW_FILE_NAME=200408alvsa08_1 SUBJECT_SAMPLE_FACTORS - A8_008 treatment:Turmor bearing-untreated RAW_FILE_NAME=200408alvsa12_1 SUBJECT_SAMPLE_FACTORS - A9_009 treatment:Turmor bearing-untreated RAW_FILE_NAME=200408alvsa04_1 SUBJECT_SAMPLE_FACTORS - A10_010 treatment:Turmor bearing-untreated RAW_FILE_NAME=200408alvsa15_1 SUBJECT_SAMPLE_FACTORS - A11_011 treatment:Turmor bearing-Zn treated RAW_FILE_NAME=200408alvsa02_1 SUBJECT_SAMPLE_FACTORS - A12_012 treatment:Turmor bearing-Zn treated RAW_FILE_NAME=200408alvsa07_1 SUBJECT_SAMPLE_FACTORS - A13_013 treatment:Turmor bearing-Zn treated RAW_FILE_NAME=200408alvsa09_1 SUBJECT_SAMPLE_FACTORS - A14_014 treatment:Turmor bearing-Zn treated RAW_FILE_NAME=200408alvsa18_1 SUBJECT_SAMPLE_FACTORS - A15_015 treatment:Turmor bearing-Zn treated RAW_FILE_NAME=200408alvsa01_1 SUBJECT_SAMPLE_FACTORS - A16_016 treatment:Turmor bearing-Zn treated RAW_FILE_NAME=200408alvsa06_1 SUBJECT_SAMPLE_FACTORS - A17_017 treatment:Turmor bearing-Zn treated RAW_FILE_NAME=200408alvsa14_1 SUBJECT_SAMPLE_FACTORS - A18_018 treatment:Turmor bearing-Zn treated RAW_FILE_NAME=200408alvsa19_1 SUBJECT_SAMPLE_FACTORS - A19_019 treatment:Turmor bearing-Zn treated RAW_FILE_NAME=200408alvsa20_1 SUBJECT_SAMPLE_FACTORS - A20_020 treatment:Turmor bearing-Zn treated RAW_FILE_NAME=200408alvsa16_1 SUBJECT_SAMPLE_FACTORS - Pool 2 treatment:Pools RAW_FILE_NAME=200408alvsa22_1 SUBJECT_SAMPLE_FACTORS - Pool 1 treatment:Pools RAW_FILE_NAME=200408alvsa21_1 #COLLECTION CO:COLLECTION_SUMMARY At sacrifice, esophagi from Zn-treated vs Zn-untreated rats were isolated (n = CO:COLLECTION_SUMMARY 10 rats per cohort). Esophageal epithelium was prepared by using a blade to CO:COLLECTION_SUMMARY remove the submucosal and muscularis layers, snap-frozen in liquid nitrogen, and CO:COLLECTION_SUMMARY stored at –80 °C. Frozen esophageal samples from Zn-untreated and CO:COLLECTION_SUMMARY Zn-treated rats (20 mg per esophagus) were shipped on dry ice to the NIH West CO:COLLECTION_SUMMARY Coast Metabolomics Center, University of California, Davis. CO:SAMPLE_TYPE Epithelial cells #TREATMENT TR:TREATMENT_SUMMARY Two treatments, 10 rats per treatment group Untreated group was given drinking TR:TREATMENT_SUMMARY water Zn-treated group was given Zn-gluconate in the drinking water. #SAMPLEPREP SP:SAMPLEPREP_SUMMARY SOP_blood-GCMS-06052020.pdf #CHROMATOGRAPHY CH:CHROMATOGRAPHY_TYPE GC CH:INSTRUMENT_NAME Leco Pegasus IV GC CH:COLUMN_NAME Restek Rtx-5Sil MS (30m x 0.25mm, 0.25um) CH:SOLVENT_A Helium CH:SOLVENT_B Helium CH:FLOW_GRADIENT 1 ml/min CH:FLOW_RATE 1 ml/min CH:COLUMN_TEMPERATURE 50 - 300 #ANALYSIS AN:ANALYSIS_TYPE MS #MS MS:INSTRUMENT_NAME Leco Pegasus HT TOF MS:INSTRUMENT_TYPE GC-TOF MS:MS_TYPE EI MS:ION_MODE POSITIVE MS:MS_COMMENTS Acquisition of masses between 85-500 Scan rate 17 spec/sec Processing with in MS:MS_COMMENTS house software #MS_METABOLITE_DATA MS_METABOLITE_DATA:UNITS normalized peak heights MS_METABOLITE_DATA_START Samples A1_001 A2_002 A3_003 A4_004 A5_005 A6_006 A7_007 A8_008 A11_011 A15_015 A16_016 A17_017 A18_018 A19_019 A20_020 Pool 2 Pool 1 Factors treatment:Turmor bearing-untreated treatment:Turmor bearing-untreated treatment:Turmor bearing-untreated treatment:Turmor bearing-untreated treatment:Turmor bearing-untreated treatment:Turmor bearing-untreated treatment:Turmor bearing-untreated treatment:Turmor bearing-untreated treatment:Turmor bearing-Zn treated treatment:Turmor bearing-Zn treated treatment:Turmor bearing-Zn treated treatment:Turmor bearing-Zn treated treatment:Turmor bearing-Zn treated treatment:Turmor bearing-Zn treated treatment:Turmor bearing-Zn treated treatment:Pools treatment:Pools succinic acid 48763 15714 56815 45448 26786 10790 22228 35159 18110 18977 18974 17496 12126 18094 9093 22618 22273 fumaric acid 31302 21365 69099 27954 35413 66282 29884 53915 36469 22831 32886 37264 45421 59289 43441 41737 40538 malic acid 53015 37704 117284 49007 43866 83832 46943 93872 59992 43348 43221 45334 53821 84907 54727 60736 57307 xylulose 3414 4037 2580 2193 1906 14024 1389 1973 1627 2534 1606 1749 2257 2194 1771 2340 1686 xylose 7858 4085 4243 4209 2706 1967 2760 2754 2326 2561 2786 1698 2907 2773 2602 2072 2066 xylonic acid isomer 2849 2681 2874 1744 1788 2530 1897 3103 1389 2190 1470 1859 851 1752 1733 1381 1472 xanthine 18543 16869 8015 8261 21559 13165 11620 11680 11586 10360 20964 17636 26261 38252 29196 19936 19841 valine 257514 580464 248231 402263 655173 99415 426050 310628 500039 522530 705643 604494 385637 288976 377726 435507 439520 uridine-5'-monophosphate 6795 2528 7802 7818 4054 1515 2680 13520 7441 5081 359 3805 1304 1272 1168 3055 3317 uridine 7804 5947 7082 5060 9680 7286 4813 5867 7405 3892 12051 9723 10203 23105 17098 9130 8700 uric acid 114663 37648 50708 96869 70904 22271 29400 74409 29242 24275 27810 32602 29846 36409 20650 43456 44776 urea 1058262 291332 1394392 1038653 595157 397809 956099 955010 786746 683318 811036 712846 971450 1041031 797850 979367 941988 uracil 33339 15851 23095 31855 32276 13786 11105 24762 12375 10836 17538 15950 31961 26218 20304 21562 21284 UDP-N-acetylglucosamine 2349 3517 6853 5376 3922 4002 4755 6002 6750 3937 4899 3757 4556 4916 3946 5096 4782 UDP-glucuronic acid 4699 711 5856 7668 6451 11689 9758 7574 12346 6874 7121 3129 1259 1165 4713 1727 5875 tyrosine 420531 555684 355449 498445 389990 140753 262704 217948 244813 298892 354566 370585 319555 276595 205329 343462 343666 tryptophan 174949 218023 134712 200952 158611 44534 91043 91968 98542 103199 125102 152456 109995 123797 82353 139890 132439 trans-4-hydroxyproline 10138 3344 18236 7148 2473 6050 1619 5016 1907 1422 2509 2451 3344 2742 3252 4440 3905 tocopherol gamma- 693 562 1156 1029 765 779 927 853 965 1458 1167 1045 2348 744 1970 896 974 tocopherol alpha- 6960 4833 12353 5842 6784 7522 7121 10565 9971 6777 5584 7504 9746 9251 7865 7739 7738 thymine 5973 927 2575 10052 4453 1052 919 1982 1153 139 600 563 605 655 449 1557 1199 thymidine 3163 1176 3673 3664 2443 2460 2352 2744 2111 361 1393 1050 1998 1333 1988 2110 1396 threonine 145649 183363 149230 180965 191373 85232 141259 153496 181316 164930 188870 178503 156208 159428 153778 156468 168508 threonic acid 859 1021 2170 3057 2254 1739 694 1683 1351 1310 679 995 1275 882 645 1502 1559 taurine 167857 184546 190952 120740 184639 391922 353849 294530 313981 285927 255847 214038 242837 305567 440531 238284 206563 sulfuric acid 1552 2850 3558 4536 1861 1445 5724 2586 2543 7048 1784 2776 6729 3650 4439 3134 3683 sucrose 258 197 434 267 346 364 246 397 776 371 235 361 223 87 314 254 401 stearic acid 553956 474994 881117 762552 554207 706323 729448 773557 711118 589866 570887 466557 606903 809458 690616 645931 632977 squalene 1646 3286 4054 2402 3871 3249 1873 4871 2328 2179 2693 984 2303 12313 1352 3256 2386 spermidine 921 438 313 890 371 232 299 287 334 842 303 539 482 848 297 852 422 sorbitol 5949 4726 14733 8210 19476 4282 18525 8335 8598 13610 6847 12537 5537 10786 8049 10764 9492 sinigrin 889 555 1260 1111 778 407 619 324 869 572 688 702 546 828 515 730 679 serine 1016266 897812 1040478 1067294 784637 783986 736365 717092 707936 687646 829525 834703 932765 855644 692751 870679 847966 saccharic acid 786 204 1748 1453 1052 417 595 1071 523 502 543 474 456 693 486 755 775 ribulose-5-phosphate 2559 2218 1462 1310 2158 6550 2901 3765 2985 2594 3649 455 1557 3554 5257 2999 2895 ribose-5-phosphate 3139 3525 2721 1997 3333 5781 3517 4886 4447 2925 5261 4177 4664 7404 6221 4043 4099 ribose 11560 30148 6166 10364 7785 5813 5723 7481 3782 10483 11119 3761 18055 12774 28364 12239 13071 ribonic acid 346 3279 2288 1854 2044 768 1958 965 4080 2031 3902 2789 4269 4137 3713 3239 3355 ribitol 1856 1132 1656 2257 1418 1215 1364 1634 1851 1164 1205 1110 1085 1504 1054 704 1578 raffinose 506 642 486 314 1304 5640 821 522 796 953 889 527 567 814 713 256 657 pyrophosphate 188326 135930 544561 287482 134749 272691 258935 412104 408517 169891 177103 195742 139451 234860 191523 264416 229616 putrescine 5404 1273 8779 12457 2472 2055 732 3660 1094 817 660 1234 834 1512 907 1961 1700 p-tolyl glucuronide 2160 915 2623 1762 1279 1375 883 3851 748 563 608 622 532 556 695 1285 1585 pseudo-uridine 8709 1955 5840 7767 5825 2828 2796 7019 2703 2254 1483 1532 2946 1506 2023 3714 3822 proline 139137 302808 129243 200515 418419 51005 141018 131162 241994 241346 384010 297034 169680 104616 121308 176249 162033 pimelic acid 1638 876 2093 2446 1876 24093 3303 2915 3131 1616 2278 1212 1322 1425 1957 1318 1784 phytosphingosine 1381 836 1925 2780 1578 466 853 1362 1199 776 1063 1010 943 1357 769 1218 1255 phosphogluconic acid 2948 838 3892 2503 4110 2918 1013 6014 2208 4062 3574 4042 3871 4176 4740 293 329 phosphoethanolamine 48041 25344 76445 60186 33767 24724 47473 73846 35933 23110 39926 45873 39080 42662 44674 81665 58129 phosphoenolpyruvate 3790 2707 3016 2163 1354 2146 3575 2458 3340 2463 4116 3268 3500 6502 4687 4576 1722 phosphate 405175 88705 544915 291699 235917 890976 366479 517162 503282 268032 426679 334508 443793 471589 550440 443161 453503 phenylpyruvate 3924 3541 885 8776 4031 2360 1328 2355 1085 2010 1826 2186 2947 859 1504 2740 2452 phenylalanine 283664 355429 257945 346266 209591 82620 152100 136216 150129 167438 223398 226658 194491 143150 105967 212694 204089 pelargonic acid 14627 15948 23884 29641 16969 37177 40579 45223 24885 12529 22200 14698 19797 36357 17644 19505 17862 parabanic acid 1797 2214 2805 2865 1827 2516 2166 3144 3070 1601 2323 1944 2103 5179 2730 3108 2481 pantothenic acid 842 754 1101 1173 503 2063 978 1145 595 983 550 965 1006 1483 1243 782 817 palmitoleic acid 1404 1340 1392 537 1243 857 774 899 1055 1023 618 1014 1671 673 481 1408 1188 palmitic acid 80820 90923 125239 134696 83596 110633 118063 111238 100263 95899 81116 75094 106651 134076 120225 104971 109484 oxoproline 1469731 1610725 1751345 1448919 1175711 1710271 1651941 1472365 1474884 1317536 1597174 1326107 1425148 1035153 1144050 1475480 1393134 ornithine 117632 168872 94521 158796 126764 55246 70535 58522 83097 122570 115641 89353 93733 84929 51637 94939 87136 O-phosphoserine 411 332 536 399 441 544 580 789 585 521 473 358 385 843 481 318 601 oleic acid 15102 17345 15459 23641 13164 325 10448 8672 9079 11947 6534 5361 20635 18441 17478 14759 13478 octadecylglycerol 3320 2633 2460 6498 3737 1414 749 3001 2109 1805 1484 2003 977 1584 269 2265 2214 noradrenaline 2283 1097 3445 5574 604 860 2530 6480 728 29842 2950 53789 11147 1728 3895 10018 7235 nicotinic acid 4064 5054 1487 5254 2331 1306 1111 1125 1147 4911 2093 1655 4773 5772 4218 2546 2839 nicotinamide 27281 24864 24443 16648 36985 53548 25283 26015 24516 17044 33871 27855 33525 50834 43655 33935 34331 N-acetylmannosamine 354 690 722 923 719 309 951 1138 1042 1360 900 972 708 1202 702 726 784 N-acetylaspartic acid 7132 2657 32964 14005 4924 3772 6488 4775 4623 3159 3593 3351 4317 4025 4060 5249 5298 myristic acid 3604 3183 4919 2144 2490 4880 3590 5058 4529 3287 3557 2902 3216 5355 3874 4193 3984 myo-inositol 593552 383327 205153 225120 255627 158377 710861 321845 430841 409489 513713 368052 661203 501759 656770 450163 450085 methionine sulfoxide 11616 14956 11228 17845 10052 6718 7374 8279 6625 10893 9747 10372 10328 9568 9554 10860 10331 methionine 121380 187897 99610 146175 131615 42754 78337 64747 78894 139582 122537 138153 123719 143375 103713 116886 119918 methanolphosphate 10716 10656 21638 6444 11480 21210 14178 19190 15608 11371 12041 12861 15509 17838 19379 16475 16633 mannose 7143 8742 8633 11355 10600 3490 12243 10466 10000 9139 15985 12850 18386 10460 13584 10192 9361 maltotriose 331 721 951 766 1317 5066 836 1291 731 442 987 1015 1666 2368 1612 2235 1026 maltose 27573 29851 21146 29070 35934 86885 17415 20469 17010 58068 25834 28266 36600 42347 47068 37087 35588 maleimide 3681 4016 6183 4690 3934 7159 4740 10468 6191 4354 5271 4197 6254 6571 5646 4546 4320 lyxitol 119 1066 4758 2257 2816 1606 3730 751 3538 2894 3445 2676 3399 1504 1273 1156 2725 lysine 23147 27627 15565 32085 19510 6153 8293 9931 9671 15174 14769 15442 12980 13217 7100 15572 14193 linoleic acid 12184 21094 12811 21915 14841 9528 10233 6930 7122 11636 5446 10104 27296 23546 18247 15038 10929 leucine 1034456 1546998 960256 1342941 1196539 345631 809231 619329 828850 897147 1276018 1146871 900501 631285 623273 994299 967762 lauric acid 13100 10020 26877 17288 10135 15638 14796 17890 19604 11352 11144 10102 13045 22902 17288 15597 15314 lanosterol 222 136 1069 661 473 305 213 628 344 198 144 142 117 326 229 388 341 lactic acid 1119129 533328 1215857 833271 847851 1615977 599174 816497 633706 421148 25304 783855 653606 1287375 862949 691913 681319 isothreonic acid 1877 640 2380 1911 1355 739 1113 1394 1085 952 1091 1063 1231 924 894 1262 1337 isomaltose 581 648 593 646 704 511 389 797 725 3462 269 1165 1132 2241 951 641 1178 isoleucine 556405 799326 486495 696393 534799 171718 392472 297003 382700 408715 584864 542789 442939 312601 297919 485946 465597 inositol-4-monophosphate 1502 1659 2364 913 2231 4199 1441 3436 2211 2347 1991 2410 1426 1756 2715 2054 1925 inosine 5'-monophosphate 47220 19076 36446 29149 53767 389084 52970 57653 13639 49858 36661 25096 35356 20038 25444 53629 58071 inosine 31262 39911 15231 16443 41024 52448 43305 32268 48021 32798 73344 60540 60570 149161 133427 57943 58539 indole-3-lactate 17027 6880 12112 39900 26669 8991 4954 11387 1683 5254 7768 5456 8169 2720 3296 10034 9743 hypoxanthine 40273 56500 14124 14325 61053 55127 39402 27895 30977 26393 58654 46887 74907 120506 124542 58294 59628 histidine 66088 85536 27812 64983 79286 5347 22187 24047 28246 45892 55214 75341 39994 47091 16165 44550 34316 hexadecylglycerol 7004 3490 4975 15705 6672 1727 1426 5431 2619 1427 1236 2468 1123 2132 1216 2728 3426 heptadecanoic acid 10399 9655 14726 17043 8039 10539 11506 15142 11955 10440 9977 8852 11462 14775 11588 11077 11921 guanosine 504 984 703 367 1512 417 435 891 1172 883 1967 1252 2417 3738 3403 1790 1013 glycine 697243 627721 779423 758128 1081029 378772 873795 873504 1097271 1012153 1185810 803478 765090 473535 713617 787625 778798 glycerol-alpha-phosphate 71100 24624 69469 53905 38121 65835 49729 76042 40837 25977 32702 31661 40717 46875 45948 42906 45370 glycerol 207113 214713 144047 171091 118349 117996 138125 129509 154369 146215 171878 145559 210187 142728 157975 156231 147457 glyceric acid 37401 11638 22344 46138 28201 7152 7006 14065 6350 6368 7515 8671 972 7358 5021 13726 13852 glutathione 5426 41959 947 23025 49161 39109 54829 31622 49162 99806 41472 46849 32759 98322 92681 48315 71257 glutamine 135454 38483 113012 101834 90034 253212 115855 92948 116847 49928 102251 69901 94847 268243 70769 107254 108629 glutamic acid 624050 473109 807498 673019 443593 298154 461532 562487 422210 393084 395444 413587 436367 363293 265270 486678 470225 glucuronic acid 4368 2844 6802 5828 4078 1541 2846 3563 1689 4367 3603 4362 3096 3907 2528 3730 4053 glucose-6-phosphate 7251 5637 1827 2208 3677 121715 6087 3294 4902 891 3401 4208 2195 8964 7522 12249 12652 glucose-1-phosphate 8622 7082 18709 1699 7492 21580 16597 12262 19040 13051 9277 7790 6045 9220 9400 9829 9829 glucose 194517 503111 104232 237894 384844 71495 266244 159602 62878 1701466 202417 766135 956154 1452426 818619 607477 627621 gluconic acid lactone 1887 338 838 3374 5331 571 716 1188 788 789 316 647 627 1602 1008 1563 1206 gluconic acid 9021 2373 2629 17129 36476 2500 2955 6416 2793 3169 1198 2031 1295 11223 229 7347 6907 gamma-aminobutyric acid 1227 2589 1388 977 2847 434 1351 1361 2043 1940 2583 2031 1564 961 1366 1635 1277 galacturonic acid 2804 2081 5431 4781 2980 1347 3354 1937 1909 5375 3142 4072 3880 4745 3325 3732 3470 galactose-6-phosphate 152 75 160 112 34 2340 217 110 233 121 160 82 152 153 130 187 200 galactinol 670 1308 726 853 758 1245 784 3536 747 1054 509 773 901 698 2285 1546 1714 fucose 2260 1618 3473 4187 2932 3546 3566 3079 4024 8477 2645 3543 3009 4607 2004 2800 4338 fructose-6-phosphate 1153 637 571 650 494 18246 2655 488 1215 589 490 822 312 1253 834 1771 1369 fructose-1-phosphate 429 809 633 585 677 739 922 797 1045 324 708 1033 484 1349 1083 709 803 fructose 2816 2151 2853 1854 4099 1609 2492 2874 3641 5983 2883 4608 4241 5307 5288 4318 3588 ethanolamine 75972 44279 62498 98321 71296 28863 43935 63197 55373 37454 52151 47567 56820 60796 45087 60790 56425 erythronic acid lactone 314 273 502 792 300 385 153 448 499 356 339 285 451 372 246 441 336 erythritol 2025 939 1115 3238 1894 1078 1515 1613 1194 1394 1520 1308 1596 1476 1180 1715 1672 epsilon-caprolactam 489 631 813 636 735 957 1087 1263 2307 817 1207 714 766 832 875 663 836 dodecanol 1443 976 1690 1527 1297 2225 1599 2126 1612 864 1330 1037 2111 2688 1381 2453 1919 docosenoic acid 2501 1551 5188 5201 4441 2404 1689 3522 3103 2068 1770 2680 2009 2767 1509 2556 2587 dihydrocholesterol 1079 1139 1478 1029 1351 1350 1118 2187 1739 1496 1303 1214 1408 1596 1624 1198 1563 D-erythro-sphingosine 9445 8808 4440 22327 10114 1409 2017 5668 5770 4502 6657 6199 4504 3593 1164 2487 7536 dehydroascorbic acid 362358 280786 447145 248833 248455 148776 392127 455401 369314 445544 355590 408462 291841 487455 345123 370455 364532 cytosin 2015 1892 2073 2009 1712 2053 1705 2191 965 533 1559 955 2275 1430 1315 1578 1481 cytidine-5-monophosphate 1188 1050 1666 1582 922 1557 1997 2064 2503 2423 1436 1360 1422 1752 1239 178 1398 cytidine 1406 368 703 287 875 301 449 1145 365 236 555 514 644 585 351 764 654 cysteine-glycine 3449 5049 2036 1297 5474 1417 3837 4754 4306 7353 4709 5794 4114 15861 4824 7198 6720 cysteine 11381 23962 7456 14544 47839 3438 19940 23553 26652 20956 35339 30923 22313 35378 23861 22583 23772 cyano-l-alanine 797 1713 833 729 1678 1400 1132 1222 2478 2390 1557 1782 1231 1033 1540 861 1102 creatinine 963302 576033 845109 695297 693902 3869264 1467350 826141 998646 644776 845301 682655 918465 1568482 1733905 887332 974865 conduritol-beta-epoxide 669 2335 754 1037 494 1085 406 3798 641 1163 482 884 1275 974 2174 1476 2238 citrulline 16958 23262 15332 21107 18613 12656 9465 14520 14820 12644 12934 15445 14362 11331 11216 13459 12779 cis-gondoic acid 550 1047 738 4032 1002 392 484 484 351 390 529 315 1038 718 678 606 558 cholesterol 884790 666842 1195304 719028 894373 978485 982967 1452189 1318515 982106 983429 896385 1047803 1183307 1190248 998806 1001800 butane-2,3-diol 36657 152737 13096 39867 29348 9423 9664 6857 3132 40849 2837 7049 61958 8828 18074 28516 25616 beta-sitosterol 7005 18400 17375 11351 14191 13832 9619 13891 22399 15439 19750 17763 23978 20383 14471 17128 16402 beta-glycerolphosphate 1620 848 1276 1169 1247 2297 1449 2235 1740 1148 977 984 679 1078 1308 816 1148 beta-alanine 2430 2402 8693 7143 3595 4093 2605 6864 1922 2496 2049 5493 5677 4932 7897 6594 5893 azelaic acid 1540 2068 1355 1157 1479 3018 2610 2550 2554 2174 1854 238 453 1514 3086 1843 2102 aspartic acid 109874 121959 193607 137802 64525 153253 174057 147659 188712 157876 136909 105584 116757 126729 136555 140519 136022 asparagine 38119 50547 33136 39228 33300 26071 27111 23393 30773 29986 34570 35114 33100 32837 27390 30286 33946 ascorbic acid 5605 3534 1352 4106 2622 5296 5479 8190 1805 3531 1524 3300 3313 2081 5215 4252 3677 arachidonic acid 30519 19429 30638 19975 28389 38114 16195 32380 30097 17879 22744 21988 27658 33147 31624 25023 25661 arachidic acid 19212 18406 27074 30218 25426 13850 15751 11463 23503 21147 22780 19231 17457 24257 14191 21500 21522 aminomalonate 34135 23228 42571 29331 24009 14506 21013 26505 25434 22836 32469 26630 27494 19602 19166 22071 21904 alpha-ketoglutarate 7078 1181 7127 9922 6933 1327 1300 5322 2428 1580 2021 1908 4400 1342 1337 3235 2744 alpha-aminoadipic acid 1357 782 2265 1367 1050 739 1171 1329 1227 1063 897 1058 1148 1111 870 1142 1062 allantoic acid 2422 2036 4031 6774 407 885 1668 1525 1156 1382 2132 253 1313 1471 832 2501 2416 alanine 1292348 1710587 174758 1057889 2089100 109402 1687310 1967512 1773439 1793409 1698227 2014184 1578878 123284 1517040 1506266 1715938 adipic acid 50689 42001 21320 13969 26450 32541 26565 33851 66011 31837 35023 33220 16316 61454 49143 33857 35680 adenosine-5-monophosphate 61405 18190 109725 58711 1154 16526 66174 97893 113155 23518 24105 33904 23397 12457 6742 38293 35430 adenosine 1135 163 441 710 268 476 433 629 924 378 331 412 225 325 360 314 296 adenine 2504 3435 6251 4035 2904 3835 3961 5012 3829 3840 3215 3836 4664 4641 3984 3702 3835 5-methoxytryptamine 12795 7382 24846 10665 7485 2190 20787 22854 24228 20574 17848 17153 13102 24317 19599 21674 17311 5-hydroxy-3-indoleacetic acid 1238 1196 830 656 3389 1129 1033 1412 943 1561 2404 1723 6903 3698 4614 2765 2575 5'-deoxy-5'-methylthioadenosine 771 686 1734 1093 888 366 731 1118 874 854 620 795 1060 1463 960 833 987 4-hydroxybutyric acid 1686 1226 2636 1509 1465 3585 1769 3100 1540 1365 366 897 1426 1596 1477 1827 1798 3-phosphoglycerate 7758 4021 6138 7048 9079 11952 13364 14288 7327 7211 12156 13256 17818 28102 1539 13719 13572 3-phenyllactic acid 7720 7081 4537 20110 13828 1491 1913 3182 804 3216 1792 1449 4333 1201 2523 4956 4450 3-hydroxybutyric acid 5929 5771 18229 16850 6567 11127 18883 37495 4554 2007 5134 2004 5722 6718 9578 13146 10644 3,6-anhydro-D-galactose 226 420 225 295 321 431 406 346 187 808 120 337 456 781 484 357 383 2-monoolein 13858 53268 8926 19740 9596 10805 10735 787 5603 17343 6185 8302 20461 20149 24860 18205 18140 2-ketoisocaproic acid 11110 4302 7325 21604 15175 8700 7526 12696 8050 5698 7116 5597 7085 7296 6533 8675 7469 2-hydroxyglutaric acid 5527 3890 6288 10049 5429 1505 2226 4385 2543 2393 2744 3351 1176 1116 1618 3985 2471 2-hydroxybutanoic acid 8542 10814 10036 13362 21837 5682 18119 16707 23815 22324 24626 14672 13481 6815 15026 13179 14073 2-aminobutyric acid 10548 17271 12020 30711 24601 7834 21370 19026 13428 4685 14550 8291 7381 7524 6616 13504 14210 2,3-dihydroxybutanoic acid 853 341 632 601 507 392 523 628 505 496 401 297 437 497 577 579 545 1-monostearin 2184 1891 2133 1572 1986 3960 2259 2939 2035 1174 2582 1562 1577 3053 2434 1871 2395 1-monopalmitin 2338 2367 3338 2300 1836 5890 2571 2828 2189 1624 2180 1872 2749 4005 3125 2829 2670 1-monoolein 8600 23079 7697 24200 7230 9647 7939 3622 3497 9283 3127 4554 8761 11228 11130 14155 13985 1-kestose 323 571 486 314 278 5384 821 522 796 600 737 466 365 848 713 256 657 MS_METABOLITE_DATA_END #METABOLITES METABOLITES_START metabolite_name PubChem KEGG retention index quantitated m/z succinic acid 1110 C00042 370608 247 fumaric acid 444972 C00122 390016 245 malic acid 525 C00711 463180 233 xylulose 439205 C00312 553450 173 xylose 135191 C00181 543267 103 xylonic acid isomer 10264 C02341 590775 189 xanthine 1188 C00385 701688 353 valine 6287 C00183 313502 144 uridine-5'-monophosphate 6030 980179 169 uridine 6029 C00299 861508 217 uric acid 1175 C00366 730691 441 urea 1176 C00086 326574 189 uracil 1174 C00106 385816 241 UDP-N-acetylglucosamine 445675 C00043 623789 226 UDP-glucuronic acid 17473 C00167 585473 217 tyrosine 6057 C00082 671252 218 tryptophan 6305 C00078 780482 202 trans-4-hydroxyproline 5810 C01157 460662 158 tocopherol gamma- 92729 C02483 1026121 223 tocopherol alpha- 638015 C00376 1067809 237 thymine 1135 C00178 420133 255 thymidine 5789 C00214 349402 170 threonine 6288 C00188 409568 218 threonic acid 5460407 C01620 497572 292 taurine 1123 C00245 556690 326 sulfuric acid 1118 C00059 285430 227 sucrose 5988 C00089 912704 271 stearic acid 5281 C01530 787622 117 squalene 638072 C00751 976237 95 spermidine 1102 C00315 792924 144 sorbitol 5780 C00794 667922 217 sinigrin 6911854 811011 361 serine 5951 C00065 395020 204 saccharic acid 33037 C00818 699211 333 ribulose-5-phosphate 439184 C00199 735908 357 ribose-5-phosphate 439167 C00117 731837 315 ribose 5779 C00121 553135 217 ribonic acid 5460677 C01685 599680 292 ribitol 827 C00474 575497 217 raffinose 439242 C00492 1120886 361 pyrophosphate 1023 C00013 327517 110 putrescine 1045 C00138 588872 174 p-tolyl glucuronide 154035 847531 180 pseudo-uridine 15047 C02067 815904 217 proline 145742 C00148 364716 142 pimelic acid 385 C02656 523205 155 phytosphingosine 122121 C12144 910976 204 phosphogluconic acid 91493 C00345 847013 299 phosphoethanolamine 1015 C00346 603912 299 phosphoenolpyruvate 58114173 C00074 518184 211 phosphate 1004 C00009 345365 314 phenylpyruvate 517753 91 phenylalanine 6140 C00079 537804 192 pelargonic acid 8158 C01601 398892 215 parabanic acid 67126 C00802 464991 100 pantothenic acid 6613 C12276 690887 291 palmitoleic acid 445638 C08362 706259 311 palmitic acid 985 C00249 713809 313 oxoproline 7405 C01879 485935 156 ornithine 6262 C00077 527113 142 O-phosphoserine 57689797 C01005 624355 356 oleic acid 445639 C00712 781527 339 octadecylglycerol 3681 C13858 928878 205 noradrenaline 439260 C00547 754841 174 nicotinic acid 938 C00253 366992 180 nicotinamide 936 C00153 469827 179 N-acetylmannosamine 439281 C00645 735323 319 N-acetylaspartic acid 65065 C01042 548028 158 myristic acid 11005 C06424 634414 285 myo-inositol 892 C00137 730022 305 methionine sulfoxide 158980 C02989 637588 128 methionine 6137 C00073 483560 176 methanolphosphate 13130 289520 241 mannose 18950 C00159 643848 205 maltotriose 439586 C01835 1176044 361 maltose 439186 C00208 946601 204 maleimide 10935 C07272 245118 154 lyxitol 439255 C00532 573587 217 lysine 5962 C00047 662197 317 linoleic acid 5280450 C01595 777414 150 leucine 6106 C00123 346101 158 lauric acid 3893 C02679 547906 117 lanosterol 246983 C01724 1129573 393 lactic acid 612 C01432 219848 191 isothreonic acid 151152 C00639 489385 292 isomaltose 439193 C00252 983199 160 isoleucine 6306 C00407 359251 158 inositol-4-monophosphate 440043 C03546 845976 315 inosine 5'-monophosphate 8582 C00130 1016811 169 inosine 6021 C00294 897184 230 indole-3-lactate 92904 C02043 764586 202 hypoxanthine 790 C00262 619128 265 histidine 6274 C00135 663102 154 hexadecylglycerol 72733 C13859 867593 205 heptadecanoic acid 10465 751309 117 guanosine 6802 C00387 954962 324 glycine 750 C00037 368707 248 glycerol-alpha-phosphate 754 C03189 590747 357 glycerol 753 C00116 344466 205 glyceric acid 752 C00258 377308 189 glutathione 124886 C00051 761296 213 glutamine 5961 C00064 600000 156 glutamic acid 33032 C00025 527086 246 glucuronic acid 94715 C00191 665901 333 glucose-6-phosphate 5958 C00092 808788 387 glucose-1-phosphate 65533 C00103 594647 217 glucose 64689 C00221 657941 319 gluconic acid lactone 7027 C00198 645815 220 gluconic acid 6857417 C00800 693148 333 gamma-aminobutyric acid 119 C00334 364801 102 galacturonic acid 441476 C08348 678231 333 galactose-6-phosphate 439404 C01113 828102 387 galactinol 11727586 C01235 1048207 204 fucose 439650 C02095 578299 160 fructose-6-phosphate 440641 C05345 804750 315 fructose-1-phosphate 439394 C01094 803180 387 fructose 439709 C02336 641863 307 ethanolamine 700 C00189 344654 174 erythronic acid lactone 5325915 C02341 407495 247 erythritol 222285 C00503 471922 217 epsilon-caprolactam 7768 C06593 353069 170 dodecanol 8193 C02277 507619 243 docosenoic acid 6433893 911928 129 dihydrocholesterol 66066 C12978 1082070 215 D-erythro-sphingosine 5280335 C00319 859500 204 dehydroascorbic acid 440667 C05422 633423 173 cytosin 597 C00380 486724 254 cytidine-5-monophosphate 6131 C00055 700635 243 cytidine 934269 223 cysteine-glycine 439498 C01419 715335 220 cysteine 5862 C00097 500158 220 cyano-l-alanine 439742 C02512 403745 141 creatinine 588 C00791 502599 115 conduritol-beta-epoxide 9989541 675635 318 citrulline 9750 C00327 621404 157 cis-gondoic acid 5282768 C16526 851223 367 cholesterol 5997 C00187 1078536 129 butane-2,3-diol 262 C03046 205778 117 beta-sitosterol 222284 C01753 1128225 129 beta-glycerolphosphate 2526 C02979 574470 243 beta-alanine 239 C00099 435564 248 azelaic acid 19347555 C08261 610551 317 aspartic acid 5960 C00049 480387 232 asparagine 6267 C00152 553078 231 ascorbic acid 54670067 C00072 672898 332 arachidonic acid 444899 C00219 834339 91 arachidic acid 10467 C06425 856421 117 aminomalonate 100714 C00872 455754 218 alpha-ketoglutarate 51 C00026 507392 198 alpha-aminoadipic acid 92136 C00956 573295 260 allantoic acid 203 C00499 723539 259 alanine 5950 C00041 240378 116 adipic acid 196 C06104 474435 111 adenosine-5-monophosphate 6083 C00020 1041375 315 adenosine 60961 C00212 918039 236 adenine 190 C00147 646534 264 5-methoxytryptamine 1833 C05659 864466 174 5-hydroxy-3-indoleacetic acid 1826 C05635 777606 290 5'-deoxy-5'-methylthioadenosine 439176 C00170 967036 236 4-hydroxybutyric acid 10413 C00989 325027 233 3-phosphoglycerate 724 C00597 610734 227 3-phenyllactic acid 3848 516011 193 3-hydroxybutyric acid 92135 C01089 278632 191 3,6-anhydro-D-galactose 16069996 C06474 588886 231 2-monoolein 5319879 941794 129 2-ketoisocaproic acid 70 C00233 310761 89 2-hydroxyglutaric acid 43 C02630 506306 247 2-hydroxybutanoic acid 440864 C05984 258161 131 2-aminobutyric acid 6657 C02721 288133 130 2,3-dihydroxybutanoic acid 250402 384796 292 1-monostearin 24699 D01947 959214 203 1-monopalmitin 14900 900644 371 1-monoolein 5283468 955584 129 1-kestose 440080 C03661 1123027 361 METABOLITES_END #END