#METABOLOMICS WORKBENCH juliehaines_20250310_124425 DATATRACK_ID:5714 STUDY_ID:ST003794 ANALYSIS_ID:AN006237 PROJECT_ID:PR002369 VERSION 1 CREATED_ON March 13, 2025, 7:40 pm #PROJECT PR:PROJECT_TITLE Advancing the Biochemical Understanding of Maple Syrup Urine Disease and the PR:PROJECT_TITLE impact of liver transplantation: A Pilot Study PR:PROJECT_SUMMARY Maple syrup urine disease (MSUD) is a rare autosomal recessive metabolic PR:PROJECT_SUMMARY disorder caused by impaired catabolism of branched-chain amino acids (BCAAs), PR:PROJECT_SUMMARY leading to severe systemic dysregulation. The disease has an incidence of PR:PROJECT_SUMMARY approximately 1 in 185,000 live births in the general U.S. population, with much PR:PROJECT_SUMMARY higher prevalence in the Mennonite communities (up to 1 in 140 live births in PR:PROJECT_SUMMARY the latter due to the c.1312T>A p.Tyr438Asn BCKDHA founder mutation). Using a PR:PROJECT_SUMMARY multi-omics approach integrating metabolomics, lipidomics, and proteomics, we PR:PROJECT_SUMMARY analyzed blood samples from three MSUD patients on a BCAA-restricted diet, two PR:PROJECT_SUMMARY post-liver transplantation patients, and six healthy controls. Gene ontology PR:PROJECT_SUMMARY analysis highlighted enriched pathways in MSUD, including glycolysis, oxidative PR:PROJECT_SUMMARY phosphorylation, and purine metabolism, revealing systemic metabolic imbalances. PR:PROJECT_SUMMARY Lipidomics indicated disruptions in sphingolipids and lysophosphatidylcholines, PR:PROJECT_SUMMARY which impact cellular signaling and membrane integrity. Liver transplantation PR:PROJECT_SUMMARY corrected some abnormalities, but several metabolites and proteins remained PR:PROJECT_SUMMARY dysregulated. Proteomic analysis revealed significant alterations in redox PR:PROJECT_SUMMARY homeostasis, energy metabolism, and cytoskeletal organization, with only partial PR:PROJECT_SUMMARY recovery post-transplantation. Post-translational modifications, such as PR:PROJECT_SUMMARY methylation and cysteine oxidation, suggested ongoing oxidative stress and PR:PROJECT_SUMMARY immune activation in the LT group. Elevated levels of L-isoleucine, L-valine, PR:PROJECT_SUMMARY and their ketoacids persisted post-transplant, correlating with impaired amino PR:PROJECT_SUMMARY acid metabolism, lipid remodeling, and protein folding. These findings provide PR:PROJECT_SUMMARY comprehensive insight into MSUD-associated metabolic dysfunctions and highlight PR:PROJECT_SUMMARY potential therapeutic targets to improve patient outcomes. PR:INSTITUTE University of Colorado Denver PR:LABORATORY Angelo D'Alessandro in collaboration with D. Holmes Morton PR:LAST_NAME Haines PR:FIRST_NAME Julie PR:ADDRESS 12801 E 17th Ave, Room 1303, Aurora, Colorado, 80045, USA PR:EMAIL julie.haines@cuanschutz.edu PR:PHONE 3037243339 #STUDY ST:STUDY_TITLE Metabolomics characterization of blood samples from patients with maple syrup ST:STUDY_TITLE urine disease (MSUD) in comparison to healthy controls ST:STUDY_SUMMARY Metabolomics analysis was performed on blood samples from MSUD patients and MSUD ST:STUDY_SUMMARY patients post-liver transplantation in comparison to healthy controls. ST:INSTITUTE University of Colorado Denver ST:LAST_NAME Haines ST:FIRST_NAME Julie ST:ADDRESS 12801 E 17th Ave, Room 1303, Aurora, Colorado, 80045, USA ST:EMAIL julie.haines@cuanschutz.edu ST:PHONE 3037243339 #SUBJECT SU:SUBJECT_TYPE Human SU:SUBJECT_SPECIES Homo sapiens SU:TAXONOMY_ID 9606 SU:GENDER Male and female #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 - AG-88-1 Disease state:Healthy control | Sample source:Whole blood RAW_FILE_NAME(raw file name)=AG-88-1 SUBJECT_SAMPLE_FACTORS - AG-88-2 Disease state:Healthy control | Sample source:Whole blood RAW_FILE_NAME(raw file name)=AG-88-2 SUBJECT_SAMPLE_FACTORS - AG-88-3 Disease state:Healthy control | Sample source:Whole blood RAW_FILE_NAME(raw file name)=AG-88-3 SUBJECT_SAMPLE_FACTORS - AG-88-4 Disease state:Healthy control | Sample source:Whole blood RAW_FILE_NAME(raw file name)=AG-88-4 SUBJECT_SAMPLE_FACTORS - AG-88-5 Disease state:Healthy control | Sample source:Whole blood RAW_FILE_NAME(raw file name)=AG-88-5 SUBJECT_SAMPLE_FACTORS - AG-88-6 Disease state:Healthy control | Sample source:Whole blood RAW_FILE_NAME(raw file name)=AG-88-6 SUBJECT_SAMPLE_FACTORS - AG-88-7 Disease state:MSUD | Sample source:Whole blood RAW_FILE_NAME(raw file name)=AG-88-7 SUBJECT_SAMPLE_FACTORS - AG-88-8 Disease state:MSUD | Sample source:Whole blood RAW_FILE_NAME(raw file name)=AG-88-8 SUBJECT_SAMPLE_FACTORS - AG-88-9 Disease state:MSUD | Sample source:Whole blood RAW_FILE_NAME(raw file name)=AG-88-9 SUBJECT_SAMPLE_FACTORS - AG-88-10 Disease state:MSUD with transplant | Sample source:Whole blood RAW_FILE_NAME(raw file name)=AG-88-10 SUBJECT_SAMPLE_FACTORS - AG-88-11 Disease state:MSUD with transplant | Sample source:Whole blood RAW_FILE_NAME(raw file name)=AG-88-11 SUBJECT_SAMPLE_FACTORS - AG-88-12 Disease state:Pool of MSUD with transplant | Sample source:Whole blood RAW_FILE_NAME(raw file name)=AG-88-12 #COLLECTION CO:COLLECTION_SUMMARY The study was conducted in accordance with the Declaration of Helsinki; CO:COLLECTION_SUMMARY specimens were collected at the Central Pennsylvania Clinic, Boston Children’s CO:COLLECTION_SUMMARY Hospital, and Lancaster General Hospitals under institutionally reviewed CO:COLLECTION_SUMMARY Protocol No. 2014-12 and upon signing of informed consent. Blood collections CO:COLLECTION_SUMMARY were carried out using standard equipment and clinical procedures. To study the CO:COLLECTION_SUMMARY metabolic changes occurring in patients with maple syrup urine disease, whole CO:COLLECTION_SUMMARY blood was collected from 3 patients having diagnosis of MSUD with a biallelic CO:COLLECTION_SUMMARY inactivating mutation of BCKDHA (c.1312T>A p.Tyr438Asn). Additional samples were CO:COLLECTION_SUMMARY collected from 6 healthy controls. Finally, samples were collected from two CO:COLLECTION_SUMMARY patients having a previous diagnosis of MSUD, but who had received liver CO:COLLECTION_SUMMARY transplantations to cure their condition. These two samples were combined 1:1, CO:COLLECTION_SUMMARY v:v, to generate a third replicate for statistical analysis. CO:SAMPLE_TYPE Blood (whole) #TREATMENT TR:TREATMENT_SUMMARY No treatment was performed #SAMPLEPREP SP:SAMPLEPREP_SUMMARY Blood aliquots were thawed on ice, then 10 uL of whole blood was treated with SP:SAMPLEPREP_SUMMARY with 90 uL of cold 5:3:2 methanol:acetonitrile:water. Samples were vortexed 30 SP:SAMPLEPREP_SUMMARY min at 4 degrees C then supernatants clarified by centrifugation (10 min, 10,000 SP:SAMPLEPREP_SUMMARY g, 4 degrees C). For negative ion mode runs, supernatants were transferred to SP:SAMPLEPREP_SUMMARY autosampler vials. For positive ion mode runs, 35 uL of extract was dried on a SP:SAMPLEPREP_SUMMARY speedvac then resuspended in 35 uL of 0.1% formic acid in water. FA solutions SP:SAMPLEPREP_SUMMARY were then transferred to autosampler vials for analysis. SP:PROCESSING_STORAGE_CONDITIONS 4℃ SP:EXTRACT_STORAGE -80℃ #CHROMATOGRAPHY CH:CHROMATOGRAPHY_SUMMARY Positive C18 CH:CHROMATOGRAPHY_TYPE Reversed phase CH:INSTRUMENT_NAME Thermo Vanquish CH:COLUMN_NAME Waters ACQUITY UPLC BEH C18 (100 x 2.1mm,1.7um) CH:SOLVENT_A 100% water; 0.1% formic acid CH:SOLVENT_B 100% acetonitrile CH:FLOW_GRADIENT 0-0.5 min hold at 0% B, 0.5-1.1 min increase to 100% B, 1.1-2.75 min hold at CH:FLOW_GRADIENT 100% B, 2.75-3 min decrease to 0% B, 3-5 min hold at 0% B CH:FLOW_RATE 0.45 mL/min CH:COLUMN_TEMPERATURE 45 CH:SAMPLE_INJECTION 10 uL #ANALYSIS AN:ANALYSIS_TYPE MS #MS MS:INSTRUMENT_NAME Thermo Orbitrap Exploris 120 MS:INSTRUMENT_TYPE Orbitrap MS:MS_TYPE ESI MS:ION_MODE POSITIVE MS:MS_COMMENTS The Q Exactive was run in positive ion mode, scanning using full MS from 65-975 MS:MS_COMMENTS m/z at 120,000 resolution. Electrospray ionization was achieved with 50 Arb MS:MS_COMMENTS sheath gas, 10 Arb auxiliary gas, and 3.4 kV spray voltage. Calibration was MS:MS_COMMENTS performed prior to the run using the PierceTM Positive and Negative Ion MS:MS_COMMENTS Calibration Solutions (Thermo Fisher Scientific). Run order of samples was MS:MS_COMMENTS randomized and technical replicates were injected after every 4 samples to MS:MS_COMMENTS assess quality control. #MS_METABOLITE_DATA MS_METABOLITE_DATA:UNITS peak area MS_METABOLITE_DATA_START Samples AG-88-1 AG-88-2 AG-88-3 AG-88-4 AG-88-5 AG-88-6 AG-88-7 AG-88-8 AG-88-9 AG-88-10 AG-88-11 AG-88-12 Factors Disease state:Healthy control | Sample source:Whole blood Disease state:Healthy control | Sample source:Whole blood Disease state:Healthy control | Sample source:Whole blood Disease state:Healthy control | Sample source:Whole blood Disease state:Healthy control | Sample source:Whole blood Disease state:Healthy control | Sample source:Whole blood Disease state:MSUD | Sample source:Whole blood Disease state:MSUD | Sample source:Whole blood Disease state:MSUD | Sample source:Whole blood Disease state:MSUD with transplant | Sample source:Whole blood Disease state:MSUD with transplant | Sample source:Whole blood Disease state:Pool of MSUD with transplant | Sample source:Whole blood L-alanine 4454691 6397874 8666188 8300264 5202707 5541672 5794820 4392898 7196577 5979146 4283846 4712234 L-arginine 385376 555381 960659 1048594 708452 478265 658835 1366834 1274296 1310763 1387528 1295247 L-asparagine 1048303 1052997 920734 884318 683476 1221396 1270617 1190353 1196613 1112514 1325520 1166671 L-aspartate 767913 698229 2153692 782595 1745339 2026175 3302346 263656 3342506 3697142 207051 1928767 L-cysteine 180420 15325 446241 137488 78216 88260 60793 57378 6031 428157 19816 137434 L-glutamate 11870935 15017167 16314203 14087912 10613203 11454129 21817202 10739231 20421746 19509862 10166220 13898365 L-glutamine 11041205 10302753 10905140 10409453 14601836 14529957 13504008 9142199 11513188 13475881 9164812 10840696 L-histidine 2696613 2752700 2542488 2783771 2563337 2753855 3298682 3551361 2853161 3356636 3364506 3293184 L-Isoleucine 84899976 78624744 122989000 45923108 45749780 65737552 139229344 211124592 211437232 132629912 204785984 172530160 L-Leucine 144846784 140640880 221289712 104064232 90478520 111462184 170112128 223169856 368055904 187878144 251225264 211668240 L-leucine/isoleucine 84899976 78624744 122989000 45923108 45749780 65737552 139229344 211124592 211437232 132629912 204785984 172530160 L-lysine 3334208 3603034 3676735 2950121 2342356 3469534 3430611 2320370 3615592 2761120 3169195 2996528 L-methionine 31600776 33544466 55219372 31655554 27300570 29996080 35699860 19114224 44790804 34035488 38694244 36504524 L-phenylalanine 329234272 364884384 389779968 273543424 304992416 352027296 338704800 261968848 452333920 373135776 407859168 371806496 L-proline 91908096 99445848 139142608 82998032 80778160 86568160 75835560 46831724 91023256 93603208 49615420 68999768 L-serine 820843 1054038 795199 787175 738276 999877 1175495 910168 1083848 919208 1090377 958791 L-threonine 3740722 3904207 4212095 3363813 3811405 4031621 4568922 4226932 5225084 3588365 6272072 4584020 L-tryptophan 75261384 65713652 70566688 45396788 75407808 77406848 55722188 69796032 61911504 63984096 93973352 69251664 L-tyrosine 75735432 99121240 134639344 73563848 52737884 115794912 64145060 74042456 152207696 75397912 80737560 75282104 L-valine 163074368 156369456 229926576 117720920 111644776 129354840 222850832 144921104 292941184 214909904 185369136 187455488 AMP 36593828 62422432 20547866 52261420 36444780 56017932 178887376 74973520 148673488 135496944 115897280 125419800 Adenosine 147456 251126 207778 155814 113838 116893 803135 184691 773300 284322 378131 312705 Adenine 244179 190652 135430 190372 91973 197923 554913 250354 478132 461941 310062 429412 GMP 399665 1286497 208597 818193 1048738 812089 16759671 1000538 2904207 4536590 1505344 2816775 Guanosine 16090 52582 6128 11577 43789 12257 163869 67131 175873 17805 29422 40374 Guanine 1348508 1536160 2414758 1343904 1119166 1288581 2187177 810268 1654192 1560857 1839626 1522314 CMP 58846 70530 130763 311210 22079 77148 105979 112696 276957 144355 166056 156821 dCMP 264077 219655 353775 233557 231818 471286 443155 415258 1325909 349782 975969 623284 Cytosine 699053 90318 533918 244199 110303 540921 703328 503055 2376140 894339 1090720 943279 dTMP 288960 348171 845068 638061 456364 1287246 1580798 447001 230567 377355 330170 256773 UMP 16366 185217 38626 151326 104095 58991 610209 163785 624254 459900 307525 432084 Uracil 229285 97131 327302 315977 397274 231514 772869 226140 386332 293890 244599 264313 Inosine 763806 8148473 82855 318428 1276830 299437 1972747 4221764 13060287 2157453 1987682 1530401 Hypoxanthine 47975456 188632016 35074288 81342120 70435992 33012656 175676048 91088168 324071104 99694696 73383512 87588408 Xanthine 211572 183725 826415 417240 318230 134037 1471752 234154 433507 909091 167760 498975 Allantoate 88752 85011 208767 141308 504869 163245 106660 55908 10730 143965 75376 72834 (S)(+)-Allantoin 363267 285601 758296 160334 162966 265320 710682 271621 559015 484285 284106 379754 5-Hydroxyisourate 5110185 5680512 5837368 5475410 4764585 6063518 6747632 4349236 7536708 5729078 4648131 5207448 3',5'-Cyclic AMP 107929 132701 180827 204569 76548 112830 306566 51769 395940 212246 84584 136468 5-6-Dihydrothymine 3187637 1463315 3034881 1114829 3418012 520499 1889773 1536817 3366127 1846258 1004212 1496257 Nicotinamide 74189648 74923464 94682696 73289768 49629408 52246100 69330168 50818644 114701640 63605668 53635108 60673244 Adenylosuccinic acid 85908 101364 41195 105535 128067 121145 397613 187775 248233 241788 171685 148772 ADP-D-ribose 5841061 229256 10312431 4855270 1927210 4087109 2253055 1966032 50755 3488835 1032674 2022883 NAD+ 99789 146398 147072 64523 33443 91194 74460 19447 111126 48653 48151 75741 Glutathione 131034968 267494448 12542673 167183888 486838688 197741136 33820388 266456912 514678176 99269912 218086016 175285296 Glutathione disulfide 55050612 71450952 81126144 61246732 64479184 84245536 135648240 35553540 140616848 56470068 42574160 46512480 S-Glutathionyl-L-cysteine 56496 33748 792887 210231 216246 222871 1320937 45690 0 348807 32361 101049 Cys-Gly 851325 1968360 67608 1223918 3744785 1442420 204518 2090255 3978119 748457 1348840 1179690 Ascorbate 10091 9003 15053 74268 318609 95305 112443 26441 3405 67280 40561 61478 Dehydroascorbate 161649 46005 574275 341584 416125 219797 55887 97971 29521 185743 91395 104253 gamma-L-Glutamyl-L-cysteine 14464 321713 76715 135179 269233 141555 1345170 158061 856460 284509 354214 275267 gamma-L-Glutamyl-D-alanine 154595 395875 687470 457243 684265 336004 501608 348742 1105270 663482 407262 448473 gamma-Glutamyl-gamma-aminobutyrate 618377 1579873 1548952 1335743 689251 629266 1672475 956213 3001088 1164814 879043 940087 Bis-gamma-glutamylcystine 138892 147109 295408 127169 68399 135472 205798 63904 136145 157793 153691 159773 (5-L-Glutamyl)-L-glutamine 248930 206677 469876 232684 132549 155159 266226 179929 791007 333433 429612 316832 5-L-Glutamyl-taurine 20093 16243 19139 47147 15897 15193 551128 16250 26896 21466670 40424 10529786 L-Homocysteine 161801 159157 126978 138961 599867 129732 116472 107457 645955 80754 187344 116471 Dimethylglycine 2548032 1543584 1742136 846724 1069652 1880577 841467 644261 755276 520276 1261192 772062 Phosphoserine 559095 871615 1284630 902514 458766 472244 1336990 546461 1693611 1026063 539545 690967 S-Adenosyl-L-homocysteine 279803 433074 329249 286436 288021 303083 627736 394201 1083170 320111 452603 326782 S-Adenosyl-L-methionine 348770 57607 145837 201014 65073 57333 28696 56160 152383 249780 37540 199807 Folate 156872 33132 145789 107742 50484 53659 42599 14134 33164 78166 11450 117880 5-10-Methenyltetrahydrofolate 335844 188789 31495 197112 118076 395075 70026 18613 50537 146025 14487 44258 Dihydrofolate 424872 106931 379053 184901 5553 25563 81712 43859 64340 345487 22944 142516 Ornithine 422081 503077 767947 365247 338206 407709 603029 716169 1228374 608796 715644 699032 L-Citrulline 2990304 3535289 4263355 4537446 4767660 4612738 4502491 3763635 3964485 5848346 3093381 4317126 Argininosuccinate 96692 118773 116056 55779 41216 35426 5268 21030 159887 13914 36905 17966 Spermidine 8313749 10435545 19532986 13343040 10004760 17534416 9767184 15166303 21309824 12182799 12278685 12614683 Spermine 4884577 27896374 23688562 17211864 35346920 12352152 9200788 8470362 29501726 10211803 15679781 14749435 alpha-D-Glucosamine 1-phosphate 192949 186035 319164 222973 115249 205267 339145 206851 413062 324322 275374 270617 D-Glucosamine 1148099 1187491 486353 974517 872856 1249199 1021013 1286246 733929 1333745 1251072 1318231 CMP-N-acetylneuraminate 3911155 4800146 5711772 4154505 5178775 5910379 9507083 2511624 9944191 4138931 3041299 3380196 Carnosine 915209 831386 1534631 1226741 412495 1675125 1119099 887286 1571709 1037392 1099312 1001756 Phosphocreatine 305791 577156 286622 593288 204553 405734 412020 1136817 823086 393044 1112598 743823 Creatine 66727580 142042896 138493392 139194976 105116280 107797304 92080536 135352704 172838864 95047936 161092144 126243112 Creatinine 13709896 9111945 17023960 8883033 13525691 9545908 21860944 8824524 12077928 23895146 8181290 15794416 4-Acetamidobutanoate 816704 671648 1042922 66034 117708 614696 73389 33646 65134 154395 76450 110455 N-Acetyl-L-citrulline 87593 280704 136354 230552 111964 173775 220438 259260 411173 153805 380792 293187 Pantothenate 4312960 60976 746911 463852 793736 433912 36138 2577894 347959 208587 12168535 5767044 5-6-Dihydrouracil 122521 111134 283932 179376 169622 186023 171605 120775 175190 141615 56554 137506 Pantetheine 453848 569504 360571 357153 364584 450529 480117 514870 587726 516028 411775 396302 Taurine 476704 1957320 2887049 3370544 2420958 1713982 2880596 2793671 2956539 2222221 3655124 2827215 L-Cysteate 58635 61712 68260 88412 76795 34398 26316 67382 28232 56097 44745 75262 (R)-S-Lactoylglutathione 1918265 9187485 280380 446807 1338068 2477509 909941 5696208 35578772 1388348 4637932 1694081 L-Methionine S-oxide 855657 1036177 595937 493164 214210 950484 543133 709280 723319 582193 858687 684049 Indole-3-acetaldehyde 66716 119412 95343 133383 70146 106919 82934 50892 80969 47016 178419 60469 6-Hydroxykynurenic acid 33508 19546 139532 109852 330747 99752 429177 40873 82214 70391 46452 27236 kynurenine 2992185 2861393 3994387 2977846 4771542 4125974 3395928 3743426 3947051 4443524 4871972 4602948 Anthranilate 500865 662267 257336 777214 1414359 2007271 287668 842015 844055 621997 732812 666859 Picolinic acid 63295 39946 83709 56601 44803 82338 88330 44325 47089 31270 790209 396212 g-Oxalo-crotonate 369918 954320 247138 515129 388537 225009 1205139 530206 1158917 607934 433812 662440 8-Methoxykynurenate 234927 195815 253116 232988 219797 237430 424186 39498 74586 218897 38905 125509 L-Adrenaline 427585 151098 273070 358929 298693 225547 178929 297642 211157 507172 189388 241094 Ectoine 218991 247239 314687 251080 110365 229324 254398 157805 211731 241929 178936 200150 N-Methylethanolamine phosphate 1307627 573775 19787332 8042274 5620536 2728906 700571 1409431 8168489 1572775 1513400 1089725 Sphingosine 74988 160118 538946 704511 910158 336182 572710 173858 318631 222452 425256 260505 Acetylcholine 19358576 22750138 35424880 29740016 28579718 18596738 20360838 18894352 35599908 20881706 20560850 20506688 CDP-choline 224213 303297 550855 235810 289689 167297 555243 301240 782654 479659 519144 523697 Choline 119641128 101379008 55407424 40073172 51972976 41784244 86419608 40712084 128687304 68978504 54512932 57943420 Sphinganine 1-phosphate 88080 78570 314073 232870 213661 161593 141147 75173 203265 241503 151087 111634 L-Carnitine 36787216 46387268 82881016 58591548 85387792 81156416 57253940 86576296 81289080 81558168 84533904 80385376 acetyl-carnitine (acyl-C2) 39302088 54003644 70479240 70801560 101456352 170822768 60400076 100771880 61825556 27679446 140181008 88523416 propionyl-carnitine (acyl-C3) 42109496 32950704 29802954 12682179 26189130 59382028 21358576 59280716 45285588 13287589 97532664 35215728 butanoyl-l-carnitine (acyl-C4) 6102352 3324567 7288173 4265915 3630065 6423916 1894251 692096 1212090 3704694 2923871 3091963 acyl-C4-OH 2486189 5669434 2947190 962507 5300267 10549837 71760 1133625 700148 33645 1567364 474418 acyl-C4-DC 18694884 21790202 27292318 20316670 10555986 15765772 18636160 22787816 38157796 20135712 25944502 22063216 acyl-C5:1 451491 245973 409891 144129 183519 370409 172266 93808 145617 111732 170534 157429 acyl-C5-OH 15246176 7003515 4927584 2515729 2963368 7552853 2450806 488164 1935615 1891356 563478 824894 acyl-C6-DC 343070 295616 399873 339257 306767 224800 402701 311271 456791 279584 424428 327764 L-octanoylcarnitine (acyl-C8) 487653 3812649 1710507 420426 14662204 1642887 980249 341133 916445 427153 259197 379739 octenoyl-l-carnitine (acyl-C8:1) 2406207 2328090 3647174 1517363 6938495 3500304 1268913 1460796 5343648 1822858 1705296 1675572 O-Decenoyl-L-carnitine (acyl-C10:1) 554985 1306196 1245547 349844 10656056 2401320 836467 382326 902123 674111 323020 473620 O-dodecanoyl-carnitine (acyl-C12) 614506 860051 903007 495668 3210112 742897 292031 391154 217783 490358 380238 365291 O-dodecenoyl-carnitine (acyl-C12:1) 283275 427928 498823 141641 3262893 727569 409538 187425 378618 430690 103547 176776 O-tetradecanoyl-L-carnitine (acyl-C14) 1031569 870038 4154302 2174963 1671103 1549630 814058 651906 1317723 1401033 1359405 1049063 Tetradecenoyl Carnitine (acyl-C14:1) 149144 312253 536656 201910 3200654 608726 278822 82418 320034 251808 105921 159896 L-Palmitoylcarnitine (acyl-C16) 11106660 7333010 31533082 23009786 14169043 13951587 13225256 5302329 11539893 16178397 10143901 10674159 Hexadecenoyl-carnitine (acyl-C16:1) 431670 535361 2285590 1261095 1953518 1197211 1091779 409863 1971185 1272531 825663 779209 Octadecanoyl-L-carnitine (acyl-C18) 9397896 6797479 20394430 15277065 12625351 14017795 8816371 3578127 6122727 9297184 7591471 6837076 O-octadecenoyl-L-carnitine (acyl-C18:1) 13366403 11499439 47746460 25645250 31042442 29080858 19169126 6782817 25071082 15591616 20281510 17240694 acyl-C18:2 (Linoleoyl-CoA) 4671743 4138215 13032707 10281227 15214272 15107997 7762408 4475200 13389176 7575661 12297556 8988575 acyl-C18:2-OH 2315498 1448781 3346055 1916871 294103 1050614 1202265 1034562 2352370 2682881 1114952 1727456 acyl-C20 77463 14277 110010 175858 202116 79234 73808 31137 29391 121038 63421 49239 acyl-C20:4 158278 232967 502432 603427 896722 793567 492121 226731 722696 347436 558675 393916 Biliverdin 61669 44051 83798 152694 513612 49829 72884 123361 70470 147198 100299 112771 2-Methylcitrate 472406 515683 875906 575874 604604 573473 528664 354529 344459 486899 458600 434560 MS_METABOLITE_DATA_END #METABOLITES METABOLITES_START metabolite_name KEGG ID Pathway m/z r.t. L-alanine C00041 Amino acids 90.0551 0.5110 L-arginine C00062 Amino acids 175.1189 0.4850 L-asparagine C00152 Amino acids 133.0608 0.5110 L-aspartate C00049 Amino acids 134.0449 0.5120 L-cysteine C00097 Amino acids 122.0273 1.6630 L-glutamate C00025 Amino acids 148.0605 0.5180 L-glutamine C00064 Amino acids 147.0764 0.5150 L-histidine C00135 Amino acids 156.0768 0.4860 L-Isoleucine C00407 Amino acids 132.1020 1.2210 L-Leucine C00123 Amino acids 132.1020 1.4220 L-leucine/isoleucine C00123 Amino acids 132.1020 1.2210 L-lysine C00047 Amino acids 147.1128 0.4270 L-methionine C00073 Amino acids 150.0584 0.8770 L-phenylalanine C00079 Amino acids 166.0862 1.5780 L-proline C00148 Amino acids 116.0708 0.5780 L-serine C00065 Amino acids 106.0501 0.5090 L-threonine C00188 Amino acids 120.0657 0.5160 L-tryptophan C00078 Amino acids 205.0972 1.5990 L-tyrosine C00082 Amino acids 182.0811 1.0380 L-valine C00183 Amino acids 118.0864 0.7200 AMP C00020 Nucleotides 348.070312 0.814 Adenosine C00212 Nucleotides 268.104065 1.537 Adenine C00147 Nucleotides 136.061996 0.79 GMP C00144 Nucleotides 364.065338 0.818 Guanosine C00387 Nucleotides 284.099579 1.575 Guanine C00242 Nucleotides 152.05574 0.837 CMP C00055 Nucleotides 324.05896 0.646 dCMP C00239 Nucleotides 308.064575 0.65 Cytosine C00380 Nucleotides 112.050774 0.681 dTMP C00364 Nucleotides 323.06897 1.567 UMP C00105 Nucleotides 325.043335 0.746 Uracil C00106 Nucleotides 113.034752 1.009 Inosine C00294 Nucleotides 269.088074 1.575 Hypoxanthine C00262 Nucleotides 137.045883 0.882 Xanthine C00385 Nucleotides 153.040527 0.919 Allantoate C00499 Nucleotides 177.061264 0.467 (S)(+)-Allantoin C02350 Nucleotides 159.051285 0.541 5-Hydroxyisourate C11821 Nucleotides 185.031143 0.518 3',5'-Cyclic AMP C00575 Nucleotides 330.058594 0.934 5-6-Dihydrothymine C00906 Nucleotides 129.065994 0.566 Nicotinamide C00153 Nucleotides 123.055428 0.928 Adenylosuccinic acid C03794 Nucleotides 464.081573 1.57 ADP-D-ribose C01882 Nucleotides 560.079163 0.714 NAD+ C00003 Nucleotides 664.116882 0.875 Glutathione C00051 GSH homeostasis 308.091003 0.885 Glutathione disulfide C00127 GSH homeostasis 613.159485 1.082 S-Glutathionyl-L-cysteine C05526 GSH homeostasis 427.095154 0.607 Cys-Gly C01419 GSH homeostasis 179.047913 0.875 Ascorbate C00072 GSH homeostasis 177.040436 1.363 Dehydroascorbate C05422 GSH homeostasis 175.023773 0.904 gamma-L-Glutamyl-L-cysteine C00669 Gamma-glutamyls 251.06958 0.888 gamma-L-Glutamyl-D-alanine C03738 Gamma-glutamyls 219.098572 0.658 gamma-Glutamyl-gamma-aminobutyrate C15767 Gamma-glutamyls 233.114304 0.812 Bis-gamma-glutamylcystine C03646 Gamma-glutamyls 499.108795 0.87 (5-L-Glutamyl)-L-glutamine C05283 Gamma-glutamyls 276.118896 0.72 5-L-Glutamyl-taurine C05844 Gamma-glutamyls 255.062775 1.694 L-Homocysteine C00155 Serine biosynthesis and one-carbon metabolism 136.042862 0.635 Dimethylglycine C01026 Serine biosynthesis and one-carbon metabolism 104.070847 0.561 Phosphoserine C02532 Serine biosynthesis and one-carbon metabolism 186.016388 0.508 S-Adenosyl-L-homocysteine C00021 Serine biosynthesis and one-carbon metabolism 385.128937 0.983 S-Adenosyl-L-methionine C00019 Serine biosynthesis and one-carbon metabolism 399.141602 1.668 Folate C00504 Folate pool (One carbon metabolism) 442.147644 1.587 5-10-Methenyltetrahydrofolate C00445 Folate pool (One carbon metabolism) 457.169098 0.641 Dihydrofolate C00415 Folate pool (One carbon metabolism) 444.16745 1.662 Ornithine C01602 Urea cycle 133.098557 1.347 L-Citrulline C00327 Urea cycle 176.102966 0.527 Argininosuccinate C03406 Urea cycle 291.132324 0.938 Spermidine C00315 Polyamines 146.165253 0.395 Spermine C00750 Polyamines 203.223007 0.407 alpha-D-Glucosamine 1-phosphate C06156 Aminosugars 260.053192 0.527 D-Glucosamine C00329 Aminosugars 180.08696 0.565 CMP-N-acetylneuraminate C00128 Aminosugars 615.154785 1.065 Carnosine C00386 Arginine and proline metabolism 227.115448 0.482 Phosphocreatine C02305 Arginine and proline metabolism 212.043228 0.556 Creatine C00300 Arginine and proline metabolism 132.076859 0.568 Creatinine C00791 Arginine and proline metabolism 114.066406 0.567 4-Acetamidobutanoate C02946 Arginine and proline metabolism 146.081253 0.536 N-Acetyl-L-citrulline C15532 Arginine and proline metabolism 218.11441 0.911 Pantothenate C00864 Panthothenate metabolism 220.117905 1.601 5-6-Dihydrouracil C00429 Panthothenate metabolism 115.0504 0.815 Pantetheine C00831 Panthothenate metabolism 279.134308 1.575 Taurine C00245 Sulfur metabolism 126.022064 0.515 L-Cysteate C00506 Sulfur metabolism 170.012375 0.843 (R)-S-Lactoylglutathione C03451 Sulfur metabolism 380.112976 1.574 L-Methionine S-oxide C02989 Sulfur metabolism 166.052673 0.535 Indole-3-acetaldehyde C00637 Indole and Tryptophan 160.075745 1.584 6-Hydroxykynurenic acid C08480 Indole and Tryptophan 206.048111 1.009 kynurenine C00328 Indole and Tryptophan 209.092056 1.579 Anthranilate C00108 Indole and Tryptophan 138.055008 0.564 Picolinic acid C10164 Indole and Tryptophan 124.039452 0.819 g-Oxalo-crotonate C03453 Indole and Tryptophan 159.027725 0.885 8-Methoxykynurenate C05830 Indole and Tryptophan 220.063065 1.573 L-Adrenaline C00788 Signaling 184.096771 1.661 Ectoine C06231 Inositol 143.081558 0.752 N-Methylethanolamine phosphate C01210 Glycerophospholipid biosynthesis 156.042175 0.487 Sphingosine C00319 Glycerophospholipid biosynthesis 300.289642 1.833 Acetylcholine C01996 Glycerophospholipid biosynthesis 146.117599 0.568 CDP-choline C00307 Glycerophospholipid biosynthesis 489.114746 0.555 Choline C00114 Glycerophospholipid biosynthesis 104.107201 0.507 Sphinganine 1-phosphate C01120 Sphingolipid biosynthesis 382.27063 2.03 L-Carnitine C00318 Carnitine and fatty acid metabolism 162.112488 0.524 acetyl-carnitine (acyl-C2) C02571 Carnitine and fatty acid metabolism 204.123001 0.832 propionyl-carnitine (acyl-C3) C03017 Carnitine and fatty acid metabolism 218.138672 1.57 butanoyl-l-carnitine (acyl-C4) C02862 Carnitine and fatty acid metabolism 232.154312 1.603 acyl-C4-OH HMDB13127 Carnitine and fatty acid metabolism 248.148117 1.628 acyl-C4-DC HMDB13133 Carnitine and fatty acid metabolism 262.128479 0.948 acyl-C5:1 HMDB02366 Carnitine and fatty acid metabolism 244.154205 1.594 acyl-C5-OH ac107 Carnitine and fatty acid metabolism 262.164978 1.577 acyl-C6-DC ac109 Carnitine and fatty acid metabolism 290.15976 1.657 L-octanoylcarnitine (acyl-C8) HMDB00791 Carnitine and fatty acid metabolism 288.216888 1.714 octenoyl-l-carnitine (acyl-C8:1) ac111 Carnitine and fatty acid metabolism 286.201233 1.67 O-Decenoyl-L-carnitine (acyl-C10:1) CID57357170 Carnitine and fatty acid metabolism 314.232513 1.744 O-dodecanoyl-carnitine (acyl-C12) HMDB02250 Carnitine and fatty acid metabolism 344.27948 1.861 O-dodecenoyl-carnitine (acyl-C12:1) HMDB13326 Carnitine and fatty acid metabolism 342.263794 1.763 O-tetradecanoyl-L-carnitine (acyl-C14) HMDB05066 Carnitine and fatty acid metabolism 372.310852 1.865 Tetradecenoyl Carnitine (acyl-C14:1) HMDB13329 Carnitine and fatty acid metabolism 370.295135 1.816 L-Palmitoylcarnitine (acyl-C16) C02990 Carnitine and fatty acid metabolism 400.342194 1.87 Hexadecenoyl-carnitine (acyl-C16:1) HMDB06317 Carnitine and fatty acid metabolism 398.326569 1.842 Octadecanoyl-L-carnitine (acyl-C18) HMDB00848 Carnitine and fatty acid metabolism 428.373444 1.897 O-octadecenoyl-L-carnitine (acyl-C18:1) HMDB06351 Carnitine and fatty acid metabolism 426.357849 1.888 acyl-C18:2 (Linoleoyl-CoA) HMDB01064 Carnitine and fatty acid metabolism 424.341888 1.845 acyl-C18:2-OH ac123 Carnitine and fatty acid metabolism 440.337006 1.77 acyl-C20 ac124 Carnitine and fatty acid metabolism 458.420471 1.917 acyl-C20:4 ac125 Carnitine and fatty acid metabolism 448.34198 1.824 Biliverdin C00500 Hemolysis markers 583.254578 1.843 2-Methylcitrate C02225 Propanoate Metabolism 207.050552 0.469 METABOLITES_END #END