#METABOLOMICS WORKBENCH Chemhnbgu24_20240410_081725 DATATRACK_ID:4768 STUDY_ID:ST003175 ANALYSIS_ID:AN005211 PROJECT_ID:PR001974 VERSION 1 CREATED_ON April 18, 2024, 6:11 pm #PROJECT PR:PROJECT_TITLE Inactivation of mitochondrial MUL1 E3 ubiquitin ligase inhibits lipogenesis and PR:PROJECT_TITLE prevents diet-induced obesity in mice PR:PROJECT_TYPE Basic Research PR:PROJECT_SUMMARY Characterize the role of mitochondrial MUL1 E3-ubiquitin ligase on energy PR:PROJECT_SUMMARY metabolism and lipogenesis using Mul1 deficient, Mul1(-/-), mice. MUL1 protein PR:PROJECT_SUMMARY is involved in mitochondrial dynamics, and innate immune response but its PR:PROJECT_SUMMARY primary function might be the regulation of lipogenesis under conditions of PR:PROJECT_SUMMARY nutritional overload. Using metabolic cages, we monitored whole body energy PR:PROJECT_SUMMARY expenditure, metabolism, and thermoregulation of the Mul1(-/-) mice under PR:PROJECT_SUMMARY standard diet (ND) or high fat diet (HFD). We examined the effect of Mul1 PR:PROJECT_SUMMARY inactivation on body weight, HFD-induced adiposity, fatty liver, glucose PR:PROJECT_SUMMARY intolerance, and insulin resistance. We performed global metabolomics, PR:PROJECT_SUMMARY lipidomic, and genome-wide mRNA sequencing using liver from Mul1(+/+) and PR:PROJECT_SUMMARY Mul1(-/-) animals on HFD. The expression level of key proteins involved in PR:PROJECT_SUMMARY lipogenesis and their regulation in the absence of MUL1 was monitored by PR:PROJECT_SUMMARY SDS-PAGE and Western blot analysis. We found that Mul1(-/-) animals have a PR:PROJECT_SUMMARY metabolic phenotype that confers robust resistance to HFD-induced obesity. PR:PROJECT_SUMMARY Several metabolic and lipidomic pathways are perturbed in the liver of Mul1(-/-) PR:PROJECT_SUMMARY animals on HFD, particularly the one driven by Stearoyl-CoA Desaturase 1 (SCD1), PR:PROJECT_SUMMARY a key regulator of lipid metabolism and obesity. In addition, key enzymes PR:PROJECT_SUMMARY involved in lipogenesis and fatty acid oxidation such as ACC1, FASN, AMPK, and PR:PROJECT_SUMMARY CTP1 were also modulated. The concerted deregulation of these enzymes, in the PR:PROJECT_SUMMARY absence of MUL1, causes reduced fat storage and increased fatty acid oxidation. PR:PROJECT_SUMMARY We identified a new function of mitochondrial MUL1 E3 ubiquitin ligase in the PR:PROJECT_SUMMARY regulation of lipogenesis and adiposity, particularly during conditions of HFD. PR:PROJECT_SUMMARY Inactivation of MUL1 provides resistance to HFD-induced obesity and can be a PR:PROJECT_SUMMARY therapeutic target for the treatment of obesity, type 2 diabetes, and PR:PROJECT_SUMMARY nonalcoholic fatty liver disease (NAFLD). PR:INSTITUTE University of Florida PR:DEPARTMENT Biochemistry PR:LABORATORY Merritt's Lab PR:LAST_NAME Merritt PR:FIRST_NAME Matthew PR:ADDRESS SW ARCHER RD, Gainesville, FL 32611 PR:EMAIL rmahar@hnbgu.ac.in PR:PHONE 9557559849 PR:FUNDING_SOURCE NIH PR:CONTRIBUTORS Lucia Cilenti, Jacopo Di Gregorio, Rohit Mahar, Fei Liu, Camilla T. Ambivero, PR:CONTRIBUTORS Muthu Periasamy, Matthew E. Merrit, and Antonis S. Zervos #STUDY ST:STUDY_TITLE Inactivation of mitochondrial MUL1 E3 ubiquitin ligase inhibits lipogenesis and ST:STUDY_TITLE prevents diet-induced obesity in mice ST:STUDY_TYPE Basic Research ST:STUDY_SUMMARY Characterize the role of mitochondrial MUL1 E3-ubiquitin ligase on energy ST:STUDY_SUMMARY metabolism and lipogenesis using Mul1 deficient, Mul1(-/-), mice. MUL1 protein ST:STUDY_SUMMARY is involved in mitochondrial dynamics, and innate immune response but its ST:STUDY_SUMMARY primary function might be the regulation of lipogenesis under conditions of ST:STUDY_SUMMARY nutritional overload. Using metabolic cages, we monitored whole body energy ST:STUDY_SUMMARY expenditure, metabolism, and thermoregulation of the Mul1(-/-) mice under ST:STUDY_SUMMARY standard diet (ND) or high fat diet (HFD). We examined the effect of Mul1 ST:STUDY_SUMMARY inactivation on body weight, HFD-induced adiposity, fatty liver, glucose ST:STUDY_SUMMARY intolerance, and insulin resistance. We performed global metabolomics, ST:STUDY_SUMMARY lipidomic, and genome-wide mRNA sequencing using liver from Mul1(+/+) and ST:STUDY_SUMMARY Mul1(-/-) animals on HFD. The expression level of key proteins involved in ST:STUDY_SUMMARY lipogenesis and their regulation in the absence of MUL1 was monitored by ST:STUDY_SUMMARY SDS-PAGE and Western blot analysis. We found that Mul1(-/-) animals have a ST:STUDY_SUMMARY metabolic phenotype that confers robust resistance to HFD-induced obesity. ST:STUDY_SUMMARY Several metabolic and lipidomic pathways are perturbed in the liver of Mul1(-/-) ST:STUDY_SUMMARY animals on HFD, particularly the one driven by Stearoyl-CoA Desaturase 1 (SCD1), ST:STUDY_SUMMARY a key regulator of lipid metabolism and obesity. In addition, key enzymes ST:STUDY_SUMMARY involved in lipogenesis and fatty acid oxidation such as ACC1, FASN, AMPK, and ST:STUDY_SUMMARY CTP1 were also modulated. The concerted deregulation of these enzymes, in the ST:STUDY_SUMMARY absence of MUL1, causes reduced fat storage and increased fatty acid oxidation. ST:STUDY_SUMMARY We identified a new function of mitochondrial MUL1 E3 ubiquitin ligase in the ST:STUDY_SUMMARY regulation of lipogenesis and adiposity, particularly during conditions of HFD. ST:STUDY_SUMMARY Inactivation of MUL1 provides resistance to HFD-induced obesity and can be a ST:STUDY_SUMMARY therapeutic target for the treatment of obesity, type 2 diabetes, and ST:STUDY_SUMMARY nonalcoholic fatty liver disease (NAFLD). ST:INSTITUTE University of Florida ST:LAST_NAME Merritt ST:FIRST_NAME Matthew ST:ADDRESS SW ARCHER RD, Gainesville, FL 32611 ST:EMAIL rmahar@hnbgu.ac.in ST:PHONE 9557559849 ST:NUM_GROUPS 2 ST:TOTAL_SUBJECTS 12 ST:NUM_MALES 6 ST:NUM_FEMALES 6 #SUBJECT SU:SUBJECT_TYPE Mammal SU:SUBJECT_SPECIES Mus musculus SU:TAXONOMY_ID 10090 SU:GENOTYPE_STRAIN Wild type and Mul1(+/+) mice SU:AGE_OR_AGE_RANGE 8 weeks SU:GENDER Male and female SU:ANIMAL_LIGHT_CYCLE 12-hour/12-hour light/dark cycle SU:ANIMAL_FEED Research Diets D12492 #FACTORS #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 - Mul1(+/+)_TZ 34 Genotype:Mul1(+/+) | Sample source:Liver SUBJECT_SAMPLE_FACTORS - Mul1(+/+)_TZ 35 Genotype:Mul1(+/+) | Sample source:Liver SUBJECT_SAMPLE_FACTORS - Mul1(+/+)_TZ 36 Genotype:Mul1(+/+) | Sample source:Liver SUBJECT_SAMPLE_FACTORS - Mul1(+/+)_TZ 37 Genotype:Mul1(+/+) | Sample source:Liver SUBJECT_SAMPLE_FACTORS - Mul1(-/-)_TZ 38 Genotype:Mul1(-/-) | Sample source:Liver SUBJECT_SAMPLE_FACTORS - Mul1(-/-)_TZ 39 Genotype:Mul1(-/-) | Sample source:Liver SUBJECT_SAMPLE_FACTORS - Mul1(-/-)_TZ 40 Genotype:Mul1(-/-) | Sample source:Liver SUBJECT_SAMPLE_FACTORS - Mul1(-/-)_TZ 41 Genotype:Mul1(-/-) | Sample source:Liver #COLLECTION CO:COLLECTION_SUMMARY Liver tissue was obtained from Mul1(+/+) and Mul1(-/-) mice following a HFD for CO:COLLECTION_SUMMARY 16 weeks and stained with H&E or Oil Red Oil. CO:SAMPLE_TYPE Liver CO:STORAGE_CONDITIONS -20℃ #TREATMENT TR:TREATMENT_SUMMARY Liver tissue was obtained from Mul1(+/+) and Mul1(-/-) mice following a HFD for TR:TREATMENT_SUMMARY 16 weeks and stained with H&E or Oil Red Oil. #SAMPLEPREP SP:SAMPLEPREP_SUMMARY liver tissues from mice were fixed overnight in 10% neutral formalin and SP:SAMPLEPREP_SUMMARY embedded in paraffin. Paraffin-embedded tissues were cut into sections and SP:SAMPLEPREP_SUMMARY stained with hematoxylin and eosin (H&E) for assessment of liver histology. SP:SAMPLEPREP_SUMMARY Liver tissue from Mul1(+/+) and Mul1(-/-) mice on HFD were subjected to the SP:SAMPLEPREP_SUMMARY Folch extraction in order to separate lipids and polar metabolites. SP:PROCESSING_STORAGE_CONDITIONS 4℃ SP:EXTRACT_STORAGE -20℃ #CHROMATOGRAPHY CH:CHROMATOGRAPHY_TYPE Reversed phase CH:INSTRUMENT_NAME Thermo Dionex Ultimate 3000 CH:COLUMN_NAME Waters ACQUITY UPLC BEH C18 (100 x 2.1mm,1.7um) CH:SOLVENT_A 60:40 acetonitrile:water; 10mM ammonium formate; 0.1% formic acid CH:SOLVENT_B 90:8:2 2-propanol:acetonitrile:water; 10mM ammonium formate; 0.1% formic acid CH:FLOW_GRADIENT 10 µl/min CH:FLOW_RATE 350 µl/min CH:COLUMN_TEMPERATURE 50 #ANALYSIS AN:ANALYSIS_TYPE MS #MS MS:INSTRUMENT_NAME Thermo Q Exactive Orbitrap MS:INSTRUMENT_TYPE Orbitrap MS:MS_TYPE ESI MS:ION_MODE POSITIVE MS:MS_COMMENTS The aqueous phase was analyzed using the Thermo Q-Exactive Orbitrap mass MS:MS_COMMENTS spectrometer with Dionex UHPLC and autosampler. All samples were analyzed in MS:MS_COMMENTS positive and negative simultaneously with heated electrospray ionization (HESI) MS:MS_COMMENTS with a mass resolution of 35,000 at m/z 200 as separate injections. The polar MS:MS_COMMENTS metabolites were analyzed on Thermo Q-Exactive Orbitrap mass spectrometer MS:MS_COMMENTS equipped with UHPLC. Data were analyzed with MZmine and features were aligned MS:MS_COMMENTS for identification across samples. The metabolites were searched against the MS:MS_COMMENTS Southeastern Center for Integrated Metabolomics (SECIM) metabolite library using MS:MS_COMMENTS retention time and corresponding mass spectral data. Lipids isolated from Folch MS:MS_COMMENTS extraction procedure were also analyzed by the same instrument. Lipidomics data MS:MS_COMMENTS were analyzed using the LipidMatch software and identified lipid entities were MS:MS_COMMENTS exported in a tabular form. #MS_METABOLITE_DATA MS_METABOLITE_DATA:UNITS A.U. MS_METABOLITE_DATA_START Samples Mul1(+/+)_TZ 34 Mul1(+/+)_TZ 35 Mul1(+/+)_TZ 36 Mul1(+/+)_TZ 37 Mul1(-/-)_TZ 38 Mul1(-/-)_TZ 39 Mul1(-/-)_TZ 40 Mul1(-/-)_TZ 41 Factors Genotype:Mul1(+/+) | Sample source:Liver Genotype:Mul1(+/+) | Sample source:Liver Genotype:Mul1(+/+) | Sample source:Liver Genotype:Mul1(+/+) | Sample source:Liver Genotype:Mul1(-/-) | Sample source:Liver Genotype:Mul1(-/-) | Sample source:Liver Genotype:Mul1(-/-) | Sample source:Liver Genotype:Mul1(-/-) | Sample source:Liver Trans-Aconitate 16384.62109 13429.04883 23449.53516 19184.64844 8318.889648 6993.270996 37761.10938 3424.447998 1-Aminocyclopropane-1-Carboxylate_1 524260.3125 484287.75 244709.0156 378251.4063 651176.875 595911.5625 796391 453275.625 1-Aminocyclopropane-1-Carboxylate_2 3.26E+07 2.47E+07 2.08E+07 2.67E+07 2.33E+07 2.22E+07 2.46E+07 2.53E+07 1-Methylnicotinamide 1.65E+07 1.75E+07 4379405.9 5991712.157 2.09E+07 2.65E+07 8105263 8024924.243 2-Acetamido-2-Deoxy-Beta-D-Glucosylamine 1.38E+07 7749322.471 1.05E+07 8996935.157 9427761.329 1.05E+07 1.49E+07 8576510.229 2-Amino-2-Methylpropanoate_1 1077060 707137.875 1095480.429 1099870.5 1657150.086 1753380.125 3692967.671 2414286.25 2-Amino-2-Methylpropanoate_2 2.59E+07 1.37E+07 1.25E+07 2.07E+07 2.03E+07 3.72E+07 6.25E+07 3.79E+07 2-Hydroxyglutarate+Na 96949.74464 139159.729 97618.65379 126724.0489 66699.75 102433.4163 171617.7509 107836.1547 2-Hydroxyglutarate-Water 305140.2013 380898.217 263530.6812 359316.2366 181033.65 307425.7214 482520.6125 318869.5955 2-Hydroxyphenylalanine 2.48E+08 1.87E+08 1.52E+08 1.68E+08 2.31E+08 2.75E+08 3.26E+08 2.40E+08 2-Methylbutyroylcarnitine_1 1060311.275 669868.8125 277930.7906 284140.3036 776124.5786 2185064.85 894489.8768 1739019.111 2-Methylbutyroylcarnitine_2 1763094.239 592609.525 436620.0875 557502.0438 1533727.118 5610121.914 1563351.071 2782329.1 2-Methylglutaric Acid 1342934.363 1266121.9 1445986.65 1475085.421 1528990.664 1379790.746 1312325.071 1330891.804 3-Aminoisobutanoate 1960672.514 1032309.82 922249.5071 1465860.821 1448733.557 2741999.486 3424714.643 1120479.37 3-Hydroxy-3-Methylglutarate_1 228273.3281 248499.3125 189558.7656 250144.75 258395.5362 340870.375 547673.6161 399150.1009 3-Hydroxy-3-Methylglutarate_2 753441.625 805405.1875 563967.6875 818378.4375 816069.5 1071476.75 1828873.418 1377664.625 3-Methylcrotonylglycine 83928.17522 57771.08504 67532.52299 112499.8558 103708.1529 123146.3228 364271.8536 61516.38147 3-Ureidopropionate_1 936459.0714 1358464.175 2693504.986 2341491.743 432751.8125 1940310.679 1596504.886 1421691.739 3-Ureidopropionate_2 1643015.236 1505031.518 2091672.443 1544840.086 339690.3545 1759715.093 1361330.489 1617044.3 3-Ureidopropionate_3 5243055.886 5912296.471 4186888.2 3616648.964 4883712.971 8919371.114 7117151.557 6141978.4 4-Acetamidobutanoate 9917.639648 8760.795898 7602.585449 12968.78125 7258.121094 11080.03223 13156.35352 13004.62109 4-Aminobenzoate_1 382648.433 145839.2042 239365.2862 151843.3228 216669.5585 443349.5446 580690.2027 339827.175 4-Aminobenzoate_2 834457.3625 317123.7786 505993.1438 342382.1134 468490.3982 981805.4661 1253774.148 696728.4063 4-Aminobutanoate (Gaba) 3114394.193 1728426.293 1719717.118 2454911.018 2487780.246 4268822.571 4637120.614 1804840.711 4-Guanidinobutanoate 1483532.261 1488307.7 947360.0357 1941422.3 2280867.536 2312173.821 8979235.629 3759475.236 4-Hydroxybenzaldehyde 616508.1562 202700.9438 263194.5964 206676.9219 124086.0078 263434.9701 239174.1161 107494.5391 4-Hydroxy-L-Phenylglycine_1 474726.5938 448999.7964 175496.7031 288731.4375 271722.7188 267139.1563 119007.3359 415656.3438 4-Hydroxy-L-Phenylglycine_2 1353249.621 897256.6875 841814.0107 963864.9286 814023.5554 805510.9821 1503376.925 872254.8036 4-Hydroxy-L-Proline_1 1179723.932 1028914.416 894242 550974.6205 1148426.875 2182754 1137124.5 965046.375 4-Hydroxy-L-Proline_2 3152086.557 2714245.664 4076123.364 3810386.493 4329706.521 6632903.457 1.27E+07 8472202.543 5-Aminolevulinic Acid 8188638.214 5003610.679 4058742.5 2352635.1 5149571.686 1.19E+07 4569077.686 4597683.379 5-Hydroxymethyl-2-Furaldehyde_1 2.04E+07 1.81E+07 1.19E+07 1.67E+07 1.14E+07 1.46E+07 2519350.25 1.70E+07 5-Hydroxymethyl-2-Furaldehyde_2 2.03E+07 1.69E+07 1.51E+07 1.81E+07 1.16E+07 1.47E+07 6228954 1.82E+07 5-Hydroxy-N-Formylkynurenine 217568.0263 262684.0688 244881.246 317667.2138 293246.0063 317905.6812 332758.3866 361521.9705 5-Oxo-D-Proline_1 3087165.907 2507218.886 2065597.168 3559170.521 2564494.25 4354380.386 8973797.371 7339143.443 5-Oxo-D-Proline_2 3.26E+07 2.84E+07 2.34E+07 3.32E+07 2.72E+07 4.44E+07 8.03E+07 7.61E+07 6C-Sugar Alcohol 657238.625 455230.4375 483200.1371 125755.3594 203524.25 213321.875 168072.8438 186179.7344 6-Hydroxynicotinate 153447.2344 175756.3281 178688.625 128061.4453 72202.9375 69696.38225 272745.7813 298627.125 7-Ketochenodeoxycholic Acid 434961.8723 394968.6563 383856.608 322781.9688 339137.6437 472173.0875 499638.2071 751687.7357 Acetylcitrulline 59802.10938 13650.27148 99018.13281 65630.25 249840.4759 263103.8196 477362.7804 70159.91406 Acetyl-Dl-Carnitine_1 352984.5625 259930.7188 343415.0625 470342.4688 160566.5 464132.1875 903025.3125 1037577.75 Acetyl-Dl-Carnitine_2 865081.9696 364126.875 610931.3196 583412.4375 449642.25 1086698.75 1335640.5 1973409.329 Acyl-Carnitine(5-Oh)_1 52804.25391 47318.72266 40333.23047 41941.66406 49431.42969 83114.34375 187483.6326 61389.17578 Acyl-Carnitine(5-Oh)_2 119285.0156 104173.9453 78491.58594 97413.25781 131270.5469 196901.4063 192749.3991 147488.9531 Acyl-Carnitine(5-Oh)_3 3011904.214 3312840.336 2876775.657 1923689.629 3471091.386 5341308.7 3624566.214 4663133.793 Adenine 1706026.875 1121930.221 1099035.436 941894.5946 2018610.5 1973939.389 2286257.439 2625499.407 Alanine/Sarcosine 3.25E+08 2.24E+08 2.93E+08 2.70E+08 2.23E+08 2.33E+08 3.41E+08 2.65E+08 Aldo/Keto-Hexose 8.50E+07 6.18E+07 6.55E+07 4.25E+07 5.43E+07 5.88E+07 4.73E+07 4.46E+07 Aldopentose 1681227.507 2124525.768 3060601.1 1431733.564 2605735.043 2972113.779 4812936.5 2927998.3 Alpha-Aminoadipate/N-Methyl-L-Glutamate_1 1212488.75 1034044.875 1220173.125 1071836.625 1221017.875 3162536.05 1.28E+07 2642026.557 Alpha-Aminoadipate/N-Methyl-L-Glutamate_2 3744840.107 4962970.6 8190297.229 6265520.157 7505808.286 2.59E+07 1.16E+08 1.96E+07 Alpha-Aminoadipate/N-Methyl-L-Glutamate_3 2.71E+07 2.91E+07 2.20E+07 2.75E+07 2.55E+07 2.35E+07 1.33E+07 2.25E+07 Alpha-D-Glucose 2.07E+07 2.10E+07 1.44E+07 2.04E+07 1.77E+07 1.70E+07 8245117.457 1.81E+07 Arabinose 668184.6875 594408.9821 696752.6821 565090.375 741446.6696 912201.6875 1042674.968 822162.4179 Aspartate 5.77E+07 3.89E+07 3.83E+07 4.25E+07 2.58E+07 2.82E+07 2.66E+07 3.70E+07 Boc-D-Phenylalanine 3.51E+07 4.49E+07 4.06E+07 4.79E+07 3.38E+07 4.12E+07 4.62E+07 3.88E+07 Butanoylcarnitine 411428.6393 431460.3813 130219.0313 170189.0011 275201.4464 844050.0321 343723.0938 722939.6411 Carnosine 1055584.25 919184.9375 1259828.5 756359.4375 1066484 989698 1621313.791 814977.6875 Cellobiose 8542104.886 8667758.486 1.09E+07 8359429.043 8236626.057 9627426.486 6166473.071 8505038.786 Choline 3.75E+08 2.66E+08 3.33E+08 4.25E+08 3.23E+08 4.10E+08 4.50E+08 2.95E+08 Citrulline_1 1.11E+07 5861978.357 6395138.9 4850557.464 7844089.786 1.11E+07 9254779.086 7993282.286 Citrulline_2 3.08E+07 1.73E+07 1.81E+07 1.31E+07 2.13E+07 2.90E+07 2.55E+07 2.23E+07 Creatine 1.26E+08 1.17E+08 1.31E+08 1.16E+08 9.54E+07 1.49E+08 1.75E+08 2.57E+08 Cytosine_1 137132.25 175523.75 84331.05469 190443.4844 235840.7344 333838.4063 876175.0696 145194.5625 Cytosine_2 46271.85547 172962.375 183920.875 265160.7813 363634.9063 593676.1875 1868376.979 288218 D-Fructose 1.58E+08 9.31E+07 5.77E+07 5.45E+07 9.63E+07 1.01E+08 8.02E+07 8.17E+07 D-Gluconate 992328.7929 1050488.229 1420164.254 1220739.052 1810306.493 2143951.457 1803770.211 1594257.8 D-Glucosamine 6-Phosphate_1 388871.875 203654.0625 201644.25 109796.2734 346631.4688 377125.3125 1359075.063 153769.3281 D-Glucosamine 6-Phosphate_2 664088.5625 368877.7188 405628.9063 192318.1875 420697.6563 629709.3125 1196349.625 407963.7188 D-Glyceric Acid 84002.14063 72072.54688 70018.90625 55482.72266 91493.8125 79704.69531 75899.52344 94746.27344 D-Mannosamine_1 9276210.729 1.07E+07 6369486.129 7273436.443 7873034.286 8221488.971 2042042.875 4021817.221 D-Mannosamine_2 5.45E+07 5.65E+07 4.09E+07 4.59E+07 5.20E+07 4.49E+07 2.95E+07 4.16E+07 D-Sorbitol 1305716.625 1203382.977 880765.125 571694.875 861921.625 679311.1875 519026.0313 652917.4375 Formate 7620356.8 5098840.257 5170425.443 6164662.957 3716715.214 3863453.871 4252844.079 4979902.514 Formyl-5-Hydroxykynurenamine 135353.454 171499.2179 157866.3353 208006.9763 181512.0388 209339.7009 219679.8754 235852.6549 Formylkynurenine 402554.9536 443613.1795 452064.0402 516351.025 435299.508 537228.7438 556461.8384 542513.9054 Gama-Muricholic Acid 1437489.596 1797802.314 947617.5304 1165182.188 3913178.186 1787746.821 2134583.168 1.17E+07 Gentiobiose_1 3167914.25 1.10E+07 1.69E+07 7807929.5 1356429.375 3386159.25 5556066.5 4486141.5 Gentiobiose_2 1.08E+08 1.05E+08 9.90E+07 9.20E+07 9.91E+07 1.00E+08 2.67E+07 9.62E+07 Glutathione Disulfide 6.08E+08 5.75E+08 4.35E+08 4.11E+08 5.07E+08 6.22E+08 6.21E+08 4.02E+08 Glu-Thr 287059.7188 187988.7344 84998.69531 94736.78125 117042.7134 139914.1281 204293.3281 129911.1875 Glycerol_1 1906903.496 1033474.163 1207956.247 1398173.855 657960.0643 847583.7607 964183.4911 1699546.518 Glycerol_2 2713689.771 1569036.082 2161819.016 1999688.843 878288.2375 1180982.721 1358153.946 2423795.971 Glycerophosphocholine 1.30E+08 1.93E+08 1.59E+08 4.24E+08 1.73E+08 1.40E+08 2.49E+08 1.73E+08 Glycine 9503933.829 7045747.729 7256707.5 1.18E+07 8292482.829 8259019.886 8258696.757 9508151.8 Guanidinoacetate 2259403.25 3116901.25 3152786.25 4927273.5 3807283 5564387.107 8129584.329 1.67E+07 Hippurate 1484619.411 503956.5759 628379.5696 487504.708 303415.1754 605494.8438 560713.0089 203519.4567 Homoserine_1 1030773.125 577712.0625 845450.5625 444472.9375 749609.4375 698971 1261317.25 586887.5 Homoserine_2 2.10E+08 1.67E+08 1.69E+08 2.03E+08 1.55E+08 1.66E+08 1.68E+08 1.54E+08 Hypoxanthine_1 1.63E+07 1.44E+07 1.08E+07 1.15E+07 1.49E+07 1.63E+07 1.50E+07 1.46E+07 Hypoxanthine_2 3.76E+08 2.54E+08 1.68E+08 1.88E+08 3.13E+08 3.41E+08 2.91E+08 2.98E+08 Indole-3-Acetaldehyde 1664430.718 1291099.196 1058250.859 1111817.621 1678402.775 1976400.625 2140625.618 1498417.404 Indoleacrylic Acid 7.77E+07 6.03E+07 4.55E+07 5.01E+07 8.02E+07 8.85E+07 8.92E+07 7.25E+07 Isocytosine 4712291.229 3887197.429 3572427.507 4442979.071 4065844.75 5363195.314 3233970.614 3878499.95 Isoleucine 2.37E+08 2.33E+08 1.63E+08 1.91E+08 2.27E+08 3.04E+08 3.93E+08 2.45E+08 L-Anserine 1001504.625 765682.4375 580256.125 507437 914344.6875 867665.5625 947570.325 822519.5 L-Arabitol 1025143.18 788247.3125 980563.8571 870548.1607 952969.1509 861381.0393 894370.375 1073223.864 L-Asparagine_1 3293709 4159502 6858786.5 4271041.5 6237696 6112951.5 7436849.586 4530196 L-Asparagine_2 9953559.729 7467013.629 7811835.4 9072634.2 5381571.729 6176381.586 6300576.029 7327639.9 L-Asparagine_3 9108993 9314372 9819135 1.01E+07 1.49E+07 1.52E+07 1.80E+07 1.23E+07 L-Asparagine_4 2.03E+07 2.21E+07 2.61E+07 3.16E+07 2.59E+07 2.78E+07 3.34E+07 2.46E+07 L-Aspartate 1746406.625 2043560.375 2952919.25 1654668.125 1761362.125 1301878 2126612 1943076.875 L-Carnitine 4.50E+08 3.45E+08 2.21E+08 2.45E+08 2.75E+08 3.33E+08 2.60E+08 3.87E+08 Leu Pro 1050840.65 719171.6964 541407.092 634466.9214 770373.0089 982081.9321 1233720.862 639897.8196 Leucine 5.15E+08 4.80E+08 3.59E+08 4.36E+08 4.68E+08 6.16E+08 7.42E+08 5.10E+08 L-Glutamic Acid_1 1399428.632 1143106.045 537366.7241 949038.6339 906089.0625 783333.9357 1021225.468 1032793.013 L-Glutamic Acid_2 1675735.75 1271672.75 1402233.25 1215123.125 1055720 1194498.625 2921698.096 1321784.375 L-Glutamic Acid_3 2.69E+08 3.72E+08 2.23E+08 2.21E+08 3.25E+08 3.69E+08 3.68E+08 3.58E+08 L-Glutamic Acid_4 7.76E+08 5.52E+08 3.57E+08 4.80E+08 4.39E+08 4.14E+08 5.49E+08 5.57E+08 L-Glutamine_1 1.14E+07 1.29E+07 9272575.857 3431876 1.57E+07 1.68E+07 1.68E+07 1.12E+07 L-Glutamine_2 8.99E+08 1.20E+09 7.59E+08 6.58E+08 1.23E+09 1.25E+09 1.14E+09 1.20E+09 L-Histidine_1 9414545.871 7126664.357 9207230.943 6358082.429 8127783.814 8689378.571 9608828.014 6520438.971 L-Histidine_2 3.28E+08 2.62E+08 2.36E+08 2.51E+08 2.78E+08 3.18E+08 3.61E+08 2.97E+08 L-Isoleucine 2057850.646 2588434.557 1745967.439 2443786.929 2107294.193 2900434.121 3807010.536 2229468.046 L-Kynurenine 1860517.993 793092.4946 1069486.427 1025163.561 963885.4964 1647151.725 3013670.279 1740883.879 L-Lactic Acid_1 397454.5938 303439.125 143273.2813 211036.3594 178233.9844 173912.2656 38070.52734 265416.4688 L-Lactic Acid_2 663580.0625 486517.3438 517018.4375 567581.75 368670.125 461613.2813 205212.2969 540607.2268 L-Lactic Acid_3 560949.8299 759016.5393 458438.4915 670456.5063 567240.8125 634252.1107 289801.4063 618073.5625 L-Lysine_1 1192726.245 1183277.488 982112.5196 1102216.114 1154660.823 1454828.586 2108771.561 1272885.78 L-Lysine_2 3494618.364 3480636.729 4316745.307 4526129.707 3615051.064 4792426.5 6014767.686 3660210.879 L-Lysine_3 2.07E+07 1.94E+07 1.69E+07 2.06E+07 1.98E+07 2.66E+07 3.49E+07 2.11E+07 L-Lysine_4 8.43E+07 7.74E+07 6.54E+07 7.82E+07 8.69E+07 1.16E+08 1.51E+08 9.34E+07 L-Methionine_1 8432697.943 9970377.714 8082149.086 1.03E+07 1.09E+07 1.29E+07 1.71E+07 9648663.343 L-Methionine_2 2.98E+07 2.53E+07 2.10E+07 2.34E+07 2.64E+07 3.53E+07 4.53E+07 2.95E+07 L-Methionine_3 3.18E+08 2.26E+08 1.97E+08 2.22E+08 2.89E+08 3.44E+08 4.05E+08 3.02E+08 L-Ornithine_1 3557372.471 3553906.171 4125897.436 4867006.329 3143862.557 4082490.207 5649146.886 3662924.029 L-Ornithine_2 1.56E+07 1.43E+07 1.15E+07 1.55E+07 1.56E+07 1.82E+07 2.39E+07 1.65E+07 L-Ornithine_3 4.19E+07 3.72E+07 2.97E+07 3.83E+07 4.21E+07 4.89E+07 6.17E+07 4.39E+07 L-Ornithine_4 4.81E+07 4.48E+07 3.40E+07 4.74E+07 4.67E+07 5.84E+07 7.48E+07 5.27E+07 L-Phenylalanine_1 9482163.757 7387605.486 6509544.129 6127382.443 8571020.943 9426661.514 1.01E+07 8687015.314 L-Phenylalanine_2 1.17E+07 9858488.071 8380371.286 9320319.543 1.08E+07 1.24E+07 1.45E+07 8881635.871 L-Phenylalanine_3 7.66E+08 6.19E+08 5.26E+08 5.05E+08 7.29E+08 7.97E+08 8.16E+08 7.07E+08 L-Pipecolic Acid_1 25945.64258 33733.30078 37606.65234 55015.62109 37504.54688 58190.25391 97380.88839 56550.86719 L-Pipecolic Acid_2 1267624.875 903841.0625 710304.5625 1856084.875 985329.875 1329716.625 3045090.5 1027994 L-Pipecolic Acid_3 5280392.429 5483093.371 3931121.771 4080053.521 3524893.457 5375666.314 8407330.1 7462760.743 L-Proline 5.20E+08 3.65E+08 3.38E+08 3.57E+08 4.86E+08 5.93E+08 7.70E+08 5.04E+08 L-Serine_1 774578.75 1094681.875 1736326.625 1497092 798023.6875 1333941.875 1396247.875 954332.4375 L-Serine_2 2.79E+07 2.41E+07 2.89E+07 4.04E+07 2.09E+07 2.14E+07 2.44E+07 2.27E+07 L-Tryptophan_1 6313764.614 5399747.729 4435078.229 4805558.364 5879484.871 6178442.314 6571898.814 5903720.171 L-Tryptophan_2 1.79E+08 1.41E+08 1.04E+08 1.18E+08 1.87E+08 2.07E+08 2.11E+08 1.66E+08 L-Tyrosine_1 1.23E+07 1.07E+07 8942125.029 1.04E+07 1.17E+07 1.36E+07 1.60E+07 1.25E+07 L-Tyrosine_2 4.04E+07 3.00E+07 2.40E+07 2.73E+07 3.78E+07 4.42E+07 5.38E+07 3.85E+07 Lumichrome 984245.1196 749958.6518 461173.0054 515287.8866 530940.608 688730.8089 397579.5259 375363.4937 L-Valine 4.44E+08 3.73E+08 3.41E+08 3.41E+08 4.72E+08 5.48E+08 6.39E+08 4.77E+08 Lysope (20:4) 92526.41808 28362.67578 26771.16602 12170.7373 20012.18359 51132.07813 35755.23438 25995.33594 Malate 4990510.9 5858333.6 6931523.343 4943289.136 5227503.243 7840560.943 1.16E+07 8089005.457 Methionine Sulfoxide 5755369.914 4492168.729 3279645 2347483.896 4255466.264 5854758.129 4346101.657 5184510.3 N1-Methyl-2-Pyridone-5-Carboxamide 1065649.741 890179.8143 1080416.277 477724.9509 529824.7723 573327.0116 732314.0018 1940529.579 N-Acetyl-D-Galactosamine 339117.75 314976.625 357819.7188 347817.4688 272638.375 317389.9688 1958760.532 388739.5 N-Acetyl-Dl-Glutamic Acid 422713.4045 328865.7964 1309727.961 380363.3929 465529.733 818473.3321 3167675.179 894518.7643 N-Acetyl-Dl-Serine 184994.258 184726.6719 305214.1004 256527.9357 226747.2857 332845.858 434162.1759 269637.2188 N-Acetylglycine_1 124379.3281 111755.7656 208247.8281 246233.1875 192666.4504 149015.4844 325390.9143 215839.3906 N-Acetylglycine_2 360358.8558 264978.6272 441165.5188 454070.4688 403164.5777 417827.8991 889435.8625 521447.7902 N-Acetyl-L-Alanine_1 448311.5937 392028.6571 319697.0732 358646.7812 417820.25 611146.3491 699704.4268 516343.0286 N-Acetyl-L-Alanine_2 1823455.904 1660999.975 1439628.264 1595266.318 1713659.161 2586932.721 3119768.771 2371671.357 N-Acetyl-L-Alanine_3 2259569.043 1978209.868 1620335.371 1836068.507 2121043.407 3113088.657 3639242.714 2515274.679 N-Acetyl-L-Aspartic Acid_1 77574.92969 60017.0856 64032.48828 48342.88214 53909.63962 84498.85156 86915.15625 93085.89732 N-Acetyl-L-Aspartic Acid_2 217516.9696 168192.5176 153565.5821 129562.5315 167437.2656 222075.5567 230050.4714 277161.5143 N-Acetyl-L-Leucine_1 101280.9219 122633.3438 42157.14063 140759.3632 96289.67969 183105.8219 173127.9531 32476.00195 N-Acetyl-L-Leucine_2 782198.5571 649785.3911 523027.6902 456976.7625 577102.5955 747038.2179 842631.0857 650832.4616 N-Acetyl-L-Leucine_3 3901024.421 3216348.8 2554686.296 2303239.229 2978298.471 3589941.414 4243412.886 3083726.764 N-Boc-L-Aspartic Acid 1868643.75 2271104.311 2189707.436 3104702.186 1723183.671 2321965.061 2511205.889 2157645.354 N-Boc-L-Tert-Leucine 1541758.375 1783316.625 1571752.875 2171150.75 1360582.125 1818713.25 2193669.25 1716181.125 N-Boc-L-Tryptophan 1.86E+07 2.14E+07 2.09E+07 2.39E+07 1.81E+07 2.03E+07 2.34E+07 2.07E+07 Nicotinamide 3.69E+08 2.76E+08 1.96E+08 1.65E+08 2.51E+08 2.84E+08 3.27E+08 2.81E+08 Nicotinate_1 711853.5 427213.9063 794921.0411 750674.1625 320778.375 759424.5 1426326.489 454020.8125 Nicotinate_2 1122174.488 785773.1125 841592.3286 1045825.464 770238.8821 928775.85 1306961.618 765305.4464 N-Methyl-L-Histidine 1.48E+07 1.03E+07 1.79E+07 1.05E+07 1.62E+07 1.24E+07 2.57E+07 1.75E+07 Norleucine 6996512.343 7298146.357 5892143 7593496.657 7062385.786 1.07E+07 1.38E+07 7599820.414 O-Acetyl-L-Serine 1046277.875 501068.7813 460613.4375 411271.5 638989.375 646917.75 1215689.5 702552.1875 Pantothenic Acid_1 264532.2813 211585.0781 163227.2656 215186.75 224875.5156 253591.8438 261947.3375 226526.6094 Pantothenic Acid_2 2.41E+07 1.82E+07 1.72E+07 1.88E+07 1.99E+07 2.45E+07 2.60E+07 2.19E+07 Phenylalanine-Hcooh 1.75E+08 1.41E+08 1.22E+08 1.17E+08 1.64E+08 1.81E+08 1.90E+08 1.62E+08 Phosphocholine 5.54E+08 2.02E+08 2.85E+08 2.22E+08 5.04E+08 4.48E+08 1.88E+08 1.60E+08 Propanoylcarnitine 1.20E+07 6115452.129 5560741.671 7942601.243 1.23E+07 1.82E+07 2.20E+07 3.82E+07 Putrescine 623074.2875 1312933.793 831471.7446 945073.7179 1125321.491 2346630.936 2196770.014 2148659.061 Pyridoxal_1 466390.7179 294414.3643 223124.3451 100240.3732 597604.1107 628877.0679 247148.8348 100442.1641 Pyridoxal_2 1360908.746 849792.7982 603671.0357 338279.5625 1492338.314 1726977.611 841750.0107 370650.5295 Sn-Glycerol 3-Phosphate 1338263.198 1136981.709 1323113.811 2626924.221 865116 672639.1397 710662.4357 1199560.736 Spermidine 2.29E+07 3.52E+07 2.42E+07 1.80E+07 4.09E+07 6.27E+07 6.66E+07 5.86E+07 Stachydrine 628775.925 831774.2839 1247656.943 1512332.154 1143412.552 844779.2232 5838169.614 3621169.486 Taurine_1 1092650 1578459.954 1196504.032 957808.8536 1185180.888 1010277.861 836136.7125 1587555.97 Taurine_2 1.69E+07 2.58E+07 2.86E+07 1.70E+07 1.49E+07 2.25E+07 1.94E+07 2.57E+07 Taurine_3 8.16E+07 1.47E+08 1.11E+08 1.03E+08 8.20E+07 1.16E+08 9.08E+07 1.49E+08 Thymine 354012.0438 221779.6813 159963.6042 145146.3484 199102.9393 283460.3571 219886.4812 283467.533 Tiglylcarnitine_1 63751.94688 43430.65625 21461.98047 29483.54297 47367.26172 69970.75781 62262.5625 56822.99219 Tiglylcarnitine_2 1144874.088 1279531.138 425915.658 761177.0321 1782336.121 2537416.539 3192666.971 3409759.05 Trans-Aconitate_1 5251267.557 5128185.5 4171251.879 4321308.143 4526103.35 5361464.957 5049091.771 5083623.986 Trigonelline_1 157800.4844 149607.4688 266009.6295 251213.8281 87682.80597 137474.4165 648438.7545 181087.625 Trigonelline_2 1549029.496 867355.3286 991152.5589 1120232.679 1070469.439 881621.3768 1962520.554 804870.6402 Tryptamine 105007.902 56527.5606 50522.95949 30947.48198 100219.4596 103651.1763 164411.7884 92482.3442 Uracil 4.22E+07 4.13E+07 2.70E+07 2.51E+07 4.02E+07 4.86E+07 4.77E+07 4.16E+07 Urate 3.77E+07 5.52E+07 2.93E+07 2.19E+07 2.30E+07 5.78E+07 6.68E+07 4.64E+07 Uridine 1.58E+07 7396291.286 8715455.043 9842615.6 1.39E+07 2.06E+07 1.63E+07 1.53E+07 Xanthine 3.65E+08 3.12E+08 2.40E+08 2.31E+08 3.28E+08 4.04E+08 3.82E+08 3.79E+08 MS_METABOLITE_DATA_END #METABOLITES METABOLITES_START metabolite_name Trans-Aconitate 1-Aminocyclopropane-1-Carboxylate_1 1-Aminocyclopropane-1-Carboxylate_2 1-Methylnicotinamide 2-Acetamido-2-Deoxy-Beta-D-Glucosylamine 2-Amino-2-Methylpropanoate_1 2-Amino-2-Methylpropanoate_2 2-Hydroxyglutarate+Na 2-Hydroxyglutarate-Water 2-Hydroxyphenylalanine 2-Methylbutyroylcarnitine_1 2-Methylbutyroylcarnitine_2 2-Methylglutaric Acid 3-Aminoisobutanoate 3-Hydroxy-3-Methylglutarate_1 3-Hydroxy-3-Methylglutarate_2 3-Methylcrotonylglycine 3-Ureidopropionate_1 3-Ureidopropionate_2 3-Ureidopropionate_3 4-Acetamidobutanoate 4-Aminobenzoate_1 4-Aminobenzoate_2 4-Aminobutanoate (Gaba) 4-Guanidinobutanoate 4-Hydroxybenzaldehyde 4-Hydroxy-L-Phenylglycine_1 4-Hydroxy-L-Phenylglycine_2 4-Hydroxy-L-Proline_1 4-Hydroxy-L-Proline_2 5-Aminolevulinic Acid 5-Hydroxymethyl-2-Furaldehyde_1 5-Hydroxymethyl-2-Furaldehyde_2 5-Hydroxy-N-Formylkynurenine 5-Oxo-D-Proline_1 5-Oxo-D-Proline_2 6C-Sugar Alcohol 6-Hydroxynicotinate 7-Ketochenodeoxycholic Acid Acetylcitrulline Acetyl-Dl-Carnitine_1 Acetyl-Dl-Carnitine_2 Acyl-Carnitine(5-Oh)_1 Acyl-Carnitine(5-Oh)_2 Acyl-Carnitine(5-Oh)_3 Adenine Alanine/Sarcosine Aldo/Keto-Hexose Aldopentose Alpha-Aminoadipate/N-Methyl-L-Glutamate_1 Alpha-Aminoadipate/N-Methyl-L-Glutamate_2 Alpha-Aminoadipate/N-Methyl-L-Glutamate_3 Alpha-D-Glucose Arabinose Aspartate Boc-D-Phenylalanine Butanoylcarnitine Carnosine Cellobiose Choline Citrulline_1 Citrulline_2 Creatine Cytosine_1 Cytosine_2 D-Fructose D-Gluconate D-Glucosamine 6-Phosphate_1 D-Glucosamine 6-Phosphate_2 D-Glyceric Acid D-Mannosamine_1 D-Mannosamine_2 D-Sorbitol Formate Formyl-5-Hydroxykynurenamine Formylkynurenine Gama-Muricholic Acid Gentiobiose_1 Gentiobiose_2 Glutathione Disulfide Glu-Thr Glycerol_1 Glycerol_2 Glycerophosphocholine Glycine Guanidinoacetate Hippurate Homoserine_1 Homoserine_2 Hypoxanthine_1 Hypoxanthine_2 Indole-3-Acetaldehyde Indoleacrylic Acid Isocytosine Isoleucine L-Anserine L-Arabitol L-Asparagine_1 L-Asparagine_2 L-Asparagine_3 L-Asparagine_4 L-Aspartate L-Carnitine Leu Pro Leucine L-Glutamic Acid_1 L-Glutamic Acid_2 L-Glutamic Acid_3 L-Glutamic Acid_4 L-Glutamine_1 L-Glutamine_2 L-Histidine_1 L-Histidine_2 L-Isoleucine L-Kynurenine L-Lactic Acid_1 L-Lactic Acid_2 L-Lactic Acid_3 L-Lysine_1 L-Lysine_2 L-Lysine_3 L-Lysine_4 L-Methionine_1 L-Methionine_2 L-Methionine_3 L-Ornithine_1 L-Ornithine_2 L-Ornithine_3 L-Ornithine_4 L-Phenylalanine_1 L-Phenylalanine_2 L-Phenylalanine_3 L-Pipecolic Acid_1 L-Pipecolic Acid_2 L-Pipecolic Acid_3 L-Proline L-Serine_1 L-Serine_2 L-Tryptophan_1 L-Tryptophan_2 L-Tyrosine_1 L-Tyrosine_2 Lumichrome L-Valine Lysope (20:4) Malate Methionine Sulfoxide N1-Methyl-2-Pyridone-5-Carboxamide N-Acetyl-D-Galactosamine N-Acetyl-Dl-Glutamic Acid N-Acetyl-Dl-Serine N-Acetylglycine_1 N-Acetylglycine_2 N-Acetyl-L-Alanine_1 N-Acetyl-L-Alanine_2 N-Acetyl-L-Alanine_3 N-Acetyl-L-Aspartic Acid_1 N-Acetyl-L-Aspartic Acid_2 N-Acetyl-L-Leucine_1 N-Acetyl-L-Leucine_2 N-Acetyl-L-Leucine_3 N-Boc-L-Aspartic Acid N-Boc-L-Tert-Leucine N-Boc-L-Tryptophan Nicotinamide Nicotinate_1 Nicotinate_2 N-Methyl-L-Histidine Norleucine O-Acetyl-L-Serine Pantothenic Acid_1 Pantothenic Acid_2 Phenylalanine-Hcooh Phosphocholine Propanoylcarnitine Putrescine Pyridoxal_1 Pyridoxal_2 Sn-Glycerol 3-Phosphate Spermidine Stachydrine Taurine_1 Taurine_2 Taurine_3 Thymine Tiglylcarnitine_1 Tiglylcarnitine_2 Trans-Aconitate_1 Trigonelline_1 Trigonelline_2 Tryptamine Uracil Urate Uridine Xanthine METABOLITES_END #END