{
"METABOLOMICS WORKBENCH":{"STUDY_ID":"ST003175","ANALYSIS_ID":"AN005211","VERSION":"1","CREATED_ON":"April 18, 2024, 6:11 pm"},

"PROJECT":{"PROJECT_TITLE":"Inactivation of mitochondrial MUL1 E3 ubiquitin ligase inhibits lipogenesis and prevents diet-induced obesity in mice","PROJECT_TYPE":"Basic Research","PROJECT_SUMMARY":"Characterize the role of mitochondrial MUL1 E3-ubiquitin ligase on energy metabolism and lipogenesis using Mul1 deficient, Mul1(-/-), mice. MUL1 protein is involved in mitochondrial dynamics, and innate immune response but its primary function might be the regulation of lipogenesis under conditions of nutritional overload. Using metabolic cages, we monitored whole body energy expenditure, metabolism, and thermoregulation of the Mul1(-/-) mice under standard diet (ND) or high fat diet (HFD). We examined the effect of Mul1 inactivation on body weight, HFD-induced adiposity, fatty liver, glucose intolerance, and insulin resistance. We performed global metabolomics, lipidomic, and genome-wide mRNA sequencing using liver from Mul1(+/+) and Mul1(-/-) animals on HFD. The expression level of key proteins involved in lipogenesis and their regulation in the absence of MUL1 was monitored by SDS-PAGE and Western blot analysis. We found that Mul1(-/-) animals have a metabolic phenotype that confers robust resistance to HFD-induced obesity. Several metabolic and lipidomic pathways are perturbed in the liver of Mul1(-/-) animals on HFD, particularly the one driven by Stearoyl-CoA Desaturase 1 (SCD1), a key regulator of lipid metabolism and obesity. In addition, key enzymes involved in lipogenesis and fatty acid oxidation such as ACC1, FASN, AMPK, and CTP1 were also modulated. The concerted deregulation of these enzymes, in the absence of MUL1, causes reduced fat storage and increased fatty acid oxidation. We identified a new function of mitochondrial MUL1 E3 ubiquitin ligase in the regulation of lipogenesis and adiposity, particularly during conditions of HFD. Inactivation of MUL1 provides resistance to HFD-induced obesity and can be a therapeutic target for the treatment of obesity, type 2 diabetes, and nonalcoholic fatty liver disease (NAFLD).","INSTITUTE":"University of Florida","DEPARTMENT":"Biochemistry","LABORATORY":"Merritt''s Lab","LAST_NAME":"Merritt","FIRST_NAME":"Matthew","ADDRESS":"SW ARCHER RD, Gainesville, FL 32611","EMAIL":"rmahar@hnbgu.ac.in","PHONE":"9557559849","FUNDING_SOURCE":"NIH","CONTRIBUTORS":"Lucia Cilenti, Jacopo Di Gregorio, Rohit Mahar, Fei Liu, Camilla T. Ambivero, Muthu Periasamy, Matthew E. Merrit, and Antonis S. Zervos"},

"STUDY":{"STUDY_TITLE":"Inactivation of mitochondrial MUL1 E3 ubiquitin ligase inhibits lipogenesis and prevents diet-induced obesity in mice","STUDY_TYPE":"Basic Research","STUDY_SUMMARY":"Characterize the role of mitochondrial MUL1 E3-ubiquitin ligase on energy metabolism and lipogenesis using Mul1 deficient, Mul1(-/-), mice. MUL1 protein is involved in mitochondrial dynamics, and innate immune response but its primary function might be the regulation of lipogenesis under conditions of nutritional overload. Using metabolic cages, we monitored whole body energy expenditure, metabolism, and thermoregulation of the Mul1(-/-) mice under standard diet (ND) or high fat diet (HFD). We examined the effect of Mul1 inactivation on body weight, HFD-induced adiposity, fatty liver, glucose intolerance, and insulin resistance. We performed global metabolomics, lipidomic, and genome-wide mRNA sequencing using liver from Mul1(+/+) and Mul1(-/-) animals on HFD. The expression level of key proteins involved in lipogenesis and their regulation in the absence of MUL1 was monitored by SDS-PAGE and Western blot analysis. We found that Mul1(-/-) animals have a metabolic phenotype that confers robust resistance to HFD-induced obesity. Several metabolic and lipidomic pathways are perturbed in the liver of Mul1(-/-) animals on HFD, particularly the one driven by Stearoyl-CoA Desaturase 1 (SCD1), a key regulator of lipid metabolism and obesity. In addition, key enzymes involved in lipogenesis and fatty acid oxidation such as ACC1, FASN, AMPK, and CTP1 were also modulated. The concerted deregulation of these enzymes, in the absence of MUL1, causes reduced fat storage and increased fatty acid oxidation. We identified a new function of mitochondrial MUL1 E3 ubiquitin ligase in the regulation of lipogenesis and adiposity, particularly during conditions of HFD. Inactivation of MUL1 provides resistance to HFD-induced obesity and can be a therapeutic target for the treatment of obesity, type 2 diabetes, and nonalcoholic fatty liver disease (NAFLD).","INSTITUTE":"University of Florida","LAST_NAME":"Merritt","FIRST_NAME":"Matthew","ADDRESS":"SW ARCHER RD, Gainesville, FL 32611","EMAIL":"rmahar@hnbgu.ac.in","PHONE":"9557559849","NUM_GROUPS":"2","TOTAL_SUBJECTS":"12","NUM_MALES":"6","NUM_FEMALES":"6"},

"SUBJECT":{"SUBJECT_TYPE":"Mammal","SUBJECT_SPECIES":"Mus musculus","TAXONOMY_ID":"10090","GENOTYPE_STRAIN":"Wild type and Mul1(+/+) mice","AGE_OR_AGE_RANGE":"8 weeks","GENDER":"Male and female","ANIMAL_LIGHT_CYCLE":"12-hour/12-hour light/dark cycle","ANIMAL_FEED":"Research Diets D12492"},
"SUBJECT_SAMPLE_FACTORS":[
{
"Subject ID":"-",
"Sample ID":"Mul1(+/+)_TZ 34",
"Factors":{"Genotype":"Mul1(+/+) ","Sample source":"Liver"}
},
{
"Subject ID":"-",
"Sample ID":"Mul1(+/+)_TZ 35",
"Factors":{"Genotype":"Mul1(+/+) ","Sample source":"Liver"}
},
{
"Subject ID":"-",
"Sample ID":"Mul1(+/+)_TZ 36",
"Factors":{"Genotype":"Mul1(+/+) ","Sample source":"Liver"}
},
{
"Subject ID":"-",
"Sample ID":"Mul1(+/+)_TZ 37",
"Factors":{"Genotype":"Mul1(+/+) ","Sample source":"Liver"}
},
{
"Subject ID":"-",
"Sample ID":"Mul1(-/-)_TZ 38",
"Factors":{"Genotype":"Mul1(-/-) ","Sample source":"Liver"}
},
{
"Subject ID":"-",
"Sample ID":"Mul1(-/-)_TZ 39",
"Factors":{"Genotype":"Mul1(-/-) ","Sample source":"Liver"}
},
{
"Subject ID":"-",
"Sample ID":"Mul1(-/-)_TZ 40",
"Factors":{"Genotype":"Mul1(-/-) ","Sample source":"Liver"}
},
{
"Subject ID":"-",
"Sample ID":"Mul1(-/-)_TZ 41",
"Factors":{"Genotype":"Mul1(-/-) ","Sample source":"Liver"}
}
],
"COLLECTION":{"COLLECTION_SUMMARY":"Liver tissue was obtained from Mul1(+/+) and Mul1(-/-) mice following a HFD for 16 weeks and stained with H&E or Oil Red Oil.","SAMPLE_TYPE":"Liver","STORAGE_CONDITIONS":"-20℃"},

"TREATMENT":{"TREATMENT_SUMMARY":"Liver tissue was obtained from Mul1(+/+) and Mul1(-/-) mice following a HFD for 16 weeks and stained with H&E or Oil Red Oil."},

"SAMPLEPREP":{"SAMPLEPREP_SUMMARY":"liver tissues from mice were fixed overnight in 10% neutral formalin and embedded in paraffin. Paraffin-embedded tissues were cut into sections and stained with hematoxylin and eosin (H&E) for assessment of liver histology. Liver tissue from Mul1(+/+) and Mul1(-/-) mice on HFD were subjected to the Folch extraction in order to separate lipids and polar metabolites.","PROCESSING_STORAGE_CONDITIONS":"4℃","EXTRACT_STORAGE":"-20℃"},

"CHROMATOGRAPHY":{"CHROMATOGRAPHY_TYPE":"Reversed phase","INSTRUMENT_NAME":"Thermo Dionex Ultimate 3000","COLUMN_NAME":"Waters ACQUITY UPLC BEH C18 (100 x 2.1mm,1.7um)","SOLVENT_A":"60:40 acetonitrile:water; 10mM ammonium formate; 0.1% formic acid","SOLVENT_B":"90:8:2 2-propanol:acetonitrile:water; 10mM ammonium formate; 0.1% formic acid","FLOW_GRADIENT":"10 µl/min","FLOW_RATE":"350 µl/min","COLUMN_TEMPERATURE":"50"},

"ANALYSIS":{"ANALYSIS_TYPE":"MS"},

"MS":{"INSTRUMENT_NAME":"Thermo Q Exactive Orbitrap","INSTRUMENT_TYPE":"Orbitrap","MS_TYPE":"ESI","ION_MODE":"POSITIVE","MS_COMMENTS":"The aqueous phase was analyzed using the Thermo Q-Exactive Orbitrap mass spectrometer with Dionex UHPLC and autosampler. All samples were analyzed in positive and negative simultaneously with heated electrospray ionization (HESI) with a mass resolution of 35,000 at m/z 200 as separate injections. The polar metabolites were analyzed on Thermo Q-Exactive Orbitrap mass spectrometer equipped with UHPLC. Data were analyzed with MZmine and features were aligned for identification across samples. The metabolites were searched against the Southeastern Center for Integrated Metabolomics (SECIM) metabolite library using retention time and corresponding mass spectral data. Lipids isolated from Folch extraction procedure were also analyzed by the same instrument. Lipidomics data were analyzed using the LipidMatch software and identified lipid entities were exported in a tabular form."},

"MS_METABOLITE_DATA":{
"Units":"A.U.",

"Data":[{"Metabolite":"Trans-Aconitate","Mul1(+/+)_TZ 34":"16384.62109","Mul1(+/+)_TZ 35":"13429.04883","Mul1(+/+)_TZ 36":"23449.53516","Mul1(+/+)_TZ 37":"19184.64844","Mul1(-/-)_TZ 38":"8318.889648","Mul1(-/-)_TZ 39":"6993.270996","Mul1(-/-)_TZ 40":"37761.10938","Mul1(-/-)_TZ 41":"3424.447998"},{"Metabolite":"1-Aminocyclopropane-1-Carboxylate_1","Mul1(+/+)_TZ 34":"524260.3125","Mul1(+/+)_TZ 35":"484287.75","Mul1(+/+)_TZ 36":"244709.0156","Mul1(+/+)_TZ 37":"378251.4063","Mul1(-/-)_TZ 38":"651176.875","Mul1(-/-)_TZ 39":"595911.5625","Mul1(-/-)_TZ 40":"796391","Mul1(-/-)_TZ 41":"453275.625"},{"Metabolite":"1-Aminocyclopropane-1-Carboxylate_2","Mul1(+/+)_TZ 34":"3.26E+07","Mul1(+/+)_TZ 35":"2.47E+07","Mul1(+/+)_TZ 36":"2.08E+07","Mul1(+/+)_TZ 37":"2.67E+07","Mul1(-/-)_TZ 38":"2.33E+07","Mul1(-/-)_TZ 39":"2.22E+07","Mul1(-/-)_TZ 40":"2.46E+07","Mul1(-/-)_TZ 41":"2.53E+07"},{"Metabolite":"1-Methylnicotinamide","Mul1(+/+)_TZ 34":"1.65E+07","Mul1(+/+)_TZ 35":"1.75E+07","Mul1(+/+)_TZ 36":"4379405.9","Mul1(+/+)_TZ 37":"5991712.157","Mul1(-/-)_TZ 38":"2.09E+07","Mul1(-/-)_TZ 39":"2.65E+07","Mul1(-/-)_TZ 40":"8105263","Mul1(-/-)_TZ 41":"8024924.243"},{"Metabolite":"2-Acetamido-2-Deoxy-Beta-D-Glucosylamine","Mul1(+/+)_TZ 34":"1.38E+07","Mul1(+/+)_TZ 35":"7749322.471","Mul1(+/+)_TZ 36":"1.05E+07","Mul1(+/+)_TZ 37":"8996935.157","Mul1(-/-)_TZ 38":"9427761.329","Mul1(-/-)_TZ 39":"1.05E+07","Mul1(-/-)_TZ 40":"1.49E+07","Mul1(-/-)_TZ 41":"8576510.229"},{"Metabolite":"2-Amino-2-Methylpropanoate_1","Mul1(+/+)_TZ 34":"1077060","Mul1(+/+)_TZ 35":"707137.875","Mul1(+/+)_TZ 36":"1095480.429","Mul1(+/+)_TZ 37":"1099870.5","Mul1(-/-)_TZ 38":"1657150.086","Mul1(-/-)_TZ 39":"1753380.125","Mul1(-/-)_TZ 40":"3692967.671","Mul1(-/-)_TZ 41":"2414286.25"},{"Metabolite":"2-Amino-2-Methylpropanoate_2","Mul1(+/+)_TZ 34":"2.59E+07","Mul1(+/+)_TZ 35":"1.37E+07","Mul1(+/+)_TZ 36":"1.25E+07","Mul1(+/+)_TZ 37":"2.07E+07","Mul1(-/-)_TZ 38":"2.03E+07","Mul1(-/-)_TZ 39":"3.72E+07","Mul1(-/-)_TZ 40":"6.25E+07","Mul1(-/-)_TZ 41":"3.79E+07"},{"Metabolite":"2-Hydroxyglutarate+Na","Mul1(+/+)_TZ 34":"96949.74464","Mul1(+/+)_TZ 35":"139159.729","Mul1(+/+)_TZ 36":"97618.65379","Mul1(+/+)_TZ 37":"126724.0489","Mul1(-/-)_TZ 38":"66699.75","Mul1(-/-)_TZ 39":"102433.4163","Mul1(-/-)_TZ 40":"171617.7509","Mul1(-/-)_TZ 41":"107836.1547"},{"Metabolite":"2-Hydroxyglutarate-Water","Mul1(+/+)_TZ 34":"305140.2013","Mul1(+/+)_TZ 35":"380898.217","Mul1(+/+)_TZ 36":"263530.6812","Mul1(+/+)_TZ 37":"359316.2366","Mul1(-/-)_TZ 38":"181033.65","Mul1(-/-)_TZ 39":"307425.7214","Mul1(-/-)_TZ 40":"482520.6125","Mul1(-/-)_TZ 41":"318869.5955"},{"Metabolite":"2-Hydroxyphenylalanine","Mul1(+/+)_TZ 34":"2.48E+08","Mul1(+/+)_TZ 35":"1.87E+08","Mul1(+/+)_TZ 36":"1.52E+08","Mul1(+/+)_TZ 37":"1.68E+08","Mul1(-/-)_TZ 38":"2.31E+08","Mul1(-/-)_TZ 39":"2.75E+08","Mul1(-/-)_TZ 40":"3.26E+08","Mul1(-/-)_TZ 41":"2.40E+08"},{"Metabolite":"2-Methylbutyroylcarnitine_1","Mul1(+/+)_TZ 34":"1060311.275","Mul1(+/+)_TZ 35":"669868.8125","Mul1(+/+)_TZ 36":"277930.7906","Mul1(+/+)_TZ 37":"284140.3036","Mul1(-/-)_TZ 38":"776124.5786","Mul1(-/-)_TZ 39":"2185064.85","Mul1(-/-)_TZ 40":"894489.8768","Mul1(-/-)_TZ 41":"1739019.111"},{"Metabolite":"2-Methylbutyroylcarnitine_2","Mul1(+/+)_TZ 34":"1763094.239","Mul1(+/+)_TZ 35":"592609.525","Mul1(+/+)_TZ 36":"436620.0875","Mul1(+/+)_TZ 37":"557502.0438","Mul1(-/-)_TZ 38":"1533727.118","Mul1(-/-)_TZ 39":"5610121.914","Mul1(-/-)_TZ 40":"1563351.071","Mul1(-/-)_TZ 41":"2782329.1"},{"Metabolite":"2-Methylglutaric Acid","Mul1(+/+)_TZ 34":"1342934.363","Mul1(+/+)_TZ 35":"1266121.9","Mul1(+/+)_TZ 36":"1445986.65","Mul1(+/+)_TZ 37":"1475085.421","Mul1(-/-)_TZ 38":"1528990.664","Mul1(-/-)_TZ 39":"1379790.746","Mul1(-/-)_TZ 40":"1312325.071","Mul1(-/-)_TZ 41":"1330891.804"},{"Metabolite":"3-Aminoisobutanoate","Mul1(+/+)_TZ 34":"1960672.514","Mul1(+/+)_TZ 35":"1032309.82","Mul1(+/+)_TZ 36":"922249.5071","Mul1(+/+)_TZ 37":"1465860.821","Mul1(-/-)_TZ 38":"1448733.557","Mul1(-/-)_TZ 39":"2741999.486","Mul1(-/-)_TZ 40":"3424714.643","Mul1(-/-)_TZ 41":"1120479.37"},{"Metabolite":"3-Hydroxy-3-Methylglutarate_1","Mul1(+/+)_TZ 34":"228273.3281","Mul1(+/+)_TZ 35":"248499.3125","Mul1(+/+)_TZ 36":"189558.7656","Mul1(+/+)_TZ 37":"250144.75","Mul1(-/-)_TZ 38":"258395.5362","Mul1(-/-)_TZ 39":"340870.375","Mul1(-/-)_TZ 40":"547673.6161","Mul1(-/-)_TZ 41":"399150.1009"},{"Metabolite":"3-Hydroxy-3-Methylglutarate_2","Mul1(+/+)_TZ 34":"753441.625","Mul1(+/+)_TZ 35":"805405.1875","Mul1(+/+)_TZ 36":"563967.6875","Mul1(+/+)_TZ 37":"818378.4375","Mul1(-/-)_TZ 38":"816069.5","Mul1(-/-)_TZ 39":"1071476.75","Mul1(-/-)_TZ 40":"1828873.418","Mul1(-/-)_TZ 41":"1377664.625"},{"Metabolite":"3-Methylcrotonylglycine","Mul1(+/+)_TZ 34":"83928.17522","Mul1(+/+)_TZ 35":"57771.08504","Mul1(+/+)_TZ 36":"67532.52299","Mul1(+/+)_TZ 37":"112499.8558","Mul1(-/-)_TZ 38":"103708.1529","Mul1(-/-)_TZ 39":"123146.3228","Mul1(-/-)_TZ 40":"364271.8536","Mul1(-/-)_TZ 41":"61516.38147"},{"Metabolite":"3-Ureidopropionate_1","Mul1(+/+)_TZ 34":"936459.0714","Mul1(+/+)_TZ 35":"1358464.175","Mul1(+/+)_TZ 36":"2693504.986","Mul1(+/+)_TZ 37":"2341491.743","Mul1(-/-)_TZ 38":"432751.8125","Mul1(-/-)_TZ 39":"1940310.679","Mul1(-/-)_TZ 40":"1596504.886","Mul1(-/-)_TZ 41":"1421691.739"},{"Metabolite":"3-Ureidopropionate_2","Mul1(+/+)_TZ 34":"1643015.236","Mul1(+/+)_TZ 35":"1505031.518","Mul1(+/+)_TZ 36":"2091672.443","Mul1(+/+)_TZ 37":"1544840.086","Mul1(-/-)_TZ 38":"339690.3545","Mul1(-/-)_TZ 39":"1759715.093","Mul1(-/-)_TZ 40":"1361330.489","Mul1(-/-)_TZ 41":"1617044.3"},{"Metabolite":"3-Ureidopropionate_3","Mul1(+/+)_TZ 34":"5243055.886","Mul1(+/+)_TZ 35":"5912296.471","Mul1(+/+)_TZ 36":"4186888.2","Mul1(+/+)_TZ 37":"3616648.964","Mul1(-/-)_TZ 38":"4883712.971","Mul1(-/-)_TZ 39":"8919371.114","Mul1(-/-)_TZ 40":"7117151.557","Mul1(-/-)_TZ 41":"6141978.4"},{"Metabolite":"4-Acetamidobutanoate","Mul1(+/+)_TZ 34":"9917.639648","Mul1(+/+)_TZ 35":"8760.795898","Mul1(+/+)_TZ 36":"7602.585449","Mul1(+/+)_TZ 37":"12968.78125","Mul1(-/-)_TZ 38":"7258.121094","Mul1(-/-)_TZ 39":"11080.03223","Mul1(-/-)_TZ 40":"13156.35352","Mul1(-/-)_TZ 41":"13004.62109"},{"Metabolite":"4-Aminobenzoate_1","Mul1(+/+)_TZ 34":"382648.433","Mul1(+/+)_TZ 35":"145839.2042","Mul1(+/+)_TZ 36":"239365.2862","Mul1(+/+)_TZ 37":"151843.3228","Mul1(-/-)_TZ 38":"216669.5585","Mul1(-/-)_TZ 39":"443349.5446","Mul1(-/-)_TZ 40":"580690.2027","Mul1(-/-)_TZ 41":"339827.175"},{"Metabolite":"4-Aminobenzoate_2","Mul1(+/+)_TZ 34":"834457.3625","Mul1(+/+)_TZ 35":"317123.7786","Mul1(+/+)_TZ 36":"505993.1438","Mul1(+/+)_TZ 37":"342382.1134","Mul1(-/-)_TZ 38":"468490.3982","Mul1(-/-)_TZ 39":"981805.4661","Mul1(-/-)_TZ 40":"1253774.148","Mul1(-/-)_TZ 41":"696728.4063"},{"Metabolite":"4-Aminobutanoate (Gaba)","Mul1(+/+)_TZ 34":"3114394.193","Mul1(+/+)_TZ 35":"1728426.293","Mul1(+/+)_TZ 36":"1719717.118","Mul1(+/+)_TZ 37":"2454911.018","Mul1(-/-)_TZ 38":"2487780.246","Mul1(-/-)_TZ 39":"4268822.571","Mul1(-/-)_TZ 40":"4637120.614","Mul1(-/-)_TZ 41":"1804840.711"},{"Metabolite":"4-Guanidinobutanoate","Mul1(+/+)_TZ 34":"1483532.261","Mul1(+/+)_TZ 35":"1488307.7","Mul1(+/+)_TZ 36":"947360.0357","Mul1(+/+)_TZ 37":"1941422.3","Mul1(-/-)_TZ 38":"2280867.536","Mul1(-/-)_TZ 39":"2312173.821","Mul1(-/-)_TZ 40":"8979235.629","Mul1(-/-)_TZ 41":"3759475.236"},{"Metabolite":"4-Hydroxybenzaldehyde","Mul1(+/+)_TZ 34":"616508.1562","Mul1(+/+)_TZ 35":"202700.9438","Mul1(+/+)_TZ 36":"263194.5964","Mul1(+/+)_TZ 37":"206676.9219","Mul1(-/-)_TZ 38":"124086.0078","Mul1(-/-)_TZ 39":"263434.9701","Mul1(-/-)_TZ 40":"239174.1161","Mul1(-/-)_TZ 41":"107494.5391"},{"Metabolite":"4-Hydroxy-L-Phenylglycine_1","Mul1(+/+)_TZ 34":"474726.5938","Mul1(+/+)_TZ 35":"448999.7964","Mul1(+/+)_TZ 36":"175496.7031","Mul1(+/+)_TZ 37":"288731.4375","Mul1(-/-)_TZ 38":"271722.7188","Mul1(-/-)_TZ 39":"267139.1563","Mul1(-/-)_TZ 40":"119007.3359","Mul1(-/-)_TZ 41":"415656.3438"},{"Metabolite":"4-Hydroxy-L-Phenylglycine_2","Mul1(+/+)_TZ 34":"1353249.621","Mul1(+/+)_TZ 35":"897256.6875","Mul1(+/+)_TZ 36":"841814.0107","Mul1(+/+)_TZ 37":"963864.9286","Mul1(-/-)_TZ 38":"814023.5554","Mul1(-/-)_TZ 39":"805510.9821","Mul1(-/-)_TZ 40":"1503376.925","Mul1(-/-)_TZ 41":"872254.8036"},{"Metabolite":"4-Hydroxy-L-Proline_1","Mul1(+/+)_TZ 34":"1179723.932","Mul1(+/+)_TZ 35":"1028914.416","Mul1(+/+)_TZ 36":"894242","Mul1(+/+)_TZ 37":"550974.6205","Mul1(-/-)_TZ 38":"1148426.875","Mul1(-/-)_TZ 39":"2182754","Mul1(-/-)_TZ 40":"1137124.5","Mul1(-/-)_TZ 41":"965046.375"},{"Metabolite":"4-Hydroxy-L-Proline_2","Mul1(+/+)_TZ 34":"3152086.557","Mul1(+/+)_TZ 35":"2714245.664","Mul1(+/+)_TZ 36":"4076123.364","Mul1(+/+)_TZ 37":"3810386.493","Mul1(-/-)_TZ 38":"4329706.521","Mul1(-/-)_TZ 39":"6632903.457","Mul1(-/-)_TZ 40":"1.27E+07","Mul1(-/-)_TZ 41":"8472202.543"},{"Metabolite":"5-Aminolevulinic Acid","Mul1(+/+)_TZ 34":"8188638.214","Mul1(+/+)_TZ 35":"5003610.679","Mul1(+/+)_TZ 36":"4058742.5","Mul1(+/+)_TZ 37":"2352635.1","Mul1(-/-)_TZ 38":"5149571.686","Mul1(-/-)_TZ 39":"1.19E+07","Mul1(-/-)_TZ 40":"4569077.686","Mul1(-/-)_TZ 41":"4597683.379"},{"Metabolite":"5-Hydroxymethyl-2-Furaldehyde_1","Mul1(+/+)_TZ 34":"2.04E+07","Mul1(+/+)_TZ 35":"1.81E+07","Mul1(+/+)_TZ 36":"1.19E+07","Mul1(+/+)_TZ 37":"1.67E+07","Mul1(-/-)_TZ 38":"1.14E+07","Mul1(-/-)_TZ 39":"1.46E+07","Mul1(-/-)_TZ 40":"2519350.25","Mul1(-/-)_TZ 41":"1.70E+07"},{"Metabolite":"5-Hydroxymethyl-2-Furaldehyde_2","Mul1(+/+)_TZ 34":"2.03E+07","Mul1(+/+)_TZ 35":"1.69E+07","Mul1(+/+)_TZ 36":"1.51E+07","Mul1(+/+)_TZ 37":"1.81E+07","Mul1(-/-)_TZ 38":"1.16E+07","Mul1(-/-)_TZ 39":"1.47E+07","Mul1(-/-)_TZ 40":"6228954","Mul1(-/-)_TZ 41":"1.82E+07"},{"Metabolite":"5-Hydroxy-N-Formylkynurenine","Mul1(+/+)_TZ 34":"217568.0263","Mul1(+/+)_TZ 35":"262684.0688","Mul1(+/+)_TZ 36":"244881.246","Mul1(+/+)_TZ 37":"317667.2138","Mul1(-/-)_TZ 38":"293246.0063","Mul1(-/-)_TZ 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34":"3.77E+07","Mul1(+/+)_TZ 35":"5.52E+07","Mul1(+/+)_TZ 36":"2.93E+07","Mul1(+/+)_TZ 37":"2.19E+07","Mul1(-/-)_TZ 38":"2.30E+07","Mul1(-/-)_TZ 39":"5.78E+07","Mul1(-/-)_TZ 40":"6.68E+07","Mul1(-/-)_TZ 41":"4.64E+07"},{"Metabolite":"Uridine","Mul1(+/+)_TZ 34":"1.58E+07","Mul1(+/+)_TZ 35":"7396291.286","Mul1(+/+)_TZ 36":"8715455.043","Mul1(+/+)_TZ 37":"9842615.6","Mul1(-/-)_TZ 38":"1.39E+07","Mul1(-/-)_TZ 39":"2.06E+07","Mul1(-/-)_TZ 40":"1.63E+07","Mul1(-/-)_TZ 41":"1.53E+07"},{"Metabolite":"Xanthine","Mul1(+/+)_TZ 34":"3.65E+08","Mul1(+/+)_TZ 35":"3.12E+08","Mul1(+/+)_TZ 36":"2.40E+08","Mul1(+/+)_TZ 37":"2.31E+08","Mul1(-/-)_TZ 38":"3.28E+08","Mul1(-/-)_TZ 39":"4.04E+08","Mul1(-/-)_TZ 40":"3.82E+08","Mul1(-/-)_TZ 41":"3.79E+08"}],

"Metabolites":[{"metabolite_name":"Trans-Aconitate"},{"metabolite_name":"1-Aminocyclopropane-1-Carboxylate_1"},{"metabolite_name":"1-Aminocyclopropane-1-Carboxylate_2"},{"metabolite_name":"1-Methylnicotinamide"},{"metabolite_name":"2-Acetamido-2-Deoxy-Beta-D-Glucosylamine"},{"metabolite_name":"2-Amino-2-Methylpropanoate_1"},{"metabolite_name":"2-Amino-2-Methylpropanoate_2"},{"metabolite_name":"2-Hydroxyglutarate+Na"},{"metabolite_name":"2-Hydroxyglutarate-Water"},{"metabolite_name":"2-Hydroxyphenylalanine"},{"metabolite_name":"2-Methylbutyroylcarnitine_1"},{"metabolite_name":"2-Methylbutyroylcarnitine_2"},{"metabolite_name":"2-Methylglutaric 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6-Phosphate_1"},{"metabolite_name":"D-Glucosamine 6-Phosphate_2"},{"metabolite_name":"D-Glyceric Acid"},{"metabolite_name":"D-Mannosamine_1"},{"metabolite_name":"D-Mannosamine_2"},{"metabolite_name":"D-Sorbitol"},{"metabolite_name":"Formate"},{"metabolite_name":"Formyl-5-Hydroxykynurenamine"},{"metabolite_name":"Formylkynurenine"},{"metabolite_name":"Gama-Muricholic Acid"},{"metabolite_name":"Gentiobiose_1"},{"metabolite_name":"Gentiobiose_2"},{"metabolite_name":"Glutathione Disulfide"},{"metabolite_name":"Glu-Thr"},{"metabolite_name":"Glycerol_1"},{"metabolite_name":"Glycerol_2"},{"metabolite_name":"Glycerophosphocholine"},{"metabolite_name":"Glycine"},{"metabolite_name":"Guanidinoacetate"},{"metabolite_name":"Hippurate"},{"metabolite_name":"Homoserine_1"},{"metabolite_name":"Homoserine_2"},{"metabolite_name":"Hypoxanthine_1"},{"metabolite_name":"Hypoxanthine_2"},{"metabolite_name":"Indole-3-Acetaldehyde"},{"metabolite_name":"Indoleacrylic 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(20:4)"},{"metabolite_name":"Malate"},{"metabolite_name":"Methionine Sulfoxide"},{"metabolite_name":"N1-Methyl-2-Pyridone-5-Carboxamide"},{"metabolite_name":"N-Acetyl-D-Galactosamine"},{"metabolite_name":"N-Acetyl-Dl-Glutamic Acid"},{"metabolite_name":"N-Acetyl-Dl-Serine"},{"metabolite_name":"N-Acetylglycine_1"},{"metabolite_name":"N-Acetylglycine_2"},{"metabolite_name":"N-Acetyl-L-Alanine_1"},{"metabolite_name":"N-Acetyl-L-Alanine_2"},{"metabolite_name":"N-Acetyl-L-Alanine_3"},{"metabolite_name":"N-Acetyl-L-Aspartic Acid_1"},{"metabolite_name":"N-Acetyl-L-Aspartic Acid_2"},{"metabolite_name":"N-Acetyl-L-Leucine_1"},{"metabolite_name":"N-Acetyl-L-Leucine_2"},{"metabolite_name":"N-Acetyl-L-Leucine_3"},{"metabolite_name":"N-Boc-L-Aspartic 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3-Phosphate"},{"metabolite_name":"Spermidine"},{"metabolite_name":"Stachydrine"},{"metabolite_name":"Taurine_1"},{"metabolite_name":"Taurine_2"},{"metabolite_name":"Taurine_3"},{"metabolite_name":"Thymine"},{"metabolite_name":"Tiglylcarnitine_1"},{"metabolite_name":"Tiglylcarnitine_2"},{"metabolite_name":"Trans-Aconitate_1"},{"metabolite_name":"Trigonelline_1"},{"metabolite_name":"Trigonelline_2"},{"metabolite_name":"Tryptamine"},{"metabolite_name":"Uracil"},{"metabolite_name":"Urate"},{"metabolite_name":"Uridine"},{"metabolite_name":"Xanthine"}]
}

}