{
"METABOLOMICS WORKBENCH":{"STUDY_ID":"ST003167","ANALYSIS_ID":"AN005197","VERSION":"1","CREATED_ON":"April 11, 2024, 8:12 am"},

"PROJECT":{"PROJECT_TITLE":"Releasing the mitochondrial respiration brake MCJ/DnaJC15 enhances CD8 CAR-T cell therapy efficacy","PROJECT_SUMMARY":"Metabolism of chimeric antigen receptor (CAR) T cells is emerging as an important area to improve CAR-T cell therapy in cancer treatment. Mitochondrial respiration is essential for survival and function of CAR-T cells, but developing strategies to specifically enhance mitochondrial respiration has been challenging. Here we identify MCJ/DnaJC15, an endogenous negative regulator of mitochondrial Complex I, as a metabolic target to enhance mitochondrial respiration in CD8 CAR-T cells. Loss of MCJ in CD8 CAR-T cells increases their in vitro and in vivo efficacy against mouse B cell leukemias. MCJ deficiency in TCR- specific CD8 cells also increases their efficacy against solid tumors in vivo. Furthermore, we reveal that human CD8 cells express MCJ and that silencing MCJ expression increases mitochondrial metabolism and anti-tumor activity of human CAR-T cells. Thus, targeting MCJ to enhance mitochondrial metabolism is a promising therapeutic strategy to improve the efficacy of adoptive T cell therapies.","INSTITUTE":"University of Colorado School of Medicine","LABORATORY":"Laboratory of Angelo D''Alessandro in collaboration with Mercedes Rincon","LAST_NAME":"Cendali","FIRST_NAME":"Francesca","ADDRESS":"13199 East Montview Boulevard, Aurora, CO, 80045, USA","EMAIL":"francesca.cendali@cuanschutz.edu","PHONE":"3037246131"},

"STUDY":{"STUDY_TITLE":"Releasing the mitochondrial respiration brake MCJ/DnaJC15 enhances CD8 CAR-T cell therapy efficacy","STUDY_SUMMARY":"Metabolism of chimeric antigen receptor (CAR) T cells is emerging as an important area to improve CAR-T cell therapy in cancer treatment. Mitochondrial respiration is essential for survival and function of CAR-T cells, but developing strategies to specifically enhance mitochondrial respiration has been challenging. Here we identify MCJ/DnaJC15, an endogenous negative regulator of mitochondrial Complex I, as a metabolic target to enhance mitochondrial respiration in CD8 CAR-T cells. Loss of MCJ in CD8 CAR-T cells increases their in vitro and in vivo efficacy against mouse B cell leukemias. MCJ deficiency in TCR- specific CD8 cells also increases their efficacy against solid tumors in vivo. Furthermore, we reveal that human CD8 cells express MCJ and that silencing MCJ expression increases mitochondrial metabolism and anti-tumor activity of human CAR-T cells. Thus, targeting MCJ to enhance mitochondrial metabolism is a promising therapeutic strategy to improve the efficacy of adoptive T cell therapies.","INSTITUTE":"University of Colorado School of Medicine","LABORATORY":"Laboratory of Angelo D''Alessandro in collaboration with Mercedes Rincon","LAST_NAME":"Cendali","FIRST_NAME":"Francesca","ADDRESS":"13199 East Montview Boulevard, Aurora, CO, 80045, USA","EMAIL":"francesca.cendali@cuanschutz.edu","PHONE":"3037246131"},

"SUBJECT":{"SUBJECT_TYPE":"Cultured cells","SUBJECT_SPECIES":"Homo sapiens"},
"SUBJECT_SAMPLE_FACTORS":[
{
"Subject ID":"-",
"Sample ID":"D16 19BBz_2",
"Factors":{"Factor":"low 19BBz","Sample source":"Cells"},
"Additional sample data":{"RAW_FILE_NAME(Raw File)":"2"}
},
{
"Subject ID":"-",
"Sample ID":"D16 19BBz_3",
"Factors":{"Factor":"low 19BBz","Sample source":"Cells"},
"Additional sample data":{"RAW_FILE_NAME(Raw File)":"3"}
},
{
"Subject ID":"-",
"Sample ID":"D16 19BBz_4",
"Factors":{"Factor":"low 19BBz","Sample source":"Cells"},
"Additional sample data":{"RAW_FILE_NAME(Raw File)":"4"}
},
{
"Subject ID":"-",
"Sample ID":"D26 19BBz_2",
"Factors":{"Factor":"high 19BBz","Sample source":"Cells"},
"Additional sample data":{"RAW_FILE_NAME(Raw File)":"11"}
},
{
"Subject ID":"-",
"Sample ID":"D26 19BBz_3",
"Factors":{"Factor":"high 19BBz","Sample source":"Cells"},
"Additional sample data":{"RAW_FILE_NAME(Raw File)":"12"}
},
{
"Subject ID":"-",
"Sample ID":"D26 19BBz_4",
"Factors":{"Factor":"high 19BBz","Sample source":"Cells"},
"Additional sample data":{"RAW_FILE_NAME(Raw File)":"13"}
}
],
"COLLECTION":{"COLLECTION_SUMMARY":"Human CD8 cells were isolated with positive selection as described. The CD8 cells were activated with anti-CD3/anti-CD28 beads (Dynabeads™ Human T-Expander CD3/CD28, Gibco), as previously described107. After 48h activation, the CD8 cells were spun (1000xg for 2h at 32C) with lentiviral supernatant containing CD19-BBz/shMCJ-1 CAR, CD19-BBz/shMCJ-2 CAR or CD19-BBz/shMCJ-2 CAR construct-packing virus with rhIL-2 (40 IU/ml) and protamine sulfate. After transduction, the anti-CD3/anti-CD28 beads were removed and CD8 cells were expanded with rhIL-2 (100 IU/ml) for the specified number of days.","SAMPLE_TYPE":"T-cells"},

"TREATMENT":{"TREATMENT_SUMMARY":"The human CD19-BBz shRNA CAR lentiviral constructs were based on a previously described CD19-BBz CAR containing the human CD19-binding scFV FMC63, CD8 hinge domain, 4-1BB costimulatory domain and CD3 chain105. Using CD19-BBz CAR plasmid as a cloning vector, we generated multiple vectors where we incorporated the RNA polymerase III U6 promotor (on the 3'' of the CD3 chain domain) followed by an shRNA: 1) a CD19-BBz/shMCJ-1 CAR construct containing the shMCJ-1 5’-GAAGATTTCAACTCCTAGC-3’ sequence106, 2) a CD19-BBz/shMCJ-2 CAR construct containing the shMCJ-2; 5’-AACCTCTAGAACAAGTTATC-3’, and 3) a CD19-BBz/c-shRNA CAR vectors expressing the shRNA encoding scramble sequences. Lentiviral supernatant was produced in the LentiX-293T packaging cell line (Clonetech) as previously described. Lentiviral supernatants were collected after 48 hours post-transfection."},

"SAMPLEPREP":{"SAMPLEPREP_SUMMARY":"CAR-T cells were isolated as described above either from in vitro culture or from bone marrow harvested in an in vivo study. The cells were washed in PBS and frozen at -80C until the assay is ready to run. Metabolites from cells were extracted at 2x106 cells/ml at 4°C (30 min) in the presence of 5:3:2 MeOH:MeCN:water (v/v/v). The samples were spun down and the resulting supernatant was transferred to new tubes and dried under a vacuum. The resulting residue was reconstituted in 0.1% formic acid at a 3x concentration, then analyzed on a Thermo Vanquish UHPLC coupled to a Thermo Q Exactive MS as previously described in detail."},

"CHROMATOGRAPHY":{"CHROMATOGRAPHY_SUMMARY":"Positive Ion Mode","CHROMATOGRAPHY_TYPE":"Reversed phase","INSTRUMENT_NAME":"Thermo Vanquish","COLUMN_NAME":"Phenomenex Kinetex C18 (30 x 2.1mm, 1.7um)","SOLVENT_A":"100% water; 0.1% formic acid","SOLVENT_B":"100% acetonitrile; 0.1% formic acid","FLOW_GRADIENT":"0-0.3 min 5% B, 0.3-.8 min hold at 95% B, .8-.81 min 95-5% B, .81-1 min hold at 5% B.","FLOW_RATE":"0.450ml/min","COLUMN_TEMPERATURE":"45"},

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

"MS":{"INSTRUMENT_NAME":"Thermo Q Exactive Orbitrap","INSTRUMENT_TYPE":"Exploris120","MS_TYPE":"ESI","ION_MODE":"POSITIVE","MS_COMMENTS":"Resolution 70,000, scan range 65-900 m/z, maximum injection time 200 ms, microscans 2, automatic gain control (AGC) 3 x 10^6 ions, source voltage 4.0 kV, capillary temperature 320 C, and sheath gas 45, auxiliary gas 15, and sweep gas 0 (all nitrogen). Data converted to mzXML using RawConverter. Metabolites were annotated and integrated using Maven in conjunction with the KEGG database."},

"MS_METABOLITE_DATA":{
"Units":"Peak Areas",

"Data":[{"Metabolite":"L-arginine","D16 19BBz_2":"4836214","D16 19BBz_3":"6785196","D16 19BBz_4":"6755478","D26 19BBz_2":"10302230","D26 19BBz_3":"9424327","D26 19BBz_4":"7626944"},{"Metabolite":"L-asparagine","D16 19BBz_2":"37503.3","D16 19BBz_3":"42690.48","D16 19BBz_4":"67833.41","D26 19BBz_2":"60725.81","D26 19BBz_3":"71021.97","D26 19BBz_4":"65893.31"},{"Metabolite":"L-aspartate","D16 19BBz_2":"28981.37","D16 19BBz_3":"41678.82","D16 19BBz_4":"14709.47","D26 19BBz_2":"16476.69","D26 19BBz_3":"14864.61","D26 19BBz_4":"12181.24"},{"Metabolite":"L-glutamate","D16 19BBz_2":"802946.3","D16 19BBz_3":"845804.8","D16 19BBz_4":"600798.2","D26 19BBz_2":"183256.9","D26 19BBz_3":"206508","D26 19BBz_4":"356782.1"},{"Metabolite":"L-glutamine","D16 19BBz_2":"3439261","D16 19BBz_3":"3939573","D16 19BBz_4":"3915508","D26 19BBz_2":"4815704","D26 19BBz_3":"4532506","D26 19BBz_4":"4128390"},{"Metabolite":"L-histidine","D16 19BBz_2":"369375.3","D16 19BBz_3":"513238.9","D16 19BBz_4":"481658.2","D26 19BBz_2":"682251.3","D26 19BBz_3":"629307.6","D26 19BBz_4":"553394.5"},{"Metabolite":"L-lysine","D16 19BBz_2":"357767.5","D16 19BBz_3":"453960","D16 19BBz_4":"490274.5","D26 19BBz_2":"584052.2","D26 19BBz_3":"651972.6","D26 19BBz_4":"428345.4"},{"Metabolite":"L-methionine","D16 19BBz_2":"3574919","D16 19BBz_3":"4810836","D16 19BBz_4":"7134604","D26 19BBz_2":"14361280","D26 19BBz_3":"19849850","D26 19BBz_4":"8304524"},{"Metabolite":"L-phenylalanine","D16 19BBz_2":"13252870","D16 19BBz_3":"24823610","D16 19BBz_4":"33770950","D26 19BBz_2":"53692260","D26 19BBz_3":"60064010","D26 19BBz_4":"36744040"},{"Metabolite":"L-proline","D16 19BBz_2":"3105265","D16 19BBz_3":"3811522","D16 19BBz_4":"2677829","D26 19BBz_2":"2095116","D26 19BBz_3":"2496928","D26 19BBz_4":"2296737"},{"Metabolite":"L-serine","D16 19BBz_2":"32324.36","D16 19BBz_3":"33420.47","D16 19BBz_4":"25410.65","D26 19BBz_2":"65750.81","D26 19BBz_3":"63232.71","D26 19BBz_4":"29389.21"},{"Metabolite":"L-threonine","D16 19BBz_2":"142195.6","D16 19BBz_3":"153783.9","D16 19BBz_4":"124187.9","D26 19BBz_2":"212152.8","D26 19BBz_3":"209963.6","D26 19BBz_4":"125985.2"},{"Metabolite":"L-tryptophan","D16 19BBz_2":"2942730","D16 19BBz_3":"4261352","D16 19BBz_4":"7024666","D26 19BBz_2":"9710075","D26 19BBz_3":"10706360","D26 19BBz_4":"6115136"},{"Metabolite":"L-valine","D16 19BBz_2":"2231444","D16 19BBz_3":"3414796","D16 19BBz_4":"3889653","D26 19BBz_2":"6098210","D26 19BBz_3":"6347984","D26 19BBz_4":"3617895"},{"Metabolite":"L-cystine","D16 19BBz_2":"64583","D16 19BBz_3":"107327","D16 19BBz_4":"98759.41","D26 19BBz_2":"144405","D26 19BBz_3":"131719.7","D26 19BBz_4":"126396.3"},{"Metabolite":"ADP","D16 19BBz_2":"59791.2","D16 19BBz_3":"94461.95","D16 19BBz_4":"58093.92","D26 19BBz_2":"22428.92","D26 19BBz_3":"30390.95","D26 19BBz_4":"21674.16"},{"Metabolite":"AMP","D16 19BBz_2":"1419016","D16 19BBz_3":"1362332","D16 19BBz_4":"4631006","D26 19BBz_2":"409236.2","D26 19BBz_3":"863352.3","D26 19BBz_4":"3470705"},{"Metabolite":"Adenosine","D16 19BBz_2":"79032.62","D16 19BBz_3":"80378.93","D16 19BBz_4":"107412.7","D26 19BBz_2":"110002.9","D26 19BBz_3":"480938.2","D26 19BBz_4":"120737.6"},{"Metabolite":"GMP","D16 19BBz_2":"58893.68","D16 19BBz_3":"70706.32","D16 19BBz_4":"96280.62","D26 19BBz_2":"16548.04","D26 19BBz_3":"24222.9","D26 19BBz_4":"62658.27"},{"Metabolite":"Guanine","D16 19BBz_2":"313441.5","D16 19BBz_3":"386815.1","D16 19BBz_4":"373353.7","D26 19BBz_2":"516909.1","D26 19BBz_3":"572704.1","D26 19BBz_4":"300565.6"},{"Metabolite":"CDP","D16 19BBz_2":"317518.8","D16 19BBz_3":"398792","D16 19BBz_4":"446556.6","D26 19BBz_2":"571555.1","D26 19BBz_3":"543438.1","D26 19BBz_4":"443421.8"},{"Metabolite":"Cytosine","D16 19BBz_2":"243299.5","D16 19BBz_3":"312363.8","D16 19BBz_4":"375206","D26 19BBz_2":"279655.5","D26 19BBz_3":"278067.8","D26 19BBz_4":"294016.2"},{"Metabolite":"Thymine","D16 19BBz_2":"41042.51","D16 19BBz_3":"78981.81","D16 19BBz_4":"102438.5","D26 19BBz_2":"178650.7","D26 19BBz_3":"196509.5","D26 19BBz_4":"116619.8"},{"Metabolite":"IMP","D16 19BBz_2":"202223.9","D16 19BBz_3":"287439.4","D16 19BBz_4":"207479.2","D26 19BBz_2":"7695.023","D26 19BBz_3":"12793.13","D26 19BBz_4":"13010.5"},{"Metabolite":"Inosine","D16 19BBz_2":"5338734","D16 19BBz_3":"8588710","D16 19BBz_4":"13515070","D26 19BBz_2":"26243070","D26 19BBz_3":"28806180","D26 19BBz_4":"14170390"},{"Metabolite":"Hypoxanthine","D16 19BBz_2":"5187894","D16 19BBz_3":"7013674","D16 19BBz_4":"8552895","D26 19BBz_2":"12458630","D26 19BBz_3":"14052880","D26 19BBz_4":"11026250"},{"Metabolite":"Xanthine","D16 19BBz_2":"128902.8","D16 19BBz_3":"188495.3","D16 19BBz_4":"306592.7","D26 19BBz_2":"574331.6","D26 19BBz_3":"585139.2","D26 19BBz_4":"309872.5"},{"Metabolite":"5-Hydroxyisourate","D16 19BBz_2":"105950.3","D16 19BBz_3":"126693.8","D16 19BBz_4":"138815.2","D26 19BBz_2":"142087.2","D26 19BBz_3":"105340.5","D26 19BBz_4":"127299.7"},{"Metabolite":"Urate","D16 19BBz_2":"180137","D16 19BBz_3":"332912.8","D16 19BBz_4":"401141.8","D26 19BBz_2":"605900.7","D26 19BBz_3":"855114.8","D26 19BBz_4":"542341.6"},{"Metabolite":"3'',5''-Cyclic AMP","D16 19BBz_2":"372240.7","D16 19BBz_3":"374187.1","D16 19BBz_4":"279015.5","D26 19BBz_2":"166721.4","D26 19BBz_3":"189206","D26 19BBz_4":"232901"},{"Metabolite":"Pyridoxal","D16 19BBz_2":"1499482","D16 19BBz_3":"2381946","D16 19BBz_4":"2602829","D26 19BBz_2":"5575752","D26 19BBz_3":"4712484","D26 19BBz_4":"3858727"},{"Metabolite":"4-Pyridoxate","D16 19BBz_2":"92575.34","D16 19BBz_3":"147170.7","D16 19BBz_4":"135681.3","D26 19BBz_2":"274874","D26 19BBz_3":"221752.3","D26 19BBz_4":"183305.3"},{"Metabolite":"Pyridoxamine 5''-phosphate","D16 19BBz_2":"21560.37","D16 19BBz_3":"43064.54","D16 19BBz_4":"55883.83","D26 19BBz_2":"174109.2","D26 19BBz_3":"185150.3","D26 19BBz_4":"91242.63"},{"Metabolite":"Nicotinamide","D16 19BBz_2":"4105021","D16 19BBz_3":"4327748","D16 19BBz_4":"5960306","D26 19BBz_2":"9815957","D26 19BBz_3":"9175447","D26 19BBz_4":"7905774"},{"Metabolite":"Glutathione","D16 19BBz_2":"3386297","D16 19BBz_3":"6186050","D16 19BBz_4":"49255.19","D26 19BBz_2":"306551.4","D26 19BBz_3":"704639.2","D26 19BBz_4":"2637615"},{"Metabolite":"Glutathione disulfide","D16 19BBz_2":"799686.1","D16 19BBz_3":"1212538","D16 19BBz_4":"367034.6","D26 19BBz_2":"15968.2","D26 19BBz_3":"44457.63","D26 19BBz_4":"346490"},{"Metabolite":"5-Oxoproline","D16 19BBz_2":"5487150","D16 19BBz_3":"9509547","D16 19BBz_4":"12104630","D26 19BBz_2":"19642490","D26 19BBz_3":"22481430","D26 19BBz_4":"13354610"},{"Metabolite":"S-Glutathionyl-L-cysteine","D16 19BBz_2":"193332.7","D16 19BBz_3":"73193.23","D16 19BBz_4":"137240.8","D26 19BBz_2":"11178.67","D26 19BBz_3":"9449.616","D26 19BBz_4":"53960.24"},{"Metabolite":"gamma-L-Glutamyl-D-alanine","D16 19BBz_2":"98246.91","D16 19BBz_3":"117512.2","D16 19BBz_4":"129246.5","D26 19BBz_2":"95466.15","D26 19BBz_3":"127197.7","D26 19BBz_4":"98780.81"},{"Metabolite":"Folate","D16 19BBz_2":"64723.56","D16 19BBz_3":"111532.2","D16 19BBz_4":"154574.2","D26 19BBz_2":"316011.2","D26 19BBz_3":"403372.9","D26 19BBz_4":"174976.3"},{"Metabolite":"Ornithine","D16 19BBz_2":"32679.47","D16 19BBz_3":"71855.24","D16 19BBz_4":"89619.16","D26 19BBz_2":"192331.6","D26 19BBz_3":"195803","D26 19BBz_4":"93312.7"},{"Metabolite":"Argininosuccinate","D16 19BBz_2":"12842.21","D16 19BBz_3":"15907.12","D16 19BBz_4":"233074.6","D26 19BBz_2":"60032.23","D26 19BBz_3":"56678.19","D26 19BBz_4":"66238.17"},{"Metabolite":"Cadaverine","D16 19BBz_2":"30384.57","D16 19BBz_3":"57404.28","D16 19BBz_4":"29127.74","D26 19BBz_2":"85229.2","D26 19BBz_3":"80728.38","D26 19BBz_4":"59815.26"},{"Metabolite":"Spermidine","D16 19BBz_2":"133397.6","D16 19BBz_3":"260838.5","D16 19BBz_4":"511260.2","D26 19BBz_2":"92443.25","D26 19BBz_3":"161260.7","D26 19BBz_4":"729062.2"},{"Metabolite":"Spermine","D16 19BBz_2":"34560.02","D16 19BBz_3":"100809.7","D16 19BBz_4":"291594.1","D26 19BBz_2":"193208.4","D26 19BBz_3":"257733.1","D26 19BBz_4":"346499.1"},{"Metabolite":"D-Glucosamine","D16 19BBz_2":"149951.5","D16 19BBz_3":"220186.3","D16 19BBz_4":"222498.9","D26 19BBz_2":"244619.9","D26 19BBz_3":"262140.4","D26 19BBz_4":"217882.6"},{"Metabolite":"Creatine","D16 19BBz_2":"680199.1","D16 19BBz_3":"781028.2","D16 19BBz_4":"993825.8","D26 19BBz_2":"869068.5","D26 19BBz_3":"870444.2","D26 19BBz_4":"907648.2"},{"Metabolite":"Guanidinoacetate","D16 19BBz_2":"36957.72","D16 19BBz_3":"49598.77","D16 19BBz_4":"79591.41","D26 19BBz_2":"121270.3","D26 19BBz_3":"157379.3","D26 19BBz_4":"93209.66"},{"Metabolite":"Pantothenol","D16 19BBz_2":"6085636","D16 19BBz_3":"10852810","D16 19BBz_4":"12377360","D26 19BBz_2":"16262290","D26 19BBz_3":"24435500","D26 19BBz_4":"12412770"},{"Metabolite":"L-Methionine S-oxide","D16 19BBz_2":"65106.59","D16 19BBz_3":"101449.9","D16 19BBz_4":"130656.8","D26 19BBz_2":"341548.4","D26 19BBz_3":"469314.5","D26 19BBz_4":"434722.1"},{"Metabolite":"Indole","D16 19BBz_2":"947706.2","D16 19BBz_3":"1416332","D16 19BBz_4":"2078088","D26 19BBz_2":"3352337","D26 19BBz_3":"3634027","D26 19BBz_4":"1988830"},{"Metabolite":"Indole-3-acetaldehyde","D16 19BBz_2":"123822.1","D16 19BBz_3":"273367.4","D16 19BBz_4":"391438","D26 19BBz_2":"491273.9","D26 19BBz_3":"557152.7","D26 19BBz_4":"461290.9"},{"Metabolite":"Indoxyl","D16 19BBz_2":"20825.97","D16 19BBz_3":"42783.77","D16 19BBz_4":"79627.47","D26 19BBz_2":"106773.8","D26 19BBz_3":"107797.8","D26 19BBz_4":"64166.84"},{"Metabolite":"kynurenine","D16 19BBz_2":"22458.14","D16 19BBz_3":"46536.79","D16 19BBz_4":"50832.14","D26 19BBz_2":"84404.9","D26 19BBz_3":"87888.23","D26 19BBz_4":"63908.09"},{"Metabolite":"N-formyl kynurenine","D16 19BBz_2":"222115.3","D16 19BBz_3":"274022.3","D16 19BBz_4":"211305.7","D26 19BBz_2":"381391.3","D26 19BBz_3":"309354.5","D26 19BBz_4":"314259"},{"Metabolite":"Anthranilate","D16 19BBz_2":"103091.8","D16 19BBz_3":"177953.5","D16 19BBz_4":"124998.4","D26 19BBz_2":"125605.8","D26 19BBz_3":"108039.6","D26 19BBz_4":"102153.1"},{"Metabolite":"L-Adrenaline","D16 19BBz_2":"299009.5","D16 19BBz_3":"515065.9","D16 19BBz_4":"646757.6","D26 19BBz_2":"858608.3","D26 19BBz_3":"1224887","D26 19BBz_4":"651910.8"},{"Metabolite":"Dopamine","D16 19BBz_2":"78815.91","D16 19BBz_3":"136858.3","D16 19BBz_4":"206040","D26 19BBz_2":"474414.2","D26 19BBz_3":"520266.4","D26 19BBz_4":"246524.2"},{"Metabolite":"L-Carnitine","D16 19BBz_2":"285153.3","D16 19BBz_3":"374549.8","D16 19BBz_4":"425253.4","D26 19BBz_2":"357406.2","D26 19BBz_3":"393370.9","D26 19BBz_4":"370966.4"},{"Metabolite":"acyl-C2 (acetyl-carnitine)","D16 19BBz_2":"577962.3","D16 19BBz_3":"983788.2","D16 19BBz_4":"1111839","D26 19BBz_2":"1023382","D26 19BBz_3":"1253770","D26 19BBz_4":"864629.7"},{"Metabolite":"acyl-C3 (propionyl-carnitine)","D16 19BBz_2":"344720.3","D16 19BBz_3":"530737.3","D16 19BBz_4":"684161.8","D26 19BBz_2":"1114068","D26 19BBz_3":"1134817","D26 19BBz_4":"998383.4"},{"Metabolite":"acyl-C4 (butanoyl-l-carnitine)","D16 19BBz_2":"174964","D16 19BBz_3":"347169.6","D16 19BBz_4":"466629.3","D26 19BBz_2":"642511.8","D26 19BBz_3":"691257.1","D26 19BBz_4":"513051.2"},{"Metabolite":"acyl-C4-OH (Hydroxybutyrylcarnitine)","D16 19BBz_2":"29291.88","D16 19BBz_3":"52056.3","D16 19BBz_4":"68738.69","D26 19BBz_2":"37887.25","D26 19BBz_3":"29717.67","D26 19BBz_4":"35012.85"},{"Metabolite":"acyl-C4-DC","D16 19BBz_2":"122402.1","D16 19BBz_3":"262860","D16 19BBz_4":"550056.6","D26 19BBz_2":"542175.7","D26 19BBz_3":"544125.7","D26 19BBz_4":"266261.8"},{"Metabolite":"acyl-C5 (isovalerylcarnitine)","D16 19BBz_2":"126088","D16 19BBz_3":"230650.2","D16 19BBz_4":"196766.1","D26 19BBz_2":"339702.1","D26 19BBz_3":"500660.2","D26 19BBz_4":"382690.2"},{"Metabolite":"acyl-C12:1 (O-dodecenoyl-carnitine)","D16 19BBz_2":"1300313","D16 19BBz_3":"1667830","D16 19BBz_4":"1524680","D26 19BBz_2":"1459152","D26 19BBz_3":"1409776","D26 19BBz_4":"1672712"}],

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}

}