#METABOLOMICS WORKBENCH silviaradenkovic_20230414_150429 DATATRACK_ID:3864 STUDY_ID:ST002562 ANALYSIS_ID:AN004223 VERSION 1 CREATED_ON 04-20-2023 #PROJECT PR:PROJECT_TITLE Metabolomic profiling of PMM2-CDG zebrafish in presence and absence of PR:PROJECT_TITLE epalrestat PR:PROJECT_SUMMARY Abnormal polyol metabolism has been predominantly associated with diabetes, PR:PROJECT_SUMMARY where excess glucose is converted to sorbitol by aldose reductase (AR). PR:PROJECT_SUMMARY Recently, abnormal polyol metabolism has also been implicated in PR:PROJECT_SUMMARY phosphomannomutase 2-congenital disorder of glycosylation (PMM2-CDG), and PR:PROJECT_SUMMARY epalrestat, an AR inhibitor, proposed as a potential therapy for this disorder. PR:PROJECT_SUMMARY Given that the PMM enzyme is not closely connected to polyol metabolism, and, PR:PROJECT_SUMMARY unlike in diabetes, PMM2-CDG does not present with hyperglycemia in blood, the PR:PROJECT_SUMMARY increased polyol production, and the therapeutic mechanism of epalrestat in PR:PROJECT_SUMMARY PMM2-CDG remained largely elusive. PMM2-CDG is caused by deficiency of the PMM PR:PROJECT_SUMMARY enzyme and results in a depletion of mannose-1-P and guanosine diphosphate PR:PROJECT_SUMMARY mannose (GDP-mannose), which is essential for glycosylation. Here, we show that PR:PROJECT_SUMMARY apart from glycosylation abnormalities, PMM2 deficiency also leads to changes in PR:PROJECT_SUMMARY intracellular glucose flux, which results in an increase in intracellular PR:PROJECT_SUMMARY polyols. Targeting AR with epalrestat decreases polyol levels and increases PR:PROJECT_SUMMARY GDP-mannose in vivo in pmm2 mutant zebrafish. PR:INSTITUTE Mayo Clinic PR:LAST_NAME Radenkovic PR:FIRST_NAME Silvia PR:ADDRESS 200 2nd Ave SW Rochester MN, USA PR:EMAIL radenkovic.silvia@mayo.edu PR:PHONE 507(77) 6-6107 PR:FUNDING_SOURCE NIH, KU Leuven PR:PUBLICATIONS Tracer metabolomics reveals the role of aldose reductase in glycosylation PR:DOI http://dx.doi.org/10.21228/M81Q6Q PR:CONTRIBUTORS Silvia Radenkovic, Anna N. Ligezka, Sneha S. Mokashi, Karen Driesen, Lynn PR:CONTRIBUTORS Dukes-Rimsky, Graeme Preston, Luckio F. Owuocha, Leila Sabbagh, Jehan Mousa, PR:CONTRIBUTORS Christina Lam, Andrew Edmondson, Austin Larson, Matthew Schultz, Pieter PR:CONTRIBUTORS Vermeersch, David Cassiman, Peter Witters, Lesa J. Beamer, Tamas Kozicz, Heather PR:CONTRIBUTORS Flanagan-Steet, Bart Ghesquière, Eva Morava #STUDY ST:STUDY_TITLE Metabolomic profiling of PMM2-CDG patient fibroblasts in presence and absence of ST:STUDY_TITLE epalrestat ST:STUDY_SUMMARY Abnormal polyol metabolism has been predominantly associated with diabetes, ST:STUDY_SUMMARY where excess glucose is converted to sorbitol by aldose reductase (AR). ST:STUDY_SUMMARY Recently, abnormal polyol metabolism has also been implicated in ST:STUDY_SUMMARY phosphomannomutase 2-congenital disorder of glycosylation (PMM2-CDG), and ST:STUDY_SUMMARY epalrestat, an AR inhibitor, proposed as a potential therapy for this disorder. ST:STUDY_SUMMARY Given that the PMM enzyme is not closely connected to polyol metabolism, and, ST:STUDY_SUMMARY unlike in diabetes, PMM2-CDG does not present with hyperglycemia in blood, the ST:STUDY_SUMMARY increased polyol production, and the therapeutic mechanism of epalrestat in ST:STUDY_SUMMARY PMM2-CDG remained largely elusive. PMM2-CDG is caused by deficiency of the PMM ST:STUDY_SUMMARY enzyme and results in a depletion of mannose-1-P and guanosine diphosphate ST:STUDY_SUMMARY mannose (GDP-mannose), which is essential for glycosylation. Here, we show that ST:STUDY_SUMMARY apart from glycosylation abnormalities, PMM2 deficiency also leads to changes in ST:STUDY_SUMMARY intracellular glucose flux, which results in an increase in intracellular ST:STUDY_SUMMARY polyols. Targeting AR with epalrestat decreases polyol levels and increases ST:STUDY_SUMMARY GDP-mannose both in vitro in patient-derived fibroblasts. ST:INSTITUTE Mayo Clinic ST:LAST_NAME Radenkovic ST:FIRST_NAME Silvia ST:ADDRESS 200 2nd Ave SW Rochester MN, USA ST:EMAIL radenkovic.silvia@mayo.edu ST:PHONE 507(77) 6-6107 ST:SUBMIT_DATE 2023-04-14 #SUBJECT SU:SUBJECT_TYPE Cultured cells SU:SUBJECT_SPECIES Homo sapiens SU:TAXONOMY_ID 9606 SU:GENOTYPE_STRAIN WT/PMM2-CDG SU:AGE_OR_AGE_RANGE 5-45 SU:GENDER Male and female #SUBJECT_SAMPLE_FACTORS: SUBJECT(optional)[tab]SAMPLE[tab]FACTORS(NAME:VALUE pairs separated by |)[tab]Additional sample data SUBJECT_SAMPLE_FACTORS P1 SR01 Genotype:PMM2-CDG | Treatment:10microM epalrestat Cell type=Skin fibroblasts; RAW_FILE_NAME=SR01 SUBJECT_SAMPLE_FACTORS P1 SR02 Genotype:PMM2-CDG | Treatment:10microM epalrestat Cell type=Skin fibroblasts; RAW_FILE_NAME=SR02 SUBJECT_SAMPLE_FACTORS P1 SR03 Genotype:PMM2-CDG | Treatment:10microM epalrestat Cell type=Skin fibroblasts; RAW_FILE_NAME=SR03 SUBJECT_SAMPLE_FACTORS P1 SR04 Genotype:PMM2-CDG | Treatment:10microM epalrestat Cell type=Skin fibroblasts; RAW_FILE_NAME=SR04 SUBJECT_SAMPLE_FACTORS P2 SR17 Genotype:PMM2-CDG | Treatment:10microM epalrestat Cell type=Skin fibroblasts; RAW_FILE_NAME=SR17 SUBJECT_SAMPLE_FACTORS P2 SR18 Genotype:PMM2-CDG | Treatment:10microM epalrestat Cell type=Skin fibroblasts; RAW_FILE_NAME=SR18 SUBJECT_SAMPLE_FACTORS P2 SR19 Genotype:PMM2-CDG | Treatment:10microM epalrestat Cell type=Skin fibroblasts; RAW_FILE_NAME=SR19 SUBJECT_SAMPLE_FACTORS P2 SR20 Genotype:PMM2-CDG | Treatment:10microM epalrestat Cell type=Skin fibroblasts; RAW_FILE_NAME=SR20 SUBJECT_SAMPLE_FACTORS P3 SR33 Genotype:PMM2-CDG | Treatment:10microM epalrestat Cell type=Skin fibroblasts; RAW_FILE_NAME=SR33 SUBJECT_SAMPLE_FACTORS P3 SR34 Genotype:PMM2-CDG | Treatment:10microM epalrestat Cell type=Skin fibroblasts; RAW_FILE_NAME=SR34 SUBJECT_SAMPLE_FACTORS P3 SR35 Genotype:PMM2-CDG | Treatment:10microM epalrestat Cell type=Skin fibroblasts; RAW_FILE_NAME=SR35 SUBJECT_SAMPLE_FACTORS P3 SR36 Genotype:PMM2-CDG | Treatment:10microM epalrestat Cell type=Skin fibroblasts; RAW_FILE_NAME=SR36 SUBJECT_SAMPLE_FACTORS P4 SR49 Genotype:PMM2-CDG | Treatment:10microM epalrestat Cell type=Skin fibroblasts; RAW_FILE_NAME=SR49 SUBJECT_SAMPLE_FACTORS P4 SR50 Genotype:PMM2-CDG | Treatment:10microM epalrestat Cell type=Skin fibroblasts; RAW_FILE_NAME=SR50 SUBJECT_SAMPLE_FACTORS P4 SR51 Genotype:PMM2-CDG | Treatment:10microM epalrestat Cell type=Skin fibroblasts; RAW_FILE_NAME=SR51 SUBJECT_SAMPLE_FACTORS P4 SR52 Genotype:PMM2-CDG | Treatment:10microM epalrestat Cell type=Skin fibroblasts; RAW_FILE_NAME=SR52 SUBJECT_SAMPLE_FACTORS P5 SR65 Genotype:PMM2-CDG | Treatment:10microM epalrestat Cell type=Skin fibroblasts; RAW_FILE_NAME=SR65 SUBJECT_SAMPLE_FACTORS P5 SR66 Genotype:PMM2-CDG | Treatment:10microM epalrestat Cell type=Skin fibroblasts; RAW_FILE_NAME=SR66 SUBJECT_SAMPLE_FACTORS P5 SR67 Genotype:PMM2-CDG | Treatment:10microM epalrestat Cell type=Skin fibroblasts; RAW_FILE_NAME=SR67 SUBJECT_SAMPLE_FACTORS P5 SR68 Genotype:PMM2-CDG | Treatment:10microM epalrestat Cell type=Skin fibroblasts; RAW_FILE_NAME=SR68 SUBJECT_SAMPLE_FACTORS P6 SR81 Genotype:PMM2-CDG | Treatment:10microM epalrestat Cell type=Skin fibroblasts; RAW_FILE_NAME=SR81 SUBJECT_SAMPLE_FACTORS P6 SR82 Genotype:PMM2-CDG | Treatment:10microM epalrestat Cell type=Skin fibroblasts; RAW_FILE_NAME=SR82 SUBJECT_SAMPLE_FACTORS P6 SR83 Genotype:PMM2-CDG | Treatment:10microM epalrestat Cell type=Skin fibroblasts; RAW_FILE_NAME=SR83 SUBJECT_SAMPLE_FACTORS P6 SR84 Genotype:PMM2-CDG | Treatment:10microM epalrestat Cell type=Skin fibroblasts; RAW_FILE_NAME=SR84 SUBJECT_SAMPLE_FACTORS P1 SR05 Genotype:PMM2-CDG | Treatment:Vehicle Cell type=Skin fibroblasts; RAW_FILE_NAME=SR05 SUBJECT_SAMPLE_FACTORS P1 SR06 Genotype:PMM2-CDG | Treatment:Vehicle Cell type=Skin fibroblasts; RAW_FILE_NAME=SR06 SUBJECT_SAMPLE_FACTORS P1 SR07 Genotype:PMM2-CDG | Treatment:Vehicle Cell type=Skin fibroblasts; RAW_FILE_NAME=SR07 SUBJECT_SAMPLE_FACTORS P1 SR08 Genotype:PMM2-CDG | Treatment:Vehicle Cell type=Skin fibroblasts; RAW_FILE_NAME=SR08 SUBJECT_SAMPLE_FACTORS P2 SR21 Genotype:PMM2-CDG | Treatment:Vehicle Cell type=Skin fibroblasts; RAW_FILE_NAME=SR21 SUBJECT_SAMPLE_FACTORS P2 SR22 Genotype:PMM2-CDG | Treatment:Vehicle Cell type=Skin fibroblasts; RAW_FILE_NAME=SR22 SUBJECT_SAMPLE_FACTORS P2 SR23 Genotype:PMM2-CDG | Treatment:Vehicle Cell type=Skin fibroblasts; RAW_FILE_NAME=SR23 SUBJECT_SAMPLE_FACTORS P2 SR24 Genotype:PMM2-CDG | Treatment:Vehicle Cell type=Skin fibroblasts; RAW_FILE_NAME=SR24 SUBJECT_SAMPLE_FACTORS P3 SR37 Genotype:PMM2-CDG | Treatment:Vehicle Cell type=Skin fibroblasts; RAW_FILE_NAME=SR37 SUBJECT_SAMPLE_FACTORS P3 SR38 Genotype:PMM2-CDG | Treatment:Vehicle Cell type=Skin fibroblasts; RAW_FILE_NAME=SR38 SUBJECT_SAMPLE_FACTORS P3 SR39 Genotype:PMM2-CDG | Treatment:Vehicle Cell type=Skin fibroblasts; RAW_FILE_NAME=SR39 SUBJECT_SAMPLE_FACTORS P3 SR40 Genotype:PMM2-CDG | Treatment:Vehicle Cell type=Skin fibroblasts; RAW_FILE_NAME=SR40 SUBJECT_SAMPLE_FACTORS P4 SR53 Genotype:PMM2-CDG | Treatment:Vehicle Cell type=Skin fibroblasts; RAW_FILE_NAME=SR53 SUBJECT_SAMPLE_FACTORS P4 SR54 Genotype:PMM2-CDG | Treatment:Vehicle Cell type=Skin fibroblasts; RAW_FILE_NAME=SR54 SUBJECT_SAMPLE_FACTORS P4 SR55 Genotype:PMM2-CDG | Treatment:Vehicle Cell type=Skin fibroblasts; RAW_FILE_NAME=SR55 SUBJECT_SAMPLE_FACTORS P4 SR56 Genotype:PMM2-CDG | Treatment:Vehicle Cell type=Skin fibroblasts; RAW_FILE_NAME=SR56 SUBJECT_SAMPLE_FACTORS P5 SR69 Genotype:PMM2-CDG | Treatment:Vehicle Cell type=Skin fibroblasts; RAW_FILE_NAME=SR69 SUBJECT_SAMPLE_FACTORS P5 SR70 Genotype:PMM2-CDG | Treatment:Vehicle Cell type=Skin fibroblasts; RAW_FILE_NAME=SR70 SUBJECT_SAMPLE_FACTORS P5 SR71 Genotype:PMM2-CDG | Treatment:Vehicle Cell type=Skin fibroblasts; RAW_FILE_NAME=SR71 SUBJECT_SAMPLE_FACTORS P5 SR72 Genotype:PMM2-CDG | Treatment:Vehicle Cell type=Skin fibroblasts; RAW_FILE_NAME=SR72 SUBJECT_SAMPLE_FACTORS P6 SR85 Genotype:PMM2-CDG | Treatment:Vehicle Cell type=Skin fibroblasts; RAW_FILE_NAME=SR85 SUBJECT_SAMPLE_FACTORS P6 SR86 Genotype:PMM2-CDG | Treatment:Vehicle Cell type=Skin fibroblasts; RAW_FILE_NAME=SR86 SUBJECT_SAMPLE_FACTORS P6 SR87 Genotype:PMM2-CDG | Treatment:Vehicle Cell type=Skin fibroblasts; RAW_FILE_NAME=SR87 SUBJECT_SAMPLE_FACTORS P6 SR88 Genotype:PMM2-CDG | Treatment:Vehicle Cell type=Skin fibroblasts; RAW_FILE_NAME=SR88 SUBJECT_SAMPLE_FACTORS C1 SR09 Genotype:WT | Treatment:10microM epalrestat Cell type=Skin fibroblasts; RAW_FILE_NAME=SR09 SUBJECT_SAMPLE_FACTORS C1 SR10 Genotype:WT | Treatment:10microM epalrestat Cell type=Skin fibroblasts; RAW_FILE_NAME=SR10 SUBJECT_SAMPLE_FACTORS C1 SR11 Genotype:WT | Treatment:10microM epalrestat Cell type=Skin fibroblasts; RAW_FILE_NAME=SR11 SUBJECT_SAMPLE_FACTORS C1 SR12 Genotype:WT | Treatment:10microM epalrestat Cell type=Skin fibroblasts; RAW_FILE_NAME=SR12 SUBJECT_SAMPLE_FACTORS C2 SR25 Genotype:WT | Treatment:10microM epalrestat Cell type=Skin fibroblasts; RAW_FILE_NAME=SR25 SUBJECT_SAMPLE_FACTORS C2 SR26 Genotype:WT | Treatment:10microM epalrestat Cell type=Skin fibroblasts; RAW_FILE_NAME=SR26 SUBJECT_SAMPLE_FACTORS C2 SR27 Genotype:WT | Treatment:10microM epalrestat Cell type=Skin fibroblasts; RAW_FILE_NAME=SR27 SUBJECT_SAMPLE_FACTORS C2 SR28 Genotype:WT | Treatment:10microM epalrestat Cell type=Skin fibroblasts; RAW_FILE_NAME=SR28 SUBJECT_SAMPLE_FACTORS C3 SR41 Genotype:WT | Treatment:10microM epalrestat Cell type=Skin fibroblasts; RAW_FILE_NAME=SR41 SUBJECT_SAMPLE_FACTORS C3 SR42 Genotype:WT | Treatment:10microM epalrestat Cell type=Skin fibroblasts; RAW_FILE_NAME=SR42 SUBJECT_SAMPLE_FACTORS C3 SR43 Genotype:WT | Treatment:10microM epalrestat Cell type=Skin fibroblasts; RAW_FILE_NAME=SR43 SUBJECT_SAMPLE_FACTORS C3 SR44 Genotype:WT | Treatment:10microM epalrestat Cell type=Skin fibroblasts; RAW_FILE_NAME=SR44 SUBJECT_SAMPLE_FACTORS C4 SR57 Genotype:WT | Treatment:10microM epalrestat Cell type=Skin fibroblasts; RAW_FILE_NAME=SR57 SUBJECT_SAMPLE_FACTORS C4 SR58 Genotype:WT | Treatment:10microM epalrestat Cell type=Skin fibroblasts; RAW_FILE_NAME=SR58 SUBJECT_SAMPLE_FACTORS C4 SR59 Genotype:WT | Treatment:10microM epalrestat Cell type=Skin fibroblasts; RAW_FILE_NAME=SR59 SUBJECT_SAMPLE_FACTORS C4 SR60 Genotype:WT | Treatment:10microM epalrestat Cell type=Skin fibroblasts; RAW_FILE_NAME=SR60 SUBJECT_SAMPLE_FACTORS C5 SR73 Genotype:WT | Treatment:10microM epalrestat Cell type=Skin fibroblasts; RAW_FILE_NAME=SR73 SUBJECT_SAMPLE_FACTORS C5 SR74 Genotype:WT | Treatment:10microM epalrestat Cell type=Skin fibroblasts; RAW_FILE_NAME=SR74 SUBJECT_SAMPLE_FACTORS C5 SR75 Genotype:WT | Treatment:10microM epalrestat Cell type=Skin fibroblasts; RAW_FILE_NAME=SR75 SUBJECT_SAMPLE_FACTORS C5 SR76 Genotype:WT | Treatment:10microM epalrestat Cell type=Skin fibroblasts; RAW_FILE_NAME=SR76 SUBJECT_SAMPLE_FACTORS C1 SR13 Genotype:WT | Treatment:Vehicle Cell type=Skin fibroblasts; RAW_FILE_NAME=SR13 SUBJECT_SAMPLE_FACTORS C1 SR14 Genotype:WT | Treatment:Vehicle Cell type=Skin fibroblasts; RAW_FILE_NAME=SR14 SUBJECT_SAMPLE_FACTORS C1 SR15 Genotype:WT | Treatment:Vehicle Cell type=Skin fibroblasts; RAW_FILE_NAME=SR15 SUBJECT_SAMPLE_FACTORS C1 SR16 Genotype:WT | Treatment:Vehicle Cell type=Skin fibroblasts; RAW_FILE_NAME=SR16 SUBJECT_SAMPLE_FACTORS C2 SR29 Genotype:WT | Treatment:Vehicle Cell type=Skin fibroblasts; RAW_FILE_NAME=SR29 SUBJECT_SAMPLE_FACTORS C2 SR30 Genotype:WT | Treatment:Vehicle Cell type=Skin fibroblasts; RAW_FILE_NAME=SR30 SUBJECT_SAMPLE_FACTORS C2 SR31 Genotype:WT | Treatment:Vehicle Cell type=Skin fibroblasts; RAW_FILE_NAME=SR31 SUBJECT_SAMPLE_FACTORS C2 SR32 Genotype:WT | Treatment:Vehicle Cell type=Skin fibroblasts; RAW_FILE_NAME=SR32 SUBJECT_SAMPLE_FACTORS C3 SR45 Genotype:WT | Treatment:Vehicle Cell type=Skin fibroblasts; RAW_FILE_NAME=SR45 SUBJECT_SAMPLE_FACTORS C3 SR46 Genotype:WT | Treatment:Vehicle Cell type=Skin fibroblasts; RAW_FILE_NAME=SR46 SUBJECT_SAMPLE_FACTORS C3 SR47 Genotype:WT | Treatment:Vehicle Cell type=Skin fibroblasts; RAW_FILE_NAME=SR47 SUBJECT_SAMPLE_FACTORS C3 SR48 Genotype:WT | Treatment:Vehicle Cell type=Skin fibroblasts; RAW_FILE_NAME=SR48 SUBJECT_SAMPLE_FACTORS C4 SR61 Genotype:WT | Treatment:Vehicle Cell type=Skin fibroblasts; RAW_FILE_NAME=SR61 SUBJECT_SAMPLE_FACTORS C4 SR62 Genotype:WT | Treatment:Vehicle Cell type=Skin fibroblasts; RAW_FILE_NAME=SR62 SUBJECT_SAMPLE_FACTORS C4 SR63 Genotype:WT | Treatment:Vehicle Cell type=Skin fibroblasts; RAW_FILE_NAME=SR63 SUBJECT_SAMPLE_FACTORS C4 SR64 Genotype:WT | Treatment:Vehicle Cell type=Skin fibroblasts; RAW_FILE_NAME=SR64 SUBJECT_SAMPLE_FACTORS C5 SR77 Genotype:WT | Treatment:Vehicle Cell type=Skin fibroblasts; RAW_FILE_NAME=SR77 SUBJECT_SAMPLE_FACTORS C5 SR78 Genotype:WT | Treatment:Vehicle Cell type=Skin fibroblasts; RAW_FILE_NAME=SR78 SUBJECT_SAMPLE_FACTORS C5 SR79 Genotype:WT | Treatment:Vehicle Cell type=Skin fibroblasts; RAW_FILE_NAME=SR79 SUBJECT_SAMPLE_FACTORS C5 SR80 Genotype:WT | Treatment:Vehicle Cell type=Skin fibroblasts; RAW_FILE_NAME=SR80 #COLLECTION CO:COLLECTION_SUMMARY Cells were washed with PBS, cells were incubated with extraction buffer for 2min CO:COLLECTION_SUMMARY before scraping and transferring to a fresh eppendorf. Samples were precipitated CO:COLLECTION_SUMMARY overnight at -80, then they were centrifuged at max rpm, 20min, 4 degrees C and CO:COLLECTION_SUMMARY supernatant transferred to an M/S vial. CO:SAMPLE_TYPE Fibroblasts CO:STORAGE_CONDITIONS -80℃ #TREATMENT TR:TREATMENT_SUMMARY Cells were treated with vehicle or 10 microM epalrestat #SAMPLEPREP SP:SAMPLEPREP_SUMMARY Metabolites were extracted with 80% Methanol and IS (d27 myristic acid) SP:PROCESSING_STORAGE_CONDITIONS -80℃ SP:EXTRACT_STORAGE -80℃ #CHROMATOGRAPHY CH:CHROMATOGRAPHY_SUMMARY C18 iP REVERSE PHASE CH:INSTRUMENT_NAME Waters Acquity CH:COLUMN_NAME C-18: Acquity UPLC -HSS T3 1. 8 μm; 2.1 x 150 mm, Waters CH:COLUMN_TEMPERATURE 40 CH:FLOW_GRADIENT The gradient started with 5% of solvent B and 95% solvent A and remained at 5% B CH:FLOW_GRADIENT until 2 min post injection. A linear gradient to 37% B was carried out until 7 CH:FLOW_GRADIENT min and increased to 41% until 14 min. Between 14 and 26 minutes the gradient CH:FLOW_GRADIENT increased to 95% of B and remained at 95% B for 4 minutes. At 30 min the CH:FLOW_GRADIENT gradient returned to 5% B. The chromatography was stopped at 40 min CH:FLOW_RATE 0.25 ml/min CH:SOLVENT_A 100% water; 10mM tributylamine; 15mM acetic acid CH:SOLVENT_B 100% methanol CH:CHROMATOGRAPHY_TYPE Reversed phase #ANALYSIS AN:ANALYSIS_TYPE MS #MS MS:INSTRUMENT_NAME Thermo Q Exactive Orbitrap MS:INSTRUMENT_TYPE Orbitrap MS:MS_TYPE ESI MS:MS_COMMENTS El-Maven polly, ThermoFisher Xcalibur, Metabolites were annotated based on the MS:MS_COMMENTS in-house metabolite library- elution time and m/z values MS:ION_MODE NEGATIVE #MS_METABOLITE_DATA MS_METABOLITE_DATA:UNITS AUC MS_METABOLITE_DATA_START Samples SR01 SR02 SR03 SR04 SR17 SR18 SR19 SR20 SR33 SR34 SR35 SR36 SR49 SR50 SR51 SR52 SR65 SR66 SR67 SR68 SR81 SR82 SR83 SR84 SR05 SR06 SR07 SR08 SR21 SR22 SR23 SR24 SR37 SR38 SR39 SR40 SR53 SR54 SR55 SR56 SR69 SR70 SR71 SR72 SR85 SR86 SR87 SR88 SR09 SR10 SR11 SR12 SR25 SR26 SR27 SR28 SR41 SR42 SR43 SR44 SR57 SR58 SR59 SR60 SR73 SR74 SR75 SR76 SR13 SR14 SR15 SR16 SR29 SR30 SR31 SR32 SR45 SR46 SR47 SR48 SR61 SR62 SR63 SR64 SR77 SR78 SR79 SR80 Factors Genotype:PMM2-CDG | Treatment:10microM epalrestat Genotype:PMM2-CDG | Treatment:10microM epalrestat Genotype:PMM2-CDG | Treatment:10microM epalrestat Genotype:PMM2-CDG | Treatment:10microM epalrestat Genotype:PMM2-CDG | Treatment:10microM epalrestat Genotype:PMM2-CDG | Treatment:10microM epalrestat Genotype:PMM2-CDG | Treatment:10microM epalrestat Genotype:PMM2-CDG | Treatment:10microM epalrestat Genotype:PMM2-CDG | Treatment:10microM epalrestat Genotype:PMM2-CDG | Treatment:10microM epalrestat Genotype:PMM2-CDG | Treatment:10microM epalrestat Genotype:PMM2-CDG | Treatment:10microM epalrestat Genotype:PMM2-CDG | Treatment:10microM epalrestat Genotype:PMM2-CDG | Treatment:10microM epalrestat Genotype:PMM2-CDG | Treatment:10microM epalrestat Genotype:PMM2-CDG | Treatment:10microM epalrestat Genotype:PMM2-CDG | Treatment:10microM epalrestat Genotype:PMM2-CDG | Treatment:10microM epalrestat Genotype:PMM2-CDG | Treatment:10microM epalrestat Genotype:PMM2-CDG | Treatment:10microM epalrestat Genotype:PMM2-CDG | Treatment:10microM epalrestat Genotype:PMM2-CDG | Treatment:10microM epalrestat Genotype:PMM2-CDG | Treatment:10microM epalrestat Genotype:PMM2-CDG | Treatment:10microM epalrestat Genotype:PMM2-CDG | Treatment:Vehicle Genotype:PMM2-CDG | Treatment:Vehicle Genotype:PMM2-CDG | Treatment:Vehicle Genotype:PMM2-CDG | Treatment:Vehicle Genotype:PMM2-CDG | Treatment:Vehicle Genotype:PMM2-CDG | Treatment:Vehicle Genotype:PMM2-CDG | Treatment:Vehicle Genotype:PMM2-CDG | Treatment:Vehicle Genotype:PMM2-CDG | Treatment:Vehicle Genotype:PMM2-CDG | Treatment:Vehicle Genotype:PMM2-CDG | Treatment:Vehicle Genotype:PMM2-CDG | Treatment:Vehicle Genotype:PMM2-CDG | Treatment:Vehicle Genotype:PMM2-CDG | Treatment:Vehicle Genotype:PMM2-CDG | Treatment:Vehicle Genotype:PMM2-CDG | Treatment:Vehicle Genotype:PMM2-CDG | Treatment:Vehicle Genotype:PMM2-CDG | Treatment:Vehicle Genotype:PMM2-CDG | Treatment:Vehicle Genotype:PMM2-CDG | Treatment:Vehicle Genotype:PMM2-CDG | Treatment:Vehicle Genotype:PMM2-CDG | Treatment:Vehicle Genotype:PMM2-CDG | Treatment:Vehicle Genotype:PMM2-CDG | Treatment:Vehicle Genotype:WT | Treatment:10microM epalrestat Genotype:WT | Treatment:10microM epalrestat Genotype:WT | Treatment:10microM epalrestat Genotype:WT | Treatment:10microM epalrestat Genotype:WT | Treatment:10microM epalrestat Genotype:WT | Treatment:10microM epalrestat Genotype:WT | Treatment:10microM epalrestat Genotype:WT | Treatment:10microM epalrestat Genotype:WT | Treatment:10microM epalrestat Genotype:WT | Treatment:10microM epalrestat Genotype:WT | Treatment:10microM epalrestat Genotype:WT | Treatment:10microM epalrestat Genotype:WT | Treatment:10microM epalrestat Genotype:WT | Treatment:10microM epalrestat Genotype:WT | Treatment:10microM epalrestat Genotype:WT | Treatment:10microM epalrestat Genotype:WT | Treatment:10microM epalrestat Genotype:WT | Treatment:10microM epalrestat Genotype:WT | Treatment:10microM epalrestat Genotype:WT | Treatment:10microM epalrestat Genotype:WT | Treatment:Vehicle Genotype:WT | Treatment:Vehicle Genotype:WT | Treatment:Vehicle Genotype:WT | Treatment:Vehicle Genotype:WT | Treatment:Vehicle Genotype:WT | Treatment:Vehicle Genotype:WT | Treatment:Vehicle Genotype:WT | Treatment:Vehicle Genotype:WT | Treatment:Vehicle Genotype:WT | Treatment:Vehicle Genotype:WT | Treatment:Vehicle Genotype:WT | Treatment:Vehicle Genotype:WT | Treatment:Vehicle Genotype:WT | Treatment:Vehicle Genotype:WT | Treatment:Vehicle Genotype:WT | Treatment:Vehicle Genotype:WT | Treatment:Vehicle Genotype:WT | Treatment:Vehicle Genotype:WT | Treatment:Vehicle Genotype:WT | Treatment:Vehicle GDP-mannose 4670000.0000 4030000.0000 5030000.0000 5380000.0000 4260000.0000 4290000.0000 5510000.0000 4650000.0000 17500.0000 2610000.0000 2380000.0000 2950000.0000 1910000.0000 3860000.0000 3780000.0000 17600.0000 5480000.0000 4660000.0000 4970000.0000 4450000.0000 6360000.0000 5000000.0000 2360000.0000 2270000.0000 2760000.0000 2330000.0000 4340000.0000 4360000.0000 8920000.0000 8850000.0000 8920000.0000 7850000.0000 5280000.0000 4590000.0000 7640000.0000 4740000.0000 4400000.0000 4940000.0000 10600000.0000 10400000.0000 9360000.0000 8670000.0000 4770000.0000 4550000.0000 22400.0000 7600000.0000 4440000.0000 Sorbitol 6060000.0000 5510000.0000 5810000.0000 4970000.0000 9040000.0000 7790000.0000 9470000.0000 8210000.0000 11200000.0000 11100000.0000 9840000.0000 9780000.0000 9940000.0000 9860000.0000 10100000.0000 9820000.0000 12100000.0000 10600000.0000 10400000.0000 10500000.0000 9340000.0000 8990000.0000 8710000.0000 8200000.0000 9440000.0000 5980000.0000 4980000.0000 6030000.0000 13000000.0000 11800000.0000 14800000.0000 11200000.0000 15100000.0000 12400000.0000 13100000.0000 11500000.0000 13000000.0000 12200000.0000 13600000.0000 13600000.0000 11400000.0000 9660000.0000 11400000.0000 15400000.0000 10400000.0000 10800000.0000 11900000.0000 11000000.0000 4930000.0000 5160000.0000 6270000.0000 4630000.0000 6000000.0000 6650000.0000 6930000.0000 5810000.0000 6390000.0000 5810000.0000 6980000.0000 6850000.0000 4300000.0000 5290000.0000 4320000.0000 4400000.0000 9050000.0000 7860000.0000 9420000.0000 11600000.0000 5420000.0000 5550000.0000 6590000.0000 5680000.0000 7900000.0000 8420000.0000 9380000.0000 9480000.0000 7410000.0000 6600000.0000 8330000.0000 8680000.0000 4060000.0000 4310000.0000 5010000.0000 5360000.0000 11000000.0000 10800000.0000 13200000.0000 16800000.0000 MS_METABOLITE_DATA_END #METABOLITES METABOLITES_START metabolite_name pubchem_id inchi_key kegg_id other_id other_id_type ri ri_type moverz_quant GDP-mannose 604.06897 Sorbitol 181.07164 METABOLITES_END #END