#METABOLOMICS WORKBENCH skambhampati_20210601_103541 DATATRACK_ID:2664 STUDY_ID:ST001811 ANALYSIS_ID:AN002935 PROJECT_ID:PR001145 VERSION 1 CREATED_ON June 1, 2021, 3:12 pm #PROJECT PR:PROJECT_TITLE Evidence that class I glutamine amidotransferase, GAT1_2.1, acts as a PR:PROJECT_TITLE glutaminase in roots of Arabidopsis thaliana PR:PROJECT_SUMMARY Carbon and Nitrogen balance in plant leaves, required for sustained growth, is PR:PROJECT_SUMMARY achieved by inter-relationships between the processes of photosynthesis, PR:PROJECT_SUMMARY respiration and amino acid metabolism in a photoperiod dependent manner. The PR:PROJECT_SUMMARY GS/GOGAT cycle is one such mechanism and is highly elucidated in plants to serve PR:PROJECT_SUMMARY as a crossroad between C and N metabolism. Non-photosynthetic tissues (e.g., PR:PROJECT_SUMMARY roots, germinating seeds), however, lack a sufficient supply of carbon skeletons PR:PROJECT_SUMMARY under high N conditions and hence may resort to other mechanisms, along with PR:PROJECT_SUMMARY GS/GOGAT cycle, to achieve the aforementioned C/N balance. Here, we propose a PR:PROJECT_SUMMARY potential role of an enzyme, GAT1_2.1, in hydrolyzing excess glutamine to Glu, PR:PROJECT_SUMMARY which channels carbon skeletons to the TCA cycle, under high N conditions, using PR:PROJECT_SUMMARY Arabidopsis as a model. GAT1_2.1, a class I glutamine amidotrasferase of unknown PR:PROJECT_SUMMARY substrate specificity, was shown to be highly responsive to N status, localized PR:PROJECT_SUMMARY in mitochondria and is highly co-expressed with Glutamate Dehydrogenase 2 PR:PROJECT_SUMMARY (GDH2). Arabidopsis mutants lacking GAT1_2.1 have elevated GABA shunt pathway PR:PROJECT_SUMMARY activity to replenish the depleted levels of Glu. This Glu may then be PR:PROJECT_SUMMARY deaminated to 2-oxoglutarate by GDH2 and channeled into the TCA cycle thus PR:PROJECT_SUMMARY providing a crossroad between C and N metabolism in root mitochondria. We use a PR:PROJECT_SUMMARY metabolomics approach to demonstrate the difference in quantities of pathway PR:PROJECT_SUMMARY intermediates between wild type Arabidopsis roots and gat1_2.1 mutants using PR:PROJECT_SUMMARY glutamine as organic nitrogen treatment and KNO3 and Glu treatments as negative PR:PROJECT_SUMMARY and positive controls, respectively. In addition, we used Arabidopsis root PR:PROJECT_SUMMARY extracts, spiked with amide nitrogen labeled (15N1) Glutamine and a purified PR:PROJECT_SUMMARY recombinant protein, both full length and glutaminase domain only versions, to PR:PROJECT_SUMMARY determine the amido group acceptor, if any, in the glutamine amidotransferase PR:PROJECT_SUMMARY reaction. PR:INSTITUTE Agriculture and Agri-Food Canada PR:DEPARTMENT London Research and Development Centre PR:LABORATORY Frederic Marsolais PR:LAST_NAME Kambhampati PR:FIRST_NAME Shrikaar PR:ADDRESS 1391 Sandford St, London, ON N5V 4T3, Canada PR:EMAIL shrikaar.k@gmail.com PR:PHONE 3144025550 PR:FUNDING_SOURCE Natural Sciences and Engineering Research Council of Canada PR:CONTRIBUTORS Shrikaar Kambhampati, Justin Renaud, Frederic Marsolais #STUDY ST:STUDY_TITLE Evidence that class I glutamine amidotransferase, GAT1_2.1, acts as a ST:STUDY_TITLE glutaminase in roots of Arabidopsis thaliana ST:STUDY_TYPE Targeted Metabolite Quantification ST:STUDY_SUMMARY In this study, we use a targeted metabolite quantification approach to ST:STUDY_SUMMARY demonstrate the difference in quantities of pathway intermediates between wild ST:STUDY_SUMMARY type Arabidopsis roots and gat1_2.1 mutants using glutamine as organic nitrogen ST:STUDY_SUMMARY treatment and KNO3 and Glu treatments as negative and positive controls, ST:STUDY_SUMMARY respectively. ST:INSTITUTE Agriculture and Agri-Food Canada ST:DEPARTMENT London Research and Development Centre ST:LABORATORY Frederic Marsolais ST:LAST_NAME Kambhampati ST:FIRST_NAME Shrikaar ST:ADDRESS 1391 Sandford St, London, ON N5V 4T3, Canada ST:EMAIL shrikaar.k@gmail.com ST:PHONE 3144025550 #SUBJECT SU:SUBJECT_TYPE Plant SU:SUBJECT_SPECIES Arabidopsis thaliana SU:TAXONOMY_ID 3702 SU:GENOTYPE_STRAIN Col-0 SU:AGE_OR_AGE_RANGE 10 day old seedlings SU:GENDER Not applicable #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 - WT-GLN-1-pos-PRM Raw file name:WT-GLN-1-pos-PRM | SampleType:Negative Control | Genotype:Wildtype RAW_FILE_NAME=10 days in 5 mM KNO3; Polarity=Pos SUBJECT_SAMPLE_FACTORS - WT-GLN-1-neg-PRM Raw file name:WT-GLN-1-neg-PRM | SampleType:Negative Control | Genotype:Wildtype RAW_FILE_NAME=10 days in 5 mM KNO3; Polarity=Neg SUBJECT_SAMPLE_FACTORS - WT-GLN-2-pos-PRM Raw file name:WT-GLN-2-pos-PRM | SampleType:Negative Control | Genotype:Wildtype RAW_FILE_NAME=10 days in 5 mM KNO3; Polarity=Pos SUBJECT_SAMPLE_FACTORS - WT-GLN-2-neg-PRM Raw file name:WT-GLN-2-neg-PRM | SampleType:Negative Control | Genotype:Wildtype RAW_FILE_NAME=10 days in 5 mM KNO3; Polarity=Neg SUBJECT_SAMPLE_FACTORS - WT-GLN-3-pos-PRM Raw file name:WT-GLN-3-pos-PRM | SampleType:Negative Control | Genotype:Wildtype RAW_FILE_NAME=10 days in 5 mM KNO3; Polarity=Pos SUBJECT_SAMPLE_FACTORS - WT-GLN-3-neg-PRM Raw file name:WT-GLN-3-neg-PRM | SampleType:Negative Control | Genotype:Wildtype RAW_FILE_NAME=10 days in 5 mM KNO3; Polarity=Neg SUBJECT_SAMPLE_FACTORS - GAT-GLN-1-pos-PRM Raw file name:GAT-GLN-1-pos-PRM | SampleType:Negative Control | Genotype:gat1_2.1 RAW_FILE_NAME=10 days in 5 mM KNO3; Polarity=Pos SUBJECT_SAMPLE_FACTORS - GAT-GLN-1-neg-PRM Raw file name:GAT-GLN-1-neg-PRM | SampleType:Negative Control | Genotype:gat1_2.1 RAW_FILE_NAME=10 days in 5 mM KNO3; Polarity=Neg SUBJECT_SAMPLE_FACTORS - GAT-GLN-2-pos-PRM Raw file name:GAT-GLN-2-pos-PRM | SampleType:Negative Control | Genotype:gat1_2.1 RAW_FILE_NAME=10 days in 5 mM KNO3; Polarity=Pos SUBJECT_SAMPLE_FACTORS - GAT-GLN-2-neg-PRM Raw file name:GAT-GLN-2-neg-PRM | SampleType:Negative Control | Genotype:gat1_2.1 RAW_FILE_NAME=10 days in 5 mM KNO3; Polarity=Neg SUBJECT_SAMPLE_FACTORS - GAT-GLN-3-pos-PRM Raw file name:GAT-GLN-3-pos-PRM | SampleType:Negative Control | Genotype:gat1_2.1 RAW_FILE_NAME=10 days in 5 mM KNO3; Polarity=Pos SUBJECT_SAMPLE_FACTORS - GAT-GLN-3-neg-PRM Raw file name:GAT-GLN-3-neg-PRM | SampleType:Negative Control | Genotype:gat1_2.1 RAW_FILE_NAME=10 days in 5 mM KNO3; Polarity=Neg SUBJECT_SAMPLE_FACTORS - WTp2GLN-1-pos-PRM Raw file name:WTp2GLN-1-pos-PRM | SampleType:Short Gln treatment | Genotype:Wildtype RAW_FILE_NAME=10 days 5 mM KNO3 + 2 hrs 10 mM Gln; Polarity=Pos SUBJECT_SAMPLE_FACTORS - WTp2GLN-1-neg-PRM Raw file name:WTp2GLN-1-neg-PRM | SampleType:Short Gln treatment | Genotype:Wildtype RAW_FILE_NAME=10 days 5 mM KNO3 + 2 hrs 10 mM Gln; Polarity=Neg SUBJECT_SAMPLE_FACTORS - WTp2GLN-2-pos-PRM Raw file name:WTp2GLN-2-pos-PRM | SampleType:Short Gln treatment | Genotype:Wildtype RAW_FILE_NAME=10 days 5 mM KNO3 + 2 hrs 10 mM Gln; Polarity=Pos SUBJECT_SAMPLE_FACTORS - WTp2GLN-2-neg-PRM Raw file name:WTp2GLN-2-neg-PRM | SampleType:Short Gln treatment | Genotype:Wildtype RAW_FILE_NAME=10 days 5 mM KNO3 + 2 hrs 10 mM Gln; Polarity=Neg SUBJECT_SAMPLE_FACTORS - WTp2GLN-3-pos-PRM Raw file name:WTp2GLN-3-pos-PRM | SampleType:Short Gln treatment | Genotype:Wildtype RAW_FILE_NAME=10 days 5 mM KNO3 + 2 hrs 10 mM Gln; Polarity=Pos SUBJECT_SAMPLE_FACTORS - WTp2GLN-3-neg-PRM Raw file name:WTp2GLN-3-neg-PRM | SampleType:Short Gln treatment | Genotype:Wildtype RAW_FILE_NAME=10 days 5 mM KNO3 + 2 hrs 10 mM Gln; Polarity=Neg SUBJECT_SAMPLE_FACTORS - GATp2GLN-1-pos-PRM Raw file name:GATp2GLN-1-pos-PRM | SampleType:Short Gln treatment | Genotype:gat1_2.1 RAW_FILE_NAME=10 days 5 mM KNO3 + 2 hrs 10 mM Gln; Polarity=Pos SUBJECT_SAMPLE_FACTORS - GATp2GLN-1-neg-PRM Raw file name:GATp2GLN-1-neg-PRM | SampleType:Short Gln treatment | Genotype:gat1_2.1 RAW_FILE_NAME=10 days 5 mM KNO3 + 2 hrs 10 mM Gln; Polarity=Neg SUBJECT_SAMPLE_FACTORS - GATp2GLN-2-pos-PRM Raw file name:GATp2GLN-2-pos-PRM | SampleType:Short Gln treatment | Genotype:gat1_2.1 RAW_FILE_NAME=10 days 5 mM KNO3 + 2 hrs 10 mM Gln; Polarity=Pos SUBJECT_SAMPLE_FACTORS - GATp2GLN-2-neg-PRM Raw file name:GATp2GLN-2-neg-PRM | SampleType:Short Gln treatment | Genotype:gat1_2.1 RAW_FILE_NAME=10 days 5 mM KNO3 + 2 hrs 10 mM Gln; Polarity=Neg SUBJECT_SAMPLE_FACTORS - GATp2GLN-3-pos-PRM Raw file name:GATp2GLN-3-pos-PRM | SampleType:Short Gln treatment | Genotype:gat1_2.1 RAW_FILE_NAME=10 days 5 mM KNO3 + 2 hrs 10 mM Gln; Polarity=Pos SUBJECT_SAMPLE_FACTORS - GATp2GLN-3-neg-PRM Raw file name:GATp2GLN-3-neg-PRM | SampleType:Short Gln treatment | Genotype:gat1_2.1 RAW_FILE_NAME=10 days 5 mM KNO3 + 2 hrs 10 mM Gln; Polarity=Neg SUBJECT_SAMPLE_FACTORS - WTp10GLN-1-pos-PRM Raw file name:WTp10GLN-1-pos-PRM | SampleType:Long Gln treatment | Genotype:Wildtype RAW_FILE_NAME=10 days in 2 mM Gln; Polarity=Pos SUBJECT_SAMPLE_FACTORS - WTp10GLN-1-neg-PRM Raw file name:WTp10GLN-1-neg-PRM | SampleType:Long Gln treatment | Genotype:Wildtype RAW_FILE_NAME=10 days in 2 mM Gln; Polarity=Neg SUBJECT_SAMPLE_FACTORS - WTp10GLN-2-pos-PRM Raw file name:WTp10GLN-2-pos-PRM | SampleType:Long Gln treatment | Genotype:Wildtype RAW_FILE_NAME=10 days in 2 mM Gln; Polarity=Pos SUBJECT_SAMPLE_FACTORS - WTp10GLN-2-neg-PRM Raw file name:WTp10GLN-2-neg-PRM | SampleType:Long Gln treatment | Genotype:Wildtype RAW_FILE_NAME=10 days in 2 mM Gln; Polarity=Neg SUBJECT_SAMPLE_FACTORS - WTp10GLN-3-pos-PRM Raw file name:WTp10GLN-3-pos-PRM | SampleType:Long Gln treatment | Genotype:Wildtype RAW_FILE_NAME=10 days in 2 mM Gln; Polarity=Pos SUBJECT_SAMPLE_FACTORS - WTp10GLN-3-neg-PRM Raw file name:WTp10GLN-3-neg-PRM | SampleType:Long Gln treatment | Genotype:Wildtype RAW_FILE_NAME=10 days in 2 mM Gln; Polarity=Neg SUBJECT_SAMPLE_FACTORS - GATp10GLN-1-pos-PRM Raw file name:GATp10GLN-1-pos-PRM | SampleType:Long Gln treatment | Genotype:gat1_2.1 RAW_FILE_NAME=10 days in 2 mM Gln; Polarity=Pos SUBJECT_SAMPLE_FACTORS - GATp10GLN-1-neg-PRM Raw file name:GATp10GLN-1-neg-PRM | SampleType:Long Gln treatment | Genotype:gat1_2.1 RAW_FILE_NAME=10 days in 2 mM Gln; Polarity=Neg SUBJECT_SAMPLE_FACTORS - GATp10GLN-2-pos-PRM Raw file name:GATp10GLN-2-pos-PRM | SampleType:Long Gln treatment | Genotype:gat1_2.1 RAW_FILE_NAME=10 days in 2 mM Gln; Polarity=Pos SUBJECT_SAMPLE_FACTORS - GATp10GLN-2-neg-PRM Raw file name:GATp10GLN-2-neg-PRM | SampleType:Long Gln treatment | Genotype:gat1_2.1 RAW_FILE_NAME=10 days in 2 mM Gln; Polarity=Neg SUBJECT_SAMPLE_FACTORS - GATp10GLN-3-pos-PRM Raw file name:GATp10GLN-3-pos-PRM | SampleType:Long Gln treatment | Genotype:gat1_2.1 RAW_FILE_NAME=10 days in 2 mM Gln; Polarity=Pos SUBJECT_SAMPLE_FACTORS - GATp10GLN-3-neg-PRM Raw file name:GATp10GLN-3-neg-PRM | SampleType:Long Gln treatment | Genotype:gat1_2.1 RAW_FILE_NAME=10 days in 2 mM Gln; Polarity=Neg SUBJECT_SAMPLE_FACTORS - WTp2GLU-1-pos-PRM Raw file name:WTp2GLU-1-pos-PRM | SampleType:Positive Control | Genotype:Wildtype RAW_FILE_NAME=10 days in 2 mM Glu; Polarity=Pos SUBJECT_SAMPLE_FACTORS - WTp2GLU-1-neg-PRM Raw file name:WTp2GLU-1-neg-PRM | SampleType:Positive Control | Genotype:Wildtype RAW_FILE_NAME=10 days in 2 mM Glu; Polarity=Neg SUBJECT_SAMPLE_FACTORS - WTp2GLU-2-pos-PRM Raw file name:WTp2GLU-2-pos-PRM | SampleType:Positive Control | Genotype:Wildtype RAW_FILE_NAME=10 days in 2 mM Glu; Polarity=Pos SUBJECT_SAMPLE_FACTORS - WTp2GLU-2-neg-PRM Raw file name:WTp2GLU-2-neg-PRM | SampleType:Positive Control | Genotype:Wildtype RAW_FILE_NAME=11 days in 2 mM Gln; Polarity=Neg SUBJECT_SAMPLE_FACTORS - WTp2GLU-3-pos-PRM Raw file name:WTp2GLU-3-pos-PRM | SampleType:Positive Control | Genotype:Wildtype RAW_FILE_NAME=10 days in 2 mM Glu; Polarity=Pos SUBJECT_SAMPLE_FACTORS - WTp2GLU-3-neg-PRM Raw file name:WTp2GLU-3-neg-PRM | SampleType:Positive Control | Genotype:Wildtype RAW_FILE_NAME=10 days in 2 mM Glu; Polarity=Neg SUBJECT_SAMPLE_FACTORS - GATp2GLU-1-pos-PRM Raw file name:GATp2GLU-1-pos-PRM | SampleType:Positive Control | Genotype:gat1_2.1 RAW_FILE_NAME=10 days in 2 mM Glu; Polarity=Pos SUBJECT_SAMPLE_FACTORS - GATp2GLU-1-neg-PRM Raw file name:GATp2GLU-1-neg-PRM | SampleType:Positive Control | Genotype:gat1_2.1 RAW_FILE_NAME=12 days in 2 mM Gln; Polarity=Neg SUBJECT_SAMPLE_FACTORS - GATp2GLU-2-pos-PRM Raw file name:GATp2GLU-2-pos-PRM | SampleType:Positive Control | Genotype:gat1_2.1 RAW_FILE_NAME=10 days in 2 mM Glu; Polarity=Pos SUBJECT_SAMPLE_FACTORS - GATp2GLU-2-neg-PRM Raw file name:GATp2GLU-2-neg-PRM | SampleType:Positive Control | Genotype:gat1_2.1 RAW_FILE_NAME=10 days in 2 mM Glu; Polarity=Neg SUBJECT_SAMPLE_FACTORS - GATp2GLU-3-pos-PRM Raw file name:GATp2GLU-3-pos-PRM | SampleType:Positive Control | Genotype:gat1_2.1 RAW_FILE_NAME=10 days in 2 mM Glu; Polarity=Pos SUBJECT_SAMPLE_FACTORS - GATp2GLU-3-neg-PRM Raw file name:GATp2GLU-3-neg-PRM | SampleType:Positive Control | Genotype:gat1_2.1 RAW_FILE_NAME=13 days in 2 mM Gln; Polarity=Neg SUBJECT_SAMPLE_FACTORS - AA-CS1-PRM Raw file name:AA-CS1-PRM | SampleType:Amino acid standard | Genotype:Standard RAW_FILE_NAME=NA; Polarity=Pos SUBJECT_SAMPLE_FACTORS - AA-CS2-PRM Raw file name:AA-CS2-PRM | SampleType:Amino acid standard | Genotype:Standard RAW_FILE_NAME=NA; Polarity=Pos SUBJECT_SAMPLE_FACTORS - AA-CS3-PRM Raw file name:AA-CS3-PRM | SampleType:Amino acid standard | Genotype:Standard RAW_FILE_NAME=NA; Polarity=Pos SUBJECT_SAMPLE_FACTORS - AA-CS4-PRM Raw file name:AA-CS4-PRM | SampleType:Amino acid standard | Genotype:Standard RAW_FILE_NAME=NA; Polarity=Pos SUBJECT_SAMPLE_FACTORS - AA-CS5-PRM Raw file name:AA-CS5-PRM | SampleType:Amino acid standard | Genotype:Standard RAW_FILE_NAME=NA; Polarity=Pos SUBJECT_SAMPLE_FACTORS - AA-CS6-PRM Raw file name:AA-CS6-PRM | SampleType:Amino acid standard | Genotype:Standard RAW_FILE_NAME=NA; Polarity=Pos SUBJECT_SAMPLE_FACTORS - OA-CS1-PRM Raw file name:OA-CS1-PRM | SampleType:Organic acid standard | Genotype:Standard RAW_FILE_NAME=NA; Polarity=Neg SUBJECT_SAMPLE_FACTORS - OA-CS2-PRM Raw file name:OA-CS2-PRM | SampleType:Organic acid standard | Genotype:Standard RAW_FILE_NAME=NA; Polarity=Neg SUBJECT_SAMPLE_FACTORS - OA-CS3-PRM Raw file name:OA-CS3-PRM | SampleType:Organic acid standard | Genotype:Standard RAW_FILE_NAME=NA; Polarity=Neg SUBJECT_SAMPLE_FACTORS - OA-CS4-PRM Raw file name:OA-CS4-PRM | SampleType:Organic acid standard | Genotype:Standard RAW_FILE_NAME=NA; Polarity=Neg SUBJECT_SAMPLE_FACTORS - OA-CS5-PRM Raw file name:OA-CS5-PRM | SampleType:Organic acid standard | Genotype:Standard RAW_FILE_NAME=NA; Polarity=Neg SUBJECT_SAMPLE_FACTORS - OA-CS6-PRM Raw file name:OA-CS6-PRM | SampleType:Organic acid standard | Genotype:Standard RAW_FILE_NAME=NA; Polarity=Neg #COLLECTION CO:COLLECTION_SUMMARY Roots from 50 seedlings grown in plates containing required treatment were CO:COLLECTION_SUMMARY collected and processed as single replicate. CO:COLLECTION_PROTOCOL_ID 001 CO:SAMPLE_TYPE Plant CO:COLLECTION_METHOD 50 mg collected and flash frozen in Liquid N2 CO:COLLECTION_LOCATION London Research and Development Center CO:STORAGE_CONDITIONS -80℃ #TREATMENT TR:TREATMENT_SUMMARY Wild-type Arabidopsis ecotype Columbia and gat1_2.1 T-DNA insertion lines were TR:TREATMENT_SUMMARY used for Gln and Glu treatments. Plants were grown on vertical plates at 22 °C TR:TREATMENT_SUMMARY under continuous light (ca. 70 μmol m-2 s-2), as previously described by Ivanov TR:TREATMENT_SUMMARY et al. (2012) on a defined nutrient medium containing a final concentration of TR:TREATMENT_SUMMARY 10 mM potassium phosphate (pH 6.5), 5 mM KNO3, 2 mM MgSO4, 1 mM CaCl2, 125 μg TR:TREATMENT_SUMMARY FeNaEDTA, micronutrients (50 mM H3BO3, 12 mM MnSO4, 1 mM ZnCl2, 1 mM CuSO4 and TR:TREATMENT_SUMMARY 0.2 mM Na2MoO4), 1% sucrose and 1% agar [28]. Ten-day old seedlings were TR:TREATMENT_SUMMARY transferred to plates containing the same medium without nitrogen as control or TR:TREATMENT_SUMMARY 10 mM Gln as sole N source. After 2 h, root tissue was harvested, frozen in TR:TREATMENT_SUMMARY liquid N2 and stored at -80 °C until total metabolite extractions was carried TR:TREATMENT_SUMMARY out. For growth in Gln and Glu, the same media and growth conditions were used TR:TREATMENT_SUMMARY with the exception of 5 mM KNO3 being substituted with either 2 mM Gln or 2 mM TR:TREATMENT_SUMMARY Glu and tissue was collected after 10 days. #SAMPLEPREP SP:SAMPLEPREP_SUMMARY Fifty mg of root tissue was excised from 10 day old seedlings of WT or gat1_2.1 SP:SAMPLEPREP_SUMMARY grown under conditions described above, collected in 2 mL Eppendorf tubes and SP:SAMPLEPREP_SUMMARY flash frozen in liquid N2. Frozen tissue was homogenized using a tissue lyser SP:SAMPLEPREP_SUMMARY and metabolites were isolated using 1 mL of methanol:water (4:1) with incubation SP:SAMPLEPREP_SUMMARY in an ultra-sonication bath for 20 min followed by shaking for 30 min at 4 °C. SP:SAMPLEPREP_SUMMARY The mixture was centrifuged at 12,000 × g for 10 min at 4 °C and 700 µl of SP:SAMPLEPREP_SUMMARY the supernatant was transferred into fresh tubes and evaporated to dryness using SP:SAMPLEPREP_SUMMARY a Vacufuge at ambient temperature. The residue was re-dissolved in 500 µl of SP:SAMPLEPREP_SUMMARY 1:1 methanol:water and the samples were filtered using a 0.2 µm PTFE microfuge SP:SAMPLEPREP_SUMMARY filter (Cytiva Whatman). Five µl of 1 µg/mL 13C6 Phe was added to the samples SP:SAMPLEPREP_SUMMARY for monitoring the quality of LC-MS runs. #CHROMATOGRAPHY CH:CHROMATOGRAPHY_TYPE HILIC CH:INSTRUMENT_NAME Agilent 1290 Infinity II CH:COLUMN_NAME SeQuant ZIC-HILIC (100 x 2.1mm, 3.5um) CH:FLOW_RATE 0.3 mL min-1 CH:COLUMN_TEMPERATURE 35 CH:METHODS_FILENAME Targeted Metabolite Analysis CH:SOLVENT_A 5 mM Ammonium Acetate pH 4.0 CH:SOLVENT_B 90% ACN 0.1% Acetic acid CH:INTERNAL_STANDARD 13C6 Phenylalanine #ANALYSIS AN:ANALYSIS_TYPE MS AN:OPERATOR_NAME Shrikaar Kambhampati AN:DETECTOR_TYPE Orbitrap AN:ACQUISITION_DATE 3/11/2016 AN:ANALYSIS_PROTOCOL_FILE Targeted_Metabolite_Analysis.pdf #MS MS:INSTRUMENT_NAME Thermo Q Exactive Orbitrap MS:INSTRUMENT_TYPE Orbitrap MS:MS_TYPE ESI MS:ION_MODE POSITIVE MS:MS_COMMENTS The following heated electrospray ionization (HESI) conditions were optimized MS:MS_COMMENTS for the analysis of amino and organic acids: spray voltage, 3.9 kV (ESI+), 3.5 MS:MS_COMMENTS kV (ESI-); capillary temperature, 250 °C; probe heater temperature, 450 °C; MS:MS_COMMENTS sheath gas, 30 arbitrary units; auxiliary gas, 8 arbitrary units; and S-Lens RF MS:MS_COMMENTS level, 60%. Injections of 5 μl were used with a flow rate of 0.3 mL min-1. MS:MS_COMMENTS Compounds were detected and monitored using targeted MS/MS, spectra were MS:MS_COMMENTS collected at 17,500 resolution, AGC target 1e6, maximum IT 65 ms, isolation MS:MS_COMMENTS window of 1 m/z, normalized collision energy of 30, intensity threshold of 1.6e5 MS:MS_COMMENTS and 10s dynamic exclusion. #MS_METABOLITE_DATA MS_METABOLITE_DATA:UNITS umol g FW-1 MS_METABOLITE_DATA_START Samples WT-GLN-1-pos-PRM WT-GLN-2-pos-PRM WT-GLN-3-pos-PRM WTp2GLN-1-pos-PRM WTp2GLN-2-pos-PRM WTp2GLN-3-pos-PRM WTp10GLN-1-pos-PRM WTp10GLN-2-pos-PRM WTp10GLN-3-pos-PRM GAT-GLN-1-pos-PRM GAT-GLN-2-pos-PRM GAT-GLN-3-pos-PRM GATp2GLN-1-pos-PRM GATp2GLN-2-pos-PRM GATp2GLN-3-pos-PRM GATp10GLN-1-pos-PRM GATp10GLN-2-pos-PRM GATp10GLN-3-pos-PRM WTp2GLU-1-pos-PRM WTp2GLU-2-pos-PRM WTp2GLU-3-pos-PRM GATp2GLU-1-pos-PRM GATp2GLU-2-pos-PRM GATp2GLU-3-pos-PRM Factors Raw file name:WT-GLN-1-pos-PRM | SampleType:Negative Control | Genotype:Wildtype Raw file name:WT-GLN-2-pos-PRM | SampleType:Negative Control | Genotype:Wildtype Raw file name:WT-GLN-3-pos-PRM | SampleType:Negative Control | Genotype:Wildtype Raw file name:WTp2GLN-1-pos-PRM | SampleType:Short Gln treatment | Genotype:Wildtype Raw file name:WTp2GLN-2-pos-PRM | SampleType:Short Gln treatment | Genotype:Wildtype Raw file name:WTp2GLN-3-pos-PRM | SampleType:Short Gln treatment | Genotype:Wildtype Raw file name:WTp10GLN-1-pos-PRM | SampleType:Long Gln treatment | Genotype:Wildtype Raw file name:WTp10GLN-2-pos-PRM | SampleType:Long Gln treatment | Genotype:Wildtype Raw file name:WTp10GLN-3-pos-PRM | SampleType:Long Gln treatment | Genotype:Wildtype Raw file name:GAT-GLN-1-pos-PRM | SampleType:Negative Control | Genotype:gat1_2.1 Raw file name:GAT-GLN-2-pos-PRM | SampleType:Negative Control | Genotype:gat1_2.1 Raw file name:GAT-GLN-3-pos-PRM | SampleType:Negative Control | Genotype:gat1_2.1 Raw file name:GATp2GLN-1-pos-PRM | SampleType:Short Gln treatment | Genotype:gat1_2.1 Raw file name:GATp2GLN-2-pos-PRM | SampleType:Short Gln treatment | Genotype:gat1_2.1 Raw file name:GATp2GLN-3-pos-PRM | SampleType:Short Gln treatment | Genotype:gat1_2.1 Raw file name:GATp10GLN-1-pos-PRM | SampleType:Long Gln treatment | Genotype:gat1_2.1 Raw file name:GATp10GLN-2-pos-PRM | SampleType:Long Gln treatment | Genotype:gat1_2.1 Raw file name:GATp10GLN-3-pos-PRM | SampleType:Long Gln treatment | Genotype:gat1_2.1 Raw file name:WTp2GLU-1-pos-PRM | SampleType:Positive Control | Genotype:Wildtype Raw file name:WTp2GLU-2-pos-PRM | SampleType:Positive Control | Genotype:Wildtype Raw file name:WTp2GLU-3-pos-PRM | SampleType:Positive Control | Genotype:Wildtype Raw file name:GATp2GLU-1-pos-PRM | SampleType:Positive Control | Genotype:gat1_2.1 Raw file name:GATp2GLU-2-pos-PRM | SampleType:Positive Control | Genotype:gat1_2.1 Raw file name:GATp2GLU-3-pos-PRM | SampleType:Positive Control | Genotype:gat1_2.1 gamma-aminobutyric acid 0.254114562 0.306378192 0.244204279 0.310491373 0.337413389 0.31847619 0.20000138 0.219400966 0.232002761 0.142202899 0.165439614 0.181554175 0.197917184 0.214266391 0.230222222 0.09410766 0.071519669 0.075432712 0.147185645 0.149884058 0.182879227 0.171029676 0.157868875 0.144507937 Glutamine 14.90781983 13.56566464 13.1814641 181.9444722 197.5057425 174.2909218 25.63896934 24.85828423 22.67552182 11.38390093 6.905922301 16.38509937 222.756916 228.4565065 189.839209 27.43972835 28.91960451 21.91121542 9.585039449 12.8031559 12.40936782 7.896434635 11.30610207 10.51123539 Glutamate 9.998529202 11.2373203 8.653461119 28.66152678 32.71096456 30.13042653 21.0926128 22.72282583 23.7718366 14.44698012 15.98420079 12.93680315 27.1456564 25.27489681 24.70128576 13.74906296 15.28201357 14.59405988 335.3897139 373.6446838 455.0011387 403.5455236 336.2845282 474.3454476 MS_METABOLITE_DATA_END #METABOLITES METABOLITES_START metabolite_name gamma-aminobutyric acid Glutamine Glutamate METABOLITES_END #END