#METABOLOMICS WORKBENCH cclish_20250922_113855 DATATRACK_ID:6468 STUDY_ID:ST004233 ANALYSIS_ID:AN007048 PROJECT_ID:PR002663 VERSION 1 CREATED_ON September 23, 2025, 5:03 pm #PROJECT PR:PROJECT_TITLE Loss of P. falciparum Amino Acid Transporter (ApiAT2) Function Increases PR:PROJECT_TITLE Intracellular Proline and Confers Resistance to Prolyl-tRNA Synthetase PR:PROJECT_TITLE Inhibitors PR:PROJECT_SUMMARY Plasmodium falciparum evades the antimalarial activity of proline-competitive PR:PROJECT_SUMMARY prolyl-tRNA synthetase (PfProRS) inhibitors, such as halofuginone (HFG), by a PR:PROJECT_SUMMARY unique resistance mechanism termed the Adaptive Proline Response (APR). The APR PR:PROJECT_SUMMARY is characterized by a marked elevation of intracellular proline following drug PR:PROJECT_SUMMARY exposure. Contrary to initial expectations, the APR is not mediated by PR:PROJECT_SUMMARY alterations in canonical proline metabolic pathways involving arginase (PfARG) PR:PROJECT_SUMMARY and ornithine aminotransferase (PfOAT). Instead, we identified loss-of-function PR:PROJECT_SUMMARY mutations in the Apicomplexan Amino acid Transporter 2 (PfApiAT2) as the primary PR:PROJECT_SUMMARY genetic driver of this resistance phenotype. Importantly, reversion of these PR:PROJECT_SUMMARY mutations to wildtype effectively suppresses the APR, establishing PfApiAT2 as PR:PROJECT_SUMMARY the molecular determinant of this novel resistance mechanism. The elucidation of PR:PROJECT_SUMMARY the APR significantly advances our understanding of antimalarial drug PR:PROJECT_SUMMARY resistance. By delineating the role of PfApiAT2 in this process, we establish PR:PROJECT_SUMMARY critical insights for the development of strategies to circumvent PfProRS PR:PROJECT_SUMMARY inhibitor resistance for future antimalarial therapies. PR:INSTITUTE Broad Institute of MIT and Harvard PR:DEPARTMENT Metabolomics Platform PR:LAST_NAME Clish PR:FIRST_NAME Clary PR:ADDRESS 300 Binney Street, Cambridge, MA, 02142, USA PR:EMAIL clary@broadinstitute.org PR:PHONE 617-714-7654 PR:FUNDING_SOURCE NIH-NIAID R01AI143723 and R21AI132981; NIH-NIGMS T32 GM008666 and F31AI129412; PR:FUNDING_SOURCE Bill and Melinda Gates Foundation OPP1132451 and OPP1086203; and the Harvard PR:FUNDING_SOURCE Defeating Malaria Initiative PR:PROJECT_COMMENTS 5 experiements PR:CONTRIBUTORS Selina Bopp, Lọla Fagbami, Amy Deik, Claudia Taccheri, Akansha Pant, Madeline PR:CONTRIBUTORS Luth, Daisy Chen, Mark A. Tye, Imran Ullah, Robert Morris, Wilhelm Haas, PR:CONTRIBUTORS Elizabeth A. Winzeler, Clary B. Clish, Amanda K. Lukens, Ralph Mazitschek, Dyann PR:CONTRIBUTORS F. Wirth #STUDY ST:STUDY_TITLE Validating the role of the arginine to proline biosynthetic pathway in the APR ST:STUDY_SUMMARY In this study, we use a custom Triplex labeled media, containing uniquely stable ST:STUDY_SUMMARY isotope labeled proline (+1), arginine (+2), and glutamine (+5) to validate the ST:STUDY_SUMMARY arginine to proline biosynthetic pathway as major driver for the elevated ST:STUDY_SUMMARY proline levels in APR parasites. Labeled proline levels were assessed in Dd2 ST:STUDY_SUMMARY (WT) parasites and Dd2 parasites with enzymes from the arginine to proline ST:STUDY_SUMMARY biosynthetic pathway disrupted, namely Dd2-ARG KO parasites (parasites with a ST:STUDY_SUMMARY disrupted arginase locus) and Dd2-OAT KO parasites (parasites with a disrupted ST:STUDY_SUMMARY ornithine amino-transferase locus). Uninfected RBCs (uRBCs) were run as a ST:STUDY_SUMMARY control. ST:INSTITUTE Broad Institute of MIT and Harvard ST:DEPARTMENT Metabolomics Platform ST:LAST_NAME Clish ST:FIRST_NAME Clary ST:ADDRESS 300 Binney Street, Cambridge, MA 02142 ST:EMAIL clary@broadinstitute.org ST:PHONE 617-714-7654 ST:NUM_GROUPS 5 ST:TOTAL_SUBJECTS 24 ST:STUDY_COMMENTS Study 2 of 5 #SUBJECT SU:SUBJECT_TYPE Cultured cells SU:SUBJECT_SPECIES Plasmodium falciparum SU:TAXONOMY_ID 5833 SU:SPECIES_GROUP Unicellular parasites #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 - Study2_uRBC_RBC_0h_R1 Sample source:uninfected RBC (uRBC) | Parasite_type:Control | Parasite_line:Control RBCs | Timepoint:0 h Replicate=1; Tracer=15N Pro 15N,13C Arg 5C13 Gln; Date Generated=1/17/2019; RAW_FILE_NAME(Raw_file_name)=0007_MAZ_Lola_MS13_HP-Control_uRBC_0h_R1.raw SUBJECT_SAMPLE_FACTORS - Study2_uRBC_RBC_0h_R2 Sample source:uninfected RBC (uRBC) | Parasite_type:Control | Parasite_line:Control RBCs | Timepoint:0 h Replicate=2; Tracer=15N Pro 15N,13C Arg 5C13 Gln; Date Generated=1/22/2019; RAW_FILE_NAME(Raw_file_name)=0023_MAZ_Lola_MS13_HP-Control_uRBC_0h_R2.raw SUBJECT_SAMPLE_FACTORS - Study2_uRBC_RBC_0h_R3 Sample source:uninfected RBC (uRBC) | Parasite_type:Control | Parasite_line:Control RBCs | Timepoint:0 h Replicate=3; Tracer=15N Pro 15N,13C Arg 5C13 Gln; Date Generated=1/24/2019; RAW_FILE_NAME(Raw_file_name)=0043_MAZ_Lola_MS13_HP-Control_uRBC_0h_R3.raw SUBJECT_SAMPLE_FACTORS - Study2_uRBC_RBC_0h_R4 Sample source:uninfected RBC (uRBC) | Parasite_type:Control | Parasite_line:Control RBCs | Timepoint:0 h Replicate=4; Tracer=15N Pro 15N,13C Arg 5C13 Gln; Date Generated=2/3/2019; RAW_FILE_NAME(Raw_file_name)=0059_MAZ_Lola_MS13_HP-Control_uRBC_0h_R4.raw SUBJECT_SAMPLE_FACTORS - Study2_uRBC_RBC_0h_R5 Sample source:uninfected RBC (uRBC) | Parasite_type:Control | Parasite_line:Control RBCs | Timepoint:0 h Replicate=5; Tracer=15N Pro 15N,13C Arg 5C13 Gln; Date Generated=2/23/2019; RAW_FILE_NAME(Raw_file_name)=0069_MAZ_Lola_MS13_HP-Control_uRBC_0h_R5.raw SUBJECT_SAMPLE_FACTORS - Study2_uRBC_RBC_0h_R6 Sample source:uninfected RBC (uRBC) | Parasite_type:Control | Parasite_line:Control RBCs | Timepoint:0 h Replicate=6; Tracer=15N Pro 15N,13C Arg 5C13 Gln; Date Generated=2/27/2019; RAW_FILE_NAME(Raw_file_name)=0085_MAZ_Lola_MS13_HP-Control_uRBC_0h_R6.raw SUBJECT_SAMPLE_FACTORS - Study2_uRBC_RBC_0h_R7 Sample source:uninfected RBC (uRBC) | Parasite_type:Control | Parasite_line:Control RBCs | Timepoint:0 h Replicate=7; Tracer=15N Pro 15N,13C Arg 5C13 Gln; Date Generated=2/25/2019; RAW_FILE_NAME(Raw_file_name)=0106_MAZ_Lola_MS13_HP-Dd2_I35_PAR_10h_R2.raw SUBJECT_SAMPLE_FACTORS - Study2_uRBC_RBC_0h_R8 Sample source:uninfected RBC (uRBC) | Parasite_type:Control | Parasite_line:Control RBCs | Timepoint:0 h Replicate=8; Tracer=15N Pro 15N,13C Arg 5C13 Gln; Date Generated=2/25/2019; RAW_FILE_NAME(Raw_file_name)=0121_MAZ_Lola_MS13_HP-Control_uRBC_0h_R8.raw SUBJECT_SAMPLE_FACTORS - Study2_uRBC_RBC_10h_R1 Sample source:uninfected RBC (uRBC) | Parasite_type:Control | Parasite_line:Control RBCs | Timepoint:10 h Replicate=1; Tracer=15N Pro 15N,13C Arg 5C13 Gln; Date Generated=1/17/2019; RAW_FILE_NAME(Raw_file_name)=0010_MAZ_Lola_MS13_HP-Control_uRBC_10h_R1.raw SUBJECT_SAMPLE_FACTORS - Study2_uRBC_RBC_10h_R2 Sample source:uninfected RBC (uRBC) | Parasite_type:Control | Parasite_line:Control RBCs | Timepoint:10 h Replicate=2; Tracer=15N Pro 15N,13C Arg 5C13 Gln; Date Generated=1/22/2019; RAW_FILE_NAME(Raw_file_name)=0028_MAZ_Lola_MS13_HP-Control_uRBC_10h_R2.raw SUBJECT_SAMPLE_FACTORS - Study2_uRBC_RBC_10h_R3 Sample source:uninfected RBC (uRBC) | Parasite_type:Control | Parasite_line:Control RBCs | Timepoint:10h Replicate=3; Tracer=15N Pro 15N, 13C Arg 5C13 Gln; Date Generated=1/24/2019; RAW_FILE_NAME(Raw_file_name)=0048_MAZ_Lola_MS13_HP-Control uRBC 10h R3.raw SUBJECT_SAMPLE_FACTORS - Study2_uRBC_RBC_10h_R4 Sample source:uninfected RBC (uRBC) | Parasite_type:Control | Parasite_line:Control RBCs | Timepoint:10 h Replicate=4; Tracer=15N Pro 15N,13C Arg 5C13 Gln; Date Generated=2/3/2019; RAW_FILE_NAME(Raw_file_name)=0062_MAZ_Lola_MS13_HP-Control_uRBC_10h_R4.raw SUBJECT_SAMPLE_FACTORS - Study2_uRBC_RBC_10h_R5 Sample source:uninfected RBC (uRBC) | Parasite_type:Control | Parasite_line:Control RBCs | Timepoint:10 h Replicate=5; Tracer=15N Pro 15N,13C Arg 5C13 Gln; Date Generated=2/23/2019; RAW_FILE_NAME(Raw_file_name)=0072_MAZ_Lola_MS13_HP-Control_uRBC_10h_R5.raw SUBJECT_SAMPLE_FACTORS - Study2_uRBC_RBC_10h_R6 Sample source:uninfected RBC (uRBC) | Parasite_type:Control | Parasite_line:Control RBCs | Timepoint:10 h Replicate=6; Tracer=15N Pro 15N,13C Arg 5C13 Gln; Date Generated=2/27/2019; RAW_FILE_NAME(Raw_file_name)=0090_MAZ_Lola_MS13_HP-Control_uRBC_10h_R6.raw SUBJECT_SAMPLE_FACTORS - Study2_uRBC_RBC_10h_R7 Sample source:uninfected RBC (uRBC) | Parasite_type:Control | Parasite_line:Control RBCs | Timepoint:10 h Replicate=7; Tracer=15N Pro 15N,13C Arg 5C13 Gln; Date Generated=2/25/2019; RAW_FILE_NAME(Raw_file_name)=0113_MAZ_Lola_MS13_HP-Dd2_I35_iRBC_0h_R2.raw SUBJECT_SAMPLE_FACTORS - Study2_uRBC_RBC_10h_R8 Sample source:uninfected RBC (uRBC) | Parasite_type:Control | Parasite_line:Control RBCs | Timepoint:10 h Replicate=8; Tracer=15N Pro 15N,13C Arg 5C13 Gln; Date Generated=2/25/2019; RAW_FILE_NAME(Raw_file_name)=0122_MAZ_Lola_MS13_HP-Control_uRBC_10h_R8.raw SUBJECT_SAMPLE_FACTORS - Study2_Dd2_iRBC_10h_R1 Sample source:infected RBC (iRBC) | Parasite_type:Dd2 WT | Parasite_line:Dd2 | Timepoint:10 h Replicate=1; Tracer=15N Pro 15N,13C Arg 5C13 Gln; Date Generated=1/22/2019; RAW_FILE_NAME(Raw_file_name)=0029_MAZ_Lola_MS13_HP-Dd2_WT_iRBC_10h_R1.raw SUBJECT_SAMPLE_FACTORS - Study2_Dd2_iRBC_10h_R2 Sample source:infected RBC (iRBC) | Parasite_type:Dd2 WT | Parasite_line:Dd2 | Timepoint:10 h Replicate=2; Tracer=15N Pro 15N,13C Arg 5C13 Gln; Date Generated=1/24/2019; RAW_FILE_NAME(Raw_file_name)=0049_MAZ_Lola_MS13_HP-Dd2_WT_iRBC_10h_R2.raw SUBJECT_SAMPLE_FACTORS - Study2_Dd2_iRBC_10h_R3 Sample source:infected RBC (iRBC) | Parasite_type:Dd2 WT | Parasite_line:Dd2 | Timepoint:10h Replicate=3; Tracer=15N Pro 15N, 13C Arg 5C13 Gln; Date Generated=2/25/2019; RAW_FILE_NAME(Raw_file_name)=0114_MAZ_Lola_MS13_HP-Control uRBC 10h R7.raw SUBJECT_SAMPLE_FACTORS - Study2_Dd2∆ARG-C1_iRBC_10h_R1 Sample source:infected RBC (iRBC) | Parasite_type:Dd2 AD7 | Parasite_line:Dd2∆ARG C1 | Timepoint:10 h Replicate=1; Tracer=15N Pro 15N,13C Arg 5C13 Gln; Date Generated=1/17/2019; RAW_FILE_NAME(Raw_file_name)=0011_MAZ_Lola_MS13_HP-Dd2_AD7_iRBC_10h_R1.raw SUBJECT_SAMPLE_FACTORS - Study2_Dd2∆ARG-C1_iRBC_10h_R2 Sample source:infected RBC (iRBC) | Parasite_type:Dd2 AD7 | Parasite_line:Dd2∆ARG C1 | Timepoint:10 h Replicate=2; Tracer=15N Pro 15N,13C Arg 5C13 Gln; Date Generated=1/22/2019; RAW_FILE_NAME(Raw_file_name)=0031_MAZ_Lola_MS13_HP-Dd2_AD7_iRBC_10h_R2.raw SUBJECT_SAMPLE_FACTORS - Study2_Dd2∆ARG-C1_iRBC_10h_R3 Sample source:infected RBC (iRBC) | Parasite_type:Dd2 AD7 | Parasite_line:Dd2∆ARG C1 | Timepoint:10 h Replicate=3; Tracer=15N Pro 15N,13C Arg 5C13 Gln; Date Generated=1/24/2019; RAW_FILE_NAME(Raw_file_name)=0051_MAZ_Lola_MS13_HP-Dd2_AD7_iRBC_10h_R3.raw SUBJECT_SAMPLE_FACTORS - Study2_Dd2∆OAT-C1_iRBC_10h_R1 Sample source:infected RBC (iRBC) | Parasite_type:Dd2 OD12 | Parasite_line:Dd2∆OAT C1 | Timepoint:10 h Replicate=1; Tracer=15N Pro 15N,13C Arg 5C13 Gln; Date Generated=2/23/2019; RAW_FILE_NAME(Raw_file_name)=0074_MAZ_Lola_MS13_HP-Dd2_OD12_iRBC_10h_R1.raw SUBJECT_SAMPLE_FACTORS - Study2_Dd2∆OAT-C1_iRBC_10h_R2 Sample source:infected RBC (iRBC) | Parasite_type:Dd2 OD12 | Parasite_line:Dd2∆OAT C1 | Timepoint:10 h Replicate=2; Tracer=15N Pro 15N,13C Arg 5C13 Gln; Date Generated=2/25/2019; RAW_FILE_NAME(Raw_file_name)=0118_MAZ_Lola_MS13_HP-Dd2_I34_iRBC_10h_R2.raw #COLLECTION CO:COLLECTION_SUMMARY Highly synchronous (within 4 h) late trophozoite stage parasites were CO:COLLECTION_SUMMARY magnetically purified with MACS LD columns (Miltenyi Biotec Inc., San Diego, CA, CO:COLLECTION_SUMMARY USA). Each sample was incubated for 10 hours with either labeled or unlabeled media, CO:COLLECTION_SUMMARY harvested by centrifugation, washed twice in PBS, and then suspended in 10 μl CO:COLLECTION_SUMMARY PBS (Life Technologies, Carlsbad, CA, USA). Polar metabolites were extracted CO:COLLECTION_SUMMARY using nine volumes of 74.9:24.9:0.2 (v/v/v) acetonitrile/methanol/formic acid CO:COLLECTION_SUMMARY containing stable isotope-labeled internal standards (0.2 ng/μL valine-d8 CO:COLLECTION_SUMMARY (Sigma Aldrich, St. Louis, MO, USA); and 0.2 ng/μL phenylalanine-d8 (Cambridge CO:COLLECTION_SUMMARY Isotope Laboratories, Tewksbury, MA, USA) and stored at −80°C prior to the CO:COLLECTION_SUMMARY metabolite profiling assays. CO:SAMPLE_TYPE Cultured cells CO:COLLECTION_LOCATION Harvard Chan School of Public Health, 665 Huntington Ave. Boston, MA 02115 CO:VOLUMEORAMOUNT_COLLECTED 100 uL CO:STORAGE_CONDITIONS -80℃ #TREATMENT TR:TREATMENT_SUMMARY Cultures were cultured in 5% human O+ hematocrit and maintained under standard TR:TREATMENT_SUMMARY conditions [RPMI 1640 (Life Technologies) supplemented with 28 mM NaHCO3 TR:TREATMENT_SUMMARY (Sigma), 25 mM HEPES (Sigma), 50 mg/ml hypoxanthine (Sigma), 25 μg/ml TR:TREATMENT_SUMMARY gentamycin (Sigma), and 0.5% AlbuMAX II (Life Technologies)] until preparation TR:TREATMENT_SUMMARY for treatment. In preparation for treatment, 25 mL synchronized parasites culture TR:TREATMENT_SUMMARY at ~5% parasitemia and 32-36hr staging at beginning of experiment were pelleted TR:TREATMENT_SUMMARY and resuspended in 4mL serum-free RPMI (Incomplete Media). Parasites were TR:TREATMENT_SUMMARY magnetically purified with an LD column (Miltenyi Biotec Inc., San Diego, CA, TR:TREATMENT_SUMMARY USA) and washed until the flow thru ran clear. The column was removed from the TR:TREATMENT_SUMMARY magnet and each sample eluted in 2mL incomplete RPMI. Samples were divided into TR:TREATMENT_SUMMARY two microfuge tubes, each receiving half (1mL) of the cell suspension. Cells TR:TREATMENT_SUMMARY were pelleted and resuspended in either incomplete RPMI (unlabeled) or our TR:TREATMENT_SUMMARY Triplex labeled RPMI media (RPMI media first prepared without proline, TR:TREATMENT_SUMMARY glutamine, or arginine and then supplemented with isotope labeled amino acids at TR:TREATMENT_SUMMARY regular RPMI concentrations: Pro+1 [0.17 mM], Arg+2 [0.38 mM], and Gln+5 [2.05 TR:TREATMENT_SUMMARY mM]). Parasites were incubated in labeled or unlabeled media for 10h at 37ºC TR:TREATMENT_SUMMARY under standard malaria gas mixture. Samples were harvested by centrifugation, TR:TREATMENT_SUMMARY washed twice, and then polar metabolites extracted. #SAMPLEPREP SP:SAMPLEPREP_SUMMARY Each sample was washed twice in PBS and then suspended in 10 μl PBS (Life SP:SAMPLEPREP_SUMMARY Technologies, Carlsbad, CA, USA). Polar metabolites were extracted using nine SP:SAMPLEPREP_SUMMARY volumes of 74.9:24.9:0.2 (v/v/v) acetonitrile/methanol/formic acid containing SP:SAMPLEPREP_SUMMARY stable isotope-labeled internal standards (0.2 ng/μL valine-d8 (Sigma Aldrich, SP:SAMPLEPREP_SUMMARY St. Louis, MO, USA); and 0.2 ng/μL phenylalanine-d8 (Cambridge Isotope SP:SAMPLEPREP_SUMMARY Laboratories, Tewksbury, MA, USA) and stored at −80°C prior to the metabolite SP:SAMPLEPREP_SUMMARY profiling assays. #CHROMATOGRAPHY CH:CHROMATOGRAPHY_SUMMARY Chromatography method 1 (HILIC-POS) CH:CHROMATOGRAPHY_TYPE HILIC CH:INSTRUMENT_NAME Shimadzu Nexera X2 CH:COLUMN_NAME Water Atlantis HILIC (150 x 2.1 mm, 3 μm) CH:SOLVENT_A 100% Water; 10 mM Ammonium formate; 0.1% Formic acid CH:SOLVENT_B 100% Acetonitrile; 0.1% Formic acid CH:FLOW_GRADIENT Chromatographic separation was performed using an isocratic elution at a flow CH:FLOW_GRADIENT rate of 250 μL/min with 5% mobile phase A (10 mM ammonium formate and 0.1% CH:FLOW_GRADIENT formic acid in water) for 1 minute. This was followed by a linear gradient to CH:FLOW_GRADIENT 40% mobile phase B (acetonitrile with 0.1% formic acid) over 10 minutes. At 10 CH:FLOW_GRADIENT minutes, the gradient was returned to initial isocratic conditions (5% mobile CH:FLOW_GRADIENT phase A) and held until 18 minutes, at which point MS acquisition was stopped. CH:FLOW_GRADIENT The column was equilibrated with 5% mobile phase A at a flow rate of CH:FLOW_GRADIENT 400 μL/min for 12 minutes, followed by a reduction to the initial flow rate CH:FLOW_GRADIENT of 250 μL/min for 2 minutes before the next injection. CH:FLOW_RATE 250 μL/min CH:COLUMN_TEMPERATURE 30°C CH:INTERNAL_STANDARD L-Phenylalanine-d8 (CIL, DLM-372-1), L-Valine-d8 (Sigma, 486027) #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 Mass spectroscopic (MS) analyses were performed by using electrospray ionization MS:MS_COMMENTS in the positive ion mode using full scan analysis over 70 to 800 m/z at 70 000 MS:MS_COMMENTS resolution and 3 Hz data acquisition rate. Other MS settings were as follows: MS:MS_COMMENTS sheath gas 40, sweep gas 2, spray voltage 3.5 kV, capillary temperature 350°C, MS:MS_COMMENTS S-lens RF 40, heater temperature 300°C, microscans 1, automatic gain control MS:MS_COMMENTS target 1e6, and maximum ion time 250 ms. Raw data were processed using MS:MS_COMMENTS TraceFinder 3.3 software (Thermo Fisher Scientific; Waltham, MA) and Progenesis MS:MS_COMMENTS QI (Nonlinear Dynamics; Newcastle upon Tyne, UK). Metabolite identities were MS:MS_COMMENTS confirmed using authentic reference standards or reference samples. #MS_METABOLITE_DATA MS_METABOLITE_DATA:UNITS peak areas MS_METABOLITE_DATA_START Samples Study2_uRBC_RBC_0h_R1 Study2_uRBC_RBC_0h_R2 Study2_uRBC_RBC_0h_R3 Study2_uRBC_RBC_0h_R4 Study2_uRBC_RBC_0h_R5 Study2_uRBC_RBC_0h_R6 Study2_uRBC_RBC_0h_R7 Study2_uRBC_RBC_0h_R8 Study2_uRBC_RBC_10h_R1 Study2_uRBC_RBC_10h_R2 Study2_uRBC_RBC_10h_R3 Study2_uRBC_RBC_10h_R4 Study2_uRBC_RBC_10h_R5 Study2_uRBC_RBC_10h_R6 Study2_uRBC_RBC_10h_R7 Study2_uRBC_RBC_10h_R8 Study2_Dd2_iRBC_10h_R1 Study2_Dd2_iRBC_10h_R2 Study2_Dd2_iRBC_10h_R3 Study2_Dd2∆ARG-C1_iRBC_10h_R1 Study2_Dd2∆ARG-C1_iRBC_10h_R2 Study2_Dd2∆ARG-C1_iRBC_10h_R3 Study2_Dd2∆OAT-C1_iRBC_10h_R1 Study2_Dd2∆OAT-C1_iRBC_10h_R2 Factors Sample source:uninfected RBC (uRBC) | Parasite_type:Control | Parasite_line:Control RBCs | Timepoint:0 h Sample source:uninfected RBC (uRBC) | Parasite_type:Control | Parasite_line:Control RBCs | Timepoint:0 h Sample source:uninfected RBC (uRBC) | Parasite_type:Control | Parasite_line:Control RBCs | Timepoint:0 h Sample source:uninfected RBC (uRBC) | Parasite_type:Control | Parasite_line:Control RBCs | Timepoint:0 h Sample source:uninfected RBC (uRBC) | Parasite_type:Control | Parasite_line:Control RBCs | Timepoint:0 h Sample source:uninfected RBC (uRBC) | Parasite_type:Control | Parasite_line:Control RBCs | Timepoint:0 h Sample source:uninfected RBC (uRBC) | Parasite_type:Control | Parasite_line:Control RBCs | Timepoint:0 h Sample source:uninfected RBC (uRBC) | Parasite_type:Control | Parasite_line:Control RBCs | Timepoint:0 h Sample source:uninfected RBC (uRBC) | Parasite_type:Control | Parasite_line:Control RBCs | Timepoint:10 h Sample source:uninfected RBC (uRBC) | Parasite_type:Control | Parasite_line:Control RBCs | Timepoint:10 h Sample source:uninfected RBC (uRBC) | Parasite_type:Control | Parasite_line:Control RBCs | Timepoint:10h Sample source:uninfected RBC (uRBC) | Parasite_type:Control | Parasite_line:Control RBCs | Timepoint:10 h Sample source:uninfected RBC (uRBC) | Parasite_type:Control | Parasite_line:Control RBCs | Timepoint:10 h Sample source:uninfected RBC (uRBC) | Parasite_type:Control | Parasite_line:Control RBCs | Timepoint:10 h Sample source:uninfected RBC (uRBC) | Parasite_type:Control | Parasite_line:Control RBCs | Timepoint:10 h Sample source:uninfected RBC (uRBC) | Parasite_type:Control | Parasite_line:Control RBCs | Timepoint:10 h Sample source:infected RBC (iRBC) | Parasite_type:Dd2 WT | Parasite_line:Dd2 | Timepoint:10 h Sample source:infected RBC (iRBC) | Parasite_type:Dd2 WT | Parasite_line:Dd2 | Timepoint:10 h Sample source:infected RBC (iRBC) | Parasite_type:Dd2 WT | Parasite_line:Dd2 | Timepoint:10h Sample source:infected RBC (iRBC) | Parasite_type:Dd2 AD7 | Parasite_line:Dd2∆ARG C1 | Timepoint:10 h Sample source:infected RBC (iRBC) | Parasite_type:Dd2 AD7 | Parasite_line:Dd2∆ARG C1 | Timepoint:10 h Sample source:infected RBC (iRBC) | Parasite_type:Dd2 AD7 | Parasite_line:Dd2∆ARG C1 | Timepoint:10 h Sample source:infected RBC (iRBC) | Parasite_type:Dd2 OD12 | Parasite_line:Dd2∆OAT C1 | Timepoint:10 h Sample source:infected RBC (iRBC) | Parasite_type:Dd2 OD12 | Parasite_line:Dd2∆OAT C1 | Timepoint:10 h phenylalanine-d8 229891523 211858717 222084296 230192704 207638104 193736311 218945879 233956091 221822519 195320318 221003778 220672310 203815789 212437918 226378721 216282679 214143070 214946819 240320118 236358660 213429167 228285616 247590026 250082835 valine-d8 112386158 97983017 103936586 116331277 111667706 90042198 108338854 116461324 113358569 99759957 113086182 120255448 108615988 105179554 104091188 100879674 116023681 113193652 115920717 111287092 120234251 111266279 121225700 113869262 1-methyladenosine 55218 95921 107877 244696 147486 107417 83234 302658 1-methylhistamine 1-methylnicotinamide 3571326 9123325 15044632 13173130 2946289 3150255 3022650 3376364 3500737 9624561 4659957 11028812 3453323 611854 3330161 4112781 699380 657892 678458 1087877 1177759 941749 687911 778606 1-pyrroline-5-carboxylate 631950 727626 816009 795978 480190 778384 611895 662219 799766 574965 674342 681757 708512 568695 373749 501905 528620 1-pyrroline-5-carboxylase[15]N 1-pyrroline-5-carboxylate[13]C1[15]N1 1-pyrroline-5-carboxylate[13]C5 2-deoxycytidine 3200901 2846189 525311 6929502 16632581 4988839 2639925 2658936 4308245 5-adenosylhomocysteine 37576 3187444 1778411 228396 3382496 3908916 4439539 1360752 2889416 3249943 5-aminolevulinic acid Study3_Dd2∆OATAPR-clone2_iRBC_10h_R2 5-hydroxytryptophan 146902 430350 231497 721834 48953 159063 1158969 73474 acetylcholine adenosine 4735669 10463047 9372180 6327959 4131605 8735267 6186600 5220018 3209170 9216287 3671930 4522564 4910329 12166197 6196688 5797087 10720910 3328013 12111978 19420224 14947529 8963572 10478154 10364248 ADMA 969045 1504314 964584 2354027 615654 780476 864914 1388356 1384397 1226007 402381 1471545 707871 25206063 792702 987228 40454586 7996298 52173038 203320334 70971111 45244525 43517462 69892581 alanine 4520423 8804069 6704163 12510975 4634616 5247418 5101267 4488168 8137343 10177265 2413059 10635751 5099425 9860896 5117486 5351076 11075245 3441587 12440903 29608184 16656398 15825649 5207352 12001498 allantoin 9202 alpha-glycerophosphocholine 98950389 278569458 61813179 90058650 126968954 127676084 151872383 126760949 109206162 267687110 15844809 78007428 144260788 145709674 155107746 147733098 124081433 28515825 157472060 223985300 226275120 96626758 113389875 123275878 anserine 295711 anthranilic acid 1055062 4803691 4529310 8292537 5983904 5400027 6919342 6920075 6334611 5111331 858865 6176079 3339886 3631238 3930472 6084624 2603516 3700783 2123333 7254677 2268299 1595477 4485690 arginine 677273265 2919457525 2262868276 2139881240 1595235246 1824783538 2123369026 1724723090 35479143 59229615 55450403 49313499 47790894 157439976 33720318 39846268 161145624 51897813 187059793 1938114288 802323694 918742310 180932290 558376555 arginine[15]N 9387053 40625846 31280378 28876617 22275203 25119644 28859464 24178288 2978123 11831990 8340538 5763776 9246231 13732910 9147107 7365427 12528139 4575252 11848936 39203066 25348143 20176852 16171377 23128260 arginine[13]C1[15]N1 12331108 19535675 21293155 20076309 19905736 21339925 17593240 18519921 507463867 2364350584 1542338013 998679826 1827610369 2120763397 1728426199 1481762555 2000676327 777758819 1813076404 2473399283 2822099794 1403093545 2723808461 3030444109 arginine [13]C5 argininosuccinate 228362 asparagine 19477526 58670481 56429147 60163084 34781022 32459621 39959010 38935566 18459207 49758578 28347587 40853327 41309423 20396263 38452215 36562245 29469946 14385968 24731468 39761140 36080387 25628335 14083706 30412700 aspartate 10154448 17110962 7998546 9460718 8937727 20594216 12925087 8184335 11691976 15994543 4933456 7599127 8737772 16635178 13719152 9746367 15871404 4240178 13311487 34545743 18286913 13547303 13838017 15521508 beta-alanine 1428278 2902189 2677957 3923325 1171543 2279440 1469627 1491004 3070259 739244 4089622 1471289 1796771 1620475 845040 betaine 2773953756 5416936593 4903889074 7209927294 3205191760 3717784146 3890626813 3630761084 2894637673 5272155716 1971626208 6358435302 3476342963 996267670 4394030814 3950219829 1132170977 1025501139 900363464 1247307082 1400866101 1318311743 909865346 1124995182 butyrobetaine carnitine 719785507 1803925771 7484551599 1864803998 1863364803 2104313832 1845342543 2535319592 794971351 1743155713 2440197800 1475504413 2189196558 103424804 2460587734 2978696903 79073353 76542735 64159638 331233864 136651182 102978545 63591545 150974650 C2 carnitine 843606537 2472741833 7262309315 2726289875 2112177325 2391398126 2382115017 2171890536 890522202 2393112406 2333578144 2235909242 2233521928 153254973 2870303585 2704277995 98900103 85110593 137500608 349170607 279710256 228409313 102521783 296920127 C3 carnitine 65359070 162807553 259939005 245687383 100460110 139257836 117767985 112449978 69285811 161464029 79067404 221696129 109802116 3816129 160786890 141629838 2882733 3768946 3028437 11079880 9408889 9387238 3652940 9936483 C3-DC-CH3 carnitine 16355151 48458193 38305114 59344445 21227683 17559020 17418180 23128223 18128006 47180084 8529752 44381455 24111346 3448293 20558133 27654670 4141198 2269935 3381694 11363060 10142517 8304712 2699227 5620920 C4 carnitine 6634113 15830691 25430422 51097031 13892517 14954718 12886348 14670851 5590685 16822563 6601040 46540837 15558800 1295151 18587719 21052811 477500 439903 1056909 1942414 1139968 997875 1017139 1756340 C4-OH carnitine 2962963 13436264 28667308 11381002 7159110 9445585 9653363 7503548 3237968 13543821 8603950 9296840 7724481 1406357 12132737 9297444 786793 1746807 3122049 2820192 1639505 1004195 2627069 C5 carnitine 4144916 11515140 15733794 22769837 8939353 10112707 9938115 9923611 4542702 11338394 4364543 20100732 10177586 723921 13286213 13141456 571784 540278 603717 1299350 1209959 1061242 642559 1282226 C5:1 carnitine C6 carnitine 3136076 7034988 5502068 3772313 7416714 9390240 8571282 6427471 3542720 8806186 3168388 5435381 8096986 10422504 10443537 123019 108235 208495 278412 292440 C7 carnitine C8 carnitine 493960 604445 381637 402792 666187 540830 461790 132766 707637 292002 475229 732731 841442 C10 carnitine 317621 963046 1280065 548030 798850 1124628 951024 776647 322418 1206538 388245 584762 955465 1385558 1423019 C10:2 carnitine C12 carnitine 388013 1986165 4002398 846215 1146132 2028602 1636804 1135829 534266 2120061 1025708 848008 1364649 58520 2224571 2131555 48352 70541 68271 93021 C12:1 carnitine 130890 540391 1072614 243638 343740 606060 410343 297030 137677 716588 313999 243602 402866 616623 537236 C14 carnitine 2868787 18024173 43561114 15632022 7293803 9579111 8028174 8139348 3419164 12084340 6808692 9520823 7529745 372664 11344706 11686612 266118 191414 254199 466698 568371 491574 473508 C14:1 carnitine 807458 5145937 10143178 2821568 1982893 3459922 2704315 2130660 954406 4251659 1979862 2029412 2240781 261554 3909664 3747649 192613 284603 191104 387906 192381 214314 261536 C14:2 carnitine 181823 1114313 1918131 570726 497523 841972 641391 594907 273696 1180320 458037 487154 557783 909784 996070 C16 carnitine 47337858 163610773 435218892 151697990 108913900 126638176 113231213 96498304 48858301 141057011 113900371 139352285 121575405 1368712 150666343 148622248 3001754 861984 2855441 1055566 4706184 2974357 C18 carnitine 54645467 158647252 303693635 115567219 95450241 99802757 97491249 75855299 68355897 153458900 100556038 118469440 99887054 6482859 125059913 114412273 6675455 7826827 5581634 14203913 10438971 13277475 4196509 11756375 C18:1 carnitine 74174448 214168619 430222289 231250461 133167726 160487045 136375852 129332071 76333851 210179621 138488107 211610876 145924459 3985063 187502660 180867388 3210594 5965755 3337617 6667448 5631280 10560002 2634000 7935682 C18:2 carnitine 11827347 33148339 74416968 43999187 25266579 30358833 21925060 29674221 13836412 33198371 22425540 36702045 27918982 31131334 37786909 447624 793634 C20 carnitine 682428 2427886 2970976 1544659 1178324 935396 806630 1292630 819345 2329418 643872 1464645 1224136 286436 914258 1596191 288633 300400 585297 519930 221958 250197 388670 C20:4 carnitine 3804194 13112820 30627049 10637730 8056226 9795476 7197205 11428942 3839975 12161749 11223728 9337039 8704584 10789321 14484022 161611 C26 carnitine 568067 2143077 2467349 1512332 1159294 874401 1239687 1229270 611804 2205605 523169 1434567 1122407 211900 986708 1646286 171984 179339 301530 445046 137309 188296 316230 cAMP 398875 238248 381352 234378 547214 112546 368672 255092 carnosine 313822 224461 60816 61868 78341 246585 78136 88120 choline 698997381 2256583308 2382121698 3817241478 1963433934 1504986783 1701499292 1788692786 858293445 2293688883 1050238271 3039069935 2167370846 2526278134 1643268989 2206722456 1951846629 1291662129 2555324002 3959968727 3083352553 1470613337 1834889050 1545664180 citrulline 4498017 9172577 7769661 10590953 5283154 4404607 4001227 7031653 4359159 9224220 2201175 9054107 5982945 466472 4324213 7402943 499331 229940 705839 1119465 547133 473032 674631 citrulline[15]N citrulline[13]C1[15]N1 citrulline[13]C5 cotinine 357024 524008 367288 287637 317916 605866 320663 653602 98130 720336 143670 374901 439353 272529 218866 261317 208095 392426 226829 239140 203374 559731 410707 creatine 1259037823 2943190729 3386437626 2460644922 1536563168 2174558335 2154687310 1741891545 1318922399 2895405105 1325626718 2138985825 1662196876 94505283 2553378689 2056079457 115855912 133860419 48779019 230758749 298718520 300987044 52732224 184519078 creatinine 24155241 66670659 127748382 43234808 36526264 82034193 78364167 90513209 20993502 83608489 47203442 39717733 40415286 3241293 125807426 111076623 2982696 2693145 2623046 3039450 4683646 2751402 2396964 6317329 cytosine 616677 1241927 1641841 1191234 645095 963847 1207334 1562323 515920 1025969 1072737 528709 859564 94840900 1184612 900445 90403804 2952998 132995837 166821352 160213334 24339861 71631837 62634247 dimethylglycine 5774538 6326023 6161790 6654652 5663932 5511083 5798432 5721180 6003618 5932794 6035252 6595938 5843038 4927304 5675075 5722894 5480653 5663916 5688939 6675812 5738292 5578824 5608371 5928694 GABA 762702 821437 882946 1248213 687911 662483 861029 759076 823250 988602 684580 1217722 747985 21588263 898246 665349 31964577 16752606 58494071 322335747 32289095 89465427 49463852 107504499 glucose 403979 1603190 1078285 698744 1161929 286950 1592047 1383076 346254 1185547 1262312 274168 1278215 211754 1358678 968182 809982 630949 353268 889035 477023 104179 778595 glutamate 51065324 92298910 43204704 32334151 85085722 68676833 95631130 71690975 32383004 44420216 21339611 22066336 38347858 53945074 33041671 35729883 67343463 30556896 48768552 77074475 73098113 63858664 40535006 86430035 glutamate[15]N 175914 255483 119889 259444 193067 298538 212879 108987 103382 53387 91268 106588 81961 196586 125462 195089 190342 182903 67204 202039 glutamate[13]C3[15]N1 glutamate[13]C5 105543 30582779 42150099 18542454 29816301 55956014 70918343 72856767 43975892 86957260 21302327 95446366 145278354 91872398 79430782 75838049 144531131 glutamine 76554935 389381611 376312055 360711722 287053421 236649779 312458438 224606463 10649502 23842565 16045836 21783117 16623863 19628332 12982860 18738664 14018923 6249446 7433547 12205987 29762116 17783114 7779637 17624109 glutamine[15]N 549665 2782574 2586813 2358984 1940769 1511056 2010904 1566140 99324 glutamine[13]C1[15]N1 glutamine[13]C5 611006 613782 280113 1715116 521193 192160 671628 77988339 372236376 345274811 163838753 376758857 99476865 253071881 236777206 252688295 142358785 97520409 45238755 309580129 120477501 63717711 171656227 glycine 5127633 16900228 23435532 15633051 9494637 10439781 9007426 10130287 7981946 14696945 5996075 11105695 12712761 3395005 11252155 12416774 4865979 1191591 4156642 10314980 4569716 4896537 1928509 4224721 histamine histidine 58910368 237612986 178350502 204718884 102568228 107540855 137118902 122493101 75112372 229626330 87796461 147231716 126584035 101252144 133560606 123187973 137403568 60051994 195008651 423412163 162426890 213868914 67648796 258656646 homocysteine 343361 92133 298923 901615 343681 275647 isoleucine 69135153 460338363 453045400 584002876 283214073 261352385 340081791 258601256 44767622 416338926 242496485 263806076 348262867 113488919 252740196 299305261 233064716 87925819 102362607 42987721 325608944 129001939 64976898 154870290 kynurenic acid 253727 158738 85603 170944 126527 106056 179181 187185 396939 leucine 62461442 389987469 373446188 498577067 268378558 251632514 332188654 239424702 76988408 361576969 221697517 238333606 323526930 138014814 236117922 287039802 276601640 96701622 154021762 146262535 366122245 177825480 87093987 231263093 lysine 24510481 215200483 143090541 183315251 64585393 67909336 96252000 86377840 27182609 156528165 72230249 67659392 82616797 145478229 82434888 63505498 342148947 48130616 276183025 542923263 406373874 247646104 1427511558 2498701141 methionine 13778661 95720169 76437215 111284892 47790799 44470610 60136826 48260009 13337269 78516659 39162367 46176196 59826504 10882933 45577735 52692157 33233357 13323473 12200551 12918863 36821730 19310022 6700634 18423934 methionine sulfoxide 1566078 3723411 11253527 6759769 3018854 3341341 3652047 3585908 2299447 3581921 3587673 3051425 4046631 1104556 3098258 3052456 1880835 1365847 1091489 1645595 2748431 1546637 772704 1777156 methylthioadenosine 719181 4450261 10382535 3359071 2411489 3808568 6502391 4281074 990418 5147931 3033393 3056343 2636263 65706784 7021775 5024343 27053680 1999712 68250503 19421865 62969073 10056254 27069046 73332097 N-carbamoyl-beta-alanine niacinamide 28543994 144266440 158512315 101144858 62001822 68295304 88152141 63743259 24967408 108019582 81361828 29259243 72115143 32234026 65206284 55575025 64626446 34289820 41640974 63130016 72468836 33145546 23760077 50248661 NMMA 466332 935474 577239 1154635 306768 423218 603162 1180328 1099101 640065 221965 672616 645122 5631018 502312 674998 13223741 2048598 15406968 74796157 26129278 23882153 10453255 22289895 ornithine 28909757 147955932 118158983 93514322 64229817 64151593 92328537 71899942 9373570 3979840 904781 7302031 3044171 2289542 3239449 3424098 2897184 1030349 3530227 9187651 3411141 3018320 112696936 210672417 ornithine[15]N 173436 950522 785170 635417 312642 432850 556532 398796 200543 649661 375746 244343 370130 354895 163586 1734536 2776351 ornithine[13]C1[15]N1 478121 235104 1106497 31360107 146358881 21055190 71419526 71108851 22551298 93511107 85517281 17835466 4348406 20187594 23479844 20701881 13853759 248580181 262429063 ornithine [13]C5 phenylalanine 27618551 156948583 174236295 217868527 90696381 91462402 116285440 96287128 33208414 110758147 77128523 86280616 106684896 55422282 82256951 105969077 99512443 37869234 69874280 78096374 113740795 82981429 34761772 104230569 phosphocholine 15601151 29120440 61440029 56875975 22097334 27633306 32287627 35491811 47584834 80825205 31627712 52387203 43400894 5107054566 37936468 24788745 3465904447 694201801 5148070825 7958762390 7561212744 2544270590 4422282687 2739967117 phosphoethanolamine 3053896 715817 37850859 30838768 2398163 62111498 91941427 75903048 17938611 55968349 47558402 pipecolic acid 788075 922643 1088486 1909680 1626954 1306153 79572378 981335 917871 150001528 17565276 153503709 622495897 209432171 106748063 3262766 837431 pipecolic acid[15]N 409766 382193 2014163 588297 411792 pipecholic acid[13]C1[15]N1 pipecolic acid [13]C5 proline 188342446 819522716 661611058 804155936 530247668 500301094 666293745 446283950 63945199 90265522 29915461 109066661 48025232 84829188 57911512 49207516 124994679 25119959 128139332 267220844 142790297 91776684 357961760 98698632 proline[15]N 1225882 2786058 3167617 2967598 3289179 2241383 2445762 2178506 179285276 741696154 486578476 424981000 535964489 147698137 507010576 389976625 307904515 146798711 140367550 90362958 415461311 198847991 102749880 188475569 proline[13]C1[15]N1 137073 9181837 37466101 24693571 21698468 27251240 104414303 26857882 20608363 77355884 10292555 107044315 108504924 61723589 24604665 5011074 9604910 proline [13]C5 putrescine 1325130 1431536 1241292 2471674 1833374 1151200 1763565 3092133 1669947 1640781 1060265 3048437 2627351 53132617 2262621 1392216 67099274 24035797 61500110 66405523 62642662 34767560 125403558 148223228 pyroglutamic acid s-adenosylmethionine 495338 2424336 2573395 1720642 909865 1454655 1580932 826165 719070 2688291 892322 1828473 1418682 68334183 1748818 1103559 24106061 4037962 36817161 17696241 51863312 12020901 37640477 26425811 sarcosine SDMA 262615 520539 395731 1124489 159269 261972 272740 362324 404120 480404 70524 819965 218657 3600330 251007 276271 8215295 1157578 9507841 40259458 15054142 8556225 7044861 15951776 serine 3596606 6510143 5576720 6887790 4575635 4744451 5677756 5518873 5231797 6166571 5303101 4653961 5651179 2495779 5162840 4722919 5120154 3332946 2690125 3474616 4838442 4107775 1874059 4107175 spermidine 348124946 1602536897 1262758430 1195935639 846046268 1145301369 1259239898 1253398532 827449930 2744934582 729727084 1369319723 1279724060 7039504868 1462764390 1076998416 7757123339 2588340931 7978201986 8807007226 7069951769 5573994925 7254286481 8285544956 taurine 12145752 37836320 47049670 42788565 20002296 22954875 24775177 23502912 12621692 37096590 11189874 34927045 23059466 1046819 28091972 29713330 699880 1078309 683941 2438397 1912693 1500149 715649 1410229 thiamine 44494216 239953817 206478908 201252722 174256189 151061214 215822028 128435667 62646706 266437407 156417901 138822448 202098937 300272623 175740331 151204900 430684120 104330828 479329815 708170489 541181046 309155077 264427349 459085261 threonine 7626249 19988423 11205030 18567965 10310488 10839932 13054514 10137518 9370748 16189141 11349204 9911221 13409707 6588646 9901607 8279128 14318026 6127834 8466510 14079142 16284376 11340107 6157888 11889474 thymidine trans-hydroxyproline 32400957 105500205 96499306 106099729 60827570 59805038 67258231 63769621 32235718 91584107 47594311 60068135 64448376 24380187 64785177 60018695 41424170 23250287 21497343 20285288 53697133 31702295 21067835 31430421 trans-hydroxyproline[15]N trans-hydroxyproline[13]C1[15]N1 trans-hydroxyproline [13]C5 trimethylamine-N-oxide 6469370 8489095 26645593 17592400 7163795 6443846 4867807 8214434 6865695 9039171 7166012 14426634 6987834 1195777 7081956 9812104 599803 609597 889437 581274 785430 587452 1036787 1088122 tryptophan 10399922 53526179 50253278 60991711 25051089 25715470 32850962 33233098 10974163 39455229 16717002 27075946 30682124 12666922 28313715 30570126 22036643 8100355 18055335 21378360 27734868 20094984 8678912 24611873 tyrosine 11891913 54528152 51905182 57653261 10169140 10317667 12311031 25109553 6090060 15368515 7250179 11521628 12240510 9318781 11305590 11954590 12751446 3326135 11884383 17616486 20487542 8444324 5392471 13597176 valine 22034014 79808902 74557268 96482335 50330942 43343173 54352828 47124128 27422703 68649118 44537968 50831283 58376576 36103381 44705650 48581543 64046950 29176621 44410154 57426594 78834100 47606583 26652827 55119138 xanthosine 1985431 729458 3115710 13474998 1502906 408989 1058436 1129365 MS_METABOLITE_DATA_END #METABOLITES METABOLITES_START metabolite_name Formula m/z RT phenylalanine-d8 C9H3NO2D8 174.1365 6.74 valine-d8 C5H3NO2D8 126.1365 7.44 1-methyladenosine C11H15N5O4 282.1197 7.74 1-methylhistamine C6H11N3 126.1026 NA 1-methylnicotinamide C7H9N2O+ 137.0715 8.28 1-pyrroline-5-carboxylate C5H7NO2 114.0549 7.87 1-pyrroline-5-carboxylase[15]N C5H7[15]NO2 115.0520 7.87 1-pyrroline-5-carboxylate[13]C1[15]N1 [13]CC4H7[15]NO2 116.0553 7.87 1-pyrroline-5-carboxylate[13]C5 [13]C5H7NO2 119.0717 7.87 2-deoxycytidine C9H13N3O4 228.0979 6.03 5-adenosylhomocysteine C14H20N6O5S 385.1289 8.13 5-aminolevulinic acid C5H9NO3 132.0655 NA 5-hydroxytryptophan C11H12N2O3 221.0921 6.53 acetylcholine C7H16NO2 146.1181 NA adenosine C10H13N5O4 268.1040 5.01 ADMA C8H18N4O2 203.1503 9.80 alanine C3H7NO2 90.0550 7.79 allantoin C4H6N4O3 159.0513 3.49 alpha-glycerophosphocholine C8H20NO6P 258.1101 10.42 anserine C10H16N4O3 241.1295 10.52 anthranilic acid C7H7NO2 138.0550 1.86 arginine C6H14N4O2 175.1190 9.17 arginine[15]N C6H14[15]N1N3O2 176.1159 9.17 arginine[13]C1[15]N1 [13]CC5H14[15]N1N3O2 177.1193 9.17 arginine [13]C5 [13]C5CH14N4O2 180.1357 9.17 argininosuccinate C10H18N4O6 291.1299 9.30 asparagine C4H8N2O3 133.0608 7.88 aspartate C4H7NO4 134.0448 7.85 beta-alanine C3H7NO2 90.0550 7.97 betaine C5H11NO2 118.0863 8.98 butyrobetaine C7H16NO2 146.1176 NA carnitine C7H15NO3 162.1125 8.80 C2 carnitine C9H17NO4 204.1230 8.67 C3 carnitine C10H19NO4 218.1387 8.32 C3-DC-CH3 carnitine C11H19NO6 262.1285 8.52 C4 carnitine C11H21NO4 232.1543 8.03 C4-OH carnitine C11H21NO5 248.1493 8.84 C5 carnitine C12H23NO4 246.1700 7.77 C5:1 carnitine C12H21NO4 244.1543 NA C6 carnitine C13H25NO4 260.1856 7.56 C7 carnitine C14H27NO4 274.2013 NA C8 carnitine C15H29NO4 288.2169 7.35 C10 carnitine C17H33NO4 316.2482 7.14 C10:2 carnitine C17H29NO4 312.2169 NA C12 carnitine C19H37NO4 344.2795 6.96 C12:1 carnitine C19H35NO4 342.2639 6.98 C14 carnitine C21H41NO4 372.3108 6.80 C14:1 carnitine C21H39NO4 370.2952 6.80 C14:2 carnitine C21H37NO4 368.2795 6.87 C16 carnitine C23H45NO4 400.3421 6.69 C18 carnitine C25H49NO4 428.3734 6.57 C18:1 carnitine C25H47NO4 426.3578 6.59 C18:2 carnitine C25H45NO4 424.3421 6.65 C20 carnitine C27H53NO4 456.4047 6.47 C20:4 carnitine C27H45NO4 448.3421 6.55 C26 carnitine C33H65NO4 540.4986 6.27 cAMP C10H12N5O6P 330.0598 6.97 carnosine C9H14N4O3 227.1139 9.79 choline C5H14NO 104.1070 8.34 citrulline C6H13N3O3 176.1030 8.33 citrulline[15]N C6H14[15]N1N3O2 177.1000 8.33 citrulline[13]C1[15]N1 [13]C1C5H14[15]N1N3O2 178.1033 8.33 citrulline[13]C5 [13]C5C1H14N4O2 177.1063 8.33 cotinine C10H12N2O 177.1022 5.15 creatine C4H9N3O2 132.0768 8.30 creatinine C4H7N3O 114.0662 6.50 cytosine C4H5N3O 112.0505 5.88 dimethylglycine C4H9NO2 104.0706 8.49 GABA C4H9NO2 104.0706 7.55 glucose C6H12O6 181.0707 4.73 glutamate C5H9NO4 148.0604 7.57 glutamate[15]N C5H9[15]NO4 149.0574 7.57 glutamate[13]C3[15]N1 [13]C3C2H9[15]NO4 150.0608 7.56 glutamate[13]C5 [13]C5H9NO4 153.0772 7.57 glutamine C5H10N2O3 147.0764 8.01 glutamine[15]N C5H10[15]N1N1O3 148.0734 8.01 glutamine[13]C1[15]N1 [13]C1C4H10[15]N1N1O3 149.0768 8.01 glutamine[13]C5 [13]C5H10N2O3 152.0932 8.01 glycine C2H5NO2 76.0393 7.90 histamine C5H9N3 112.0869 NA histidine C6H9N3O2 156.0768 9.25 homocysteine C4H9NO2S 136.0427 7.03 isoleucine C6H13NO2 132.1019 7.12 kynurenic acid C10H7NO3 190.0499 5.24 leucine C6H13NO2 132.1019 6.99 lysine C6H14N2O2 147.1128 9.39 methionine C5H11NO2S 150.0583 7.05 methionine sulfoxide C5H11NO3S 166.0532 8.62 methylthioadenosine C11H15N5O3S 298.0968 4.24 N-carbamoyl-beta-alanine C4H8N2O3 133.0608 NA niacinamide C6H6N2O 123.0553 3.78 NMMA C7H16N4O2 189.1346 9.39 ornithine C5H12N2O2 133.0972 9.28 ornithine[15]N C5H12[15]N1N1O2 134.0941 9.28 ornithine[13]C1[15]N1 [13]CC4H12[15]N1N1O2 135.0975 9.28 ornithine [13]C5 [13]C5H12N2O2 138.1139 9.28 phenylalanine C9H11NO2 166.0863 6.73 phosphocholine C5H15NO4P 184.0733 11.08 phosphoethanolamine C2H8NO4P 142.0264 8.92 pipecolic acid C6H11NO2 130.0863 8.00 pipecolic acid[15]N C6H11[15]NO2 131.0832 8.00 pipecholic acid[13]C1[15]N1 [13]CC5H11[15]NO2 132.0866 8.00 pipecolic acid [13]C5 [13]C5CH11NO2 135.1030 8.00 proline C5H9NO2 116.0706 8.12 proline[15]N C5H9[15]NO2 117.0676 8.12 proline[13]C1[15]N1 [13]CC4H9[15]NO2 118.0710 8.12 proline [13]C5 [13]C5H9NO2 121.0874 8.12 putrescine C4H12N2 89.1073 9.45 pyroglutamic acid C5H7NO3 130.0499 NA s-adenosylmethionine C15H23N6O5S 399.1451 10.16 sarcosine C3H7NO2 90.0550 NA SDMA C8H18N4O2 203.1503 9.69 serine C3H7NO3 106.0499 7.63 spermidine C7H19N3 146.1652 10.70 taurine C2H7NO3S 126.0219 6.05 thiamine C12H17N4OS 265.1118 9.86 threonine C4H9NO3 120.0655 7.58 thymidine C10H14N2O5 243.0976 NA trans-hydroxyproline C5H9NO3 132.0655 7.87 trans-hydroxyproline[15]N C5H9[15]NO3 133.0625 7.87 trans-hydroxyproline[13]C1[15]N1 [13]CC4H9[15]NO3 134.0659 7.87 trans-hydroxyproline [13]C5 [13]C5H9NO3 137.0823 7.87 trimethylamine-N-oxide C3H9NO 76.0757 8.11 tryptophan C11H12N2O2 205.0972 6.52 tyrosine C9H11NO3 182.0812 6.82 valine C5H11NO2 118.0863 7.43 xanthosine C10H12N4O6 285.0830 4.33 METABOLITES_END #END