#METABOLOMICS WORKBENCH cclish_20250922_115218 DATATRACK_ID:6469 STUDY_ID:ST004244 ANALYSIS_ID:AN007065 PROJECT_ID:PR002663 VERSION 1 CREATED_ON September 22, 2025, 12:01 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 Parasites with a disrupted arginine to proline pathway can still mount an APR ST:STUDY_SUMMARY Plasmodium falciparum evades the antimalarial activity of proline-competitive ST:STUDY_SUMMARY prolyl-tRNA synthetase (PfProRS) inhibitors, such as halofuginone (HFG), by a ST:STUDY_SUMMARY unique resistance mechanism termed the Adaptive Proline Response (APR). The APR ST:STUDY_SUMMARY is characterized by a marked elevation of intracellular proline following drug ST:STUDY_SUMMARY exposure. Contrary to initial expectations, the APR is not mediated by ST:STUDY_SUMMARY alterations in canonical proline metabolic pathways involving arginase (PfARG) ST:STUDY_SUMMARY and ornithine aminotransferase (PfOAT). Instead, we identified loss-of-function ST:STUDY_SUMMARY mutations in the Apicomplexan Amino acid Transporter 2 (PfApiAT2) as the primary ST:STUDY_SUMMARY genetic driver of this resistance phenotype. Importantly, reversion of these ST:STUDY_SUMMARY mutations to wildtype effectively suppresses the APR, establishing PfApiAT2 as ST:STUDY_SUMMARY the molecular determinant of this novel resistance mechanism. The elucidation of ST:STUDY_SUMMARY the APR significantly advances our understanding of antimalarial drug ST:STUDY_SUMMARY resistance. By delineating the role of PfApiAT2 in this process, we establish ST:STUDY_SUMMARY critical insights for the development of strategies to circumvent PfProRS ST:STUDY_SUMMARY inhibitor resistance for future antimalarial therapies. In this study, we use a ST:STUDY_SUMMARY custom Triplex labeled media, containing uniquely stable isotope labeled proline ST:STUDY_SUMMARY (+1), arginine (+2), and glutamine (+5) to validate the arginine to proline ST:STUDY_SUMMARY biosynthetic pathway as major driver for the elevated proline levels in APR ST:STUDY_SUMMARY parasites. Labeled proline levels were assessed in Dd2-OAT KO parasites ST:STUDY_SUMMARY (parasites with a disrupted ornithine amino-transferase locus) and Dd2-OAT KO ST:STUDY_SUMMARY parasites exposed to HFG to induce the APR. Induced/APR Dd2-OAT KO parasites ST:STUDY_SUMMARY were analyzed as a bulk population after drug treatment as well as individual ST:STUDY_SUMMARY clonal populations (clones 1, 2, 3) isolated from the bulk population by ST:STUDY_SUMMARY limiting dilution. Uninfected RBCs (uRBCs) were run as a 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 6 ST:TOTAL_SUBJECTS 36 ST:STUDY_COMMENTS Study 3 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 - Study3_uRBCs_RBC_10h_R1 Sample source:uninfected RBC (uRBC) | Parasite_type:uninfected RBCs | Parasite_line:Control RBCs | Timepoint:10 h Replicate=1; Tracer=15N Pro 15N,13C Arg 5C13 Gln; Date Generated=3/28/2021; RAW_FILE_NAME(Raw_file_name)=67_MAZ_Akansha_HP-67.raw SUBJECT_SAMPLE_FACTORS - Study3_uRBCs_RBC_10h_R2 Sample source:uninfected RBC (uRBC) | Parasite_type:uninfected RBCs | Parasite_line:Control RBCs | Timepoint:10 h Replicate=2; Tracer=15N Pro 15N,13C Arg 5C13 Gln; Date Generated=3/30/2021; RAW_FILE_NAME(Raw_file_name)=95_MAZ_Akansha_HP-95.raw SUBJECT_SAMPLE_FACTORS - Study3_uRBCs_RBC_10h_R3 Sample source:uninfected RBC (uRBC) | Parasite_type:uninfected RBCs | Parasite_line:Control RBCs | Timepoint:10 h Replicate=3; Tracer=15N Pro 15N,13C Arg 5C13 Gln; Date Generated=4/1/2021; RAW_FILE_NAME(Raw_file_name)=123_MAZ_Akansha_HP-123.raw SUBJECT_SAMPLE_FACTORS - Study3_uRBCs_RBC_10h_R4 Sample source:uninfected RBC (uRBC) | Parasite_type:uninfected RBCs | Parasite_line:Control RBCs | Timepoint:10 h Replicate=4; Tracer=15N Pro 15N,13C Arg 5C13 Gln; Date Generated=4/5/2021; RAW_FILE_NAME(Raw_file_name)=151_MAZ_Akansha_HP-151.raw SUBJECT_SAMPLE_FACTORS - Study3_uRBCs_RBC_10h_R5 Sample source:uninfected RBC (uRBC) | Parasite_type:uninfected RBCs | Parasite_line:Control RBCs | Timepoint:10 h Replicate=5; Tracer=15N Pro 15N,13C Arg 5C13 Gln; Date Generated=4/7/2021; RAW_FILE_NAME(Raw_file_name)=0179_MAZ_Akansha_HP-180.raw SUBJECT_SAMPLE_FACTORS - Study3_uRBCs_RBC_10h_R6 Sample source:uninfected RBC (uRBC) | Parasite_type:uninfected RBCs | Parasite_line:Control RBCs | Timepoint:10 h Replicate=6; Tracer=15N Pro 15N,13C Arg 5C13 Gln; Date Generated=4/9/2021; RAW_FILE_NAME(Raw_file_name)=0207_MAZ_Akansha_HP-208.raw SUBJECT_SAMPLE_FACTORS - Study3_Dd2∆OAT-C1_iRBC_10h_R1 Sample source:infected RBC (iRBC) | Parasite_type:del OAT D12 | Parasite_line:Dd2∆OAT C1 | Timepoint:10 h Replicate=1; Tracer=15N Pro 15N,13C Arg 5C13 Gln; Date Generated=3/28/2021; RAW_FILE_NAME(Raw_file_name)=0047_MAZ_Akansha_HP-47.raw SUBJECT_SAMPLE_FACTORS - Study3_Dd2∆OAT-C1_iRBC_10h_R2 Sample source:infected RBC (iRBC) | Parasite_type:del OAT D12 | Parasite_line:Dd2∆OAT C1 | Timepoint:10 h Replicate=2; Tracer=15N Pro 15N,13C Arg 5C13 Gln; Date Generated=3/30/2021; RAW_FILE_NAME(Raw_file_name)=75_MAZ_Akansha_HP-75.raw SUBJECT_SAMPLE_FACTORS - Study3_Dd2∆OAT-C1_iRBC_10h_R3 Sample source:infected RBC (iRBC) | Parasite_type:del OAT D12 | Parasite_line:Dd2∆OAT C1 | Timepoint:10 h Replicate=3; Tracer=15N Pro 15N,13C Arg 5C13 Gln; Date Generated=4/1/2021; RAW_FILE_NAME(Raw_file_name)=103_MAZ_Akansha_HP-103.raw SUBJECT_SAMPLE_FACTORS - Study3_Dd2∆OAT-C1_iRBC_10h_R4 Sample source:infected RBC (iRBC) | Parasite_type:del OAT D12 | Parasite_line:Dd2∆OAT C1 | Timepoint:10 h Replicate=4; Tracer=15N Pro 15N,13C Arg 5C13 Gln; Date Generated=4/5/2021; RAW_FILE_NAME(Raw_file_name)=131_MAZ_Akansha_HP-131.raw SUBJECT_SAMPLE_FACTORS - Study3_Dd2∆OAT-C1_iRBC_10h_R5 Sample source:infected RBC (iRBC) | Parasite_type:del OAT D12 | Parasite_line:Dd2∆OAT C1 | Timepoint:10 h Replicate=5; Tracer=15N Pro 15N,13C Arg 5C13 Gln; Date Generated=4/7/2021; RAW_FILE_NAME(Raw_file_name)=0159_MAZ_Akansha_HP-160.raw SUBJECT_SAMPLE_FACTORS - Study3_Dd2∆OAT-C1_iRBC_10h_R6 Sample source:infected RBC (iRBC) | Parasite_type:del OAT D12 | Parasite_line:Dd2∆OAT C1 | Timepoint:10 h Replicate=6; Tracer=15N Pro 15N,13C Arg 5C13 Gln; Date Generated=4/9/2021; RAW_FILE_NAME(Raw_file_name)=0187_MAZ_Akansha_HP-188.raw SUBJECT_SAMPLE_FACTORS - Study3_Dd2∆OATAPR-bulk_iRBC_10h_R1 Sample source:infected RBC (iRBC) | Parasite_type:del OAT 6491 bulk | Parasite_line:Dd2∆OATAPR2 bulk | Timepoint:10 h Replicate=1; Tracer=15N Pro 15N,13C Arg 5C13 Gln; Date Generated=3/28/2021; RAW_FILE_NAME(Raw_file_name)=0051_MAZ_Akansha_HP-51.raw SUBJECT_SAMPLE_FACTORS - Study3_Dd2∆OATAPR-bulk_iRBC_10h_R2 Sample source:infected RBC (iRBC) | Parasite_type:del OAT 6491 bulk | Parasite_line:Dd2∆OATAPR2 bulk | Timepoint:10 h Replicate=2; Tracer=15N Pro 15N,13C Arg 5C13 Gln; Date Generated=3/30/2021; RAW_FILE_NAME(Raw_file_name)=79_MAZ_Akansha_HP-79.raw SUBJECT_SAMPLE_FACTORS - Study3_Dd2∆OATAPR-bulk_iRBC_10h_R3 Sample source:infected RBC (iRBC) | Parasite_type:del OAT 6491 bulk | Parasite_line:Dd2∆OATAPR2 bulk | Timepoint:10 h Replicate=3; Tracer=15N Pro 15N,13C Arg 5C13 Gln; Date Generated=4/1/2021; RAW_FILE_NAME(Raw_file_name)=107_MAZ_Akansha_HP-107.raw SUBJECT_SAMPLE_FACTORS - Study3_Dd2∆OATAPR-bulk_iRBC_10h_R4 Sample source:infected RBC (iRBC) | Parasite_type:del OAT 6491 bulk | Parasite_line:Dd2∆OATAPR2 bulk | Timepoint:10 h Replicate=4; Tracer=15N Pro 15N,13C Arg 5C13 Gln; Date Generated=4/5/2021; RAW_FILE_NAME(Raw_file_name)=135_MAZ_Akansha_HP-135.raw SUBJECT_SAMPLE_FACTORS - Study3_Dd2∆OATAPR-bulk_iRBC_10h_R5 Sample source:infected RBC (iRBC) | Parasite_type:del OAT 6491 bulk | Parasite_line:Dd2∆OATAPR2 bulk | Timepoint:10 h Replicate=5; Tracer=15N Pro 15N,13C Arg 5C13 Gln; Date Generated=4/7/2021; RAW_FILE_NAME(Raw_file_name)=0163_MAZ_Akansha_HP-164.raw SUBJECT_SAMPLE_FACTORS - Study3_Dd2∆OATAPR-bulk_iRBC_10h_R6 Sample source:infected RBC (iRBC) | Parasite_type:del OAT 6491 bulk | Parasite_line:Dd2∆OATAPR2 bulk | Timepoint:10 h Replicate=6; Tracer=15N Pro 15N,13C Arg 5C13 Gln; Date Generated=4/9/2021; RAW_FILE_NAME(Raw_file_name)=0191_MAZ_Akansha_HP-192.raw SUBJECT_SAMPLE_FACTORS - Study3_Dd2∆OATAPR-clone1_iRBC_10h_R1 Sample source:infected RBC (iRBC) | Parasite_type:del OAT D12 clone B9 | Parasite_line:Dd2∆OATAPR2 clone 1 | Timepoint:10 h Replicate=1; Tracer=15N Pro 15N,13C Arg 5C13 Gln; Date Generated=3/28/2021; RAW_FILE_NAME(Raw_file_name)=55_MAZ_Akansha_HP-55.raw SUBJECT_SAMPLE_FACTORS - Study3_Dd2∆OATAPR-clone1_iRBC_10h_R2 Sample source:infected RBC (iRBC) | Parasite_type:del OAT D12 clone B9 | Parasite_line:Dd2∆OATAPR2 clone 1 | Timepoint:10 h Replicate=2; Tracer=15N Pro 15N,13C Arg 5C13 Gln; Date Generated=3/30/2021; RAW_FILE_NAME(Raw_file_name)=83_MAZ_Akansha_HP-83.raw SUBJECT_SAMPLE_FACTORS - Study3_Dd2∆OATAPR-clone1_iRBC_10h_R3 Sample source:infected RBC (iRBC) | Parasite_type:del OAT D12 clone B9 | Parasite_line:Dd2∆OATAPR2 clone 1 | Timepoint:10 h Replicate=3; Tracer=15N Pro 15N,13C Arg 5C13 Gln; Date Generated=4/1/2021; RAW_FILE_NAME(Raw_file_name)=111_MAZ_Akansha_HP-111.raw SUBJECT_SAMPLE_FACTORS - Study3_Dd2∆OATAPR-clone1_iRBC_10h_R4 Sample source:infected RBC (iRBC) | Parasite_type:del OAT D12 clone B9 | Parasite_line:Dd2∆OATAPR2 clone 1 | Timepoint:10 h Replicate=4; Tracer=15N Pro 15N,13C Arg 5C13 Gln; Date Generated=4/5/2021; RAW_FILE_NAME(Raw_file_name)=139_MAZ_Akansha_HP-139.raw SUBJECT_SAMPLE_FACTORS - Study3_Dd2∆OATAPR-clone1_iRBC_10h_R5 Sample source:infected RBC (iRBC) | Parasite_type:del OAT D12 clone B9 | Parasite_line:Dd2∆OATAPR2 clone 1 | Timepoint:10 h Replicate=5; Tracer=15N Pro 15N,13C Arg 5C13 Gln; Date Generated=4/7/2021; RAW_FILE_NAME(Raw_file_name)=0167_MAZ_Akansha_HP-168.raw SUBJECT_SAMPLE_FACTORS - Study3_Dd2∆OATAPR-clone1_iRBC_10h_R6 Sample source:infected RBC (iRBC) | Parasite_type:del OAT D12 clone B9 | Parasite_line:Dd2∆OATAPR2 clone 1 | Timepoint:10 h Replicate=6; Tracer=15N Pro 15N,13C Arg 5C13 Gln; Date Generated=4/9/2021; RAW_FILE_NAME(Raw_file_name)=0195_MAZ_Akansha_HP-196.raw SUBJECT_SAMPLE_FACTORS - Study3_Dd2∆OATAPR-clone2_iRBC_10h_R1 Sample source:infected RBC (iRBC) | Parasite_type:del OAT D12 clone A6 | Parasite_line:Dd2∆OATAPR2 clone 2 | Timepoint:10 h Replicate=1; Tracer=15N Pro 15N,13C Arg 5C13 Gln; Date Generated=3/28/2021; RAW_FILE_NAME(Raw_file_name)=59_MAZ_Akansha_HP-59.raw SUBJECT_SAMPLE_FACTORS - Study3_Dd2∆OATAPR-clone2_iRBC_10h_R2 Sample source:infected RBC (iRBC) | Parasite_type:del OAT D12 clone A6 | Parasite_line:Dd2∆OATAPR2 clone 2 | Timepoint:10 h Replicate=2; Tracer=15N Pro 15N,13C Arg 5C13 Gln; Date Generated=3/30/2021; RAW_FILE_NAME(Raw_file_name)=87_MAZ_Akansha_HP-87.raw SUBJECT_SAMPLE_FACTORS - Study3_Dd2∆OATAPR-clone2_iRBC_10h_R3 Sample source:infected RBC (iRBC) | Parasite_type:del OAT D12 clone A6 | Parasite_line:Dd2∆OATAPR2 clone 2 | Timepoint:10 h Replicate=3; Tracer=15N Pro 15N,13C Arg 5C13 Gln; Date Generated=4/1/2021; RAW_FILE_NAME(Raw_file_name)=115_MAZ_Akansha_HP-115.raw SUBJECT_SAMPLE_FACTORS - Study3_Dd2∆OATAPR-clone2_iRBC_10h_R4 Sample source:infected RBC (iRBC) | Parasite_type:del OAT D12 clone A6 | Parasite_line:Dd2∆OATAPR2 clone 2 | Timepoint:10 h Replicate=4; Tracer=15N Pro 15N,13C Arg 5C13 Gln; Date Generated=4/5/2021; RAW_FILE_NAME(Raw_file_name)=143_MAZ_Akansha_HP-143.raw SUBJECT_SAMPLE_FACTORS - Study3_Dd2∆OATAPR-clone2_iRBC_10h_R5 Sample source:infected RBC (iRBC) | Parasite_type:del OAT D12 clone A6 | Parasite_line:Dd2∆OATAPR2 clone 2 | Timepoint:10 h Replicate=5; Tracer=15N Pro 15N,13C Arg 5C13 Gln; Date Generated=4/7/2021; RAW_FILE_NAME(Raw_file_name)=0171_MAZ_Akansha_HP-172.raw SUBJECT_SAMPLE_FACTORS - Study3_Dd2∆OATAPR-clone2_iRBC_10h_R6 Sample source:infected RBC (iRBC) | Parasite_type:del OAT D12 clone A6 | Parasite_line:Dd2∆OATAPR2 clone 2 | Timepoint:10 h Replicate=6; Tracer=15N Pro 15N,13C Arg 5C13 Gln; Date Generated=4/9/2021; RAW_FILE_NAME(Raw_file_name)=0199_MAZ_Akansha_HP-200.raw SUBJECT_SAMPLE_FACTORS - Study3_Dd2∆OATAPR-clone3_iRBC_10h_R1 Sample source:infected RBC (iRBC) | Parasite_type:del OAT D12 clone F7 | Parasite_line:Dd2∆OATAPR2 clone 3 | Timepoint:10 h Replicate=1; Tracer=15N Pro 15N,13C Arg 5C13 Gln; Date Generated=3/28/2021; RAW_FILE_NAME(Raw_file_name)=63_MAZ_Akansha_HP-63.raw SUBJECT_SAMPLE_FACTORS - Study3_Dd2∆OATAPR-clone3_iRBC_10h_R2 Sample source:infected RBC (iRBC) | Parasite_type:del OAT D12 clone F7 | Parasite_line:Dd2∆OATAPR2 clone 3 | Timepoint:10 h Replicate=2; Tracer=15N Pro 15N,13C Arg 5C13 Gln; Date Generated=3/30/2021; RAW_FILE_NAME(Raw_file_name)=91_MAZ_Akansha_HP-91.raw SUBJECT_SAMPLE_FACTORS - Study3_Dd2∆OATAPR-clone3_iRBC_10h_R3 Sample source:infected RBC (iRBC) | Parasite_type:del OAT D12 clone F7 | Parasite_line:Dd2∆OATAPR2 clone 3 | Timepoint:10 h Replicate=3; Tracer=15N Pro 15N,13C Arg 5C13 Gln; Date Generated=4/1/2021; RAW_FILE_NAME(Raw_file_name)=119_MAZ_Akansha_HP-119.raw SUBJECT_SAMPLE_FACTORS - Study3_Dd2∆OATAPR-clone3_iRBC_10h_R4 Sample source:infected RBC (iRBC) | Parasite_type:del OAT D12 clone F7 | Parasite_line:Dd2∆OATAPR2 clone 3 | Timepoint:10 h Replicate=4; Tracer=15N Pro 15N,13C Arg 5C13 Gln; Date Generated=4/5/2021; RAW_FILE_NAME(Raw_file_name)=147_MAZ_Akansha_HP-147.raw SUBJECT_SAMPLE_FACTORS - Study3_Dd2∆OATAPR-clone3_iRBC_10h_R5 Sample source:infected RBC (iRBC) | Parasite_type:del OAT D12 clone F7 | Parasite_line:Dd2∆OATAPR2 clone 3 | Timepoint:10 h Replicate=5; Tracer=15N Pro 15N,13C Arg 5C13 Gln; Date Generated=4/7/2021; RAW_FILE_NAME(Raw_file_name)=0175_MAZ_Akansha_HP-176.raw SUBJECT_SAMPLE_FACTORS - Study3_Dd2∆OATAPR-clone3_iRBC_10h_R6 Sample source:infected RBC (iRBC) | Parasite_type:del OAT D12 clone F7 | Parasite_line:Dd2∆OATAPR2 clone 3 | Timepoint:10 h Replicate=6; Tracer=15N Pro 15N,13C Arg 5C13 Gln; Date Generated=4/9/2021; RAW_FILE_NAME(Raw_file_name)=0203_MAZ_Akansha_HP-204.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 10hr with unlabeled media, harvested by CO:COLLECTION_SUMMARY centrifugation, washed twice in PBS, and then suspended in 10 μl PBS (Life CO:COLLECTION_SUMMARY Technologies, Carlsbad, CA, USA). Polar metabolites were extracted using nine CO:COLLECTION_SUMMARY volumes of 74.9:24.9:0.2 (v/v/v) acetonitrile/methanol/formic acid containing CO:COLLECTION_SUMMARY stable isotope-labeled internal standards (0.2 ng/μl valine-d8 (Sigma Aldrich, CO:COLLECTION_SUMMARY St. Louis, MO, USA); and 0.2 ng/μl phenylalanine-d8 (Cambridge Isotope CO:COLLECTION_SUMMARY Laboratories, Tewksbury, MA, USA) and stored at −80°C prior to the metabolite CO:COLLECTION_SUMMARY 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, 25mL 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 incomplete RPMI (unlabeled). Parasites were TR:TREATMENT_SUMMARY incubated in unlabeled media for 10h at 37ºC under standard malaria gas TR:TREATMENT_SUMMARY mixture. Samples were harvested by centrifugation, washed twice, and then polar TR:TREATMENT_SUMMARY 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 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 HF hybrid 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 MS:MS_COMMENTS 120 000 resolution and 3 Hz data acquisition rate. Other MS settings were as MS:MS_COMMENTS follows: sheath gas 40, sweep gas 2, spray voltage 3.5 kV, capillary temperature MS:MS_COMMENTS 350 °C, S-lens RF 40, heater temperature 300 °C, microscans 1, automatic gain MS:MS_COMMENTS control 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 Study3_uRBCs_RBC_10h_R1 Study3_uRBCs_RBC_10h_R2 Study3_uRBCs_RBC_10h_R3 Study3_uRBCs_RBC_10h_R4 Study3_uRBCs_RBC_10h_R5 Study3_uRBCs_RBC_10h_R6 Study3_Dd2∆OAT-C1_iRBC_10h_R1 Study3_Dd2∆OAT-C1_iRBC_10h_R2 Study3_Dd2∆OAT-C1_iRBC_10h_R3 Study3_Dd2∆OAT-C1_iRBC_10h_R4 Study3_Dd2∆OAT-C1_iRBC_10h_R5 Study3_Dd2∆OAT-C1_iRBC_10h_R6 Study3_Dd2∆OATAPR-bulk_iRBC_10h_R1 Study3_Dd2∆OATAPR-bulk_iRBC_10h_R2 Study3_Dd2∆OATAPR-bulk_iRBC_10h_R3 Study3_Dd2∆OATAPR-bulk_iRBC_10h_R4 Study3_Dd2∆OATAPR-bulk_iRBC_10h_R5 Study3_Dd2∆OATAPR-bulk_iRBC_10h_R6 Study3_Dd2∆OATAPR-clone1_iRBC_10h_R1 Study3_Dd2∆OATAPR-clone1_iRBC_10h_R2 Study3_Dd2∆OATAPR-clone1_iRBC_10h_R3 Study3_Dd2∆OATAPR-clone1_iRBC_10h_R4 Study3_Dd2∆OATAPR-clone1_iRBC_10h_R5 Study3_Dd2∆OATAPR-clone1_iRBC_10h_R6 Study3_Dd2∆OATAPR-clone2_iRBC_10h_R1 Study3_Dd2∆OATAPR-clone2_iRBC_10h_R2 Study3_Dd2∆OATAPR-clone2_iRBC_10h_R3 Study3_Dd2∆OATAPR-clone2_iRBC_10h_R4 Study3_Dd2∆OATAPR-clone2_iRBC_10h_R5 Study3_Dd2∆OATAPR-clone2_iRBC_10h_R6 Study3_Dd2∆OATAPR-clone3_iRBC_10h_R1 Study3_Dd2∆OATAPR-clone3_iRBC_10h_R2 Study3_Dd2∆OATAPR-clone3_iRBC_10h_R3 Study3_Dd2∆OATAPR-clone3_iRBC_10h_R4 Study3_Dd2∆OATAPR-clone3_iRBC_10h_R5 Study3_Dd2∆OATAPR-clone3_iRBC_10h_R6 Factors Sample source:uninfected RBC (uRBC) | Parasite_type:uninfected RBCs | Parasite_line:Control RBCs | Timepoint:10 h Sample source:uninfected RBC (uRBC) | Parasite_type:uninfected RBCs | Parasite_line:Control RBCs | Timepoint:10 h Sample source:uninfected RBC (uRBC) | Parasite_type:uninfected RBCs | Parasite_line:Control RBCs | Timepoint:10 h Sample source:uninfected RBC (uRBC) | Parasite_type:uninfected RBCs | Parasite_line:Control RBCs | Timepoint:10 h Sample source:uninfected RBC (uRBC) | Parasite_type:uninfected RBCs | Parasite_line:Control RBCs | Timepoint:10 h Sample source:uninfected RBC (uRBC) | Parasite_type:uninfected RBCs | Parasite_line:Control RBCs | Timepoint:10 h Sample source:infected RBC (iRBC) | Parasite_type:del OAT D12 | Parasite_line:Dd2∆OAT C1 | Timepoint:10 h Sample source:infected RBC (iRBC) | Parasite_type:del OAT D12 | Parasite_line:Dd2∆OAT C1 | Timepoint:10 h Sample source:infected RBC (iRBC) | Parasite_type:del OAT D12 | Parasite_line:Dd2∆OAT C1 | Timepoint:10 h Sample source:infected RBC (iRBC) | Parasite_type:del OAT D12 | Parasite_line:Dd2∆OAT C1 | Timepoint:10 h Sample source:infected RBC (iRBC) | Parasite_type:del OAT D12 | Parasite_line:Dd2∆OAT C1 | Timepoint:10 h Sample source:infected RBC (iRBC) | Parasite_type:del OAT D12 | Parasite_line:Dd2∆OAT C1 | Timepoint:10 h Sample source:infected RBC (iRBC) | Parasite_type:del OAT 6491 bulk | Parasite_line:Dd2∆OATAPR2 bulk | Timepoint:10 h Sample source:infected RBC (iRBC) | Parasite_type:del OAT 6491 bulk | Parasite_line:Dd2∆OATAPR2 bulk | Timepoint:10 h Sample source:infected RBC (iRBC) | Parasite_type:del OAT 6491 bulk | Parasite_line:Dd2∆OATAPR2 bulk | Timepoint:10 h Sample source:infected RBC (iRBC) | Parasite_type:del OAT 6491 bulk | Parasite_line:Dd2∆OATAPR2 bulk | Timepoint:10 h Sample source:infected RBC (iRBC) | Parasite_type:del OAT 6491 bulk | Parasite_line:Dd2∆OATAPR2 bulk | Timepoint:10 h Sample source:infected RBC (iRBC) | Parasite_type:del OAT 6491 bulk | Parasite_line:Dd2∆OATAPR2 bulk | Timepoint:10 h Sample source:infected RBC (iRBC) | Parasite_type:del OAT D12 clone B9 | Parasite_line:Dd2∆OATAPR2 clone 1 | Timepoint:10 h Sample source:infected RBC (iRBC) | Parasite_type:del OAT D12 clone B9 | Parasite_line:Dd2∆OATAPR2 clone 1 | Timepoint:10 h Sample source:infected RBC (iRBC) | Parasite_type:del OAT D12 clone B9 | Parasite_line:Dd2∆OATAPR2 clone 1 | Timepoint:10 h Sample source:infected RBC (iRBC) | Parasite_type:del OAT D12 clone B9 | Parasite_line:Dd2∆OATAPR2 clone 1 | Timepoint:10 h Sample source:infected RBC (iRBC) | Parasite_type:del OAT D12 clone B9 | Parasite_line:Dd2∆OATAPR2 clone 1 | Timepoint:10 h Sample source:infected RBC (iRBC) | Parasite_type:del OAT D12 clone B9 | Parasite_line:Dd2∆OATAPR2 clone 1 | Timepoint:10 h Sample source:infected RBC (iRBC) | Parasite_type:del OAT D12 clone A6 | Parasite_line:Dd2∆OATAPR2 clone 2 | Timepoint:10 h Sample source:infected RBC (iRBC) | Parasite_type:del OAT D12 clone A6 | Parasite_line:Dd2∆OATAPR2 clone 2 | Timepoint:10 h Sample source:infected RBC (iRBC) | Parasite_type:del OAT D12 clone A6 | Parasite_line:Dd2∆OATAPR2 clone 2 | Timepoint:10 h Sample source:infected RBC (iRBC) | Parasite_type:del OAT D12 clone A6 | Parasite_line:Dd2∆OATAPR2 clone 2 | Timepoint:10 h Sample source:infected RBC (iRBC) | Parasite_type:del OAT D12 clone A6 | Parasite_line:Dd2∆OATAPR2 clone 2 | Timepoint:10 h Sample source:infected RBC (iRBC) | Parasite_type:del OAT D12 clone A6 | Parasite_line:Dd2∆OATAPR2 clone 2 | Timepoint:10 h Sample source:infected RBC (iRBC) | Parasite_type:del OAT D12 clone F7 | Parasite_line:Dd2∆OATAPR2 clone 3 | Timepoint:10 h Sample source:infected RBC (iRBC) | Parasite_type:del OAT D12 clone F7 | Parasite_line:Dd2∆OATAPR2 clone 3 | Timepoint:10 h Sample source:infected RBC (iRBC) | Parasite_type:del OAT D12 clone F7 | Parasite_line:Dd2∆OATAPR2 clone 3 | Timepoint:10 h Sample source:infected RBC (iRBC) | Parasite_type:del OAT D12 clone F7 | Parasite_line:Dd2∆OATAPR2 clone 3 | Timepoint:10 h Sample source:infected RBC (iRBC) | Parasite_type:del OAT D12 clone F7 | Parasite_line:Dd2∆OATAPR2 clone 3 | Timepoint:10 h Sample source:infected RBC (iRBC) | Parasite_type:del OAT D12 clone F7 | Parasite_line:Dd2∆OATAPR2 clone 3 | Timepoint:10 h phenylalanine-d8 163481923 147570451 167338733 171711042 154325831 170950301 199655140 163165032 181573832 169540706 180772429 179298956 185027848 195330353 180841108 197594143 156284411 178277728 209142031 198844207 193954012 191816601 166774206 177441801 206562565 173638214 166443605 155462242 166082888 166025166 168069544 175089652 167942104 185598354 144867589 182105554 valine-d8 39439639 30737551 34201572 33821038 36593210 35815809 37556530 37571366 34448800 41954414 41495115 33820820 40135260 39142485 32253260 36427269 33715776 34679849 38418604 37914807 33839988 39008769 38271485 42179799 39223931 33304379 35236581 34438002 35656206 36780937 39217503 33313418 33401358 37444083 34796470 36497700 1-methyladenosine 1-methylhistamine 1-methylnicotinamide 2083888 1333726 785450 3169809 1602521 808667 249771 140335 155145 114346 636872 129885 265746 251443 145790 200388 541497 10867 214071 253279 174354 198411 234616 139876 369461 269694 293612 563147 665413 135882 283380 191197 133885 183459 183663 181589 1-pyrroline-5-carboxylate 1-pyrroline-5-carboxylase[15]N 1-pyrroline-5-carboxylate[13]C1[15]N1 1-pyrroline-5-carboxylate[13]C5 2-deoxycytidine 6205931 4884775 2994888 2054797 958207 3210289 4969462 5329217 1873192 2258907 1393490 2740037 5154255 4861016 2474818 1931621 697611 2827698 5291107 4317272 2631760 2107107 1381932 3119978 4245346 4064949 1006560 2280305 664575 2336513 5-adenosylhomocysteine 62350 1834487 1719188 1122524 656921 432110 1261508 1123227 1500516 722558 953557 729821 980670 1676030 1655877 1073049 611100 264117 905367 1713744 1630840 1366230 909681 725404 982806 1328541 1497866 502977 878895 351308 759610 5-aminolevulinic acid 5-hydroxytryptophan 2186672 2775669 4326786 3693704 2295156 1728319 60736 111289 44039 acetylcholine 169411 334284 119754 101642 270060 1010471 269895 481255 119211 108266 1821528 120307 256886 144718 adenosine 2229280 7821374 9351957 5047129 8292756 3991405 12064362 10224743 2998678 14246803 5147602 11417861 10821290 12691161 3758767 6218977 4382123 5306452 17241148 6665804 6359727 4009734 1541810 3620671 4512426 9168238 8479143 15338172 4565297 5501616 16639650 14204136 1756239 6599668 1454317 3970391 ADMA 506876 717804 41819 7831 20348 7571 105499739 81967914 52096814 20643768 9802374 44481718 75036267 96010365 37112208 53584863 27855694 57619467 136484857 98786354 71189739 31090016 12341288 36544424 122135543 84125088 57530539 44896983 25606671 48894756 94946752 88585249 30909562 41573697 11046859 36666987 alanine 7363828 5856375 6559694 7260721 6073115 7330900 738251 512971 363207 363263 657423 433503 936061 746062 373290 477707 432788 454634 773087 639886 563966 535127 343800 1074459 556889 566856 961202 385446 375878 887278 541446 385124 603585 411832 510518 allantoin alpha-glycerophosphocholine 160507907 240432467 263786307 196451849 141362743 152130397 32008340 23686979 22191388 11772838 11506442 25006058 26880528 26506705 18102327 21526999 16487323 25253914 34230623 28531394 29500096 17780664 9872763 20317829 33474573 23791941 24251418 18944705 15086030 23538663 29634113 23013321 14226788 21150827 11815151 20238964 anserine 63781 74241 421520 276788 285586 anthranilic acid 299954 355065 489051 794504 493251 243899 407115 286422 337398 249730 475954 357844 394703 179693 582634 390578 372373 223066 104766 124033 420880 533480 412379 149643 270739 307210 261036 444632 229311 192892 164253 340625 arginine 32059005 44139604 43304638 27872117 23769370 24824074 211803844 165369557 141222471 41199785 37542623 121198280 198303382 205973818 138357113 128556562 87354100 135385370 271064600 190488469 149533498 117101990 40819121 110665146 243555810 183390106 571263814 153233102 77276916 135897920 210893235 190989521 76939539 117982045 28108284 110987566 arginine[15]N 5501616 7777848 6288490 4729969 5154538 4669859 8414015 7743702 5819116 2216229 1818270 6592584 7487171 9615990 5234933 5442593 4396209 7450457 10175777 8968873 6526708 4671216 1810862 4851683 9790034 8187482 10588484 6542139 3882362 5850709 8357047 8744362 3674843 4794861 1541430 4705068 arginine[13]C1[15]N1 1028200023 1417792235 1157616067 936916943 976966449 883186148 1135391417 1083828612 781594036 312747400 235234697 1007934675 956354198 1370298287 700123152 759445839 569304769 1135574146 1303625652 1266725570 905508212 618730869 226494490 684620242 1320248848 1141130057 497213085 887111582 506369080 804874162 1147130414 1243834278 481666647 692238353 209683237 651803470 arginine [13]C5 argininosuccinate asparagine 47337605 47435168 51892745 62953964 53806179 51529203 8173540 6989705 6092442 3280898 3528400 9365994 6288835 9721608 4723243 6261041 4154962 10317156 9181735 9803327 9015473 4957392 2564937 6818044 10571060 7910305 6531439 6525145 3852083 8203872 8968526 7945411 3805705 7406260 3411561 6837578 aspartate 27030540 29264944 28161835 20411783 24451701 30638789 6704296 5235556 3439279 2296064 3192312 4062556 5762082 6460426 3357956 4178972 3597789 3603681 7029115 5734481 4014294 4039091 2204520 3145986 7137302 5380646 8158726 5013636 3427967 4014800 5902513 5008135 2547990 4792361 2807946 3744447 beta-alanine 6111200 5550915 6028187 7260721 6073115 6490844 662217 512971 351046 363263 657423 433503 936061 746062 373290 477707 432788 454634 707877 639886 563966 535127 300919 343800 1074459 489655 488363 961202 385446 375878 833818 541446 385124 603585 411832 510518 betaine 1970822613 1941273891 1885831849 4678750645 3359202676 3005141148 285932079 223890144 226296517 237030771 290305803 258044915 252689397 266847809 234595820 267468648 241140492 278515734 272805078 247984512 253354897 270944358 247733697 248821949 298729271 207021332 240520088 274601515 235777052 234183953 273013474 242340336 222614083 270945608 278794055 287795673 butyrobetaine carnitine 125486598 94530263 66648472 1197060692 287187043 153949309 33090125 42318072 50519163 32020577 50990695 63903746 29703373 68802133 50363904 51811939 37356761 58000791 60057383 60420172 54355692 47469559 38547641 48571258 44605834 34698264 44436728 42801595 35748910 39847581 65528949 69721550 46075672 55674933 52138790 68436838 C2 carnitine 474015752 283932315 154468143 1725036588 750116888 411067258 28410222 32145387 42485239 22265149 39280740 66500792 22639186 61261709 40401847 40034665 27777945 48879491 49702958 49877591 50012570 34867274 21327316 38980664 43354549 26279093 41915474 31013802 21242586 30080012 56419625 61600627 34311835 44074340 34667485 62398874 C3 carnitine 17200843 8291892 4034180 103885073 35554784 15950050 1074626 1465338 2152472 1694200 2932214 2565367 883041 2992288 2060419 2730942 1770812 1867487 2460414 2389278 2192817 2320681 1388937 1607175 1677298 1235560 1822631 2031491 1345389 1318185 2760219 3166798 1508014 2679285 2404954 2688828 C3-DC-CH3 carnitine 17416114 20838685 20189065 29268385 20036980 18824144 1049967 737858 744682 558253 818392 695981 1189991 662015 760255 1155828 1015601 1134696 385034 589501 1552444 730961 910299 578809 1228774 1047535 614890 885710 536955 819022 C4 carnitine 8101897 5730436 3728802 7818122 3570215 2245729 280859 332805 535922 777514 680799 561768 511710 593820 446141 593365 514897 634722 655040 326802 866427 C4-OH carnitine 5359708 4450858 1841697 9453403 4987855 4080830 915044 296357 1860476 1196981 935914 478598 1420379 910710 1077686 1232465 1071986 557746 1136543 855300 945700 1243589 683901 642127 1732609 C5 carnitine 3387303 2362715 1633560 4900436 2436256 1635839 234061 274628 416205 265685 384339 688326 277512 515356 457092 258104 191001 470534 378639 453925 423905 271216 160171 385792 386605 284947 400757 805332 169860 313528 532331 461625 320352 333681 205269 676724 C5:1 carnitine 382240 319740 242863 994793 507092 440753 C6 carnitine C7 carnitine 168943 83048 47232 285220 124878 C8 carnitine C10 carnitine C10:2 carnitine C12 carnitine 108880 372175 142908 63916 C12:1 carnitine 83047 C14 carnitine 2859042 2021518 1364641 18884366 5675860 2308268 28897 21193 14633 21293 12867 14905 37021 C14:1 carnitine 185850 66366 767070 215612 208647 C14:2 carnitine 129446 764511 227617 64996 C16 carnitine 97802506 71862222 39674115 375915824 176103411 74285623 276814 296940 669928 577403 1137291 821513 289490 591346 689954 650631 831138 701820 568842 510368 648523 663061 878762 575687 579909 251117 463774 513248 669500 579491 516523 611844 598239 660009 1414481 884230 C18 carnitine 146709514 121663268 98899530 366204933 285750194 166740976 5943394 5780959 7133818 8972365 8686370 14049612 5622321 6949893 7340515 10172700 7716616 12978104 8006892 7184053 9165034 9101943 6513842 10700962 8504325 5648483 6202380 9157841 6365685 9369151 8047561 6921938 6676090 11224675 9759268 11164750 C18:1 carnitine 47035713 35368300 28074129 211457881 99611881 57274313 516554 472502 1022761 1124216 2038902 1197694 575597 1028620 1124472 1396866 1369686 1097912 952313 765566 1189671 1609613 1360035 1086319 1043081 554256 819627 1205435 914755 1014161 1102221 1036133 1146515 1437366 2347376 1477081 C18:2 carnitine 16271002 13090438 9388983 101094117 37612885 10166992 145263 131308 129908 157602 159322 C20 carnitine 1280346 1237237 1100215 2438619 1652587 1228256 295664 197265 203618 161840 139845 377303 227931 277377 174859 239533 119448 334813 340614 272243 270022 180123 80843 222884 325920 227933 249968 188813 111352 251993 307877 267793 121013 269545 111092 236879 C20:4 carnitine 728355 488409 196903 14539684 3124043 691332 54466 66497 115589 87546 60610 48302 45856 69400 63997 59321 47920 86706 86468 111154 67319 108533 C26 carnitine 752153 745609 587249 2072436 857446 666797 210081 131977 147086 96079 94750 215677 180033 200463 130347 148120 89208 194918 245592 214282 213879 107881 66997 158548 280882 169025 196549 113203 105236 157621 196958 174309 100023 134347 73267 145521 cAMP 23449 69593 36361 59761 3804 69491 51814 50521 24048 27589 4503 38540 47838 9405 33863 20769 8262 48403 58755 21337 8378 44437 61206 36262 21641 14595 33901 61472 24981 carnosine 95529 99409 77262 188757 119705 128802 73951 56995 82442 48831 60868 77236 83287 69611 60233 60331 71816 122690 72714 56796 70746 54956 91440 107091 71076 49921 89417 54429 52625 108917 66296 51557 71992 50983 94151 choline 2095265814 2445018583 2579789626 3345496423 2693257398 2659146831 1142271554 986478596 637148300 551790920 341785831 1419044805 712506969 878831865 428641382 566234739 472315876 1135550223 995451141 1036621553 802794696 379093984 241018493 692370177 1053445072 819462016 612009361 502421700 456025783 720027273 871708258 822872010 288027350 576114809 287229860 608565505 citrulline 1936195 1284416 949362 4199660 2164214 1416578 196862 157915 125308 159740 252620 198711 629533 219110 127718 160095 136459 168881 215956 193493 273618 199831 111212 177635 424097 253693 189076 922293 164138 165144 253640 198282 158970 177575 132440 314769 citrulline[15]N citrulline[13]C1[15]N1 citrulline[13]C5 cotinine 392826 176965 118335 75459 219314 209030 134991 96749 116240 309167 249966 93310 97011 301817 663908 84370 87932 326442 231394 253138 93985 84894 creatine 1007567485 867809452 697154570 1479387990 964929664 746593203 57831363 33352287 42248410 25125122 40049710 42756227 39807150 68376886 43336953 41036942 31336383 35286689 62050742 55859708 64010234 39184170 29506997 30364795 78473763 22997529 42008707 31171562 21935306 24319519 71876395 60212232 40273082 44995765 44016628 49678033 creatinine 32891094 33184143 21140593 57556971 25818370 36977430 2309470 1874884 3004176 1251708 4677609 1997832 2488590 3235199 3867442 2197974 1873529 1653336 3001311 2664757 2800778 2848630 3250948 1956539 2817544 2033813 2555784 5082592 2248070 1626699 3807413 2850599 3343804 2845211 3116708 2910228 cytosine 141733 163857 191906 191579 62368 221913 2436514 2586741 2148190 504562 705255 1884411 2411419 3191413 1599261 1273125 967702 1304121 3105241 2338553 1635197 958232 400253 1642654 3163025 2184331 1774769 1178468 986261 1715513 2054662 2071146 804385 1137749 416625 1361606 dimethylglycine 1480843 1271705 1288785 1252680 1407392 1502933 1724654 1517782 1428103 1536961 1495889 1427030 1816475 1728053 2161546 1567229 1376939 1410929 1598464 1570536 1520216 1545702 1479697 1669326 1962887 1633155 1866330 2350514 1297714 1728621 1737887 1473854 1334002 1529666 1536921 1370490 GABA glucose glutamate 72110597 95585563 86051699 52427250 69679399 79741866 6512785 6857133 4741283 3853575 4405797 5783241 6814510 8618685 4540889 5903680 4976830 5516770 7868723 6671343 6403928 5294710 3312197 5071034 7594245 6240953 26516375 6219548 4312981 4929717 7643552 6756354 3588825 6419267 4107421 5075060 glutamate[15]N 146485 201691 82156 94258 168128 glutamate[13]C3[15]N1 glutamate[13]C5 glutamine 75550478 56454701 104540892 118908416 100949790 86773635 3455081 1588934 1991943 1341595 2310505 2979461 1956834 3455858 1590701 2748035 1843392 3165633 2781700 2574509 3568724 2564323 1421718 2089037 5206372 1348795 3149676 2453668 1133347 1909369 3581191 2515482 1725977 3050308 2541620 3195137 glutamine[15]N 426192 289134 571231 724287 563035 541467 glutamine[13]C1[15]N1 glutamine[13]C5 154492492 147980928 167467570 203380577 173077597 161793633 6516997 4200539 7902886 2756484 5905567 14295214 4715653 9520197 6011909 7757547 4947057 21408010 6205237 7624766 15046261 5758315 3897345 11256757 11102487 4055138 5767694 10477882 4876894 10528928 11616649 6966508 5105553 8003848 5503557 11084314 glycine 3387849 3335160 3307658 5312055 3625352 3306398 181869 163500 101674 196615 262179 253086 130566 149654 245933 245270 250356 232393 371144 268912 155870 364584 106278 339974 195323 166398 147751 200980 histamine 243722 360787 478086 248775 153237 148773 158587 292743 125809 279410 228730 204527 136094 201198 274072 222666 146690 217312 139327 193878 188927 253828 260955 534065 200978 177388 166459 179491 178132 158198 110318 188935 histidine 118744388 138056373 137045804 130042499 116307029 118747184 23122002 19657695 19788286 8342326 9954826 20292824 17720042 27254316 14866537 17033140 12116804 25856991 27530364 24436277 26964207 14639270 6801303 16305681 32499035 22056741 23038771 27642309 12024410 19365065 23232098 24251545 15342424 19281003 8235886 18523312 homocysteine isoleucine 219593777 296652741 316483692 328951200 264470395 252468317 10985984 5986333 6835250 5765694 7275711 10017449 8925712 14205047 6441347 8975761 6695470 13247571 11014755 12431948 13927242 8715674 4832508 9074465 18983714 8157393 9636237 10862100 6532644 10209272 15521019 11053599 6391274 11239787 7152951 11471981 kynurenic acid 637796 642867 654463 577977 399928 634514 878593 694649 743550 234925 1320909 709852 710429 809589 598810 838127 883511 847523 918047 801077 783157 775339 747782 847383 883025 747385 925769 1602255 1038590 683132 737935 822732 719693 668766 688082 717611 leucine 156066837 218401412 231054360 235235132 209158022 188115614 9662482 5434050 5654241 4805664 6225170 8119146 14695808 21605448 9023331 12278259 8928686 20757430 18470618 22747306 17455495 10269798 5451374 13717347 25304852 16635276 14457166 13602389 8065879 15705291 20753029 18484058 6869636 14369615 7924025 14116032 lysine 83711385 100640098 113224280 86774690 71762035 84487629 1483718837 1328263742 818060060 392155081 271689538 703864348 1279348711 1463686792 866663446 927658585 472958780 1028000356 1909090490 1479724915 1278303779 599983926 294964571 764098444 1917932728 1271221730 1017065315 753619772 529163700 807339775 1564111235 1368497031 637826855 818230120 271488484 730646311 methionine 45507652 61939776 66063139 67559728 50649674 50887957 1696271 852588 915853 602767 861899 1262781 1168219 1810436 846002 1109345 713727 1243199 1666858 1521610 1720358 1067338 530005 871926 2732603 894423 1232148 1181541 576590 894170 2221960 1290982 740240 1453941 881400 1211221 methionine sulfoxide 2224074 2536053 3989998 3908710 3245484 2262577 150378 139493 131331 74264 185638 210691 178482 217306 108882 179529 131752 218997 103260 222349 210968 152362 90288 195429 179950 158072 184913 297270 120347 183645 201595 222409 113284 176652 111697 217331 methylthioadenosine 3530806 4622943 2925590 4983761 2009049 2232127 26651916 35647073 32272115 12945227 16754507 29583217 20353927 42289909 31670122 27175071 10952960 24431272 43019121 37730545 24929698 18641995 10112121 18062900 29640572 35999996 32124322 14509158 11999591 26277672 46946772 38834666 17599793 31920563 6530278 22134904 N-carbamoyl-beta-alanine niacinamide 127941321 184161496 150364424 172504056 68154449 168613423 46309558 41346353 46129443 37434483 21639809 134157029 45959558 54797459 58968699 54902700 27595093 103411760 74854332 62105766 78144641 40511213 14163454 46793243 43758232 48505105 78575634 40819667 24820678 67709977 81024270 63121747 21711024 47476019 16928075 45863934 NMMA 210033 92012 17097097 14889368 10158711 6442992 3397879 8383687 13726246 16330578 8065031 12229580 6347979 9978008 21644537 15882683 12709884 7569603 3577048 8488014 18313743 15246449 11795458 9919294 6585261 10673955 15356318 15054251 6444613 10257120 2931965 7568904 ornithine 11107666 15686022 16959025 5902482 4926326 6294222 267442425 222460956 142391802 71433409 33286460 155005907 205645779 250285320 113829207 168771405 73623873 198427904 325361293 262606763 196875697 95496725 33350296 142756976 310680783 226980418 303850164 141905367 77252155 151876509 243785786 227706240 93367751 163423064 33763768 127109751 ornithine[15]N 712848 949004 828773 360632 309273 265369 4432283 3771071 2220841 1103578 461344 2909176 3387079 4496361 1789615 2714498 1175064 3669786 5230402 4483583 3199557 1490720 428678 2449306 4850322 3962910 3020238 2236891 1219463 2444489 3837857 3979628 1387028 2621878 454093 2206944 ornithine[13]C1[15]N1 150741973 194531367 164019397 89739343 71072728 69642055 538985938 500188704 278656966 139003793 57831534 388893910 405460933 569786149 214687426 327027419 148430747 476076597 593542413 584498037 392903380 184371269 53934926 311039536 609338482 500493599 182800780 277234746 143238661 320412658 470875694 523971333 161973340 329524063 58765114 276012666 ornithine [13]C5 phenylalanine 116370952 173982281 196050132 181962348 137057604 144549540 8576863 4552015 4755559 3495616 5356651 7052836 6801304 9464046 4373851 6115257 4096703 7246027 8088749 7969783 9307473 5648628 3015372 5257701 13972604 5245655 5562266 7396919 3757934 5040674 10792163 7106176 3865662 7451567 4586709 7045913 phosphocholine 9032464 8840431 5784241 10181075 7018574 8338970 3561013086 3223002041 2094446807 891739954 881785289 2401027940 2398835939 2978802395 1356590139 1798343407 1329142822 1898684718 3274202119 3357127360 2024346687 1169392133 639700487 1501296929 3191218090 2923042231 2752516645 1529627834 1257010953 1887791037 2590686100 2835333639 821488134 1751111974 599143024 1414054388 phosphoethanolamine 77634861 66503596 34609078 18696814 15921647 65247534 61241630 70306560 23503619 40106730 22861632 55793834 83521079 77466554 38641168 24180955 10457151 35871351 76253693 65748551 49953744 32940336 22379207 40556715 63620562 63597574 12630595 38524953 11457849 28272224 pipecolic acid 2270337 1990757 2472740 1825512 1693569 1899641 326057 650734 713327 327223 485124 287662 604409 865027 828159 532208 384241 481093 855660 777241 264553 420019 557288 828317 774282 852349 550912 320434 307980 pipecolic acid[15]N pipecholic acid[13]C1[15]N1 pipecolic acid [13]C5 proline 47550706 55046280 55677004 80355925 65936058 57268056 6235986 4208990 3299346 3103590 5070807 5057719 80296286 74909307 33924225 40164235 24008199 65840820 97783349 84511623 44574292 34166481 12668105 50564268 99292995 72697106 50339229 43846297 22091029 59124507 82685507 69246642 20997839 40019810 14816650 44571240 proline[15]N 265411813 255269844 305702232 320295685 319380754 235943449 11176000 4827196 6129808 4255178 6374636 7593379 14032157 20974087 9421557 12441240 9760337 19006443 20622855 19207434 18208647 10332031 5824415 12109491 30458321 12996750 7095166 12369379 7475894 11741304 24826246 16321689 6980262 13271868 9538576 13152374 proline[13]C1[15]N1 14225195 14781866 17785271 18706403 17587197 12703373 1021761 1460830 proline [13]C5 putrescine 957198 724976 272784 463346 497273 461103 154101247 145246477 94273373 78227845 57577301 126539808 149009384 160569648 97544910 112063230 77945402 140243744 186658216 160100667 113064272 86470003 57833802 111194769 170563501 141606485 118205357 92340859 72229936 111393313 163535621 142333300 72877650 115448586 58725424 101287163 pyroglutamic acid 37892468 32307324 60251557 56860321 47865008 46660457 1703844 854815 1062187 784758 1066173 1408345 1115467 1900215 891270 1393157 967307 1608757 1460471 1394204 2092909 1348499 777323 1206617 2683189 658261 2116194 1332529 598021 992625 1720015 1304252 1061034 1649322 1254701 1749998 s-adenosylmethionine 405235 451646 270433 471204 166254 158107 11578783 9541241 7050943 2466732 2072928 7606952 6920029 9522340 5403605 5725725 4717772 9250859 13347893 8730713 7722173 3892301 2090981 5022031 11351744 8634790 8163895 7575222 4052240 7264727 7225802 8923422 4979742 4321429 1824356 5273733 sarcosine SDMA serine 6976800 6540956 6963364 9045352 8148309 7848049 838575 766789 615579 518505 863765 899619 906756 1087383 550682 753500 565655 1016210 828426 981148 939214 733138 425217 802245 1249699 762327 700596 1786086 509287 692289 1017540 824539 489510 943410 571723 874061 spermidine 23723045 63835297 24410070 28264339 5497740818 4523214380 3703346351 2364256965 1834903816 4446979006 4906048338 4906380398 3486852049 3439779283 2646821691 4182393627 5868049764 5223023637 3751247469 2993536481 1367259876 3716380226 5920093844 4977378954 3776136251 3872380659 2435064809 3525483667 4849069938 4872841261 2406199480 3441829751 1065417983 2949579123 taurine 2528340 1121480 863919 13911154 4646426 2162585 869136 596119 788942 617451 835891 937976 833492 850385 655141 798218 625588 857001 847839 798895 1046169 906026 668520 859062 1231159 591387 750470 1670130 684873 701292 913421 752139 737326 834878 801356 1160568 thiamine 179715222 239017948 225706673 230278726 167005244 174343882 339375526 277014326 179613110 164611708 87942082 200110092 268502558 299004402 148882665 189377707 123372430 199840990 362648103 324295284 213660384 144505990 68244218 174308169 351398568 283311364 226267552 164539224 113224055 188860942 298539829 283274468 93200355 193265890 65144674 151635979 threonine 3545669 3496158 4226641 5366001 4848309 4670354 1084289 1050022 779517 588780 700357 1344934 1237455 1631764 902129 1033171 834904 1620100 1531188 1612943 1423281 841854 423162 1262311 1938803 1158025 1233936 1283643 743394 1210591 1625744 1329595 537287 1315476 590415 1115238 thymidine 443735 266112 354788 210026 250810 84200 370705 285196 197869 110576 116014 497528 252894 190677 875416 170912 191277 trans-hydroxyproline 38685754 42355349 48601173 58192653 46048679 41152923 4005529 3040342 2682626 1791750 2036580 4242140 4076036 5956655 2696644 3699556 2543246 4988255 5119399 5384814 4680303 3028383 1528218 3889974 6332245 4460880 3949775 3906569 2099980 3731316 5745599 4797327 2209927 4100643 2245246 3812887 trans-hydroxyproline[15]N trans-hydroxyproline[13]C1[15]N1 trans-hydroxyproline [13]C5 trimethylamine-N-oxide 212746 153399 190274 187570 270625 235780 379621 402986 384857 361094 486807 395194 363601 444468 354629 309187 353238 348257 372581 411549 372874 338184 367367 336087 435876 411851 357655 600866 353738 398938 381819 405792 220615 422831 366532 429288 tryptophan 44104558 53434305 46562676 47345542 39913878 43918681 3187418 1944901 2331948 1297511 2504160 2586153 2757705 3944915 2400933 2264990 2048539 3277016 3396694 3274755 4080961 2628996 1632721 2900643 5599035 2799000 2981764 3521457 2024874 3107552 3496678 3093671 2489366 3207156 2413420 3420112 tyrosine 53016889 66648120 65849047 69912375 45223324 53283864 5483734 3584740 3370263 2061256 2264630 5081570 4616585 6475338 2951263 3890671 2234934 6310966 6584236 6347166 6275662 3550466 1525636 4138850 9022464 4792418 4274817 4408525 2379355 4857053 6638829 5608520 2445286 4584976 2162770 4674943 valine 22755644 24600630 27440773 28630434 23822665 21421869 2298011 1923549 1588323 2246315 1863774 2749299 2371764 2877772 1608917 1900467 1586744 2897009 2545658 2914512 2659332 1834236 1201800 2654720 3085395 2309533 1641704 2964140 1486193 2505127 2856142 2482076 1407272 2550832 1282267 2592690 xanthosine 56846 204748 121723 280125 119163 244233 241709 230961 187452 254793 94711 72928 184231 150345 200283 189372 172085 192603 173012 141765 MS_METABOLITE_DATA_END #METABOLITES METABOLITES_START metabolite_name Formula m/z RT phenylalanine-d8 C9H3NO2D8 174.1365 6.94 valine-d8 C5H3NO2D8 126.1365 7.63 1-methyladenosine C11H15N5O4 282.1197 NA 1-methylhistamine C6H11N3 126.1026 NA 1-methylnicotinamide C7H9N2O+ 137.0715 8.43 1-pyrroline-5-carboxylate C5H7NO2 114.0549 8.09 1-pyrroline-5-carboxylase[15]N C5H7[15]NO2 115.0520 8.50 1-pyrroline-5-carboxylate[13]C1[15]N1 [13]CC4H7[15]NO2 116.0553 8.30 1-pyrroline-5-carboxylate[13]C5 [13]C5H7NO2 119.0717 8.30 2-deoxycytidine C9H13N3O4 228.0979 6.22 5-adenosylhomocysteine C14H20N6O5S 385.1289 8.33 5-aminolevulinic acid C5H9NO3 132.0655 NA 5-hydroxytryptophan C11H12N2O3 221.0921 6.93 acetylcholine C7H16NO2 146.1181 7.95 adenosine C10H13N5O4 268.1040 5.23 ADMA C8H18N4O2 203.1503 9.95 alanine C3H7NO2 90.0550 8.02 allantoin C4H6N4O3 159.0513 NA alpha-glycerophosphocholine C8H20NO6P 258.1101 10.64 anserine C10H16N4O3 241.1295 10.70 anthranilic acid C7H7NO2 138.0550 1.98 arginine C6H14N4O2 175.1190 9.37 arginine[15]N C6H14[15]N1N3O2 176.1159 9.37 arginine[13]C1[15]N1 [13]CC5H14[15]N1N3O2 177.1193 9.37 arginine [13]C5 [13]C5CH14N4O2 180.1357 9.37 argininosuccinate C10H18N4O6 291.1299 NA asparagine C4H8N2O3 133.0608 8.14 aspartate C4H7NO4 134.0448 8.15 beta-alanine C3H7NO2 90.0550 8.01 betaine C5H11NO2 118.0863 9.15 butyrobetaine C7H16NO2 146.1176 NA carnitine C7H15NO3 162.1125 9.01 C2 carnitine C9H17NO4 204.1230 8.85 C3 carnitine C10H19NO4 218.1387 8.50 C3-DC-CH3 carnitine C11H19NO6 262.1285 8.74 C4 carnitine C11H21NO4 232.1543 8.20 C4-OH carnitine C11H21NO5 248.1493 9.02 C5 carnitine C12H23NO4 246.1700 7.96 C5:1 carnitine C12H21NO4 244.1543 8.06 C6 carnitine C13H25NO4 260.1856 NA C7 carnitine C14H27NO4 274.2013 7.65 C8 carnitine C15H29NO4 288.2169 NA C10 carnitine C17H33NO4 316.2482 NA C10:2 carnitine C17H29NO4 312.2169 NA C12 carnitine C19H37NO4 344.2795 7.14 C12:1 carnitine C19H35NO4 342.2639 7.20 C14 carnitine C21H41NO4 372.3108 6.99 C14:1 carnitine C21H39NO4 370.2952 6.99 C14:2 carnitine C21H37NO4 368.2795 7.05 C16 carnitine C23H45NO4 400.3421 6.86 C18 carnitine C25H49NO4 428.3734 6.74 C18:1 carnitine C25H47NO4 426.3578 6.77 C18:2 carnitine C25H45NO4 424.3421 6.83 C20 carnitine C27H53NO4 456.4047 6.65 C20:4 carnitine C27H45NO4 448.3421 6.72 C26 carnitine C33H65NO4 540.4986 6.43 cAMP C10H12N5O6P 330.0598 7.18 carnosine C9H14N4O3 227.1139 9.99 choline C5H14NO 104.1070 8.47 citrulline C6H13N3O3 176.1030 8.55 citrulline[15]N C6H14[15]N1N3O2 177.1000 8.55 citrulline[13]C1[15]N1 [13]C1C5H14[15]N1N3O2 178.1033 8.55 citrulline[13]C5 [13]C5C1H14N4O2 177.1063 8.55 cotinine C10H12N2O 177.1022 5.22 creatine C4H9N3O2 132.0768 8.52 creatinine C4H7N3O 114.0662 6.68 cytosine C4H5N3O 112.0505 6.40 dimethylglycine C4H9NO2 104.0706 8.70 GABA C4H9NO2 104.0706 NA glucose C6H12O6 181.0707 NA glutamate C5H9NO4 148.0604 7.81 glutamate[15]N C5H9[15]NO4 149.0574 7.81 glutamate[13]C3[15]N1 [13]C3C2H9[15]NO4 150.0608 7.81 glutamate[13]C5 [13]C5H9NO4 153.0772 7.81 glutamine C5H10N2O3 147.0764 8.25 glutamine[15]N C5H10[15]N1N1O3 148.0734 8.25 glutamine[13]C1[15]N1 [13]C1C4H10[15]N1N1O3 149.0768 8.25 glutamine[13]C5 [13]C5H10N2O3 152.0932 8.25 glycine C2H5NO2 76.0393 8.14 histamine C5H9N3 112.0869 9.41 histidine C6H9N3O2 156.0768 9.48 homocysteine C4H9NO2S 136.0427 NA isoleucine C6H13NO2 132.1019 7.30 kynurenic acid C10H7NO3 190.0499 NA leucine C6H13NO2 132.1019 7.17 lysine C6H14N2O2 147.1128 9.60 methionine C5H11NO2S 150.0583 7.25 methionine sulfoxide C5H11NO3S 166.0532 8.83 methylthioadenosine C11H15N5O3S 298.0968 4.44 N-carbamoyl-beta-alanine C4H8N2O3 133.0608 NA niacinamide C6H6N2O 123.0553 3.95 NMMA C7H16N4O2 189.1346 9.57 ornithine C5H12N2O2 133.0972 9.49 ornithine[15]N C5H12[15]N1N1O2 134.0941 9.49 ornithine[13]C1[15]N1 [13]CC4H12[15]N1N1O2 135.0975 9.49 ornithine [13]C5 [13]C5H12N2O2 138.1139 9.49 phenylalanine C9H11NO2 166.0863 6.93 phosphocholine C5H15NO4P 184.0733 11.49 phosphoethanolamine C2H8NO4P 142.0264 9.21 pipecolic acid C6H11NO2 130.0863 8.17 pipecolic acid[15]N C6H11[15]NO2 131.0832 8.17 pipecholic acid[13]C1[15]N1 [13]CC5H11[15]NO2 132.0866 8.17 pipecolic acid [13]C5 [13]C5CH11NO2 135.1030 8.17 proline C5H9NO2 116.0706 8.30 proline[15]N C5H9[15]NO2 117.0676 8.30 proline[13]C1[15]N1 [13]CC4H9[15]NO2 118.0710 8.30 proline [13]C5 [13]C5H9NO2 121.0874 8.30 putrescine C4H12N2 89.1073 9.58 pyroglutamic acid C5H7NO3 130.0499 8.25 s-adenosylmethionine C15H23N6O5S 399.1451 10.35 sarcosine C3H7NO2 90.0550 NA SDMA C8H18N4O2 203.1503 NA serine C3H7NO3 106.0499 7.89 spermidine C7H19N3 146.1652 10.78 taurine C2H7NO3S 126.0219 6.32 thiamine C12H17N4OS 265.1118 9.84 threonine C4H9NO3 120.0655 7.82 thymidine C10H14N2O5 243.0976 3.07 trans-hydroxyproline C5H9NO3 132.0655 8.14 trans-hydroxyproline[15]N C5H9[15]NO3 133.0625 8.14 trans-hydroxyproline[13]C1[15]N1 [13]CC4H9[15]NO3 134.0659 8.14 trans-hydroxyproline [13]C5 [13]C5H9NO3 137.0823 8.14 trimethylamine-N-oxide C3H9NO 76.0757 8.29 tryptophan C11H12N2O2 205.0972 6.72 tyrosine C9H11NO3 182.0812 7.04 valine C5H11NO2 118.0863 7.62 xanthosine C10H12N4O6 285.0830 4.58 METABOLITES_END #END