#METABOLOMICS WORKBENCH stephensondj_20240227_094013 DATATRACK_ID:4676 STUDY_ID:ST003108 ANALYSIS_ID:AN005087 PROJECT_ID:PR001931 VERSION 1 CREATED_ON February 27, 2024, 10:57 am #PROJECT PR:PROJECT_TITLE Complete absence of GLUT1 does not impair human terminal erythroid PR:PROJECT_TITLE differentiation PR:PROJECT_SUMMARY The Glucose transporter 1 (GLUT1) is one of the most abundant proteins within PR:PROJECT_SUMMARY the erythrocyte membrane and is required for glucose and dehydroascorbic acid PR:PROJECT_SUMMARY (Vitamin C precursor) transport. It is widely recognized as a key protein for PR:PROJECT_SUMMARY red cell structure, function, and metabolism. Previous reports highlighted the PR:PROJECT_SUMMARY importance of GLUT1 activity within these uniquely glycolysis-dependent cells, PR:PROJECT_SUMMARY in particular for increasing antioxidant capacity needed to avoid irreversible PR:PROJECT_SUMMARY damage from oxidative stress in humans. However, studies of glucose transporter PR:PROJECT_SUMMARY roles in erythroid cells are complicated by species-specific differences between PR:PROJECT_SUMMARY humans and mice. Here, using CRISPRmediated gene editing of immortalized PR:PROJECT_SUMMARY erythroblasts and adult CD34+ hematopoietic progenitor cells, we generate PR:PROJECT_SUMMARY committed human erythroid cells completely deficient in expression of GLUT1. We PR:PROJECT_SUMMARY show that absence of GLUT1 does not impede human erythroblast proliferation, PR:PROJECT_SUMMARY differentiation, or enucleation. This work demonstrates for the first-time PR:PROJECT_SUMMARY generation of enucleated human reticulocytes lacking GLUT1. The GLUT1-deficient PR:PROJECT_SUMMARY reticulocytes possess no tangible alterations to membrane composition or PR:PROJECT_SUMMARY deformability in reticulocytes. Metabolomic analyses of GLUT1-deficient PR:PROJECT_SUMMARY reticulocytes reveal hallmarks of reduced glucose import, downregulated PR:PROJECT_SUMMARY metabolic processes and upregulated AMPK-signalling, alongside alterations in PR:PROJECT_SUMMARY antioxidant metabolism, resulting in increased osmotic fragility and metabolic PR:PROJECT_SUMMARY shifts indicative of higher oxidant stress. Despite detectable metabolic changes PR:PROJECT_SUMMARY in GLUT1 deficient reticulocytes, the absence of developmental phenotype, PR:PROJECT_SUMMARY detectable proteomic compensation or impaired deformability comprehensively PR:PROJECT_SUMMARY alters our understanding of the role of GLUT1 in red blood cell structure, PR:PROJECT_SUMMARY function and metabolism. It also provides cell biological evidence supporting PR:PROJECT_SUMMARY clinical consensus that reduced GLUT1 expression does not cause anaemia in GLUT1 PR:PROJECT_SUMMARY deficiency syndrome. PR:INSTITUTE University of Colorado PR:LAST_NAME Stephenson PR:FIRST_NAME Daniel PR:ADDRESS Research 1 South L18-1303 12801 E. 17th Ave., Aurora, Colorado, 80045, USA PR:EMAIL daniel.stephenson@cuanschutz.edu PR:PHONE 303-724-3339 #STUDY ST:STUDY_TITLE Complete absence of GLUT1 does not impair human terminal erythroid ST:STUDY_TITLE differentiation ST:STUDY_SUMMARY The Glucose transporter 1 (GLUT1) is one of the most abundant proteins within ST:STUDY_SUMMARY the erythrocyte membrane and is required for glucose and dehydroascorbic acid ST:STUDY_SUMMARY (Vitamin C precursor) transport. It is widely recognized as a key protein for ST:STUDY_SUMMARY red cell structure, function, and metabolism. Previous reports highlighted the ST:STUDY_SUMMARY importance of GLUT1 activity within these uniquely glycolysis-dependent cells, ST:STUDY_SUMMARY in particular for increasing antioxidant capacity needed to avoid irreversible ST:STUDY_SUMMARY damage from oxidative stress in humans. However, studies of glucose transporter ST:STUDY_SUMMARY roles in erythroid cells are complicated by species-specific differences between ST:STUDY_SUMMARY humans and mice. Here, using CRISPRmediated gene editing of immortalized ST:STUDY_SUMMARY erythroblasts and adult CD34+ hematopoietic progenitor cells, we generate ST:STUDY_SUMMARY committed human erythroid cells completely deficient in expression of GLUT1. We ST:STUDY_SUMMARY show that absence of GLUT1 does not impede human erythroblast proliferation, ST:STUDY_SUMMARY differentiation, or enucleation. This work demonstrates for the first-time ST:STUDY_SUMMARY generation of enucleated human reticulocytes lacking GLUT1. The GLUT1-deficient ST:STUDY_SUMMARY reticulocytes possess no tangible alterations to membrane composition or ST:STUDY_SUMMARY deformability in reticulocytes. Metabolomic analyses of GLUT1-deficient ST:STUDY_SUMMARY reticulocytes reveal hallmarks of reduced glucose import, downregulated ST:STUDY_SUMMARY metabolic processes and upregulated AMPK-signalling, alongside alterations in ST:STUDY_SUMMARY antioxidant metabolism, resulting in increased osmotic fragility and metabolic ST:STUDY_SUMMARY shifts indicative of higher oxidant stress. Despite detectable metabolic changes ST:STUDY_SUMMARY in GLUT1 deficient reticulocytes, the absence of developmental phenotype, ST:STUDY_SUMMARY detectable proteomic compensation or impaired deformability comprehensively ST:STUDY_SUMMARY alters our understanding of the role of GLUT1 in red blood cell structure, ST:STUDY_SUMMARY function and metabolism. It also provides cell biological evidence supporting ST:STUDY_SUMMARY clinical consensus that reduced GLUT1 expression does not cause anaemia in GLUT1 ST:STUDY_SUMMARY deficiency syndrome. ST:INSTITUTE University of Colorado ST:LAST_NAME Stephenson ST:FIRST_NAME Daniel ST:ADDRESS Research 1 South L18-1303 12801 E. 17th Ave., Aurora, Colorado, 80045, USA ST:EMAIL daniel.stephenson@cuanschutz.edu ST:PHONE 303-724-3339 #SUBJECT SU:SUBJECT_TYPE Cultured cells SU:SUBJECT_SPECIES Homo sapiens SU:TAXONOMY_ID 9606 #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 Donor 1 DS1-095-001+ Sample source:cultured reticulocytes | Assay:04CF29 RAW_FILE_NAME(Raw File Name)=DS1-095-001+.mzXML; Pellet size=10 Million; Analysis=Metabolomics; Polarity=Positive SUBJECT_SAMPLE_FACTORS Donor 1 DS1-095-002+ Sample source:cultured reticulocytes | Assay:04CF29 RAW_FILE_NAME(Raw File Name)=DS1-095-002+.mzXML; Pellet size=10 Million; Analysis=Metabolomics; Polarity=Positive SUBJECT_SAMPLE_FACTORS Donor 4 DS1-095-003+ Sample source:cultured reticulocytes | Assay:04CF29 RAW_FILE_NAME(Raw File Name)=DS1-095-003+.mzXML; Pellet size=10 Million; Analysis=Metabolomics; Polarity=Positive SUBJECT_SAMPLE_FACTORS Donor 4 DS1-095-004+ Sample source:cultured reticulocytes | Assay:04CF29 RAW_FILE_NAME(Raw File Name)=DS1-095-004+.mzXML; Pellet size=10 Million; Analysis=Metabolomics; Polarity=Positive SUBJECT_SAMPLE_FACTORS Donor 5 DS1-095-005+ Sample source:cultured reticulocytes | Assay:04CF29 RAW_FILE_NAME(Raw File Name)=DS1-095-005+.mzXML; Pellet size=10 Million; Analysis=Metabolomics; Polarity=Positive SUBJECT_SAMPLE_FACTORS Donor 5 DS1-095-006+ Sample source:cultured reticulocytes | Assay:04CF29 RAW_FILE_NAME(Raw File Name)=DS1-095-006+.mzXML; Pellet size=10 Million; Analysis=Metabolomics; Polarity=Positive SUBJECT_SAMPLE_FACTORS Donor A DS1-095-007+ Sample source:cultured reticulocytes | Assay:01CF19 RAW_FILE_NAME(Raw File Name)=DS1-095-007+.mzXML; Pellet size=10 Million; Analysis=Metabolomics; Polarity=Positive SUBJECT_SAMPLE_FACTORS Donor C DS1-095-008+ Sample source:cultured reticulocytes | Assay:01CF19 RAW_FILE_NAME(Raw File Name)=DS1-095-008+.mzXML; Pellet size=10 Million; Analysis=Metabolomics; Polarity=Positive SUBJECT_SAMPLE_FACTORS Donor D DS1-095-009+ Sample source:cultured reticulocytes | Assay:01CF19 RAW_FILE_NAME(Raw File Name)=DS1-095-009+.mzXML; Pellet size=10 Million; Analysis=Metabolomics; Polarity=Positive SUBJECT_SAMPLE_FACTORS Donor A DS1-095-010+ Sample source:cultured reticulocytes | Assay:01CF19 RAW_FILE_NAME(Raw File Name)=DS1-095-010+.mzXML; Pellet size=10 Million; Analysis=Metabolomics; Polarity=Positive SUBJECT_SAMPLE_FACTORS Donor C DS1-095-011+ Sample source:cultured reticulocytes | Assay:01CF19 RAW_FILE_NAME(Raw File Name)=DS1-095-011+.mzXML; Pellet size=10 Million; Analysis=Metabolomics; Polarity=Positive SUBJECT_SAMPLE_FACTORS Donor D DS1-095-012+ Sample source:cultured reticulocytes | Assay:01CF19 RAW_FILE_NAME(Raw File Name)=DS1-095-012+.mzXML; Pellet size=10 Million; Analysis=Metabolomics; Polarity=Positive SUBJECT_SAMPLE_FACTORS Donor A DS1-095-013+ Sample source:cultured reticulocytes | Assay:01CF19 RAW_FILE_NAME(Raw File Name)=DS1-095-013+.mzXML; Pellet size=10 Million; Analysis=Metabolomics; Polarity=Positive SUBJECT_SAMPLE_FACTORS Donor C DS1-095-014+ Sample source:cultured reticulocytes | Assay:01CF19 RAW_FILE_NAME(Raw File Name)=DS1-095-014+.mzXML; Pellet size=10 Million; Analysis=Metabolomics; Polarity=Positive SUBJECT_SAMPLE_FACTORS Donor D DS1-095-015+ Sample source:cultured reticulocytes | Assay:01CF19 RAW_FILE_NAME(Raw File Name)=DS1-095-015+.mzXML; Pellet size=10 Million; Analysis=Metabolomics; Polarity=Positive SUBJECT_SAMPLE_FACTORS Donor A DS1-095-016+ Sample source:Red blood cells | Assay:01CF19 RAW_FILE_NAME(Raw File Name)=DS1-095-016+.mzXML; Pellet size=10 Million; Analysis=Metabolomics; Polarity=Positive SUBJECT_SAMPLE_FACTORS Donor C DS1-095-017+ Sample source:Red blood cells | Assay:01CF19 RAW_FILE_NAME(Raw File Name)=DS1-095-017+.mzXML; Pellet size=10 Million; Analysis=Metabolomics; Polarity=Positive SUBJECT_SAMPLE_FACTORS Donor D DS1-095-018+ Sample source:Red blood cells | Assay:01CF19 RAW_FILE_NAME(Raw File Name)=DS1-095-018+.mzXML; Pellet size=10 Million; Analysis=Metabolomics; Polarity=Positive SUBJECT_SAMPLE_FACTORS Donor 1 DS1-095-001- Sample source:cultured reticulocytes | Assay:04CF29 RAW_FILE_NAME(Raw File Name)=DS1-095-001-.mzXML; Pellet size=10 Million; Analysis=Metabolomics; Polarity=Negative SUBJECT_SAMPLE_FACTORS Donor 1 DS1-095-002- Sample source:cultured reticulocytes | Assay:04CF29 RAW_FILE_NAME(Raw File Name)=DS1-095-002-.mzXML; Pellet size=10 Million; Analysis=Metabolomics; Polarity=Negative SUBJECT_SAMPLE_FACTORS Donor 4 DS1-095-003- Sample source:cultured reticulocytes | Assay:04CF29 RAW_FILE_NAME(Raw File Name)=DS1-095-003-.mzXML; Pellet size=10 Million; Analysis=Metabolomics; Polarity=Negative SUBJECT_SAMPLE_FACTORS Donor 4 DS1-095-004- Sample source:cultured reticulocytes | Assay:04CF29 RAW_FILE_NAME(Raw File Name)=DS1-095-004-.mzXML; Pellet size=10 Million; Analysis=Metabolomics; Polarity=Negative SUBJECT_SAMPLE_FACTORS Donor 5 DS1-095-005- Sample source:cultured reticulocytes | Assay:04CF29 RAW_FILE_NAME(Raw File Name)=DS1-095-005-.mzXML; Pellet size=10 Million; Analysis=Metabolomics; Polarity=Negative SUBJECT_SAMPLE_FACTORS Donor 5 DS1-095-006- Sample source:cultured reticulocytes | Assay:04CF29 RAW_FILE_NAME(Raw File Name)=DS1-095-006-.mzXML; Pellet size=10 Million; Analysis=Metabolomics; Polarity=Negative SUBJECT_SAMPLE_FACTORS Donor A DS1-095-007- Sample source:cultured reticulocytes | Assay:01CF19 RAW_FILE_NAME(Raw File Name)=DS1-095-007-.mzXML; Pellet size=10 Million; Analysis=Metabolomics; Polarity=Negative SUBJECT_SAMPLE_FACTORS Donor C DS1-095-008- Sample source:cultured reticulocytes | Assay:01CF19 RAW_FILE_NAME(Raw File Name)=DS1-095-008-.mzXML; Pellet size=10 Million; Analysis=Metabolomics; Polarity=Negative SUBJECT_SAMPLE_FACTORS Donor D DS1-095-009- Sample source:cultured reticulocytes | Assay:01CF19 RAW_FILE_NAME(Raw File Name)=DS1-095-009-.mzXML; Pellet size=10 Million; Analysis=Metabolomics; Polarity=Negative SUBJECT_SAMPLE_FACTORS Donor A DS1-095-010- Sample source:cultured reticulocytes | Assay:01CF19 RAW_FILE_NAME(Raw File Name)=DS1-095-010-.mzXML; Pellet size=10 Million; Analysis=Metabolomics; Polarity=Negative SUBJECT_SAMPLE_FACTORS Donor C DS1-095-011- Sample source:cultured reticulocytes | Assay:01CF19 RAW_FILE_NAME(Raw File Name)=DS1-095-011-.mzXML; Pellet size=10 Million; Analysis=Metabolomics; Polarity=Negative SUBJECT_SAMPLE_FACTORS Donor D DS1-095-012- Sample source:cultured reticulocytes | Assay:01CF19 RAW_FILE_NAME(Raw File Name)=DS1-095-012-.mzXML; Pellet size=10 Million; Analysis=Metabolomics; Polarity=Negative SUBJECT_SAMPLE_FACTORS Donor A DS1-095-013- Sample source:cultured reticulocytes | Assay:01CF19 RAW_FILE_NAME(Raw File Name)=DS1-095-013-.mzXML; Pellet size=10 Million; Analysis=Metabolomics; Polarity=Negative SUBJECT_SAMPLE_FACTORS Donor C DS1-095-014- Sample source:cultured reticulocytes | Assay:01CF19 RAW_FILE_NAME(Raw File Name)=DS1-095-014-.mzXML; Pellet size=10 Million; Analysis=Metabolomics; Polarity=Negative SUBJECT_SAMPLE_FACTORS Donor D DS1-095-015- Sample source:cultured reticulocytes | Assay:01CF19 RAW_FILE_NAME(Raw File Name)=DS1-095-015-.mzXML; Pellet size=10 Million; Analysis=Metabolomics; Polarity=Negative SUBJECT_SAMPLE_FACTORS Donor A DS1-095-016- Sample source:Red blood cells | Assay:01CF19 RAW_FILE_NAME(Raw File Name)=DS1-095-016-.mzXML; Pellet size=10 Million; Analysis=Metabolomics; Polarity=Negative SUBJECT_SAMPLE_FACTORS Donor C DS1-095-017- Sample source:Red blood cells | Assay:01CF19 RAW_FILE_NAME(Raw File Name)=DS1-095-017-.mzXML; Pellet size=10 Million; Analysis=Metabolomics; Polarity=Negative SUBJECT_SAMPLE_FACTORS Donor D DS1-095-018- Sample source:Red blood cells | Assay:01CF19 RAW_FILE_NAME(Raw File Name)=DS1-095-018-.mzXML; Pellet size=10 Million; Analysis=Metabolomics; Polarity=Negative SUBJECT_SAMPLE_FACTORS Donor 1 DS1-095-001L+ Sample source:cultured reticulocytes | Assay:04CF29 RAW_FILE_NAME(Raw File Name)=DS1-095-001L+.RAW; Pellet size=10 Million; Analysis=Lipidomics; Polarity=Positive SUBJECT_SAMPLE_FACTORS Donor 1 DS1-095-002L+ Sample source:cultured reticulocytes | Assay:04CF29 RAW_FILE_NAME(Raw File Name)=DS1-095-002L+.RAW; Pellet size=10 Million; Analysis=Lipidomics; Polarity=Positive SUBJECT_SAMPLE_FACTORS Donor 4 DS1-095-003L+ Sample source:cultured reticulocytes | Assay:04CF29 RAW_FILE_NAME(Raw File Name)=DS1-095-003L+.RAW; Pellet size=10 Million; Analysis=Lipidomics; Polarity=Positive SUBJECT_SAMPLE_FACTORS Donor 4 DS1-095-004L+ Sample source:cultured reticulocytes | Assay:04CF29 RAW_FILE_NAME(Raw File Name)=DS1-095-004L+.RAW; Pellet size=10 Million; Analysis=Lipidomics; Polarity=Positive SUBJECT_SAMPLE_FACTORS Donor 5 DS1-095-005L+ Sample source:cultured reticulocytes | Assay:04CF29 RAW_FILE_NAME(Raw File Name)=DS1-095-005L+.RAW; Pellet size=10 Million; Analysis=Lipidomics; Polarity=Positive SUBJECT_SAMPLE_FACTORS Donor 5 DS1-095-006L+ Sample source:cultured reticulocytes | Assay:04CF29 RAW_FILE_NAME(Raw File Name)=DS1-095-006L+.RAW; Pellet size=10 Million; Analysis=Lipidomics; Polarity=Positive SUBJECT_SAMPLE_FACTORS Donor A DS1-095-007L+ Sample source:cultured reticulocytes | Assay:01CF19 RAW_FILE_NAME(Raw File Name)=DS1-095-007L+.RAW; Pellet size=10 Million; Analysis=Lipidomics; Polarity=Positive SUBJECT_SAMPLE_FACTORS Donor C DS1-095-008L+ Sample source:cultured reticulocytes | Assay:01CF19 RAW_FILE_NAME(Raw File Name)=DS1-095-008L+.RAW; Pellet size=10 Million; Analysis=Lipidomics; Polarity=Positive SUBJECT_SAMPLE_FACTORS Donor D DS1-095-009L+ Sample source:cultured reticulocytes | Assay:01CF19 RAW_FILE_NAME(Raw File Name)=DS1-095-009L+.RAW; Pellet size=10 Million; Analysis=Lipidomics; Polarity=Positive SUBJECT_SAMPLE_FACTORS Donor A DS1-095-010L+ Sample source:cultured reticulocytes | Assay:01CF19 RAW_FILE_NAME(Raw File Name)=DS1-095-010L+.RAW; Pellet size=10 Million; Analysis=Lipidomics; Polarity=Positive SUBJECT_SAMPLE_FACTORS Donor C DS1-095-011L+ Sample source:cultured reticulocytes | Assay:01CF19 RAW_FILE_NAME(Raw File Name)=DS1-095-011L+.RAW; Pellet size=10 Million; Analysis=Lipidomics; Polarity=Positive SUBJECT_SAMPLE_FACTORS Donor D DS1-095-012L+ Sample source:cultured reticulocytes | Assay:01CF19 RAW_FILE_NAME(Raw File Name)=DS1-095-012L+.RAW; Pellet size=10 Million; Analysis=Lipidomics; Polarity=Positive SUBJECT_SAMPLE_FACTORS Donor A DS1-095-013L+ Sample source:cultured reticulocytes | Assay:01CF19 RAW_FILE_NAME(Raw File Name)=DS1-095-013L+.RAW; Pellet size=10 Million; Analysis=Lipidomics; Polarity=Positive SUBJECT_SAMPLE_FACTORS Donor C DS1-095-014L+ Sample source:cultured reticulocytes | Assay:01CF19 RAW_FILE_NAME(Raw File Name)=DS1-095-014L+.RAW; Pellet size=10 Million; Analysis=Lipidomics; Polarity=Positive SUBJECT_SAMPLE_FACTORS Donor D DS1-095-015L+ Sample source:cultured reticulocytes | Assay:01CF19 RAW_FILE_NAME(Raw File Name)=DS1-095-015L+.RAW; Pellet size=10 Million; Analysis=Lipidomics; Polarity=Positive SUBJECT_SAMPLE_FACTORS Donor A DS1-095-016L+ Sample source:Red blood cells | Assay:01CF19 RAW_FILE_NAME(Raw File Name)=DS1-095-016L+.RAW; Pellet size=10 Million; Analysis=Lipidomics; Polarity=Positive SUBJECT_SAMPLE_FACTORS Donor C DS1-095-017L+ Sample source:Red blood cells | Assay:01CF19 RAW_FILE_NAME(Raw File Name)=DS1-095-017L+.RAW; Pellet size=10 Million; Analysis=Lipidomics; Polarity=Positive SUBJECT_SAMPLE_FACTORS Donor D DS1-095-018L+ Sample source:Red blood cells | Assay:01CF19 RAW_FILE_NAME(Raw File Name)=DS1-095-018L+.RAW; Pellet size=10 Million; Analysis=Lipidomics; Polarity=Positive SUBJECT_SAMPLE_FACTORS Donor 1 DS1-095-001L- Sample source:cultured reticulocytes | Assay:04CF29 RAW_FILE_NAME(Raw File Name)=DS1-095-001L-.RAW; Pellet size=10 Million; Analysis=Lipidomics; Polarity=Negative SUBJECT_SAMPLE_FACTORS Donor 1 DS1-095-002L- Sample source:cultured reticulocytes | Assay:04CF29 RAW_FILE_NAME(Raw File Name)=DS1-095-002L-.RAW; Pellet size=10 Million; Analysis=Lipidomics; Polarity=Negative SUBJECT_SAMPLE_FACTORS Donor 4 DS1-095-003L- Sample source:cultured reticulocytes | Assay:04CF29 RAW_FILE_NAME(Raw File Name)=DS1-095-003L-.RAW; Pellet size=10 Million; Analysis=Lipidomics; Polarity=Negative SUBJECT_SAMPLE_FACTORS Donor 4 DS1-095-004L- Sample source:cultured reticulocytes | Assay:04CF29 RAW_FILE_NAME(Raw File Name)=DS1-095-004L-.RAW; Pellet size=10 Million; Analysis=Lipidomics; Polarity=Negative SUBJECT_SAMPLE_FACTORS Donor 5 DS1-095-005L- Sample source:cultured reticulocytes | Assay:04CF29 RAW_FILE_NAME(Raw File Name)=DS1-095-005L-.RAW; Pellet size=10 Million; Analysis=Lipidomics; Polarity=Negative SUBJECT_SAMPLE_FACTORS Donor 5 DS1-095-006L- Sample source:cultured reticulocytes | Assay:04CF29 RAW_FILE_NAME(Raw File Name)=DS1-095-006L-.RAW; Pellet size=10 Million; Analysis=Lipidomics; Polarity=Negative SUBJECT_SAMPLE_FACTORS Donor A DS1-095-007L- Sample source:cultured reticulocytes | Assay:01CF19 RAW_FILE_NAME(Raw File Name)=DS1-095-007L-.RAW; Pellet size=10 Million; Analysis=Lipidomics; Polarity=Negative SUBJECT_SAMPLE_FACTORS Donor C DS1-095-008L- Sample source:cultured reticulocytes | Assay:01CF19 RAW_FILE_NAME(Raw File Name)=DS1-095-008L-.RAW; Pellet size=10 Million; Analysis=Lipidomics; Polarity=Negative SUBJECT_SAMPLE_FACTORS Donor D DS1-095-009L- Sample source:cultured reticulocytes | Assay:01CF19 RAW_FILE_NAME(Raw File Name)=DS1-095-009L-.RAW; Pellet size=10 Million; Analysis=Lipidomics; Polarity=Negative SUBJECT_SAMPLE_FACTORS Donor A DS1-095-010L- Sample source:cultured reticulocytes | Assay:01CF19 RAW_FILE_NAME(Raw File Name)=DS1-095-010L-.RAW; Pellet size=10 Million; Analysis=Lipidomics; Polarity=Negative SUBJECT_SAMPLE_FACTORS Donor C DS1-095-011L- Sample source:cultured reticulocytes | Assay:01CF19 RAW_FILE_NAME(Raw File Name)=DS1-095-011L-.RAW; Pellet size=10 Million; Analysis=Lipidomics; Polarity=Negative SUBJECT_SAMPLE_FACTORS Donor D DS1-095-012L- Sample source:cultured reticulocytes | Assay:01CF19 RAW_FILE_NAME(Raw File Name)=DS1-095-012L-.RAW; Pellet size=10 Million; Analysis=Lipidomics; Polarity=Negative SUBJECT_SAMPLE_FACTORS Donor A DS1-095-013L- Sample source:cultured reticulocytes | Assay:01CF19 RAW_FILE_NAME(Raw File Name)=DS1-095-013L-.RAW; Pellet size=10 Million; Analysis=Lipidomics; Polarity=Negative SUBJECT_SAMPLE_FACTORS Donor C DS1-095-014L- Sample source:cultured reticulocytes | Assay:01CF19 RAW_FILE_NAME(Raw File Name)=DS1-095-014L-.RAW; Pellet size=10 Million; Analysis=Lipidomics; Polarity=Negative SUBJECT_SAMPLE_FACTORS Donor D DS1-095-015L- Sample source:cultured reticulocytes | Assay:01CF19 RAW_FILE_NAME(Raw File Name)=DS1-095-015L-.RAW; Pellet size=10 Million; Analysis=Lipidomics; Polarity=Negative SUBJECT_SAMPLE_FACTORS Donor A DS1-095-016L- Sample source:Red blood cells | Assay:01CF19 RAW_FILE_NAME(Raw File Name)=DS1-095-016L-.RAW; Pellet size=10 Million; Analysis=Lipidomics; Polarity=Negative SUBJECT_SAMPLE_FACTORS Donor C DS1-095-017L- Sample source:Red blood cells | Assay:01CF19 RAW_FILE_NAME(Raw File Name)=DS1-095-017L-.RAW; Pellet size=10 Million; Analysis=Lipidomics; Polarity=Negative SUBJECT_SAMPLE_FACTORS Donor D DS1-095-018L- Sample source:Red blood cells | Assay:01CF19 RAW_FILE_NAME(Raw File Name)=DS1-095-018L-.RAW; Pellet size=10 Million; Analysis=Lipidomics; Polarity=Negative #COLLECTION CO:COLLECTION_SUMMARY For flow cytometry, cells were fixed (1% paraformaldehyde, 0.0075% CO:COLLECTION_SUMMARY glutaraldehyde) to prevent antibody agglutination, except for assays using CO:COLLECTION_SUMMARY GLUT1.RBD. Samples were labelled with primary antibodies in PBSAG (PBS with 1% CO:COLLECTION_SUMMARY (w/v) Glucose and 0.5%(w/v) |Bovine Serum Albumin (BSA)) supplemented with extra CO:COLLECTION_SUMMARY 1%(w/v) BSA for 30min, in the dark. METAFORA’s GLUT1.RBD was incubated at CO:COLLECTION_SUMMARY 37°C and all remaining antibodies incubated at 4°C. Cells were washed 2x PBSAG CO:COLLECTION_SUMMARY and, if required, incubated with appropriate secondary antibody under the same CO:COLLECTION_SUMMARY conditions as described for primary. Cells were washed 2x with PBSAG and CO:COLLECTION_SUMMARY analysed on a Miltenyi MACSQuant 10 flow cytometer. Data was analysed using CO:COLLECTION_SUMMARY FlowJo v10.7 (FlowJo). Reticulocytes were identified by gating on the CO:COLLECTION_SUMMARY Hoechst-negative population. 4 Cells were sorted using a BD Influx Cell Sorter CO:COLLECTION_SUMMARY (BD Biosciences). BEL-A CRISPR edited populations were single cell sorted based CO:COLLECTION_SUMMARY on viability (DRAQ7 negativity). Primary GLUT1 KO cultures were sorted on days 6 CO:COLLECTION_SUMMARY or 7 of differentiation using DRAQ7 and the eGFP-fused GLUT1.RBD to purify the CO:COLLECTION_SUMMARY negative population with a gate based on non-targeting guide control cells. CO:SAMPLE_TYPE Cultured cells #TREATMENT TR:TREATMENT_SUMMARY Filtered reticulocytes (1-2 x105/well) were incubated in decreasing NaCl TR:TREATMENT_SUMMARY concentrations (0.9–0%) for 10min at 37°C. Lysis was stopped by adding 4x TR:TREATMENT_SUMMARY volume of PBSAG. Live cells, considered as having a normal FSC/SSC profile as TR:TREATMENT_SUMMARY defined by the 0.9% NaCl control, were counted by flow cytometry using the TR:TREATMENT_SUMMARY MACSQuant10 #SAMPLEPREP SP:SAMPLEPREP_SUMMARY Extraction of metabolites and lipids from red cell pellets was as follows: 36 SP:SAMPLEPREP_SUMMARY µL of cold MeOH:MeCN:H2O (5:3:2, v:v:v) was added to all pellets (pellet size SP:SAMPLEPREP_SUMMARY pre-determined to be 10 million prior to extraction). Samples were vortexed at SP:SAMPLEPREP_SUMMARY 4°C for 30 minutes. Insoluble material was pelleted by centrifugation (18000g, SP:SAMPLEPREP_SUMMARY 10 min) and supernatants were isolated for analysis by UHPLC-MS for metabolomics SP:SAMPLEPREP_SUMMARY and lipidomics. #CHROMATOGRAPHY CH:CHROMATOGRAPHY_SUMMARY Metabolomics Positive CH:CHROMATOGRAPHY_TYPE Reversed phase CH:INSTRUMENT_NAME Thermo Vanquish CH:COLUMN_NAME Phenomenex Kinetex C18 (150 x 2.1mm,1.7um) CH:SOLVENT_A 0.1% Formic Acid in Water CH:SOLVENT_B 0.1% Formic Acid in ACN CH:FLOW_GRADIENT 0 min - 0.45 ml/min - 5% B, 0.5 min - 0.45ml/min - 5% B, 1.1 min - 0.45ml/min - CH:FLOW_GRADIENT 95% B, 2.75 min - 0.45ml/min - 95% B, 3 min - 0.45ml/min - 5% B, 5min - CH:FLOW_GRADIENT 0.45ml/min - 5%B CH:FLOW_RATE 0.45 ml/min CH:COLUMN_TEMPERATURE 45 #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 El-Maven used for data analysis #MS_METABOLITE_DATA MS_METABOLITE_DATA:UNITS area MS_METABOLITE_DATA_START Samples DS1-095-001+ DS1-095-002+ DS1-095-003+ DS1-095-004+ DS1-095-005+ DS1-095-006+ DS1-095-007+ DS1-095-008+ DS1-095-009+ DS1-095-010+ DS1-095-011+ DS1-095-012+ DS1-095-013+ DS1-095-014+ DS1-095-015+ DS1-095-016+ DS1-095-017+ DS1-095-018+ Factors Sample source:cultured reticulocytes | Assay:04CF29 Sample source:cultured reticulocytes | Assay:04CF29 Sample source:cultured reticulocytes | Assay:04CF29 Sample source:cultured reticulocytes | Assay:04CF29 Sample source:cultured reticulocytes | Assay:04CF29 Sample source:cultured reticulocytes | Assay:04CF29 Sample source:cultured reticulocytes | Assay:01CF19 Sample source:cultured reticulocytes | Assay:01CF19 Sample source:cultured reticulocytes | Assay:01CF19 Sample source:cultured reticulocytes | Assay:01CF19 Sample source:cultured reticulocytes | Assay:01CF19 Sample source:cultured reticulocytes | Assay:01CF19 Sample source:cultured reticulocytes | Assay:01CF19 Sample source:cultured reticulocytes | Assay:01CF19 Sample source:cultured reticulocytes | Assay:01CF19 Sample source:Red blood cells | Assay:01CF19 Sample source:Red blood cells | Assay:01CF19 Sample source:Red blood cells | Assay:01CF19 L-alanine 4.73E+06 4.35E+06 2.75E+06 3.20E+06 4.96E+06 4.77E+06 3.88E+06 3.76E+06 3.26E+06 7.96E+06 9.62E+06 4.75E+06 5.32E+06 3.16E+06 6.33E+06 1.04E+06 9.02E+05 1.14E+06 L-arginine 8.78E+04 9.29E+04 1.00E+05 6.25E+04 2.20E+05 2.55E+05 4.54E+04 6.00E+04 1.09E+05 1.02E+05 1.79E+05 2.26E+05 5.65E+04 4.77E+04 5.12E+05 9.18E+04 5.36E+04 8.62E+04 L-asparagine 3.21E+05 2.12E+05 1.62E+05 1.32E+05 2.00E+05 1.63E+05 1.56E+05 1.34E+05 1.40E+05 3.58E+05 4.24E+05 1.47E+05 1.94E+05 1.37E+05 2.04E+05 4.03E+04 3.14E+04 8.58E+04 L-cysteine 2.36E+04 1.91E+04 2.04E+04 2.31E+04 2.55E+04 1.56E+04 2.07E+04 2.41E+04 2.14E+04 3.03E+04 3.52E+04 4.81E+04 3.68E+04 2.58E+04 2.96E+04 1.91E+04 2.57E+04 1.67E+04 glycine 8.29E+05 6.56E+05 5.84E+05 5.64E+05 9.29E+05 6.01E+05 1.02E+06 8.83E+05 6.85E+05 1.65E+06 2.25E+06 8.52E+05 1.53E+06 9.25E+05 1.78E+06 1.80E+05 1.67E+05 2.83E+05 L-histidine 6.87E+05 4.95E+05 2.23E+05 2.16E+05 7.71E+05 6.56E+05 7.96E+05 7.31E+05 3.98E+05 2.14E+06 1.76E+06 4.31E+05 3.59E+05 2.18E+05 3.48E+05 5.33E+05 3.97E+05 5.96E+05 L-leucine/isoluecine 4.42E+05 4.54E+05 4.35E+05 4.15E+05 3.81E+05 3.85E+05 5.79E+05 4.74E+05 8.98E+05 5.82E+05 6.18E+05 7.47E+05 7.76E+05 8.99E+05 1.06E+06 3.59E+05 3.26E+05 3.32E+05 L-lysine 6.50E+05 4.05E+05 3.25E+05 2.31E+05 6.36E+05 5.07E+05 7.62E+05 7.59E+05 5.47E+05 1.70E+06 1.80E+06 5.29E+05 6.52E+05 5.65E+05 6.49E+05 4.56E+05 3.23E+05 5.00E+05 L-methionine 5.70E+04 4.82E+04 4.42E+04 3.56E+04 5.07E+04 5.09E+04 7.09E+04 4.62E+04 6.32E+04 9.96E+04 6.34E+04 3.74E+04 8.59E+04 4.92E+04 8.53E+04 1.05E+04 1.61E+04 4.94E+04 L-phenylalanine 2.71E+05 1.87E+05 2.35E+05 2.58E+05 1.76E+05 2.38E+05 2.75E+05 2.63E+05 4.25E+05 3.37E+05 2.79E+05 3.98E+05 3.29E+05 4.38E+05 4.96E+05 1.63E+05 1.75E+05 1.40E+05 L-proline 5.52E+06 6.53E+06 3.12E+06 4.74E+06 5.22E+06 5.82E+06 4.54E+06 3.45E+06 5.00E+06 1.06E+07 1.29E+07 8.09E+06 6.94E+06 3.85E+06 1.30E+07 2.72E+06 2.23E+06 3.88E+06 L-serine 3.49E+05 2.81E+05 1.59E+05 1.32E+05 3.15E+05 1.93E+05 4.81E+05 2.62E+05 3.59E+05 7.11E+05 6.93E+05 2.59E+05 7.04E+05 2.28E+05 7.23E+05 7.90E+04 6.85E+04 1.20E+05 L-threonine 6.99E+05 8.47E+05 3.28E+05 4.84E+05 7.30E+05 7.77E+05 7.99E+05 5.25E+05 7.12E+05 1.64E+06 1.67E+06 1.11E+06 1.16E+06 5.76E+05 1.78E+06 1.28E+05 1.17E+05 1.61E+05 L-tryptophan 5.51E+05 9.18E+05 5.66E+05 1.27E+06 9.15E+05 1.45E+06 8.88E+05 5.24E+05 6.06E+05 2.28E+06 1.43E+06 1.07E+06 7.83E+05 5.48E+05 1.12E+06 7.65E+05 8.22E+05 5.58E+05 L-tyrosine 1.52E+05 2.70E+05 1.55E+05 2.40E+05 3.05E+05 4.54E+05 2.30E+05 1.78E+05 1.81E+05 8.65E+05 4.28E+05 1.43E+05 2.38E+05 1.24E+05 3.32E+05 2.02E+05 1.76E+05 1.94E+05 L-valine 5.73E+06 4.97E+06 2.50E+06 2.15E+06 4.76E+06 4.56E+06 5.60E+06 7.54E+06 5.23E+06 2.98E+06 4.93E+06 2.09E+06 3.63E+06 4.80E+06 3.98E+06 3.39E+07 4.63E+07 3.90E+07 L-cystine 4.65E+03 8.39E+03 8.97E+03 7.00E+03 1.32E+03 9.84E+03 1.51E+03 8.20E+02 1.02E+03 1.92E+03 9.43E+02 1.94E+03 3.06E+03 1.43E+03 5.00E+03 6.30E+04 1.80E+04 4.93E+04 Adenine 7.33E+04 6.98E+04 8.65E+04 8.54E+04 5.68E+04 5.99E+04 4.43E+04 7.70E+04 6.80E+04 9.88E+04 1.18E+05 4.86E+04 9.60E+04 8.80E+04 1.90E+05 1.53E+06 1.22E+06 5.24E+05 Guanine 2.68E+03 5.35E+03 6.27E+03 5.26E+03 4.79E+03 8.40E+03 5.80E+03 3.79E+03 8.84E+03 9.53E+03 7.92E+03 1.52E+04 9.16E+03 1.34E+04 5.37E+04 3.71E+03 5.14E+03 5.09E+03 Cytosine 8.67E+04 4.90E+04 4.99E+04 2.02E+04 6.27E+04 3.50E+04 6.11E+04 6.94E+04 3.31E+04 1.26E+05 1.63E+05 7.73E+04 1.27E+05 1.24E+05 1.09E+05 2.07E+04 1.25E+04 3.65E+04 Thymine 4.52E+04 3.67E+04 2.92E+04 1.71E+04 4.91E+04 4.76E+04 8.41E+04 1.26E+05 9.62E+04 5.41E+04 9.13E+04 6.97E+04 6.07E+04 5.55E+04 5.95E+04 2.04E+04 2.33E+04 3.24E+04 Hypoxanthine 2.59E+05 1.32E+05 1.63E+05 1.24E+05 1.01E+05 8.02E+04 1.60E+05 1.35E+05 1.20E+05 2.28E+05 1.57E+05 6.71E+04 1.84E+05 8.96E+04 2.95E+05 1.74E+05 1.48E+05 2.10E+05 Xanthine 2.60E+04 3.03E+04 3.03E+04 2.42E+04 3.19E+04 2.94E+04 4.80E+04 3.76E+04 4.53E+04 2.43E+04 3.82E+04 2.80E+04 2.98E+04 3.65E+04 2.58E+04 2.94E+04 3.38E+04 3.36E+04 5-Hydroxyisourate 3.41E+06 1.63E+06 1.02E+06 1.10E+06 2.00E+06 1.28E+06 1.29E+06 1.63E+06 6.26E+05 6.55E+06 6.39E+06 9.54E+05 2.66E+06 1.12E+06 1.64E+06 5.29E+04 5.76E+04 1.92E+04 Allantoate 1.45E+05 1.16E+05 1.02E+05 8.42E+04 1.94E+05 1.86E+05 1.28E+05 1.31E+05 1.62E+05 2.32E+05 2.82E+05 1.89E+05 1.59E+05 1.74E+05 1.39E+05 3.57E+05 3.80E+05 2.45E+05 3',5'-Cyclic AMP 2.64E+05 2.92E+04 4.42E+04 1.85E+04 3.12E+05 2.72E+04 2.75E+05 1.93E+05 4.43E+04 3.31E+05 2.20E+05 1.77E+04 1.38E+05 4.06E+04 3.81E+04 0.00E+00 0.00E+00 1.34E+04 5-6-Dihydrothymine 8.38E+06 5.69E+06 5.65E+06 5.59E+06 9.35E+06 6.13E+06 1.03E+07 1.30E+07 1.34E+07 4.15E+06 4.80E+06 3.23E+06 5.00E+06 4.27E+06 6.94E+06 5.52E+05 1.35E+06 3.56E+05 Pyridoxal 4.72E+04 6.71E+04 5.99E+04 8.50E+04 9.72E+04 1.19E+05 3.06E+04 5.23E+04 7.96E+04 4.02E+04 4.08E+04 3.63E+04 5.23E+04 3.94E+04 4.68E+04 4.60E+04 1.93E+04 1.57E+04 Pyridoxamine 5'-phosphate 1.29E+04 2.36E+04 1.14E+04 2.49E+04 1.65E+04 2.67E+04 1.36E+04 1.13E+04 9.52E+03 3.03E+04 2.93E+04 1.49E+04 1.13E+04 8.09E+03 1.19E+04 1.08E+04 1.61E+04 1.06E+04 Nicotinamide 7.58E+05 5.71E+05 4.54E+05 3.12E+05 4.75E+05 4.41E+05 5.04E+05 5.07E+05 4.42E+05 6.95E+05 6.36E+05 2.89E+05 5.63E+05 4.73E+05 6.16E+05 2.53E+06 3.24E+06 1.49E+06 NAD+ 6.60E+05 2.59E+05 3.21E+05 1.99E+05 3.98E+05 1.09E+05 2.62E+05 2.70E+05 1.93E+05 6.06E+05 6.52E+05 1.74E+05 5.51E+05 2.01E+05 5.83E+05 6.19E+04 3.83E+04 1.35E+05 Mannitol/Sorbitol/Glucitol/Iditol 2.01E+04 3.20E+04 1.28E+04 2.38E+04 2.10E+04 5.28E+04 2.14E+04 2.97E+04 1.46E+04 7.44E+04 2.42E+04 2.34E+04 1.90E+04 1.47E+04 1.05E+04 1.78E+05 1.67E+05 2.45E+05 D-Rhamnose 4.43E+03 1.35E+04 5.20E+03 5.64E+03 6.78E+03 1.99E+04 1.31E+04 1.96E+04 2.72E+04 8.05E+03 9.40E+03 2.39E+04 2.66E+03 8.76E+03 1.01E+04 1.50E+05 1.46E+05 2.60E+05 Cys-Gly 7.11E+05 5.45E+05 6.28E+05 5.84E+05 8.44E+05 4.73E+05 8.00E+05 9.48E+05 9.04E+05 1.57E+06 1.08E+06 7.87E+05 1.50E+06 8.90E+05 1.53E+06 7.16E+05 5.35E+05 6.95E+05 gamma-L-Glutamyl-L-cysteine 3.74E+04 3.00E+04 2.32E+04 2.76E+04 3.06E+04 1.61E+04 2.95E+04 3.78E+04 2.32E+04 4.10E+04 4.35E+04 1.12E+04 4.73E+04 2.92E+04 4.99E+04 3.72E+04 3.22E+04 8.04E+04 gamma-Glutamyl-Se-methylselenocysteine 3.82E+04 3.43E+04 2.00E+04 3.31E+04 4.57E+04 5.26E+04 3.15E+04 3.60E+04 5.98E+04 4.94E+04 6.37E+04 6.92E+04 4.65E+04 6.67E+04 4.71E+04 1.47E+05 1.27E+05 9.07E+04 S-Adenosyl-L-homocysteine 1.48E+04 8.93E+03 7.18E+03 6.04E+03 6.73E+03 3.06E+03 9.66E+03 9.57E+03 3.51E+03 1.71E+03 1.23E+04 0.00E+00 0.00E+00 1.57E+04 1.07E+04 3.07E+05 3.98E+05 3.29E+05 S-Adenosyl-L-methionine 1.17E+04 1.97E+04 1.39E+04 2.30E+04 1.62E+04 2.32E+04 2.73E+04 3.05E+04 1.48E+03 3.63E+04 3.81E+04 0.00E+00 1.99E+04 2.85E+04 4.43E+04 6.44E+04 2.13E+04 1.01E+05 5-10-Methenyltetrahydrofolate 0.00E+00 0.00E+00 0.00E+00 0.00E+00 0.00E+00 0.00E+00 0.00E+00 0.00E+00 0.00E+00 0.00E+00 0.00E+00 0.00E+00 0.00E+00 0.00E+00 0.00E+00 1.23E+05 2.62E+05 4.66E+04 Ornithine 1.72E+05 1.23E+05 1.01E+05 8.24E+04 1.94E+05 1.35E+05 1.51E+05 1.90E+05 1.89E+05 3.89E+05 4.37E+05 1.32E+05 1.71E+05 1.59E+05 1.51E+05 2.99E+05 2.41E+05 2.70E+05 L-Citrulline 4.01E+03 2.20E+03 7.40E+03 0.00E+00 2.59E+03 1.47E+04 0.00E+00 3.30E+03 1.56E+04 1.94E+03 0.00E+00 1.29E+04 5.16E+03 8.80E+03 2.56E+04 1.74E+05 1.70E+05 1.82E+05 Putrescine 5.15E+04 6.42E+04 4.96E+04 7.54E+04 3.44E+04 4.80E+04 8.15E+04 4.81E+04 8.29E+04 1.14E+05 1.14E+05 8.27E+04 1.25E+05 1.08E+05 1.13E+05 3.06E+04 3.21E+04 3.14E+04 Spermidine 7.99E+06 9.45E+06 6.42E+06 9.75E+06 4.56E+06 7.58E+06 9.46E+06 6.61E+06 1.42E+07 1.09E+07 9.83E+06 1.28E+07 1.51E+07 1.20E+07 1.54E+07 4.36E+06 3.97E+06 3.64E+06 Spermine 2.33E+07 3.67E+07 2.75E+07 6.56E+07 3.07E+07 5.62E+07 3.12E+07 3.78E+07 3.17E+07 2.68E+07 3.15E+07 3.10E+07 4.05E+07 5.16E+07 2.77E+07 1.83E+06 3.80E+06 1.94E+06 alpha-D-Glucosamine 1-phosphate 2.90E+05 3.32E+05 1.48E+05 2.41E+05 2.88E+05 2.35E+05 1.46E+05 2.18E+05 4.64E+04 3.38E+05 5.48E+05 8.58E+04 3.26E+05 2.14E+05 1.68E+05 9.86E+04 1.12E+05 1.40E+05 Carnosine 1.20E+05 8.53E+04 8.04E+04 8.59E+04 1.65E+05 1.13E+05 2.72E+05 2.22E+05 1.76E+05 3.83E+05 5.84E+05 1.67E+05 1.95E+05 1.35E+05 1.01E+05 9.36E+04 5.83E+04 3.67E+04 Creatine 1.69E+07 1.73E+07 1.22E+07 1.03E+07 1.95E+07 1.63E+07 1.98E+07 2.60E+07 2.60E+07 6.65E+07 9.01E+07 5.80E+07 6.34E+07 6.34E+07 7.52E+07 6.47E+07 4.70E+07 7.02E+07 Creatinine 1.59E+05 1.27E+05 1.04E+05 1.06E+05 2.41E+05 1.67E+05 2.07E+05 2.10E+05 2.18E+05 6.35E+05 6.46E+05 4.92E+05 5.68E+05 5.66E+05 6.18E+05 1.64E+06 2.37E+06 1.35E+06 4-Acetamidobutanoate 5.68E+03 8.81E+03 9.36E+03 1.22E+04 1.51E+04 9.74E+03 7.05E+03 4.56E+03 0.00E+00 7.02E+03 1.55E+04 6.44E+03 0.00E+00 5.74E+03 1.90E+04 4.29E+05 9.31E+04 1.27E+05 N-Acetyl-L-ornithine 2.07E+03 6.23E+03 1.07E+04 3.07E+03 9.67E+03 4.04E+03 4.90E+03 0.00E+00 6.72E+03 6.96E+03 6.46E+03 1.86E+03 1.41E+03 2.60E+03 1.30E+04 7.75E+04 6.74E+04 3.45E+04 Guanidinoacetate 6.94E+03 1.41E+04 1.02E+04 3.87E+03 8.87E+03 7.95E+03 0.00E+00 1.20E+04 5.08E+03 6.98E+03 9.22E+03 6.90E+03 0.00E+00 0.00E+00 4.11E+03 5.01E+04 3.71E+04 1.45E+04 Indole-3-acetate 3.03E+05 2.23E+05 2.97E+05 2.15E+05 3.99E+05 2.99E+05 3.51E+05 3.26E+05 2.79E+05 3.67E+05 4.49E+05 1.77E+05 3.42E+05 3.07E+05 2.59E+05 1.01E+03 1.59E+03 1.20E+03 Indolepyruvate 2.16E+04 6.91E+04 2.72E+04 4.20E+04 3.40E+04 9.24E+04 2.56E+04 0.00E+00 1.27E+03 8.21E+04 3.37E+04 1.81E+04 0.00E+00 0.00E+00 0.00E+00 0.00E+00 0.00E+00 0.00E+00 6-Hydroxykynurenic acid 1.24E+04 1.12E+04 2.26E+04 1.26E+04 9.89E+03 4.10E+04 1.56E+04 1.59E+04 1.55E+04 2.03E+04 2.20E+04 7.41E+03 1.09E+04 1.60E+04 2.38E+05 1.01E+04 1.14E+04 1.08E+04 L-Tryptophanamide 2.42E+04 3.06E+04 1.64E+04 1.74E+04 7.86E+03 1.59E+04 1.66E+04 1.18E+04 3.11E+04 3.00E+04 2.54E+04 2.98E+04 2.62E+04 1.64E+04 4.26E+04 5.61E+03 3.03E+03 5.85E+03 Picolinic acid 5.35E+04 6.29E+04 8.45E+04 6.13E+04 9.38E+04 6.84E+04 1.41E+05 1.01E+05 1.17E+05 8.07E+04 1.15E+05 1.04E+05 7.75E+04 1.39E+05 6.95E+04 8.15E+04 1.26E+05 9.66E+04 g-Oxalo-crotonate 1.18E+03 1.62E+03 1.31E+03 1.68E+03 6.45E+02 1.06E+03 0.00E+00 0.00E+00 6.46E+03 0.00E+00 0.00E+00 2.08E+03 2.23E+03 1.00E+03 1.05E+04 3.96E+04 4.77E+04 4.99E+04 Dopamine 2.30E+03 3.41E+03 4.44E+03 2.02E+03 2.39E+03 3.56E+03 2.39E+03 4.03E+03 6.13E+03 3.00E+03 7.73E+03 1.96E+03 5.07E+03 2.05E+03 8.41E+03 2.80E+03 0.00E+00 0.00E+00 Choline 1.30E+07 1.09E+07 4.20E+07 2.63E+07 7.56E+06 6.13E+06 3.24E+07 9.42E+06 1.44E+07 6.30E+07 3.67E+07 5.71E+07 8.03E+07 2.41E+07 3.64E+07 8.90E+06 6.21E+06 9.79E+06 Acetylcholine 1.38E+07 8.08E+06 6.07E+06 3.68E+06 1.37E+07 5.57E+06 8.44E+06 1.30E+07 1.17E+07 1.20E+07 2.02E+07 1.42E+07 1.83E+07 1.78E+07 1.80E+07 2.22E+07 1.38E+07 1.77E+07 L-Carnitine 3.46E+06 5.85E+06 1.37E+06 4.37E+06 2.05E+06 5.13E+06 4.25E+06 6.78E+06 7.07E+06 8.96E+06 1.37E+07 1.68E+07 1.30E+07 1.78E+07 2.09E+07 1.67E+07 2.45E+07 2.25E+07 AC(2:0) 6.69E+06 1.83E+07 4.01E+06 1.26E+07 4.60E+06 1.48E+07 9.84E+06 1.22E+07 7.39E+06 5.95E+07 4.65E+07 3.15E+07 5.16E+07 4.60E+07 2.85E+07 2.33E+07 2.30E+07 2.04E+07 AC(3:0) 2.99E+05 4.41E+05 1.62E+05 3.89E+05 1.27E+05 2.84E+05 3.16E+05 5.32E+05 5.36E+05 1.87E+06 2.50E+06 2.47E+06 1.84E+06 2.77E+06 1.47E+06 1.37E+06 1.16E+06 2.11E+06 AC(4:0) 6.16E+04 1.59E+05 3.05E+04 8.98E+04 3.78E+04 7.02E+04 9.27E+04 6.43E+04 1.78E+05 2.88E+05 3.04E+05 1.68E+06 2.14E+05 1.77E+05 1.27E+06 1.12E+05 1.40E+05 1.02E+05 AC(4-OH) 2.43E+04 3.60E+04 8.51E+03 3.48E+04 1.55E+04 3.12E+04 1.74E+04 1.43E+04 9.72E+03 2.41E+05 1.46E+05 1.53E+05 1.76E+05 2.20E+05 1.77E+05 2.32E+05 3.43E+05 1.85E+05 AC(4-DC) 1.60E+04 2.79E+04 3.55E+03 3.74E+04 9.44E+03 1.62E+04 6.81E+03 1.68E+04 8.10E+03 7.81E+04 5.00E+04 4.69E+04 3.57E+04 5.82E+04 5.39E+04 2.41E+06 2.66E+06 2.38E+06 AC(5:0) 7.38E+04 1.34E+05 4.40E+04 9.33E+04 6.19E+04 1.18E+05 2.02E+05 1.54E+05 1.09E+05 4.91E+05 6.20E+05 4.08E+05 2.94E+05 2.30E+05 2.39E+05 1.35E+05 2.01E+05 1.65E+05 AC(5-OH) 3.52E+04 3.96E+04 1.25E+04 3.18E+04 1.81E+04 4.63E+04 4.69E+04 4.99E+04 2.81E+04 8.72E+04 8.35E+04 6.14E+04 6.02E+04 7.56E+04 4.59E+04 4.59E+05 5.56E+05 1.99E+06 AC(8:0) 3.91E+04 5.74E+04 1.51E+04 5.72E+04 3.89E+04 9.48E+04 1.21E+05 1.27E+05 1.41E+05 2.85E+05 4.67E+05 6.36E+05 2.11E+05 1.98E+05 1.86E+05 4.05E+04 3.26E+04 2.63E+04 AC(10:0) 8.35E+03 1.25E+04 1.52E+03 7.84E+03 8.24E+03 1.48E+04 2.28E+04 2.00E+04 1.55E+04 5.00E+04 1.03E+05 1.12E+05 4.76E+04 4.61E+04 3.21E+04 9.55E+03 1.29E+04 7.88E+03 AC(12:0) 9.78E+03 1.81E+04 2.55E+03 1.28E+04 8.01E+03 1.71E+04 2.10E+04 2.80E+04 2.13E+04 1.03E+05 1.87E+05 2.09E+05 8.23E+04 6.78E+04 6.36E+04 4.49E+03 6.99E+03 6.23E+03 AC(14:0) 3.16E+05 3.58E+05 1.19E+05 2.06E+05 1.93E+05 2.22E+05 1.52E+05 1.45E+05 1.20E+05 5.06E+05 5.15E+05 6.71E+05 3.93E+05 2.95E+05 3.23E+05 1.25E+05 1.19E+05 1.48E+05 AC(14:1) 5.60E+03 9.44E+03 2.95E+03 1.10E+04 4.19E+03 1.18E+04 2.21E+04 1.48E+04 1.31E+04 7.71E+04 1.01E+05 1.31E+05 5.09E+04 4.24E+04 5.62E+04 2.60E+04 3.47E+04 2.56E+04 AC(16:0) 2.94E+06 3.04E+06 7.04E+05 1.75E+06 1.45E+06 2.40E+06 1.92E+06 1.94E+06 1.25E+06 5.18E+06 4.61E+06 4.91E+06 3.61E+06 2.75E+06 3.13E+06 5.82E+06 3.18E+06 3.88E+06 AC(16:1) 1.24E+05 1.89E+05 4.29E+04 9.79E+04 8.02E+04 1.31E+05 1.90E+05 1.91E+05 1.18E+05 3.19E+05 4.01E+05 3.75E+05 2.93E+05 2.95E+05 2.59E+05 1.56E+05 1.28E+05 1.63E+05 AC(18:0) 6.12E+05 7.85E+05 1.26E+05 5.96E+05 6.35E+05 4.89E+05 1.27E+06 7.17E+05 7.13E+05 1.97E+06 1.65E+06 1.96E+06 2.97E+06 3.09E+06 1.98E+06 2.33E+06 1.57E+06 2.19E+06 AC(18:1) 9.49E+05 1.48E+06 1.81E+05 8.52E+05 5.66E+05 1.22E+06 1.52E+06 9.45E+05 6.18E+05 1.67E+06 1.35E+06 1.56E+06 1.57E+06 1.21E+06 1.30E+06 7.82E+06 5.04E+06 5.14E+06 AC(18:2) 6.64E+05 9.91E+05 1.40E+05 5.44E+05 3.68E+05 6.66E+05 1.06E+06 7.35E+05 5.08E+05 1.39E+06 1.25E+06 1.52E+06 1.68E+06 1.40E+06 1.23E+06 3.16E+06 1.93E+06 1.76E+06 AC(20:4) 2.83E+04 5.98E+04 7.77E+03 3.99E+04 1.56E+04 5.48E+04 5.09E+04 3.70E+04 1.61E+04 1.69E+05 1.78E+05 1.47E+05 1.56E+05 1.21E+05 1.28E+05 6.50E+05 4.74E+05 7.69E+05 Sphingosine 4.26E+05 3.31E+05 2.49E+05 2.51E+05 3.59E+05 2.77E+05 3.33E+05 3.87E+05 3.63E+05 4.36E+05 9.21E+05 7.24E+05 8.77E+05 6.94E+05 9.14E+05 2.56E+04 3.39E+04 4.10E+04 MS_METABOLITE_DATA_END #METABOLITES METABOLITES_START metabolite_name CmpdID Pathway m/z RT Polarity L-alanine C00041 Amino acids 90.056 0.621 [M+H]+ L-arginine C00062 Amino acids 175.119 0.614 [M+H]+ L-asparagine C00152 Amino acids 133.061 0.634 [M+H]+ L-cysteine C00097 Amino acids 122.027 1.711 [M+H]+ glycine C00037 Amino acids 76.040 0.652 [M+H]+ L-histidine C00135 Amino acids 156.077 0.605 [M+H]+ L-leucine/isoluecine C00123 Amino acids 132.102 0.821 [M+H]+ L-lysine C00047 Amino acids 147.113 0.598 [M+H]+ L-methionine C00073 Amino acids 150.058 0.664 [M+H]+ L-phenylalanine C00079 Amino acids 166.086 1.062 [M+H]+ L-proline C00148 Amino acids 116.071 0.657 [M+H]+ L-serine C00065 Amino acids 106.050 0.628 [M+H]+ L-threonine C00188 Amino acids 120.066 0.627 [M+H]+ L-tryptophan C00078 Amino acids 205.097 1.695 [M+H]+ L-tyrosine C00082 Amino acids 182.081 0.665 [M+H]+ L-valine C00183 Amino acids 118.086 0.693 [M+H]+ L-cystine C00491 Amino acids 241.029 0.696 [M+H]+ Adenine C00147 Nucleotides 136.062 0.737 [M+H]+ Guanine C00242 Nucleotides 152.057 0.707 [M+H]+ Cytosine C00380 Nucleotides 112.051 0.681 [M+H]+ Thymine C00178 Nucleotides 127.050 0.659 [M+H]+ Hypoxanthine C00262 Nucleotides 137.046 0.688 [M+H]+ Xanthine C00385 Nucleotides 153.039 0.563 [M+H]+ 5-Hydroxyisourate C11821 Nucleotides 185.031 0.625 [M+H]+ Allantoate C00499 Nucleotides 177.061 0.586 [M+H]+ 3',5'-Cyclic AMP C00575 Nucleotides 330.058 0.761 [M+H]+ 5-6-Dihydrothymine C00906 Nucleotides 129.066 0.655 [M+H]+ Pyridoxal C00250 Nucleotides 168.065 0.674 [M+H]+ Pyridoxamine 5'-phosphate C00647 Nucleotides 249.061 1.711 [M+H]+ Nicotinamide C00153 Nucleotides 123.056 0.754 [M+H]+ NAD+ C00003 Nucleotides 664.114 0.655 [M+H]+ Mannitol/Sorbitol/Glucitol/Iditol C00392 Other sugars 183.085 0.673 [M+H]+ D-Rhamnose C01684 Other sugars 165.077 0.634 [M+H]+ Cys-Gly C01419 GSH homeostasis 179.048 0.692 [M+H]+ gamma-L-Glutamyl-L-cysteine C00669 Gamma-glutamyls 251.069 0.705 [M+H]+ gamma-Glutamyl-Se-methylselenocysteine C05695 Gamma-glutamyls 313.031 0.624 [M+H]+ S-Adenosyl-L-homocysteine C00021 Serine biosynthesis and one-carbon metabolism 385.129 0.653 [M+H]+ S-Adenosyl-L-methionine C00019 Serine biosynthesis and one-carbon metabolism 399.144 0.617 [M+H]+ 5-10-Methenyltetrahydrofolate C00445 Folate pool (One carbon metabolism) 457.169 0.651 [M+H]+ Ornithine C01602 Urea cycle 133.097 0.626 [M+H]+ L-Citrulline C00327 Urea cycle 176.103 0.662 [M+H]+ Putrescine C00134 Polyamines 89.108 0.559 [M+H]+ Spermidine C00315 Polyamines 146.165 0.57 [M+H]+ Spermine C00750 Polyamines 203.223 0.575 [M+H]+ alpha-D-Glucosamine 1-phosphate C06156 Aminosugars 260.053 0.648 [M+H]+ Carnosine C00386 Arginine and proline metabolism 227.114 0.593 [M+H]+ Creatine C00300 Arginine and proline metabolism 132.077 0.639 [M+H]+ Creatinine C00791 Arginine and proline metabolism 114.066 0.644 [M+H]+ 4-Acetamidobutanoate C02946 Arginine and proline metabolism 146.081 0.651 [M+H]+ N-Acetyl-L-ornithine C00437 Arginine and proline metabolism 175.108 0.64 [M+H]+ Guanidinoacetate C00581 Arginine and proline metabolism 118.061 0.669 [M+H]+ Indole-3-acetate C00954 Indole and Tryptophan 176.071 1.884 [M+H]+ Indolepyruvate C00331 Indole and Tryptophan 204.063 0.656 [M+H]+ 6-Hydroxykynurenic acid C08480 Indole and Tryptophan 206.045 1.712 [M+H]+ L-Tryptophanamide C00977 Indole and Tryptophan 204.111 0.549 [M+H]+ Picolinic acid C10164 Indole and Tryptophan 124.040 0.543 [M+H]+ g-Oxalo-crotonate C03453 Indole and Tryptophan 159.028 0.677 [M+H]+ Dopamine C03758 Signaling 154.085 0.666 [M+H]+ Choline C00114 Glycerophospholipid biosynthesis 104.107 0.623 [M+H]+ Acetylcholine C01996 Glycerophospholipid biosynthesis 146.117 0.652 [M+H]+ L-Carnitine C00318 Carnitine and fatty acid metabolsim 162.112 0.627 [M+H]+ AC(2:0) C02571 Carnitine and fatty acid metabolsim 204.123 0.661 [M+H]+ AC(3:0) C03017 Carnitine and fatty acid metabolsim 218.139 0.669 [M+H]+ AC(4:0) C02862 Carnitine and fatty acid metabolsim 232.154 1.685 [M+H]+ AC(4-OH) HMDB13127 Carnitine and fatty acid metabolsim 248.149 0.662 [M+H]+ AC(4-DC) HMDB13133 Carnitine and fatty acid metabolsim 262.129 0.666 [M+H]+ AC(5:0) C20826 Carnitine and fatty acid metabolsim 246.170 1.715 [M+H]+ AC(5-OH) ac107 Carnitine and fatty acid metabolsim 262.165 0.669 [M+H]+ AC(8:0) HMDB00791 Carnitine and fatty acid metabolsim 288.217 1.838 [M+H]+ AC(10:0) HMDB00651 Carnitine and fatty acid metabolsim 316.248 1.889 [M+H]+ AC(12:0) HMDB02250 Carnitine and fatty acid metabolsim 344.279 1.932 [M+H]+ AC(14:0) HMDB05066 Carnitine and fatty acid metabolsim 372.310 1.991 [M+H]+ AC(14:1) HMDB13329 Carnitine and fatty acid metabolsim 370.295 1.96 [M+H]+ AC(16:0) C02990 Carnitine and fatty acid metabolsim 400.342 2.044 [M+H]+ AC(16:1) HMDB06317 Carnitine and fatty acid metabolsim 398.327 1.994 [M+H]+ AC(18:0) HMDB00848 Carnitine and fatty acid metabolsim 428.373 2.112 [M+H]+ AC(18:1) HMDB06351 Carnitine and fatty acid metabolsim 426.357 2.052 [M+H]+ AC(18:2) HMDB01064 Carnitine and fatty acid metabolsim 424.342 2.017 [M+H]+ AC(20:4) ac125 Carnitine and fatty acid metabolsim 448.341 2.005 [M+H]+ Sphingosine C00319 Sphingolipid biosynthesis 300.289 1.979 [M+H]+ METABOLITES_END #END