{
"METABOLOMICS WORKBENCH":{"STUDY_ID":"ST002499","ANALYSIS_ID":"AN004106","VERSION":"1","CREATED_ON":"March 2, 2023, 3:25 pm"},

"PROJECT":{"PROJECT_TITLE":"Metabolic profiles of murine stress erythroid progenitors","PROJECT_SUMMARY":"Inflammation alters hematopoiesis, skewing production to generate myeloid effector cells at the expense of steady state erythropoiesis. To compensate, stress erythropoiesis is induced to maintain homeostasis until the inflammation is resolved. Unlike the constant production of steady state erythropoiesis, stress erythropoiesis generates a bolus of new erythrocytes by first producing immature progenitor cells, which then transition to committed erythroid progenitors and differentiate. We hypothesize that the proliferation of early progenitor cells and their transition to differentiation is regulated by changes in metabolism. Metabolomics and isotope tracing analysis was performed to assess the intracellular metabolic profiles in proliferating progenitors isolated from in vitro stress erythropoiesis cultures. We observed an active engagement of glucose metabolism in glycolysis and anabolic biosynthesis, while the levels of TCA intermediates suggested that TCA cycle and mitochondrial respiration were blocked. Concomitantly, inducible nitric oxide synthase (iNOS) was induced in progenitor cells to increase the production of nitric oxide (NO), which was demonstrated to be crucial for proliferating progenitor metabolism. Inhibition or genetic mutation of iNOS decreased NO levels resulting in the suppression of progenitor proliferation in vitro and in vivo. As evaluated by RNA-seq, inhibition of iNOS suppressed cell proliferation-related pathways including cell cycle and nucleotide metabolism, while upregulating erythroid differentiation genes. These data suggest that iNOS-derived NO production establishes a metabolism that promotes the proliferation of progenitor cells while inhibiting their differentiation. In contrast, the transition to differentiation is marked by decreased Nos2 expression and a change in metabolism to support induction of the erythroid gene expression program. These data support a model where increased pro-inflammatory signals inhibit steady state erythropoiesis, while at the same time promoting stress erythropoiesis to maintain homeostasis.","INSTITUTE":"Pennsylvania State University","DEPARTMENT":"Veterinary and Biomedical Sciences","LABORATORY":"Paulson Lab","LAST_NAME":"Ruan","FIRST_NAME":"Baiye","ADDRESS":"228 AVBS Building, Shortlidge Road, University Park, PA 16802","EMAIL":"bur27@psu.edu","PHONE":"814-863-6306"},

"STUDY":{"STUDY_TITLE":"Metabolomics analysis of stress erythroid progenitors","STUDY_SUMMARY":"A time course study to assess the intracellular metabolic changes of splenic Kit+ stress erythroid progenitors","INSTITUTE":"Pennsylvania State University","DEPARTMENT":"Veterinary and Biomedical Sciences","LABORATORY":"Paulson Lab","LAST_NAME":"Ruan","FIRST_NAME":"Baiye","ADDRESS":"228 AVBS Building Shortlidge Road University Park, PA 16802","EMAIL":"bur27@psu.edu","PHONE":"814-863-6306"},

"SUBJECT":{"SUBJECT_TYPE":"Mammal","SUBJECT_SPECIES":"Mus musculus","TAXONOMY_ID":"10090"},
"SUBJECT_SAMPLE_FACTORS":[
{
"Subject ID":"-",
"Sample ID":"0-1",
"Factors":{"Time_point(days)":"0"},
"Additional sample data":{"Cell_type":"Kit+ stress progenitors","Organism":"Mus musculus","Mouse_strain":"wild type C57BL/6","Treatment":"untreated","RAW_FILE_NAME":"0-1.mzML"}
},
{
"Subject ID":"-",
"Sample ID":"0-2",
"Factors":{"Time_point(days)":"0"},
"Additional sample data":{"Cell_type":"Kit+ stress progenitors","Organism":"Mus musculus","Mouse_strain":"wild type C57BL/6","Treatment":"untreated","RAW_FILE_NAME":"0-2.mzML"}
},
{
"Subject ID":"-",
"Sample ID":"0-3",
"Factors":{"Time_point(days)":"0"},
"Additional sample data":{"Cell_type":"Kit+ stress progenitors","Organism":"Mus musculus","Mouse_strain":"wild type C57BL/6","Treatment":"untreated","RAW_FILE_NAME":"0-3.mzML"}
},
{
"Subject ID":"-",
"Sample ID":"0-4",
"Factors":{"Time_point(days)":"0"},
"Additional sample data":{"Cell_type":"Kit+ stress progenitors","Organism":"Mus musculus","Mouse_strain":"wild type C57BL/6","Treatment":"untreated","RAW_FILE_NAME":"0-4.mzML"}
},
{
"Subject ID":"-",
"Sample ID":"0-5",
"Factors":{"Time_point(days)":"0"},
"Additional sample data":{"Cell_type":"Kit+ stress progenitors","Organism":"Mus musculus","Mouse_strain":"wild type C57BL/6","Treatment":"untreated","RAW_FILE_NAME":"0-5.mzML"}
},
{
"Subject ID":"-",
"Sample ID":"1-1",
"Factors":{"Time_point(days)":"1"},
"Additional sample data":{"Cell_type":"Kit+ stress progenitors","Organism":"Mus musculus","Mouse_strain":"wild type C57BL/6","Treatment":"PHZ","RAW_FILE_NAME":"1-1.mzML"}
},
{
"Subject ID":"-",
"Sample ID":"1-2",
"Factors":{"Time_point(days)":"1"},
"Additional sample data":{"Cell_type":"Kit+ stress progenitors","Organism":"Mus musculus","Mouse_strain":"wild type C57BL/6","Treatment":"PHZ","RAW_FILE_NAME":"1-2.mzML"}
},
{
"Subject ID":"-",
"Sample ID":"1-3",
"Factors":{"Time_point(days)":"1"},
"Additional sample data":{"Cell_type":"Kit+ stress progenitors","Organism":"Mus musculus","Mouse_strain":"wild type C57BL/6","Treatment":"PHZ","RAW_FILE_NAME":"1-3.mzML"}
},
{
"Subject ID":"-",
"Sample ID":"1-4",
"Factors":{"Time_point(days)":"1"},
"Additional sample data":{"Cell_type":"Kit+ stress progenitors","Organism":"Mus musculus","Mouse_strain":"wild type C57BL/6","Treatment":"PHZ","RAW_FILE_NAME":"1-4.mzML"}
},
{
"Subject ID":"-",
"Sample ID":"1-5",
"Factors":{"Time_point(days)":"1"},
"Additional sample data":{"Cell_type":"Kit+ stress progenitors","Organism":"Mus musculus","Mouse_strain":"wild type C57BL/6","Treatment":"PHZ","RAW_FILE_NAME":"1-5.mzML"}
},
{
"Subject ID":"-",
"Sample ID":"3-1",
"Factors":{"Time_point(days)":"3"},
"Additional sample data":{"Cell_type":"Kit+ stress progenitors","Organism":"Mus musculus","Mouse_strain":"wild type C57BL/6","Treatment":"PHZ","RAW_FILE_NAME":"3-1.mzML"}
},
{
"Subject ID":"-",
"Sample ID":"3-2",
"Factors":{"Time_point(days)":"3"},
"Additional sample data":{"Cell_type":"Kit+ stress progenitors","Organism":"Mus musculus","Mouse_strain":"wild type C57BL/6","Treatment":"PHZ","RAW_FILE_NAME":"3-2.mzML"}
},
{
"Subject ID":"-",
"Sample ID":"3-3",
"Factors":{"Time_point(days)":"3"},
"Additional sample data":{"Cell_type":"Kit+ stress progenitors","Organism":"Mus musculus","Mouse_strain":"wild type C57BL/6","Treatment":"PHZ","RAW_FILE_NAME":"3-3.mzML"}
},
{
"Subject ID":"-",
"Sample ID":"3-4",
"Factors":{"Time_point(days)":"3"},
"Additional sample data":{"Cell_type":"Kit+ stress progenitors","Organism":"Mus musculus","Mouse_strain":"wild type C57BL/6","Treatment":"PHZ","RAW_FILE_NAME":"3-4.mzML"}
},
{
"Subject ID":"-",
"Sample ID":"3-5",
"Factors":{"Time_point(days)":"3"},
"Additional sample data":{"Cell_type":"Kit+ stress progenitors","Organism":"Mus musculus","Mouse_strain":"wild type C57BL/6","Treatment":"PHZ","RAW_FILE_NAME":"3-5.mzML"}
},
{
"Subject ID":"-",
"Sample ID":"8-1",
"Factors":{"Time_point(days)":"8"},
"Additional sample data":{"Cell_type":"Kit+ stress progenitors","Organism":"Mus musculus","Mouse_strain":"wild type C57BL/6","Treatment":"HKBA","RAW_FILE_NAME":"8-1.mzML"}
},
{
"Subject ID":"-",
"Sample ID":"8-2",
"Factors":{"Time_point(days)":"8"},
"Additional sample data":{"Cell_type":"Kit+ stress progenitors","Organism":"Mus musculus","Mouse_strain":"wild type C57BL/6","Treatment":"HKBA","RAW_FILE_NAME":"8-2.mzML"}
},
{
"Subject ID":"-",
"Sample ID":"8-3",
"Factors":{"Time_point(days)":"8"},
"Additional sample data":{"Cell_type":"Kit+ stress progenitors","Organism":"Mus musculus","Mouse_strain":"wild type C57BL/6","Treatment":"HKBA","RAW_FILE_NAME":"8-3.mzML"}
},
{
"Subject ID":"-",
"Sample ID":"8-4",
"Factors":{"Time_point(days)":"8"},
"Additional sample data":{"Cell_type":"Kit+ stress progenitors","Organism":"Mus musculus","Mouse_strain":"wild type C57BL/6","Treatment":"HKBA","RAW_FILE_NAME":"8-4.mzML"}
},
{
"Subject ID":"-",
"Sample ID":"8-5",
"Factors":{"Time_point(days)":"8"},
"Additional sample data":{"Cell_type":"Kit+ stress progenitors","Organism":"Mus musculus","Mouse_strain":"wild type C57BL/6","Treatment":"HKBA","RAW_FILE_NAME":"8-5.mzML"}
}
],
"COLLECTION":{"COLLECTION_SUMMARY":"Murine spleens were harvested and disassociated to single cell suspension at a concentration of 1 x 10^8 cells/mL. Labeling reagent was added at a concentation of 50 μL/mL of sample. Cells were mixed and incubated at RT for 15 mins. Selection cocktail was added to sample at a 70 μL/mL of sample. Cells were mixed and incubated at RT for 15 mins. RapidSpheres were added to sample at a 50 μL/mL of sample. Cells were mixed and incubated at RT for 10 mins. Cells were washed with FACS buffer for 4 times, and were resuspended for downstream metabolomics analysis.","SAMPLE_TYPE":"Stem cells"},

"TREATMENT":{"TREATMENT_SUMMARY":"Phenylhydrazine (PHZ)-induced hemolytic anemia To induce acute hemolytic anemia, age- and sex-matched mice were injected intraperitoneally with a single dose (100 mg/kg body weight) of freshly prepared phenylhydrazine (Sigma-Aldrich, dissolved in PBS). Mice were sacrificed at indicated time points for spleen sample collection and Kit cell enrichment. Brucella abortus-induced inflammatory anemia Heat-killed Brucella abortus (HKBA, strain 1119-3) was used to induce anemia of inflammation following a previously described method(1). To induce stress erythropoiesis, age- and sex-matched mice were administered with 5 x 108 particles of HKBA via intraperitoneal injection.Mice were sacrificed at indicated time points for spleen sample collection and Kit cell enrichment."},

"SAMPLEPREP":{"SAMPLEPREP_SUMMARY":"Cell pellets were extracted with 1 ml pre-chilled 50:50 HPLC-grade water:methanol (v/v) containing 1 µM chlorpropamide as the internal standard. The samples were vortexed briefly followed by thorough homogenization. The samples were then snap frozen with liquid nitrogen and immediately thawed at room temperature. This step was repeated for three times followed by centrifuging for 10 min at 12,000 x g and 4 °C. The supernatants were transferred into fresh microfuge tubes. The remaining cell pellets were re-extracted with 0.5 ml 50% methanol containing 1 µM chlorpropamide, homogenized, frozen and thawed three times, spun down, and the supernatants were combined with the first extraction. Metabolites-containing supernatants were concentrated to dryness at room temperature in a SpeedVac concentrator and re-dissolved in 100 µl 97:3 water:methanol (v/v). After centrifuging for 10 min at 13000 × g and 4°C, 70 µl of supernatants were transferred into autosampler vials for LC-MS analysis. Two types of control were prepared in triplicates to run in concert with the experimental samples: the process blank control, and the pooled control containing an equal volume from each experimental sample."},

"CHROMATOGRAPHY":{"CHROMATOGRAPHY_SUMMARY":"The sample run order was randomized to reduce bias from instrument drift. 10 µl sample was subjected to LC-MS analysis on a Exactive Plus Orbitrap mass spectrometer (Thermo Fisher Scientific) coupled to an Ultimate 3000 UHPLC system (Thermo Fisher Scientific). Reversed-phase chromatography mode was used to separate compounds on a Xselect C18 HSS column (Waters) with solvent A (97:3 water:methanol (v/v), 10 mM tributylamine, and 15 mM acetic acid ) and solvent B (methanol). The flow rate was 200 µl/min, and the total run time was 25 min. The gradient was 0 min, 0% B; 5 min, 20% B; 7.5 min, 55% B; 15 min, 65% B; 17.5 min, 95% B; and 21 min, 0% B. The mass spectrometer was operated in a negative-ion mode at a resolution of 140,000 at m/z 200 and with a scan range of 85 to 1000 m/z.","CHROMATOGRAPHY_TYPE":"Reversed phase","INSTRUMENT_NAME":"Thermo Dionex Ultimate 3000","COLUMN_NAME":"Waters XBridge C18 (50 x 2.1mm,3um)","SOLVENT_A":"97:3 water:methanol (v/v), 10 mM tributylamine, and 15 mM acetic acid","SOLVENT_B":"methanol","FLOW_GRADIENT":"0 min, 0% B; 5 min, 20% B; 7.5 min, 55% B; 15 min, 65% B; 17.5 min, 95% B; and 21 min, 0% B.","FLOW_RATE":"200 µl/min","COLUMN_TEMPERATURE":"standard"},

"ANALYSIS":{"ANALYSIS_TYPE":"MS"},

"MS":{"INSTRUMENT_NAME":"Thermo Exactive Plus Orbitrap","INSTRUMENT_TYPE":"Orbitrap","MS_TYPE":"ESI","ION_MODE":"NEGATIVE","MS_COMMENTS":"Raw data files were converted to .mzML file format using the ProteoWizard software, and they were analyzed by the MS-DIAL software. Metabolites were identified by comparison to an in-house reference library of pure metabolite standards which included mass-to-charge ratio (m/z) and retention time. For quantification of metabolite abundance, peak areas of identified metabolites were first normalized to the internal standard chlorpropamide, and then normalized to cell numbers from each sample. Data were analyzed using R and Cytoscape software."},

"MS_METABOLITE_DATA":{
"Units":"peak area normalized to IS and cell number",

"Data":[{"Metabolite":"Pyruvate","0-1":"0.0781171","0-2":"0.075739521","0-3":"0.046675136","0-4":"0.097275332","0-5":"0.084606164","1-1":"0.062302729","1-2":"0.057855074","1-3":"0.128987132","1-4":"0.105897256","1-5":"0.118214166","3-1":"0.139361579","3-2":"0.106224463","3-3":"0.212483238","3-4":"0.172753602","3-5":"0.169101628","8-1":"0.061509917","8-2":"0.058379876","8-3":"0.061965875","8-4":"0.05626","8-5":"0.062609223"},{"Metabolite":"Alanine/Sacrosine","0-1":"0.012485309","0-2":"0.01210366","0-3":"0.006861107","0-4":"0.011709645","0-5":"0.009232346","1-1":"0.008831756","1-2":"0.008429879","1-3":"0.014645969","1-4":"0.012577182","1-5":"0.012603288","3-1":"0.014132607","3-2":"0.012891598","3-3":"0.020813436","3-4":"0.024461585","3-5":"0.020701753","8-1":"0.008388031","8-2":"0.009381693","8-3":"0.008361877","8-4":"0.009353764","8-5":"0.009686917"},{"Metabolite":"Lactate","0-1":"0.211782637","0-2":"0.123305682","0-3":"0.070735976","0-4":"0.155245569","0-5":"0.127551598","1-1":"0.12924365","1-2":"0.076301274","1-3":"0.175768786","1-4":"0.188992056","1-5":"0.165518808","3-1":"0.205602027","3-2":"0.196352587","3-3":"0.654433468","3-4":"0.44949005","3-5":"0.362866556","8-1":"0.060190714","8-2":"0.068669251","8-3":"0.061748743","8-4":"0.071399842","8-5":"0.059357043"},{"Metabolite":"Acetoacetate","0-1":"0.000398291","0-2":"0.000939158","0-3":"0.000348125","0-4":"0.00260656","0-5":"0.001979894","1-1":"0.001367456","1-2":"0.000977968","1-3":"0.002957484","1-4":"0.001143959","1-5":"0.000755357","3-1":"0.002543577","3-2":"0.002884899","3-3":"0.004476345","3-4":"0.004377769","3-5":"0.005157684","8-1":"0.0014481","8-2":"0.003625545","8-3":"0.001305469","8-4":"0.000747832","8-5":"0.000420465"},{"Metabolite":"Serine","0-1":"0.013376953","0-2":"0.014662874","0-3":"0.007708712","0-4":"0.011319545","0-5":"0.009542208","1-1":"0.00888324","1-2":"0.009774786","1-3":"0.016168816","1-4":"0.010104873","1-5":"0.011111259","3-1":"0.008032665","3-2":"0.007282316","3-3":"0.00761375","3-4":"0.018023169","3-5":"0.012397951","8-1":"0.011341929","8-2":"0.013019827","8-3":"0.013662875","8-4":"0.012995656","8-5":"0.014883841"},{"Metabolite":"Proline","0-1":"0.016654917","0-2":"0.018585092","0-3":"0.012729826","0-4":"0.015455517","0-5":"0.013088752","1-1":"0.017269776","1-2":"0.018838689","1-3":"0.026094036","1-4":"0.019595104","1-5":"0.01751889","3-1":"0.036943411","3-2":"0.029679924","3-3":"0.032227354","3-4":"0.045487683","3-5":"0.040046294","8-1":"0.016914265","8-2":"0.016133803","8-3":"0.016369431","8-4":"0.016104697","8-5":"0.020073989"},{"Metabolite":"Fumarate","0-1":"0.000442709","0-2":"0.000121302","0-3":"2.11E-05","0-4":"0.000174764","0-5":"0.000296768","1-1":"0.00010395","1-2":"2.85E-05","1-3":"0.000302824","1-4":"0.000307349","1-5":"0.000185107","3-1":"0.000252976","3-2":"0.000310575","3-3":"0.000713779","3-4":"0.000995933","3-5":"0.000226204","8-1":"0.000189402","8-2":"3.47E-05","8-3":"0.000212496","8-4":"3.73E-05","8-5":"4.31E-05"},{"Metabolite":"Maleic acid","0-1":"0.002082825","0-2":"0.001787896","0-3":"0.001108215","0-4":"0.002039504","0-5":"0.001771435","1-1":"0.001480469","1-2":"0.001711728","1-3":"0.003177961","1-4":"0.002276133","1-5":"0.002404137","3-1":"0.002995351","3-2":"0.002323816","3-3":"0.005157503","3-4":"0.004959094","3-5":"0.004490396","8-1":"0.001999357","8-2":"0.002403529","8-3":"0.002444888","8-4":"0.001819957","8-5":"0.001989318"},{"Metabolite":"2-Keto-isovalerate","0-1":"0.009509354","0-2":"0.006450283","0-3":"0.004144369","0-4":"0.009982963","0-5":"0.008740025","1-1":"0.005968911","1-2":"0.005076737","1-3":"0.012067584","1-4":"0.010657005","1-5":"0.012911477","3-1":"0.012019545","3-2":"0.008294359","3-3":"0.02339836","3-4":"0.021806479","3-5":"0.019338392","8-1":"0.005329646","8-2":"0.00592242","8-3":"0.005416387","8-4":"0.006025286","8-5":"0.006299001"},{"Metabolite":"Acetyl-glycine","0-1":"0.001279079","0-2":"0.000993846","0-3":"0.000471437","0-4":"0.001366203","0-5":"0.001101248","1-1":"0.000933475","1-2":"0.00076676","1-3":"0.001916686","1-4":"0.001418265","1-5":"0.001456153","3-1":"0.001962314","3-2":"0.001293296","3-3":"0.00307906","3-4":"0.00278266","3-5":"0.00229977","8-1":"0.000761443","8-2":"0.000672658","8-3":"0.000773359","8-4":"0.00067695","8-5":"0.000787783"},{"Metabolite":"Guanidoacetic acid","0-1":"0.000110796","0-2":"0.000110432","0-3":"5.00E-05","0-4":"0.000110882","0-5":"6.59E-05","1-1":"7.14E-05","1-2":"6.90E-05","1-3":"7.33E-05","1-4":"0.000111001","1-5":"6.98E-05","3-1":"0.000315519","3-2":"0.000243569","3-3":"0.000225129","3-4":"0.000393122","3-5":"0.000333437","8-1":"0.000194608","8-2":"0.00024613","8-3":"0.00021141","8-4":"0.000185964","8-5":"0.000211419"},{"Metabolite":"Valine/5-Aminopentanoic acid","0-1":"0.039913119","0-2":"0.045499895","0-3":"0.029248482","0-4":"0.031470158","0-5":"0.023384278","1-1":"0.032469975","1-2":"0.036073852","1-3":"0.04551819","1-4":"0.033690759","1-5":"0.033081047","3-1":"0.029906445","3-2":"0.032413568","3-3":"0.055236628","3-4":"0.048020931","3-5":"0.039902136","8-1":"0.039015531","8-2":"0.046820506","8-3":"0.046614323","8-4":"0.039019836","8-5":"0.045935015"},{"Metabolite":"Succinate/Methylmalonic 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"Metabolites":[{"metabolite_name":"Pyruvate"},{"metabolite_name":"Alanine/Sacrosine"},{"metabolite_name":"Lactate"},{"metabolite_name":"Acetoacetate"},{"metabolite_name":"Serine"},{"metabolite_name":"Proline"},{"metabolite_name":"Fumarate"},{"metabolite_name":"Maleic acid"},{"metabolite_name":"2-Keto-isovalerate"},{"metabolite_name":"Acetyl-glycine"},{"metabolite_name":"Guanidoacetic acid"},{"metabolite_name":"Valine/5-Aminopentanoic acid"},{"metabolite_name":"Succinate/Methylmalonic acid"},{"metabolite_name":"Threonine/Homoserine"},{"metabolite_name":"Taurine"},{"metabolite_name":"Pyroglutamic acid"},{"metabolite_name":"Pipecolic Acid"},{"metabolite_name":"Citraconic acid"},{"metabolite_name":"Ketoleucine"},{"metabolite_name":"Hydroxyproline/Aminolevulinate"},{"metabolite_name":"N-Acetyl-L-alanine"},{"metabolite_name":"Isoleucine"},{"metabolite_name":"Leucine"},{"metabolite_name":"Asparagine"},{"metabolite_name":"Hydroxyisocaproic acid"},{"metabolite_name":"Ornithine"},{"metabolite_name":"Aspartate"},{"metabolite_name":"Malate"},{"metabolite_name":"p-Hydroxybenzoate"},{"metabolite_name":"Alpha-ketoglutarate"},{"metabolite_name":"Glutamine"},{"metabolite_name":"Lysine"},{"metabolite_name":"O-Acetyl-serine"},{"metabolite_name":"2-Oxo-4-methylthiobutanoate"},{"metabolite_name":"Methionine"},{"metabolite_name":"Ribose"},{"metabolite_name":"Xanthine"},{"metabolite_name":"2,3-Dihydroxybenzoic acid"},{"metabolite_name":"Histidine"},{"metabolite_name":"Allantoin"},{"metabolite_name":"Phenylpyruvate"},{"metabolite_name":"Phenyllactic acid"},{"metabolite_name":"Quinolinate"},{"metabolite_name":"Phosphoenolpyruvate"},{"metabolite_name":"Glyceraldehdye-3-phosphate"},{"metabolite_name":"sn-Glycerol-3-phosphate"},{"metabolite_name":"Aconitate"},{"metabolite_name":"N-Acetyl-L-ornithine"},{"metabolite_name":"Arginine"},{"metabolite_name":"Citrulline"},{"metabolite_name":"Allantoate"},{"metabolite_name":"2-Isopropylmalic acid"},{"metabolite_name":"Glucono-_-lactone"},{"metabolite_name":"Glucosamine"},{"metabolite_name":"Hydroxyphenylpyruvate"},{"metabolite_name":"Glucose"},{"metabolite_name":"Tyrosine"},{"metabolite_name":"4-Pyridoxic acid"},{"metabolite_name":"3-Phosphoglycerate"},{"metabolite_name":"Acetyllysine"},{"metabolite_name":"Citrate/isocitrate"},{"metabolite_name":"2-Keto-D-gluconate"},{"metabolite_name":"Gluconate"},{"metabolite_name":"Tryptophan"},{"metabolite_name":"Deoxyribose-phosphate"},{"metabolite_name":"Pantothenate"},{"metabolite_name":"Cystathionine"},{"metabolite_name":"Ribulose-5-phosphate"},{"metabolite_name":"Ribose-5-phosphate"},{"metabolite_name":"Tetrahydrobiopterin"},{"metabolite_name":"Cytidine"},{"metabolite_name":"Uridine"},{"metabolite_name":"Leu-Asp (LD)"},{"metabolite_name":"Glucose-1/6-phosphate@6.5"},{"metabolite_name":"Glucose-1/6-phosphate@7.23"},{"metabolite_name":"Fructose-6-phosphate"},{"metabolite_name":"6-Phospho-D-gluconate"},{"metabolite_name":"Xanthosine"},{"metabolite_name":"D-Sedoheptulose-1/7-phosphate"},{"metabolite_name":"N-Acetyl-glucosamine-1/6-phosphate"},{"metabolite_name":"dCMP"},{"metabolite_name":"Glutathione"},{"metabolite_name":"dTMP"},{"metabolite_name":"UMP"},{"metabolite_name":"Cyclic-AMP"},{"metabolite_name":"dAMP"},{"metabolite_name":"Trehalose/Sucrose"},{"metabolite_name":"dGMP"},{"metabolite_name":"AMP"},{"metabolite_name":"GMP"},{"metabolite_name":"dCDP"},{"metabolite_name":"5-Phosphoribosyl-1-pyrophosphate"},{"metabolite_name":"dTDP"},{"metabolite_name":"CDP"},{"metabolite_name":"UDP"},{"metabolite_name":"Cholic acid"},{"metabolite_name":"ADP"},{"metabolite_name":"dCTP"},{"metabolite_name":"dTTP"},{"metabolite_name":"CTP"},{"metabolite_name":"UTP"},{"metabolite_name":"dATP"},{"metabolite_name":"dGTP"},{"metabolite_name":"GTP"},{"metabolite_name":"UDP-D-glucose"},{"metabolite_name":"UDP-N-acetyl-glucosamine"},{"metabolite_name":"Glutathione disulfide"}]
}

}