#METABOLOMICS WORKBENCH NOZOMU_20230315_151134 DATATRACK_ID:3787 STUDY_ID:ST002506 ANALYSIS_ID:AN004128 PROJECT_ID:PR001619 VERSION 1 CREATED_ON March 20, 2023, 7:35 am #PROJECT PR:PROJECT_TITLE Lactate-dependent Transcriptional Regulation Controls Mammalian Eye PR:PROJECT_TITLE Morphogenesis PR:PROJECT_SUMMARY Mammalian retinal metabolism favors aerobic glycolysis. However, the role of PR:PROJECT_SUMMARY glycolytic metabolism in retinal morphogenesis remains unknown. Here we report PR:PROJECT_SUMMARY that aerobic glycolysis is necessary for the early stages of retinal PR:PROJECT_SUMMARY development. Taking advantage of an unbiased approach that combines the use of PR:PROJECT_SUMMARY eye organoids and single-cell RNA sequencing we identified specific glucose PR:PROJECT_SUMMARY transporters and glycolytic genes in retinal progenitors. Next, we determined PR:PROJECT_SUMMARY that the optic vesicle territory of mouse embryos displays elevated levels of PR:PROJECT_SUMMARY glycolytic activity. At the functional level, we found that removal of Glut1 PR:PROJECT_SUMMARY (also known as Slc2a1) and Lactate dehydrogenase A (Ldha) gene activity from PR:PROJECT_SUMMARY developing retinal progenitors arrested eye morphogenesis. Surprisingly, we PR:PROJECT_SUMMARY uncovered that lactate-mediated upregulation of key eye-field transcription PR:PROJECT_SUMMARY factors was controlled by the epigenetic modification of histone H3 acetylation PR:PROJECT_SUMMARY through histone deacetylase (Hdac) activity. Our results identify a novel PR:PROJECT_SUMMARY bioenergetic independent role of lactate as a signaling molecule necessary for PR:PROJECT_SUMMARY mammalian eye morphogenesis. PR:INSTITUTE Northwestern University PR:LAST_NAME TAKATA PR:FIRST_NAME NOZOMU PR:ADDRESS 303 East Superior Street, 10-220, Chicago, Illinois, 60611, USA PR:EMAIL nozomu.takata@northwestern.edu PR:PHONE 13125036066 #STUDY ST:STUDY_TITLE Natural abundance of isotopic metabolite detection in mouse eye orgnaoids. ST:STUDY_SUMMARY Because the natural abundance of isotopic metabolites in the early eye organoids ST:STUDY_SUMMARY has not yet been reported, we have performed LC-MS/MS without exogenous isotopic ST:STUDY_SUMMARY labeling to show the natural abundance of isotopic carbons. Cell Name AES0145 : ST:STUDY_SUMMARY Rx-GFP K/I EB5 (RIKEN Cell Bank): Organoid method (PMID: 21475194). ST:INSTITUTE Northwestern University ST:LAST_NAME TAKATA ST:FIRST_NAME NOZOMU ST:ADDRESS 303 East Superior Street, 10-220 ST:EMAIL nozomu.takata@northwestern.edu ST:PHONE 3125036066 #SUBJECT SU:SUBJECT_TYPE Mammal SU:SUBJECT_SPECIES Mus musculus SU:TAXONOMY_ID 10090 #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 - Natural_abundance1 Genotype:Wild-type | Treatment:Control RAW_FILE_NAME=Natural_abundance-biological_independent1.raw SUBJECT_SAMPLE_FACTORS - Natural_abundance2 Genotype:Wild-type | Treatment:Control RAW_FILE_NAME=Natural_abundance-biological_independent2.raw SUBJECT_SAMPLE_FACTORS - Natural_abundance3 Genotype:Wild-type | Treatment:Control RAW_FILE_NAME=Natural_abundance-biological_independent3.raw #COLLECTION CO:COLLECTION_SUMMARY Collect embryonic stem cell derived eye organoids without isotopic labeling. CO:COLLECTION_SUMMARY Three biologically independent repeated samples were collected. CO:COLLECTION_PROTOCOL_FILENAME Glucose_and_lactate_isotope_labeling.pdf CO:SAMPLE_TYPE Retina #TREATMENT TR:TREATMENT_SUMMARY No treatment was perfomed. #SAMPLEPREP SP:SAMPLEPREP_SUMMARY The eye organoids were collected and washed twice with PBS before pellets were SP:SAMPLEPREP_SUMMARY flash-frozen and stored at −80°C until metabolite extraction. Metabolite SP:SAMPLEPREP_SUMMARY analysis was performed as described previously (PMID: 33931446). Briefly, for SP:SAMPLEPREP_SUMMARY metabolite extraction, 80% methanol was used followed by the rapid freeze-thaw SP:SAMPLEPREP_SUMMARY method to break the tissues. The supernatant underwent speedvac drying. The SP:SAMPLEPREP_SUMMARY samples were prepared in 80% acetonitrile and were analyzed by High-Resolution SP:SAMPLEPREP_SUMMARY Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS). #CHROMATOGRAPHY CH:CHROMATOGRAPHY_TYPE HILIC CH:INSTRUMENT_NAME Q-exactive CH:COLUMN_NAME Waters XBridge BEH Amide (100 x 3.0mm, 3.5um) CH:SOLVENT_A 95% water/5% acetonitrile; 10 mM ammonium hydroxide; 10 mM ammonium acetate, pH CH:SOLVENT_A 9.0 CH:SOLVENT_B 100% acetonitrile CH:FLOW_GRADIENT 0 min, 15% A; 2.5 min, 30% A; 7 min, 43% A; 16 min, 62% A; 16.1-18 min, 75% A; CH:FLOW_GRADIENT 18-25 min, 15% A with a flow rate of 150 μL/min CH:FLOW_RATE 150 μL/mi CH:COLUMN_TEMPERATURE 40 #ANALYSIS AN:ANALYSIS_TYPE MS #MS MS:INSTRUMENT_NAME Thermo Q Exactive Orbitrap MS:INSTRUMENT_TYPE Orbitrap MS:MS_TYPE ESI MS:ION_MODE UNSPECIFIED MS:MS_COMMENTS The capillary of the ESI source was set to 275 °C, with sheath gas at 35 MS:MS_COMMENTS arbitrary units, auxiliary gas at 5 arbitrary units and the spray voltage at 4.0 MS:MS_COMMENTS kV. In positive/negative polarity switching mode, an m/z scan range from 60 to MS:MS_COMMENTS 900 was chosen and MS1 data was collected at a resolution of 70,000. The MS:MS_COMMENTS automatic gain control (AGC) target was set at 1 × 106 and the maximum MS:MS_COMMENTS injection time was 200 ms. The top 5 precursor ions were subsequently MS:MS_COMMENTS fragmented, in a data-dependent manner, using the higher energy collisional MS:MS_COMMENTS dissociation (HCD) cell set to 30% normalized collision energy in MS2 at a MS:MS_COMMENTS resolution power of 17,500. Besides matching m/z, metabolites are identified by MS:MS_COMMENTS matching either retention time with analytical standards and/or MS2 MS:MS_COMMENTS fragmentation pattern. Data acquisition and analysis were carried out by MS:MS_COMMENTS Xcalibur 4.1 software and Tracefinder 4.1 software, respectively (both from MS:MS_COMMENTS Thermo Fisher Scientific) #MS_METABOLITE_DATA MS_METABOLITE_DATA:UNITS Peak area MS_METABOLITE_DATA_START Samples Natural_abundance1 Natural_abundance2 Natural_abundance3 Factors Genotype:Wild-type | Treatment:Control Genotype:Wild-type | Treatment:Control Genotype:Wild-type | Treatment:Control Total Ion Count 400443050025 304853183842 512026697581 1,3-diphosphoglycerate 0 0 0 1,3-diphosphoglycerate_13C1 0 0 0 1,3-diphosphoglycerate_13C2 0 0 0 1,3-diphosphoglycerate_13C3 0 0 0 2,3-diphosphoglycerate 20639 0 0 2,3-diphosphoglycerate_13C1 0 0 0 2,3-diphosphoglycerate_13C2 0 0 0 2,3-diphosphoglycerate_13C3 0 0 0 2/3-phosphoglycerate 0 15488 0 2/3-phosphoglycerate_13C1 0 0 0 2/3-phosphoglycerate_13C2 0 0 0 2/3-phosphoglycerate_13C3 0 0 0 2-HG 1604679 69559931 642376 2-HG_13C1 0 3028143 0 2-HG_13C2 0 0 0 2-HG_13C3 163650 0 0 2-HG_13C4 0 0 0 2-HG_13C5 89070 100999 0 3-phospho-serine 0 135530 0 3-phospho-serine_13C1 0 0 0 3-phospho-serine_13C2 0 0 0 3-phospho-serine_13C3 0 0 0 6-phospho-D-gluconate 0 0 0 6-phospho-D-gluconate_13C1 0 0 0 6-phospho-D-gluconate_13C2 0 0 0 6-phospho-D-gluconate_13C3 0 0 0 6-phospho-D-gluconate_13C4 0 0 0 6-phospho-D-gluconate_13C5 0 0 0 6-phospho-D-gluconate_13C6 0 0 0 acetoacetate / succinic semialdehyde_13C1 0 0 0 acetoacetate / succinic semialdehyde_13C2 0 0 0 acetoacetate / succinic semialdehyde_13C3 0 0 0 acetoacetate / succinic semialdehyde_13C4 0 0 0 acetoacetic acid / succinic semialdehyde 0 0 0 acetyl-CoA + 0 70066 0 acetyl-CoA_13C1 + 0 0 0 acetyl-CoA_13C2 + 0 0 0 aconitic acid - 81103 21274331 0 aconitic acid_13C1 - 0 941451 0 aconitic acid_13C2 - 0 0 0 adenosine 562372 614479 897648 adenosine_13C10 0 0 0 adenosine_13C5 0 0 0 adenosine_13C6 0 0 0 adenosine_13C7 0 0 0 adenosine_13C8 0 0 0 adenosine_13C9 0 0 0 ADP / dGDP 1015665 3855359 225620 ADP / dGDP_13C1 0 0 0 ADP / dGDP_13C10 0 0 0 ADP / dGDP_13C2 0 0 0 ADP / dGDP_13C3 0 0 0 ADP / dGDP_13C4 0 0 0 ADP / dGDP_13C5 0 0 0 ADP / dGDP_13C6 4508325 996940 78327 ADP / dGDP_13C7 71506 66354 0 ADP / dGDP_13C8 0 0 0 ADP / dGDP_13C9 0 0 0 AICAR 0 0 0 AICAR_13C5 0 0 0 AICAR_13C6 0 0 0 AICAR_13C7 0 0 0 AICAR_13C8 0 0 0 AICAR_13C9 0 0 0 a-KG 12585829 109741621 1787218 a-KG_13C1 460663 5101652 0 a-KG_13C2 41759 42528 0 a-KG_13C3 0 0 0 a-KG_13C4 0 0 0 a-KG_13C5 0 0 0 alanine 287755183 355797865 107817154 alanine_13C1 8384848 8103127 2270232 alanine_13C2 0 0 0 alanine_13C3 0 0 0 AMP / dGMP 282938 1977943 76374 AMP / dGMP_13C1 0 0 0 AMP / dGMP_13C10 0 0 0 AMP / dGMP_13C2 57995 513533 0 AMP / dGMP_13C5 0 0 0 AMP / dGMP_13C6 0 0 0 AMP / dGMP_13C7 0 0 0 AMP / dGMP_13C8 0 0 0 AMP / dGMP_13C9 0 0 0 aspartate 94581191 137017738 97158509 aspartate_13C1 3923175 5145744 3584794 aspartate_13C2 336067 123296 98908 aspartate_13C3 3923175 5145744 3584794 aspartate_13C4 0 0 0 ATP / dGTP 255517 2828488 35651 ATP / dGTP_13C10 0 0 0 ATP / dGTP_13C5 0 0 0 ATP / dGTP_13C6 0 0 0 ATP / dGTP_13C7 0 0 0 ATP / dGTP_13C8 0 79109 90743 ATP / dGTP_13C9 0 0 0 choline+ 4063201895 3984726246 3508082958 choline_13C1+ 226237337 225151307 197023447 choline_13C2+ 3720830 3531344 3459396 choline_13C3+ 0 0 0 choline_13C4+ 0 0 0 choline_13C5+ 0 0 0 citrate(iso)/citrate 11368469 12654096 13811270 citrate(iso)/citrate_13C1 60582 33306 403815 citrate(iso)/citrate_13C2 233822 276845 0 citrate(iso)/citrate_13C3 0 0 0 citrate(iso)/citrate_13C4 0 0 0 citrate(iso)/citrate_13C5 0 0 0 citrate(iso)/citrate_13C6 0 0 0 CMP 0 0 0 CMP_13C5 0 0 0 CMP_13C6 0 0 0 CMP_13C7 0 0 0 CMP_13C8 0 0 0 CMP_13C9 0 0 0 Crotonyl-CoA 0 0 0 CTP 2320067 4499224 116319 CTP_13C5 0 0 0 CTP_13C6 0 0 0 CTP_13C7 0 0 0 CTP_13C8 0 0 0 CTP_13C9 0 0 0 cystathionine 808774 2957255 848910 cystathionine_13C1 0 25218 0 cysteine 105313774 55721331 39668648 cysteine_13C1 2781351 1318448 1007398 cysteine_13C2 0 0 0 cysteine_13C3 0 0 0 dATP 0 0 0 dATP_13C10 0 0 0 dATP_13C5 0 0 0 dATP_13C6 0 0 0 dATP_13C7 0 0 0 dATP_13C8 0 0 0 dATP_13C9 0 0 0 dCTP 0 0 0 dCTP_13C5 0 0 0 dCTP_13C6 0 0 0 dCTP_13C7 0 0 0 dCTP_13C8 0 0 0 dCTP_13C9 0 0 50106 deoxyguanosine 9993705 13107602 17479818 deoxyguanosine_13C10 0 0 0 deoxyguanosine_13C5 0 0 0 deoxyguanosine_13C6 0 0 0 deoxyguanosine_13C7 0 0 0 deoxyguanosine_13C8 0 0 0 deoxyguanosine_13C9 0 0 0 D-galactosamine/glucosamine-1/6-phosphate 0 0 0 D-galactosamine/glucosamine-1/6-phosphate_13C6 0 0 0 D-ribose-1/5-phosphate 656528 683988 566828 D-ribose-1/5-phosphate_13C1 0 55696 0 D-ribose-1/5-phosphate_13C2 0 0 0 D-ribose-1/5-phosphate_13C3 0 7501991 0 D-ribose-1/5-phosphate_13C4 0 309065 0 D-ribose-1/5-phosphate_13C5 0 0 0 D-sedoheptulose-7-phosphate 340247 68312 147810 D-sedoheptulose-7-phosphate_13C1 0 0 0 D-sedoheptulose-7-phosphate_13C2 0 0 0 D-sedoheptulose-7-phosphate_13C3 0 0 0 D-sedoheptulose-7-phosphate_13C4 0 0 0 D-sedoheptulose-7-phosphate_13C5 0 0 0 D-sedoheptulose-7-phosphate_13C6 0 0 0 D-sedoheptulose-7-phosphate_13C7 0 0 0 dTTP 0 0 0 dTTP_13C10 0 0 0 dTTP_13C5 0 0 0 dTTP_13C6 0 0 0 dTTP_13C7 0 0 0 dTTP_13C8 0 0 0 dTTP_13C9 0 0 0 dUTP 0 0 0 dUTP_13C5 0 0 0 dUTP_13C6 0 0 0 dUTP_13C7 0 0 0 dUTP_13C8 0 0 0 dUTP_13C9 0 0 0 F-1,6/2,6-P 791722 2254498 119341 F-1,6/2,6-P_13C1 0 0 0 F-1,6/2,6-P_13C2 0 0 0 F-1,6/2,6-P_13C3 0 0 0 F-1,6/2,6-P_13C4 0 0 0 F-1,6/2,6-P_13C5 16994 0 0 F-1,6/2,6-P_13C6 705836 116051 17874 F6P/G1P/G6P 7885305 3760336 7351105 F6P/G1P/G6P_13C1 57802 0 74901 F6P/G1P/G6P_13C2 0 0 0 F6P/G1P/G6P_13C3 0 0 0 F6P/G1P/G6P_13C4 0 0 0 F6P/G1P/G6P_13C5 0 0 0 F6P/G1P/G6P_13C6 0 0 0 fructose / mannose 49018252 22072967 31986360 fumarate 3921039 103428034 4672231 fumarate_13C1 0 3028653 63674 fumarate_13C2 0 0 0 fumarate_13C3 0 0 0 fumarate_13C4 0 0 0 galactose / glucose 1107046271 142623179 2131333895 GAP / DHAP 0 62864 81644 GAP / DHAP_13C1 0 0 0 GAP / DHAP_13C2 0 0 0 GAP / DHAP_13C3 4150362 17674398 511910 glucose_13C6 5180994 3028275 5314519 glutamate 580901010 1601111337 516655388 glutamate_13C1 30778003 92835241 27742345 glutamate_13C2 192172 629315 118623 glutamate_13C3 0 0 0 glutamate_13C4 0 0 0 glutamate_13C5 0 0 0 glutamine 57374500 439946867 47441776 glutamine_13C1 2406153 22119383 1894880 glutamine_13C2 0 0 0 glutamine_13C3 1503597 604566 1483843 glutamine_13C4 0 0 0 glutamine_13C5 0 0 0 glutathione 25628495 281795240 231700 glutathione_13C1 2701196 27995272 0 glutathione_13C2 0 5516285 0 glutathione_13C3 0 128372 0 glutathione_13C4 0 0 0 glutathione_13C5 0 0 0 glutathione disulfide 324082 235248 0 glutathione disulfide_13C1 0 0 0 glutathione disulfide_13C2 0 0 0 glutathione disulfide_13C3 0 0 0 glutathione disulfide_13C4 0 0 0 glutathione disulfide_13C5 0 0 0 glycerate 64761144 75297421 8078691 glycerate_13C1 1478355 1346422 0 glycerate_13C2 0 0 0 glycerate_13C3 0 0 0 glycerol-2/3-phosphate 718107 746467 526615 glycerol-2/3-phosphate_13C2 0 0 0 glycerol-2/3-phosphate_13C3 0 0 0 glycine 372274666 773074502 523712689 glycine_13C1 7453294 14022813 10582742 glycine_13C2 0 0 0 GMP 0 0 0 GMP_13C10 0 0 0 GMP_13C5 0 0 0 GMP_13C6 0 0 0 GMP_13C7 0 0 0 GMP_13C8 0 0 0 GMP_13C9 0 0 0 GTP 190372 750363 22682 GTP_13C10 0 0 0 GTP_13C5 0 0 0 GTP_13C6 0 0 0 GTP_13C7 0 0 0 GTP_13C8 0 0 0 GTP_13C9 0 0 0 guanosine 14078512 20097590 20030831 guanosine_13C10 0 0 0 guanosine_13C5 0 0 0 guanosine_13C6 0 0 0 guanosine_13C7 0 0 0 guanosine_13C8 0 0 0 guanosine_13C9 0 0 0 IDP 0 0 0 IDP_13C10 0 0 0 IDP_13C5 0 0 0 IDP_13C6 0 0 0 IDP_13C7 0 0 0 IDP_13C8 0 0 0 IDP_13C9 0 0 0 IMP 0 0 0 IMP_13C10 0 0 0 IMP_13C5 0 0 0 IMP_13C6 0 0 0 IMP_13C7 0 0 0 IMP_13C8 0 0 0 IMP_13C9 0 0 0 itaconic acid 0 0 0 itaconic acid_13C1 0 0 0 itaconic acid_13C2 0 0 0 lactate 20399717814 11347789896 37490607227 lactate_13C1 668039709 381701252 699909363 lactate_13C2 51009179 28730575 102850734 lactate_13C3 0 689674278 2612183269 leucine / leucine(iso) 26121105632 17700889789 34732970377 leucine / leucine(iso)_13C1 1741254238 1195250748 2357884543 leucine / leucine(iso)_13C2 36559187 24910433 50636755 leucine / leucine(iso)_13C3 0 110332 14873 leucine / leucine(iso)_13C6 18568 0 0 malate 55265810 1183394635 59753138 malate_13C1 1426339 50267284 1651509 malate_13C2 0 441748 0 malate_13C3 0 0 0 malate_13C4 0 0 0 mevalonate 1230514 922919 7838801 mevalonate_13C1 0 0 0 mevalonate_13C2 0 0 0 mevalonate_13C3 0 0 0 mevalonate_13C4 0 0 0 mevalonate_13C5 0 0 0 mevalonate_13C6 0 0 0 N-acetyl-glucosamine-1/6-phosphate 497379 876202 553865 N-acetyl-glucosamine-1/6-phosphate_13C6 0 0 0 N-acetyl-glucosamine-1/6-phosphate_13C8 0 0 0 NAD+ 856342 1621371 420477 NADH 0 1254667 0 NADP+ 0 0 0 NADPH 0 44327 0 N-carbamoyl-L-aspartate 1068368 1467063 1326056 N-carbamoyl-L-aspartate_13C1 0 0 0 N-carbamoyl-L-aspartate_13C2 71591 0 0 N-carbamoyl-L-aspartate_13C3 0 0 0 N-carbamoyl-L-aspartate_13C4 0 0 0 N-carbamoyl-L-aspartate_13C5 0 0 0 oxaloacetate 0 0 85080 oxaloacetate_13C1 0 0 0 oxaloacetate_13C2 0 0 0 oxaloacetate_13C3 0 0 0 oxaloacetate_13C4 0 0 0 phosphoenolpyruvate 0 0 0 phosphoenolpyruvate_13C1 0 0 0 phosphoenolpyruvate_13C2 0 0 0 phosphoenolpyruvate_13C3 0 0 0 PRPP 0 0 0 PRPP_13C1 0 0 0 PRPP_13C2 0 0 0 PRPP_13C3 0 0 0 PRPP_13C4 0 0 0 PRPP_13C5 0 0 0 pyruvate 112741299 195696978 244326259 pyruvate_13C1 3068474 5081416 6944018 pyruvate_13C2 0 0 0 pyruvate_13C3 0 0 0 S-adenosyl-L-homoCysteine 0 139391 0 S-adenosyl-L-homoCysteine_13C1 0 0 0 S-adenosyl-L-methionine 16424811 15958919 6767309 S-adenosyl-L-methionine_13C1 2216480 2352936 870729 S-adenosyl-L-methionine_13C2 20580 0 0 S-adenosyl-L-methionine_13C3 0 0 0 S-adenosyl-L-methionine_13C4 0 0 0 S-adenosyl-L-methionine_13C5 0 0 0 S-adenosyl-L-methionine_13C6 0 0 0 S-adenosyl-L-methionine_13C7 0 0 0 S-adenosyl-L-methionine_13C8 0 0 0 S-adenosyl-L-methionine_13C9 0 0 0 serine 17228147 51486050 35432054 serine_13C1 66285 1240067 651424 serine_13C2 0 0 0 serine_13C3 0 0 0 sorbitol / galactitol / L-iditol / manitol 52511704 115389641 127213762 sorbitol / galactitol / L-iditol / manitol_13C6 0 43282 0 succinate 105915555 1185620009 36047765 succinate_13C1 3827596 48687049 930972 succinate_13C2 425830 377945 0 succinate_13C3 0 0 0 succinate_13C4 0 0 0 thiamine diphosphate+ 0 0 0 thiamine phosphate+ 0 0 0 thiamine+ 1182603322 1164258747 1471652509 UDP-N-acetyl-galactosamine/glucosamine 3722963 5368102 4301531 UDP-N-acetyl-galactosamine/glucosamine_13C13 0 0 0 UDP-N-acetyl-galactosamine/glucosamine_13C6 0 0 0 UDP-N-acetyl-galactosamine/glucosamine_13C8 0 0 0 UMP 1999840 2743581 2432508 UMP_13C5 0 0 0 UMP_13C6 0 0 0 UMP_13C7 0 0 0 UMP_13C8 0 0 0 UMP_13C9 0 0 0 UTP 2127444 6517313 0 UTP_13C5 0 0 0 UTP_13C6 0 0 0 UTP_13C7 0 0 0 UTP_13C8 0 0 0 UTP_13C9 0 0 0 xylitol / arabitol / ribito 8106563 8464042 1010180 xylitol / arabitol / ribito_13C5 102067 57266 0 MS_METABOLITE_DATA_END #METABOLITES METABOLITES_START metabolite_name KEGG ID Total Ion Count 1,3-diphosphoglycerate C00236 1,3-diphosphoglycerate_13C1 1,3-diphosphoglycerate_13C2 1,3-diphosphoglycerate_13C3 2,3-diphosphoglycerate C01159 2,3-diphosphoglycerate_13C1 2,3-diphosphoglycerate_13C2 2,3-diphosphoglycerate_13C3 2/3-phosphoglycerate C00631 / C00197 2/3-phosphoglycerate_13C1 2/3-phosphoglycerate_13C2 2/3-phosphoglycerate_13C3 2-HG C02630 2-HG_13C1 2-HG_13C2 2-HG_13C3 2-HG_13C4 2-HG_13C5 3-phospho-serine C01005 3-phospho-serine_13C1 3-phospho-serine_13C2 3-phospho-serine_13C3 6-phospho-D-gluconate C00345 6-phospho-D-gluconate_13C1 6-phospho-D-gluconate_13C2 6-phospho-D-gluconate_13C3 6-phospho-D-gluconate_13C4 6-phospho-D-gluconate_13C5 6-phospho-D-gluconate_13C6 acetoacetate / succinic semialdehyde_13C1 acetoacetate / succinic semialdehyde_13C2 acetoacetate / succinic semialdehyde_13C3 acetoacetate / succinic semialdehyde_13C4 acetoacetic acid / succinic semialdehyde C00164 / C00232 acetyl-CoA + C00024 acetyl-CoA_13C1 + acetyl-CoA_13C2 + aconitic acid - C6H6O6 aconitic acid_13C1 - aconitic acid_13C2 - adenosine C00212 adenosine_13C10 adenosine_13C5 adenosine_13C6 adenosine_13C7 adenosine_13C8 adenosine_13C9 ADP / dGDP C00008 / C00361 ADP / dGDP_13C1 ADP / dGDP_13C10 ADP / dGDP_13C2 ADP / dGDP_13C3 ADP / dGDP_13C4 ADP / dGDP_13C5 ADP / dGDP_13C6 ADP / dGDP_13C7 ADP / dGDP_13C8 ADP / dGDP_13C9 AICAR C04677 AICAR_13C5 AICAR_13C6 AICAR_13C7 AICAR_13C8 AICAR_13C9 a-KG C00026 a-KG_13C1 a-KG_13C2 a-KG_13C3 a-KG_13C4 a-KG_13C5 alanine C00041-C00133 alanine_13C1 alanine_13C2 alanine_13C3 AMP / dGMP C00020 / C00362 AMP / dGMP_13C1 AMP / dGMP_13C10 AMP / dGMP_13C2 AMP / dGMP_13C5 AMP / dGMP_13C6 AMP / dGMP_13C7 AMP / dGMP_13C8 AMP / dGMP_13C9 aspartate C16433-C00049 aspartate_13C1 aspartate_13C2 aspartate_13C3 aspartate_13C4 ATP / dGTP C00002 / C00286 ATP / dGTP_13C10 ATP / dGTP_13C5 ATP / dGTP_13C6 ATP / dGTP_13C7 ATP / dGTP_13C8 ATP / dGTP_13C9 choline+ C00114 choline_13C1+ choline_13C2+ choline_13C3+ choline_13C4+ choline_13C5+ citrate(iso)/citrate C00311 / C00063 citrate(iso)/citrate_13C1 citrate(iso)/citrate_13C2 citrate(iso)/citrate_13C3 citrate(iso)/citrate_13C4 citrate(iso)/citrate_13C5 citrate(iso)/citrate_13C6 CMP C00055 CMP_13C5 CMP_13C6 CMP_13C7 CMP_13C8 CMP_13C9 Crotonyl-CoA C00877 CTP C00063 CTP_13C5 CTP_13C6 CTP_13C7 CTP_13C8 CTP_13C9 cystathionine C00542 cystathionine_13C1 cysteine C00736-C00097 cysteine_13C1 cysteine_13C2 cysteine_13C3 dATP C00131 dATP_13C10 dATP_13C5 dATP_13C6 dATP_13C7 dATP_13C8 dATP_13C9 dCTP C00458 dCTP_13C5 dCTP_13C6 dCTP_13C7 dCTP_13C8 dCTP_13C9 deoxyguanosine C00330 deoxyguanosine_13C10 deoxyguanosine_13C5 deoxyguanosine_13C6 deoxyguanosine_13C7 deoxyguanosine_13C8 deoxyguanosine_13C9 D-galactosamine/glucosamine-1/6-phosphate C03783 / C00352 / C06156 / C00352 D-galactosamine/glucosamine-1/6-phosphate_13C6 D-ribose-1/5-phosphate C00620 / C00117 D-ribose-1/5-phosphate_13C1 D-ribose-1/5-phosphate_13C2 D-ribose-1/5-phosphate_13C3 D-ribose-1/5-phosphate_13C4 D-ribose-1/5-phosphate_13C5 D-sedoheptulose-7-phosphate C05382 D-sedoheptulose-7-phosphate_13C1 D-sedoheptulose-7-phosphate_13C2 D-sedoheptulose-7-phosphate_13C3 D-sedoheptulose-7-phosphate_13C4 D-sedoheptulose-7-phosphate_13C5 D-sedoheptulose-7-phosphate_13C6 D-sedoheptulose-7-phosphate_13C7 dTTP C00459 dTTP_13C10 dTTP_13C5 dTTP_13C6 dTTP_13C7 dTTP_13C8 dTTP_13C9 dUTP C00460 dUTP_13C5 dUTP_13C6 dUTP_13C7 dUTP_13C8 dUTP_13C9 F-1,6/2,6-P C00354 / C00665 F-1,6/2,6-P_13C1 F-1,6/2,6-P_13C2 F-1,6/2,6-P_13C3 F-1,6/2,6-P_13C4 F-1,6/2,6-P_13C5 F-1,6/2,6-P_13C6 F6P/G1P/G6P C00085 / C00103 / C00092 F6P/G1P/G6P_13C1 F6P/G1P/G6P_13C2 F6P/G1P/G6P_13C3 F6P/G1P/G6P_13C4 F6P/G1P/G6P_13C5 F6P/G1P/G6P_13C6 fructose / mannose C00095 / C00159 fumarate C00122 fumarate_13C1 fumarate_13C2 fumarate_13C3 fumarate_13C4 galactose / glucose C00124 / C00267 GAP / DHAP C00118 / C00111 GAP / DHAP_13C1 GAP / DHAP_13C2 GAP / DHAP_13C3 glucose_13C6 glutamate C00302-C00025 glutamate_13C1 glutamate_13C2 glutamate_13C3 glutamate_13C4 glutamate_13C5 glutamine C00303-C00064 glutamine_13C1 glutamine_13C2 glutamine_13C3 glutamine_13C4 glutamine_13C5 glutathione C00051 glutathione_13C1 glutathione_13C2 glutathione_13C3 glutathione_13C4 glutathione_13C5 glutathione disulfide C00127 glutathione disulfide_13C1 glutathione disulfide_13C2 glutathione disulfide_13C3 glutathione disulfide_13C4 glutathione disulfide_13C5 glycerate C00258 glycerate_13C1 glycerate_13C2 glycerate_13C3 glycerol-2/3-phosphate C02979 / C00093 glycerol-2/3-phosphate_13C2 glycerol-2/3-phosphate_13C3 glycine C00037 glycine_13C1 glycine_13C2 GMP C00144 GMP_13C10 GMP_13C5 GMP_13C6 GMP_13C7 GMP_13C8 GMP_13C9 GTP C00044 GTP_13C10 GTP_13C5 GTP_13C6 GTP_13C7 GTP_13C8 GTP_13C9 guanosine C00387 guanosine_13C10 guanosine_13C5 guanosine_13C6 guanosine_13C7 guanosine_13C8 guanosine_13C9 IDP C00104 IDP_13C10 IDP_13C5 IDP_13C6 IDP_13C7 IDP_13C8 IDP_13C9 IMP C00130 IMP_13C10 IMP_13C5 IMP_13C6 IMP_13C7 IMP_13C8 IMP_13C9 itaconic acid C00490 itaconic acid_13C1 itaconic acid_13C2 lactate C01432-C00186 lactate_13C1 lactate_13C2 lactate_13C3 leucine / leucine(iso) C16439-C00123 / C16434-C00407 leucine / leucine(iso)_13C1 leucine / leucine(iso)_13C2 leucine / leucine(iso)_13C3 leucine / leucine(iso)_13C6 malate C00711-C00149 malate_13C1 malate_13C2 malate_13C3 malate_13C4 mevalonate C00418 mevalonate_13C1 mevalonate_13C2 mevalonate_13C3 mevalonate_13C4 mevalonate_13C5 mevalonate_13C6 N-acetyl-glucosamine-1/6-phosphate C04256 / C00357 N-acetyl-glucosamine-1/6-phosphate_13C6 N-acetyl-glucosamine-1/6-phosphate_13C8 NAD+ C00003 NADH C00004 NADP+ C00006 NADPH C00005 N-carbamoyl-L-aspartate C00438 N-carbamoyl-L-aspartate_13C1 N-carbamoyl-L-aspartate_13C2 N-carbamoyl-L-aspartate_13C3 N-carbamoyl-L-aspartate_13C4 N-carbamoyl-L-aspartate_13C5 oxaloacetate C00036 oxaloacetate_13C1 oxaloacetate_13C2 oxaloacetate_13C3 oxaloacetate_13C4 phosphoenolpyruvate C00074 phosphoenolpyruvate_13C1 phosphoenolpyruvate_13C2 phosphoenolpyruvate_13C3 PRPP C00119 PRPP_13C1 PRPP_13C2 PRPP_13C3 PRPP_13C4 PRPP_13C5 pyruvate C00022 pyruvate_13C1 pyruvate_13C2 pyruvate_13C3 S-adenosyl-L-homoCysteine C00021 S-adenosyl-L-homoCysteine_13C1 S-adenosyl-L-methionine C00019 S-adenosyl-L-methionine_13C1 S-adenosyl-L-methionine_13C2 S-adenosyl-L-methionine_13C3 S-adenosyl-L-methionine_13C4 S-adenosyl-L-methionine_13C5 S-adenosyl-L-methionine_13C6 S-adenosyl-L-methionine_13C7 S-adenosyl-L-methionine_13C8 S-adenosyl-L-methionine_13C9 serine C00716-C00065 serine_13C1 serine_13C2 serine_13C3 sorbitol / galactitol / L-iditol / manitol C00794 / C01697 / C01507 / C00392 sorbitol / galactitol / L-iditol / manitol_13C6 succinate C00042 succinate_13C1 succinate_13C2 succinate_13C3 succinate_13C4 thiamine diphosphate+ C00068 thiamine phosphate+ C01081 thiamine+ C00378 UDP-N-acetyl-galactosamine/glucosamine C00203 / C00043 UDP-N-acetyl-galactosamine/glucosamine_13C13 UDP-N-acetyl-galactosamine/glucosamine_13C6 UDP-N-acetyl-galactosamine/glucosamine_13C8 UMP C00105 UMP_13C5 UMP_13C6 UMP_13C7 UMP_13C8 UMP_13C9 UTP C00075 UTP_13C5 UTP_13C6 UTP_13C7 UTP_13C8 UTP_13C9 xylitol / arabitol / ribito C00379/ C01904 / C00532 / C00474 xylitol / arabitol / ribito_13C5 METABOLITES_END #END