#METABOLOMICS WORKBENCH bur27_20211205_110601 DATATRACK_ID:2963 STUDY_ID:ST002009 ANALYSIS_ID:AN003275 VERSION 1 CREATED_ON 02-13-2024 #PROJECT PR:PROJECT_TITLE Metabolic profiles of murine stress erythroid progenitors PR:PROJECT_SUMMARY Inflammation alters hematopoiesis, skewing production to generate myeloid PR:PROJECT_SUMMARY effector cells at the expense of steady state erythropoiesis. To compensate, PR:PROJECT_SUMMARY stress erythropoiesis is induced to maintain homeostasis until the inflammation PR:PROJECT_SUMMARY is resolved. Unlike the constant production of steady state erythropoiesis, PR:PROJECT_SUMMARY stress erythropoiesis generates a bolus of new erythrocytes by first producing PR:PROJECT_SUMMARY immature progenitor cells, which then transition to committed erythroid PR:PROJECT_SUMMARY progenitors and differentiate. We hypothesize that the proliferation of early PR:PROJECT_SUMMARY progenitor cells and their transition to differentiation is regulated by changes PR:PROJECT_SUMMARY in metabolism. Metabolomics and isotope tracing analysis was performed to assess PR:PROJECT_SUMMARY the intracellular metabolic profiles in proliferating progenitors isolated from PR:PROJECT_SUMMARY in vitro stress erythropoiesis cultures. We observed an active engagement of PR:PROJECT_SUMMARY glucose metabolism in glycolysis and anabolic biosynthesis, while the levels of PR:PROJECT_SUMMARY TCA intermediates suggested that TCA cycle and mitochondrial respiration were PR:PROJECT_SUMMARY blocked. Concomitantly, inducible nitric oxide synthase (iNOS) was induced in PR:PROJECT_SUMMARY progenitor cells to increase the production of nitric oxide (NO), which was PR:PROJECT_SUMMARY demonstrated to be crucial for proliferating progenitor metabolism. Inhibition PR:PROJECT_SUMMARY or genetic mutation of iNOS decreased NO levels resulting in the suppression of PR:PROJECT_SUMMARY progenitor proliferation in vitro and in vivo. As evaluated by RNA-seq, PR:PROJECT_SUMMARY inhibition of iNOS suppressed cell proliferation-related pathways including cell PR:PROJECT_SUMMARY cycle and nucleotide metabolism, while upregulating erythroid differentiation PR:PROJECT_SUMMARY genes. These data suggest that iNOS-derived NO production establishes a PR:PROJECT_SUMMARY metabolism that promotes the proliferation of progenitor cells while inhibiting PR:PROJECT_SUMMARY their differentiation. In contrast, the transition to differentiation is marked PR:PROJECT_SUMMARY by decreased Nos2 expression and a change in metabolism to support induction of PR:PROJECT_SUMMARY the erythroid gene expression program. These data support a model where PR:PROJECT_SUMMARY increased pro-inflammatory signals inhibit steady state erythropoiesis, while at PR:PROJECT_SUMMARY the same time promoting stress erythropoiesis to maintain homeostasis. PR:INSTITUTE Pennsylvania State University PR:DEPARTMENT Veterinary and Biomedical Sciences PR:LABORATORY Paulson Lab PR:LAST_NAME Paulson PR:FIRST_NAME Robert PR:ADDRESS 228 AVBS Building, Shortlidge Road, University Park, PA 16802 PR:EMAIL rfp5@psu.edu PR:PHONE 814-863-6306 PR:DOI http://dx.doi.org/10.21228/M89402 #STUDY ST:STUDY_TITLE Metabolomics analysis of stress erythroid progenitors ST:STUDY_SUMMARY A time course study to assess the intracellular metabolic changes of progenitors ST:STUDY_SUMMARY isolated from stress erythropoiesis expansion culture. ST:INSTITUTE Pennsylvania State University ST:DEPARTMENT Veterinary and Biomedical Sciences ST:LABORATORY Paulson Lab ST:LAST_NAME Paulson ST:FIRST_NAME Robert ST:ADDRESS 228 AVBS Building Shortlidge Road University Park, PA 16802 ST:EMAIL rfp5@psu.edu ST:PHONE 814-863-6306 ST:SUBMIT_DATE 2021-12-05 #SUBJECT SU:SUBJECT_TYPE Cultured cells SU:SUBJECT_SPECIES Mus musculus SU:TAXONOMY_ID 10090 #SUBJECT_SAMPLE_FACTORS: SUBJECT(optional)[tab]SAMPLE[tab]FACTORS(NAME:VALUE pairs separated by |)[tab]Additional sample data SUBJECT_SAMPLE_FACTORS Mus musculus D1_1 Mouse_strain:wild type C57BL/6 | Culture_stage:Expansion stage | Time_point(days):1 Cell_type=Stress erythroid progenitor cells; RAW_FILE_NAME=D1_1.mzML SUBJECT_SAMPLE_FACTORS Mus musculus D1_2 Mouse_strain:wild type C57BL/6 | Culture_stage:Expansion stage | Time_point(days):1 Cell_type=Stress erythroid progenitor cells; RAW_FILE_NAME=D1_2.mzML SUBJECT_SAMPLE_FACTORS Mus musculus D1_3 Mouse_strain:wild type C57BL/6 | Culture_stage:Expansion stage | Time_point(days):1 Cell_type=Stress erythroid progenitor cells; RAW_FILE_NAME=D1_3.mzML SUBJECT_SAMPLE_FACTORS Mus musculus D1_4 Mouse_strain:wild type C57BL/6 | Culture_stage:Expansion stage | Time_point(days):1 Cell_type=Stress erythroid progenitor cells; RAW_FILE_NAME=D1_4.mzML SUBJECT_SAMPLE_FACTORS Mus musculus D1_5 Mouse_strain:wild type C57BL/6 | Culture_stage:Expansion stage | Time_point(days):1 Cell_type=Stress erythroid progenitor cells; RAW_FILE_NAME=D1_5.mzML SUBJECT_SAMPLE_FACTORS Mus musculus D3_1 Mouse_strain:wild type C57BL/6 | Culture_stage:Expansion stage | Time_point(days):3 Cell_type=Stress erythroid progenitor cells; RAW_FILE_NAME=D3_1.mzML SUBJECT_SAMPLE_FACTORS Mus musculus D3_2 Mouse_strain:wild type C57BL/6 | Culture_stage:Expansion stage | Time_point(days):3 Cell_type=Stress erythroid progenitor cells; RAW_FILE_NAME=D3_2.mzML SUBJECT_SAMPLE_FACTORS Mus musculus D3_3 Mouse_strain:wild type C57BL/6 | Culture_stage:Expansion stage | Time_point(days):3 Cell_type=Stress erythroid progenitor cells; RAW_FILE_NAME=D3_3.mzML SUBJECT_SAMPLE_FACTORS Mus musculus D3_4 Mouse_strain:wild type C57BL/6 | Culture_stage:Expansion stage | Time_point(days):3 Cell_type=Stress erythroid progenitor cells; RAW_FILE_NAME=D3_4.mzML SUBJECT_SAMPLE_FACTORS Mus musculus D3_5 Mouse_strain:wild type C57BL/6 | Culture_stage:Expansion stage | Time_point(days):3 Cell_type=Stress erythroid progenitor cells; RAW_FILE_NAME=D3_5.mzML SUBJECT_SAMPLE_FACTORS Mus musculus D5_1 Mouse_strain:wild type C57BL/6 | Culture_stage:Expansion stage | Time_point(days):5 Cell_type=Stress erythroid progenitor cells; RAW_FILE_NAME=D5_1.mzML SUBJECT_SAMPLE_FACTORS Mus musculus D5_2 Mouse_strain:wild type C57BL/6 | Culture_stage:Expansion stage | Time_point(days):5 Cell_type=Stress erythroid progenitor cells; RAW_FILE_NAME=D5_2.mzML SUBJECT_SAMPLE_FACTORS Mus musculus D5_3 Mouse_strain:wild type C57BL/6 | Culture_stage:Expansion stage | Time_point(days):5 Cell_type=Stress erythroid progenitor cells; RAW_FILE_NAME=D5_3.mzML SUBJECT_SAMPLE_FACTORS Mus musculus D5_4 Mouse_strain:wild type C57BL/6 | Culture_stage:Expansion stage | Time_point(days):5 Cell_type=Stress erythroid progenitor cells; RAW_FILE_NAME=D5_4.mzML SUBJECT_SAMPLE_FACTORS Mus musculus D5_5 Mouse_strain:wild type C57BL/6 | Culture_stage:Expansion stage | Time_point(days):5 Cell_type=Stress erythroid progenitor cells; RAW_FILE_NAME=D5_5.mzML #COLLECTION CO:COLLECTION_SUMMARY Unfractionated wild-type bone marrow cells were cultured in stress CO:COLLECTION_SUMMARY erythropoiesis expansion medium (SEEM). At indicated time point, stress CO:COLLECTION_SUMMARY erythroid progenitor cells were counted, washed with PBS and snap frozen in CO:COLLECTION_SUMMARY liquid nitrogen. CO:SAMPLE_TYPE Stem cells #TREATMENT TR:TREATMENT_SUMMARY All cells are untreated. #SAMPLEPREP SP:SAMPLEPREP_SUMMARY Cell pellets were extracted with 1 ml pre-chilled 50:50 HPLC-grade SP:SAMPLEPREP_SUMMARY water:methanol (v/v) containing 1 µM chlorpropamide as the internal standard. SP:SAMPLEPREP_SUMMARY The samples were vortexed briefly followed by thorough homogenization. The SP:SAMPLEPREP_SUMMARY samples were then snap frozen with liquid nitrogen and immediately thawed at SP:SAMPLEPREP_SUMMARY room temperature. This step was repeated for three times followed by SP:SAMPLEPREP_SUMMARY centrifuging for 10 min at 12,000 x g and 4 °C. The supernatants were SP:SAMPLEPREP_SUMMARY transferred into fresh microfuge tubes. The remaining cell pellets were SP:SAMPLEPREP_SUMMARY re-extracted with 0.5 ml 50% methanol containing 1 µM chlorpropamide, SP:SAMPLEPREP_SUMMARY homogenized, frozen and thawed three times, spun down, and the supernatants were SP:SAMPLEPREP_SUMMARY combined with the first extraction. Metabolites-containing supernatants were SP:SAMPLEPREP_SUMMARY concentrated to dryness at room temperature in a SpeedVac concentrator and SP:SAMPLEPREP_SUMMARY re-dissolved in 100 µl 97:3 water:methanol (v/v). After centrifuging for 10 min SP:SAMPLEPREP_SUMMARY at 13000 × g and 4°C, 70 µl of supernatants were transferred into autosampler SP:SAMPLEPREP_SUMMARY vials for LC-MS analysis. Two types of control were prepared in triplicates to SP:SAMPLEPREP_SUMMARY run in concert with the experimental samples: the process blank control, and the SP:SAMPLEPREP_SUMMARY pooled control containing an equal volume from each experimental sample. #CHROMATOGRAPHY CH:CHROMATOGRAPHY_SUMMARY The sample run order was randomized to reduce bias from instrument drift. 10 µl CH:CHROMATOGRAPHY_SUMMARY sample was subjected to LC-MS analysis on a Exactive Plus Orbitrap mass CH:CHROMATOGRAPHY_SUMMARY spectrometer (Thermo Fisher Scientific) coupled to an Ultimate 3000 UHPLC system CH:CHROMATOGRAPHY_SUMMARY (Thermo Fisher Scientific). Reversed-phase chromatography mode was used to CH:CHROMATOGRAPHY_SUMMARY separate compounds on a Xselect C18 HSS column (Waters) with solvent A (97:3 CH:CHROMATOGRAPHY_SUMMARY water:methanol (v/v), 10 mM tributylamine, and 15 mM acetic acid ) and solvent B CH:CHROMATOGRAPHY_SUMMARY (methanol). The flow rate was 200 µl/min, and the total run time was 25 min. CH:CHROMATOGRAPHY_SUMMARY The gradient was 0 min, 0% B; 5 min, 20% B; 7.5 min, 55% B; 15 min, 65% B; 17.5 CH:CHROMATOGRAPHY_SUMMARY min, 95% B; and 21 min, 0% B. The mass spectrometer was operated in a CH:CHROMATOGRAPHY_SUMMARY negative-ion mode at a resolution of 140,000 at m/z 200 and with a scan range of CH:CHROMATOGRAPHY_SUMMARY 85 to 1000 m/z. CH:INSTRUMENT_NAME Thermo Dionex Ultimate 3000 CH:COLUMN_NAME Waters SSelect HSS C18 CH: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 CH:FLOW_GRADIENT 21 min, 0% B. CH:FLOW_RATE 200 µl/min CH:SOLVENT_A 97% water/3% methanol; 15 mM acetic acid; 10 mM tributylamine CH:SOLVENT_B 100% methanol CH:CHROMATOGRAPHY_TYPE Reversed phase #ANALYSIS AN:ANALYSIS_TYPE MS #MS MS:INSTRUMENT_NAME Thermo Exactive Plus Orbitrap MS:INSTRUMENT_TYPE Orbitrap MS:MS_TYPE ESI MS:MS_COMMENTS Raw data files were converted to .mzML file format using the ProteoWizard MS:MS_COMMENTS software, and they were analyzed by the MS-DIAL software. Metabolites were MS:MS_COMMENTS identified by comparison to an in-house reference library of pure metabolite MS:MS_COMMENTS standards which included mass-to-charge ratio (m/z) and retention time. For MS:MS_COMMENTS quantification of metabolite abundance, peak areas of identified metabolites MS:MS_COMMENTS were first normalized to the internal standard chlorpropamide, and then MS:MS_COMMENTS normalized to cell numbers from each sample. Data were analyzed using R and MS:MS_COMMENTS Cytoscape software. MS:ION_MODE NEGATIVE #MS_METABOLITE_DATA MS_METABOLITE_DATA:UNITS Normalized peak area MS_METABOLITE_DATA_START Samples D1_1 D1_2 D1_3 D1_4 D1_5 D3_1 D3_2 D3_3 D3_4 D3_5 D5_1 D5_2 D5_3 D5_4 D5_5 Factors Mouse_strain:wild type C57BL/6 | Culture_stage:Expansion stage | Time_point(days):1 Mouse_strain:wild type C57BL/6 | Culture_stage:Expansion stage | Time_point(days):1 Mouse_strain:wild type C57BL/6 | Culture_stage:Expansion stage | Time_point(days):1 Mouse_strain:wild type C57BL/6 | Culture_stage:Expansion stage | Time_point(days):1 Mouse_strain:wild type C57BL/6 | Culture_stage:Expansion stage | Time_point(days):1 Mouse_strain:wild type C57BL/6 | Culture_stage:Expansion stage | Time_point(days):3 Mouse_strain:wild type C57BL/6 | Culture_stage:Expansion stage | Time_point(days):3 Mouse_strain:wild type C57BL/6 | Culture_stage:Expansion stage | Time_point(days):3 Mouse_strain:wild type C57BL/6 | Culture_stage:Expansion stage | Time_point(days):3 Mouse_strain:wild type C57BL/6 | Culture_stage:Expansion stage | Time_point(days):3 Mouse_strain:wild type C57BL/6 | Culture_stage:Expansion stage | Time_point(days):5 Mouse_strain:wild type C57BL/6 | Culture_stage:Expansion stage | Time_point(days):5 Mouse_strain:wild type C57BL/6 | Culture_stage:Expansion stage | Time_point(days):5 Mouse_strain:wild type C57BL/6 | Culture_stage:Expansion stage | Time_point(days):5 Mouse_strain:wild type C57BL/6 | Culture_stage:Expansion stage | Time_point(days):5 2_3-Dihydroxybenzoic acid 0.9685 0.7181 0.9808 0.8208 1.5118 2.3243 1.6640 1.6175 2.2272 1.8140 2.6140 2.5111 3.0011 2.5153 2.3772 2_3-Diphosphoglyceric acid 1.3875 0.8520 0.8147 0.8978 1.0481 1.7485 1.3036 1.8834 1.2509 1.9552 0.8310 0.6492 0.6949 0.8262 0.9381 2-Aminooctanoic acid 1.0219 0.7749 0.6995 1.0398 1.4639 1.1428 0.7104 0.7969 1.4082 0.8416 1.5975 1.6445 1.5446 1.6836 1.5016 2-Isopropylmalic acid 0.9664 0.6939 0.9030 1.0524 1.3843 1.3131 0.8048 0.8563 1.3277 1.2600 1.3129 1.2872 1.3435 1.4582 1.3610 2-Keto-D-gluconate 0.7569 1.1071 0.9194 0.8274 1.3892 2.4883 2.1424 2.4661 2.2092 1.9662 4.1852 5.5116 6.2231 7.1965 4.1991 2-Keto-isovalerate 0.9755 0.6889 0.8758 1.0369 1.4229 1.4985 0.8491 0.8305 1.4362 1.1219 1.4212 1.4407 1.5665 1.5208 1.5963 2-Oxobutanoate 0.7702 0.6038 1.1316 1.3005 1.1938 1.2363 0.7006 0.7120 1.1291 0.9945 1.9222 1.2999 1.2966 1.3369 2.2033 3-Hydroxybutyric acid 0.8109 0.6591 0.8589 1.0919 1.5793 1.5513 0.9081 0.8923 1.4444 1.3004 1.6988 1.7836 1.8042 1.9354 1.9492 3-Methylphenylacetic acid 0.9583 0.7024 0.9128 1.1086 1.3179 1.6981 0.9799 0.8804 1.9142 1.5522 1.3243 1.5542 1.5485 1.5196 1.6564 3-Phosphoglycerate 0.5333 0.7456 1.2190 1.2342 1.2679 10.7805 13.0988 18.3099 10.2167 21.2654 1.8702 2.3372 3.8093 7.5261 2.0086 3-Phospho-serine 0.8109 0.3304 0.7982 1.1274 1.9331 0.3777 0.0701 0.4655 0.3373 0.1432 0.1455 4-Aminobutyrate 0.8181 0.8049 0.9501 1.1047 1.3222 4.4278 3.4252 3.9964 4.6813 4.4411 3.3122 3.3164 3.3811 4.7040 3.2055 4-Phosphopantothenate 1.1896 0.6659 1.9490 0.8023 0.3932 1.1191 0.8867 1.0175 1.0415 1.3487 9.0271 9.3289 12.4721 6.2863 8.2904 4-Pyridoxic acid 0.8263 0.6895 0.9363 1.0476 1.5003 2.6136 1.7945 1.5658 2.9721 3.5008 1.2206 1.3815 1.3029 1.4829 1.3960 5-Phosphoribosyl-1-pyrophosphate 0.5801 1.0592 1.2675 1.0495 1.0437 4.6114 4.0856 6.3343 2.9151 4.8899 3.5610 4.4976 6.8039 10.3616 2.5956 6-Phospho-D-gluconate 0.1488 0.4526 1.2740 0.6483 2.4762 0.9198 0.6373 0.6895 1.1629 2.2155 0.2565 0.3409 0.3332 0.4174 0.2644 Acetoacetate 0.9172 0.7143 0.9010 1.0210 1.4466 1.6153 0.9299 0.9466 1.5071 1.3282 1.5565 1.5558 1.5556 1.5967 1.6020 Acetyl-aspartate 0.7316 1.0047 1.1523 0.9316 1.1798 1.2840 1.4413 1.5837 1.4041 1.5693 1.3791 1.9236 1.9753 3.0323 1.5100 Acetylcarnitine 1.0367 0.6693 0.7955 1.1735 1.3249 0.3575 0.2620 0.2313 0.1840 0.3750 0.7228 0.8913 0.3794 0.7000 0.3671 Acetyl-glycine 0.9203 0.7215 0.9718 1.0711 1.3152 2.4490 2.1304 2.9991 3.0840 2.5890 3.5064 4.6862 4.6176 4.6201 3.1101 Acetyllysine 0.7871 0.7250 0.9503 1.2566 1.2809 1.4886 1.6124 4.5471 2.5065 1.8451 1.4488 3.4299 10.3480 3.8082 5.4510 Aconitate 1.1839 0.8733 1.0728 0.9158 0.9542 0.7572 0.4049 0.4127 0.6438 0.5317 0.7096 0.7492 0.8082 0.7915 0.9270 ADP 0.7275 0.8730 0.9399 0.9001 1.5594 1.6724 1.0405 0.9188 1.6706 1.4837 0.7662 0.9949 1.1986 1.0141 0.9558 ADP-D-glucose 0.7508 0.7710 1.1793 1.0430 1.2560 3.3235 2.6452 2.9852 2.8491 2.4360 3.3764 3.6382 4.4344 6.5624 2.3316 Alanine/Sacrosine 0.8713 0.8007 0.7931 1.1051 1.4297 2.6903 2.2351 3.0022 4.3268 3.3788 3.3100 3.4983 3.3840 4.6726 2.6682 Allantoate 0.8114 0.8775 0.9829 1.0086 1.3196 13.5716 10.0369 10.1354 12.2307 24.0881 3.8367 4.7924 4.5151 6.0674 3.1327 Allantoin 0.8180 0.8289 0.8522 0.9918 1.5091 3.4704 2.3100 2.3686 3.1131 3.6762 1.5262 1.8266 1.8820 2.4580 1.4390 Alpha-ketoglutarate 1.8711 0.8758 0.7957 0.6904 0.7670 4.7021 2.2825 2.4143 3.5515 3.1996 12.7026 10.9622 1.1388 1.1253 1.0664 Aminoadipic acid 0.8789 0.8615 0.8846 1.1610 1.2140 3.5861 2.2094 2.8554 5.5759 3.5258 2.3340 2.5739 2.6504 4.4780 2.3169 AMP 0.8974 0.8972 1.1333 1.0784 0.9936 1.4047 1.3842 1.3408 1.4741 1.4196 0.7576 1.0172 0.9112 0.7828 0.7398 Arginine 1.9486 0.2212 0.2195 0.3295 2.2813 1.1996 0.5858 0.9795 13.9269 1.4732 15.5185 2.0780 1.7153 3.0530 12.2305 Asparagine 1.0840 0.7997 0.6697 1.0284 1.4182 1.6518 1.5544 2.2811 2.2165 1.6578 6.6282 6.8020 5.6352 7.7807 5.4808 Aspartate 0.9461 0.9996 0.4127 1.2706 1.3709 1.1129 0.7387 0.8358 3.1227 1.1578 4.9955 5.2709 5.4260 7.5064 5.7492 ATP 0.0080 0.8460 0.0065 1.0039 3.1355 2.3482 0.8896 0.0051 1.8567 0.0103 0.7547 0.8821 0.0103 1.2841 1.0150 CDP 0.7221 0.8467 1.0199 1.0554 1.3559 2.8641 1.5992 1.4142 2.4389 2.1035 1.7822 2.2048 2.5516 2.5122 1.8748 CDP-choline 5.0000 54.1925 93.6017 120.7290 92.7911 62.8882 99.8300 117.2104 70.1863 196.9441 60.3261 CDP-ethanolamine 0.8661 0.8796 1.1783 1.0421 1.0339 5.5726 2.4816 3.7460 3.3241 3.1037 4.5380 5.9749 6.4089 9.5414 4.3378 Citraconic acid 0.8455 0.7073 0.9628 1.0877 1.3966 1.6975 1.0786 1.1080 1.6159 1.5187 1.7991 1.9391 1.9432 1.9515 1.9718 Citrate/isocitrate 0.7590 0.9559 1.0825 0.9456 1.2569 2.3493 1.8812 2.0922 2.5536 2.5954 3.5582 4.3270 4.1390 5.0403 3.0793 Citrulline 1.6635 0.5146 0.5794 0.8850 1.3575 3.0109 1.2153 3.6435 2.3281 2.3076 13.8929 14.7261 12.6580 9.9533 10.3251 CMP 0.8684 0.7154 1.3281 1.1551 0.9330 0.0397 3.9159 1.5665 2.8016 1.9358 2.3974 2.8789 2.5654 2.3703 1.8079 Coenzyme A 0.6603 0.6432 0.9734 0.8271 1.8960 5.1196 6.3196 9.9782 9.3807 6.0512 11.6602 13.6221 16.3649 19.7425 10.7438 CTP 0.4702 0.5052 0.6540 0.8679 2.5027 3.0958 0.7985 0.6410 2.4029 1.6324 1.4890 1.6764 2.9484 2.9167 2.1792 Cysteine 0.7528 0.8532 0.9263 1.0780 1.3897 3.7983 2.9276 4.4255 5.3844 3.0312 7.3652 7.0070 5.2176 12.3549 3.8249 Cytidine 0.9826 0.8490 0.9650 1.0716 1.1318 0.4302 0.2928 0.3713 0.3322 0.2000 1.5781 1.7475 1.7938 0.5752 1.3297 dAMP 0.8409 0.9065 1.3108 1.1307 0.8111 6.6438 7.9136 10.1148 9.4512 9.7624 8.5753 10.2788 9.3249 11.1462 5.3466 dCDP 0.9097 1.2801 1.2626 0.5064 1.0412 8.8160 8.0453 7.2763 7.4612 7.3580 4.1096 5.8116 4.9390 6.7054 3.7746 dCMP 0.9247 1.1083 0.9821 1.4158 0.5691 7.0111 7.5356 9.7353 12.9428 8.2139 11.9511 17.0110 12.0007 14.8111 7.6079 Deoxyribose-phosphate 0.9345 0.9845 1.0297 0.8164 1.2349 3.2236 3.0956 3.3157 3.5247 2.6833 4.7945 5.8561 4.9687 5.1808 3.8985 Dephospho-CoA 1.1097 1.4997 1.2651 1.1256 4.4237 5.9689 5.8188 5.3097 2.0309 4.5572 4.4372 5.0274 8.1606 2.8892 dGDP 0.7907 0.7811 0.8713 1.0205 1.5363 0.8656 0.6746 0.3656 0.8723 0.5479 0.7524 0.4932 0.7495 0.3551 0.5432 dGTP 1.1495 0.8115 0.7059 0.6673 1.6658 1.2460 0.5792 0.3754 1.0305 0.6358 0.7649 1.0558 0.4839 0.7350 0.7998 Dihydroxy-acetone-phosphate 0.7406 1.1507 1.3747 1.1523 0.5818 6.6017 7.8299 9.2635 9.6213 11.4978 4.3494 6.2821 5.3105 6.3934 1.3782 D-Sedoheptulose-1/7-phosphate 0.7305 0.7848 0.9363 1.1534 1.3951 2.7154 2.6482 3.3707 3.3187 3.8292 5.0168 4.4830 4.1044 4.6300 3.9661 dTDP 0.5416 0.9746 1.3544 0.9695 1.1599 11.0141 9.0988 10.8883 9.3203 10.9408 3.7489 4.7129 5.3619 7.5871 3.8351 dTMP 0.9904 1.0866 1.1238 1.0870 0.7122 6.7435 7.5294 8.5004 9.9591 8.1143 6.2397 9.4422 7.2383 8.1009 4.6616 dTTP 1.5968 0.6123 0.7320 0.6643 1.3946 6.2543 3.0352 2.5746 5.4465 5.2451 1.8366 2.1664 3.8931 4.9098 2.8476 dUMP 0.4892 0.7354 1.2410 0.6271 1.9074 7.0940 6.2869 7.7766 5.5229 4.8862 3.5930 4.2829 6.8640 6.8090 7.6970 Erythrose-4-phosphate 0.7454 0.7882 0.8079 1.1357 1.5227 0.5833 0.4284 0.3058 1.3689 0.6946 0.8208 1.0478 0.7653 0.6817 0.7928 FAD 0.6289 0.9961 1.1269 1.0091 1.2390 3.0019 2.6847 2.7134 3.0427 2.6641 4.0525 3.9203 4.3437 5.6273 2.6355 Folate 0.8796 0.7845 1.4369 1.2680 0.6311 19.1347 14.7162 10.4439 13.8746 28.7590 0.3689 Fructose-1_6-bisphosphate 0.6184 0.9970 1.0925 1.0686 1.2235 1.7707 2.3907 2.0729 2.1203 2.8279 0.8656 1.3708 1.0186 1.4082 0.6419 Fructose-6-phosphate 0.9246 1.0166 1.0203 1.0544 0.9841 2.7786 3.1778 2.1520 3.7454 3.2817 1.6545 1.1648 0.8763 2.4180 0.6669 Fumarate 0.8962 1.0234 1.2620 1.0579 0.7606 8.3436 7.2821 9.4492 6.7150 6.6962 4.3674 5.8281 5.7911 9.5761 3.3155 GDP 0.5659 1.0539 1.2587 0.9522 1.1692 1.9486 1.5473 1.6940 1.6669 1.2966 1.4218 1.5810 2.2937 2.0204 1.3920 Gluconate 0.9467 0.9320 1.0335 0.8732 1.2147 13.1149 11.5141 14.3269 12.1797 14.9957 41.0693 63.3671 60.8062 86.9956 44.7062 Glucono-_-lactone 1.0997 0.8214 0.9769 0.9533 1.1486 1.3742 0.8318 0.7644 1.2185 1.1277 1.2667 1.3986 1.4693 1.4611 1.3091 Glucosamine-1/6-phosphate 0.8274 0.7225 0.8666 1.1629 1.4205 0.2960 0.1105 0.1137 0.5196 0.2220 0.1151 0.1210 0.1179 0.4860 0.1731 Glucose 1.0235 0.5443 1.0825 1.3031 1.0466 10.9314 4.7541 3.5514 5.5069 8.2053 0.2171 0.2200 0.2434 0.1606 0.2599 Glucose-1/6-phosphate 0.6781 0.8315 0.8638 1.1454 1.4812 0.3467 0.4261 0.1279 1.3392 0.3575 0.5538 0.8648 0.4722 0.4411 0.6325 Glutamate 0.8497 0.8225 0.9962 1.0678 1.2638 4.0051 2.9388 3.2778 3.8896 3.6815 2.8546 2.8975 2.9383 3.9402 2.7505 Glutamine 0.9773 0.6843 0.7280 1.0952 1.5152 3.1536 2.2454 2.2070 4.3588 4.5714 0.5370 0.5198 0.4294 0.4984 0.5321 Glutathione 0.8219 0.8327 0.9859 1.0072 1.3523 2.4256 1.8720 2.0651 2.5658 2.1718 2.1642 2.1908 2.2175 3.1212 2.0313 Glutathione disulfide 0.9555 0.9980 0.8896 1.4204 0.7365 4.1386 2.3852 1.5957 1.7620 2.9556 0.6889 0.6470 0.8935 2.9363 1.0675 Glycerate 0.8595 0.6825 0.9282 1.0682 1.4615 1.8613 1.0797 1.1825 4.0019 1.7631 1.6930 1.7447 1.6579 1.9232 1.6809 Glycine 0.9449 0.7476 0.7048 1.0920 1.5107 2.1674 1.7569 2.3886 3.8301 2.4317 3.6696 4.0428 3.4659 5.4546 3.3521 GTP 0.4470 0.6320 0.8024 0.8515 2.2671 2.6947 1.2042 0.9009 1.8950 1.3945 1.1276 1.3083 2.3503 2.5704 1.4963 Histidine 1.0166 0.8765 1.0499 0.8817 1.1753 7.1991 6.2448 6.7343 9.5091 13.1849 3.5376 5.3428 3.9330 6.4784 3.5626 Homocysteic acid 0.8131 0.8430 0.9260 0.8758 1.5421 1.3291 1.5830 1.4609 1.3691 1.6177 0.8194 0.9948 0.8421 1.3609 0.8823 Homocysteine/Methylcysteine 0.7392 1.1899 0.9946 1.1929 0.8834 5.6742 5.8218 9.9491 8.7259 8.7814 7.8477 8.5751 9.0198 12.5589 5.1167 Hydroxyisocaproic acid 0.8503 0.7041 0.8955 1.0729 1.4772 1.5838 0.8993 0.8612 1.4419 1.2646 1.6013 1.7467 1.6963 1.7995 1.9457 Hydroxyphenylacetic acid 1.1502 0.6500 0.8310 0.9384 1.4303 2.5986 0.6702 2.5786 1.1139 0.9360 1.1503 0.8806 1.0714 1.1761 1.2235 Hydroxyphenylpyruvate 0.9529 0.9364 1.0197 0.8849 1.2061 7.2322 5.9114 5.2464 6.6272 11.0910 2.0297 1.9898 2.0205 1.7691 1.6975 Hydroxyproline/Aminolevulinate 0.8277 0.9640 0.8052 1.0500 1.3531 1.3641 0.9787 0.1792 1.5469 1.4332 1.1821 1.3356 1.2665 2.2911 1.5356 IMP 1.0290 1.2346 1.2287 0.9821 0.5255 2.7164 2.0189 2.5229 2.3832 1.6327 1.7063 1.3456 1.7005 2.1234 1.3645 Isopentyl-pyrophosphate 0.8464 0.7484 0.8761 1.1293 1.3997 1.1274 0.6907 0.7327 1.2661 0.8803 0.8058 1.1122 1.3679 1.2839 1.6039 Itaconate 0.8211 0.8588 1.0531 1.0164 1.2506 0.0530 0.0582 0.0590 0.0572 0.0658 1.5803 1.9505 0.0688 0.0643 1.6245 Ketoleucine 0.8801 0.7093 0.8906 1.0856 1.4345 1.3673 0.7408 0.7053 1.2580 1.0263 1.3086 1.4503 1.3775 1.3616 1.4216 Kynurenic acid 0.9053 0.6944 0.9128 1.0581 1.4295 1.4486 0.6305 0.7641 0.9318 1.0405 0.9800 0.7714 0.7379 0.6631 1.1211 Lactate 1.0523 0.6154 0.9890 0.9748 1.3685 1.8302 1.0711 1.1347 1.7289 1.7669 2.0415 2.0130 2.2770 2.3760 2.1006 Leu-Asp (LD) 0.8306 0.5871 0.5504 1.0674 1.9646 1.1408 0.9473 0.7071 1.2008 0.3936 2.4416 2.6818 2.5117 3.1588 2.7385 Leucine/Isoleucine 0.7934 0.7221 1.1231 1.1208 1.2406 14.0297 10.2400 10.2758 13.7279 22.5642 3.6696 4.3324 4.0200 5.8881 3.0401 Lysine 1.1838 1.1747 0.7775 1.0263 0.8377 8.8830 6.1686 6.0409 11.1285 13.7740 8.9795 10.0768 7.9908 13.4131 7.1810 Malate 0.7424 0.7963 1.1186 1.1005 1.2422 6.3948 4.7935 5.6954 6.5922 6.0144 4.8783 6.2915 6.6681 7.7081 4.3676 Maleic acid 0.7226 0.7881 1.1018 1.0972 1.2904 6.1199 4.6839 5.8169 6.7382 6.1233 4.9219 6.3663 6.6783 7.9572 4.6392 Methionine 0.8384 0.7363 1.0113 1.1263 1.2876 10.4770 7.9656 8.7758 11.1167 17.3505 10.5379 12.1103 11.7177 15.2844 8.2448 N-Acetyl-glucosamine-1/6-phosphate 0.8119 0.5267 0.6359 1.2672 1.7583 0.6371 0.5029 0.6478 1.4519 0.8231 0.8238 0.8695 0.7849 0.8811 0.8319 N-Acetyl-glutamate 1.0471 0.8586 1.1132 0.9657 1.0154 7.1325 6.4695 8.3547 7.5376 6.5056 8.8920 9.3886 11.1097 13.8041 7.0610 N-Acetyl-glutamine 0.9328 0.7573 0.8567 1.1046 1.3486 1.9189 1.8142 2.4005 3.2626 2.0478 5.0451 5.9866 5.7036 6.6100 4.0770 N-Acetyl-L-alanine 0.9195 0.8838 1.0241 1.0329 1.1397 3.7859 3.9016 5.1669 4.7416 4.1302 8.7834 10.3002 10.9631 12.7402 6.5735 N-Acetyl-L-ornithine 0.9172 0.8419 0.9106 1.0739 1.2564 4.0432 3.7758 7.8753 6.0615 8.1206 3.4335 4.7994 6.0956 4.5257 4.0267 NAD+ 0.4658 0.7213 0.8546 0.8780 2.0802 1.3540 0.6279 1.0006 1.1391 0.8581 0.3987 0.5593 0.4000 NADH 0.1419 0.4467 1.6681 1.2257 1.5175 3.9308 7.7794 6.6091 2.5549 5.0236 1.2232 1.5197 NADP+ 0.4170 0.5471 0.8050 0.8146 2.4163 0.9690 0.3309 0.4050 1.0015 0.4788 0.0869 N-Carbamoyl-L-aspartate 1.1177 0.7993 1.0759 0.5608 1.4463 12.1229 7.4281 9.1360 12.9526 14.8175 1.6034 2.1679 1.8873 2.1171 2.7955 Nicotinate 0.8187 1.2799 0.7738 0.9514 1.1762 3.9692 2.8913 2.7911 5.8914 6.5270 1.2586 1.2000 1.5823 2.1471 1.3568 O-Acetyl-serine 0.8312 1.1359 1.0975 0.9250 1.0104 0.7785 0.5252 0.7663 1.1563 0.8473 1.1478 1.4185 1.0061 1.1281 1.5752 Octoluse bisphosphate 0.8734 0.9750 0.9353 1.0667 1.1497 6.2463 7.5352 8.9316 5.2540 8.3078 3.1976 3.1902 3.1166 3.5561 1.8383 Orotate 0.8883 0.6714 0.8949 1.0136 1.5317 1.3740 0.7447 0.6883 1.1864 1.0497 1.3200 1.4262 1.5103 1.4951 1.7259 Pantothenate 0.8882 0.9630 1.0651 1.0303 1.0534 6.7803 5.6850 6.2099 6.9978 10.1188 1.7057 2.1180 2.0352 3.8657 1.3576 Phenyllactic acid 1.0130 0.8364 1.0672 0.9288 1.1546 3.3632 3.1808 7.6205 4.5232 5.6958 1.1019 1.8788 1.8115 2.2999 1.3460 Phenylpyruvate 0.7713 0.7966 0.8182 1.2757 1.3382 1.8374 1.1249 1.0200 1.8821 1.5943 1.9788 1.5339 1.7977 2.3737 2.0689 Phosphoenolpyruvate 0.4593 0.7140 1.1821 1.4176 1.2270 9.9299 12.9320 19.5591 10.4314 20.8222 2.0529 1.9728 3.3239 7.0206 1.9424 p-Hydroxybenzoate 1.2326 0.7993 0.8999 0.9528 1.1155 1.2070 0.6220 0.5914 0.9097 0.7461 0.8747 0.8649 0.8054 0.9020 0.8862 Pro-Asp (PD) 0.9837 1.0967 0.8662 0.9566 1.0967 2.9594 2.5319 3.2676 2.8175 2.6458 3.7248 4.3942 4.0586 6.2310 2.7265 Pro-Glu (PE) 0.9829 0.8610 1.0854 1.0512 1.0195 4.6335 3.7778 4.2454 4.6932 4.4042 3.7134 4.6562 4.0997 5.5601 3.3295 Proline 0.9017 0.7922 0.9393 1.0853 1.2814 4.3118 3.4097 4.2951 5.2385 4.6963 2.5021 2.5745 2.6000 3.6207 2.3302 Pyroglutamic acid 0.8963 0.6290 0.9295 1.1932 1.3521 14.1150 10.0906 9.7882 16.1090 22.1023 1.5826 1.6349 1.6134 3.7177 1.3306 Pyruvate 0.8935 0.6938 0.9843 1.1334 1.2950 3.2137 1.5863 1.6133 3.4735 2.8909 1.7371 1.7682 1.7146 1.8643 1.3874 Quinolinate 0.9260 0.7267 1.1248 0.9437 1.2789 13.5166 10.7357 14.1881 10.9319 13.6502 10.5125 10.3863 9.0536 11.1796 9.2466 Ribose 0.9238 0.7215 1.1073 1.2128 1.0346 6.9155 3.0277 1.9532 3.4301 4.7338 1.8806 1.9194 1.6550 1.6248 1.2305 Ribose-5-phosphate 0.8428 0.9111 1.2780 1.0726 0.8955 2.9345 2.3941 2.6322 1.8408 2.8149 1.2551 1.4153 1.3463 1.6549 0.7792 Ribulose-5-phosphate 0.8292 0.8553 1.2932 1.0541 0.9682 3.1924 1.2477 1.5162 2.8383 3.0615 1.7922 2.0538 1.4557 2.1630 0.9399 Sedoheptoluse bisphosphate 0.7922 1.0104 1.2486 0.8545 1.0944 3.1087 2.9754 2.9847 3.5351 2.9529 3.5290 3.7324 3.7106 4.5874 2.4034 Ser-Asp (SD) 0.6645 0.8280 1.2879 1.0260 1.1935 3.2348 3.0790 3.6834 4.3891 3.5245 6.0789 7.2014 7.1434 8.8524 4.8688 Serine 0.9551 0.7399 0.6390 1.0860 1.5801 1.8569 1.5206 1.9944 3.6123 2.7612 3.3066 3.5040 3.0479 4.7367 2.3319 sn-Glycerol-3-phosphate 0.5613 1.0849 1.2992 1.1580 0.8966 10.2482 11.2439 19.1321 7.2159 17.6649 2.2159 2.4151 4.4375 6.6715 1.5980 Succinate/Methylmalonic acid 0.7841 0.8573 1.0167 1.0294 1.3125 4.3195 3.3156 4.6037 4.4147 4.7813 3.6403 4.3999 4.7999 4.3684 3.0970 Taurine 0.8743 0.8307 0.7156 1.0704 1.5090 0.9812 1.0959 1.2874 1.7507 1.0056 2.1938 2.6184 2.0971 3.3088 2.0450 Thiamine 1.1568 0.8732 0.9921 0.9248 1.0530 6.3525 5.2204 5.5036 7.2636 8.7174 4.4791 3.6675 3.7160 4.4083 2.6697 Threonine/Homoserine 0.9186 0.7893 0.7906 1.1208 1.3807 3.4772 2.7455 3.0565 4.1929 4.4592 2.6209 2.7738 2.5012 3.8005 2.2978 Trehalose/Sucrose 0.6767 0.6173 0.5370 2.4626 0.7064 0.9452 1.7378 1.6899 3.0768 0.8015 1.1640 1.1089 0.8749 3.8439 1.0653 Tryptophan 0.9363 0.7961 0.9970 1.1261 1.1444 8.7601 5.7053 5.5890 7.9915 13.6805 4.6548 5.2404 4.8697 5.6770 3.7427 Tyrosine 1.0279 0.7382 0.8449 1.0845 1.3044 1.2086 0.5270 3.1120 0.6838 8.6165 1.1738 0.7208 0.9974 0.7317 0.8972 UDP 0.6414 0.9671 1.1921 1.0276 1.1717 2.0074 1.1689 1.0231 1.4790 1.1611 0.7872 0.8483 1.1436 1.0877 0.9859 UDP-D-glucose 0.7018 0.9124 1.1015 1.0727 1.2116 3.4681 3.3284 3.5910 3.0105 2.8663 1.2077 1.4934 1.4041 2.3496 1.0361 UDP-D-glucuronate 0.7326 0.9331 1.1454 1.0347 1.1542 2.2530 1.8069 2.3149 1.7062 1.5586 2.3048 2.9219 2.6353 3.4192 1.4255 UDP-N-acetyl-glucosamine 0.7713 1.0528 1.1295 1.0135 1.0330 2.7208 2.8219 3.4077 2.1199 2.2490 2.3818 2.8343 2.8700 4.1496 1.7949 UMP 0.8900 0.9610 1.1153 1.1115 0.9223 2.5534 3.1386 3.4815 3.1392 2.9090 1.7414 2.1989 1.8540 1.8472 1.5849 Uracil 0.9193 0.7120 0.9338 1.0564 1.3784 1.4788 0.8606 0.8299 1.3771 1.1754 1.3935 1.5928 1.6601 1.6108 1.7936 Uric acid 0.9519 1.1719 1.0815 0.8100 0.9847 2.6521 3.1835 3.9164 2.4677 3.9746 2.0983 3.6994 8.6115 9.1104 4.6329 Uridine 0.8648 0.9967 1.1393 0.9065 1.0926 4.1396 3.8127 4.2288 5.1875 6.9048 2.1474 2.8921 3.0122 3.4678 1.3369 UTP 0.5130 0.6110 0.7029 0.8527 2.3203 2.4113 0.6913 0.4901 1.5678 1.1142 0.6198 0.6828 1.2885 1.3775 1.0093 Val-Asp (VD) 0.9529 0.9305 1.2004 1.0886 0.8276 1.6552 1.7283 2.3324 2.0391 1.9032 4.3738 5.3402 5.1501 4.9490 3.3395 Valine/5-Aminopentanoic acid 0.9092 0.8786 0.7718 1.0803 1.3602 1.1824 1.1209 1.3621 1.9477 1.1842 1.2886 1.4915 1.2806 1.3978 1.1138 Xanthine 0.7160 1.0195 1.1760 1.0829 1.0055 4.4696 4.3759 5.7755 4.4261 4.6832 7.3046 9.2033 10.5010 16.0703 6.7463 Xanthosine 1.0294 2.0466 1.2990 0.6250 9.5290 13.0532 19.9673 12.2884 7.9339 12.9032 16.0207 11.1923 33.3590 7.9483 Xanthosine-5-phosphate 0.8510 1.4932 1.1356 0.8118 0.7084 10.7787 9.6352 18.2483 12.8847 14.4292 7.7123 8.7833 10.3361 17.7288 6.5594 MS_METABOLITE_DATA_END #METABOLITES METABOLITES_START metabolite_name pubchem_id inchi_key kegg_id other_id other_id_type ri ri_type moverz_quant 2,3-Dihydroxybenzoic acid 2,3-Diphosphoglyceric acid 2-Aminooctanoic acid 2-Isopropylmalic acid 2-Keto-D-gluconate 2-Keto-isovalerate 2-Oxobutanoate 3-Hydroxybutyric acid 3-Methylphenylacetic acid 3-Phosphoglycerate 3-Phospho-serine 4-Aminobutyrate 4-Phosphopantothenate 4-Pyridoxic acid 5-Phosphoribosyl-1-pyrophosphate 6-Phospho-D-gluconate Acetoacetate Acetyl-aspartate Acetylcarnitine Acetyl-glycine Acetyllysine Aconitate ADP ADP-D-glucose Alanine/Sacrosine Allantoate Allantoin Alpha-ketoglutarate Aminoadipic acid AMP Arginine Asparagine Aspartate ATP CDP CDP-choline CDP-ethanolamine Citraconic acid Citrate/isocitrate Citrulline CMP Coenzyme A CTP Cysteine Cytidine dAMP dCDP dCMP Deoxyribose-phosphate Dephospho-CoA dGDP dGTP Dihydroxy-acetone-phosphate D-Sedoheptulose-1/7-phosphate dTDP dTMP dTTP dUMP Erythrose-4-phosphate FAD Folate Fructose-1,6-bisphosphate Fructose-6-phosphate Fumarate GDP Gluconate Glucono-_-lactone Glucosamine-1/6-phosphate Glucose Glucose-1/6-phosphate Glutamate Glutamine Glutathione Glutathione disulfide Glycerate Glycine GTP Histidine Homocysteic acid Homocysteine/Methylcysteine Hydroxyisocaproic acid Hydroxyphenylacetic acid Hydroxyphenylpyruvate Hydroxyproline/Aminolevulinate IMP Isopentyl-pyrophosphate Itaconate Ketoleucine Kynurenic acid Lactate Leu-Asp (LD) Leucine/Isoleucine Lysine Malate Maleic acid Methionine N-Acetyl-glucosamine-1/6-phosphate N-Acetyl-glutamate N-Acetyl-glutamine N-Acetyl-L-alanine N-Acetyl-L-ornithine NAD+ NADH NADP+ N-Carbamoyl-L-aspartate Nicotinate O-Acetyl-serine Octoluse bisphosphate Orotate Pantothenate Phenyllactic acid Phenylpyruvate Phosphoenolpyruvate p-Hydroxybenzoate Pro-Asp (PD) Pro-Glu (PE) Proline Pyroglutamic acid Pyruvate Quinolinate Ribose Ribose-5-phosphate Ribulose-5-phosphate Sedoheptoluse bisphosphate Ser-Asp (SD) Serine sn-Glycerol-3-phosphate Succinate/Methylmalonic acid Taurine Thiamine Threonine/Homoserine Trehalose/Sucrose Tryptophan Tyrosine UDP UDP-D-glucose UDP-D-glucuronate UDP-N-acetyl-glucosamine UMP Uracil Uric acid Uridine UTP Val-Asp (VD) Valine/5-Aminopentanoic acid Xanthine Xanthosine Xanthosine-5-phosphate METABOLITES_END #END