#METABOLOMICS WORKBENCH jsto1886_20240119_074244 DATATRACK_ID:4596 STUDY_ID:ST003249 ANALYSIS_ID:AN005322 PROJECT_ID:PR002017 VERSION 1 CREATED_ON June 5, 2024, 5:11 pm #PROJECT PR:PROJECT_TITLE Mitochondrial respiration in microglia is essential for response to PR:PROJECT_TITLE demyelinating injury but not proliferation. PR:PROJECT_SUMMARY Microglia are necessary for CNS function during development and play roles in PR:PROJECT_SUMMARY aging, Alzheimer’s Disease (AD) and the response to demyelinating injury1–5. PR:PROJECT_SUMMARY Mitochondrial respiratory chain (RC) controls macrophage-dependent immune PR:PROJECT_SUMMARY responses6–9. However, whether mitochondrial RC is essential to microglia PR:PROJECT_SUMMARY function is not known. We conditionally deleted the mitochondrial complex III PR:PROJECT_SUMMARY subunit Rieske Iron-Sulfur Protein (RISP) in the microglia of adult mice to PR:PROJECT_SUMMARY assess the requirement of microglial RC for survival, proliferation, and adult PR:PROJECT_SUMMARY CNS function in vivo. Surprisingly, mitochondrial RC function was not required PR:PROJECT_SUMMARY for survival or proliferation of microglia in vivo. RNA-seq analysis showed that PR:PROJECT_SUMMARY loss of RC function in microglia caused changes in gene expression distinct from PR:PROJECT_SUMMARY aged or disease-associated microglia (DAM). Microglia-specific loss of PR:PROJECT_SUMMARY mitochondrial RC function did not affect cognitive decline during aging or in PR:PROJECT_SUMMARY the 5xFAD model of Alzheimer’s disease (AD). However, Abeta plaque coverage PR:PROJECT_SUMMARY decreased and microglial interaction with Abeta plaques increased in the PR:PROJECT_SUMMARY hippocampus of 5xFAD mice with mitochondrial RC-deficient microglia. PR:PROJECT_SUMMARY Microglia-specific loss of mitochondrial RC function did impair remyelination PR:PROJECT_SUMMARY following an acute, reversible demyelinating event. Thus, mitochondrial PR:PROJECT_SUMMARY respiration in microglia is dispensable for maintenance of normal cognitive PR:PROJECT_SUMMARY function but is essential to maintain a proper response to CNS demyelinating PR:PROJECT_SUMMARY injury. PR:INSTITUTE Northwestern University Feinberg School of Medicine PR:LAST_NAME Stoolman PR:FIRST_NAME Joshua PR:ADDRESS 303 E Superior Street, PR:EMAIL joshua.stoolman@northwestern.edu PR:PHONE 7343559440 #STUDY ST:STUDY_TITLE Mitochondrial respiration impairment in microglia dampens response to ST:STUDY_TITLE demyelinating injury but is not sufficient to induce an aging phenotype ST:STUDY_SUMMARY Microglia are necessary for CNS function during development and play roles in ST:STUDY_SUMMARY aging, Alzheimer’s Disease (AD) and the response to demyelinating injury1–5. ST:STUDY_SUMMARY Mitochondrial respiratory chain (RC) controls macrophage-dependent immune ST:STUDY_SUMMARY responses6–9. However, whether mitochondrial RC is essential to microglia ST:STUDY_SUMMARY function is not known. We conditionally deleted the mitochondrial complex III ST:STUDY_SUMMARY subunit Rieske Iron-Sulfur Protein (RISP) in the microglia of adult mice to ST:STUDY_SUMMARY assess the requirement of microglial RC for survival, proliferation, and adult ST:STUDY_SUMMARY CNS function in vivo. Surprisingly, mitochondrial RC function was not required ST:STUDY_SUMMARY for survival or proliferation of microglia in vivo. RNA-seq analysis showed that ST:STUDY_SUMMARY loss of RC function in microglia caused changes in gene expression distinct from ST:STUDY_SUMMARY aged or disease-associated microglia (DAM). Microglia-specific loss of ST:STUDY_SUMMARY mitochondrial RC function did not affect cognitive decline during aging or in ST:STUDY_SUMMARY the 5xFAD model of Alzheimer’s disease (AD). However, Abeta plaque coverage ST:STUDY_SUMMARY decreased and microglial interaction with Abeta plaques increased in the ST:STUDY_SUMMARY hippocampus of 5xFAD mice with mitochondrial RC-deficient microglia. ST:STUDY_SUMMARY Microglia-specific loss of mitochondrial RC function did impair remyelination ST:STUDY_SUMMARY following an acute, reversible demyelinating event. Thus, mitochondrial ST:STUDY_SUMMARY respiration in microglia is dispensable for maintenance of normal cognitive ST:STUDY_SUMMARY function but is essential to maintain a proper response to CNS demyelinating ST:STUDY_SUMMARY injury. ST:INSTITUTE Northwestern University ST:LAST_NAME Stoolman ST:FIRST_NAME Joshua ST:ADDRESS 303 E Superior Street, ST:EMAIL joshua.stoolman@northwestern.edu ST:PHONE 7343559440 #SUBJECT SU:SUBJECT_TYPE Mammal SU:SUBJECT_SPECIES Mus musculus SU:TAXONOMY_ID 10090 SU:AGE_OR_AGE_RANGE 1 year SU:GENDER Male and female #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 Run Ctrl Nav-Jos-20220209-01 Genotype:NA | Sample source:Plasma RAW_FILE_NAME(Raw data file)=Nav-Jos-20220209-01 SUBJECT_SAMPLE_FACTORS CXR769 Nav-Jos-20220209-02 Genotype:HET | Sample source:Microglia RAW_FILE_NAME(Raw data file)=Nav-Jos-20220209-02 SUBJECT_SAMPLE_FACTORS CXR768 Nav-Jos-20220209-03 Genotype:KO | Sample source:Microglia RAW_FILE_NAME(Raw data file)=Nav-Jos-20220209-03 SUBJECT_SAMPLE_FACTORS CXR771 Nav-Jos-20220209-04 Genotype:HET | Sample source:Microglia RAW_FILE_NAME(Raw data file)=Nav-Jos-20220209-04 SUBJECT_SAMPLE_FACTORS CXR772 Nav-Jos-20220209-05 Genotype:KO | Sample source:Microglia RAW_FILE_NAME(Raw data file)=Nav-Jos-20220209-05 SUBJECT_SAMPLE_FACTORS Run Ctrl Nav-Jos-20220209-06 Genotype:NA | Sample source:Plasma RAW_FILE_NAME(Raw data file)=Nav-Jos-20220209-06 SUBJECT_SAMPLE_FACTORS CXR825 Nav-Jos-20220209-07 Genotype:HET | Sample source:Microglia RAW_FILE_NAME(Raw data file)=Nav-Jos-20220209-07 SUBJECT_SAMPLE_FACTORS CXR826 Nav-Jos-20220209-08 Genotype:KO | Sample source:Microglia RAW_FILE_NAME(Raw data file)=Nav-Jos-20220209-08 SUBJECT_SAMPLE_FACTORS CXR1033 Nav-Jos-20220209-09 Genotype:HET | Sample source:Microglia RAW_FILE_NAME(Raw data file)=Nav-Jos-20220209-09 SUBJECT_SAMPLE_FACTORS CXR1034 Nav-Jos-20220209-10 Genotype:KO | Sample source:Microglia RAW_FILE_NAME(Raw data file)=Nav-Jos-20220209-10 SUBJECT_SAMPLE_FACTORS Run Ctrl Nav-Jos-20220209-16 Genotype:NA | Sample source:Plasma RAW_FILE_NAME(Raw data file)=Nav-Jos-20220209-16 SUBJECT_SAMPLE_FACTORS CXR1153 Nav-Jos-20220209-19 Genotype:HET | Sample source:Microglia RAW_FILE_NAME(Raw data file)=Nav-Jos-20220209-19 SUBJECT_SAMPLE_FACTORS CXR1151 Nav-Jos-20220209-20 Genotype:KO | Sample source:Microglia RAW_FILE_NAME(Raw data file)=Nav-Jos-20220209-20 SUBJECT_SAMPLE_FACTORS CXR1129 Nav-Jos-20220209-21 Genotype:KO | Sample source:Microglia RAW_FILE_NAME(Raw data file)=Nav-Jos-20220209-21 SUBJECT_SAMPLE_FACTORS CXR1152 Nav-Jos-20220209-22 Genotype:HET | Sample source:Microglia RAW_FILE_NAME(Raw data file)=Nav-Jos-20220209-22 #COLLECTION CO:COLLECTION_SUMMARY Following CNS isolation, 100,000 YFP+TdTomato+ cells were sorted at 4°C on the CO:COLLECTION_SUMMARY MACS Tyto, centrifuged at 500xg, resuspended in 30μL (3,333 cells/µL) 80% CO:COLLECTION_SUMMARY acetonitrile in HPLC-grade H2O, vortexed vigorously for 1 minute and then CO:COLLECTION_SUMMARY quickly frozen on dry ice. The samples were stored at -80°C for a minimum of 12 CO:COLLECTION_SUMMARY hours prior to performing 3 additional freeze thaw cycles with a warm water bath CO:COLLECTION_SUMMARY and liquid nitrogen. Samples were then centrifuged at 16000xg for 30 minutes at CO:COLLECTION_SUMMARY 4°C. Supernatants were transferred to a fresh tube for analysis. CO:SAMPLE_TYPE Microglia #TREATMENT TR:TREATMENT_SUMMARY Cx3CR1-creERT2 with RISP (Fx/Fx) or RISP (Fx/Wt) genotype were given tamoxifen TR:TREATMENT_SUMMARY chow for 3 weeks starting at 8 weeks of age to generate microglia-targeted KO of TR:TREATMENT_SUMMARY mitochondrial complex III subunit RISP. At 1 yr of age microglia from these mice TR:TREATMENT_SUMMARY were isolated for untargeted metabolomics analysis. #SAMPLEPREP SP:SAMPLEPREP_SUMMARY A 15μl aliquot of the sample was used for high-resolution HPLC-tandem mass SP:SAMPLEPREP_SUMMARY spectrometry. High-resolution HPLC-tandem mass spectrometry was performed on a SP:SAMPLEPREP_SUMMARY Q-Exactive (ThermoFisher Scientific) in line with an electrospray source and an SP:SAMPLEPREP_SUMMARY UltiMate 3000 (ThermoFisher Scientific) series HPLC consisting of a binary pump, SP:SAMPLEPREP_SUMMARY degasser and autosampler outfitted with a Xbridge Amide column (Waters; 4.6 mm SP:SAMPLEPREP_SUMMARY × 100 mm dimension and a 3.5 μm particle size). Mobile phase A contained water SP:SAMPLEPREP_SUMMARY and acetonitrile (95/5, v/v), 10 mM ammonium hydroxide and 10 mM ammonium SP:SAMPLEPREP_SUMMARY acetate (pH 9.0). Mobile phase B was 100% acetonitrile. The gradient was set to SP:SAMPLEPREP_SUMMARY 0 min, 15% A; 2.5 min, 30% A; 7 min, 43% A; 16 min, 62% A; 16.1–18 min, 75% A; SP:SAMPLEPREP_SUMMARY 18–25 min, 15% A, with a flow rate of 400 μl min–1. The capillary of the SP:SAMPLEPREP_SUMMARY electrospray ionization source was set to 275 °C, with sheath gas at 45 SP:SAMPLEPREP_SUMMARY arbitrary units, auxiliary gas at 5 arbitrary units and the spray voltage at 4.0 SP:SAMPLEPREP_SUMMARY kV. A mass/charge ratio scan ranging from 70 to 850 was used in SP:SAMPLEPREP_SUMMARY positive/negative polarity switching mode. MS1 data were collected at a SP:SAMPLEPREP_SUMMARY resolution The automatic gain control (AGC) target was set at 1 × 106, with a SP:SAMPLEPREP_SUMMARY maximum injection time of 200 ms. The top five precursor ions were fragmented SP:SAMPLEPREP_SUMMARY using the higher-energy collisional dissociation cell with normalized collision SP:SAMPLEPREP_SUMMARY energy of 30% in MS2 at a resolution of 17,500. Data were acquired with Xcalibur SP:SAMPLEPREP_SUMMARY software (v.4.1; ThermoFisher Scientific). #CHROMATOGRAPHY CH:CHROMATOGRAPHY_SUMMARY Solvent A at pH 9.0 CH:CHROMATOGRAPHY_TYPE HILIC CH:INSTRUMENT_NAME Thermo Dionex Ultimate 3000 CH:COLUMN_NAME Waters XBridge BEH Amide (100 x 3mm, 3.5um) CH:SOLVENT_A 95% water/5% acetonitrile; 20 mM ammonium hydroxide; 20 mM ammonium acetate 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 to 18 min, 75% CH:FLOW_GRADIENT A; and 18 to 25 min, 15% A CH:FLOW_RATE 400 uL/min CH:COLUMN_TEMPERATURE 25 CH:INJECTION_TEMPERATURE 275 #ANALYSIS AN:ANALYSIS_TYPE MS #MS MS:INSTRUMENT_NAME Thermo Q Exactive Plus Orbitrap MS:INSTRUMENT_TYPE Orbitrap MS:MS_TYPE ESI MS:ION_MODE UNSPECIFIED MS:MS_COMMENTS A 15μl aliquot of the sample was used for high-resolution HPLC-tandem mass MS:MS_COMMENTS spectrometry. High-resolution HPLC-tandem mass spectrometry was performed on a MS:MS_COMMENTS Q-Exactive (ThermoFisher Scientific) in line with an electrospray source and an MS:MS_COMMENTS UltiMate 3000 (ThermoFisher Scientific) series HPLC consisting of a binary pump, MS:MS_COMMENTS degasser and autosampler outfitted with a Xbridge Amide column (Waters; 4.6 mm MS:MS_COMMENTS × 100 mm dimension and a 3.5 μm particle size). Mobile phase A contained water MS:MS_COMMENTS and acetonitrile (95/5, v/v), 10 mM ammonium hydroxide and 10 mM ammonium MS:MS_COMMENTS acetate (pH 9.0). Mobile phase B was 100% acetonitrile. The gradient was set to MS:MS_COMMENTS 0 min, 15% A; 2.5 min, 30% A; 7 min, 43% A; 16 min, 62% A; 16.1–18 min, 75% A; MS:MS_COMMENTS 18–25 min, 15% A, with a flow rate of 400 μl min–1. The capillary of the MS:MS_COMMENTS electrospray ionization source was set to 275 °C, with sheath gas at 45 MS:MS_COMMENTS arbitrary units, auxiliary gas at 5 arbitrary units and the spray voltage at 4.0 MS:MS_COMMENTS kV. A mass/charge ratio scan ranging from 70 to 850 was used in MS:MS_COMMENTS positive/negative polarity switching mode. MS1 data were collected at a MS:MS_COMMENTS resolution The automatic gain control (AGC) target was set at 1 × 106, with a MS:MS_COMMENTS maximum injection time of 200 ms. The top five precursor ions were fragmented MS:MS_COMMENTS using the higher-energy collisional dissociation cell with normalized collision MS:MS_COMMENTS energy of 30% in MS2 at a resolution of 17,500. Data were acquired with Xcalibur MS:MS_COMMENTS software (v.4.1; ThermoFisher Scientific). #MS_METABOLITE_DATA MS_METABOLITE_DATA:UNITS Peak area MS_METABOLITE_DATA_START Samples Nav-Jos-20220209-01 Nav-Jos-20220209-02 Nav-Jos-20220209-03 Nav-Jos-20220209-04 Nav-Jos-20220209-05 Nav-Jos-20220209-06 Nav-Jos-20220209-07 Nav-Jos-20220209-08 Nav-Jos-20220209-09 Nav-Jos-20220209-10 Nav-Jos-20220209-16 Nav-Jos-20220209-19 Nav-Jos-20220209-20 Nav-Jos-20220209-21 Nav-Jos-20220209-22 Factors Genotype:NA | Sample source:Plasma Genotype:HET | Sample source:Microglia Genotype:KO | Sample source:Microglia Genotype:HET | Sample source:Microglia Genotype:KO | Sample source:Microglia Genotype:NA | Sample source:Plasma Genotype:HET | Sample source:Microglia Genotype:KO | Sample source:Microglia Genotype:HET | Sample source:Microglia Genotype:KO | Sample source:Microglia Genotype:NA | Sample source:Plasma Genotype:HET | Sample source:Microglia Genotype:KO | Sample source:Microglia Genotype:KO | Sample source:Microglia Genotype:HET | Sample source:Microglia 1,3-bisphospho-D-glycerate 0 0 0 0 0 0 11183 0 0 0 0 0 0 8382 0 1-methylnicotinamide+ 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1-phenylethylamine 0 2026036 1951981 0 0 0 417758 2003963 2266207 3316306 0 37738284 79962671 29834920 19300411 2- / 3-phosphoglycerate 94729 247501 86259 29672 42538 66043 131688 119172 164057 80684 34777 159044 45049 89969 47692 2-(Formamido)-N1-(5-phospho-D-ribosyl)acetamidine 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 2,3-bisphospho-D-glycerate 0 8792 4555 0 0 0 9923 0 0 0 0 0 0 0 0 2-aminobutanoate / 2-/3-aminoisobutanoate 1201449 0 0 1686109 0 0 0 2638978 0 0 2163345 1388649 2540126 0 0 2-HG 884193 2129991 4596686 2204902 15251253 697394 3948533 4270001 2559561 20303641 508799 1611872 26646107 28309925 2081691 2-hydroxybutanoic acid 969240 0 1120957 0 0 0 0 0 0 0 0 0 319989 0 0 2-keto-3-deoxy-d-gluconic acid 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 2-keto-isovaleric acid 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 2-ketovaleric acid 4618124 0 0 0 0 0 0 0 0 0 0 0 2720552 0 0 2-oxoadipic acid 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 2-oxobutanoic acid 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 3- / 4-hydroxyphenylacetic acid 3130808 0 1670254 270216 526392 441569 0 891826 0 625047 592388 276741 166082 130966 145335 3- / 7-methylguanine 6388 37409 17978 39767 41855 28405 129947 160334 55011 43143 12256 96964 95519 22865 38094 3,4-dihydroxymandelic acid 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 3,4-dihydroxyphenylpropanoate 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 3-hydroxy-anthranilic acid 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 3-hydroxybutanoic acid 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 3-hydroxykynurenine 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 3-hydroxypropanoic acid 18014203 35266103 66515305 22299528 5558923 3146910 10141058 15431170 1416270 29334101 5336098 597910 23421712 1019942 6676428 3-methoxytyramine 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 3-phosphohydroxypyruvic acid 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 3-phospho-serine 0 33225 0 6285 0 0 62993 0 0 4537 0 47106 0 0 20578 3-ureidopropionic acid 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 4-hydroxybutanoic acid 296042 195035 302396 283640 1734748 913736 478139 776852 455842 687762 360123 482969 392837 375289 226989 4-hydroxyphenylpyruvic acid 9810 0 0 0 0 0 0 5537 0 0 0 0 0 0 0 4-hydroxyproline / 5-aminolevulinate NaN 1807799 1762663 1921853 2052088 NaN 8045986 12272221 1924826 2222081 NaN 4394241 4857303 3438077 3144856 5-aminopentanoic acid 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 5'-deoxyadenosine 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 5-HIAA 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 5-methylcytosine 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 5-methyl-THF 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 5'-methylthioadenosine 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 6-aminohexanoate 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 6-O-methylguanine 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 6-phosphogluconic acid 17986 17975 8888 0 7090 5772 15905 8263 0 0 0 8167 0 19584 0 6-phosphoglucono-D-lactone 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 acetoacetic acid 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 acetoin - 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 acetylcarnitine+ 0 5504827 980462 2581834 3442736 0 4238853 2760639 1054131 2400585 0 6658955 4358302 2665780 3833751 acetylcholine+ NaN 4871647 3425141 3982172 4540227 NaN 4392014 2874573 11727780 6519383 NaN 5892358 7630069 9180038 4419149 acetyl-CoA 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 aconitic acid 7874 459381 207551 248215 173609 10704 747420 436600 333099 297348 11601 857542 427578 361918 513414 acrylic acid 0 0 0 0 0 384457 10094147 15197391 0 0 278355 1644541 3269628 2720024 0 adenine 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 adenosine 0 0 0 451972 631151 0 779934 0 462480 741262 0 803924 623878 496046 330187 adenylosuccinate 0 0 0 0 32691 0 0 0 50791 37542 0 0 27449 33912 0 ADP / dGDP 79300 971036 287644 412169 871353 17306 902415 165256 2342196 1282081 20859 1199279 1786912 1978654 876279 ADP-D-glucose 0 0 0 0 15050 0 0 0 0 0 0 22404 37354 36182 21026 agmatine NaN 100618 47587 12543 0 5529 0 0 0 0 0 4373 4456 0 0 AICA ribonucleotide 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 a-KG 0 519288 272080 554711 288296 122307 851682 434668 492068 423170 26372 854832 725014 421945 516454 alanine 0 0 0 4734169 4501863 0 8105797 8328445 5602548 7169249 0 4507370 8634636 6457333 3727370 alanine methyl ester 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 allantoin 0 136147 158194 837560 703565 0 7950311 8727056 503330 886564 0 947080 1697525 661615 638517 AMP / dGMP 1769923 347721 584268 679495 2533403 560348 116081 52347 2532163 2637205 137126 392133 3023063 3130340 378765 anandamide 0 0 0 0 0 0 470978 140433 7601 0 0 105074 10782 89168 0 arginine 0 6632565 2533903 5428029 9483966 0 8222933 1136280 16344806 12735671 0 19902454 21426464 18278378 10980713 ascorbic acid 0 0 9441 5535454 192309 0 0 0 118053 0 0 4077120 250244 0 1505509 asparagine 0 712568 403291 860063 985875 0 486439 361717 520384 777081 0 3501256 4019815 2501780 3014209 aspartic acid 855057 4249906 0 12509226 4665235 1111654 14413603 3638789 11832013 5909764 995350 14902586 8104165 7701089 10493074 ATP / dGTP 0 1948233 36289 1393417 281650 0 4069134 209623 586974 23855 16637 6617380 803018 522805 3607206 b-alanine 217047 544780 361025 1638478 597241 0 2548709 1817382 4770063 1510006 160800 2525543 1913152 1425464 1297448 betaine+ 1393073 6187181 10542608 47175469 26617327 1314648 89400970 127288846 18563107 34888166 1585633 37974302 48672849 23882073 18484193 bilirubin 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 biotin 0 0 0 0 0 8291 9809 38262 0 0 0 0 9388 0 0 butyric acid 0 92219 0 0 0 0 0 138860 0 0 0 0 0 0 0 butyric acid(iso) 0 699757 0 0 0 0 154018 360067 0 0 0 0 0 0 0 caffeic acid 0 0 0 0 0 0 6918 0 0 0 0 0 13643 0 0 cAMP(2',3') / cAMP(3',5') 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 carbamoyl phosphate 281408 68731 1269031 726799 819624 176654 1086903 1674302 836297 1131125 136661 1010869 904416 1059029 912527 carnitine+ 329406 9952294 10474918 12385660 31008670 965786 61601456 58538971 35437750 56899863 815004 64752935 71206330 64714250 42023695 cCMP(2',3'-) 0 10818 0 0 55158 0 196857 122100 13792 72408 0 17978 41917 13253 0 CDP 0 0 6996 0 0 0 0 0 0 0 0 0 0 0 0 CDP-choline+ 0 0 0 0 197151 0 0 0 189865 184320 0 49704 541972 528380 53105 cGMP 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 choline+ 3244427 237872905 132007644 282427635 389979887 2337672 549435499 488829727 336577075 601808272 1705230 503106262 729945354 549984981 373281706 citraconic acid 894428 531805 1022072 943355 674994 0 1093502 1015726 704400 954694 518769 1672664 1820240 865506 983949 citramalic acid 1852815 3086048 2046299 1826455 3599548 1101154 3284479 5748518 5241147 3087466 1213990 3417328 2767132 4264530 2738249 citrate / citrate(iso) 5828300 14420791 8669119 4690878 3987388 2300421 4842622 3880178 4350242 3994289 1398356 3926308 3156546 2836575 2712794 citrulline 71208 77455 69952 774098 732733 117508 1640311 1876861 480971 498834 112579 664885 784380 769021 418021 CMP 0 0 0 24651 44076 0 0 0 57705 54610 4288 77863 186014 191838 47420 Coenzyme A + 0 0 0 0 5218 0 0 0 0 5739 0 0 0 5081 0 cortisol 0 0 0 0 37767 0 0 0 0 0 0 0 0 0 0 creatine 677552 66280561 59555305 91387584 158709158 1547370 192160523 150597456 282340007 318893718 1080427 184687774 305596247 328811252 98144125 creatinine 0 0 0 3921176 6121436 0 50903911 86002953 6512139 8888184 0 11424070 16264647 7794330 7833773 CTP 0 6838 0 0 0 0 0 0 0 0 0 15973 0 0 4953 cystathionine 0 0 0 0 7163 0 38188 133893 19981 5288 0 8382 0 7200 0 cysteine 435107 1222854 528804 772314 454355 452363 410861 323912 267155 364717 115688 214175 222475 154880 156694 cysteine-S-sulfate 0 12571 11104 10332 0 0 48314 94206 0 0 0 0 9975 0 0 cystine 42217 726442 141544 32186 34391 6011 259443 1070278 73699 24102 0 68610 6715 0 27897 cytidine 0 0 0 13353 19920 0 208559 317860 9004 42194 0 17895 149656 103124 0 cytosine 0 178753 0 436386 264733 0 699966 450601 0 126459 169387 0 0 0 0 dADP 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 dAMP 0 0 5948 0 0 0 0 0 0 0 0 0 0 0 0 D-arabinono-1,4-lactone 0 1757529 459026 838331 1629695 0 1799988 0 1554450 1685651 0 2280641 1820835 1886787 1676448 dATP 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 dCDP 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 dCMP 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 dCTP 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 dehydroascorbic acid 12592 9268749 2286541 13538649 8701310 12059 8817236 145057 5716066 13854280 0 18104430 14866334 6971393 14001245 deoxyadenosine 0 0 0 0 10541 15345 7044 16931 4582 6669 13676 36873 0 28788 34032 deoxycarnitine+ 0 1294148 737361 2840904 3775657 0 7809149 6403805 4054711 5583093 0 6558650 8340757 7156517 3686211 deoxycytidine 0 0 0 0 0 0 39240 63303 0 7777 0 0 7820 0 6271 deoxyguanosine 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 deoxyinosine 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 deoxyuridine 661724 0 0 0 0 0 74848 115719 1815564 0 0 0 0 1877728 0 D-erythrose-4-phosphate 8315 0 0 0 0 0 0 0 0 0 0 0 0 0 0 D-galactonic acid / D-gluconic acid 12905956 27224874 20040449 10590623 11855721 3511687 12245746 12851479 6422001 8331534 2218760 5058451 5467363 4969208 4082805 D-galactosamine/glucosamine-1/6-phosphate 19210 30626 14699 65832 67346 10888 4936 0 37269 31414 0 135063 71424 85497 68078 D-glucuronolactone 0 0 10010 9531 23805 0 1160405 2207637 201726 199989 0 309324 382683 386077 159232 dihydroorotate 10232 9532 24482 10439 22507 54249 9925 13916 17237 87778 15916 21184 91786 63561 90963 dimethylglycine 0 351798 0 0 549430 0 583236 468410 619817 724763 0 585921 988679 853123 501682 DL-DOPA 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 DOPAC 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 dopamine 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 D-ribose-1/5-phosphate / D-ribulose 5-phosphate 0 0 0 0 0 0 0 0 0 0 0 8916 0 10109 0 D-sedoheptulose 14626 0 0 0 30236 8904 246660 472010 23204 30858 0 33341 86804 40698 0 D-sedoheptulose-7-phosphate 18551 22701 12015 0 10039 0 18278 0 0 0 0 22472 11905 0 9969 dTMP 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 dTTP 0 0 0 0 0 0 8306 0 0 0 0 0 0 0 0 dUMP 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 dUTP 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 epinephrine / normetanephrine 3292171 6648859 4770663 5683285 5203391 4049924 4409301 4419602 2388883 3414472 2267260 2454850 2522787 2566101 2048038 ethyl acetate 0 3800285 2676304 0 0 0 0 0 2086140 2028500 0 0 0 0 0 F-1,6/2,6-DP 0 29882 52247 0 8878 0 42147 31808 24084 9824 0 18186 0 10377 8810 F1P 8136 9836 0 0 0 0 8034 0 0 0 0 0 11984 0 0 F6P / G1P / G6P 1937402 1759713 918887 659579 465559 232049 872745 269050 373465 222386 11463 1023841 125061 75396 628893 FAD 0 0 0 0 7917 0 0 0 0 9525 0 9054 0 0 0 FMN 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 folate 0 0 0 0 0 0 8769 0 0 0 0 0 10412 5536 0 fructose / mannose 0 579912 688712 4646788 6770818 0 25587230 36518198 3711406 6151256 0 6829841 10348454 4941427 4796349 fumaric acid 0 290336 0 594885 665096 0 794156 420905 723425 783318 0 729381 1850476 1147613 647051 GABA 466842 3197468 1534988 3243434 4458405 228518 4934112 2635647 6648212 6681322 0 7058591 6696033 6892965 5055197 galactosamine / glucosamine / mannosamine 3119907 2041099 1876293 1977623 1618962 1587752 1462364 1439408 1113732 957539 840846 747184 677652 731629 665834 galactose / glucose 0 1101720 777887 2690138 2237406 0 83437336 131555264 8742001 14917566 0 19486231 29466566 17810183 12689886 GalNAC / GlcNAC 327905 347997 219253 0 0 261760 321845 470989 505106 248174 230984 324153 180002 345509 288929 GAP / DHAP 0 12628 0 0 0 0 0 0 0 9975 0 0 0 0 0 GDP 0 7071 0 0 32524 0 0 0 290402 115269 0 21678 64166 120091 0 GDP-L-fucose 0 0 0 0 0 0 0 0 0 0 0 9796 20105 17173 11688 geranyl-PP 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 glucono-lactone 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 glutaconic acid 406910 14582966 2724191 8509873 14139839 0 23491526 1113998 5919842 13207874 394799 12589197 10854562 6565106 9146396 glutamate 800822 6194149 5282692 9106769 29968771 915532 29006408 24530840 14019367 31585468 911890 19167143 47107951 41278359 12186533 glutamine 430509 10318096 2685750 13620039 19264123 645760 52678703 51603540 14027737 11488195 493167 18623675 21564362 18381523 11392317 glutathione 21083097 17232843 14899591 12855626 14329976 12130461 14890935 9511657 15416341 20750340 9231107 23618264 22756235 23300504 18155439 glutathione disulfide 1696950 2413168 1796254 1917801 2673350 1061754 1946769 1077820 1695826 2211964 636232 2075759 2482407 2284295 1472840 glyceraldehyde 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 glyceric acid 0 1203917 968377 1276857 707029 433896 2373211 3424150 866395 685244 586654 583805 1645181 814124 912436 glycerol 2/3-phosphate 484897 94915 297986 297313 2465262 123879 90564 97523 455184 4884414 24595 812097 6152461 5279367 648221 glycine 0 1078680 624513 1241211 2656467 0 4962167 5465602 1868051 2732177 0 1972608 4205596 4725998 2494488 glycylglycine 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 glyoxylic acid 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 GMP 11944 49909 161177 21018 805757 0 0 16000 796849 1165328 0 17333 1177558 1090669 6577 GTP 0 58714 6243 0 0 0 119433 0 6097 5208 0 380613 5870 722 94373 guanidine 459086 1243340 1871832 993293 761235 2653154 6973206 3854686 701310 35059228 645912 902484 944292 792399 10182125 guanidinoacetate 5266 407131 266490 436664 1025227 5864 613310 407612 999920 1543942 7187 1069693 1810256 1658567 640471 guanine 15228 88095 112675 51885 394270 46712 48538 163495 119389 407474 32947 134895 581126 461095 37587 guanosine 0 0 0 0 0 0 0 0 0 0 0 0 11284 5553 0 gulonic-lactone 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 histamine NaN 1743345 NaN 3948975 3145477 NaN 504469 NaN 1092045 544967 NaN 3762796 NaN 1753446 2417800 histidine 14552747 16526229 14100345 16932813 19567308 13207248 25143460 27415474 18194105 17323089 12232692 22831131 28310625 24013906 18799928 homocysteine 0 0 0 0 11685 0 0 40778 0 8314 0 0 0 0 4830 homocystine 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 homogentisic acid 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 homoserine / threonine / allothreonine 0 2480710 957947 2129542 2789710 0 7680929 12103282 1816388 2037180 0 5693359 6794001 5419510 3699558 hydroxyphenyllactic acid / HVA 0 0 0 0 0 0 262957 389029 0 0 9695 0 172721 0 18298 hydroxypyruvic acid 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 hypoxanthine 156598 5297919 2955987 3932368 22638824 0 20306462 31075639 6342741 25533522 0 5092469 61190845 30237726 3934511 IDP 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 imidazole-4-acetate 0 119405 677272 228830 297153 0 900268 631052 277082 216625 0 558107 496862 301369 0 IMP 14819 6418 52264 23550 3182380 7398 0 0 2222285 2904608 0 312195 4820189 4302743 255866 inosine 0 0 0 9169 31088 0 0 0 37144 43015 0 40259 208482 148933 0 isonictinic acid 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 isopentenyl pyrophosphate 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 itaconic acid 301346 1084679 209929 1094243 1037549 346926 2661598 222926 1759379 1700550 226933 1908964 1752324 2424011 1603541 kynurenic acid 11773 30691 37455 35290 34805 18213 114652 171584 0 20357 9041 8228 23114 54106 0 kynurenine 0 78681 220886 312359 117447 0 335138 345428 65767 275921 0 131329 164915 153508 141706 lactic acid 0 0 0 0 61461038 0 263058716 631154714 105906569 57912483 0 105642749 165462282 82403942 56497954 lactose / maltose / sucrose 0 0 0 0 10726 0 0 0 0 0 0 0 0 0 0 L-arginino-succinate 0 8156 0 0 14299 0 104646 155147 117045 54879 0 152637 129326 83401 67481 L-cysteic acid 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 leucine / leucine(iso) / norleucine 0 0 0 0 16329787 0 45644665 67394947 0 0 0 34257011 51031047 20371420 31919778 levulinic acid 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 lipoamide 0 0 0 0 0 0 0 0 0 0 0 0 0 7112 0 L-NMMA 0 0 0 21341 55648 0 611506 1145068 44111 6145 0 34924 85987 53920 0 L-tyrosine methyl ester 0 290478 510368 449615 150393 0 234387 596047 698351 184939 0 352769 608770 391667 0 lysine 0 2202999 813578 1523874 3073576 0 12596178 17058005 4112616 3199316 0 4650611 6393827 5139210 2686729 maleic acid 0 594680 1515596 2182778 1291615 0 1262827 1378032 0 410743 0 754733 1007545 0 537991 malic acid 0 632819 726170 1726754 1112557 0 1712740 786922 2842920 2079028 0 3393171 3064953 2796934 2342747 malonic acid 874215 2876226 4418600 2597321 3380217 2080601 4201256 4423724 1665653 4359368 2069309 3508607 3202270 5014317 2432258 malonyl-CoA 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 mandelic acid / vanillin 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 ManNAC 92445 117325 224253 126591 202250 27071 239998 403787 0 450206 130000 259054 371568 362801 245060 mesaconic acid 855151 1957224 1111512 992117 3095217 0 2480920 2256227 1550422 4525740 714070 1904932 6685949 6348150 1615926 methionine 0 1072594 700473 844484 1407819 0 3414720 4790671 860879 1182144 0 3890000 5615627 2463892 2610792 methyl acetoacetate 1316338 0 0 0 0 0 0 614894 0 0 0 0 620320 0 0 methylglyoxal 456266 1340231 2095738 2107176 0 556578 652916 0 0 1153900 0 0 2390529 2283076 0 methylmalonic acid 980348 0 0 405880 0 0 1663289 2487313 0 1423150 0 1183936 1387102 1277628 843699 mevalonic acid 329943 378671 500365 118322 341547 0 344336 435319 139199 192364 249694 287004 84947 231416 237276 N1/N8-acetylspermidine NaN 171704 882642 180451 328018 NaN 27676 911123 352043 413912 NaN 1126503 488937 207211 79531 N1-acetylspermine 805214 350636 395513 411370 439211 523092 437825 313728 505437 434314 140733 52526 57979 29461 21252 N-acetylaspartic acid 0 3207297 1155309 4362426 5210721 0 5669797 467870 9904332 8188597 0 6412541 4785377 5058656 4918240 N-acetylaspartylglutamic acid 0 0 0 0 38636 0 0 0 0 0 0 0 0 0 0 N-acetyl-b-alanine 0 0 0 0 0 788810 0 1394530 0 1305425 0 0 0 0 0 N-acetyl-DL-alanine 0 0 0 0 0 2015724 0 1057711 0 1264853 0 410135 449901 0 0 N-acetyl-DL-serine / O-acetyl-L-serine 321359 211712 365135 699042 321819 328864 610178 459633 139938 277143 307129 297225 255870 355502 71020 N-acetylglucosamine 1/6-phosphate 0 0 0 0 0 0 27279 0 0 0 0 26676 17659 15940 22248 N-acetylglycine 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 N-acetyl-L-glutamic acid 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 NAD+ 0 0 0 391857 253700 0 0 0 114159 149315 0 213556 510542 472695 296586 NADH 0 0 32665 6884 364422 0 6364 0 0 235604 0 0 123461 106711 0 NADP+ 0 73969 0 11902 61764 0 97684 0 70117 96854 0 139165 85953 90777 8318 NADPH 6328 0 0 0 0 0 0 0 0 0 0 0 0 0 0 N-carbamoyl-L-aspartate 0 0 0 0 0 0 0 0 0 0 0 8853 0 0 0 nebularine 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 N-formyl-L-methionine 0 0 0 110861 0 0 0 0 0 0 0 0 0 0 0 nicotinamide 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 nicotinamide riboside+ 6075 7400 9038 6568 426901 5732 0 0 0 311460 7605 44672 713359 977215 4904 nicotinic acid 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 N-methyl-alanine 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 N-methylaspartic acid 1043588 10239684 8283853 13054149 43490795 1228829 34973008 33221502 22210297 48310982 1123005 31793656 74814561 63016255 19645981 N-methyltryptamine 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 NMN 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 norepinephrine / pyridoxine 0 0 81779 0 0 0 0 1376542 0 340911 0 429758 507296 362021 173258 octopamine 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 ornithine 178023 167119 248364 180705 400018 95426 19848389 30863979 2901614 3198556 183183 3309655 5106479 3800657 1917931 orotic acid 0 0 0 0 35626 0 0 0 0 0 0 0 28385 0 0 orotidylic acid 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 O-succinyl-homoserine 0 0 0 0 5157 7582 0 0 0 5722 0 6439 0 0 0 oxalacetic acid 0 0 0 0 0 0 0 0 7103 6501 0 0 7561 0 0 pantothenic acid 17658 66750 20530 303827 414031 10172 1434425 2298716 0 412975 0 400306 659854 386591 258857 phenethylamine 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 phenylalanine 0 0 0 3496781 2905674 0 12649675 18396294 0 2774292 0 8579621 10719405 4436148 4969204 phenylephrine / synephrine 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 phenylethanolamine 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 phosphocreatine 0 3455119 48938 7541543 1132702 6466 8368217 0 64082 0 16911 19684960 441501 644883 14988630 phosphoenolpyruvate 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 phosphorylcholine+ 8935131 12122580 5688613 8751839 7613940 2898562 17254783 2935544 13911531 9141280 1513311 19438499 13290955 14293626 13531528 picolinic acid 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 proline 0 0 0 0 0 0 54335677 81359375 14923759 22340360 0 38166839 45554610 23227506 16966668 propionic acid 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 PRPP 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 pseudouridine 12063 22614 21952 94692 83243 10260 664799 1070917 82571 133129 0 149397 182325 75690 110433 purine 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 putrescine NaN 398605 88060 61562 6042 NaN 54065 35718 74625 83370 NaN 119020 79869 44601 29137 pyridoxal 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 pyroglutamic acid 0 8402000 5804692 14079449 19679346 0 48738631 63937846 4549152 19953474 0 16387801 22636985 17252027 11688849 pyrroline hydroxycarboxylic acid 0 6066004 2198734 8240287 16355390 0 31288155 31006348 9916380 12711709 0 13524189 21150024 17710228 8013830 pyruvic acid 0 1891664 1256267 2057049 1878090 0 15702618 25223193 2044250 3017188 0 7046751 3303628 2329842 4361892 quinolinic acid 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 S-adenosyl-L-homocysteine 0 0 0 0 0 0 0 0 0 0 0 0 56712 47957 0 S-adenosyl-L-methionine+ 0 133524 0 0 155454 0 265737 0 327564 257464 0 471739 540538 430763 225376 S-adenosylmethioninamine+ 0 0 0 0 0 0 0 0 0 4779 0 4870 0 0 0 SAICAR 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 sarcosine 1224325 628121 628825 967613 0 124779 299595 0 2076138 0 0 0 0 0 285235 serine 0 3103963 2950612 4867105 5096354 1593193 9415087 10432841 3781117 4055809 0 6881865 8091946 6550453 5865037 serotonin 0 429613 210678 301120 0 0 0 632884 0 0 0 0 0 0 0 sorbitol / galactitol / L-iditol / manitol 0 209521 363611 2075775 3354128 0 15564313 24253624 2068556 2780644 0 3446736 5102074 3382077 2645683 spermidine NaN 374146773 384710325 383581907 385794244 NaN 332805141 311453935 326310508 354357606 NaN 280798535 246334291 210415865 242514332 spermine NaN 137569889 141054786 141261840 147994682 NaN 140385983 132867477 133544320 143414638 NaN 152018476 141608548 123239219 144344288 succinic acid 1811223 7834133 10138830 8122855 31203200 3351391 46947140 68100734 21288564 38405624 2573776 11220730 45935110 40509220 10149667 succinic semialdehyde 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 succinyl-CoA 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 taurine 140371 110852094 35491797 122738657 144462645 289355 163293655 12910702 106016809 211686891 293566 213043173 255651966 229023656 147186723 thiamine diphosphate+ 14492 19836 0 0 14123 0 0 6442 9790 2255 4284 4078 0 10070 4371 thiamine phosphate+ 11431 14468 8519 0 6874 5674 5404 0 5964 17474 5769 5668 5105 5558 4031 thiamine+ 58979 197785 101031 95894 333246 15506 2481261 4284344 529621 621319 0 642737 1293256 1090772 333331 thymidine 0 27741 65277 26207 35817 0 320133 484455 0 37437 0 52392 75901 4126693 51535 thymine 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 tryptamine 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 tryptophan 0 485770 0 1146183 1029425 0 2946222 4180338 533843 845611 0 1852470 1894256 959911 1021115 tyramine 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 tyrosine 0 1003905 2402441 3557578 2525169 0 4731683 6892686 1331362 1173099 0 3977295 3889303 2479724 2793317 UDP 0 0 0 0 0 0 0 0 25680 8885 0 8969 0 11081 8272 UDP-D-galactose / UDP-D-glucose 0 0 0 0 0 0 0 0 0 0 0 84809 59382 49565 41515 UDP-N-acetyl-galactosamine/UDP-N-acetyl-glucosamine 0 0 0 341679 0 0 0 0 56329 73402 0 381925 166225 263704 347947 UMP 0 0 0 0 0 0 0 0 34243 11056 0 0 0 0 0 uracil 0 0 0 0 0 0 3143536 4452053 0 0 0 0 0 0 0 uracil 5-carboxylic acid 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 urea 0 0 0 0 0 0 1166661 2337806 0 0 0 0 0 0 0 uric acid 11818 46409 10088 721469 570234 0 2738896 4476449 404985 398446 0 594318 806552 510625 362402 uridine 0 8303 28105 22013 41991 8111 100639 137684 56569 62678 0 8141 133990 21453 0 UTP 0 8750 0 0 0 0 10132 0 0 0 0 26971 0 0 7307 valine / norvaline 0 0 0 0 0 0 10081988 18833510 0 0 0 7146845 9658445 7473254 6258212 vitamin B2 0 0 0 0 0 0 0 0 0 0 0 0 7617 0 0 xanthine 6595 477632 299371 1531164 3534181 11191 7439585 11190655 1435858 2938851 12965 4609244 8060219 3138908 3282225 xanthosine 0 0 0 0 8934 0 0 10588 0 0 0 10724 33604 22190 9641 xanthurenic acid 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 XMP 18511 0 0 5158 7142 12518 0 0 13660 18679 29612 5075 31287 51542 0 xylitol / arabitol / ribito 0 0 0 0 1032446 0 3264321 4632362 675099 921490 0 454884 1094669 1104516 383856 y-glutamylcysteine 72772 77317 36803 11093 17211 6293 73021 24047 93176 143991 11860 76179 170315 145452 60365 MS_METABOLITE_DATA_END #METABOLITES METABOLITES_START metabolite_name 1,3-bisphospho-D-glycerate 1-methylnicotinamide+ 1-phenylethylamine 2- / 3-phosphoglycerate 2-(Formamido)-N1-(5-phospho-D-ribosyl)acetamidine 2,3-bisphospho-D-glycerate 2-aminobutanoate / 2-/3-aminoisobutanoate 2-HG 2-hydroxybutanoic acid 2-keto-3-deoxy-d-gluconic acid 2-keto-isovaleric acid 2-ketovaleric acid 2-oxoadipic acid 2-oxobutanoic acid 3- / 4-hydroxyphenylacetic acid 3- / 7-methylguanine 3,4-dihydroxymandelic acid 3,4-dihydroxyphenylpropanoate 3-hydroxy-anthranilic acid 3-hydroxybutanoic acid 3-hydroxykynurenine 3-hydroxypropanoic acid 3-methoxytyramine 3-phosphohydroxypyruvic acid 3-phospho-serine 3-ureidopropionic acid 4-hydroxybutanoic acid 4-hydroxyphenylpyruvic acid 4-hydroxyproline / 5-aminolevulinate 5-aminopentanoic acid 5'-deoxyadenosine 5-HIAA 5-methylcytosine 5-methyl-THF 5'-methylthioadenosine 6-aminohexanoate 6-O-methylguanine 6-phosphogluconic acid 6-phosphoglucono-D-lactone acetoacetic acid acetoin - acetylcarnitine+ acetylcholine+ acetyl-CoA aconitic acid acrylic acid adenine adenosine adenylosuccinate ADP / dGDP ADP-D-glucose agmatine AICA ribonucleotide a-KG alanine alanine methyl ester allantoin AMP / dGMP anandamide arginine ascorbic acid asparagine aspartic acid ATP / dGTP b-alanine betaine+ bilirubin biotin butyric acid butyric acid(iso) caffeic acid cAMP(2',3') / cAMP(3',5') carbamoyl phosphate carnitine+ cCMP(2',3'-) CDP CDP-choline+ cGMP choline+ citraconic acid citramalic acid citrate / citrate(iso) citrulline CMP Coenzyme A + cortisol creatine creatinine CTP cystathionine cysteine cysteine-S-sulfate cystine cytidine cytosine dADP dAMP D-arabinono-1,4-lactone dATP dCDP dCMP dCTP dehydroascorbic acid deoxyadenosine deoxycarnitine+ deoxycytidine deoxyguanosine deoxyinosine deoxyuridine D-erythrose-4-phosphate D-galactonic acid / D-gluconic acid D-galactosamine/glucosamine-1/6-phosphate D-glucuronolactone dihydroorotate dimethylglycine DL-DOPA DOPAC dopamine D-ribose-1/5-phosphate / D-ribulose 5-phosphate D-sedoheptulose D-sedoheptulose-7-phosphate dTMP dTTP dUMP dUTP epinephrine / normetanephrine ethyl acetate F-1,6/2,6-DP F1P F6P / G1P / G6P FAD FMN folate fructose / mannose fumaric acid GABA galactosamine / glucosamine / mannosamine galactose / glucose GalNAC / GlcNAC GAP / DHAP GDP GDP-L-fucose geranyl-PP glucono-lactone glutaconic acid glutamate glutamine glutathione glutathione disulfide glyceraldehyde glyceric acid glycerol 2/3-phosphate glycine glycylglycine glyoxylic acid GMP GTP guanidine guanidinoacetate guanine guanosine gulonic-lactone histamine histidine homocysteine homocystine homogentisic acid homoserine / threonine / allothreonine hydroxyphenyllactic acid / HVA hydroxypyruvic acid hypoxanthine IDP imidazole-4-acetate IMP inosine isonictinic acid isopentenyl pyrophosphate itaconic acid kynurenic acid kynurenine lactic acid lactose / maltose / sucrose L-arginino-succinate L-cysteic acid leucine / leucine(iso) / norleucine levulinic acid lipoamide L-NMMA L-tyrosine methyl ester lysine maleic acid malic acid malonic acid malonyl-CoA mandelic acid / vanillin ManNAC mesaconic acid methionine methyl acetoacetate methylglyoxal methylmalonic acid mevalonic acid N1/N8-acetylspermidine N1-acetylspermine N-acetylaspartic acid N-acetylaspartylglutamic acid N-acetyl-b-alanine N-acetyl-DL-alanine N-acetyl-DL-serine / O-acetyl-L-serine N-acetylglucosamine 1/6-phosphate N-acetylglycine N-acetyl-L-glutamic acid NAD+ NADH NADP+ NADPH N-carbamoyl-L-aspartate nebularine N-formyl-L-methionine nicotinamide nicotinamide riboside+ nicotinic acid N-methyl-alanine N-methylaspartic acid N-methyltryptamine NMN norepinephrine / pyridoxine octopamine ornithine orotic acid orotidylic acid O-succinyl-homoserine oxalacetic acid pantothenic acid phenethylamine phenylalanine phenylephrine / synephrine phenylethanolamine phosphocreatine phosphoenolpyruvate phosphorylcholine+ picolinic acid proline propionic acid PRPP pseudouridine purine putrescine pyridoxal pyroglutamic acid pyrroline hydroxycarboxylic acid pyruvic acid quinolinic acid S-adenosyl-L-homocysteine S-adenosyl-L-methionine+ S-adenosylmethioninamine+ SAICAR sarcosine serine serotonin sorbitol / galactitol / L-iditol / manitol spermidine spermine succinic acid succinic semialdehyde succinyl-CoA taurine thiamine diphosphate+ thiamine phosphate+ thiamine+ thymidine thymine tryptamine tryptophan tyramine tyrosine UDP UDP-D-galactose / UDP-D-glucose UDP-N-acetyl-galactosamine/UDP-N-acetyl-glucosamine UMP uracil uracil 5-carboxylic acid urea uric acid uridine UTP valine / norvaline vitamin B2 xanthine xanthosine xanthurenic acid XMP xylitol / arabitol / ribito y-glutamylcysteine METABOLITES_END #END