#METABOLOMICS WORKBENCH adavison_20220513_073938 DATATRACK_ID:3248 STUDY_ID:ST002179 ANALYSIS_ID:AN003569 PROJECT_ID:PR001387 VERSION 1 CREATED_ON May 26, 2022, 5:52 pm #PROJECT PR:PROJECT_TITLE Impact of nitisinone on the cerebrospinal fluid metabolome of a murine model of PR:PROJECT_TITLE alkaptonuria PR:PROJECT_SUMMARY Background: Nitisinone induced hypertyrosinaemia is well documented in PR:PROJECT_SUMMARY Alkaptonuria (AKU), and there is uncertainty over whether it may contribute to a PR:PROJECT_SUMMARY decline in cognitive function and or mood by altering neurotransmitter PR:PROJECT_SUMMARY metabolism. The aim of this work was to evaluate the impact of nitisinone on the PR:PROJECT_SUMMARY cerebrospinal fluid (CSF) metabolome in a murine model of AKU, with a view to PR:PROJECT_SUMMARY providing additional insight into metabolic changes that occur following PR:PROJECT_SUMMARY treatment with nitisinone. Methods: 17 CSF samples were collected from BALB/c PR:PROJECT_SUMMARY Hgd-/-mice (n=8, treated with nitisinone – 4 mg/L and n=9, no treatment). PR:PROJECT_SUMMARY Samples were diluted 1:1 with deionised water and analysed using a 1290 Infinity PR:PROJECT_SUMMARY II liquid chromatography system coupled to a 6550 quadrupole time-of-flight mass PR:PROJECT_SUMMARY spectrometry (Agilent, Cheadle, UK). Raw data were processed using a targeted PR:PROJECT_SUMMARY feature extraction algorithm and an established in-house accurate mass retention PR:PROJECT_SUMMARY time database. Matched entities (±10 ppm theoretical accurate mass and ±0.3 PR:PROJECT_SUMMARY minutes retention time window) were filtered based on their frequency and PR:PROJECT_SUMMARY variability. Experimental groups were compared using a moderated t-test with PR:PROJECT_SUMMARY Benjamini-Hochberg false-discovery rate adjustment. Results: Tyrosine, PR:PROJECT_SUMMARY acetyl-tyrosine, γ-glutamyl-tyrosine, p-hydroxyphenylacetic acid and PR:PROJECT_SUMMARY 3-(4-hydroxyphenyl)lactic acid were shown to increase in abundance (log2 fold PR:PROJECT_SUMMARY change 2.6-6.9, 3/5 were significant p<0.05) in the mice that received PR:PROJECT_SUMMARY nitisinone. Several other metabolites of interest were matched but no PR:PROJECT_SUMMARY significant differences were observed, including the aromatic amino acids PR:PROJECT_SUMMARY phenylalanine and tryptophan, and monoamine metabolites adrenaline, PR:PROJECT_SUMMARY 3-methoxy-4-hydroxyphenylglycol and octopamine. Conclusions: Evaluation of the PR:PROJECT_SUMMARY CSF metabolome of a murine model of AKU showed a significant difference in the PR:PROJECT_SUMMARY abundance of a limited number of metabolites. None of these have been reported PR:PROJECT_SUMMARY in CSF from a murine model of AKU previously. Moreover this study confirms that PR:PROJECT_SUMMARY some monoamine metabolites do not appear to be altered following nitisinone PR:PROJECT_SUMMARY therapy. PR:INSTITUTE University of Liverpool Institute of Life Course & Medical Sciences PR:LAST_NAME Davison PR:FIRST_NAME Andrew PR:ADDRESS 1. Department of Clinical Biochemistry and Metabolic Medicine, Liverpool PR:ADDRESS Clinical Laboratories, Liverpool University Hospitals NHS Foundation Trust, PR:ADDRESS Liverpool, UK; 2. Department of Musculoskeletal and Ageing Science, Institute of PR:ADDRESS Life Course and Medical Sciences, University of Liverpool, Liverpool, UK 3. PR:ADDRESS School of Exercise Science, Liverpool John Moores University, Liverpool, UK PR:EMAIL andrew.davison@liverpoolft.nhs.uk PR:PHONE 0151 706 4011 PR:CONTRIBUTORS Davison AS1,2,*, Norman BP2, Sutherland H2,3, Milan AM1,2, Jarvis JC3, Gallagher PR:CONTRIBUTORS JA2, Ranganath LR1,2 #STUDY ST:STUDY_TITLE Impact of nitisinone on the cerebrospinal fluid metabolome of a murine model of ST:STUDY_TITLE alkaptonuria ST:STUDY_SUMMARY Background: Nitisinone induced hypertyrosinaemia is well documented in ST:STUDY_SUMMARY Alkaptonuria (AKU), and there is uncertainty over whether it may contribute to a ST:STUDY_SUMMARY decline in cognitive function and or mood by altering neurotransmitter ST:STUDY_SUMMARY metabolism. The aim of this work was to evaluate the impact of nitisinone on the ST:STUDY_SUMMARY cerebrospinal fluid (CSF) metabolome in a murine model of AKU, with a view to ST:STUDY_SUMMARY providing additional insight into metabolic changes that occur following ST:STUDY_SUMMARY treatment with nitisinone. Methods: 17 CSF samples were collected from BALB/c ST:STUDY_SUMMARY Hgd-/-mice (n=8, treated with nitisinone – 4 mg/L and n=9, no treatment). ST:STUDY_SUMMARY Samples were diluted 1:1 with deionised water and analysed using a 1290 Infinity ST:STUDY_SUMMARY II liquid chromatography system coupled to a 6550 quadrupole time-of-flight mass ST:STUDY_SUMMARY spectrometry (Agilent, Cheadle, UK). Raw data were processed using a targeted ST:STUDY_SUMMARY feature extraction algorithm and an established in-house accurate mass retention ST:STUDY_SUMMARY time database. Matched entities (±10 ppm theoretical accurate mass and ±0.3 ST:STUDY_SUMMARY minutes retention time window) were filtered based on their frequency and ST:STUDY_SUMMARY variability. Experimental groups were compared using a moderated t-test with ST:STUDY_SUMMARY Benjamini-Hochberg false-discovery rate adjustment. Results: Tyrosine, ST:STUDY_SUMMARY acetyl-tyrosine, γ-glutamyl-tyrosine, p-hydroxyphenylacetic acid and ST:STUDY_SUMMARY 3-(4-hydroxyphenyl)lactic acid were shown to increase in abundance (log2 fold ST:STUDY_SUMMARY change 2.6-6.9, 3/5 were significant p<0.05) in the mice that received ST:STUDY_SUMMARY nitisinone. Several other metabolites of interest were matched but no ST:STUDY_SUMMARY significant differences were observed, including the aromatic amino acids ST:STUDY_SUMMARY phenylalanine and tryptophan, and monoamine metabolites adrenaline, ST:STUDY_SUMMARY 3-methoxy-4-hydroxyphenylglycol and octopamine. Conclusions: Evaluation of the ST:STUDY_SUMMARY CSF metabolome of a murine model of AKU showed a significant difference in the ST:STUDY_SUMMARY abundance of a limited number of metabolites. None of these have been reported ST:STUDY_SUMMARY in CSF from a murine model of AKU previously. Moreover this study confirms that ST:STUDY_SUMMARY some monoamine metabolites do not appear to be altered following nitisinone ST:STUDY_SUMMARY therapy. ST:INSTITUTE University of Liverpool Institute of Life Course & Medical Sciences ST:LAST_NAME Davison ST:FIRST_NAME Andrew ST:ADDRESS 1. Department of Clinical Biochemistry and Metabolic Medicine, Liverpool ST:ADDRESS Clinical Laboratories, Liverpool University Hospitals NHS Foundation Trust, ST:ADDRESS Liverpool, UK; 2. Department of Musculoskeletal and Ageing Science, Institute of ST:ADDRESS Life Course and Medical Sciences, University of Liverpool, Liverpool, UK 3. ST:ADDRESS School of Exercise Science, Liverpool John Moores University, Liverpool, UK ST:EMAIL andrew.davison@liverpoolft.nhs.uk ST:PHONE 0151 706 4011 ST:NUM_GROUPS 2 ST:TOTAL_SUBJECTS 17 #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 - Hgd81.1 + Nitisinone NEG Treatment group:Nitisinone RAW_FILE_NAME=NEG_AKU_+ NTBC_81.1_CSF SUBJECT_SAMPLE_FACTORS - Hgd81.2 + Nitisinone NEG Treatment group:Nitisinone RAW_FILE_NAME=NEG_AKU_+ NTBC_81.2_CSF SUBJECT_SAMPLE_FACTORS - Hgd81.3 + Nitisinone NEG Treatment group:Nitisinone RAW_FILE_NAME=NEG_AKU_+ NTBC_81.3_CSF SUBJECT_SAMPLE_FACTORS - Hgd82.1 + Nitisinone NEG Treatment group:Nitisinone RAW_FILE_NAME=NEG_AKU_+ NTBC_82.1_CSF SUBJECT_SAMPLE_FACTORS - Hgd82.2 + Nitisinone NEG Treatment group:Nitisinone RAW_FILE_NAME=NEG_AKU_+ NTBC_82.2_CSF SUBJECT_SAMPLE_FACTORS - Hgd83.1 + Nitisinone NEG Treatment group:Nitisinone RAW_FILE_NAME=NEG_AKU_+ NTBC_83.1_CSF SUBJECT_SAMPLE_FACTORS - Hgd83.2 - No treatment NEG Treatment group:Nitisinone RAW_FILE_NAME=NEG_AKU_+ NTBC_83.2_CSF SUBJECT_SAMPLE_FACTORS - Hgd80.3 - No treatment NEG Treatment group:No Treatment (control) RAW_FILE_NAME=NEG_AKU_80.3_CSF SUBJECT_SAMPLE_FACTORS - Hgd80.4 - No treatment NEG Treatment group:No Treatment (control) RAW_FILE_NAME=NEG_AKU_80.4_CSF SUBJECT_SAMPLE_FACTORS - Hgd81.4 - No treatment NEG Treatment group:No Treatment (control) RAW_FILE_NAME=NEG_AKU_81.4_CSF SUBJECT_SAMPLE_FACTORS - Hgd81.5 - No treatment NEG Treatment group:No Treatment (control) RAW_FILE_NAME=NEG_AKU_81.5_CSF SUBJECT_SAMPLE_FACTORS - Hgd81.6 - No treatment NEG Treatment group:No Treatment (control) RAW_FILE_NAME=NEG_AKU_81.6_CSF SUBJECT_SAMPLE_FACTORS - Hgd82.3 - No treatment NEG Treatment group:No Treatment (control) RAW_FILE_NAME=NEG_AKU_82.3_CSF SUBJECT_SAMPLE_FACTORS - Hgd82.4 - No treatment NEG Treatment group:No Treatment (control) RAW_FILE_NAME=NEG_AKU_82.4_CSF SUBJECT_SAMPLE_FACTORS - Hgd83.3 - No treatment NEG Treatment group:No Treatment (control) RAW_FILE_NAME=NEG_AKU_83.3_CSF SUBJECT_SAMPLE_FACTORS - Hgd83.4 - No treatment NEG Treatment group:No Treatment (control) RAW_FILE_NAME=NEG_AKU_83.4_CSF SUBJECT_SAMPLE_FACTORS - Hgd80.2 + Nitisinone POS Treatment group:Nitisinone RAW_FILE_NAME=POS_AKU_+ NTBC_80.2_CSF SUBJECT_SAMPLE_FACTORS - Hgd81.1 + Nitisinone POS Treatment group:Nitisinone RAW_FILE_NAME=POS_AKU_+ NTBC_81.1_CSF SUBJECT_SAMPLE_FACTORS - Hgd81.2 + Nitisinone POS Treatment group:Nitisinone RAW_FILE_NAME=POS_AKU_+ NTBC_81.2_CSF SUBJECT_SAMPLE_FACTORS - Hgd81.3 + Nitisinone POS Treatment group:Nitisinone RAW_FILE_NAME=POS_AKU_+ NTBC_81.3_CSF SUBJECT_SAMPLE_FACTORS - Hgd82.1 + Nitisinone POS Treatment group:Nitisinone RAW_FILE_NAME=POS_AKU_+ NTBC_82.1_CSF SUBJECT_SAMPLE_FACTORS - Hgd82.2 + Nitisinone POS Treatment group:Nitisinone RAW_FILE_NAME=POS_AKU_+ NTBC_82.2_CSF SUBJECT_SAMPLE_FACTORS - Hgd83.1 + Nitisinone POS Treatment group:Nitisinone RAW_FILE_NAME=POS_AKU_+ NTBC_83.1_CSF SUBJECT_SAMPLE_FACTORS - Hgd83.2 - No treatment POS Treatment group:Nitisinone RAW_FILE_NAME=POS_AKU_+ NTBC_83.2_CSF SUBJECT_SAMPLE_FACTORS - Hgd80.3 - No treatment POS Treatment group:No Treatment (control) RAW_FILE_NAME=POS_AKU_80.3_CSF SUBJECT_SAMPLE_FACTORS - Hgd80.4 - No treatment POS Treatment group:No Treatment (control) RAW_FILE_NAME=POS_AKU_80.4_CSF SUBJECT_SAMPLE_FACTORS - Hgd81.4 - No treatment POS Treatment group:No Treatment (control) RAW_FILE_NAME=POS_AKU_81.4_CSF SUBJECT_SAMPLE_FACTORS - Hgd81.5 - No treatment POS Treatment group:No Treatment (control) RAW_FILE_NAME=POS_AKU_81.5_CSF SUBJECT_SAMPLE_FACTORS - Hgd81.6 - No treatment POS Treatment group:No Treatment (control) RAW_FILE_NAME=POS_AKU_81.6_CSF SUBJECT_SAMPLE_FACTORS - Hgd82.3 - No treatment POS Treatment group:No Treatment (control) RAW_FILE_NAME=POS_AKU_82.3_CSF SUBJECT_SAMPLE_FACTORS - Hgd82.4 - No treatment POS Treatment group:No Treatment (control) RAW_FILE_NAME=POS_AKU_82.4_CSF SUBJECT_SAMPLE_FACTORS - Hgd83.3 - No treatment POS Treatment group:No Treatment (control) RAW_FILE_NAME=POS_AKU_83.3_CSF SUBJECT_SAMPLE_FACTORS - Hgd83.4 - No treatment POS Treatment group:No Treatment (control) RAW_FILE_NAME=POS_AKU_83.4_CSF #COLLECTION CO:COLLECTION_SUMMARY A murine model of AKU was used for all experiments as described previously CO:COLLECTION_SUMMARY (Preston et al., 2014). Seventeen BALB/c Hgd-/- mice (Figure 5 for age and CO:COLLECTION_SUMMARY gender) were included in this study, 8 mice were administered nitisinone (4 CO:COLLECTION_SUMMARY mg/L) through their drinking water for 6 days, the remaining 9 mice received no CO:COLLECTION_SUMMARY nitisinone. All animals were housed in air conditioned rooms (with a 12 h CO:COLLECTION_SUMMARY dark/light cycle) at 20 °C and 53 % humidity, with access to food and water ad CO:COLLECTION_SUMMARY libitum at Liverpool John Moores University. All animal experiments complied CO:COLLECTION_SUMMARY with the ARRIVE guidelines and were carried out in accordance with the U.K. CO:COLLECTION_SUMMARY Animals (Scientific Procedures) Act, 1986 and associated guidelines, EU CO:COLLECTION_SUMMARY Directive 2010/63/EU for animal experiments. All mice were culled by carbon CO:COLLECTION_SUMMARY dioxide asphyxiation and CSF was removed from the cisterna magna following the CO:COLLECTION_SUMMARY puncture technique of Liu et al. (56), with some modifications. The cisterna CO:COLLECTION_SUMMARY magna was exposed by dissecting skin and overlaying muscles. Cauterisation was CO:COLLECTION_SUMMARY used to dry up any bleeding from surrounding tissues. A pulled glass pipette CO:COLLECTION_SUMMARY with an internal diameter of ~0.4 mm was attached to silicone tubing and CO:COLLECTION_SUMMARY connected to a 1 mL syringe with a 19 g needle. The tip of the glass pipette was CO:COLLECTION_SUMMARY used to puncture the membrane and held still just below the membrane by 1 CO:COLLECTION_SUMMARY person. Through a double-headed microscope a second person then used the 1 mL CO:COLLECTION_SUMMARY syringe to apply gentle pressure to encourage the CSF to flow up the capillary CO:COLLECTION_SUMMARY tube. Only clear CSF samples (i.e. non blood stained) were collected. Once CO:COLLECTION_SUMMARY collected CSF samples were transferred to clear Eppendorf tubes and stored at CO:COLLECTION_SUMMARY -80 °C until analysis. Samples were not acidified. The same glass pipette was CO:COLLECTION_SUMMARY used to collect CSF from each animal, and was washed with pure water between CO:COLLECTION_SUMMARY each animal. CO:SAMPLE_TYPE CSF #TREATMENT TR:TREATMENT_SUMMARY 9 mice control 8 mice received 4 mg/L nitisinone for 6 days in drinking water #SAMPLEPREP SP:SAMPLEPREP_SUMMARY Murine CSF samples were prepared by diluting 2 µL CSF with 2 µL deionized SP:SAMPLEPREP_SUMMARY water (DIRECT-Q 3UV Millipore water purification system). CSF samples were SP:SAMPLEPREP_SUMMARY pipetted directly into a 150 µL glass insert with polymer feet, which sat in a SP:SAMPLEPREP_SUMMARY 2 mL amber screw vial (Agilent, Cheadle, UK). These vials were used to ensure SP:SAMPLEPREP_SUMMARY maximal recovery of sample. Deionised water was also added directly to the glass SP:SAMPLEPREP_SUMMARY insert, and mixed with the CSF sample using a pipette. The glass vials were SP:SAMPLEPREP_SUMMARY centrifuged at 600 rpm for 10 min to ensure the diluted sample was at the bottom SP:SAMPLEPREP_SUMMARY of the vial for sampling. 1 µL of diluted CSF was analysed in negative and SP:SAMPLEPREP_SUMMARY positive polarities, respectively. #CHROMATOGRAPHY CH:CHROMATOGRAPHY_SUMMARY Liquid chromatography (LC) was performed on an Agilent 1290 Infinity II LC CH:CHROMATOGRAPHY_SUMMARY system. An Atlantis dC18 column (3.0x100mm, 3µm, Waters, UK) was maintained at CH:CHROMATOGRAPHY_SUMMARY 60°C with a flow rate of 0.4mL/min. Mobile phases were (A) water and (B) CH:CHROMATOGRAPHY_SUMMARY methanol both containing 5mmol/L ammonium formate and 0.1% formic acid. The CH:CHROMATOGRAPHY_SUMMARY elution gradient started at 5% mobile phase B at 0-1 min increasing linearly to CH:CHROMATOGRAPHY_SUMMARY 100% B by 12 min, held at 100% B until 14 min, returning to 95% A for 5 min to CH:CHROMATOGRAPHY_SUMMARY recondition the column. Injection volume was 1µL. CH:CHROMATOGRAPHY_TYPE Reversed phase CH:INSTRUMENT_NAME Agilent Infinity II CH:COLUMN_NAME Atlantis dC18 column (3.0x100mm, 3µm, Waters, UK) #ANALYSIS AN:ANALYSIS_TYPE MS #MS MS:INSTRUMENT_NAME Agilent 6550 QTOF MS:INSTRUMENT_TYPE Triple quadrupole MS:MS_TYPE ESI MS:ION_MODE NEGATIVE MS:MS_COMMENTS Quadrupole time-of-flight mass spectrometry (QTOF-MS) conditions An Agilent 6550 MS:MS_COMMENTS QTOF-MS equipped with a dual jet stream electrospray ionisation source was MS:MS_COMMENTS operated in 2GHz mode, over the mass range of 50-1700, in negative and positive MS:MS_COMMENTS polarities. A reference mass correction solution was continually infused at a MS:MS_COMMENTS flow rate of 0.5 mL/min via an external isocratic pump (Agilent, UK) for MS:MS_COMMENTS constant mass correction (see Preparation of reference mass correction MS:MS_COMMENTS solution). Capillary and fragmentor voltages were 4000 V and 380 V, MS:MS_COMMENTS respectively. Desolvation gas temperature was 200 °C with flow rate at 15 MS:MS_COMMENTS L/min. The sheath gas temperature was 300 °C with flow rate at 12 L/min and MS:MS_COMMENTS nebulizer pressure was 40 psi and nozzle voltage 1000 V. Data acquisition rate MS:MS_COMMENTS was 3 spectra/s. Preparation of reference mass correction solution Reference MS:MS_COMMENTS mass correction solution was prepared in 95:5 methanol:water containing 5 mmol/L MS:MS_COMMENTS purine (CAS No. 120-73-0), 100 mmol/L trifluoroacetic acid ammonium salt (TFA, MS:MS_COMMENTS CAS No. 3336-58-1) and 2.5 mmol/L hexakis(1H, 1H, MS:MS_COMMENTS 3H-tetrafluoropropoxy)phosphazine (HP-0921, CAS No. 58943-98-9) (Agilent, MS:MS_COMMENTS Cheadle, UK). Reference ions monitored were: purine (m/z 121.0509) and HP-0921 MS:MS_COMMENTS (m/z 922.0098) (positive polarity) and TFA (m/z 112.9856), purine (m/z 119.0363) MS:MS_COMMENTS and HP-0921 (HP-0921 + formate adduct: m/z 966.0007) (negative polarity). Data MS:MS_COMMENTS acquisition and handling parameters Data were acquired using Acquisition (Build MS:MS_COMMENTS 06.00, Agilent, Cheadle, UK). Quality checks and processing of raw data files MS:MS_COMMENTS (Agilent ‘.d’ files) were performed with Qualitative Analysis software MS:MS_COMMENTS (Build 07.00, Agilent, Cheadle, UK). Extracted ion chromatograms of reference MS:MS_COMMENTS masses were performed to check mass accuracy remained <5 ppm throughout the run MS:MS_COMMENTS and that the reference ion signal did not drop out during the chromatographic MS:MS_COMMENTS run. In addition, to check chromatographic reproducibility binary pump pressure MS:MS_COMMENTS curves for injections across each analytical sequence were overlaid. Mass MS:MS_COMMENTS accuracy and chromatographic reproducibility were acceptable for all experiments MS:MS_COMMENTS performed. Acquired profiling sample data were mined for signals against an MS:MS_COMMENTS established in-house AMRT database of compounds (contains theoretical accurate MS:MS_COMMENTS mass, measured retention time, and empirical formula for 469 intermediary MS:MS_COMMENTS metabolites, MW 72-785) using ‘targeted feature extraction’ with Profinder MS:MS_COMMENTS software (Build 08.00, Agilent, Cheadle, UK). Targeted feature extraction uses MS:MS_COMMENTS the molecular formulae from the AMRT database to extract and group spectral MS:MS_COMMENTS signals (i.e. adducts, isotopes and multimers) that correspond to individual MS:MS_COMMENTS database compounds. Feature extraction employed a window of theoretical accurate MS:MS_COMMENTS mass ±10 ppm and database retention time ±0.3 min. Allowed species were: H+, MS:MS_COMMENTS Na+ and NH4+ (positive polarity) and H- and CHO2- (negative polarity). Dimers MS:MS_COMMENTS were allowed for both polarities. Charge state range was 1-2. Data files were MS:MS_COMMENTS then exported from Profinder as ‘.CEF’ files as a whole batch for each MS:MS_COMMENTS profiling experiment and imported to Mass Profiler Professional (MPP) software MS:MS_COMMENTS for statistical analysis (Build 14.5, Agilent, Cheadle, UK). #MS_METABOLITE_DATA MS_METABOLITE_DATA:UNITS area MS_METABOLITE_DATA_START Samples Hgd81.1 + Nitisinone NEG Hgd81.2 + Nitisinone NEG Hgd81.3 + Nitisinone NEG Hgd82.1 + Nitisinone NEG Hgd82.2 + Nitisinone NEG Hgd83.1 + Nitisinone NEG Hgd83.2 - No treatment NEG Hgd80.3 - No treatment NEG Hgd80.4 - No treatment NEG Hgd81.4 - No treatment NEG Hgd81.5 - No treatment NEG Hgd81.6 - No treatment NEG Hgd82.3 - No treatment NEG Hgd82.4 - No treatment NEG Hgd83.3 - No treatment NEG Hgd83.4 - No treatment NEG Factors Treatment group:Nitisinone Treatment group:Nitisinone Treatment group:Nitisinone Treatment group:Nitisinone Treatment group:Nitisinone Treatment group:Nitisinone Treatment group:Nitisinone Treatment group:No Treatment (control) Treatment group:No Treatment (control) Treatment group:No Treatment (control) Treatment group:No Treatment (control) Treatment group:No Treatment (control) Treatment group:No Treatment (control) Treatment group:No Treatment (control) Treatment group:No Treatment (control) Treatment group:No Treatment (control) Inosine 1128769 600575 750496 1462769 1081718 1146996 1220644 939141 925632 1077156 1152140 1134742 1056061 1044233 1287162 1216464 Adipic acid 9009 1 43272 20022 11036 17297 105525 11153 9282 11231 16915 10864 32357 31038 11722 23134 Sarcosine 217770 147203 282444 994577 496851 251892 302044 244631 5745 210810 285484 376666 175021 407808 299528 233228 Ethylmalonic acid 19773 19126 21867 48514 63018 17879 43690 15494 28961 14809 31800 27553 19485 44167 29256 32284 D-(-)-Lyxose 278483 163289 181334 201718 245345 187892 206847 235213 199127 244772 322068 224985 216133 197387 244992 346072 Hippuric acid 2412 1 1 5434 3354 1 3028 3474 3182 600 15233 4499 1144 4175 1 2190 Uridine monophosphate (UMP) 1 1 1 30086 7092 1 1 10320 121338 1 3706 1 1 11672 1 1725 Methyl jasmonate 8881 13159 10510 8229 12124 11495 10983 10348 8196 10797 10048 14307 13706 4872 11810 9912 Dulcitol 55303 27062 29867 46732 41499 45039 35229 54540 44443 40408 148242 47346 32609 41290 43610 32190 Galactaric acid 48382 1 1 69057 1 1 55759 33817 114492 55835 77637 52185 441202 76819 74688 1 meso-Tartaric acid 1 21326 37919 114442 27532 1 1 97576 227109 32080 37255 48418 39909 112178 1 1 Hypoxanthine 891435 469625 717384 1058502 976339 800484 815486 711909 684307 600007 847670 727415 667770 856116 737045 779124 Phosphocreatine 17913 12358 1 22265 1 15307 18793 25432 25971 19550 20785 18714 37834 21835 21115 25110 Thymidine 7050 1 5108 7456 7577 7567 7607 5855 1 5865 6233 6457 7059 7469 6903 7760 Orotic acid 130834 78807 79097 66028 78837 79447 106516 120671 98824 131426 110715 101884 130432 104003 105175 144899 Uric acid 260623 166502 234730 218442 245572 241133 253019 236867 202750 198674 261913 239876 222290 152171 270200 293044 Gluconic acid 1390079 672667 920394 1456643 1473088 1241182 1178866 1638406 1205748 1225294 1435025 1225167 1474564 1568685 1499215 1314853 Aceturic acid 11347 1 1 1 1 1 1 1 1 9742 1 1 13135 12098 10595 1 ?-Linolenic Acid 1 1727 1 1548 1407 1 2391 1 3032 1 1 1 1989 7178 1 1 L-Tryptophan 30486 16706 26212 26666 26745 24586 38620 30869 33063 24125 40285 32731 14159 29862 32632 43392 Cytidine 16632 11513 14980 18469 19805 17800 18307 15140 12932 15297 16479 17222 14221 18985 16382 15694 L-Threonine 48560 117283 95799 43820 63163 62046 66332 63431 55995 54300 63861 64302 33153 52984 78782 87400 4-Hydroxyphenyllactic acid 1376458 536068 604074 1298520 811041 865084 978715 30188 32308 29815 34761 38660 42736 36405 44618 55018 Malic acid 825379 559524 1060503 3585395 2028170 949236 1855575 888399 979005 834057 1398644 2045739 1107212 2247099 1339087 1526760 L-Isoleucine 25892 18253 10342 47403 34682 29152 37252 31283 28531 26649 31988 31053 24939 14800 35529 36085 N-Acetyl-L-glutamic acid 1 1 1 1 1 1 1 1 1 1 1 1 1 23759 1 1 D-Mannitol 55303 27062 29867 46732 41499 45039 35229 54540 44443 40408 148242 47346 32609 41290 43610 32190 L-Aspartic Acid 114303 44461 79175 99559 101651 89570 94463 92501 1 78718 113746 78106 92289 116478 92698 135695 Myristic acid 1 2910 1 2618 1 2458 3000 1 1907 1 1 1 2671 5225 1 1 phosphoenol pyruvate 1 1 1 246210 42275 1 26911 31493 45026 29480 25286 19327 1 89739 35380 40275 Oxoglutaric acid 11050 10611 20916 37807 26686 1 9974 218196 61542 58659 15379 17825 17888 19536 60255 14341 Citric acid 2039994 2446245 2471211 3749292 4156968 2197859 3406313 2426531 2756584 2440273 3659776 3753129 5294389 4533789 2938319 3364858 Succinic acid 261864 204846 348569 700447 811825 319805 674079 199920 319347 203442 417370 406116 235224 711046 437307 402747 Methyl N-(a-methylbutyryl)glycine 34583 32491 288107 84954 59610 84977 595783 49514 39168 55642 74959 61644 828908 154006 62365 72866 D-Aspartic acid 114635 44633 79627 100265 102256 89703 94894 92550 1 78718 114250 78649 92511 117101 92897 136217 12-Hydroxydodecanoic acid 1 6698 15217 5546 7639 7047 25442 5000 1 1 1 4608 13909 10171 1 4799 Pantothenic Acid 450261 269316 335589 314520 320484 560943 582807 505320 552106 532948 609399 481084 264297 311180 647807 665806 Dehydroascorbic acid 53897 18043 36011 1 33845 42492 49049 40601 20216 22724 61738 36802 46718 12208 47105 54602 Glutamine 1688220 1453556 1616356 1447027 1819199 1555354 1639762 1795624 1694370 1492094 1696140 1605798 1485114 1702206 1810762 1652460 Arabinose 278482 163289 181334 201718 245345 187892 206850 235213 199127 244772 322068 224985 216133 197387 244992 346072 Palmitic acid 34909 35665 34944 44299 47212 41272 39666 40482 41344 36536 37368 38499 36586 51786 38053 37278 Itaconic acid 16775 17403 18824 24675 25646 26541 26347 17191 15951 16895 11471 29083 26193 17821 21518 20265 DL-a-Hydroxybutyric acid 24167 75119 27120 68574 99855 27156 48896 23890 52315 36367 58498 50304 52586 100495 27376 39148 Adenosine5'-monophosphate 1 5824 45308 396358 30994 12303 7965 26690 95369 23480 17710 4715 18060 169935 7567 11444 D-Mannose 6-phosphate 8969 1 35419 114088 40176 1 27439 1 41603 13533 29840 1 1 44126 10400 1 Dihydroxyacetone phosphate 1 29206 22413 191209 21096 1 23609 1 1 1 4013 1 1 53487 1 1 a-N-Acetylglucosamine 1 1 1 8477 1 1 1 1 8285 8124 1 1 1 8202 1 1 N-Acetyl-DL-serine 267193 109833 150007 101758 119872 215604 207582 186052 140090 176672 183125 166533 188559 183457 222128 247464 Linoleic acid 14059 19087 16661 42002 15802 15811 23173 22093 33321 15774 14762 20432 26726 70706 15682 16625 L-Anserine 23065 9103 9280 25784 13020 16788 21182 21669 18627 16612 21861 16405 20501 18328 22659 22332 D-Fructose 6-phosphate 8969 1 35419 114088 40176 1 27439 1 41603 13533 29840 1 1 44126 10400 1 Maleic acid 26932 33022 30552 24647 54659 61853 48042 36833 27130 31288 1 48684 38852 37116 31762 52326 Pimelic acid 1 1 18312 1 1 6219 36522 1 1 1 5040 1 15589 11247 1 7799 Suberic acid 16537 13107 96177 27733 22775 24653 168704 19923 17174 23032 29458 19621 69454 49335 24327 25998 tartaric acid 1 21326 37919 114442 27532 1 1 97576 227109 32080 37255 48418 39909 112178 1 1 D-Ribose 278479 163289 181334 201718 245345 187892 206866 235213 199127 244772 322068 224985 216133 197387 244992 346072 ?-D-Glucose 1-phosphate 8969 1 35419 114088 40176 1 27439 1 41603 13533 29840 1 1 44126 10400 1 Xanthine 515121 273122 462125 591375 568278 459478 486384 409252 383343 340912 465477 466259 446330 508223 430102 353640 Glyceryl phosphate 265991 241780 395647 495986 461139 273197 286019 400200 365513 263601 347804 376373 197980 481055 324324 301046 L-Norleucine 25849 18253 10342 47403 34682 29152 37252 31102 28552 26649 32009 31082 24954 14800 35507 36122 L-Serine 26769 60674 49098 26684 37131 32851 29564 29476 24545 33000 31137 37984 19663 30071 42374 43469 Xanthosine 6821 1 1 6878 6115 5969 1 4520 1 3227 4512 3259 1 8864 2405 3736 D-(+)-Xylose 278483 163289 181334 201718 245345 187892 206847 235213 199127 244772 322068 224985 216133 197387 244992 346072 N-Acetyl-?-D-mannosamine 1 1 1 8477 1 1 1 1 8285 8124 1 1 1 8202 1 1 DL-Homoserine 48560 117283 95799 43820 63163 62046 66332 63431 55995 54300 63861 64302 33153 52984 78782 87400 D-(+)-Malic acid 803962 533285 1030614 3495055 1979574 927578 1802824 870857 974210 805193 1368476 1972900 1076367 2200004 1297429 1483643 L-Phenylalanine 69288 35148 43927 82162 66328 57555 71332 63719 60992 48777 75370 67295 50312 70100 62896 76246 3-hydroxy-3-methyl-Glutaric acid 21702 12301 19098 21721 31997 23921 26413 21315 26070 13292 27946 39954 30935 22679 31467 18824 L-Methionine 49274 27827 43066 51075 46460 49064 51330 56934 50853 33160 52568 48958 34571 44007 50786 51083 ?-D-Glucose 394687 425412 285885 199750 66344 52674 26196 23025 180623 249120 229114 30677 195056 31615 27162 28018 Nicotinamide adenine dinucleotide (NAD) 1 1 2493 2273 1 1 1 1 1 1 1 1 1 11755 1 1 Elaidic Acid 53739 61404 52523 90076 55377 55596 67188 65363 76034 60907 53296 61659 60182 112295 56588 57842 N-Acetyl-L-alanine 20352 11111 13453 22539 19069 16985 20914 16604 16445 16714 20535 19519 20102 21077 19894 18621 cis-9-palmitoleic acid 5747 10898 9344 16623 6601 9606 34882 6988 9842 7983 3897 7980 11279 39558 10665 9455 trans-Aconitate 226505 151786 190795 231769 401135 203920 234898 247130 309868 198857 322855 457119 253854 363646 305449 255774 Citramalic acid 44627 6957 18579 62722 65274 12274 21415 76314 51444 12967 49801 30311 67405 12040 17359 73762 4-Hydroxybenzaldehyde 1 1 1 12621 7171 5541 9988 1 1 5060 1 1 1 14714 1 1 ?-Alanine 217770 147203 282444 994577 496849 251892 302044 244631 240431 210810 285484 376666 175021 407808 299488 233228 Glyoxylic acid 62670 1 74766 90064 82327 83204 90348 77549 75664 98154 1 87415 84347 133381 1 76553 Inosine 5'-monophosphate (IMP) 1 1 1 406858 1 1 1 1 1 1 1 1 13549 24727 1 1 Taurine 194490 250695 371728 1546039 688593 260088 333158 184756 223268 217557 300648 375004 160310 372510 308488 236042 D-Glucuronic acid 118644 62984 90324 131243 125282 103792 99224 174578 121976 192105 132867 107278 122458 171074 127769 115361 L-Asparagine 1 7766 9648 1 1 6892 1 1 1 1 1 1 1 6815 1 8595 D-(+)-GALACTURONIC ACID 118644 62984 90324 131243 125282 103792 99224 174578 121976 192105 132867 107278 122458 171074 127769 115361 Urocanic acid 376708 311405 263657 172839 329815 369087 381179 197665 163466 323606 385710 330231 318293 209005 429552 455551 D-Glucose 6-phosphate 8969 1 35419 114088 40176 1 27439 1 41603 13533 29840 1 1 44126 10400 1 Retinoic acid 27649 33858 36904 26932 29124 28424 42014 26929 29583 27271 27320 26764 28312 34435 27159 30553 Allantoin 41924 38990 58030 52013 50770 46315 37962 74725 61883 61628 47138 44588 46072 67122 48610 41878 L-Lysine 23126 22649 20571 19611 17418 23171 20338 25572 26806 26777 19345 22067 27243 16559 12984 32910 Allothreonine 48560 117283 95799 43820 63163 62046 66332 63431 55995 54300 63861 64302 33153 52984 78782 87400 Citrulline 10971 8183 9961 12245 10089 10483 13429 13102 12108 11845 14161 15230 1 13065 13840 38570 D-Tryptophan 30486 16706 26212 26666 26745 24586 38620 30869 33063 24125 40285 32731 14159 29862 32632 43392 Isocitrate 1273843 466382 684960 176292 1004184 962509 1098103 826469 817903 930663 1735094 872804 1267581 4399441 1147744 1591957 Glycerol 2-phosphate 265991 241780 395647 495986 461139 273197 286019 400200 365513 263601 347804 376373 197980 481055 324324 301046 3-Hydroxybenzaldehyde 1 1 1 12621 7169 5541 9988 1 1 5060 1 1 1 14714 1 1 D-Sorbitol 55303 27062 29867 46732 41499 45039 35229 54540 44443 40408 148242 47346 32609 41290 43610 32190 ?-D-Galactose 1-phosphate 8969 1 35419 114088 40176 1 27439 1 41603 13533 29840 1 1 44126 10400 1 Uridine 543288 298498 401553 629180 519181 560797 565114 407336 385598 421635 479753 440789 458179 509094 462782 500018 2-hydroxy-butanoic acid 24167 75119 27120 68574 99794 27155 48896 23890 52315 36367 58498 50304 52586 100570 27376 39177 L-Norvaline 10052 6257 1 14132 11076 8181 10652 10916 1 7899 11645 10374 7996 10694 12122 12024 L-Leucine 25862 18253 10342 47403 34682 29152 37252 31107 28548 26649 32004 31076 24951 14800 35515 36114 Lauric acid 1 1 1 1 1 1 2240 1 1 1 1 1 1 1516 1 1 L-Arginine 23747 18352 20518 23524 24526 23225 28969 28619 29030 25920 32885 30850 27638 30997 28829 34027 Fumaric acid 26932 33022 30552 24647 54659 61853 48042 36833 27144 31288 1 48684 38852 37116 31762 52326 Stearic acid 16607 17329 16673 22043 41516 18105 20340 20345 23894 18521 19043 16731 16896 25601 19541 19006 L-Tyrosine 786327 439203 521239 771238 638155 648572 808583 70103 75230 52644 85508 77829 62135 84383 106267 104767 (4Z,7Z,10Z,13Z,16Z,19Z)-4,7,10,13,1 6,19-Docosahexaenoic acid 1961 1 1 77214 3410 1802 1408 14093 31980 7374 1963 12102 4205 42372 1943 1191 N-acetylaspartate 350364 224128 452949 263134 315184 491038 737232 228688 747485 311765 402382 917572 132306 292135 502995 403900 3-Methylglutaric acid 9009 1 43272 20497 11036 17297 105525 11153 9282 11231 16915 10864 32357 31038 11722 23134 Pyridoxal (Vitamin B6) 13568 1 7430 1 6059 15287 12185 9538 11241 11280 12208 12249 12249 10656 15230 9066 N-Acetylneuraminic Acid 1589609 1325414 1561745 1695347 1216490 1470361 1325846 1882922 1770237 1742253 1465367 1492001 1513459 1658889 1535410 1356779 D-(-)-Arabinose 278483 163289 181334 201718 245345 187892 206850 235213 199127 244772 322068 224985 216133 197387 244992 346072 Malonic acid 93926 62826 77042 57132 75838 89558 96383 88775 70995 93374 105914 144004 111805 79206 124228 125665 2-Methylglutaric acid 9009 1 43272 20497 11036 17297 105525 11153 9282 11231 16915 10864 32357 31038 11722 23134 Adenine 228682 121071 169742 108467 146409 284558 286644 171133 153601 133866 175851 180113 169274 180367 306238 208266 Pyroglutamic acid 498716 353848 333422 717282 469822 361549 458484 541186 422830 421049 595883 638384 445500 542838 640164 857606 Uracil 154499 71139 102309 124731 154816 131300 120897 123079 84890 101380 136212 106810 33813 94038 112612 111689 L-Valine 10052 6257 1 14132 11076 8181 10652 10916 1 7899 11645 10374 7996 10694 12122 12024 N-ALPHA-ACETYL-L-ASPARAGINE 48715 12955 24533 13692 23663 31060 28527 27991 20208 25837 29334 18646 35170 27583 30558 45534 L-Histidine 20001 16163 1 14508 1 15375 18081 13711 1 14642 14867 1 16310 1 17940 21019 Acetyl-L-tyrosine 4251 1 1 4043 2609 3569 4342 1 1 1 1 1 1 1 1 1 Guanosine 37039 24135 11759 11384 18974 39053 46198 20091 11075 39468 38564 46700 29335 1 49793 40580 NTBC HT-1 25255 14303 24763 37774 13604 14287 18481 1 1 1 1 1 1 1 13511 1 2,5-Dihydroxybenzaldehyde 3881 1569 1 1 1 1 6601 1 1 3815 4940 1 1 1 1 1 3-(2-Hydroxyphenyl)propionic acid 1 3484 1 1 5703 1 5940 1 1 1 1 1 1 1 1 1 4-Pyridoxic acid 1 4073 1 1 6881 6583 7297 1 1 1 7319 8552 1 1 1 1 Deoxyuridine monophosphate (dUMP) 1 1 1 1 1 1 14468 1 1 1 1 1 1 1 14193 1 O-Phosphorylethanolamine 1 1 12569 1 15125 1 1 9354 16998 1 1 1 6300 1 7999 1 Glucuronolactone 1 1 1 1 1 1 1 1 1 130315 1 1 1 1 1 1 Quinic acid 1 1 1 1 1 1 1 1 1 1 31959 1 1 1 1 32017 Methylglyoxal 1 1 1 1 1 1 1 1 1 1 43922 1 1 1 1 1 Glutamyl-Tyrosine 1 1 1 1 1 1 1 1 1 1 1 1 1 1 2400 1 ?,?-Trehalose 1 1 1 1 1 1 1 1 1 1 1 1 13131 1 1 1 Phenyl acetate 1 1 1524 1 1 3102 1 1 1 1 1 1 1 1 1 1 L-Ornithine 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 11604 MS_METABOLITE_DATA_END #METABOLITES METABOLITES_START metabolite_name Mass Retention Time CAS Number Inosine 268.0816 2.9830005 58-63-9 Adipic acid 146.058 4.6969995 124-04-9 Sarcosine 89.0481 1.367 107-97-1 Ethylmalonic acid 132.0422 3.9659998 601-75-2 D-(-)-Lyxose 150.0531 1.5060003 1114-34-7 Hippuric acid 179.0588 5.6160007 495-69-2 Uridine monophosphate (UMP) 324.0359 1.71 58-97-9 Methyl jasmonate 224.1413 10.360998 39924-52-2 Dulcitol 182.0792 1.351 608-66-2 Galactaric acid 210.0381 1.356 526-99-8 meso-Tartaric acid 150.0169 1.4540001 147-73-9 Hypoxanthine 136.0389 2.1690001 68-94-0 Phosphocreatine 211.0373 1.389 67-07-2 Thymidine 242.0904 3.9710004 50-89-5 Orotic acid 156.0172 1.7539998 65-86-1 Uric acid 168.0287 2.004 69-93-2 Gluconic acid 196.0592 1.353 526-95-4 Aceturic acid 117.0428 1.699 543-24-8 ?-Linolenic Acid 278.2244 13.231001 506-26-3 L-Tryptophan 204.09 4.61 73-22-3 Cytidine 243.0858 1.531 65-46-3 L-Threonine 119.0581 1.3150003 72-19-5 4-Hydroxyphenyllactic acid 182.0585 4.8720007 6482-98-0 Malic acid 134.0219 1.6189996 6915-15-7 L-Isoleucine 131.0951 2.657 73-32-5 N-Acetyl-L-glutamic acid 189.0643 2.274 1188-37-0 D-Mannitol 182.0792 1.351 69-65-8 L-Aspartic Acid 133.0375 1.545 56-84-8 Myristic acid 228.2093 13.173002 544-63-8 phosphoenol pyruvate 167.983 1.5760001 138-08-9 Oxoglutaric acid 146.022 1.7859998 328-50-7 Citric acid 192.0279 1.8859998 77-92-9 Succinic acid 118.0266 2.326 110-15-6 Methyl N-(a-methylbutyryl)glycine 188.1053 8.199999 123-99-9 D-Aspartic acid 133.0375 1.545 1783-96-6 12-Hydroxydodecanoic acid 216.173 10.632001 505-95-3 Pantothenic Acid 219.1115 4.354 137-08-6 Dehydroascorbic acid 174.0167 1.6079999 490-83-5 Glutamine 146.0695 1.3 56-85-9 Arabinose 150.0531 1.5060003 147-81-9 Palmitic acid 256.2402 13.606998 57-10-3 Itaconic acid 130.0269 3.2890005 97-65-4 DL-a-Hydroxybutyric acid 104.0474 3.1549997 600-15-7 Adenosine5'-monophosphate 347.0635 1.7999997 149022-20-8 D-Mannose 6-phosphate 260.0264 1.3529999 3672-15-9 Dihydroxyacetone phosphate 169.9981 1.3599999 57-04-5 a-N-Acetylglucosamine 221.0901 1.469 7512-17-6 N-Acetyl-DL-serine 147.0536 1.691 94-14-3 Linoleic acid 280.2404 13.445002 60-33-3 L-Anserine 240.1221 1.286 10030-52-1 D-Fructose 6-phosphate 260.0264 1.3529999 643-13-0 Maleic acid 116.0112 2.1790004 110-16-7 Pimelic acid 160.074 5.986 111-16-0 Suberic acid 174.0893 7.18 505-48-6 tartaric acid 150.0169 1.4540001 87-69-4 D-Ribose 150.0531 1.5060003 50-69-1 ?-D-Glucose 1-phosphate 260.0264 1.3529999 59-56-3 Xanthine 152.034 2.3800006 69-89-6 Glyceryl phosphate 172.0143 1.3689997 57-03-4 L-Norleucine 131.0951 2.657 327-57-1 L-Serine 105.0424 1.2889998 56-45-1 Xanthosine 284.0761 3.539 146-80-5 D-(+)-Xylose 150.0531 1.5060003 58-86-6 N-Acetyl-?-D-mannosamine 221.0901 1.469 7772-94-3 DL-Homoserine 119.0581 1.3150003 1927-25-9 D-(+)-Malic acid 134.0219 1.6189996 636-61-3 L-Phenylalanine 165.0794 3.813 63-91-2 3-hydroxy-3-methyl-Glutaric acid 162.0534 2.78 503-49-1 L-Methionine 149.0513 1.8570002 63-68-3 ?-D-Glucose 180.0634 1.332 492-62-6 Nicotinamide adenine dinucleotide (NAD) 663.1075 1.861 53-84-9 Elaidic Acid 282.256 13.690998 112-79-8 N-Acetyl-L-alanine 131.0584 2.6139998 97-69-8 cis-9-palmitoleic acid 254.2249 13.328999 373-49-9 trans-Aconitate 174.0167 2.292 4023-65-8 Citramalic acid 148.0377 2.4090002 2306-22-1 4-Hydroxybenzaldehyde 122.0371 5.944 123-08-0 ?-Alanine 89.0481 1.368 107-95-9 Glyoxylic acid 74.0007 1.457 298-12-4 Inosine 5'-monophosphate (IMP) 348.0472 1.919 131-99-7 Taurine 125.0148 1.293 107-35-7 D-Glucuronic acid 194.043 1.34 03-12-6556 L-Asparagine 132.053 1.289 70-47-3 D-(+)-GALACTURONIC ACID 194.043 1.34 91510-62-2 Urocanic acid 138.0421 1.413 104-98-3 D-Glucose 6-phosphate 260.0264 1.3529999 56-73-5 Retinoic acid 300.209 13.020003 302-79-4 Allantoin 158.0441 1.3929998 97-59-6 L-Lysine 146.1053 1.1099999 56-87-1 Allothreonine 119.0581 1.3150003 144-98-9 Citrulline 175.0961 1.3190001 372-75-8 D-Tryptophan 204.09 4.61 153-94-6 Isocitrate 192.0279 1.6079999 320-77-4 Glycerol 2-phosphate 172.0143 1.3689997 17181-54-3 3-Hydroxybenzaldehyde 122.0371 5.944 100-83-4 D-Sorbitol 182.0792 1.351 50-70-4 ?-D-Galactose 1-phosphate 260.0264 1.3529999 2255-14-3 Uridine 244.0703 2.2700002 58-96-8 2-hydroxy-butanoic acid 104.0474 3.1549997 600-15-7 L-Norvaline 117.0794 1.6730002 6600-40-4 L-Leucine 131.0951 2.657 61-90-5 Lauric acid 200.1774 12.625 143-07-7 L-Arginine 174.1115 1.2679999 74-79-3 Fumaric acid 116.0112 2.1790004 110-17-8 Stearic acid 284.2713 13.988999 57-11-4 L-Tyrosine 181.0743 2.2229998 60-18-4 (4Z,7Z,10Z,13Z,16Z,19Z)-4,7,10,13,1 6,19-Docosahexaenoic acid 328.2402 13.384002 6217-54-5 N-acetylaspartate 175.0484 1.8700004 997-55-7 3-Methylglutaric acid 146.058 4.6969995 626-51-7 Pyridoxal (Vitamin B6) 167.0586 1.743 66-72-8 N-Acetylneuraminic Acid 309.107 1.4570001 131-48-6 D-(-)-Arabinose 150.0531 1.5060003 10323-20-3 Malonic acid 104.011 1.691 141-82-2 2-Methylglutaric acid 146.058 4.6969995 617-62-9 Adenine 135.0546 1.7339997 73-24-5 Pyroglutamic acid 129.0431 2.114 98-79-3 Uracil 112.0274 1.8559995 66-22-8 L-Valine 117.0794 1.6730002 72-18-4 N-ALPHA-ACETYL-L-ASPARAGINE 174.0645 1.6329999 4033-40-3 L-Histidine 155.0691 1.2869998 71-00-1 Acetyl-L-tyrosine 223.085 5.041 537-55-3 Guanosine 283.092 3.0289996 118-00-3 NTBC HT-1 329.0511 10.38 104206-65-7 2,5-Dihydroxybenzaldehyde 138.0322 5.407 1194-98-5 3-(2-Hydroxyphenyl)propionic acid 166.0629 6.913 495-78-3 4-Pyridoxic acid 183.0534 3.268 82-82-6 Deoxyuridine monophosphate (dUMP) 308.0422 1.933 964-26-1 O-Phosphorylethanolamine 141.0193 1.288 1071-23-4 Glucuronolactone 176.0326 1.519 32449-92-6 Quinic acid 192.0637 1.492 77-95-2 Methylglyoxal 72.0214 1.936 78-98-8 Glutamyl-Tyrosine 310.1196 3.893 9046-27-9 ?,?-Trehalose 342.1077 1.3 99-20-7 Phenyl acetate 136.0524 4.87 122-79-2 L-Ornithine 132.0896 1.319 3184-13-2 METABOLITES_END #END