#METABOLOMICS WORKBENCH roser09_20241022_085609 DATATRACK_ID:5303 STUDY_ID:ST003566 ANALYSIS_ID:AN006190 PROJECT_ID:PR002200 VERSION 1 CREATED_ON March 5, 2025, 10:20 am #PROJECT PR:PROJECT_TITLE Unraveling cysteine deficiency-associated rapid weight loss PR:PROJECT_SUMMARY Forty percent of the US population and 1 in 6 individuals worldwide are obese, PR:PROJECT_SUMMARY with the incidence surging globally. Various dietary interventions, including PR:PROJECT_SUMMARY carbohydrate, fat and more recently amino acid restriction, have been explored PR:PROJECT_SUMMARY to combat this epidemic. We investigated the impact of removing individual PR:PROJECT_SUMMARY amino acids on the weight profiles of mice. Here, we show that conditional PR:PROJECT_SUMMARY cysteine restriction resulted in the most dramatic weight loss when compared to PR:PROJECT_SUMMARY essential amino acid restriction, amounting to 30% within one week, which was PR:PROJECT_SUMMARY readily reversed. We found that cysteine deficiency activated the integrated PR:PROJECT_SUMMARY stress response and oxidative stress response, which amplify each other, leading PR:PROJECT_SUMMARY to the induction of GDF15 and FGF21, which partly explained the phenotype. PR:PROJECT_SUMMARY Surprisingly, we observed lower tissue coenzyme A (CoA), which has been PR:PROJECT_SUMMARY considered to be extremely stable10, resulting in reduced mitochondrial PR:PROJECT_SUMMARY functionality and metabolic rewiring. This results in energetically inefficient PR:PROJECT_SUMMARY anaerobic glycolysis and defective TCA cycle, with sustained urinary excretion PR:PROJECT_SUMMARY of pyruvate, orotate, citrate, α-ketoglutarate, nitrogen rich compounds, and PR:PROJECT_SUMMARY amino acids In summary, our investigation reveals that cysteine restriction, by PR:PROJECT_SUMMARY depleting GSH and CoA, exerts a maximal impact on weight loss, metabolism, and PR:PROJECT_SUMMARY stress signaling compared to other amino acid restrictions. These findings PR:PROJECT_SUMMARY suggest novel strategies for addressing a range of metabolic diseases and the PR:PROJECT_SUMMARY growing obesity crisis. PR:INSTITUTE NYU Grossman School of Medicine PR:LAST_NAME Varghese PR:FIRST_NAME Alan PR:ADDRESS 550 First Avenue, NY, NY 10016 PR:EMAIL Alan.Varghese@nyulangone.org PR:PHONE 212-263-7520 #STUDY ST:STUDY_TITLE Unraveling cysteine deficiency-associated rapid weight loss ST:STUDY_SUMMARY Forty percent of the US population and 1 in 6 individuals worldwide are obese, ST:STUDY_SUMMARY with the incidence surging globally. Various dietary interventions, including ST:STUDY_SUMMARY carbohydrate, fat and more recently amino acid restriction, have been explored ST:STUDY_SUMMARY to combat this epidemic. We investigated the impact of removing individual ST:STUDY_SUMMARY amino acids on the weight profiles of mice. Here, we show that conditional ST:STUDY_SUMMARY cysteine restriction resulted in the most dramatic weight loss when compared to ST:STUDY_SUMMARY essential amino acid restriction, amounting to 30% within one week, which was ST:STUDY_SUMMARY readily reversed. We found that cysteine deficiency activated the integrated ST:STUDY_SUMMARY stress response and oxidative stress response, which amplify each other, leading ST:STUDY_SUMMARY to the induction of GDF15 and FGF21, which partly explained the phenotype. ST:STUDY_SUMMARY Surprisingly, we observed lower tissue coenzyme A (CoA), which has been ST:STUDY_SUMMARY considered to be extremely stable10, resulting in reduced mitochondrial ST:STUDY_SUMMARY functionality and metabolic rewiring. This results in energetically inefficient ST:STUDY_SUMMARY anaerobic glycolysis and defective TCA cycle, with sustained urinary excretion ST:STUDY_SUMMARY of pyruvate, orotate, citrate, α-ketoglutarate, nitrogen rich compounds, and ST:STUDY_SUMMARY amino acids In summary, our investigation reveals that cysteine restriction, by ST:STUDY_SUMMARY depleting GSH and CoA, exerts a maximal impact on weight loss, metabolism, and ST:STUDY_SUMMARY stress signaling compared to other amino acid restrictions. These findings ST:STUDY_SUMMARY suggest novel strategies for addressing a range of metabolic diseases and the ST:STUDY_SUMMARY growing obesity crisis. ST:INSTITUTE NYU Grossman School of Medicine ST:LAST_NAME Varghese ST:FIRST_NAME Alan ST:ADDRESS 550 First Avenue, NY, NY 10016 ST:EMAIL Alan.Varghese@nyulangone.org ST:PHONE 212-263-7520 #SUBJECT SU:SUBJECT_TYPE Mammal SU:SUBJECT_SPECIES Mus musculus SU:TAXONOMY_ID 10090 #FACTORS #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 - AMP WT1 Factor:Wild Type | Sample source:Stool RAW_FILE_NAME(Raw file name)=S30609 SUBJECT_SAMPLE_FACTORS - AMP WT2 Factor:Wild Type | Sample source:Stool RAW_FILE_NAME(Raw file name)=S30610 SUBJECT_SAMPLE_FACTORS - AMP WT3 Factor:Wild Type | Sample source:Stool RAW_FILE_NAME(Raw file name)=S30611 SUBJECT_SAMPLE_FACTORS - AMP KO1 Factor:Knockout | Sample source:Stool RAW_FILE_NAME(Raw file name)=S30612 SUBJECT_SAMPLE_FACTORS - AMP KO2 Factor:Knockout | Sample source:Stool RAW_FILE_NAME(Raw file name)=S30613 SUBJECT_SAMPLE_FACTORS - AMP KO3 Factor:Knockout | Sample source:Stool RAW_FILE_NAME(Raw file name)=S30614 SUBJECT_SAMPLE_FACTORS - F1 Factor:Food | Sample source:food RAW_FILE_NAME(Raw file name)=S30615 SUBJECT_SAMPLE_FACTORS - F2 Factor:Food | Sample source:food RAW_FILE_NAME(Raw file name)=S30616 SUBJECT_SAMPLE_FACTORS - F3 Factor:Food | Sample source:food RAW_FILE_NAME(Raw file name)=S30617 SUBJECT_SAMPLE_FACTORS - SQ1403_Blank_0 Factor:Blank | Sample source:blank RAW_FILE_NAME(Raw file name)=SQ1403_Blank_0 SUBJECT_SAMPLE_FACTORS - SQ1403_Blank_1 Factor:Blank | Sample source:blank RAW_FILE_NAME(Raw file name)=SQ1403_Blank_1 SUBJECT_SAMPLE_FACTORS - SQ1403_Blank_2 Factor:Blank | Sample source:blank RAW_FILE_NAME(Raw file name)=SQ1403_Blank_2 SUBJECT_SAMPLE_FACTORS - SQ1403_Blank_3 Factor:Blank | Sample source:blank RAW_FILE_NAME(Raw file name)=SQ1403_Blank_3 SUBJECT_SAMPLE_FACTORS - SQ1403_Blank_4 Factor:Blank | Sample source:blank RAW_FILE_NAME(Raw file name)=SQ1403_Blank_4 SUBJECT_SAMPLE_FACTORS - SQ1403_Blank_5 Factor:Blank | Sample source:blank RAW_FILE_NAME(Raw file name)=SQ1403_Blank_5 SUBJECT_SAMPLE_FACTORS - SQ1403_Blank_6 Factor:Blank | Sample source:blank RAW_FILE_NAME(Raw file name)=SQ1403_Blank_6 SUBJECT_SAMPLE_FACTORS - SQ1403_Blank_7 Factor:Blank | Sample source:blank RAW_FILE_NAME(Raw file name)=SQ1403_Blank_7 SUBJECT_SAMPLE_FACTORS - SQ1403_ISTD_0 Factor:ISTD | Sample source:standard RAW_FILE_NAME(Raw file name)=SQ1403_ISTD_0 SUBJECT_SAMPLE_FACTORS - SQ1403_ISTD_1 Factor:ISTD | Sample source:standard RAW_FILE_NAME(Raw file name)=SQ1403_ISTD_1 SUBJECT_SAMPLE_FACTORS - SQ1403_ISTD_2 Factor:ISTD | Sample source:standard RAW_FILE_NAME(Raw file name)=SQ1403_ISTD_2 SUBJECT_SAMPLE_FACTORS - SQ1403_ISTD_3 Factor:ISTD | Sample source:standard RAW_FILE_NAME(Raw file name)=SQ1403_ISTD_3 SUBJECT_SAMPLE_FACTORS - SQ1441_U6 Factor:No Cys WT | Sample source:urine RAW_FILE_NAME(Raw file name)=S31073 SUBJECT_SAMPLE_FACTORS - SQ1441_U7 Factor:No Cys WT | Sample source:urine RAW_FILE_NAME(Raw file name)=S31074 SUBJECT_SAMPLE_FACTORS - SQ1441_U8 Factor:No Cys KO | Sample source:urine RAW_FILE_NAME(Raw file name)=S31075 SUBJECT_SAMPLE_FACTORS - SQ1441_U9 Factor:No Cys KO | Sample source:urine RAW_FILE_NAME(Raw file name)=S31076 SUBJECT_SAMPLE_FACTORS - SQ1441_U10 Factor:No Cys KO | Sample source:urine RAW_FILE_NAME(Raw file name)=S31077 SUBJECT_SAMPLE_FACTORS - SQ1441_U16 Factor:No Cys WT | Sample source:urine RAW_FILE_NAME(Raw file name)=S31083 SUBJECT_SAMPLE_FACTORS - SQ1441_U17 Factor:No Cys WT | Sample source:urine RAW_FILE_NAME(Raw file name)=S31084 SUBJECT_SAMPLE_FACTORS - SQ1441_U18 Factor:No Cys WT | Sample source:urine RAW_FILE_NAME(Raw file name)=S31085 SUBJECT_SAMPLE_FACTORS - SQ1441_U19 Factor:No Cys WT | Sample source:urine RAW_FILE_NAME(Raw file name)=S31086 SUBJECT_SAMPLE_FACTORS - SQ1441_U20 Factor:No Cys KO | Sample source:urine RAW_FILE_NAME(Raw file name)=S31087 SUBJECT_SAMPLE_FACTORS - SQ1441_U21 Factor:No Cys KO | Sample source:urine RAW_FILE_NAME(Raw file name)=S31088 SUBJECT_SAMPLE_FACTORS - SQ1441_U22 Factor:No Cys KO | Sample source:urine RAW_FILE_NAME(Raw file name)=S31089 SUBJECT_SAMPLE_FACTORS - SQ1441_U23 Factor:No Cys KO | Sample source:urine RAW_FILE_NAME(Raw file name)=S31090 SUBJECT_SAMPLE_FACTORS - SQ1441_Blank_0 Factor:Blank | Sample source:blank RAW_FILE_NAME(Raw file name)=SQ1441_Blank_0 SUBJECT_SAMPLE_FACTORS - SQ1441_Blank_1 Factor:Blank | Sample source:blank RAW_FILE_NAME(Raw file name)=SQ1441_Blank_1 SUBJECT_SAMPLE_FACTORS - SQ1441_Blank_2 Factor:Blank | Sample source:blank RAW_FILE_NAME(Raw file name)=SQ1441_Blank_2 SUBJECT_SAMPLE_FACTORS - SQ1441_Blank_3 Factor:Blank | Sample source:blank RAW_FILE_NAME(Raw file name)=SQ1441_Blank_3 SUBJECT_SAMPLE_FACTORS - SQ1441_Blank_4 Factor:Blank | Sample source:blank RAW_FILE_NAME(Raw file name)=SQ1441_Blank_4 SUBJECT_SAMPLE_FACTORS - SQ1441_Blank_5 Factor:Blank | Sample source:blank RAW_FILE_NAME(Raw file name)=SQ1441_Blank_5 SUBJECT_SAMPLE_FACTORS - SQ1441_Blank_6 Factor:Blank | Sample source:blank RAW_FILE_NAME(Raw file name)=SQ1441_Blank_6 SUBJECT_SAMPLE_FACTORS - SQ1441_Blank_7 Factor:Blank | Sample source:blank RAW_FILE_NAME(Raw file name)=SQ1441_Blank_7 SUBJECT_SAMPLE_FACTORS - SQ1441_Blank_8 Factor:Blank | Sample source:blank RAW_FILE_NAME(Raw file name)=SQ1441_Blank_8 SUBJECT_SAMPLE_FACTORS - SQ1441_Blank_9 Factor:Blank | Sample source:blank RAW_FILE_NAME(Raw file name)=SQ1441_Blank_9 SUBJECT_SAMPLE_FACTORS - SQ1432_L8 Factor:No Cys WT | Sample source:liver RAW_FILE_NAME(Raw file name)=S30953 SUBJECT_SAMPLE_FACTORS - SQ1432_L9 Factor:No Cys WT | Sample source:liver RAW_FILE_NAME(Raw file name)=S30954 SUBJECT_SAMPLE_FACTORS - SQ1432_L10 Factor:No Cys WT | Sample source:liver RAW_FILE_NAME(Raw file name)=S30955 SUBJECT_SAMPLE_FACTORS - SQ1432_L11 Factor:No Cys WT | Sample source:liver RAW_FILE_NAME(Raw file name)=S30956 SUBJECT_SAMPLE_FACTORS - SQ1432_L12 Factor:No Cys KO | Sample source:liver RAW_FILE_NAME(Raw file name)=S30957 SUBJECT_SAMPLE_FACTORS - SQ1432_L13 Factor:No Cys KO | Sample source:liver RAW_FILE_NAME(Raw file name)=S30958 SUBJECT_SAMPLE_FACTORS - SQ1432_L14 Factor:No Cys KO | Sample source:liver RAW_FILE_NAME(Raw file name)=S30959 SUBJECT_SAMPLE_FACTORS - SQ1432_Blank_0 Factor:Blank | Sample source:blank RAW_FILE_NAME(Raw file name)=SQ1432_Blank_0 SUBJECT_SAMPLE_FACTORS - SQ1432_Blank_1 Factor:Blank | Sample source:blank RAW_FILE_NAME(Raw file name)=SQ1432_Blank_1 SUBJECT_SAMPLE_FACTORS - SQ1432_Blank_2 Factor:Blank | Sample source:blank RAW_FILE_NAME(Raw file name)=SQ1432_Blank_2 SUBJECT_SAMPLE_FACTORS - SQ1432_Blank_3 Factor:Blank | Sample source:blank RAW_FILE_NAME(Raw file name)=SQ1432_Blank_3 SUBJECT_SAMPLE_FACTORS - SQ1432_Blank_4 Factor:Blank | Sample source:blank RAW_FILE_NAME(Raw file name)=SQ1432_Blank_4 SUBJECT_SAMPLE_FACTORS - SQ1432_Blank_5 Factor:Blank | Sample source:blank RAW_FILE_NAME(Raw file name)=SQ1432_Blank_5 SUBJECT_SAMPLE_FACTORS - SQ1432_ISTD_0 Factor:ISTD | Sample source:standard RAW_FILE_NAME(Raw file name)=SQ1432_ISTD_0 SUBJECT_SAMPLE_FACTORS - SQ1432_ISTD_1 Factor:ISTD | Sample source:standard RAW_FILE_NAME(Raw file name)=SQ1432_ISTD_1 SUBJECT_SAMPLE_FACTORS - SQ1432_ISTD_2 Factor:ISTD | Sample source:standard RAW_FILE_NAME(Raw file name)=SQ1432_ISTD_2 SUBJECT_SAMPLE_FACTORS - SQ1615_L1 Factor:Het 45 min | Sample source:liver RAW_FILE_NAME(Raw file name)=S34898 SUBJECT_SAMPLE_FACTORS - SQ1615_L2 Factor:Het 45 min | Sample source:liver RAW_FILE_NAME(Raw file name)=S34899 SUBJECT_SAMPLE_FACTORS - SQ1615_L3 Factor:KO 45 min | Sample source:liver RAW_FILE_NAME(Raw file name)=S34900 SUBJECT_SAMPLE_FACTORS - SQ1615_L4 Factor:KO 45 min | Sample source:liver RAW_FILE_NAME(Raw file name)=S34901 SUBJECT_SAMPLE_FACTORS - SQ1615_L5 Factor:Het 45 min | Sample source:liver RAW_FILE_NAME(Raw file name)=S34902 SUBJECT_SAMPLE_FACTORS - SQ1615_L6 Factor:Het 45 min | Sample source:liver RAW_FILE_NAME(Raw file name)=S34903 SUBJECT_SAMPLE_FACTORS - SQ1615_L7 Factor:KO 45 min | Sample source:liver RAW_FILE_NAME(Raw file name)=S34904 SUBJECT_SAMPLE_FACTORS - SQ1615_L8 Factor:KO 45 min | Sample source:liver RAW_FILE_NAME(Raw file name)=S34905 SUBJECT_SAMPLE_FACTORS - SQ1615_Blank_0 Factor:Blank | Sample source:blank RAW_FILE_NAME(Raw file name)=SQ1615_Blank_0 SUBJECT_SAMPLE_FACTORS - SQ1615_Blank_1 Factor:Blank | Sample source:blank RAW_FILE_NAME(Raw file name)=SQ1615_Blank_1 SUBJECT_SAMPLE_FACTORS - SQ1615_Blank_2 Factor:Blank | Sample source:blank RAW_FILE_NAME(Raw file name)=SQ1615_Blank_2 SUBJECT_SAMPLE_FACTORS - SQ1615_Blank_3 Factor:Blank | Sample source:blank RAW_FILE_NAME(Raw file name)=SQ1615_Blank_3 SUBJECT_SAMPLE_FACTORS - SQ1615_Blank_4 Factor:Blank | Sample source:blank RAW_FILE_NAME(Raw file name)=SQ1615_Blank_4 SUBJECT_SAMPLE_FACTORS - SQ1615_Blank_5 Factor:Blank | Sample source:blank RAW_FILE_NAME(Raw file name)=SQ1615_Blank_5 SUBJECT_SAMPLE_FACTORS - SQ1615_Blank_6 Factor:Blank | Sample source:blank RAW_FILE_NAME(Raw file name)=SQ1615_Blank_6 SUBJECT_SAMPLE_FACTORS - SQ1615_Blank_7 Factor:Blank | Sample source:blank RAW_FILE_NAME(Raw file name)=SQ1615_Blank_7 SUBJECT_SAMPLE_FACTORS - SQ1615_ISTD_0 Factor:ISTD | Sample source:standard RAW_FILE_NAME(Raw file name)=SQ1615_ISTD_0 SUBJECT_SAMPLE_FACTORS - SQ1615_ISTD_1 Factor:ISTD | Sample source:standard RAW_FILE_NAME(Raw file name)=SQ1615_ISTD_1 SUBJECT_SAMPLE_FACTORS - SQ1615_ISTD_2 Factor:ISTD | Sample source:standard RAW_FILE_NAME(Raw file name)=SQ1615_ISTD_2 SUBJECT_SAMPLE_FACTORS - SQ1615_ISTD_3 Factor:ISTD | Sample source:standard RAW_FILE_NAME(Raw file name)=SQ1615_ISTD_3 SUBJECT_SAMPLE_FACTORS - SQ1616_U1 Factor:Het 2 hr | Sample source:urine RAW_FILE_NAME(Raw file name)=S34919 SUBJECT_SAMPLE_FACTORS - SQ1616_U2 Factor:Het 2 hr | Sample source:urine RAW_FILE_NAME(Raw file name)=S34920 SUBJECT_SAMPLE_FACTORS - SQ1616_U3 Factor:KO 2 hr | Sample source:urine RAW_FILE_NAME(Raw file name)=S34921 SUBJECT_SAMPLE_FACTORS - SQ1616_U4 Factor:KO 2 hr | Sample source:urine RAW_FILE_NAME(Raw file name)=S34922 SUBJECT_SAMPLE_FACTORS - SQ1616_U5 Factor:Het 2 hr | Sample source:urine RAW_FILE_NAME(Raw file name)=S34923 SUBJECT_SAMPLE_FACTORS - SQ1616_U6 Factor:Het 2 hr | Sample source:urine RAW_FILE_NAME(Raw file name)=S34924 SUBJECT_SAMPLE_FACTORS - SQ1616_U7 Factor:KO 2 hr | Sample source:urine RAW_FILE_NAME(Raw file name)=S34925 SUBJECT_SAMPLE_FACTORS - SQ1616_U8 Factor:Het 2 hr | Sample source:urine RAW_FILE_NAME(Raw file name)=S34926 SUBJECT_SAMPLE_FACTORS - SQ1616_U9 Factor:Het 2 hr | Sample source:urine RAW_FILE_NAME(Raw file name)=S34927 SUBJECT_SAMPLE_FACTORS - SQ1616_U10 Factor:KO 2 hr | Sample source:urine RAW_FILE_NAME(Raw file name)=S34928 SUBJECT_SAMPLE_FACTORS - SQ1616_Blank_0 Factor:Blank | Sample source:blank RAW_FILE_NAME(Raw file name)=SQ1616_Blank_0 SUBJECT_SAMPLE_FACTORS - SQ1616_Blank_1 Factor:Blank | Sample source:blank RAW_FILE_NAME(Raw file name)=SQ1616_Blank_1 SUBJECT_SAMPLE_FACTORS - SQ1616_Blank_2 Factor:Blank | Sample source:blank RAW_FILE_NAME(Raw file name)=SQ1616_Blank_2 SUBJECT_SAMPLE_FACTORS - SQ1616_Blank_3 Factor:Blank | Sample source:blank RAW_FILE_NAME(Raw file name)=SQ1616_Blank_3 SUBJECT_SAMPLE_FACTORS - SQ1616_Blank_4 Factor:Blank | Sample source:blank RAW_FILE_NAME(Raw file name)=SQ1616_Blank_4 SUBJECT_SAMPLE_FACTORS - SQ1616_Blank_5 Factor:Blank | Sample source:blank RAW_FILE_NAME(Raw file name)=SQ1616_Blank_5 SUBJECT_SAMPLE_FACTORS - SQ1616_Blank_6 Factor:Blank | Sample source:blank RAW_FILE_NAME(Raw file name)=SQ1616_Blank_6 SUBJECT_SAMPLE_FACTORS - SQ1616_Blank_7 Factor:Blank | Sample source:blank RAW_FILE_NAME(Raw file name)=SQ1616_Blank_7 SUBJECT_SAMPLE_FACTORS - SQ1616_ISTD_0 Factor:ISTD | Sample source:standard RAW_FILE_NAME(Raw file name)=SQ1616_ISTD_0 SUBJECT_SAMPLE_FACTORS - SQ1616_ISTD_1 Factor:ISTD | Sample source:standard RAW_FILE_NAME(Raw file name)=SQ1616_ISTD_1 SUBJECT_SAMPLE_FACTORS - SQ1616_ISTD_2 Factor:ISTD | Sample source:standard RAW_FILE_NAME(Raw file name)=SQ1616_ISTD_2 SUBJECT_SAMPLE_FACTORS - SQ1616_ISTD_3 Factor:ISTD | Sample source:standard RAW_FILE_NAME(Raw file name)=SQ1616_ISTD_3 #COLLECTION CO:COLLECTION_SUMMARY Food pellets were weighed into bead blaster tubes containing zircon beads. CO:COLLECTION_SUMMARY Extraction buffer containing 80% methanol with 500nM Metabolomics amino acid CO:COLLECTION_SUMMARY standard mix (Cambridge Isotopes Laboratory, MA) was added to each to reach a CO:COLLECTION_SUMMARY final concentration of 10 mg/mL. Samples were homogenized using D2400 BeadBlaster CO:COLLECTION_SUMMARY homogenizer (Benchmark Scientific, NJ) then spun at 21 kg for 3min. Then, 450uL CO:COLLECTION_SUMMARY of metabolite extract was transferred to a new 1.5mL Eppendorf tube and dried CO:COLLECTION_SUMMARY using Speedvac. Samples were reconstituted in 50uL of MS grade water and CO:COLLECTION_SUMMARY sonicated for 2 mins. Then, samples were spun at 21,000 g for 3 mins. Samples CO:COLLECTION_SUMMARY were transferred to glass LC vials for analysis by LCMS. Liver Samples CO:COLLECTION_SUMMARY Approximately 300 mg of liver was homogenized in 1 mL of PBS and then subjected CO:COLLECTION_SUMMARY to three freeze-thaw cycles. Liver samples were filtered using a 10kDa filter. CO:COLLECTION_SUMMARY Protein concentrations prior to deproteinization were measured using BSA standard CO:COLLECTION_SUMMARY curve and found to be between 12.8 – 42.0 mg/mL. For metabolomics extracts, on CO:COLLECTION_SUMMARY average protein concentration was determined to be 28.58 mg/mL per 300 mg of CO:COLLECTION_SUMMARY tissue. This value was used to scale all liver extracts to each other. Scaled CO:COLLECTION_SUMMARY liver extracts were transferred to bead blaster tubes with zircon beads and CO:COLLECTION_SUMMARY homogenized using D2400 BeadBlaster homogenizer (Benchmark Scientific, NJ) in CO:COLLECTION_SUMMARY cold 80% methanol spiked with 500 nM Metabolomics amino acid standard mix CO:COLLECTION_SUMMARY (Cambridge Isotopes Laboratory, MA). Samples were centrifuged at 21,000 g for 3 CO:COLLECTION_SUMMARY min to pellet any insoluble materials. Then, 450 µL of metabolite extract was CO:COLLECTION_SUMMARY transferred to a new 1.5mL Eppendorf tube and dried down using Speedvac. Samples CO:COLLECTION_SUMMARY were reconstituted in 50uL of MS grade water and sonicated for 2 mins. Then, CO:COLLECTION_SUMMARY samples were spun at 21,000 g for 3 min. Samples were transferred to glass LC CO:COLLECTION_SUMMARY vials for analysis by LCMS. Urine Samples Urine samples were collected and CO:COLLECTION_SUMMARY stored as frozen aliquots between ~5-7 µL. For metabolite extraction, 5µL of CO:COLLECTION_SUMMARY urine was transferred to a glass insert and extracted using 195 µL of cold 80% CO:COLLECTION_SUMMARY methanol spiked with 500nM Metabolomics amino acid standard mix (Cambridge CO:COLLECTION_SUMMARY Isotopes Laboratory, MA). Glass inserts were transferred into 1.5 mL Eppendorf CO:COLLECTION_SUMMARY tubes and spun at 3 kg for 10 min to pellet insoluble material. Then, 180 µL of CO:COLLECTION_SUMMARY extract was transferred to a 1.5 mL Eppendorf tube and dried down completely CO:COLLECTION_SUMMARY using Speedvac. To each, 20 µL of MS grade water was added to reconstitute CO:COLLECTION_SUMMARY metabolites. Samples were sonicated for 2 mins and then centrifuged for 3 min at CO:COLLECTION_SUMMARY 21 kg. Then 15 µL of samples was transferred to a glass LCMS vial for analysis. CO:SAMPLE_TYPE urine, liver, food #TREATMENT TR:TREATMENT_SUMMARY All custom diets were procured from TestDiet. All diets were based on the TR:TREATMENT_SUMMARY defined amino acid diet 5CC7. For individual or dual amino acid depleted diets, TR:TREATMENT_SUMMARY the specific amino acid(s) was completely removed, and all other amino acids TR:TREATMENT_SUMMARY were increased in proportion. For pantothenic acid-deficient diet, it was TR:TREATMENT_SUMMARY removed from the same 5CC7 defined diet. Unless specified control diet refers to TR:TREATMENT_SUMMARY the 5CC7 diet. D-Galactose (Sigma G0750) and D-Glucose (Sigma G8270) were TR:TREATMENT_SUMMARY purchased from Sigma and were dissolved in water and filter sterilized. A list TR:TREATMENT_SUMMARY of diet names is available on request. #SAMPLEPREP SP:SAMPLEPREP_SUMMARY Food pellets were weighed into bead blaster tubes containing zircon beads. SP:SAMPLEPREP_SUMMARY Extraction buffer containing 80% methanol with 500nM Metabolomics amino acid SP:SAMPLEPREP_SUMMARY standard mix (Cambridge Isotopes Laboratory, MA) was added to each to reach a SP:SAMPLEPREP_SUMMARY final concentration of 10 mg/mL. Samples were homogenized using D2400 BeadBlaster SP:SAMPLEPREP_SUMMARY homogenizer (Benchmark Scientific, NJ) then spun at 21 kg for 3min. Then, 450 µL SP:SAMPLEPREP_SUMMARY of metabolite extract was transferred to a new 1.5 mL Eppendorf tube and dried SP:SAMPLEPREP_SUMMARY using Speedvac. Samples were reconstituted in 50 µL of MS grade water and SP:SAMPLEPREP_SUMMARY sonicated for 2 mins. Then, samples were spun at 21,000 g for 3 mins. Samples SP:SAMPLEPREP_SUMMARY were transferred to glass LC vials for analysis by LCMS. Liver Samples SP:SAMPLEPREP_SUMMARY Approximately 300 mg of liver was homogenized in 1 mL of PBS and then subjected SP:SAMPLEPREP_SUMMARY to three freeze-thaw cycles. Liver samples were filtered using a 10 kDa filter. SP:SAMPLEPREP_SUMMARY Protein concentrations prior to deproteinization were measured using BSA standard SP:SAMPLEPREP_SUMMARY curve and found to be between 12.8 – 42.0 mg/mL. For metabolomics extracts, on SP:SAMPLEPREP_SUMMARY average protein concentration was determined to be 28.58 mg/mL per 300 mg of SP:SAMPLEPREP_SUMMARY tissue. This value was used to scale all liver extracts to each other. Scaled SP:SAMPLEPREP_SUMMARY liver extracts were transferred to bead blaster tubes with zircon beads and SP:SAMPLEPREP_SUMMARY homogenized using D2400 BeadBlaster homogenizer (Benchmark Scientific, NJ) in SP:SAMPLEPREP_SUMMARY cold 80% methanol spiked with 500 nM Metabolomics amino acid standard mix SP:SAMPLEPREP_SUMMARY (Cambridge Isotopes Laboratory, MA). Samples were centrifuged at 21,000 g for 3 SP:SAMPLEPREP_SUMMARY min to pellet any insoluble materials. Then, 450 µL of metabolite extract was SP:SAMPLEPREP_SUMMARY transferred to a new 1.5mL Eppendorf tube and dried down using Speedvac. Samples SP:SAMPLEPREP_SUMMARY were reconstituted in 50uL of MS grade water and sonicated for 2 mins. Then, SP:SAMPLEPREP_SUMMARY samples were spun at 21,000 g for 3 min. Samples were transferred to glass LC SP:SAMPLEPREP_SUMMARY vials for analysis by LCMS. Urine Samples Urine samples were collected and SP:SAMPLEPREP_SUMMARY stored as frozen aliquots between ~5-7 µL. For metabolite extraction, 5µL of SP:SAMPLEPREP_SUMMARY urine was transferred to a glass insert and extracted using 195µL of cold 80% SP:SAMPLEPREP_SUMMARY methanol spiked with 500nM Metabolomics amino acid standard mix (Cambridge SP:SAMPLEPREP_SUMMARY Isotopes Laboratory, MA). Glass inserts were transferred into 1.5mL Eppendorf SP:SAMPLEPREP_SUMMARY tubes and spun at 3 kg for 10 min to pellet insoluble material. Then, 180 µL of SP:SAMPLEPREP_SUMMARY extract was transferred to a 1.5 mL Eppendorf tube and dried down completely SP:SAMPLEPREP_SUMMARY using Speedvac. To each, 20 µL of MS grade water was added to reconstitute SP:SAMPLEPREP_SUMMARY metabolites. Samples were sonicated for 2 mins and then centrifuged for 3 min at SP:SAMPLEPREP_SUMMARY 21 kg. Then 15 µL of samples was transferred to a glass LCMS vial for analysis. #CHROMATOGRAPHY CH:CHROMATOGRAPHY_TYPE HILIC CH:INSTRUMENT_NAME Thermo Ultimate 3000 RS CH:COLUMN_NAME SeQuant ZIC-HILIC (150 x 2.1mm,5um) CH:SOLVENT_A 100% Water; 10 mM ammonium carbonate in water, pH 9.0 CH:SOLVENT_B 100% Acetonitrile CH:FLOW_GRADIENT 80-20%B (0-30 min), 20-80%B (30-31 min), 80-80%B (31-42 min) CH:FLOW_RATE 0.1 mL/min CH:COLUMN_TEMPERATURE 25 #ANALYSIS AN:ANALYSIS_TYPE MS #MS MS:INSTRUMENT_NAME Thermo Q Exactive Orbitrap MS:INSTRUMENT_TYPE Orbitrap MS:MS_TYPE ESI MS:ION_MODE UNSPECIFIED MS:MS_COMMENTS both positive and negative polarities were collected in the same acquisition MS:MS_COMMENTS during polarity switching mechanism #MS_METABOLITE_DATA MS_METABOLITE_DATA:UNITS absolute intensity MS_METABOLITE_DATA_START Samples AMP WT1 AMP WT2 AMP WT3 AMP KO1 AMP KO2 AMP KO3 F1 F2 F3 SQ1441_U6 SQ1441_U7 SQ1441_U8 SQ1441_U9 SQ1441_U10 SQ1441_U16 SQ1441_U17 SQ1441_U18 SQ1441_U19 SQ1441_U20 SQ1441_U21 SQ1441_U22 SQ1441_U23 SQ1432_L8 SQ1432_L9 SQ1432_L10 SQ1432_L11 SQ1432_L12 SQ1432_L13 SQ1432_L14 SQ1615_L1 SQ1615_L2 SQ1615_L3 SQ1615_L4 SQ1615_L5 SQ1615_L6 SQ1615_L7 SQ1615_L8 SQ1616_U1 SQ1616_U2 SQ1616_U3 SQ1616_U4 SQ1616_U5 SQ1616_U6 SQ1616_U7 SQ1616_U8 SQ1616_U9 SQ1616_U10 Factors Factor:Wild Type | Sample source:Stool Factor:Wild Type | Sample source:Stool Factor:Wild Type | Sample source:Stool Factor:Knockout | Sample source:Stool Factor:Knockout | Sample source:Stool Factor:Knockout | Sample source:Stool Factor:Food | Sample source:food Factor:Food | Sample source:food Factor:Food | Sample source:food Factor:No Cys WT | Sample source:urine Factor:No Cys WT | Sample source:urine Factor:No Cys KO | Sample source:urine Factor:No Cys KO | Sample source:urine Factor:No Cys KO | Sample source:urine Factor:No Cys WT | Sample source:urine Factor:No Cys WT | Sample source:urine Factor:No Cys WT | Sample source:urine Factor:No Cys WT | Sample source:urine Factor:No Cys KO | Sample source:urine Factor:No Cys KO | Sample source:urine Factor:No Cys KO | Sample source:urine Factor:No Cys KO | Sample source:urine Factor:No Cys WT | Sample source:liver Factor:No Cys WT | Sample source:liver Factor:No Cys WT | Sample source:liver Factor:No Cys WT | Sample source:liver Factor:No Cys KO | Sample source:liver Factor:No Cys KO | Sample source:liver Factor:No Cys KO | Sample source:liver Factor:Het 45 min | Sample source:liver Factor:Het 45 min | Sample source:liver Factor:KO 45 min | Sample source:liver Factor:KO 45 min | Sample source:liver Factor:Het 45 min | Sample source:liver Factor:Het 45 min | Sample source:liver Factor:KO 45 min | Sample source:liver Factor:KO 45 min | Sample source:liver Factor:Het 2 hr | Sample source:urine Factor:Het 2 hr | Sample source:urine Factor:KO 2 hr | Sample source:urine Factor:KO 2 hr | Sample source:urine Factor:Het 2 hr | Sample source:urine Factor:Het 2 hr | Sample source:urine Factor:KO 2 hr | Sample source:urine Factor:Het 2 hr | Sample source:urine Factor:Het 2 hr | Sample source:urine Factor:KO 2 hr | Sample source:urine 1-Methylnicotinamide 9290648 8536322 9248169 14608763 12944421 33326788 - - - 248221168 189559008 395093344 221858992 341434912 173570432 677641216 139683648 212303600 354053632 670026048 327513984 352031008 1576216 3742440 2851648 1749308 - 2817848 2386108 1563046 - - - - 1779715 - - 22508444 21017038 - - - - - - - - 2,3-Diphosphoglyceric acid - - - - - - - - - - - - 81200 - 50270 418147 18640 36725 - 39639 - - - - - - 20976 13718 17910 - - - - - - - - - 31257 17168 29701 26328 - - 25568 - - 3-Hydroxybutyric acid - - - - - - 779918 607648 639387 2045781 2504074 5757150 2971974 15604128 1006566 2888664 113100 1608877 7028778 3488282 2761976 1079253 1640901 1140188 1144469 1024610 2036393 1059047 1439990 772288 935640 1300798 825786 1654823 1842282 1124224 610884 214862 589598 505499 89148 164193 40049 73486 112328 171700 100632 3-Phosphoglyceric acid - - - - - - 15439 - - 2079602 1494562 978260 3501038 4768094 692015 5765586 1706723 360593 3999262 - 2540007 1297373 1200888 2065062 1972934 2610472 3790972 3947470 4434940 4084548 5118164 4082483 5134257 4499195 5363829 3590478 4915718 1576457 2079172 - - 2222845 - - - - - 4,5-Dihydroorotic acid - - - - - - - - 21818 26491 - 121456 5097826 265771 34991 40777 - - 86256 286897 118380 167646 - 13583 - - 849217 503932 334402 - - 41665 21394 - - 12193 194647 - 19304 21444 41152 19838 25748 23161 20490 25784 247277 4-Hydroxyproline 166039 138185 134494 69302 - 83225 898418 1324874 2146272 4867524 2229126 1146844 4252694 7405100 3118713 4121380 1793169 2249498 8165317 8505210 789539 1352884 12303259 13381492 16505571 14792094 1615938 8353413 12254646 4606804 3450799 1091695 1370867 1732444 2270789 1054763 1067049 1744318 2697144 2143847 940134 5077822 1884404 802513 3121178 2390267 1399032 5'-Methylthioadenosine - - - - - - 9730226 1878576 8031584 1996616 1363540 2736594 3838523 2417555 3594307 10215737 4642496 10361648 6170812 6327788 8538171 3848565 351964 943753 599555 558476 2426502 1579960 1745482 916873 1069988 1785375 1870806 2328711 1046685 2218018 2590823 - - - - - - - - - - 5-Phosphoribosylamine - - - - - - 18583 - - 66486 - - 70769 - - - - - - - - - 18368 23630 34328 15297 18469 18990 25561 - - - 13721 - - - - 32813 12611 - - 23763 18988 - 36739 14386 34942 6-Phosphogluconic acid - - - - - - - - - - - - - 16392 - - - - 13764 25196 - - 30089 34667 49472 39079 37905 81367 72671 46757 61178 42014 56402 37813 50425 31719 64981 - 35057 19637 - - - - 24920 - 35963 Acetoacetic acid 416599 404015 386037 462172 326697 333460 807771 543706 492350 747749 528284 1018637 1836885 1766624 1719227 1980400 186481 457065 1732894 2795941 727560 402822 505160 680835 577953 469822 267619 536109 497408 4088614 4553413 4173809 4786036 3713464 4299334 3693072 4165670 57776 164161 205136 81313 170180 91784 58041 259266 165215 251825 Acetyl-CoA 64808 - - - - - - - - - - - - - - - 12016 - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - Acetylcysteine 46114 36526 35665 21430 32473 49155 - 113439 131909 357128 318520 515923 334749 256838 483186 587612 162382 333985 321020 698694 334595 443540 63305 94276 171735 93144 85361 63458 73389 - - - 12627 - - - - 73778 119110 101816 108637 261829 81177 73458 227399 162534 318958 Adenine 2769212 2219998 2003440 3751874 2791246 4454193 178978992 159705168 215736736 4889329 4142668 8841626 6704588 7025294 4139513 7782056 1651316 8647799 4296188 4258581 3429435 2478960 8833458 7972515 9227195 8743893 11866579 9633940 10182458 4242425 6092923 5819526 3451578 3453262 4252630 4062574 6534578 3134292 3299220 4046336 3457820 2638920 2092849 1669950 3576866 2608386 2331048 Adenosine - - - - - - - - 4908394 12027428 35465684 38567308 42413004 53106968 53471244 64116956 24531920 46010800 43606376 36889188 42655440 29755276 3452184 2581535 1701734 2521497 2974443 2362443 3729813 2752847 2426212 3004690 2923675 2619208 2454119 6289502 2946163 27488864 27693664 30628620 25093802 25740760 13484440 12936507 29969686 24349624 26363404 Adenosine diphosphate ribose - - - - - - - - - - - - - - - - - - - - - - 44946 43095 52714 23121 51193 73036 774800 42132 111496 116484 77293 36156 113124 38682 84572 - - - - - - - - 12549 - Adenosine monophosphate - - - - - - - - - 99256 69199 - - - 89959 144888 49105 48646 - - 38391 - 97180360 108229920 68819144 95511816 67530520 99165432 129253272 24216356 20351314 26573416 17126378 21764748 31006362 34358004 48423824 79360 40634 54770 45197 62905 109672 89999 54776 61086 - Adenosine triphosphate - - - - - - 63358 - - - - - - - - - - - 14248 - - - - - - - - - - - - - - - - - - - - - - - - - - - - Adenylsuccinic acid - - - - - - - - - - - - - - - - - - - - - - 84462 112604 116576 83175 132499 163643 89656 59763 87852 175206 73337 115469 95052 215449 281032 - - - - - - - - - - ADP - - - - - - 220556 - - - - 13385 - - - - - - - - - - 62081 154509 74789 147773 135353 83081 67519 567047 885039 760909 699546 971357 784697 887120 895445 - - - - - - - - - - Allantoin 386021 359277 343187 673298 514165 1128349 - - 20570 139351680 86843032 163567600 209151376 125294664 200569328 244956096 65354700 111540928 190835200 150848272 163556480 123028984 13665093 19051534 18884548 14129777 4229112 5511520 6881204 701991 384282 386505 318828 478225 597517 303746 348290 48314516 87533160 62375196 53869660 94593768 39472388 38771440 85670872 66416848 94091208 Aminoadipic acid 993586 1036904 1050998 1400789 929144 1644621 993284 955272 1154941 87326400 32986626 36035836 53635108 45507552 23250120 44905312 14284494 28870222 51025452 77919000 49051644 73668400 478993 515217 363742 243991 294998 268189 310328 156231 258342 211119 106532 213163 300866 223193 325522 35177448 59348644 33123444 12859106 33412580 10546891 6144394 17319584 25524544 24286406 Argininosuccinic acid 10254 - - - - - - - - 108282 26154 2612738 6409040 4451298 309795 78587 35819 73685 3388132 4729310 3797075 4973375 - 12224 13044 21817 72916 123455 117110 24184 - - 34931 25277 - 32176 - - - 5857912 8663712 - 1909450 3519355 - - 11694868 Beta-Alanine - - - - - - 213707 - - 640902 8504069 22665680 5748752 7935926 866392 7294244 1292497 6145350 21322140 764864 24111152 24404024 3290389 4190364 10249478 3911840 19078610 19782680 17419048 1245024 1008340 2006646 1621869 1211454 1209686 1369456 2118709 24474032 24579554 25448190 25106026 27184538 20979600 25352334 27516148 24121788 25374394 Betaine 107335984 31360012 54343940 23815974 31473858 43457660 333241920 326179040 359034592 548891008 478804320 513540800 621730688 1113327104 557371200 587145472 184439440 398641216 911776064 777618432 525021120 276307424 510330080 887402688 624971392 417934176 136461616 257567120 184419984 603508160 797016768 194497184 139755616 658397952 522322688 91843408 216673536 161321200 265762016 301906528 374085376 464814880 146097408 622587200 614017984 154786816 834267520 Butyrylcarnitine 1361443 1524173 1408330 1486964 1198256 1712856 76145 75750 76953 740376 476879 868329 1396504 2163512 638390 1581024 310460 782910 1027217 1205389 554572 272450 78839 217515 236434 130281 334524 361757 423063 2464391 744053 975918 705646 673585 656067 123081 1725254 143182 459676 122713 134221 436519 110732 46931 238503 342582 200139 Carbamoyl phosphate 197227 104420 115247 - - 391968 2002362 2024270 1977172 - 72648 1779613 160271 - 1483500 - - 28155 134827 22347 31487 26669 780062 996534 886753 919925 - 1066107 912310 - - - - - - - - - - - - - - - - - - Carnosine 33005 22262 28404 - - 26749 69502 38361 90493 195234 568639 2082620 6676290 8015962 1055814 699822 196605 380104 3290860 3253453 1720271 953218 91198 190811 120848 146738 112418 210919 137592 127666 152665 120730 109141 74517 99310 73550 85546 - - 873851 2126006 1271816 2221945 3160227 1306483 1064864 3870830 CDP - - - - - - 25225 - - - - - - - - - - - - - - - - - - - - - - - - - 12852 - - 13764 - - - - - - - - - - - Choline - - - - - - 26768878 2195764 10159575 86738360 1268398 24487760 147517616 143219024 136337 35721708 3381694 5823108 161307104 84581936 45225280 16759345 841781 303343 - 210947 23392016 748795 2051065 140026144 199491968 137481504 167733696 135598688 155288768 152388848 133229800 35344496 98363880 39525408 139625584 82966536 29786340 52685448 200897808 44707044 133356536 cis-Aconitic acid - - - - - - 696875 611297 822542 85323352 26677738 250996752 221806336 242945104 62382648 142657424 84691120 136184928 246567104 392836800 168640304 182446368 133601 100917 79616 64393 55690 286214 85026 295571 363186 245399 403190 467990 527728 244271 215270 - 56638604 84788056 66336816 93046456 58769188 35294084 79875920 62538624 79252480 Citric acid - - 954318 - - - 31522164 20949600 16410486 129657312 - 234437552 339866016 109391400 - 60145680 83107592 12944350 164566496 262530512 21941802 46237192 7831488 6583386 6747344 5677908 5998880 11213170 6732948 10026624 11107309 10532946 12842927 12603071 13264278 10103316 9032390 - - 120032576 - - 83237272 - - - 132756944 Citrulline 3174211 5657115 4715002 6467516 4641971 3782284 3794186 4964376 5440434 5909040 3625416 52611696 174236000 76744384 9066763 6435104 4260838 4251339 75696840 84075456 63224976 53333788 17120534 32845168 24850148 17716888 407271904 254199968 271942560 47288484 34114696 271875008 243283600 15928171 91945128 162954672 324430240 - 107928608 26204874 227772512 - 55254976 533634592 224233760 - 256923504 Creatine 631325696 252582640 327589376 376451232 422961600 517944384 - - - 1749954944 1908782592 2180086272 2228699136 2202050560 1976239616 1706470912 1050208576 1812387584 2257848320 2070314752 2198068224 2281245696 369062816 644271424 505280576 565171072 805577856 699257024 604176448 417882848 378375456 580907968 578487360 438592224 325808384 453490272 596389888 1763635072 1766652928 1815280768 1764823424 1864620928 1697402496 1659874432 1987854336 1738600576 2009167616 Creatinine 60581460 58649284 56987324 96170600 89110600 114778752 - - 523830 1183035008 1158338688 1388022400 1379933312 1386455168 1267753600 1658127872 1024767616 1245401728 1475759616 1645268864 1276920448 1357871488 14644774 22102882 18919586 16509147 27652672 22776834 24227648 10663864 8976570 20216946 12322327 11056166 9104590 10604519 12903882 759865408 877589440 858331200 811618176 874031040 705286464 564900928 867238592 805226112 831207296 Cyclic AMP 46114 41641 - - - - 22871 14323 20067 3246356 2473600 3364015 9138458 4972517 3446644 5300360 807546 1841491 3949560 4342444 4519788 1967981 - - - 17657 - - - - - - - - - - - 1857094 3552546 3409206 2983641 2681283 1059845 4441281 3225432 2079577 6901356 Cytidine 27095450 25262254 25397950 21169694 16634992 4389638 229352 241506 270276 317822 273170 281120 458190 360422 281029 387132 144450 259161 255398 234453 296388 162108 2637364 2907722 2614596 2287261 3241568 3048262 3507966 2625112 2286654 1360642 2569633 2461163 2484218 1688575 2293705 92669 234907 155630 95943 230130 157706 120592 329231 177412 452233 Cytidine monophosphate - - - - - - - - - - - - 13137 15497 14504 - - - 17035 - - - 1665101 2133974 1843034 1526669 1878940 2514245 2480497 1597883 1426995 1621901 2810838 1763663 1787907 1820131 2623714 - - - - - - - - - - Cytidine triphosphate - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - Cytosine - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - D-2-Hydroxyglutaric acid - - - - - - 5356698 3003322 3643862 4503098 4358916 41745048 94411864 116377784 271153504 508349568 10978618 36412320 693347392 134355648 7320380 5408542 5888643 5905216 4871354 3010308 3816736 1577893 4482260 1500511 1027782 1413556 2447430 2084071 1886582 2439502 1832206 16288478 59161732 65780256 38347648 83209840 25840722 17063896 72431432 63307608 50139976 D-Glucose 12562404 8546662 9398432 8702593 7099840 5057073 12818796 8829684 8643660 7516054 6123510 9467786 12883611 11451409 16659912 20257916 5928576 11476124 9844371 11789503 5892461 5101483 490734 310042 1387655 806538 1630807 4970508 3670129 914167 876186 543242 573328 479629 557138 771993 521624 5430792 13181275 20514184 4365224 15218344 5577214 2225034 17329236 17066410 17278168 D-Glyceraldehyde 3-phosphate - - - - - - 15835 - - - - - - 31770 - - - - - - - - - 30431 26648 22448 122281 255603 297353 - - 75086 118588 124903 74571 153665 - - 31028 - - 88944 35078 - 43835 53850 - Dihydrofolic acid - - - - - - 22312 20805 31078 - - - - - - - - - 18122 16036 - - - - - - - - - - - - - - - - - - - - - - - - - - - Dihydroxyacetone phosphate - - - - - - 16014 - - - 46148 - - 105761 29857 - - - - 62884 22387 41671 190531 206944 440295 19596 44079 776431 3102838 - - 36077 51795 46772 39073 69101 - 29579 26011 - - 77178 26206 - 36933 34152 30113 D-Ribose 5-phosphate - 10707 12768 - - - - - - - - - - - 32249 - - - - 40732 - - 1328593 1617705 1891268 1061621 1678286 3782008 4528866 1495160 1884429 1395239 1726266 935575 1784977 870331 1477715 43860 76787 49767 32898 126929 40011 - 96612 102092 88554 D-Sedoheptulose 7-phosphate - - - - - - - - - 72145 32895 70274 41031 - 57317 192732 33041 38204 60369 69766 41555 30428 1742251 2762592 2114156 2187407 7495485 11850496 11602222 3758110 2956736 2846980 4369888 2992442 2818411 4285256 2985214 - - - - - - - - - 72166 dTDP - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - 13259 - - - - - - - - - - FAD - - - - - - 31853 - - - - - - - - - - - - - - - 13705 17677 23866 17376 - - - - - - - - - - - - - 17029 - - - - - - - Folic acid - - - - - - 109026 163862 214547 - - - - - - - - - - - - - - - - - - - 11274 - - - - - - - - - - - - - - - - - - Fructose 1,6-bisphosphate - - - - - - - - - - - - 31860 - - - - - - - - - - - 18439 14839 31325 22088 18095 39426 86114 80392 100071 54288 55275 53724 97821 - - - - - - - - - - Fructose 6-phosphate - - - - - - 65854 32573 47729 82786 76188 90456 110291 147302 84233 154558 38347 49117 187389 143965 121691 123451 2724379 3730195 3757501 3023065 13780930 30531976 27600352 6379963 5780161 7213213 10853585 7329946 6727311 9681457 5271690 - 25615 - 22104 28508 31011 - 28775 302136 644083 Fumaric acid 216876 - - - - - 236558 206060 223418 - 169914 185342 298842 305659 - 187433 - 3490026 185045 263149 - - 9315718 10614918 11131797 9129771 12317148 18301332 12070243 8957063 9276905 10184031 11902264 8310808 8267554 9400630 10362535 242534 - 240988 - 422944 374573 - 461838 - 361302 Glucose 6-phosphate - - - - - - - - - 107013 105312 130745 - 90762 58069 103186 - - 167095 94905 59054 33113 7952657 11637901 9193146 9403066 40919880 82392144 77726368 10873087 11188024 11775990 19110518 15178288 12199308 20368806 - - 153308 - 171585 207168 385607 - 204252 1351897 1737717 Glutathione 42953 38768 31352 - - 30491 - - - - 74909 76245 244085 230112 64283 40994 - - 131188 115426 90820 73922 86082848 52227996 3541001 77782656 2336658 9503375 24907718 34136 70279 - - - - 100596 48768 40914 103681 95950 68709 131205 84934 47605 195290 144648 302434 Glycerol 3-phosphate 251033 149102 150415 - - 33991 - - - 3433711 21781770 1961293 15169541 32259246 24573140 38505980 7997984 11982539 24223660 32268890 14383296 10072334 21913008 26026796 16280232 24561612 40588000 42330488 41554152 6495402 7573353 7308700 7225521 4835590 5462226 14223518 6930292 16298433 23467796 17858590 11278005 25524738 6371839 3665632 21236718 20268286 13946800 Glycine - - 658393 - - - 173468064 69700664 79491832 6049554 3764138 7387700 4972909 4465698 7064824 6110492 3012471 4730546 9089246 10109300 8718010 6981894 8495860 9217117 8355910 8548684 6589813 9658156 8031805 2479200 2909351 2530698 2042534 2340088 2076638 2375011 2336857 7190088 8392664 5765914 3891079 7055672 2061303 2464421 3029588 6178386 3954848 Guanidoacetic acid 876307 231370 319686 269343 447134 880472 270335 61571 70029 571260160 494996192 637402560 716052544 741772672 605725184 728095552 386664832 538931392 756470592 753270592 647106624 682110272 10202525 11491424 10217873 9055068 11216304 10205072 7018003 7578246 10181650 12305012 6817282 7363464 4944970 7640660 13685436 221622608 311027744 404573408 414089344 271274976 203418608 284125248 272853984 220628048 423581184 Guanine 51798916 48739496 48890560 35543000 32229406 43845920 2355182 3469994 4798088 4364194 2630008 12321538 14034247 4359594 7856910 10892279 2187761 5486718 5550988 9074361 4687734 4928250 - - 222870 - - 245901 - 677772 857397 550363 799804 733245 600852 514388 469774 3244978 2860948 1836590 2583892 3541526 2661962 - 2825726 3069580 2449078 Guanosine 33316702 31859496 29501890 22819640 21176784 29266158 - 107666 114571 481515 254198 354104 756680 582482 469341 566113 163396 387138 467504 519900 468823 488314 129439 97608 109516 85364 169180 119420 186235 180269 224691 185649 213620 187997 156852 122188 136737 176397 226638 219433 194404 216204 136312 - 250451 151422 281501 Guanosine diphosphate - - - - - - 24037 - - - - - - - - 14603 - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - Guanosine monophosphate - - - - - - - - - - - 28004 211100 25982 - - - - 27035 39077 13584 19489 4162214 5016167 3747216 3910940 2477850 2166251 2682308 1926212 2455010 2395584 1690334 2640660 2546182 2572558 2553376 52439 93609 46144 74260 110090 74985 29177 94977 88478 75982 Guanosine triphosphate - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - Homocysteine - - - - - - - - - - - 459180 390354 318281 - - - - 377015 245928 275817 95248 - - - - - - - - - - - - - - - - - - 15117 - - - - - 17831 Hypotaurine 32953 10892 14719 - - 16935 - - - 2555262 3804756 147045 237777 103586 7037014 7935165 2673996 7107848 115920 736308 117827 199211 3155150 8278272 3575929 3560950 146675 124717 100813 1497929 5476108 - 193168 2332058 1078891 - - 2187065 2285611 128982 292714 3083401 1419484 522814 4733860 3078366 1004128 Hypoxanthine 160045696 163077600 154631280 167346560 171814416 230950896 - - - 15609985 22268022 70219600 82587928 30346140 44133184 31347812 24034230 18612812 23635064 25864612 28194086 18243788 431562976 473152800 414013920 423195936 446393632 486667392 477924608 298080416 288845312 305764032 323669888 271189088 265234800 267170736 319852192 8198896 9678086 8006414 13810484 29907568 12668999 12374852 19505344 9339915 20187034 Inosine 6179847 6893581 5954773 6792101 6847495 7174354 - - - 1073630 259073 629322 806737 542310 313944 583316 108397 247682 467029 528484 433081 273845 24934386 21696680 22437672 24973366 42836372 33679284 38817520 23011230 22161674 23923458 25649230 24966456 18949064 23438940 17424204 62552 83186 103711 91629 118173 49391 43964 104090 57311 157645 Inosinic acid - - - - - - 24871 - - - - - - - - - - - - - - - 3675206 1428806 1616595 3479480 6244182 3713128 3552523 771986 1367991 781151 1295588 1932572 2036081 2764436 2937445 - - - - - - - - - - L-Acetylcarnitine 9056887 9800183 8646975 8195258 7670482 9852724 99323 - - 39751380 17391570 36999480 51041020 108959096 17253528 65940936 20766984 42116876 49121004 58483648 35860488 49239248 1585227 2337183 2839132 5003028 11052529 17108468 21546900 39674240 19929544 33364124 37264300 16728922 36582548 3998129 26640994 16022132 21455160 12348549 4329769 17209450 5046738 - 7116293 15408683 10495396 L-Alanine 14446564 6669014 7909675 9132274 10221775 11627458 283181312 273703328 285109728 20301132 22687266 26820244 26310006 25930652 23086300 20181416 12887728 21501198 27983144 24471602 24964952 24911004 58735184 73838704 76075752 62017376 60956904 74161992 77120048 23201582 23277584 19679832 18793030 19901316 20503612 22393624 20660232 28292092 28279344 27360002 30499914 31169668 27350810 28746902 29505170 27435738 30355732 L-Arginine - - - - - - 748148416 625089536 799267264 32374696 13119282 50035868 41399264 62421888 47915068 47922836 22050058 18242292 57379060 44047196 32171244 31195056 - - - - 2828577 - - - - - - - - - - - 41463436 - 31154842 - - 51341396 - - 40176704 L-Asparagine 4030062 3629498 4141886 4142434 2938672 3793559 345539712 400017280 407777472 2475034 2052595 3943109 5491481 10263475 2810081 3575675 1138842 1829466 8539421 3856610 3680374 2386294 7766144 9145961 8426546 8969461 9798781 10542249 9892301 4244924 5410852 6896040 6062680 4931555 4964018 11452103 3611332 628241 982410 2545686 1547304 2042830 1064470 565085 2286064 1972560 1521723 L-Aspartic acid 1105648 547101 647212 789573 665504 - 9505122 6699718 9101824 - - - - - - - - - - - - - 13694009 17785974 13648071 9931322 5338921 11604190 10796974 8575466 7982800 8449603 6144765 4416054 5945536 5555606 13459006 - - - - - - - - - - L-Carnitine 21207848 22060954 23025862 30430678 23228302 46355496 283619 284136 298137 88016424 112083536 123356600 212779184 941608896 220782704 312109248 86726216 119786832 144208096 270513248 115241800 51094292 398142336 567804992 441855648 429669088 405548160 463337408 426458784 395152256 400642304 427943808 321159552 395082400 368891488 276979232 411312608 19731492 44626928 24151860 34878464 106188872 42121764 42388380 79596872 46925672 134373504 L-Cystathionine - 28179 - 688736 672711 587641 31267 25758 43631 - - 441266016 475881408 32875504 - - 9356054 - 635815616 343845856 612717248 637279936 - - - - 231930544 341841568 341818496 38859700 30155808 185185696 176658928 - 43915256 177831488 203278592 - - 410736608 360032544 - 113160616 177785728 130298624 - 429726720 L-Cysteine 75066 38314 54235 37066 22894 31533 - - - - - 102502 461667 53644 33604 36079 - 33010 102709 82113 526813 53662 - - - - - 28176 47846 - - 21736 20411 - - 19435 33777 - 21651 66707 52594 20912 - - - 20657 51897 L-Cystine - - - - - - 15862 - 20179 510170 399441 140437 213810 193025 536279 1096151 213880 192312 268668 297172 169633 249056 - - - - - - - 18742 - - - - - - - 77394 236206 92198 228092 320066 193004 1099243 943013 182826 347020 L-Glutamic acid 21957616 13302902 15027891 6446784 6707050 5296034 274376608 261088048 318657536 3711212 1639669 2147862 3054276 8504559 965580 2910220 1038415 1820005 3026903 7847022 2393540 1630023 25252996 26062776 17293078 17409402 23826292 17987656 19964100 19322504 23578522 31483654 27096648 17412968 18865776 30892950 21101846 - 782236 5325582 1466112 1649042 2711030 - 1444427 1524108 7695702 L-Glutamine 24169214 26079356 27231248 26081750 19186472 26918486 508324352 565497152 599153792 83464656 70233152 92432672 111914624 153009120 82234976 112320048 48137164 70422480 91279288 101236960 69451840 62468244 329035168 246634976 271322080 284476832 372236192 380746080 400959968 174468560 201580912 200985408 204634832 218679472 228665536 230101008 168338656 28511502 33388166 46913784 25108386 40259400 29982096 41177296 37247936 36216932 21735016 L-Histidine 9186307 10611768 11539633 15328450 10427893 12639661 875641024 664696960 768749760 1719827 895193 10852589 726022 16400231 12185610 11851753 8922181 9231803 9572773 3278045 - - 112783184 135910688 177596752 121243736 217278576 254397248 221697456 74074632 71931152 95861520 102988496 78448080 99885712 80901120 79375136 - - - - - - 18784096 - - - L-Isoleucine 24670618 20360772 22032932 29425180 19159242 27556736 1135404672 1158111104 1216480768 18982118 9928877 17748726 46979464 26892260 13190311 22021326 5869548 13006472 30602334 29520438 14703624 16801428 76155296 90075672 84149080 76222120 69237936 75330032 81098648 22539260 21606366 19907164 19734602 24376892 24900580 20740162 32589142 3350015 6362798 5559738 6973966 15017487 5291080 6555564 18278030 5723960 20531852 L-Kynurenine 1780794 1639664 1565528 614593 841879 977068 1467049 1180510 1177418 336595 300925 274167 161746 178153 298050 76688 59489 274613 141001 166042 124271 176127 1019543 2825213 3485072 2214066 1118229 759947 1134159 1537100 616396 434337 504072 505298 1056285 208690 686023 136963 441224 79680 56782 148014 108842 30052 180318 129690 50190 L-Lactic acid - - - - - - - 3182726 - - - - - - - 12677906 - 15203908 - 18901580 - - 117216560 182583536 192392048 179832928 289422048 315548832 299924000 67946656 69742552 62807972 64562160 64979456 74257440 61362608 60989564 1282663 1550903 1262089 947009 2425637 679281 540547 2677193 976405 2418920 L-Leucine 18676754 15749375 17604740 24995576 17196122 21881794 1178993536 1142174848 1275160064 23678360 13085871 32465730 32330360 41274460 23477296 36314884 12388230 23411466 42276200 60943852 38971180 29345392 31474438 33008122 36949192 32435114 45649616 40319764 47091596 10669442 7405266 11667517 10898417 10217852 13763603 11985744 21058996 5771891 11787837 11177744 7245066 12018853 5442662 3451108 10014995 11416046 13639053 L-Lysine - - - - - - 614469568 576618176 539366848 4529374 - 8869884 10461035 28989460 6456706 11906604 2879465 4587604 16380186 13075847 6309682 6511252 3061584 8658425 7709814 6934912 37594340 14712135 7562086 - - - - - 44450092 - - - 12064432 6620840 - - - 18244838 6888354 - 6035880 L-Malic acid 2013289 928157 - - - - 2407371 1857409 2232680 - 5218272 3604944 5808638 - 4522218 4690625 - 41906168 - 10155042 - - 99061296 108668344 118182376 98538272 132319408 185124064 129998072 80336040 82319760 88762328 100689968 72198104 73112360 81348688 89330888 4040443 4067070 4917852 3392670 6582483 4863026 2928273 7796110 3925603 7195867 L-Methionine 11472066 11409515 11680225 15741439 11008660 13170894 993120576 990733824 921051776 2404762 2518621 3364256 6812909 21836884 6015461 6098882 2295983 3828203 8825217 7343833 4098314 3749890 52928256 66731004 52967200 53091224 40785072 49893444 48331212 14080542 12347168 10069993 8666177 12378009 10198533 10963498 13254089 951596 1017353 2212137 701472 1388862 2114178 651764 900432 721844 1877361 L-Phenylalanine 27440948 25794996 25536134 35415536 24789188 30814714 2032983424 1729008896 1879948032 8882618 6455258 7522116 9726272 20036460 12390850 9124674 2243919 4714928 10970525 10574579 4955320 4653652 64976600 77310136 75002848 66509336 66082804 76481568 72304792 25493104 23845820 22077554 21780582 24568010 26489676 23439080 31021372 2854569 4634063 4796480 6368618 7544949 2874231 5863773 7404955 5296466 8313520 L-Proline 191921040 60962668 84094864 75469424 65359420 92179680 1325285376 1338580864 1439157376 39597608 23414478 19080672 32645664 68155216 33160504 33429730 12705048 17547032 36758260 45536556 25222488 17791526 198536576 275261312 256521760 206590896 253797056 268479488 228267440 89805168 88419584 98391200 97649984 89007528 77094768 127594176 116241688 18307910 18554084 22392372 31703744 49805888 16839870 25958126 38874980 21259312 38207912 L-Serine 3650498 2845252 3212436 3310956 2762752 3297281 357062400 313317632 320980000 1584204 952391 1197139 1496117 8012210 1609844 1845724 649836 842680 4048278 2874058 1574170 1261559 12805774 15910099 15520300 12794357 4341390 10006267 7479896 4147620 4229055 1887427 1944744 3918568 3448986 2562309 2233420 965770 450972 540061 702756 2064157 720554 512362 979043 1046382 807402 L-Threonine 857773 794970 895775 1464373 - 1169780 229912480 254535008 285572256 484451 358506 1091221 1539621 1951362 1044179 2200397 278237 334034 3291732 2311130 1101000 804733 4245950 5069124 6990300 4628094 4260423 8897670 8387441 - - - - - - - 798593 - - - 341332 243505 - 2629849 559448 - 559664 L-Tryptophan 6163850 5593460 6014010 10016555 6215694 8307102 598842624 559618112 612314496 31733 - 38357 24763 22276 28477 40181 20523 - 41120 42289 - 39382 9558091 10630296 9014393 9138226 9114430 10499260 11176149 2636752 2857769 2659418 3052154 3234202 3123829 3050345 3814520 148930 210487 284228 240968 285801 156305 204977 284783 240676 218864 L-Tyrosine 11646844 10839452 11200415 14854688 10326679 13292053 708646976 666516672 733318144 3240554 2477538 2623590 2704179 4153290 7334876 6541608 2479385 3506725 4633804 1938573 2477224 2854067 30866102 39695200 43071008 36230996 31492418 22395474 24579638 11901841 10228540 9128195 9591098 11327387 10766220 9556104 15230177 1219106 1460677 1026659 2668161 2585164 1396553 9094366 4144390 1510419 2334210 L-Valine 25193248 20979542 23313916 33517272 22375686 29857936 725524160 753747520 872891328 810300 1783902 1858645 2138846 104688616 284797 1010409 1054740 2012737 1058873 1425867 1888070 3627678 52700908 67395520 60546360 50160664 53534924 54689936 53045524 24561272 19485056 17254540 15259635 22479070 27462852 15475057 31304892 2910198 3901991 2858338 5631784 6204110 2935720 13328717 7523363 3379917 56151788 N6-Acetyl-L-lysine 47667 - - - - - - - - - - - - 48470 55707 - - 48892 65391 69433 - - - - - - - - - 202906 1612136 1525862 943169 263951 209796 143903 1392672 - 21609 22323 25165 36646 27376 - 38382 26407 95546 N-Acetylglutamic acid 85375 67584 68761 - - - 287580 190539 204534 22576480 8094634 4603542 40000832 77860744 12505027 6332549 6240514 8672757 7276036 74278568 16733466 6764742 4231067 10664481 8210600 5698942 6821776 7805290 6779922 1346975 1407674 3424934 1358623 2240124 1277432 1017976 5537236 5744728 9459349 37204388 17943294 16482725 22958606 2103819 16590578 14320974 54144400 N-Acetylglutamine 98865 77861 77203 - - 62697 1085610 904651 961303 98543608 53795284 138615008 199553648 158902432 32573886 57872684 31546416 53189548 33600556 161894528 91104712 167663248 4310880 4192845 5984729 4390904 3890539 5281480 9158537 1768608 3422422 2528262 1313929 3003881 2645588 2043225 1565994 17321074 13849263 20624750 9559061 19551408 14846288 7927282 16138778 9320083 34277940 N-Acetyl-L-alanine 948105 736803 729379 227873 222305 451684 186881 180591 274836 3825692 1365260 3247766 10878305 8260003 504324 553521 515786 685877 2631454 3821259 4015887 3022375 838767 886213 736874 750993 855898 867592 931978 187715 149939 139847 85621 173122 132685 274816 190231 863042 652817 2799742 6456138 2838190 2817462 6918326 2240523 1071040 7748358 N-Acetyl-L-methionine 907806 875353 842675 226760 224789 362942 93575 86443 116711 223860 284741 206205 270456 235640 310347 449621 268979 169467 468721 428536 413403 283626 229034 210189 230622 222316 284267 257498 446309 76889 53884 108898 45287 58889 27169 113320 68284 273964 363578 320988 211982 427674 334620 127299 421890 309822 1557638 N-Acetyl-L-phenylalanine - - - - - - 980782 553026 653006 523866 1041826 898036 1612735 2279400 3149574 2484149 948015 1225064 1620057 1842425 1571980 2026183 178363 383061 279564 271601 330286 106839 137250 162000 - 339868 169546 169198 124448 170456 254623 326338 828697 1196873 1137689 1267677 692504 3899118 2001198 2925041 3337315 N-Acetylornithine 303258 222113 257591 191047 143742 264749 9383095 7276232 7301940 685726 238444 1408820 2730648 5126532 568334 384891 213600 505742 1673042 1984867 1424364 1024656 586916 925176 677281 623506 381253 315048 326098 669103 736625 291559 489620 990887 1145148 359204 506633 - 468154 839238 1904279 764643 598206 10344627 1499200 737640 4894025 N-Acetylserine 2109537 1850479 1884370 1428877 1045240 2109832 4898193 4175578 5199063 21027780 15406799 15750815 35604524 60660612 11342074 5718830 2148062 5321413 14209524 57379912 29341856 29299174 1689263 2680719 2341550 1259402 924439 1739120 2034362 343943 618514 354175 207410 532190 487356 373329 753193 8480769 3841739 10896075 5176654 6873964 8102544 7851902 9172560 2963024 25468944 NAD - - - - - - 108990 - - - - - - - - - - - - - - - 35017 - 27882 56814 38204 38163 - 38463 21292 - 18696 39098 25049 20323 - - - - - - - - - 10076 - NADH - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - NADP - - - - - - - 18049 - 19281 - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - 11565 NADPH - - - - - - - - - - - - - - - - - - - - 10051 - - - - - - - - - - - - - - - - - - - - - - 10936 - - - Niacinamide 10682915 10120878 10650558 6633294 6832502 4880844 - - - 67601168 104342408 123833760 31508528 161892304 11232644 67509840 25417680 64451624 69065400 47947884 64918808 58457820 755423040 849950016 736947072 775425664 858148736 888136640 909474752 565778048 603365312 580361216 582773056 599082048 593694080 572798784 631075392 110405168 125105920 65315840 181837856 117309176 36628448 215968304 154925760 76023216 89147136 Nicotinic acid - - - - - - 236028 208105 252127 - 30196 595397 374963 - 31424 29338 - 381528 - - 382055 1453788 - - - - 50878 - 111140 - - - - - - - - - - 33826 51502 38775 25284 38151 59590 31432 89785 O-Phosphoethanolamine - - - - - - - - - 165202 180605 118517 74130 176589 114967 379747 91869 57243 227887 202958 139293 128553 1651226 2640580 1691342 1641215 1092473 1797382 1851540 1767464 1787244 1126942 1467127 1071614 1436156 941416 1164185 71740 96339 88721 62567 90229 - - 70561 65908 63847 Ornithine - - - - - - 3151385 2514020 2509353 1352782 - 1091274 1989479 3045892 2798382 1606250 1195868 871009 2619012 1930072 915346 3208092 12104428 16145415 15183568 13777068 9421714 29097044 18494152 12684074 - 12524321 17664414 - 19427674 17990930 17599864 - - - - - - - - - - Orotic acid 212929 192870 202132 212130 164206 564583 - - - 142906992 73844680 518695008 1176130176 443620864 100565632 265856768 49087232 139603712 1202956288 1150445440 448341216 505511840 13779 34582 18844 - 1674250 1511518 646894 - - 391712 73851 - 14996 45891 1257095 11424017 24260256 10719812 33127204 18128346 13453479 37039296 22103426 14001727 85053416 Orotidylic acid - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - 35947 Oxidized glutathione - - - - - - - - - - - - - - - - - - - - - - 12217742 17852654 21161782 13831258 7433745 6884969 6271036 12481631 11336095 10490970 13306187 12461113 12518332 11607728 14299046 - - - - - - - - - - Oxoadipic acid 258528 175755 212121 93430 76469 117939 77058 67411 53892 - 33657 73036 74909 69019 24523 355774 - - 56306 58755 40830 23831 - - - - - - - - - - - - - - - - 48836 43331 59479 57153 48892 34414 67934 55833 325076 Oxoglutaric acid - - - - - - 1630014 2096490 2875170 289848 4592670 20997216 104916072 31029912 22216190 22127418 7180997 2784978 48231988 120960936 17264698 12076426 621755 799485 268311 919553 94904 91251 187060 - - - - - - - - - 2563943 2729636 3609738 15824399 7742542 - 10059671 3128006 12367654 Palmitic acid - 3163366 3240679 - - - 16286318 15452117 22092518 2764317 2403952 4346499 - 3065725 - 2456217 - 6752225 2459116 2185653 - 7012790 2009029 - - - 1815945 - - - - - 11277370 - 19319856 39894340 41671616 5019024 3197126 - - 2703581 - - - 2305951 - Pantothenic acid 2574718 2288915 2272417 1644518 1306731 4356566 113426472 110303600 135882928 34935512 25335186 58901864 197095840 362421760 42229028 52472084 29569754 40053388 49342872 67184752 70764936 16927126 8613492 10091849 6379802 6933826 7679422 9316709 9973377 4716260 4442840 4730070 3711810 6433348 5377928 4737388 3607246 5480930 11345742 2290802 35425924 61785076 49480988 15530040 84181064 46439736 63357188 Phenol - - - - - - - - - 39674772 9710095 16882602 32695164 7830710 76322392 58119580 27423894 42080788 47207972 71444928 32059120 59505876 - 125432 - - - - - - 3871153 - - 4502670 4252498 4248446 4027097 21468200 14613803 19243524 16534255 31219010 12924525 6391087 37232396 17925128 23871090 Phosphocreatine - - - - - - - - - 35735 - - - - 118478 - - - - - - - - 22140 22167 - 68120 43204 24108 69525 75423 170651 179544 62892 43244 102857 232300 - - - - - - 91721 - - - Phosphoenolpyruvic acid - - - - - - - - - 1613796 895273 1306276 199191 2525594 852023 616309 - - 3647316 562950 1843078 433988 765444 1706754 1411622 1910741 3152717 4061301 4896122 - 1390940 - 1391561 - 1472310 - - - 1457079 - - 2107836 - - - 1469405 - Phosphoribosyl pyrophosphate - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - Phosphorylcholine - - 48874 - 42628 - 760190 586983 670897 29645832 24110758 16861208 802296 3559420 1912287 22839718 77459344 2957358 26698884 135087 13817115 9756160 107135672 147830864 131914248 106427784 106406744 217979024 182496576 321387712 246247136 183702704 295505792 235937056 245822560 185859744 313906336 31884508 49485784 57015964 51263276 59909860 11412355 13987804 49960816 44156208 28349892 Phosphoserine - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - Pipecolic acid 1051509 523928 642447 387145 437612 668487 15878480 10592507 11604276 325586048 262534480 371939680 345043680 536443872 276252512 452285728 197411968 312531072 430267168 425505600 348595616 285119040 7901147 8722068 8879540 9417339 13321900 7987938 10215123 10793294 7293571 8626465 9974572 9503954 10499913 6518786 11424960 148007200 234787792 215179920 182566384 220359280 105761008 131247664 204853056 199195120 219353360 Propionylcarnitine 2167190 2271978 2130598 2941166 2448774 2882681 109109 100107 150232 266955 159430 249962 456410 1159332 306653 361392 169081 165637 223015 416014 231504 196296 1257979 1956793 2712600 1171994 2963098 3880157 3266636 10084547 6734394 9326860 4984489 4908350 7519542 1595824 10796078 55437 81464 152136 108133 99750 31825 - 68027 71728 83634 Pyruvic acid - - - - - - 42272 66394 99929 334265 421302 1604673 3959265 4525682 2327330 2544262 453717 108179 4774106 5709333 2357917 1171315 132239 369389 208382 308015 236174 158826 197849 369155 343541 394492 365181 394384 278208 378957 271903 126263 368523 487285 434153 501946 242953 243340 578893 450861 1052823 Ribose 1-phosphate 13806 - - - - - 10799 - - 26988 14910 67208 72953 39418 28960 107945 19797 16568 27017 37629 26680 17420 6522193 9467708 8342415 9001586 12216349 12102947 12123457 16632275 18562590 16293575 17999194 16292037 18901192 13531191 17512952 - 57092 129281 - - - - - - - Saccharopine - - - - - - 24754 - 25094 - - 152545 194931 107855 20173 12635 - - 188661 117374 81602 117671 353663 420936 280987 528906 355395 220643 78841 538198 352260 663253 678607 239301 543254 211353 858134 - - 68732 93649 - - 133081 - - 119427 S-Adenosylhomocysteine 126325 100845 95519 76696 71137 61966 - - - - - 93648 105482 24005 - - - 10789 27889 17254 - - 332709 207361 323705 344015 4489107 3175300 4104173 37427 36391 1016247 228539 67354 47396 1594219 1535589 - - 42789 78571 - 21196 100943 23103 49973 112001 S-Adenosylmethionine 80803 64063 75018 243533 155511 178214 40415 19950 24041 7043559 9109086 6771984 2443190 7746565 13374248 20854332 9402032 11673435 3777060 7741929 7471018 4557898 108340 877828 573122 141162 332699 1073162 1773676 - - - - - - - - - - - - - - - - - - Sarcosine 173680 - - - - 158105 18270064 13459911 14550406 23209330 17238196 15269788 11689897 9623873 27110386 22003572 11393614 13715184 9613803 19846952 10400049 14601990 14204851 17937970 7919652 10972591 19575328 19062658 23688366 4544758 5078413 4897674 4386266 3827040 4776848 4062206 5873516 9461342 10341477 8693693 7222274 14568590 6749136 4622350 11160541 13069378 7951226 Succinic acid - - - - - - 1318481 795820 939296 4782648 3341760 29020766 22147138 10654253 6295248 11960983 1212397 4565840 3107354 13044103 1857808 1992464 442828 897620 412609 748127 892864 942173 719397 497865 351437 372158 529774 331084 424176 360512 505716 142771 1298025 1645168 1086918 1752413 834703 1042590 2707235 1362144 3559106 Taurine 2718194 724984 938971 1350070 1294548 3191129 - - - 244786736 307499808 105677464 253714288 103779368 609909760 613806016 229435104 423297664 136275632 473348672 115587936 217646256 228807856 225569696 246079424 279476096 254747072 256717504 307571488 190957760 147968320 148094752 153835248 185292720 203309360 152425632 91981504 294948448 389170528 196500176 490690176 352189600 228275696 444427968 423460960 253801392 567517504 Thymidine 5772410 5249004 5358761 8980129 6413254 7633924 - - - 1865796 866702 2070595 5325582 6900741 1156002 2707028 160548 1241337 3355475 3521314 2286000 424672 - - - - - - - - - - - - - - - 184663 563905 788264 238633 2653816 511192 68403 2704066 1409769 2377410 Uracil 13570314 14310180 13217231 12865106 13839003 11892884 - - - 1148651 585560 815703 1476110 1319496 443831 2303386 185322 1367067 2975748 800976 1417858 983186 2511686 2433423 2586084 2098215 8539059 16024968 11696388 1943336 2510617 5765240 7805910 2909224 1665560 3198410 4328292 128236 129941 176675 580502 217362 152940 1283076 424915 251056 1113634 Ureidopropionic acid - - - - - - 81819992 99157224 109056736 45929 40665 1321553 540843 159203 61193 78502 18933 29998 207662 151405 89987 77412 2313650 2427678 2194634 2205300 2042040 2704285 2686486 317681 330492 360573 - 403469 - 398694 586243 - 161949 290246 166431 253639 118691 - 236843 199983 195913 Ureidosuccinic acid - - - - - - - - - 15486 - 1325028 21490412 1883464 2147796 2311274 13140 44078 12379605 3315492 273254 302427 - 18922 - - 509994 329946 254298 - - 23183 - - - - 94666 - - 106747 3112609 - 145916 1305902 136982 - 1667744 Uric acid 101763 70411 58858 91666 75248 212232 - - - 4083362 2175045 4129454 6899394 2201081 2784830 2938494 800282 1819017 2233791 5398006 3972014 1287050 - 17443 - 45501 - 21317 33769 48575 11547 - 14975 13623 31196 - 12362 380841 1068373 442839 1128188 2707583 314552 617196 4235395 1060819 3677777 Uridine 5972858 5525736 5442427 5554678 4881699 5114210 254863 194265 244765 308204 214274 550988 542250 2631490 206829 547730 88956 227377 664185 464874 383821 104730 2304420 2312033 2821954 1826756 5424087 11280243 8229334 1742857 1736460 3769561 4145598 1494573 1297837 1935782 2638421 43986 139137 71788 58742 373299 75595 35610 415056 171979 507861 Uridine 5'-diphosphate - - - - - - 32863 - - - - - - - - - - - - - - - 1467954 1578920 1473085 1187790 1108629 673467 1255122 407218 673633 479708 515863 139091 334443 201959 1468940 - - - - - - - - - - Uridine 5'-monophosphate - - - - - - - - - - - - - - 10806 - - - - - - - 13184725 16497259 12221096 13467716 16742133 23709450 20930202 7990209 8362483 15466976 11107025 7503142 7846713 11411918 20954722 - - - - - - - - - - Uridine diphosphate glucose - - - - - - - - - - - - - - - 12771 - - - - - - 7578419 6976859 7056286 5857462 5789532 4201473 6227141 1538418 1850972 1680287 1754016 492453 1179848 543986 4527262 - - - - - - - - - - Uridine diphosphate-N-acetylglucosamine - - - - - - - - - - - - - - - - - - - - - - 454426 456244 357969 388832 339304 778379 1095730 129045 171241 359483 412318 170747 122055 160438 503282 - - - - - - - - - - Uridine triphosphate - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - Valerylcarnitine 6709744 7249170 6606384 8303038 6402165 10949224 50729 - 30827 123746 58415 279114 559325 508032 89893 125632 48797 82608 143874 227292 61302 105625 68879 88146 134027 183542 147697 151288 148042 980452 265289 326367 207253 171354 308300 52769 678758 18778 46175 29680 64758 66000 24193 35656 77647 45877 143912 Xanthine 5608654 5333568 4941937 15063509 8762040 4423872 531322 564394 641576 10067103 8107582 24272060 19389590 13366703 15408447 20429474 5566927 7785851 15483996 21785208 12821655 11423673 42542476 44189556 37132252 40590464 35656964 43571832 46348980 41886396 39289400 36255664 39883684 34679548 41081388 35309244 41235952 2843308 5681521 3208242 4430147 11275597 2461084 1987242 8459801 4035360 6989351 Xanthosine 100572 106395 80678 422755 281531 119361 183590 124955 177587 178201 167238 227747 367784 325150 149341 396331 106431 127003 227400 330096 311772 238057 501812 356695 344427 604906 433356 145728 199201 1123391 531166 543955 788473 722695 1110496 577002 871491 60114 65887 44474 49536 75003 27701 27910 80567 62706 100985 Xanthylic acid - - - - - - - - - - - - - - 26319 22333 20002 11854 52866 - 10914 11054 74365 91081 55093 104132 87994 132694 131400 - - - - - - - - 64248 34050 - 23037 36550 - - 31211 31708 43956 MS_METABOLITE_DATA_END #METABOLITES METABOLITES_START metabolite_name 1-Methylnicotinamide 2,3-Diphosphoglyceric acid 3-Hydroxybutyric acid 3-Phosphoglyceric acid 4,5-Dihydroorotic acid 4-Hydroxyproline 5'-Methylthioadenosine 5-Phosphoribosylamine 6-Phosphogluconic acid Acetoacetic acid Acetyl-CoA Acetylcysteine Adenine Adenosine Adenosine diphosphate ribose Adenosine monophosphate Adenosine triphosphate Adenylsuccinic acid ADP Allantoin Aminoadipic acid Argininosuccinic acid Beta-Alanine Betaine Butyrylcarnitine Carbamoyl phosphate Carnosine CDP Choline cis-Aconitic acid Citric acid Citrulline Creatine Creatinine Cyclic AMP Cytidine Cytidine monophosphate Cytidine triphosphate Cytosine D-2-Hydroxyglutaric acid D-Glucose D-Glyceraldehyde 3-phosphate Dihydrofolic acid Dihydroxyacetone phosphate D-Ribose 5-phosphate D-Sedoheptulose 7-phosphate dTDP FAD Folic acid Fructose 1,6-bisphosphate Fructose 6-phosphate Fumaric acid Glucose 6-phosphate Glutathione Glycerol 3-phosphate Glycine Guanidoacetic acid Guanine Guanosine Guanosine diphosphate Guanosine monophosphate Guanosine triphosphate Homocysteine Hypotaurine Hypoxanthine Inosine Inosinic acid L-Acetylcarnitine L-Alanine L-Arginine L-Asparagine L-Aspartic acid L-Carnitine L-Cystathionine L-Cysteine L-Cystine L-Glutamic acid L-Glutamine L-Histidine L-Isoleucine L-Kynurenine L-Lactic acid L-Leucine L-Lysine L-Malic acid L-Methionine L-Phenylalanine L-Proline L-Serine L-Threonine L-Tryptophan L-Tyrosine L-Valine N6-Acetyl-L-lysine N-Acetylglutamic acid N-Acetylglutamine N-Acetyl-L-alanine N-Acetyl-L-methionine N-Acetyl-L-phenylalanine N-Acetylornithine N-Acetylserine NAD NADH NADP NADPH Niacinamide Nicotinic acid O-Phosphoethanolamine Ornithine Orotic acid Orotidylic acid Oxidized glutathione Oxoadipic acid Oxoglutaric acid Palmitic acid Pantothenic acid Phenol Phosphocreatine Phosphoenolpyruvic acid Phosphoribosyl pyrophosphate Phosphorylcholine Phosphoserine Pipecolic acid Propionylcarnitine Pyruvic acid Ribose 1-phosphate Saccharopine S-Adenosylhomocysteine S-Adenosylmethionine Sarcosine Succinic acid Taurine Thymidine Uracil Ureidopropionic acid Ureidosuccinic acid Uric acid Uridine Uridine 5'-diphosphate Uridine 5'-monophosphate Uridine diphosphate glucose Uridine diphosphate-N-acetylglucosamine Uridine triphosphate Valerylcarnitine Xanthine Xanthosine Xanthylic acid METABOLITES_END #END