#METABOLOMICS WORKBENCH hormel101_20161202_130330_mwtab.txt DATATRACK_ID:785 STUDY_ID:ST000514 ANALYSIS_ID:AN000787 PROJECT_ID:PR000383 VERSION 1 CREATED_ON December 8, 2016, 3:23 pm #PROJECT PR:PROJECT_TITLE Mayo Metabolomics Pilot and Feasibility Award: Role of muscle insulin and IGF-1 PR:PROJECT_TITLE signaling on serum and muscle metabolite profiles PR:PROJECT_SUMMARY Skeletal muscle insulin resistance is a cardinal feature of the pathogenesis of PR:PROJECT_SUMMARY type 2 diabetes. Insulin and IGF-1 signal through their highly related receptors PR:PROJECT_SUMMARY to impact on many aspects of muscle physiology including glucose homeostasis, PR:PROJECT_SUMMARY protein metabolism, and mitochondrial function. Early physiological studies, as PR:PROJECT_SUMMARY well as recent large scale metabolomic studies, have shown that changes in PR:PROJECT_SUMMARY specific pools of circulating amino acid metabolites, such as branched chain PR:PROJECT_SUMMARY amino acids (BCAAs), are associated with insulin resistance and can predict PR:PROJECT_SUMMARY future diabetes, but the source and impact of these changes in amino acids are PR:PROJECT_SUMMARY not fully understood. We have recently generated mice which lack insulin PR:PROJECT_SUMMARY receptors (IR) or IGF-1 receptors (IGF1R) or both in muscle using Cre lox PR:PROJECT_SUMMARY recombination. We find that mice which lack only IR or only IGF1R in muscle show PR:PROJECT_SUMMARY minimal changes in muscle mass, but do display increases in proteasomal activity PR:PROJECT_SUMMARY and autophagy in muscle. On the other hand, mice with combined loss of both IR PR:PROJECT_SUMMARY and IGF1R display markedly decreased muscle mass and enhanced degradation PR:PROJECT_SUMMARY pathways, associated with increased protein synthesis, and display changes in PR:PROJECT_SUMMARY mitochondrial gene regulation, indicating that both receptors can compensate to PR:PROJECT_SUMMARY some extent for loss of the other. We hypothesize that IR and IGF1R signaling in PR:PROJECT_SUMMARY muscle coordinate amino acid metabolite turnover and fuel PR:PROJECT_SUMMARY substrate/mitochondrial metabolism, and that in insulin resistant states, PR:PROJECT_SUMMARY changes in protein metabolism and mitochondrial function disrupt relative PR:PROJECT_SUMMARY proportions of amino acid metabolites, which in turn contribute to diabetes risk PR:PROJECT_SUMMARY and/or muscle pathology. We propose to test this hypothesis by performing large PR:PROJECT_SUMMARY scale metabolomics on serum and muscle from mice lacking IR, IGF1R or both in PR:PROJECT_SUMMARY muscle, and we will compare these changes to both insulin deficient PR:PROJECT_SUMMARY streptozotocin-treated and insulin resistant diet-induced obese mouse models. To PR:PROJECT_SUMMARY gain insight into which pathways are critical for metabolite changes, we will PR:PROJECT_SUMMARY also treat mice with specific inhibitors of mTOR, a common protein synthesis PR:PROJECT_SUMMARY pathway, as well as inhibitors of autophagy or proteasomal degradation and PR:PROJECT_SUMMARY determine metabolite concentrations in muscle and serum. These studies will PR:PROJECT_SUMMARY identify specific pathways that impact amino acid and mitochondrial metabolite PR:PROJECT_SUMMARY flux which are perturbed in insulin resistant states, and potentially provide PR:PROJECT_SUMMARY insights into how changes in amino acid metabolites contribute to diabetes risk. PR:INSTITUTE Mayo Clinic PR:LAST_NAME O'Neill PR:FIRST_NAME Brian PR:ADDRESS One Joslin Place, Boston, MA 02215 PR:EMAIL brian.o'neill@joslin.harvard.edu PR:PHONE 617-309-2400 #STUDY ST:STUDY_TITLE Inhibition of autophagy/proteasome degradation or inhibition of protein ST:STUDY_TITLE synthesis in models of muscle insulin resistance affect amino acids metabolites ST:STUDY_TITLE in serum ST:STUDY_SUMMARY To determine which protein degradation pathways downstream of IR and IGF1R ST:STUDY_SUMMARY contribute to changes in amino acid and mitochondrial metabolite pools, we will ST:STUDY_SUMMARY treat control, M-IR-/-, MIGIRKO, and HFD obese mice with inhibitors of autophagy ST:STUDY_SUMMARY or proteasome. We will treat 5 animals each of control, M-IR-/-, MIGIRKO, and ST:STUDY_SUMMARY HFD mice with vehicle, colchicine to inhibit autophagy, or MG132 to inhibit ST:STUDY_SUMMARY proteasome activity, then measure amino acid metabolites in serum. ST:INSTITUTE Mayo Clinic ST:LAST_NAME O'Neill ST:FIRST_NAME Brian ST:ADDRESS One Joslin Place, Boston, MA 02215 ST:EMAIL brian.o'neill@joslin.harvard.edu ST:PHONE 617-309-2400 #SUBJECT SU:SUBJECT_TYPE Mouse SU:SUBJECT_SPECIES Mus musculus SU:TAXONOMY_ID 10090 #SUBJECT_SAMPLE_FACTORS: SUBJECT(optional)[tab]SAMPLE[tab]FACTORS(NAME:VALUE pairs separated by |)[tab]Additional sample data SUBJECT_SAMPLE_FACTORS 613 ms5629-1 Group:control | Genotype:Irlox IGFRlox | Treatment:saline assay=Concentration of AA + metabolites in serum SUBJECT_SAMPLE_FACTORS 595 ms5629-2 Group:control | Genotype:Irlox IGFRlox | Treatment:saline assay=Concentration of AA + metabolites in serum SUBJECT_SAMPLE_FACTORS 1837 ms5629-3 Group:control | Genotype:Irlox IGFRlox | Treatment:saline assay=Concentration of AA + metabolites in serum SUBJECT_SAMPLE_FACTORS 2005 ms5629-4 Group:control | Genotype:Irlox | Treatment:saline assay=Concentration of AA + metabolites in serum SUBJECT_SAMPLE_FACTORS 1942 ms5629-5 Group:control | Genotype:Irlox | Treatment:saline assay=Concentration of AA + metabolites in serum SUBJECT_SAMPLE_FACTORS 1956 ms5629-6 Group:control | Genotype:Irlox | Treatment:saline assay=Concentration of AA + metabolites in serum SUBJECT_SAMPLE_FACTORS 1989 ms5629-7 Group:control | Genotype:IR -/- IGFR -/- | Treatment:saline assay=Concentration of AA + metabolites in serum SUBJECT_SAMPLE_FACTORS 615 ms5629-8 Group:MIGIRKO | Genotype:IR -/- IGFR -/- | Treatment:saline assay=Concentration of AA + metabolites in serum SUBJECT_SAMPLE_FACTORS 597 ms5629-9 Group:MIGIRKO | Genotype:IR -/- IGFR -/- | Treatment:saline assay=Concentration of AA + metabolites in serum SUBJECT_SAMPLE_FACTORS 1838 ms5629-10 Group:MIGIRKO | Genotype:IR -/- IGFR -/- | Treatment:saline assay=Concentration of AA + metabolites in serum SUBJECT_SAMPLE_FACTORS 1815 ms5629-11 Group:MIGIRKO | Genotype:IR -/- IGFR -/- | Treatment:saline assay=Concentration of AA + metabolites in serum SUBJECT_SAMPLE_FACTORS 2028 ms5629-12 Group:MIGIRKO | Genotype:IR -/- IGFR -/- | Treatment:saline assay=Concentration of AA + metabolites in serum SUBJECT_SAMPLE_FACTORS 2029 ms5629-13 Group:MIGIRKO | Genotype:IR -/- IGFR -/- | Treatment:saline assay=Concentration of AA + metabolites in serum SUBJECT_SAMPLE_FACTORS 1947 ms5629-14 Group:HFD | Genotype:Irlox | Treatment:saline assay=Concentration of AA + metabolites in serum SUBJECT_SAMPLE_FACTORS 1950 ms5629-15 Group:HFD | Genotype:Irlox | Treatment:saline assay=Concentration of AA + metabolites in serum SUBJECT_SAMPLE_FACTORS 1960 ms5629-16 Group:HFD | Genotype:Irlox | Treatment:saline assay=Concentration of AA + metabolites in serum SUBJECT_SAMPLE_FACTORS 1964 ms5629-17 Group:HFD | Genotype:Irlox IGFRlox | Treatment:saline assay=Concentration of AA + metabolites in serum SUBJECT_SAMPLE_FACTORS 1988 ms5629-18 Group:HFD | Genotype:Irlox | Treatment:saline assay=Concentration of AA + metabolites in serum SUBJECT_SAMPLE_FACTORS 1849 ms5629-19 Group:Control colch | Genotype:Irlox IGFRlox | Treatment:Colch assay=Concentration of AA + metabolites in serum SUBJECT_SAMPLE_FACTORS 606 ms5629-20 Group:Control colch | Genotype:Irlox IGFRlox | Treatment:Colch assay=Concentration of AA + metabolites in serum SUBJECT_SAMPLE_FACTORS 1826 ms5629-21 Group:Control colch | Genotype:Irlox IGFRlox | Treatment:Colch assay=Concentration of AA + metabolites in serum SUBJECT_SAMPLE_FACTORS 1847 ms5629-22 Group:Control colch | Genotype:Irlox IGFRlox | Treatment:Colch assay=Concentration of AA + metabolites in serum SUBJECT_SAMPLE_FACTORS 1818 ms5629-23 Group:Control colch | Genotype:- | Treatment:Colch assay=Concentration of AA + metabolites in serum SUBJECT_SAMPLE_FACTORS 1944 ms5629-24 Group:Control colch | Genotype:Irlox | Treatment:Colch assay=Concentration of AA + metabolites in serum SUBJECT_SAMPLE_FACTORS 1958 ms5629-25 Group:Control colch | Genotype:Irlox | Treatment:Colch assay=Concentration of AA + metabolites in serum SUBJECT_SAMPLE_FACTORS 1852 ms5629-26 Group:MIGIRKO colch | Genotype:IR -/- IGFR -/- | Treatment:Colch assay=Concentration of AA + metabolites in serum SUBJECT_SAMPLE_FACTORS 1853 ms5629-27 Group:MIGIRKO colch | Genotype:IR -/- IGFR -/- | Treatment:Colch assay=Concentration of AA + metabolites in serum SUBJECT_SAMPLE_FACTORS 1856 ms5629-28 Group:MIGIRKO colch | Genotype:IR -/- IGFR -/- | Treatment:Colch assay=Concentration of AA + metabolites in serum SUBJECT_SAMPLE_FACTORS 1817 ms5629-29 Group:MIGIRKO colch | Genotype:IR -/- IGFR -/- | Treatment:Colch assay=Concentration of AA + metabolites in serum SUBJECT_SAMPLE_FACTORS 607 ms5629-30 Group:MIGIRKO colch | Genotype:IR -/- IGFR -/- | Treatment:Colch assay=Concentration of AA + metabolites in serum SUBJECT_SAMPLE_FACTORS 1824 ms5629-31 Group:MIGIRKO colch | Genotype:IR -/- IGFR -/- | Treatment:Colch assay=Concentration of AA + metabolites in serum SUBJECT_SAMPLE_FACTORS 1951 ms5629-32 Group:HFD + Colch | Genotype:Irlox | Treatment:Colch assay=Concentration of AA + metabolites in serum SUBJECT_SAMPLE_FACTORS 1952 ms5629-33 Group:HFD + Colch | Genotype:Irlox | Treatment:Colch assay=Concentration of AA + metabolites in serum SUBJECT_SAMPLE_FACTORS 1965 ms5629-34 Group:HFD + Colch | Genotype:Irlox IGFRlox | Treatment:Colch assay=Concentration of AA + metabolites in serum SUBJECT_SAMPLE_FACTORS 1991 ms5629-35 Group:HFD + Colch | Genotype:Irlox | Treatment:Colch assay=Concentration of AA + metabolites in serum SUBJECT_SAMPLE_FACTORS 1994 ms5629-36 Group:HFD + Colch | Genotype:Irlox | Treatment:Colch assay=Concentration of AA + metabolites in serum #COLLECTION CO:COLLECTION_SUMMARY mouse serum #TREATMENT TR:TREATMENT_SUMMARY To determine which protein degradation pathways downstream of IR and IGF1R TR:TREATMENT_SUMMARY contribute to changes in amino acid and mitochondrial metabolite pools, we will TR:TREATMENT_SUMMARY treat control, M-IR-/-, MIGIRKO, and HFD obese mice with inhibitors of autophagy TR:TREATMENT_SUMMARY or proteasome. We will treat 5 animals each of control, M-IR-/-, MIGIRKO, and TR:TREATMENT_SUMMARY HFD mice with vehicle, colchicine to inhibit autophagy, or MG132 to inhibit TR:TREATMENT_SUMMARY proteasome activity, then measure amino acid metabolites in serum as well as TCA TR:TREATMENT_SUMMARY cycle and amino acid metabolites in muscle tissue. #SAMPLEPREP SP:SAMPLEPREP_SUMMARY Concentration of amino acid metabolites in serum #CHROMATOGRAPHY CH:CHROMATOGRAPHY_TYPE Reversed phase CH:INSTRUMENT_NAME Waters Acquity CH:COLUMN_NAME Waters Acquity BEH C18 (150 x 2.1mm, 1.7um) #ANALYSIS AN:ANALYSIS_TYPE MS #MS MS:MS_COMMENTS - MS:INSTRUMENT_NAME Thermo Quantum Ultra MS:INSTRUMENT_TYPE Triple quadrupole MS:MS_TYPE ESI MS:ION_MODE POSITIVE #MS_METABOLITE_DATA MS_METABOLITE_DATA:UNITS uM MS_METABOLITE_DATA_START Samples ms5629-1 ms5629-2 ms5629-3 ms5629-4 ms5629-5 ms5629-6 ms5629-7 ms5629-8 ms5629-9 ms5629-10 ms5629-11 ms5629-12 ms5629-13 ms5629-14 ms5629-15 ms5629-16 ms5629-17 ms5629-18 ms5629-19 ms5629-20 ms5629-21 ms5629-22 ms5629-23 ms5629-24 ms5629-25 ms5629-26 ms5629-27 ms5629-28 ms5629-29 ms5629-30 ms5629-31 ms5629-32 ms5629-33 ms5629-34 ms5629-35 ms5629-36 Factors Group:control | Genotype:Irlox IGFRlox | Treatment:saline Group:control | Genotype:Irlox IGFRlox | Treatment:saline Group:control | Genotype:Irlox IGFRlox | Treatment:saline Group:control | Genotype:Irlox | Treatment:saline Group:control | Genotype:Irlox | Treatment:saline Group:control | Genotype:Irlox | Treatment:saline Group:control | Genotype:IR -/- IGFR -/- | Treatment:saline Group:MIGIRKO | Genotype:IR -/- IGFR -/- | Treatment:saline Group:MIGIRKO | Genotype:IR -/- IGFR -/- | Treatment:saline Group:MIGIRKO | Genotype:IR -/- IGFR -/- | Treatment:saline Group:MIGIRKO | Genotype:IR -/- IGFR -/- | Treatment:saline Group:MIGIRKO | Genotype:IR -/- IGFR -/- | Treatment:saline Group:MIGIRKO | Genotype:IR -/- IGFR -/- | Treatment:saline Group:HFD | Genotype:Irlox | Treatment:saline Group:HFD | Genotype:Irlox | Treatment:saline Group:HFD | Genotype:Irlox | Treatment:saline Group:HFD | Genotype:Irlox IGFRlox | Treatment:saline Group:HFD | Genotype:Irlox | Treatment:saline Group:Control colch | Genotype:Irlox IGFRlox | Treatment:Colch Group:Control colch | Genotype:Irlox IGFRlox | Treatment:Colch Group:Control colch | Genotype:Irlox IGFRlox | Treatment:Colch Group:Control colch | Genotype:Irlox IGFRlox | Treatment:Colch Group:Control colch | Genotype:- | Treatment:Colch Group:Control colch | Genotype:Irlox | Treatment:Colch Group:Control colch | Genotype:Irlox | Treatment:Colch Group:MIGIRKO colch | Genotype:IR -/- IGFR -/- | Treatment:Colch Group:MIGIRKO colch | Genotype:IR -/- IGFR -/- | Treatment:Colch Group:MIGIRKO colch | Genotype:IR -/- IGFR -/- | Treatment:Colch Group:MIGIRKO colch | Genotype:IR -/- IGFR -/- | Treatment:Colch Group:MIGIRKO colch | Genotype:IR -/- IGFR -/- | Treatment:Colch Group:MIGIRKO colch | Genotype:IR -/- IGFR -/- | Treatment:Colch Group:HFD + Colch | Genotype:Irlox | Treatment:Colch Group:HFD + Colch | Genotype:Irlox | Treatment:Colch Group:HFD + Colch | Genotype:Irlox IGFRlox | Treatment:Colch Group:HFD + Colch | Genotype:Irlox | Treatment:Colch Group:HFD + Colch | Genotype:Irlox | Treatment:Colch Histidine 36.8 35.4 36.0 52.4 40.2 47.9 33.0 37.5 28.5 32.0 25.7 34.8 42.1 39.6 26.4 35.9 26.3 35.7 30.8 24.1 32.5 24.7 32.1 27.7 20.7 26.9 25.9 27.8 29.9 21.4 19.5 18.2 16.0 22.1 21.3 21.7 Hydroxyproline 14.7 17.0 18.6 19.0 20.0 14.8 12.2 14.9 14.9 19.5 16.1 16.8 22.3 19.3 12.8 15.4 13.5 11.4 20.7 15.9 24.3 13.7 21.5 20.0 18.0 14.3 14.4 18.6 19.7 15.9 17.2 8.3 7.8 9.3 9.4 9.6 1-Methylhistidine 0.0 0.7 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 1.1 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 3-Methylhistidine 1.5 7.2 6.9 7.3 7.2 7.5 2.6 6.6 4.6 5.7 1.7 1.3 3.4 1.6 4.6 5.5 3.7 5.1 3.4 3.0 7.9 3.7 5.1 10.7 6.7 6.0 3.4 5.9 3.5 3.6 4.4 2.3 4.4 7.3 2.9 4.5 Phosphoethanolamine 4.9 4.5 6.8 5.1 6.2 8.2 7.3 7.4 6.6 7.9 6.4 6.9 7.4 12.3 5.9 8.7 6.0 6.5 7.3 5.8 7.5 6.2 9.5 4.0 6.3 7.0 7.2 8.7 5.5 4.5 7.5 9.9 4.8 6.7 7.1 7.1 Carnosine 0.0 1.1 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 Anserine 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 Ethanolamine 8.6 10.9 15.4 17.9 16.2 22.1 19.7 10.9 8.6 12.5 9.8 10.6 13.5 20.0 19.2 24.4 20.1 15.7 16.9 10.2 19.3 15.0 12.9 15.7 14.5 13.1 12.4 12.2 9.3 8.8 12.4 17.0 13.3 16.2 16.6 14.1 Aspartic Acid 7.7 6.8 12.5 6.6 10.6 9.9 11.6 8.1 7.6 10.4 8.8 10.2 13.5 13.3 10.3 13.7 9.3 10.3 14.0 8.7 23.0 10.1 13.7 6.9 8.7 11.4 8.9 9.3 7.4 6.8 12.8 9.0 5.7 7.4 10.3 9.3 Sarcosine 0.8 1.9 1.0 0.6 1.5 0.4 0.8 0.5 0.5 0.8 0.5 0.6 1.1 0.0 0.0 0.0 0.3 0.5 1.1 1.1 1.7 0.9 0.5 2.3 1.6 0.8 0.6 1.0 0.9 0.8 0.8 0.0 0.0 0.2 0.0 0.2 beta-alanine 1.0 2.5 1.4 0.8 2.1 0.5 1.0 0.6 0.6 1.1 0.5 0.7 1.5 -0.1 -0.2 -0.2 0.5 0.9 1.4 1.4 2.6 1.1 0.6 3.1 2.1 1.0 0.8 1.4 1.0 1.0 1.0 -0.1 -0.1 0.3 0.0 0.2 gamma-Amino-N-butyric-acid 0.1 0.1 0.2 0.2 0.3 0.9 1.2 0.2 0.1 0.2 0.1 0.1 0.1 0.2 0.3 0.2 0.2 0.3 0.2 0.1 0.4 0.2 0.2 0.2 0.2 0.2 0.2 0.1 0.2 0.1 0.2 0.2 0.2 0.1 0.5 0.1 alpha-Aminoadipic-acid 12.4 5.6 9.0 6.2 6.8 3.3 3.7 14.1 7.2 8.3 8.2 5.8 6.0 10.9 15.2 15.3 10.5 11.0 6.4 7.8 9.2 7.0 12.1 10.7 7.5 6.5 7.4 7.2 11.5 6.6 9.1 11.5 11.2 10.4 9.6 14.2 beta-Aminoisobutyric-acid 0.0 0.0 0.0 0.0 0.0 0.1 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.1 0.1 0.1 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.1 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 Hydroxylysine 1 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 Hydroxylysine 2 0.9 1.2 0.8 0.5 0.8 0.5 0.2 0.5 0.4 0.3 0.4 0.3 0.6 0.0 0.0 0.0 0.1 0.0 0.4 0.2 0.5 0.3 0.6 0.4 0.4 0.4 0.2 0.0 0.4 0.3 0.2 0.0 0.0 0.0 0.0 0.0 alpha-Amino-N-butyric-acid 5.2 2.8 3.1 3.9 4.2 3.3 3.6 3.0 2.2 3.5 1.8 4.1 4.2 38.7 52.4 58.3 3.1 6.6 3.4 5.0 1.7 2.5 2.2 7.1 3.0 3.6 3.9 3.8 2.7 2.2 1.6 10.1 8.7 4.6 9.4 8.3 Cystathionine 1 2.2 3.0 2.2 1.6 2.8 1.5 0.7 0.9 0.3 2.0 0.6 2.1 1.7 2.1 1.4 3.2 1.1 3.2 1.9 6.4 2.6 1.7 1.7 5.3 3.9 0.9 1.7 0.9 1.1 2.1 1.3 1.1 0.5 3.2 2.3 2.2 Cystathionine 2 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 Methionine 78.4 129.2 55.2 64.7 96.4 61.2 34.6 60.4 62.6 55.4 64.8 52.3 74.7 59.6 57.2 82.2 62.9 65.7 72.1 63.6 107.4 58.0 77.1 97.0 84.8 51.9 42.4 46.5 70.9 62.4 69.5 40.4 41.8 48.5 51.4 50.6 allo-Isoleucine 0.0 0.6 0.7 0.0 0.0 0.0 0.0 0.0 0.0 0.5 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.4 0.0 0.0 0.0 0.4 0.0 0.2 0.0 0.0 0.0 Homocystine 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 Asparagine 45.0 77.7 43.0 68.7 66.4 76.4 60.6 60.2 54.0 53.6 44.4 50.3 83.0 65.7 68.3 104.0 73.2 101.1 55.3 51.3 78.7 37.3 51.1 88.1 63.3 42.3 39.2 60.0 59.7 68.5 38.7 42.9 59.2 47.7 79.2 91.6 Arginine 80.8 107.4 97.5 74.4 89.1 62.0 48.7 61.1 51.4 65.0 79.9 53.1 95.1 74.5 30.5 61.9 54.3 97.7 94.4 70.6 157.3 75.4 89.4 98.6 82.0 93.9 67.4 54.0 92.5 70.3 60.6 58.3 41.2 55.1 54.6 65.2 Taurine 446.4 587.1 723.3 608.3 573.3 530.1 518.1 521.4 388.9 574.6 431.1 438.2 626.7 895.4 854.9 1187.3 703.2 991.5 745.3 572.5 1027.8 577.4 636.3 661.4 564.5 577.6 604.2 662.4 510.4 383.5 555.2 627.8 545.9 673.1 750.7 832.9 Serine 121.4 180.4 143.6 156.5 173.0 151.6 135.0 167.6 145.6 143.7 134.0 161.7 224.1 152.9 156.4 225.8 188.1 252.5 138.5 130.1 190.4 108.4 152.9 172.8 137.9 140.2 133.1 166.6 171.5 171.2 123.7 105.2 115.1 143.3 209.4 200.2 Glutamine 456.5 438.1 660.2 624.8 573.6 581.7 688.0 432.8 446.2 620.3 586.7 557.4 787.5 703.0 738.0 1082.6 725.3 748.7 632.8 504.3 616.3 534.7 634.7 729.1 654.6 651.2 609.6 617.5 624.8 454.8 359.0 619.8 618.1 556.1 751.3 878.9 Glycine 221.7 379.5 281.5 329.8 336.3 290.8 263.0 323.3 267.1 290.1 235.3 248.0 372.3 146.8 135.4 148.9 291.3 307.6 249.5 214.8 312.7 214.8 226.4 320.7 255.2 247.0 274.3 373.7 254.6 247.0 224.5 128.1 142.5 230.3 223.3 244.4 Citrulline 40.6 69.8 66.3 67.4 67.7 61.0 60.7 29.4 36.0 49.7 34.4 30.9 59.1 61.1 55.9 94.5 61.7 72.9 68.0 62.8 99.5 56.5 53.8 98.4 77.6 60.7 45.5 49.1 46.0 33.9 43.3 40.0 45.1 44.8 66.7 55.4 Glutamic Acid 32.1 34.5 78.3 30.8 39.8 47.7 53.8 40.0 33.2 49.9 33.9 35.6 55.2 64.6 48.4 71.7 33.3 46.1 53.7 37.9 100.1 47.7 59.0 28.0 40.2 51.7 45.6 55.5 41.7 29.4 56.0 41.5 24.0 39.5 37.5 34.8 Threonine 147.7 228.8 137.5 128.9 159.8 93.0 81.6 155.9 141.3 139.2 130.1 135.2 202.0 193.0 195.3 252.6 200.8 188.8 134.0 151.7 197.4 116.4 162.4 176.2 129.5 121.2 113.8 120.7 184.2 166.6 118.2 112.6 117.3 166.4 187.4 194.7 Alanine 384.0 678.0 461.9 755.8 621.1 585.7 435.1 417.1 415.4 464.1 346.9 452.8 937.1 642.7 655.5 905.4 754.3 1009.9 470.9 441.0 802.3 382.9 475.9 954.1 603.0 423.5 330.4 545.2 460.4 404.3 391.1 358.8 434.6 397.0 776.8 683.9 Proline 104.4 154.7 91.4 111.9 128.0 129.1 76.4 88.8 83.9 79.7 77.0 61.0 138.9 98.9 80.9 147.7 111.0 127.6 102.7 84.9 167.3 74.8 101.7 173.4 116.8 75.9 61.9 80.5 96.0 83.2 72.8 51.6 60.7 62.5 99.5 92.0 Ornithine 49.6 63.1 45.3 42.1 39.8 38.1 36.7 42.7 43.8 40.1 43.9 41.1 70.0 51.0 73.0 94.9 44.4 44.3 44.7 32.4 49.2 28.9 46.5 39.4 26.7 38.7 33.4 42.8 47.2 39.9 34.4 19.4 21.4 22.8 32.4 31.6 Lysine 343.7 384.7 274.4 275.2 272.3 198.1 158.8 317.5 298.0 337.8 337.9 306.1 451.3 394.3 298.0 466.7 399.5 422.3 291.3 291.5 371.5 255.3 322.4 382.7 253.5 272.3 269.4 256.5 409.8 318.5 258.2 234.9 194.3 272.6 293.3 276.7 Cystine 13.7 8.5 6.7 11.0 11.1 7.8 2.0 14.8 7.7 5.9 15.9 5.4 4.5 3.7 9.1 9.5 16.0 16.4 10.9 9.5 14.9 4.2 19.0 39.7 4.7 7.8 6.9 7.2 21.2 16.3 3.9 7.7 9.7 7.1 14.8 15.4 Tyrosine 88.9 150.5 85.1 85.9 101.4 119.4 80.2 96.9 83.2 81.3 77.7 53.7 71.5 69.8 72.1 84.1 61.5 88.5 63.6 68.9 121.1 62.9 68.3 103.0 74.5 58.2 48.0 59.5 78.3 78.1 67.7 43.2 43.5 40.3 57.2 60.7 Valine 192.5 226.3 153.6 164.0 223.6 163.1 136.2 158.8 147.6 177.1 164.1 177.5 229.5 198.5 207.5 261.6 221.7 273.5 184.0 188.1 259.5 163.3 172.2 225.2 156.4 169.1 168.2 219.5 203.5 193.4 138.9 140.0 148.3 158.5 219.2 245.9 MS_METABOLITE_DATA_END #METABOLITES METABOLITES_START metabolite_name Histidine Hydroxyproline 1-Methylhistidine 3-Methylhistidine Phosphoethanolamine Carnosine Anserine Ethanolamine Aspartic Acid Sarcosine beta-alanine gamma-Amino-N-butyric-acid alpha-Aminoadipic-acid beta-Aminoisobutyric-acid Hydroxylysine 1 Hydroxylysine 2 alpha-Amino-N-butyric-acid Cystathionine 1 Cystathionine 2 Methionine allo-Isoleucine Homocystine Asparagine Arginine Taurine Serine Glutamine Glycine Citrulline Glutamic Acid Threonine Alanine Proline Ornithine Lysine Cystine Tyrosine Valine METABOLITES_END #END