#METABOLOMICS WORKBENCH hormel101_20161118_135930 DATATRACK_ID:779 STUDY_ID:ST000511 ANALYSIS_ID:AN000784 PROJECT_ID:PR000383 VERSION 1 CREATED_ON December 8, 2016, 2:56 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 Determine how inhibition of autophagy/proteasome degradation or inhibition of ST:STUDY_TITLE protein synthesis in models of muscle insulin resistance affect amino acid ST:STUDY_TITLE metabolites 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 in muscle tissue. 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 ms5475-1 Group:Control | Treatment:Saline mouse=613; tissue_mg=10; array=Concentration of AA + metabolites in muscle tissue SUBJECT_SAMPLE_FACTORS 595 ms5475-2 Group:Control | Treatment:Saline mouse=595; tissue_mg=10; array=Concentration of AA + metabolites in muscle tissue SUBJECT_SAMPLE_FACTORS 1837 ms5475-3 Group:Control | Treatment:Saline mouse=1837; tissue_mg=10; array=Concentration of AA + metabolites in muscle tissue SUBJECT_SAMPLE_FACTORS 1916 ms5475-4 Group:Control | Treatment:Saline mouse=1916; tissue_mg=10; array=Concentration of AA + metabolites in muscle tissue SUBJECT_SAMPLE_FACTORS 1942 ms5475-5 Group:Control | Treatment:Saline mouse=1942; tissue_mg=10; array=Concentration of AA + metabolites in muscle tissue SUBJECT_SAMPLE_FACTORS 1956 ms5475-6 Group:Control | Treatment:Saline mouse=1956; tissue_mg=10; array=Concentration of AA + metabolites in muscle tissue SUBJECT_SAMPLE_FACTORS 1989 ms5475-7 Group:Control | Treatment:Saline mouse=1989; tissue_mg=10; array=Concentration of AA + metabolites in muscle tissue SUBJECT_SAMPLE_FACTORS 615 ms5475-8 Group:MIGIRKO | Treatment:Saline mouse=615; tissue_mg=10; array=Concentration of AA + metabolites in muscle tissue SUBJECT_SAMPLE_FACTORS 597 ms5475-9 Group:MIGIRKO | Treatment:Saline mouse=597; tissue_mg=10; array=Concentration of AA + metabolites in muscle tissue SUBJECT_SAMPLE_FACTORS 1838 ms5475-10 Group:MIGIRKO | Treatment:Saline mouse=1838; tissue_mg=10; array=Concentration of AA + metabolites in muscle tissue SUBJECT_SAMPLE_FACTORS 1815 ms5475-11 Group:MIGIRKO | Treatment:Saline mouse=1815; tissue_mg=10; array=Concentration of AA + metabolites in muscle tissue SUBJECT_SAMPLE_FACTORS 1970 ms5475-12 Group:MIGIRKO | Treatment:Saline mouse=1970; tissue_mg=10; array=Concentration of AA + metabolites in muscle tissue SUBJECT_SAMPLE_FACTORS 1972 ms5475-13 Group:MIGIRKO | Treatment:Saline mouse=1972; tissue_mg=10; array=Concentration of AA + metabolites in muscle tissue SUBJECT_SAMPLE_FACTORS 1943 ms5475-14 Group:IRKO | Treatment:Saline mouse=1943; tissue_mg=10; array=Concentration of AA + metabolites in muscle tissue SUBJECT_SAMPLE_FACTORS 1957 ms5475-15 Group:IRKO | Treatment:Saline mouse=1957; tissue_mg=10; array=Concentration of AA + metabolites in muscle tissue SUBJECT_SAMPLE_FACTORS 1948 ms5475-16 Group:IRKO | Treatment:Saline mouse=1948; tissue_mg=10; array=Concentration of AA + metabolites in muscle tissue SUBJECT_SAMPLE_FACTORS 1990 ms5475-17 Group:IRKO | Treatment:Saline mouse=1990; tissue_mg=10; array=Concentration of AA + metabolites in muscle tissue SUBJECT_SAMPLE_FACTORS 1992 ms5475-18 Group:IRKO | Treatment:Saline mouse=1992; tissue_mg=10; array=Concentration of AA + metabolites in muscle tissue SUBJECT_SAMPLE_FACTORS 1947 ms5475-19 Group:HFD | Treatment:Saline mouse=1947; tissue_mg=10; array=Concentration of AA + metabolites in muscle tissue SUBJECT_SAMPLE_FACTORS 1950 ms5475-20 Group:HFD | Treatment:Saline mouse=1950; tissue_mg=10; array=Concentration of AA + metabolites in muscle tissue SUBJECT_SAMPLE_FACTORS 1960 ms5475-21 Group:HFD | Treatment:Saline mouse=1960; tissue_mg=10; array=Concentration of AA + metabolites in muscle tissue SUBJECT_SAMPLE_FACTORS 1964 ms5475-22 Group:HFD | Treatment:Saline mouse=1964; tissue_mg=10; array=Concentration of AA + metabolites in muscle tissue SUBJECT_SAMPLE_FACTORS 1988 ms5475-23 Group:HFD | Treatment:Saline mouse=1988; tissue_mg=10; array=Concentration of AA + metabolites in muscle tissue SUBJECT_SAMPLE_FACTORS 1849 ms5475-24 Group:Control | Treatment:Colch mouse=1849; tissue_mg=10; array=Concentration of AA + metabolites in muscle tissue SUBJECT_SAMPLE_FACTORS 606 ms5475-25 Group:Control | Treatment:Colch mouse=606; tissue_mg=10; array=Concentration of AA + metabolites in muscle tissue SUBJECT_SAMPLE_FACTORS 1826 ms5475-26 Group:Control | Treatment:Colch mouse=1826; tissue_mg=10; array=Concentration of AA + metabolites in muscle tissue SUBJECT_SAMPLE_FACTORS 1847 ms5475-27 Group:Control | Treatment:Colch mouse=1847; tissue_mg=10; array=Concentration of AA + metabolites in muscle tissue SUBJECT_SAMPLE_FACTORS 1855 ms5475-28 Group:Control | Treatment:Colch mouse=1855; tissue_mg=10; array=Concentration of AA + metabolites in muscle tissue SUBJECT_SAMPLE_FACTORS 1944 ms5475-29 Group:Control | Treatment:Colch mouse=1944; tissue_mg=10; array=Concentration of AA + metabolites in muscle tissue SUBJECT_SAMPLE_FACTORS 1958 ms5475-30 Group:Control | Treatment:Colch mouse=1958; tissue_mg=10; array=Concentration of AA + metabolites in muscle tissue SUBJECT_SAMPLE_FACTORS 1852 ms5475-31 Group:MIGIRKO | Treatment:Colch mouse=1852; tissue_mg=10; array=Concentration of AA + metabolites in muscle tissue SUBJECT_SAMPLE_FACTORS 1853 ms5475-32 Group:MIGIRKO | Treatment:Colch mouse=1853; tissue_mg=10; array=Concentration of AA + metabolites in muscle tissue SUBJECT_SAMPLE_FACTORS 1856 ms5475-33 Group:MIGIRKO | Treatment:Colch mouse=1856; tissue_mg=10; array=Concentration of AA + metabolites in muscle tissue SUBJECT_SAMPLE_FACTORS 1817 ms5475-34 Group:MIGIRKO | Treatment:Colch mouse=1817; tissue_mg=10; array=Concentration of AA + metabolites in muscle tissue SUBJECT_SAMPLE_FACTORS 607 ms5475-35 Group:MIGIRKO | Treatment:Colch mouse=607; tissue_mg=10; array=Concentration of AA + metabolites in muscle tissue SUBJECT_SAMPLE_FACTORS 1824 ms5475-36 Group:MIGIRKO | Treatment:Colch mouse=1824; tissue_mg=10; array=Concentration of AA + metabolites in muscle tissue SUBJECT_SAMPLE_FACTORS 1945 ms5475-37 Group:IRKO | Treatment:Colch mouse=1945; tissue_mg=10; array=Concentration of AA + metabolites in muscle tissue SUBJECT_SAMPLE_FACTORS 1954 ms5475-38 Group:IRKO | Treatment:Colch mouse=1954; tissue_mg=10; array=Concentration of AA + metabolites in muscle tissue SUBJECT_SAMPLE_FACTORS 1955 ms5475-39 Group:IRKO | Treatment:Colch mouse=1955; tissue_mg=10; array=Concentration of AA + metabolites in muscle tissue SUBJECT_SAMPLE_FACTORS 1959 ms5475-40 Group:IRKO | Treatment:Colch mouse=1959; tissue_mg=10; array=Concentration of AA + metabolites in muscle tissue SUBJECT_SAMPLE_FACTORS 1993 ms5475-41 Group:IRKO | Treatment:Colch mouse=1993; tissue_mg=10; array=Concentration of AA + metabolites in muscle tissue SUBJECT_SAMPLE_FACTORS 1951 ms5475-42 Group:HFD+Colch | Treatment:Colch mouse=1951; tissue_mg=10; array=Concentration of AA + metabolites in muscle tissue SUBJECT_SAMPLE_FACTORS 1952 ms5475-43 Group:HFD+Colch | Treatment:Colch mouse=1952; tissue_mg=10; array=Concentration of AA + metabolites in muscle tissue SUBJECT_SAMPLE_FACTORS 1965 ms5475-44 Group:HFD+Colch | Treatment:Colch mouse=1965; tissue_mg=10; array=Concentration of AA + metabolites in muscle tissue SUBJECT_SAMPLE_FACTORS 1991 ms5475-45 Group:HFD+Colch | Treatment:Colch mouse=1991; tissue_mg=10; array=Concentration of AA + metabolites in muscle tissue SUBJECT_SAMPLE_FACTORS 1994 ms5475-46 Group:HFD+Colch | Treatment:Colch mouse=1994; tissue_mg=10; array=Concentration of AA + metabolites in muscle tissue #COLLECTION CO:COLLECTION_SUMMARY mouse gastrocnemius muscle tissue #TREATMENT TR:TREATMENT_SUMMARY Mice lacking insulin receptors (IR -/- genotype), or IGF-1 receptors (ICF-1 -/- TR:TREATMENT_SUMMARY genotype), or both were generated using Cre lox recombination. Controls were IR TR:TREATMENT_SUMMARY lox/lox, IGF-1 lox/lox, or both. Additional, 10 mice were included that were fed TR:TREATMENT_SUMMARY different diets for 8 weeks, chow or high fat diet. #SAMPLEPREP SP:SAMPLEPREP_SUMMARY Concentration of amino acid metabolites in muscle tissue #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 picomoles/mg MS_METABOLITE_DATA_START Samples ms5475-1 ms5475-2 ms5475-3 ms5475-4 ms5475-5 ms5475-6 ms5475-7 ms5475-8 ms5475-9 ms5475-10 ms5475-11 ms5475-12 ms5475-13 ms5475-14 ms5475-15 ms5475-16 ms5475-17 ms5475-18 ms5475-19 ms5475-20 ms5475-21 ms5475-22 ms5475-23 ms5475-24 ms5475-25 ms5475-26 ms5475-27 ms5475-28 ms5475-29 ms5475-30 ms5475-31 ms5475-32 ms5475-33 ms5475-34 ms5475-35 ms5475-36 ms5475-37 ms5475-38 ms5475-39 ms5475-40 ms5475-41 ms5475-42 ms5475-43 ms5475-44 ms5475-45 ms5475-46 Factors Group:Control | Treatment:Saline Group:Control | Treatment:Saline Group:Control | Treatment:Saline Group:Control | Treatment:Saline Group:Control | Treatment:Saline Group:Control | Treatment:Saline Group:Control | Treatment:Saline Group:MIGIRKO | Treatment:Saline Group:MIGIRKO | Treatment:Saline Group:MIGIRKO | Treatment:Saline Group:MIGIRKO | Treatment:Saline Group:MIGIRKO | Treatment:Saline Group:MIGIRKO | Treatment:Saline Group:IRKO | Treatment:Saline Group:IRKO | Treatment:Saline Group:IRKO | Treatment:Saline Group:IRKO | Treatment:Saline Group:IRKO | Treatment:Saline Group:HFD | Treatment:Saline Group:HFD | Treatment:Saline Group:HFD | Treatment:Saline Group:HFD | Treatment:Saline Group:HFD | Treatment:Saline Group:Control | Treatment:Colch Group:Control | Treatment:Colch Group:Control | Treatment:Colch Group:Control | Treatment:Colch Group:Control | Treatment:Colch Group:Control | Treatment:Colch Group:Control | Treatment:Colch Group:MIGIRKO | Treatment:Colch Group:MIGIRKO | Treatment:Colch Group:MIGIRKO | Treatment:Colch Group:MIGIRKO | Treatment:Colch Group:MIGIRKO | Treatment:Colch Group:MIGIRKO | Treatment:Colch Group:IRKO | Treatment:Colch Group:IRKO | Treatment:Colch Group:IRKO | Treatment:Colch Group:IRKO | Treatment:Colch Group:IRKO | Treatment:Colch Group:HFD+Colch | Treatment:Colch Group:HFD+Colch | Treatment:Colch Group:HFD+Colch | Treatment:Colch Group:HFD+Colch | Treatment:Colch Group:HFD+Colch | Treatment:Colch Histidine 135.2 120.7 181.3 137.4 99.5 127.8 152.3 127.9 120.1 150.0 100.0 118.0 137.7 114.3 118.8 90.6 127.8 165.4 75.3 85.4 100.6 95.7 72.6 61.8 101.6 85.6 99.7 97.6 70.5 69.1 100.4 108.6 106.6 130.2 141.3 84.7 114.5 117.5 78.2 135.2 85.6 70.0 75.5 75.6 101.2 103.2 1-Methylhistidine' 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 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' 0.7 1.0 3.3 0.5 2.0 1.2 3.6 2.7 8.1 9.9 0.5 10.5 0.0 1.7 2.5 2.1 1.3 0.0 0.5 0.0 2.4 1.4 0.6 3.7 5.1 3.4 1.2 4.1 4.3 1.9 4.1 0.9 1.8 1.8 3.3 0.7 7.9 0.8 4.9 0.6 0.7 6.4 2.3 0.0 2.3 1.1 Asparagine 35.4 65.4 52.6 87.4 68.7 89.7 88.7 100.4 149.6 137.3 94.4 115.7 126.8 95.7 129.5 70.2 142.5 186.0 74.5 73.9 101.3 79.4 70.6 61.4 56.1 57.9 57.2 57.7 69.6 46.0 109.3 136.3 146.6 162.7 131.7 115.2 129.7 151.8 76.8 148.4 66.7 57.4 60.3 69.7 82.0 78.1 Phosphoethanolamine 8.5 9.0 8.8 7.3 9.0 8.6 12.3 25.2 36.1 30.8 24.6 28.8 37.2 11.7 27.7 21.0 17.4 34.1 5.9 8.1 5.6 6.1 9.9 7.7 7.1 7.4 11.6 13.0 9.2 8.3 24.8 53.5 29.9 35.0 39.0 17.8 22.3 12.1 16.1 18.5 19.5 7.6 8.1 8.0 8.4 8.1 Arginine 344.6 238.5 352.8 132.4 285.1 128.9 101.7 289.0 194.9 201.0 271.1 178.6 185.6 172.9 203.1 238.8 131.4 124.2 139.9 129.1 148.7 149.3 163.9 254.4 198.1 239.3 269.1 286.4 180.5 259.3 284.4 266.8 168.3 325.3 294.6 241.8 139.3 146.6 153.4 116.8 168.3 72.1 68.6 150.6 140.9 108.8 Carnosine 1144.2 1741.7 1246.3 1237.6 1488.1 1470.5 1363.3 337.9 352.7 287.8 304.5 252.1 212.8 829.2 770.7 649.7 816.7 651.9 1239.3 1607.1 919.9 1150.9 1450.0 1219.6 1177.9 897.9 893.6 901.4 1030.0 1490.8 308.7 210.6 328.0 320.5 226.0 367.2 662.4 946.6 682.5 751.9 791.7 1038.7 1098.6 1187.6 1077.4 1132.4 Anserine 1376.4 2014.4 1366.0 1471.6 1207.5 1207.5 1088.2 236.9 306.7 208.1 256.1 170.5 113.5 691.0 657.0 412.1 717.0 551.8 1944.5 2342.9 1788.4 1735.7 2071.1 1146.2 1043.2 1047.9 1047.1 975.6 961.5 1105.0 175.7 136.8 179.3 226.7 189.0 224.1 562.7 805.6 412.6 595.4 744.7 1839.6 1895.0 1615.7 1865.7 1891.5 Ethanolamine 18.9 21.6 18.8 30.8 26.9 36.5 39.2 25.0 26.8 31.1 25.6 26.2 26.5 42.0 26.1 26.8 32.1 32.3 20.7 35.0 38.1 27.0 42.9 23.3 18.0 18.3 21.9 24.1 30.9 25.2 23.0 27.6 28.0 25.0 22.3 16.8 41.0 40.1 28.4 33.4 16.3 25.6 22.9 30.3 34.1 31.5 Aspartic Acid 152.4 187.9 185.5 163.1 151.3 126.0 185.7 243.2 372.9 368.8 228.3 536.5 423.3 167.4 199.1 178.5 136.5 229.7 174.9 194.9 226.5 207.6 219.5 135.5 172.7 150.1 125.4 179.8 145.5 103.2 234.6 337.3 321.4 313.8 328.7 204.9 171.1 137.2 104.1 140.7 179.7 200.2 229.2 200.0 272.0 252.9 Sarcosine 4.4 6.8 5.5 2.2 6.3 2.9 4.8 3.0 4.4 3.9 3.0 5.9 2.0 2.9 8.5 4.9 4.5 4.6 1.2 0.8 0.1 1.3 1.5 5.3 6.8 2.2 4.1 5.4 3.2 6.4 6.0 3.2 3.8 3.9 5.3 4.6 2.7 3.0 4.3 4.2 11.6 0.4 0.6 0.7 0.4 0.2 Citrulline 119.8 172.5 198.8 175.5 145.4 167.9 222.3 122.2 167.8 198.0 151.7 164.4 113.3 146.2 187.2 132.9 226.0 225.9 197.0 145.0 183.6 147.5 120.0 175.5 180.3 173.6 162.4 176.7 153.6 207.1 237.8 153.8 182.5 204.3 169.9 173.6 158.6 187.7 152.5 150.1 235.1 113.0 132.9 136.9 149.8 130.0 Glutamic Acid 523.1 504.1 356.1 461.2 445.1 297.4 555.9 1394.7 1577.2 1605.5 1216.9 1906.2 1459.8 451.6 850.0 511.9 590.8 910.6 260.0 170.6 179.2 290.0 109.9 415.2 518.9 289.9 450.1 487.7 291.7 209.2 1304.9 1396.6 1383.0 1578.1 1783.9 1104.4 746.6 612.3 387.5 569.9 933.6 204.7 233.2 390.8 377.9 490.0 beta-alanine 8.7 14.2 11.0 4.9 12.2 5.8 9.6 6.3 8.8 8.4 6.7 14.0 4.1 6.1 15.9 8.7 8.5 9.2 2.7 2.2 0.7 2.8 3.3 10.1 14.5 4.8 7.8 10.9 7.0 12.9 12.0 6.4 8.2 8.7 10.5 9.2 5.7 6.3 8.5 7.8 22.8 1.1 1.3 1.6 1.1 0.9 Threonine 167.2 293.2 218.3 139.0 217.5 143.1 154.9 300.2 363.1 341.1 273.5 272.0 257.5 185.2 322.7 231.8 181.5 258.3 352.0 296.1 362.6 284.3 199.2 189.2 221.1 199.5 180.3 212.0 219.1 179.2 301.1 315.8 329.6 471.3 410.9 325.9 196.6 235.2 196.1 197.1 283.8 213.2 181.0 281.6 261.8 245.8 gamma-Amino-N-butyric-acid 0.4 0.8 1.2 1.8 0.9 2.5 4.5 11.5 6.5 5.7 4.6 7.4 7.0 2.7 1.7 1.9 5.7 5.2 1.1 0.7 0.6 0.0 1.5 1.2 0.9 1.2 1.6 0.7 0.7 0.6 8.2 8.7 6.7 7.5 8.1 5.2 4.7 5.0 1.3 5.5 2.2 1.0 1.3 0.3 0.1 0.9 alpha-Aminoadipic-acid 5.0 2.5 2.8 1.3 4.5 1.5 2.8 13.3 9.0 10.4 7.4 10.4 9.5 2.5 6.6 5.9 4.5 5.6 2.3 1.9 2.6 2.5 2.8 3.7 2.4 2.3 2.8 3.1 2.3 2.1 8.4 9.8 9.8 15.5 9.3 10.7 4.1 3.1 2.8 3.3 7.6 2.4 3.8 2.8 3.0 2.5 beta-Aminoisobutyric-acid 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.2 0.0 0.0 0.1 0.1 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 1.4 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.1 0.0 0.0 0.2 0.1 0.1 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 Proline 0.4 0.8 1.2 1.8 0.9 2.5 4.5 11.5 6.5 5.7 4.6 7.4 7.0 2.7 1.7 1.9 5.7 5.2 1.1 0.7 0.6 0.0 1.5 1.2 0.9 1.2 1.6 0.7 0.7 0.6 8.2 8.7 6.7 7.5 8.1 5.2 4.7 5.0 1.3 5.5 2.2 1.0 1.3 0.3 0.1 0.9 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 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 Hydroxylysine 2 0.5 0.2 0.2 0.1 0.3 0.1 0.0 0.1 0.0 0.1 0.2 0.2 0.2 0.0 0.1 0.0 0.0 0.2 0.0 0.0 0.0 0.0 0.0 0.1 0.0 0.1 0.1 0.0 0.0 0.3 0.0 0.0 0.0 0.2 0.1 0.2 0.0 0.0 0.0 0.0 0.1 0.0 0.0 0.0 0.0 0.0 alpha-Amino-N-butyric-acid 3.1 2.1 2.3 1.6 3.3 3.0 3.5 2.6 1.9 3.2 1.7 7.0 3.2 3.6 4.2 4.0 4.4 4.7 45.9 41.2 48.2 2.5 4.5 2.2 3.7 0.7 1.9 1.6 4.2 2.6 3.0 4.4 4.3 2.7 2.4 2.0 2.4 2.9 3.8 2.1 2.6 9.9 7.6 3.7 8.0 5.6 Ornithine 43.6 47.9 28.3 45.0 46.7 45.4 37.7 80.3 74.8 65.3 71.5 62.2 52.2 40.5 35.4 43.8 42.9 40.1 28.2 23.9 20.6 37.1 30.1 35.6 28.7 30.5 22.0 31.3 26.2 34.7 62.3 53.5 62.8 91.0 69.0 91.1 45.5 58.1 33.8 43.8 38.5 15.3 12.8 22.8 22.7 22.8 Cystathionine 1 2.5 3.8 2.3 2.1 3.7 2.3 0.5 2.5 0.9 1.3 0.4 0.9 0.7 1.0 2.0 3.6 0.9 0.2 2.0 0.4 2.7 2.1 1.6 2.5 9.3 3.0 1.9 0.7 2.2 3.6 1.8 1.4 0.7 1.7 1.8 1.2 1.5 0.5 0.9 0.6 3.0 2.2 0.4 1.0 0.6 0.0 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 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 Lysine 848.8 604.1 653.5 481.2 879.2 488.2 283.8 985.2 806.9 634.7 751.0 655.7 495.7 557.5 480.2 762.8 315.0 306.5 890.0 517.7 619.0 978.5 697.1 796.6 783.4 641.2 634.8 737.8 714.2 733.4 652.5 511.9 535.0 994.0 696.3 922.0 462.9 428.3 500.5 346.8 476.5 401.0 375.4 786.6 669.6 509.2 Cystine 3.4 2.4 4.9 2.4 6.8 4.3 4.5 7.3 9.2 10.0 7.3 7.3 7.7 6.0 13.5 8.1 7.2 9.6 2.9 3.3 4.6 5.0 5.9 3.3 3.0 3.2 3.5 3.5 5.2 2.8 6.3 9.3 8.7 9.2 5.9 7.4 7.9 7.4 5.1 6.7 6.6 2.4 3.0 3.6 3.1 3.0 Tyrosine 79.0 139.0 82.3 120.5 91.8 117.0 95.6 98.3 129.0 107.2 87.6 82.2 61.3 92.1 124.7 89.5 102.2 106.5 75.0 86.1 79.8 62.6 81.0 63.1 69.7 81.5 72.5 61.7 89.8 71.8 76.1 89.0 79.5 115.7 86.2 88.8 122.3 136.6 83.7 119.5 96.8 51.3 48.5 53.4 63.7 64.5 Methionine 57.8 97.1 48.1 65.6 73.8 52.8 43.1 60.8 90.5 72.5 63.1 58.0 54.0 46.3 107.6 70.6 47.0 61.7 52.5 59.0 67.4 57.8 54.2 61.3 53.7 66.2 56.2 52.7 65.5 60.2 60.9 72.1 66.8 101.1 71.9 80.4 68.6 95.2 64.0 70.7 70.4 47.6 45.0 50.9 50.3 53.2 Valine 94.4 144.6 120.1 112.9 137.2 110.7 114.5 124.8 137.7 158.7 114.7 156.5 133.1 104.1 166.3 116.1 125.0 168.2 175.0 151.2 169.1 152.0 148.7 112.5 119.1 126.9 115.5 120.6 139.0 100.8 126.3 157.8 184.6 191.5 139.2 124.0 137.8 163.3 95.2 119.6 125.4 122.7 106.8 108.9 143.7 161.2 Isoleucine 37.6 51.4 47.6 39.4 53.2 39.9 44.3 57.6 72.9 73.9 61.0 75.5 63.1 40.7 83.0 39.4 56.9 84.4 68.4 68.1 69.6 62.4 62.6 48.8 57.5 59.5 51.5 57.0 61.8 36.3 72.6 96.9 102.5 98.4 72.5 58.2 57.1 71.2 39.5 53.0 65.6 60.9 58.0 52.2 57.6 57.1 allo-Isoleucine 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 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 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 Leucine 79.4 111.7 86.3 76.2 105.8 77.6 83.7 116.2 165.3 142.8 124.3 148.6 126.3 75.7 175.4 84.3 109.3 151.7 124.0 132.0 144.3 115.8 142.6 103.1 104.7 111.1 97.9 116.8 120.4 71.5 151.0 206.5 202.9 215.0 150.4 132.2 113.4 144.4 84.3 112.7 129.9 116.0 108.2 102.0 139.5 148.4 Phenylalanine 56.5 85.7 56.7 73.8 67.5 67.2 73.6 68.9 96.5 86.5 73.0 80.3 66.9 61.8 95.2 60.0 78.9 91.1 60.8 75.8 63.0 65.9 75.4 65.4 59.4 66.2 63.8 75.1 74.7 60.4 83.1 105.8 101.0 121.4 84.9 77.5 99.5 130.0 63.6 94.1 82.7 67.6 61.8 72.5 83.2 83.6 Tryptophan 17.3 21.3 16.6 18.7 17.2 16.1 16.9 27.1 31.7 27.4 27.2 22.6 22.8 15.9 22.3 16.6 23.3 28.0 20.6 28.5 24.7 16.0 20.8 17.3 19.6 21.2 18.1 17.0 21.7 19.4 20.4 25.4 24.2 34.6 31.4 21.4 25.7 25.9 15.9 21.9 22.6 17.7 17.2 19.7 19.8 19.5 Hydroxyproline 311.2 338.6 386.7 283.7 428.6 205.5 415.3 252.8 311.8 331.4 238.4 298.1 274.6 291.7 585.0 483.5 239.1 254.6 317.5 140.4 174.5 232.5 140.4 462.7 391.0 262.3 255.6 266.2 240.0 480.4 273.5 282.7 317.9 313.8 317.8 258.7 315.9 283.4 303.9 192.6 482.3 120.1 96.0 133.8 121.8 93.1 Taurine 12452.2 13072.8 14388.2 13443.5 12765.0 13020.5 14200.4 11874.6 12173.7 11917.3 10912.9 11950.6 10728.0 12711.6 11543.5 13777.0 11444.4 10315.3 11785.3 12510.7 14179.6 14589.4 12843.1 12467.4 12590.9 13230.1 12324.7 12587.0 13153.2 12548.0 9955.7 9305.1 10286.1 11397.5 10242.8 9457.5 11083.3 12058.4 11387.9 9600.9 10931.5 12001.3 11822.8 11574.6 11838.3 12046.9 Serine 160.4 287.0 296.1 292.2 291.6 315.2 344.8 414.1 559.8 549.4 419.7 435.1 474.6 291.3 448.2 314.8 446.9 541.3 302.7 276.1 328.4 316.1 263.5 278.9 243.8 238.6 232.6 256.9 257.6 237.2 528.9 630.9 656.6 623.3 737.4 482.6 331.8 444.5 284.1 453.9 337.1 243.9 201.9 248.3 257.3 265.5 Glutamine 1063.2 1100.0 1293.9 1253.8 1180.1 1235.6 1526.6 1936.5 2069.7 2562.2 2228.4 2014.1 2228.0 1818.1 1999.0 1571.7 2338.5 2789.8 1457.1 1351.7 1732.8 1160.4 1113.1 1127.7 838.0 979.5 1238.1 1267.2 1073.8 1282.1 2442.6 2401.2 3018.5 2478.7 2177.1 1997.4 1573.0 2041.7 1414.8 2118.8 1634.7 981.4 1027.3 887.4 1495.7 1450.5 Glycine 886.8 1955.3 1655.3 1515.6 1584.0 1853.7 2193.0 2141.7 2779.7 2780.7 1863.2 2661.0 2292.7 2040.2 3210.6 2097.6 2610.8 3098.5 1178.2 1015.2 954.2 1407.0 1029.7 1315.9 1211.1 874.9 1121.0 1419.9 1097.1 1456.5 2084.1 2364.3 3006.1 2002.3 2473.8 1958.5 2162.8 2107.4 1305.0 2398.1 2344.1 663.1 662.7 863.4 674.2 591.9 Alanine 1043.0 1293.9 1445.2 1315.9 1352.1 1471.3 1282.0 1596.1 1839.8 1624.3 1355.9 1566.0 1733.0 1177.0 1811.6 1475.6 1487.5 1869.1 1900.8 1456.4 1912.4 1608.1 1234.6 1405.6 1260.1 1422.3 1334.9 1399.6 1210.1 1302.3 1482.9 1467.4 1586.0 1712.1 1451.6 1607.5 1440.6 1677.7 1161.9 1393.5 1329.2 1192.7 1092.0 1072.4 1176.0 1096.4 MS_METABOLITE_DATA_END #METABOLITES METABOLITES_START metabolite_name Histidine 1-Methylhistidine' 3-Methylhistidine' Asparagine Phosphoethanolamine Arginine Carnosine Anserine Ethanolamine Aspartic Acid Sarcosine Citrulline Glutamic Acid beta-alanine Threonine gamma-Amino-N-butyric-acid alpha-Aminoadipic-acid beta-Aminoisobutyric-acid Proline Hydroxylysine 1 Hydroxylysine 2 alpha-Amino-N-butyric-acid Ornithine Cystathionine 1 Cystathionine 2 Lysine Cystine Tyrosine Methionine Valine Isoleucine allo-Isoleucine Homocystine Leucine Phenylalanine Tryptophan Hydroxyproline Taurine Serine Glutamine Glycine Alanine METABOLITES_END #END