#METABOLOMICS WORKBENCH u023968_20190212_180200 DATATRACK_ID:1620 STUDY_ID:ST001136 ANALYSIS_ID:AN001863 PROJECT_ID:PR000760 VERSION 1 CREATED_ON February 13, 2019, 5:54 pm #PROJECT PR:PROJECT_TITLE Antidiabetic and cardiovascular beneficial effects of a liver-localized PR:PROJECT_TITLE mitochondrial uncoupler PR:PROJECT_SUMMARY Inducing mitochondrial uncoupling (mUncoupling) is an attractive therapeutic PR:PROJECT_SUMMARY strategy for treating metabolic diseases because it leads to calorie-wasting by PR:PROJECT_SUMMARY reducing the efficiency of oxidative phosphorylation (OXPHOS) in mitochondria. PR:PROJECT_SUMMARY Here we report a safe mUncoupler, OPC-163493, which has unique pharmacokinetic PR:PROJECT_SUMMARY characteristics. OPC-163493 shows a good bioavailability upon oral PR:PROJECT_SUMMARY administration and primarily distributed to specific organs: the liver and PR:PROJECT_SUMMARY kidneys, avoiding systemic toxicities. It exhibitsinsulin-independent PR:PROJECT_SUMMARY antidiabetic effects in multiple animal models of type I and type II diabetes PR:PROJECT_SUMMARY and antisteatotic effects in fatty liver models. These beneficial effects can be PR:PROJECT_SUMMARY explained by the improvement of glucose metabolism and enhancement of energy PR:PROJECT_SUMMARY expenditure by OPC-163493 in the liver. Moreover, OPC-163493 treatment lowered PR:PROJECT_SUMMARY blood pressure, extended survival, and improved renal function in the rat model PR:PROJECT_SUMMARY of stroke/hypertension, possibly by enhancing NO bioavailability in blood PR:PROJECT_SUMMARY vessels and reducing mitochondrial ROS production. OPC-163493 is a PR:PROJECT_SUMMARY liver-localized/targeted mUncoupler that ameliorates various complications of PR:PROJECT_SUMMARY diabetes. PR:INSTITUTE Otsuka Pharmaceuticals PR:LAST_NAME Kanemoto PR:FIRST_NAME Naohide PR:ADDRESS 463-10 Kagasuno Kawauchi-cho Tokushima 771-0192, Japan PR:EMAIL Kanemoto.Naohide@otsuka.jp PR:PHONE 81-03-6717-1400 #STUDY ST:STUDY_TITLE Metabolme analysis of OPC-163493 on the Liver of ZDF rats (part-II) ST:STUDY_TYPE Long-term in vivo test ST:STUDY_SUMMARY Metabolome analysis were on the 24 samples of ZDF rats that were treated with ST:STUDY_SUMMARY OPC-163493 for 6-weeks. The 24 samples were composed of 3 different groups ST:STUDY_SUMMARY (Vehicles, OPC-163493 treatment, and baseline control; each n=8). ST:INSTITUTE Otsuka Pharmaceuticals ST:LAST_NAME Kanemoto ST:FIRST_NAME Naohide ST:ADDRESS 463-10 Kagasuno Kawauchi-cho Tokushima 771-0192, Japan ST:EMAIL Kanemoto.Naohide@otsuka.jp ST:PHONE 81-03-6717-1400 #SUBJECT SU:SUBJECT_TYPE Mammal SU:SUBJECT_SPECIES Rattus norvegicus SU:TAXONOMY_ID 10116 SU:GENOTYPE_STRAIN ZDF rats SU:GENDER Not applicable #SUBJECT_SAMPLE_FACTORS: SUBJECT(optional)[tab]SAMPLE[tab]FACTORS(NAME:VALUE pairs separated by |)[tab]Additional sample data SUBJECT_SAMPLE_FACTORS - Vehicle-1 Genotype:17-week-old ZDF rat | Treatment:- | Duration (weeks):6 SUBJECT_SAMPLE_FACTORS - Vehicle-2 Genotype:17-week-old ZDF rat | Treatment:- | Duration (weeks):6 SUBJECT_SAMPLE_FACTORS - Vehicle-3 Genotype:17-week-old ZDF rat | Treatment:- | Duration (weeks):6 SUBJECT_SAMPLE_FACTORS - Vehicle-4 Genotype:17-week-old ZDF rat | Treatment:- | Duration (weeks):6 SUBJECT_SAMPLE_FACTORS - Vehicle-5 Genotype:17-week-old ZDF rat | Treatment:- | Duration (weeks):6 SUBJECT_SAMPLE_FACTORS - Vehicle-6 Genotype:17-week-old ZDF rat | Treatment:- | Duration (weeks):6 SUBJECT_SAMPLE_FACTORS - Vehicle-7 Genotype:17-week-old ZDF rat | Treatment:- | Duration (weeks):6 SUBJECT_SAMPLE_FACTORS - Vehicle-8 Genotype:17-week-old ZDF rat | Treatment:- | Duration (weeks):6 SUBJECT_SAMPLE_FACTORS - OPC-9 Genotype:17-week-old ZDF rat | Treatment:6 | Duration (weeks):6 SUBJECT_SAMPLE_FACTORS - OPC-10 Genotype:17-week-old ZDF rat | Treatment:6 | Duration (weeks):6 SUBJECT_SAMPLE_FACTORS - OPC-11 Genotype:17-week-old ZDF rat | Treatment:6 | Duration (weeks):6 SUBJECT_SAMPLE_FACTORS - OPC-12 Genotype:17-week-old ZDF rat | Treatment:6 | Duration (weeks):6 SUBJECT_SAMPLE_FACTORS - OPC-13 Genotype:17-week-old ZDF rat | Treatment:6 | Duration (weeks):6 SUBJECT_SAMPLE_FACTORS - OPC-14 Genotype:17-week-old ZDF rat | Treatment:6 | Duration (weeks):6 SUBJECT_SAMPLE_FACTORS - OPC-15 Genotype:17-week-old ZDF rat | Treatment:6 | Duration (weeks):6 SUBJECT_SAMPLE_FACTORS - OPC-16 Genotype:17-week-old ZDF rat | Treatment:6 | Duration (weeks):6 SUBJECT_SAMPLE_FACTORS - Baseline control-101 Genotype:11-week-old ZDF rat | Treatment:- | Duration (weeks):- SUBJECT_SAMPLE_FACTORS - Baseline control-102 Genotype:11-week-old ZDF rat | Treatment:- | Duration (weeks):- SUBJECT_SAMPLE_FACTORS - Baseline control-103 Genotype:11-week-old ZDF rat | Treatment:- | Duration (weeks):- SUBJECT_SAMPLE_FACTORS - Baseline control-104 Genotype:11-week-old ZDF rat | Treatment:- | Duration (weeks):- SUBJECT_SAMPLE_FACTORS - Baseline control-105 Genotype:11-week-old ZDF rat | Treatment:- | Duration (weeks):- SUBJECT_SAMPLE_FACTORS - Baseline control-106 Genotype:11-week-old ZDF rat | Treatment:- | Duration (weeks):- SUBJECT_SAMPLE_FACTORS - Baseline control-107 Genotype:11-week-old ZDF rat | Treatment:- | Duration (weeks):- SUBJECT_SAMPLE_FACTORS - Baseline control-108 Genotype:11-week-old ZDF rat | Treatment:- | Duration (weeks):- #COLLECTION CO:COLLECTION_SUMMARY After euthanasia by exsanguination under isoflurane anesthesia, a piece of liver CO:COLLECTION_SUMMARY was taken from the left lateral lobe on the treated rats, weighed at CO:COLLECTION_SUMMARY approximately 50mg, and immediately frozen in liquid nitrogen. CO:SAMPLE_TYPE Liver CO:STORAGE_CONDITIONS -80℃ #TREATMENT TR:TREATMENT_SUMMARY The baseline control, the liver samples of ZDF rats were taken from the baseline TR:TREATMENT_SUMMARY control group of 11-week-old ZDF rats. And at the same time, the other 2 TR:TREATMENT_SUMMARY comparing groups were started on oral administration of OPC-163493 or vehicle TR:TREATMENT_SUMMARY solution for 6-weeks. After 6-week dosing, liver samples were taken from both TR:TREATMENT_SUMMARY groups, and the liver metabolites of all three groups including the baseline TR:TREATMENT_SUMMARY controls were analyzed. TR:TREATMENT_DOSE 0mg/kg/day, 6mg/kg/day #SAMPLEPREP SP:SAMPLEPREP_SUMMARY The frozen liver samples were plunged into 50% acetonitrile/Milli-Q water SP:SAMPLEPREP_SUMMARY containing internal standard. The sample was homogenized and then centrifuged. SP:SAMPLEPREP_SUMMARY Subsequently, 800 uL of upper aqueous layer was filtered through a 5-kDa cutoff SP:SAMPLEPREP_SUMMARY filter. The filtrate was centrifugally concentrated and re-suspended in 50 uL of SP:SAMPLEPREP_SUMMARY Milli-Q water. SP:PROCESSING_STORAGE_CONDITIONS 4℃ SP:EXTRACT_STORAGE -80℃ SP:SAMPLE_RESUSPENSION 50 uL Mili-Q #CHROMATOGRAPHY CH:CHROMATOGRAPHY_SUMMARY capillary electrophoresis was connected with time-of-flight mass spectrometry CH:CHROMATOGRAPHY_SUMMARY (CE-TOFMS) for cation analysis and tandem mass spectrometry (CE-MS/MS) for CH:CHROMATOGRAPHY_SUMMARY anion. CH:CHROMATOGRAPHY_TYPE CE CH:INSTRUMENT_NAME Agilent 7100 CE CH:COLUMN_NAME Fused silica capillary, i.d. 50 µm × 80 cm #ANALYSIS AN:ANALYSIS_TYPE MS #MS MS:INSTRUMENT_NAME Agilent 6460 QQQ MS:INSTRUMENT_TYPE Triple quadrupole MS:MS_TYPE ESI MS:ION_MODE UNSPECIFIED MS:MS_COMMENTS The spectrometer was scanned from m/z 50 to 1,000. Peaks were extracted using MS:MS_COMMENTS MasterHands, automatic integration software (Keio University, Tsuruoka, MS:MS_COMMENTS Yamagata, Japan) and MassHunter Quantitative Analysis B.04.00 (Agilent MS:MS_COMMENTS Technologies) in order to obtain peak information including m/z, peak area, and MS:MS_COMMENTS migration time (MT). Signal peaks were annotated according to the HMT metabolite MS:MS_COMMENTS database based on their m/z values with the MTs. The peak area of each MS:MS_COMMENTS metabolite was normalized with respect to the area of the internal standard and MS:MS_COMMENTS metabolite concentration was evaluated by standard curves with three-point MS:MS_COMMENTS calibrations using each standard compound. #MS_METABOLITE_DATA MS_METABOLITE_DATA:UNITS Concentration (nmol/g tissue) MS_METABOLITE_DATA_START Samples Vehicle-1 Vehicle-2 Vehicle-3 Vehicle-4 Vehicle-5 Vehicle-6 Vehicle-7 Vehicle-8 OPC-9 OPC-10 OPC-11 OPC-12 OPC-13 OPC-14 OPC-15 OPC-16 Baseline control-101 Baseline control-102 Baseline control-103 Baseline control-104 Baseline control-105 Baseline control-106 Baseline control-107 Baseline control-108 Factors Genotype:17-week-old ZDF rat | Treatment:- | Duration (weeks):6 Genotype:17-week-old ZDF rat | Treatment:- | Duration (weeks):6 Genotype:17-week-old ZDF rat | Treatment:- | Duration (weeks):6 Genotype:17-week-old ZDF rat | Treatment:- | Duration (weeks):6 Genotype:17-week-old ZDF rat | Treatment:- | Duration (weeks):6 Genotype:17-week-old ZDF rat | Treatment:- | Duration (weeks):6 Genotype:17-week-old ZDF rat | Treatment:- | Duration (weeks):6 Genotype:17-week-old ZDF rat | Treatment:- | Duration (weeks):6 Genotype:17-week-old ZDF rat | Treatment:6 | Duration (weeks):6 Genotype:17-week-old ZDF rat | Treatment:6 | Duration (weeks):6 Genotype:17-week-old ZDF rat | Treatment:6 | Duration (weeks):6 Genotype:17-week-old ZDF rat | Treatment:6 | Duration (weeks):6 Genotype:17-week-old ZDF rat | Treatment:6 | Duration (weeks):6 Genotype:17-week-old ZDF rat | Treatment:6 | Duration (weeks):6 Genotype:17-week-old ZDF rat | Treatment:6 | Duration (weeks):6 Genotype:17-week-old ZDF rat | Treatment:6 | Duration (weeks):6 Genotype:11-week-old ZDF rat | Treatment:- | Duration (weeks):- Genotype:11-week-old ZDF rat | Treatment:- | Duration (weeks):- Genotype:11-week-old ZDF rat | Treatment:- | Duration (weeks):- Genotype:11-week-old ZDF rat | Treatment:- | Duration (weeks):- Genotype:11-week-old ZDF rat | Treatment:- | Duration (weeks):- Genotype:11-week-old ZDF rat | Treatment:- | Duration (weeks):- Genotype:11-week-old ZDF rat | Treatment:- | Duration (weeks):- Genotype:11-week-old ZDF rat | Treatment:- | Duration (weeks):- Adenine 10.59 6.89 4.77 6.10 8.33 6.35 7.08 6.13 7.39 5.51 8.05 6.16 5.24 7.23 4.05 6.34 6.70 8.44 5.77 6.88 5.69 6.63 5.34 9.07 Adenosine 128.8 200.0 97.2 176.7 216.2 183.4 172.9 300.9 125.4 212.3 212.1 282.5 256.6 208.9 65.6 262.6 390.3 319.5 368.5 344.3 267.9 414.2 291.1 400.8 Alanine 3319 3534 2542 2450 2459 3303 4290 2377 4346 2707 2482 2896 3146 2880 3115 2908 3205 3915 3133 3257 2849 2394 2863 2937 Arginine 1.69 1.76 1.80 2.27 1.95 1.87 1.64 1.83 1.94 1.77 1.80 1.34 1.51 1.76 1.87 1.55 1.69 1.78 1.96 2.09 2.09 1.62 1.70 1.83 Argininosuccinic acid 7.02 12.79 12.17 16.51 8.85 12.38 12.28 14.31 8.31 13.87 10.45 10.58 12.95 13.66 12.01 10.26 9.42 8.20 11.38 10.53 10.43 10.34 8.96 11.84 Asparagine 50.8 53.7 48.8 53.5 41.9 53.6 47.3 47.1 47.1 52.3 48.4 42.7 46.7 48.3 50.1 43.6 49.8 57.5 58.8 63.0 52.7 50.4 51.0 56.6 Aspartic acid 1223 2061 1162 1559 1070 1891 1704 1517 1167 1488 1320 1313 2211 1767 1604 1649 1132 1220 1694 1374 1586 1094 1160 1256 Beta-Alanine 52 51 38 54 37 52 49 51 44 39 48 38 43 49 47 39 47 51 51 63 46 40 44 49 Betaine 1444 1021 1923 1598 2798 993 1055 2021 1126 932 1249 1198 1049 2065 1328 899 1112 574 1041 1286 585 982 789 1069 Betaine aldehyde 7.20 11.99 12.61 15.07 10.25 8.47 10.23 15.08 7.31 10.68 9.55 10.99 14.45 15.51 13.35 13.20 8.55 7.00 9.60 10.86 9.87 11.30 9.60 13.38 Carnitine 336 341 342 295 286 317 320 322 358 298 308 366 297 310 363 283 211 282 230 233 267 218 202 220 Choline 70.3 109.2 91.8 153.5 80.7 51.9 71.9 122.0 53.9 76.9 93.7 73.0 116.2 125.7 101.3 92.8 57.4 49.0 94.4 100.3 80.8 68.0 84.0 112.0 cis-3-hydroxyproline 11.3 12.2 11.9 12.2 11.5 12.3 12.6 12.8 11.0 11.6 12.1 10.7 11.2 11.9 12.2 10.6 18.6 18.9 19.0 18.4 17.2 14.6 15.9 15.8 Citrulline 7.42 13.10 13.00 19.62 9.58 14.16 12.99 13.82 9.03 15.21 11.94 10.13 9.69 14.48 10.84 9.25 11.98 11.73 13.99 13.79 12.74 12.67 10.28 14.56 Creatine 542 720 791 846 559 793 728 692 722 724 757 619 570 569 689 607 883 757 596 567 778 834 655 709 Creatinine 10.8 13.1 12.9 11.9 11.8 11.6 11.2 14.1 11.7 12.9 12.4 12.0 12.0 15.3 11.7 12.8 12.6 13.2 12.1 12.9 11.9 10.9 9.7 11.5 Cystathionine 4.47 5.47 4.72 4.73 4.37 4.56 4.72 4.47 5.84 4.28 4.13 4.18 4.09 4.05 5.16 3.89 4.95 5.19 5.50 5.11 6.24 4.84 5.67 5.90 Cysteine 5.02 6.85 10.57 12.35 5.77 8.92 8.71 5.39 15.82 19.77 11.97 8.14 8.18 7.65 7.10 12.13 3.53 6.73 7.69 6.91 6.31 5.32 6.03 5.23 Dimethylglycine 24.9 25.8 33.7 27.0 32.9 16.8 19.0 22.4 21.9 15.4 16.3 20.3 18.0 21.0 28.2 12.0 22.9 18.3 19.3 22.4 18.1 22.5 20.9 27.8 Gamma-Aminobutyric acid 15.11 15.69 14.75 10.51 11.35 12.35 13.25 10.29 19.49 15.61 14.17 11.50 11.18 12.84 13.28 10.33 12.56 17.89 12.83 21.57 10.61 10.46 9.88 9.31 Glutamic acid 5188 4420 3555 3038 2382 4264 3687 3814 5035 5341 4412 5710 3635 3425 3547 4931 4755 5105 4049 4279 4985 4485 5314 4274 Glutamine 5535 6039 5074 5450 5132 6064 7158 5873 6550 5490 6492 5761 6303 6577 6469 6331 4908 4584 6249 6418 5984 5688 5605 4784 Glutathione 2862 4936 4857 4533 3834 5009 5063 4538 5892 5129 4857 4971 4635 4577 5000 5258 4732 4720 4810 4917 5019 5102 5153 4654 Glycine 1387 1550 1572 1939 1538 1628 1751 1725 1644 1511 1535 1296 1730 1808 1681 1402 1592 1514 1769 1533 1407 1732 1280 1598 Guanine 1.397 1.109 1.498 0.939 1.311 1.126 1.277 1.558 0.820 1.292 1.033 1.178 0.933 1.090 0.813 1.354 1.072 1.273 1.367 1.134 1.221 1.210 1.161 0.978 Guanosine 20.4 36.3 38.5 30.4 30.9 32.5 33.9 45.6 22.8 30.8 30.8 42.1 42.9 44.8 37.5 40.2 60.0 45.7 51.6 59.4 44.5 57.5 50.4 55.8 Histidine 431 474 457 397 398 460 481 470 461 437 411 419 437 518 433 395 374 372 337 361 364 377 358 427 Hypoxanthine 47.4 65.7 43.9 76.1 58.5 59.8 66.0 48.0 64.3 62.8 84.9 58.8 58.2 74.1 76.0 51.9 55.2 58.4 95.0 122.9 76.5 72.4 82.5 104.6 Inosine 330 491 465 497 448 406 601 366 398 399 493 411 461 706 784 421 550 527 745 1152 554 634 662 791 Isoleucine 115 139 149 146 120 143 145 153 131 141 121 106 120 154 116 94 104 112 128 144 109 116 110 128 Leucine 234 270 271 283 241 274 284 284 244 256 239 213 229 288 224 186 198 227 252 289 218 221 222 244 Lysine 326 374 336 370 367 402 388 387 337 356 335 326 380 396 329 253 308 338 347 360 304 295 294 410 Methionine 18.1 18.8 23.5 22.3 19.4 20.4 19.4 19.7 15.2 18.4 17.1 18.3 18.8 18.1 19.1 18.1 21.9 23.0 24.8 24.2 21.7 22.7 20.4 22.6 Ornithine 76.7 88.0 85.0 78.1 76.9 97.8 97.2 98.4 91.0 100.5 95.4 80.1 104.0 153.8 91.6 79.0 136.1 131.1 134.2 167.6 119.7 117.5 118.5 138.8 Oxidized glutathione 1991 1246 827 1159 942 1175 1133 1007 656 691 992 881 866 1095 739 1083 1210 1271 814 831 952 1154 870 1092 Phenylalanine 72.3 73.7 66.3 68.8 61.5 70.8 70.5 69.5 68.5 63.2 65.2 60.5 63.4 71.8 60.5 56.5 68.5 73.9 66.9 84.7 63.3 65.5 65.0 75.2 Putrescine 1.8 1.2 1.3 1.0 1.6 N.D. 1.2 1.4 1.4 1.2 1.1 1.4 1.2 1.5 1.4 1.4 1.5 1.5 1.2 1.2 1.3 N.D. 1.5 1.2 S-Adenosylhomocysteine 12.9 17.3 16.4 15.2 15.0 16.6 14.9 17.1 17.7 15.3 15.3 14.8 14.0 15.9 16.1 12.3 12.0 12.5 12.1 15.9 12.1 12.1 12.4 18.1 S-Adenosylmethionine 52.4 70.3 85.8 56.0 53.8 61.2 53.8 76.1 70.6 70.3 66.5 71.6 69.3 72.7 63.3 56.3 51.6 61.9 50.5 58.4 48.3 49.4 50.4 64.9 Sarcosine 13 16 14 12 15 12 12 13 14 10 9.2 11 12 13 15 6.7 6.4 11 11 17 9.8 9.0 12 16 Serine 156 134 150 159 147 132 144 202 131 156 177 131 140 199 157 121 148 136 177 197 155 156 138 176 Spermidine 10.94 14.68 17.89 14.32 14.92 11.27 12.06 12.11 12.00 10.54 10.45 11.38 12.04 13.33 14.14 12.51 10.51 10.43 9.63 10.94 9.89 8.34 9.66 13.52 Spermine 6.50 17.04 13.90 9.30 10.96 11.49 14.43 14.41 13.47 14.31 15.87 11.44 12.05 14.43 13.64 14.00 10.96 14.98 12.32 13.21 10.90 11.38 9.59 13.74 Threonine 105.1 109.6 92.7 114.9 92.3 110.9 114.5 118.9 106.8 114.2 103.7 84.5 100.0 127.4 103.5 80.1 95.3 98.8 116.9 116.4 95.1 97.4 82.4 109.4 Tryptophan 23.3 27.8 26.0 24.8 23.8 27.0 24.7 25.7 24.7 26.8 24.5 24.0 25.4 27.9 25.3 23.1 25.5 29.3 26.7 29.4 25.4 26.7 24.6 26.5 Tyrosine 77.9 89.5 65.2 74.6 51.4 81.1 77.1 63.2 72.9 89.0 75.0 71.2 72.8 74.0 70.9 65.8 67.9 98.1 85.6 93.0 82.1 83.8 69.8 84.7 Urea 5938 6675 5312 6938 5426 5899 6384 6361 6539 5953 5809 5660 5378 6000 5684 5594 4986 5497 4976 5766 5471 4591 4786 4776 Valine 239 279 278 300 238 288 298 301 264 283 247 228 249 294 221 191 192 221 236 263 211 214 212 246 MS_METABOLITE_DATA_END #METABOLITES METABOLITES_START metabolite_name KEGG ID HMDB ID Adenine C00147 HMDB00034 Adenosine C00212 HMDB00050 Alanine C00041,C00133,C01401 HMDB00161,HMDB01310 Arginine C00062,C00792 HMDB00517,HMDB03416 Argininosuccinic acid C03406 HMDB00052 Asparagine C00152,C01905,C16438 HMDB00168 Aspartic acid C00049,C00402,C16433 HMDB00191,HMDB06483 Beta-Alanine C00099 HMDB00056 Betaine C00719 HMDB00043 Betaine aldehyde C00576 HMDB01252 Carnitine C00318,C00487,C15025 HMDB00062 Choline C00114 HMDB00097 cis-3-hydroxyproline C01015,C01157 HMDB06055,HMDB00725 Citrulline C00327 HMDB00904 Creatine C00300 HMDB00064 Creatinine C00791 HMDB00562 Cystathionine C00542,C02291 HMDB00099 Cysteine C00097,C00736,C00793 HMDB00574,HMDB03417 Dimethylglycine C01026 HMDB00092 Gamma-Aminobutyric acid C00334 HMDB00112 Glutamic acid C00025,C00217,C00302 HMDB00148,HMDB03339 Glutamine C00064,C00303,C00819 HMDB00641,HMDB03423 Glutathione C00051 HMDB00125 Glycine C00037 HMDB00123 Guanine C00242 HMDB00132 Guanosine C00387 HMDB00133 Histidine C00135,C00768,C06419 HMDB00177 Hypoxanthine C00262 HMDB00157 Inosine C00294 HMDB00195 Isoleucine C00407,C06418,C16434 HMDB00172 Leucine C00123,C01570,C16439 HMDB00687 Lysine C00047,C00739,C16440 HMDB00182,HMDB03405 Methionine C00073,C00855,C01733 HMDB00696 Ornithine C00077,C00515,C01602 HMDB00214,HMDB03374 Oxidized glutathione C00127 HMDB03337 Phenylalanine C00079,C02057,C02265 HMDB00159 Putrescine C00134 HMDB01414 S-Adenosylhomocysteine C00021 HMDB00939 S-Adenosylmethionine C00019 HMDB01185 Sarcosine C00213 HMDB00271 Serine C00065,C00716,C00740 HMDB00187,HMDB03406 Spermidine C00315 HMDB01257 Spermine C00750 HMDB01256 Threonine C00188,C00820 HMDB00167 Tryptophan C00078,C00525,C00806 HMDB00929 Tyrosine C00082,C01536,C06420 HMDB00158 Urea C00086 HMDB00294 Valine C00183,C06417,C16436 HMDB00883 METABOLITES_END #END