#METABOLOMICS WORKBENCH u023968_20190212_180200 DATATRACK_ID:1620 STUDY_ID:ST001136 ANALYSIS_ID:AN001862 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 6210 TOF MS:INSTRUMENT_TYPE Other 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 automatic integration software MasterHands (Keio University, Tsuruoka, Japan) in MS:MS_COMMENTS order to obtain peak information including m/z, migration time for CE-TOFMS MS:MS_COMMENTS measurement (MT) and peak area. Signal peaks corresponding to isotopomers, MS:MS_COMMENTS adduct ions, and other product ions of known metabolites were excluded, and MS:MS_COMMENTS remaining peaks were annotated with putative metabolites from the HMT metabolite MS:MS_COMMENTS database based on their MTs and m/z values determined by TOFMS. The tolerance MS:MS_COMMENTS range for the peak annotation was configured at ±0.5 min for MT and ±10 ppm MS:MS_COMMENTS for m/z. In addition, peak areas were normalized against those of the internal MS:MS_COMMENTS standards and then the resultant relative area values were further normalized by MS:MS_COMMENTS sample amount. #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):- 2,3-Diphosphoglyceric acid 93.0 139.2 129.9 135.1 114.9 119.1 120.4 103.8 97.8 120.7 122.0 98.5 90.1 127.3 128.7 113.9 74.7 85.0 81.8 85.5 91.2 87.0 70.6 74.0 2-hydroxyglutaric acid 3.8 1.7 2.6 1.4 1.4 2.1 1.4 1.9 3.4 3.1 1.6 3.1 1.3 2.2 1.7 3.2 4.9 4.3 4.3 3.8 3.5 4.1 4.9 2.8 2-Phosphoglyceric acid 1.264 1.309 1.679 2.234 1.557 1.321 1.118 1.676 1.010 1.330 0.975 1.268 1.040 1.057 1.472 1.109 0.668 0.507 0.386 0.424 0.312 0.798 0.419 0.562 3',5' cyclic AMP 0.364 0.399 0.340 0.569 0.291 0.328 0.408 0.307 0.348 0.486 0.447 0.260 0.367 0.467 0.435 0.354 0.351 0.435 0.452 0.425 0.460 0.423 0.507 0.482 3-hydroxy-3-methylglutaryl-CoA 0.191 0.199 0.156 0.233 0.270 0.189 0.185 0.198 0.169 0.152 0.149 0.133 0.220 0.175 0.163 0.152 0.114 0.145 0.141 0.204 0.139 0.161 0.175 0.137 3-Phosphoglyceric acid 10.74 12.80 19.24 20.62 13.63 12.92 11.28 13.60 9.57 12.02 9.35 12.04 10.50 11.91 13.70 10.45 6.63 6.31 4.14 5.03 6.11 7.73 5.38 5.90 6-Phosphogluconic acid 42.2 37.0 35.2 46.9 43.4 38.8 52.1 38.9 34.3 37.3 40.2 29.7 41.0 50.3 38.7 37.8 21.4 32.5 22.1 36.3 26.4 21.7 30.5 37.6 Acetyl-CoA 14.96 9.24 7.36 10.83 18.99 11.58 16.43 15.95 13.49 11.26 12.97 11.62 11.61 14.60 8.51 10.14 9.99 11.93 7.28 12.47 6.76 6.76 8.54 10.12 Adenylsuccinic acid 44.2 50.0 30.1 53.3 39.8 43.5 49.4 42.7 38.5 46.7 59.7 41.8 53.3 56.4 50.1 47.3 43.5 50.1 65.3 84.3 52.7 51.8 58.6 61.9 ADP 1042 1003 1025 825 1027 898 892 1059 1086 924 944 986 902 892 935 940 807 742 762 579 941 836 808 739 ADP-ribose 52.5 31.5 25.3 49.2 37.7 25.8 37.9 26.7 35.6 32.0 57.0 21.5 12.8 26.6 42.9 25.2 34.9 46.7 43.3 53.6 41.6 19.6 45.4 37.8 AMP 1426 1301 1337 1499 1387 1350 1253 1355 1458 1490 1753 1562 1356 1540 1526 1394 1226 1433 1423 1452 1587 1590 1741 1549 ATP 1135 1072 1141 673 1164 810 791 1135 1077 735 607 827 755 665 672 803 671 513 421 261 586 498 449 340 Cis-Aconitic acid 1.6 0.8 1.3 1.0 1.4 0.9 0.8 1.4 1.4 1.3 1.5 1.6 0.5 0.6 1.0 1.3 1.6 0.8 1.3 1.3 1.9 1.7 1.8 1.1 Citric acid 165 108 135 116 119 119 109 153 162 165 156 163 98 121 113 161 185 124 162 141 209 181 185 130 Coenzyme A 204 193 255 227 212 241 252 242 236 233 200 230 219 223 214 209 177 183 186 193 198 225 191 167 Dihydroxyacetone phosphate 73.0 60.6 37.2 63.9 48.8 51.6 59.3 41.9 66.5 50.9 60.8 29.0 46.6 47.1 56.1 43.5 25.4 34.1 23.8 47.3 26.1 23.7 34.5 30.8 Fructose-1,6-biphosphate 12.41 11.23 11.16 10.51 11.17 7.65 9.29 9.93 9.88 9.50 11.24 10.19 7.94 8.22 9.24 9.31 8.12 8.00 7.05 5.90 8.69 7.81 8.54 8.53 Fructose-1-phosphate 23.51 17.11 13.76 14.38 23.57 17.10 26.88 21.58 15.75 26.33 22.58 23.97 24.58 29.74 19.40 19.82 20.56 17.86 16.48 22.03 9.51 17.17 12.63 22.34 Fructose-6-phosphate 86.1 80.9 60.5 55.7 97.6 64.6 118.9 86.6 77.7 61.9 71.3 74.6 71.5 96.6 66.0 72.4 89.5 67.6 65.4 75.3 69.9 84.6 81.7 90.7 Fumaric acid 458 529 324 461 429 482 509 379 420 387 432 320 512 443 503 469 339 407 568 577 491 367 408 368 Galactose-1-phosphate 13.4 14.1 12.7 16.3 15.3 12.7 18.2 14.3 13.7 13.9 15.7 13.1 14.8 16.8 16.9 12.0 16.8 15.1 10.3 20.9 20.2 18.3 18.7 21.8 GDP 52.2 49.0 57.0 43.4 51.0 45.3 49.9 53.7 47.7 44.0 41.6 46.4 47.2 58.1 49.1 52.8 52.5 44.0 47.3 40.3 51.1 48.1 43.4 42.9 Glucose-1-phosphate 41.7 40.2 31.1 26.8 42.0 40.6 48.0 42.1 31.2 24.8 33.9 33.9 35.8 36.0 22.4 30.7 38.4 28.6 29.3 39.4 25.6 36.0 39.7 42.4 Glucose-6-phosphate 439 404 350 343 506 365 517 404 413 374 403 366 387 461 340 382 412 359 356 427 393 390 435 480 Glyceraldehyde-3-phosphate 2.031 0.734 1.291 1.123 1.699 1.382 2.163 0.818 N.D. 1.277 1.170 1.180 0.710 3.043 0.646 0.617 1.169 N.D. N.D. 1.999 N.D. 0.795 1.468 1.322 Glycerol 3-phosphate 1986 2291 1721 1784 2036 2203 2394 1607 2160 1713 1716 1584 2191 2222 2328 1847 1892 2217 2169 2558 1930 1807 1875 1789 GMP 264 271 251 294 259 285 260 252 291 270 313 290 281 307 266 258 253 291 286 316 309 287 323 303 GTP 58.2 61.4 63.8 35.1 64.5 47.5 50.5 63.1 57.5 36.2 29.6 40.2 43.7 44.4 43.1 49.4 42.3 31.4 28.7 21.4 34.4 30.8 26.8 22.0 IMP 329 524 313 455 396 553 641 301 396 341 405 311 531 596 463 395 453 397 399 454 257 292 369 457 Lactic acid 5352 5240 3797 3503 5056 4733 5876 3758 6815 4074 4590 4176 4193 5193 5565 4627 5005 6548 5974 7155 4734 4527 4828 4640 Malic acid 1165 1308 830 1144 1053 1149 1167 911 1024 991 974 674 1274 985 1282 1200 692 985 1289 1387 1207 797 972 848 N-acetylglutamic acid 22 21 18 34 24 24 27 25 20 26 20 18 16 22 19 13 11 19 13 15 15 16 17 20 NAD+ 684 686 714 712 659 712 703 708 600 695 641 634 662 775 584 665 513 599 566 550 570 606 534 524 NADH 9.51 9.32 8.84 9.24 8.96 9.62 11.69 10.96 10.02 10.19 10.15 10.50 9.29 10.91 9.97 9.25 10.11 7.86 10.09 9.89 9.60 11.14 8.79 7.98 NADP+ 464 486 465 532 458 479 466 472 431 444 461 368 389 472 426 432 280 398 349 410 362 377 383 389 NADPH 24.1 13.5 13.6 12.7 18.6 18.3 30.5 28.4 44.2 25.5 34.7 43.3 23.3 23.9 12.2 26.9 68.4 16.9 56.3 24.6 29.6 44.3 23.7 21.5 N-carbamoylaspartic acid 0.271 0.395 0.304 0.461 0.246 0.286 0.368 0.307 0.273 0.278 0.312 0.248 0.245 0.253 0.387 0.244 0.231 0.373 0.174 0.194 0.342 0.263 0.254 0.184 Phosphocreatine 8.36 10.71 8.65 10.35 7.67 8.42 7.75 7.86 9.49 9.15 8.05 5.67 6.01 6.63 9.96 6.28 10.60 7.99 4.50 3.75 7.68 7.60 5.83 6.36 Phosphoenolpyruvic acid 3.39 4.23 6.57 7.05 4.82 4.54 4.06 4.96 2.94 4.13 2.61 4.01 3.57 3.59 4.16 3.46 2.04 1.62 1.10 1.17 1.62 2.40 1.39 1.50 Phosphoribosyl pyrophosphate 0.142 N.D. 0.177 0.137 0.254 0.183 0.132 0.100 N.D. 0.187 0.153 0.106 N.D. 0.171 N.D. 0.200 0.160 0.133 0.130 0.089 0.112 0.104 0.142 0.133 Pyruvic acid 87 91 72 66 126 107 142 106 143 99 78 176 139 131 132 134 231 119 216 153 146 189 131 121 Ribose-1-phosphate 195 214 145 211 233 216 258 163 209 172 225 176 195 269 212 174 182 210 247 316 193 190 218 247 Ribose-5-phosphate 58.5 56.1 55.2 66.1 51.5 55.4 81.3 40.8 50.8 79.3 76.6 64.8 80.8 102.6 92.6 86.1 67.7 70.0 67.2 69.9 61.3 61.3 73.6 73.4 Ribulose-5-phosphate 24.1 28.3 17.1 29.0 26.2 23.1 30.6 27.8 22.9 28.5 23.7 26.1 26.0 31.2 29.5 30.7 26.0 20.9 23.4 22.4 21.5 28.1 24.7 21.9 Sedoheptulose 7-phosphate 115.7 93.3 76.7 82.0 120.7 79.2 133.4 107.3 119.0 94.0 118.5 101.4 98.0 184.5 90.2 97.2 114.5 108.6 98.3 140.3 85.8 95.5 113.1 133.2 Succinic acid 1300 959 849 882 899 1009 950 824 1059 1083 1107 969 857 979 989 1007 1279 1436 1301 1646 1217 1203 1207 1076 UDP-glucose 493 517 501 456 552 507 542 496 534 504 548 564 481 641 527 469 446 515 453 472 430 508 465 552 Uric acid 5.6 4.8 4.0 6.6 6.0 4.8 7.2 3.7 4.8 3.9 5.3 3.5 4.6 6.2 5.2 4.6 5.7 5.8 14 20 6.5 5.4 7.9 7.6 Xanthine 53.4 66.5 47.1 68.6 69.1 52.4 71.2 46.4 74.0 58.1 65.4 51.9 53.4 71.1 77.9 51.2 56.6 44.6 80.1 102.4 59.4 53.1 65.3 67.6 XMP 0.230 0.257 0.247 0.372 0.333 0.304 0.370 0.254 0.307 0.171 0.199 0.194 0.349 0.567 0.228 0.269 0.372 0.253 0.276 0.461 0.137 0.254 0.167 0.225 Xylulose-5-phosphate 30.4 20.2 27.0 26.5 20.9 23.0 32.5 24.8 16.2 20.5 36.2 19.5 17.7 42.6 22.3 19.1 22.2 24.3 16.7 15.5 12.1 20.2 18.1 30.4 MS_METABOLITE_DATA_END #METABOLITES METABOLITES_START metabolite_name KEGG ID HMDB ID 2,3-Diphosphoglyceric acid C01159 HMDB01294 2-hydroxyglutaric acid C02630,C01087,C03196 HMDB00606,HMDB00694 2-Phosphoglyceric acid C00631 HMDB03391 3',5' cyclic AMP C00575 HMDB00058 3-hydroxy-3-methylglutaryl-CoA C00356 HMDB01375 3-Phosphoglyceric acid C00197 HMDB00807 6-Phosphogluconic acid C00345 HMDB01316 Acetyl-CoA C00024 HMDB01206 Adenylsuccinic acid C03794 HMDB00536 ADP C00008 HMDB01341 ADP-ribose C00301 HMDB01178 AMP C00020 HMDB00045 ATP C00002 HMDB00538 Cis-Aconitic acid C00417 HMDB00072 Citric acid C00158 HMDB00094 Coenzyme A C00010 HMDB01423 Dihydroxyacetone phosphate C00111 HMDB01473 Fructose-1,6-biphosphate C00354 HMDB01058 Fructose-1-phosphate C01094,C02976 HMDB01076 Fructose-6-phosphate C05345,C00085 HMDB00124 Fumaric acid C00122 HMDB00134 Galactose-1-phosphate C00446 HMDB00645 GDP C00035 HMDB01201 Glucose-1-phosphate C00103 HMDB01586 Glucose-6-phosphate C00668,C01172,C00092 HMDB01401 Glyceraldehyde-3-phosphate C00118,C00661 HMDB01112 Glycerol 3-phosphate C00093 HMDB00126 GMP C00144 HMDB01397 GTP C00044 HMDB01273 IMP C00130 HMDB00175 Lactic acid C00186,C00256,C01432 HMDB00190,HMDB01311 Malic acid C00149,C00497,C00711 HMDB00156,HMDB00744 N-acetylglutamic acid C00624 HMDB01138 NAD+ C00003 HMDB00902 NADH C00004 HMDB01487 NADP+ C00006 HMDB00217 NADPH C00005 HMDB00221 N-carbamoylaspartic acid C00438 HMDB00828 Phosphocreatine C02305 HMDB01511 Phosphoenolpyruvic acid C00074 HMDB00263 Phosphoribosyl pyrophosphate C00119 HMDB00280 Pyruvic acid C00022 HMDB00243 Ribose-1-phosphate C00620 HMDB01489 Ribose-5-phosphate C00117 HMDB01548 Ribulose-5-phosphate C00199,C01101 HMDB00618 Sedoheptulose 7-phosphate C05382 HMDB01068 Succinic acid C00042 HMDB00254 UDP-glucose C00029 HMDB00286 Uric acid C00366 HMDB00289 Xanthine C00385 HMDB00292 XMP C00655 HMDB01554 Xylulose-5-phosphate C00231,C03291 HMDB00868 METABOLITES_END #END