#METABOLOMICS WORKBENCH KDSpencer77_20230821_110949 DATATRACK_ID:4236 STUDY_ID:ST002836 ANALYSIS_ID:AN004636 PROJECT_ID:PR001776 VERSION 1 CREATED_ON August 22, 2023, 12:00 pm #PROJECT PR:PROJECT_TITLE Bacterial tryptophan metabolites increased by prebiotic galactooligosaccharide PR:PROJECT_TITLE reduce microglial reactivity and are associated with lower anxiety-like behavior PR:PROJECT_SUMMARY Prebiotic galactooligosaccharides (GOS) reduce anxiety-like behaviors in mice PR:PROJECT_SUMMARY and humans. However, the biological pathways behind these behavioral changes are PR:PROJECT_SUMMARY not well understood. To begin to study these pathways, C57BL/6 mice were fed a PR:PROJECT_SUMMARY standard diet with or without GOS supplementation for 3 weeks prior to testing PR:PROJECT_SUMMARY on the open field. After behavioral testing, colonic contents and serum were PR:PROJECT_SUMMARY collected for bacteriome (16S rRNA gene sequencing, colonic contents only) and PR:PROJECT_SUMMARY metabolome (UPLC-MS, colonic contents and serum data) analyses. As expected, GOS PR:PROJECT_SUMMARY significantly reduced anxiety-like behavior (i.e., increased time in the center PR:PROJECT_SUMMARY (p < 0.05)). Time in the center was significantly correlated with serum PR:PROJECT_SUMMARY methyl-indole-3-acetate (mI3A). This metabolite, which is a methylated form of PR:PROJECT_SUMMARY indole-3-acetate, is derived from bacterial metabolism of tryptophan. Sequencing PR:PROJECT_SUMMARY analyses showed that GOS significantly increased Akkermansia, which is known to PR:PROJECT_SUMMARY metabolize both GOS and tryptophan. To test the hypothesis that mI3A can reduce PR:PROJECT_SUMMARY anxiety-like behavior and affect microglial activity, we first tested mI3A PR:PROJECT_SUMMARY effects on LPS-stimulated BV2 microglia. Cells treated with mI3A produced PR:PROJECT_SUMMARY significantly less CCL2 and TNF-α than vehicle-treated cells (p<.05). We then PR:PROJECT_SUMMARY treated mice with an intraperitoneal injection of mI3A or vehicle control, and PR:PROJECT_SUMMARY found that mice given mI3A had lower CCL2 in the prefrontal cortex and PR:PROJECT_SUMMARY hippocampus, as well as a reduction in a composite behavioral score in the open PR:PROJECT_SUMMARY field. Together, these data support a novel pathway through which GOS reduces PR:PROJECT_SUMMARY anxiety-like behaviors in mice, and suggests that the bacterial metabolite mI3A, PR:PROJECT_SUMMARY which is elevated by GOS, reduces microglial CCL2, which in turn reduces PR:PROJECT_SUMMARY anxiety-like behavior. PR:INSTITUTE National Center for Advancing Translational Sciences PR:LAST_NAME Spencer PR:FIRST_NAME Kyle PR:ADDRESS 9800 Medical Center Dr, Rockville, MD 20850 PR:EMAIL kyle.spencer@nih.gov PR:PHONE 989-708-4858 #STUDY ST:STUDY_TITLE Bacterial tryptophan metabolites increased by prebiotic galactooligosaccharide ST:STUDY_TITLE reduce microglial reactivity and are associated with lower anxiety-like behavior ST:STUDY_TITLE (Intestine) ST:STUDY_SUMMARY Prebiotic galactooligosaccharides (GOS) reduce anxiety-like behaviors in mice ST:STUDY_SUMMARY and humans. However, the biological pathways behind these behavioral changes are ST:STUDY_SUMMARY not well understood. To begin to study these pathways, C57BL/6 mice were fed a ST:STUDY_SUMMARY standard diet with or without GOS supplementation for 3 weeks prior to testing ST:STUDY_SUMMARY on the open field. After behavioral testing, colonic contents and serum were ST:STUDY_SUMMARY collected for bacteriome (16S rRNA gene sequencing, colonic contents only) and ST:STUDY_SUMMARY metabolome (UPLC-MS, colonic contents and serum data) analyses. As expected, GOS ST:STUDY_SUMMARY significantly reduced anxiety-like behavior (i.e., increased time in the center ST:STUDY_SUMMARY (p < 0.05)). Time in the center was significantly correlated with serum ST:STUDY_SUMMARY methyl-indole-3-acetate (mI3A). This metabolite, which is a methylated form of ST:STUDY_SUMMARY indole-3-acetate, is derived from bacterial metabolism of tryptophan. Sequencing ST:STUDY_SUMMARY analyses showed that GOS significantly increased Akkermansia, which is known to ST:STUDY_SUMMARY metabolize both GOS and tryptophan. To test the hypothesis that mI3A can reduce ST:STUDY_SUMMARY anxiety-like behavior and affect microglial activity, we first tested mI3A ST:STUDY_SUMMARY effects on LPS-stimulated BV2 microglia. Cells treated with mI3A produced ST:STUDY_SUMMARY significantly less CCL2 and TNF-α than vehicle-treated cells (p<.05). We then ST:STUDY_SUMMARY treated mice with an intraperitoneal injection of mI3A or vehicle control, and ST:STUDY_SUMMARY found that mice given mI3A had lower CCL2 in the prefrontal cortex and ST:STUDY_SUMMARY hippocampus, as well as a reduction in a composite behavioral score in the open ST:STUDY_SUMMARY field. Together, these data support a novel pathway through which GOS reduces ST:STUDY_SUMMARY anxiety-like behaviors in mice, and suggests that the bacterial metabolite mI3A, ST:STUDY_SUMMARY which is elevated by GOS, reduces microglial CCL2, which in turn reduces ST:STUDY_SUMMARY anxiety-like behavior. ST:INSTITUTE National Center for Advancing Translational Sciences ST:LAST_NAME Spencer ST:FIRST_NAME Kyle ST:ADDRESS 9800 Medical Center Dr, Rockville, MD 20850 ST:EMAIL kyle.spencer@nih.gov ST:PHONE 989-708-4858 #SUBJECT SU:SUBJECT_TYPE Mammal SU:SUBJECT_SPECIES Mus musculus SU:TAXONOMY_ID 10090 #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 - NACH-00282 GROUP_ID:GOS SUBJECT_SAMPLE_FACTORS - NACH-00283 GROUP_ID:GOS SUBJECT_SAMPLE_FACTORS - NACH-00284 GROUP_ID:GOS SUBJECT_SAMPLE_FACTORS - NACH-00285 GROUP_ID:GOS SUBJECT_SAMPLE_FACTORS - NACH-00286 GROUP_ID:GOS SUBJECT_SAMPLE_FACTORS - NACH-00287 GROUP_ID:GOS SUBJECT_SAMPLE_FACTORS - NACH-00288 GROUP_ID:CON SUBJECT_SAMPLE_FACTORS - NACH-00289 GROUP_ID:CON SUBJECT_SAMPLE_FACTORS - NACH-00290 GROUP_ID:CON SUBJECT_SAMPLE_FACTORS - NACH-00291 GROUP_ID:CON SUBJECT_SAMPLE_FACTORS - NACH-00292 GROUP_ID:CON SUBJECT_SAMPLE_FACTORS - NACH-00293 GROUP_ID:CON #COLLECTION CO:COLLECTION_SUMMARY After euthanasia the colonic contents of the mice were collected and sent to CO:COLLECTION_SUMMARY Metabolon Inc for UPLC-MS Analysis. CO:SAMPLE_TYPE Intestine #TREATMENT TR:TREATMENT_SUMMARY The mice were fed either a control diet or a diet supplemented with 10% TR:TREATMENT_SUMMARY galactooligosaccharide for 3 weeks. After the 3 weeks had elapsed the mice were TR:TREATMENT_SUMMARY euthanized and the colonic contents were collected. #SAMPLEPREP SP:SAMPLEPREP_SUMMARY The colonic contents were sent to Metabolon who then performed the sample SP:SAMPLEPREP_SUMMARY preparation prior to UPLC-MS analysis. #CHROMATOGRAPHY CH:CHROMATOGRAPHY_SUMMARY HILIC (LC/MS Polar Neg) CH:CHROMATOGRAPHY_TYPE HILIC CH:INSTRUMENT_NAME Waters Acquity CH:COLUMN_NAME Waters Acquity BEH Amide (150 x 2.1mm, 1.7um) CH:SOLVENT_A - CH:SOLVENT_B - CH:FLOW_GRADIENT - CH:FLOW_RATE - CH:COLUMN_TEMPERATURE - #ANALYSIS AN:ANALYSIS_TYPE MS #MS MS:INSTRUMENT_NAME Thermo Q Exactive Orbitrap MS:INSTRUMENT_TYPE Orbitrap MS:MS_TYPE Other MS:ION_MODE NEGATIVE MS:MS_COMMENTS Metabolon (LC/MS Polar) #MS_METABOLITE_DATA MS_METABOLITE_DATA:UNITS Relative Abundance MS_METABOLITE_DATA_START Samples NACH-00282 NACH-00283 NACH-00284 NACH-00285 NACH-00286 NACH-00287 NACH-00288 NACH-00289 NACH-00290 NACH-00291 NACH-00292 NACH-00293 Factors GROUP_ID:GOS GROUP_ID:GOS GROUP_ID:GOS GROUP_ID:GOS GROUP_ID:GOS GROUP_ID:GOS GROUP_ID:CON GROUP_ID:CON GROUP_ID:CON GROUP_ID:CON GROUP_ID:CON GROUP_ID:CON 2,3-dihydroxyisovalerate 1.0135 1.7091 0.752 0.6987 1.3988 2.8288 0.3756 0.9865 1.143 0.6164 1.3356 0.7331 2-hydroxy-4-(methylthio)butanoic acid 0.752 0.9066 2.4049 1 0.9732 2.2794 3.2909 8.0785 1.1837 0.5105 0.5105 0.8405 2-hydroxybutyrate/2-hydroxyisobutyrate 0.5742 2.6007 1.2385 0.8926 4.6774 1.0947 0.772 1.3488 0.876 0.5818 1.7659 0.9053 2-hydroxyheptanoate* 0.6229 0.6229 1.7416 0.8903 1.5609 1 0.9243 2.5918 0.6328 1.3119 0.7971 1.1481 2-hydroxylignocerate* 1.3669 0.5955 0.7005 2.1765 0.4367 2.6105 0.7942 0.8515 1.1485 1.889 0.3708 1.2574 2-isopropylmalate 0.5073 1.2822 0.5073 0.5073 1.3934 3.924 0.5073 0.7178 0.5073 0.6763 1.9832 0.6226 2R,3R-dihydroxybutyrate 0.44 2.571 0.44 0.7768 4.5544 1 0.44 0.8778 0.44 0.44 2.7856 0.44 2S,3R-dihydroxybutyrate 0.8774 1.3465 1 1.5468 3.5878 1.2719 0.5251 0.7622 1.3371 0.6655 0.5251 0.5327 3,4-dihydroxybutyrate 1.5652 0.9724 0.9103 1 1.7438 1.7831 0.5568 0.9111 1.2413 0.5568 0.5568 0.5568 3-hydroxy-3-methylglutarate 0.6795 1.6665 0.5793 1.4568 3.23 2.7987 0.3234 0.6563 0.3234 0.3234 1.3205 0.5479 3-hydroxybutyrate (BHBA) 0.8974 3.8078 0.4013 1.1844 9.2352 0.3172 1 1.129 0.7348 0.3172 4.8249 0.4225 3-hydroxyisobutyrate 0.0954 1.1091 0.2854 0.0954 2.1056 0.0954 0.0954 1.4713 0.0954 0.0954 0.8909 0.0954 3-hydroxysebacate 0.2996 0.4538 1.0432 1.7432 0.811 4.597 0.9541 0.8354 1.5673 1.1738 0.9568 1.3728 3-hydroxysuberate 0.5453 0.6974 0.8694 0.8298 0.2269 2.5593 1.2734 1.11 1.531 1.2377 0.89 1.8607 3-hydroxyvalerate 0.5097 2.391 0.5097 0.5097 3.8952 0.5097 0.6316 1.5431 0.7393 0.6584 1.7896 1 3-methyl-2-oxobutyrate 1.3907 0.6937 0.8356 1.2184 0.6156 2.3118 0.7728 1.5136 1.9612 1.001 0.7151 0.999 6-oxopiperidine-2-carboxylate 0.4946 1.0523 0.366 0.366 1.3355 1.5318 0.366 0.4349 0.9477 1.4302 1.2875 0.8336 allantoin 0.2129 3.6148 0.4853 18.6256 6.7469 0.3088 0.3411 1.5147 0.1985 2.2336 2.4319 0.1961 allo-threonine 2.2458 0.2881 1.173 1 0.2881 2.6492 0.2881 0.2881 0.2881 0.9056 0.2881 0.9288 alpha-hydroxyisovalerate 0.5515 2.0107 0.9011 1.0097 4.0832 0.9903 1.1469 1.8037 0.8678 0.8131 2.2399 0.9307 alpha-ketoglutaramate* 0.9331 0.5434 0.8261 1.047 1.1252 1.4586 0.6649 1.8934 1.1193 0.9837 0.8048 1.0163 alpha-ketoglutarate 1.4511 0.508 0.5878 1.188 0.7094 3.1462 0.915 0.6267 2.3349 1.2779 0.5 1.085 arabinose 0.5085 0.5085 0.5085 4.7183 0.5085 14.3838 0.7828 0.5085 0.5085 1.2172 0.5702 0.5085 arabonate/xylonate 0.5679 2.5626 0.6123 1.9403 7.644 1.1714 0.4598 1.1673 0.3887 0.8327 2.105 0.4452 ascorbic acid 3-sulfate* 0.1333 1 0.1333 10.3107 3.1906 0.2026 0.1333 0.1333 0.1333 1.3112 0.5534 0.1333 beta-hydroxyisovalerate 0.9104 1.3766 1.5978 0.7708 2.1193 1.0866 0.671 2.8701 0.8153 0.5317 1.1757 0.9134 dimethylmalonic acid 1.4187 1.2243 1.0842 0.9158 0.6216 1.6094 0.6231 0.4714 0.3693 1.5305 0.7984 1.2702 erythronate* 0.7058 2.215 0.6341 1.9476 6.0356 1.505 0.3947 0.7027 0.3598 1.2942 1.6439 0.586 ethylmalonate 1.1858 1.9682 0.6732 4.7713 4.4255 5.1485 0.5025 0.3496 0.5085 0.4057 1.6308 0.8142 fructose 1.3102 3.1282 0.5628 1.1066 3.6847 1.8446 0.5304 0.6698 0.9911 1.0089 0.8957 0.5813 fucose 0.6382 4.2551 0.9479 2.2451 12.2988 0.651 0.7824 1.2256 0.6262 1.0521 6.3151 0.5724 fumarate 0.7448 2.9546 1.2552 3.4251 8.9181 2.3228 0.5725 0.479 0.3284 0.4607 1.8215 0.3981 galactitol (dulcitol) 1.1258 2.4907 0.3059 6.2612 4.8613 2.092 0.3831 0.5584 0.8708 0.8742 1.3209 0.4757 galactonate 0.089 2.4694 0.089 1.4278 6.5931 0.8433 0.089 0.1224 0.089 0.2911 1.1567 0.089 gluconate 0.5757 5.9376 0.1632 0.7528 30.652 2.5345 0.1632 0.1632 0.1632 0.3579 1.2472 0.1632 glucose 2.1993 0.7002 1.0156 1.2303 0.5407 1.7994 0.977 0.6565 1.3943 1.2646 0.654 0.9844 glucose 6-phosphate 0.0425 0.0425 0.0425 0.0425 1.9575 0.0425 0.0425 0.0425 0.0425 0.0425 0.0425 0.0425 glucuronate 0.8138 2.0929 0.715 1.9313 3.2336 1.3823 0.6763 1.2066 0.8128 0.7198 1.1862 0.6685 glutarate (C5-DC) 1.5409 1.2545 0.8367 5.6123 3.3564 8.9382 0.7658 0.6367 0.9926 0.8408 1.0074 0.5503 glycerate 1.1456 2.8604 0.6968 1.521 4.0046 3.0453 0.3484 0.7001 0.6923 0.8544 1.8103 0.7418 glycerophosphoglycerol 0.6534 3.9729 0.9606 1.0394 3.9679 4.0978 0.432 2.0604 0.628 0.6913 10.2247 0.5341 homoserine 5.0184 0.5454 0.3826 0.9454 1.8309 3.2948 1.0546 0.3744 0.5989 0.3744 0.3744 1.1781 inositol 1-phosphate (I1P) 0.0868 0.0868 0.0868 0.0868 1.9132 0.0868 0.0868 0.0868 0.0868 0.0868 0.0868 0.0868 lactate 0.6604 8.4979 1.2019 1.3658 15.9483 0.7714 0.512 2.8747 0.6178 0.4943 5.7396 0.7981 maltose 1.3748 0.2755 1.5432 0.9988 0.2755 1.5847 1.329 0.7255 0.9673 0.7093 0.2755 1.0012 mannitol/sorbitol 2.8528 2.129 0.6767 1.2986 3.7155 2.2402 0.552 0.4951 1.0675 0.9325 0.6673 0.5509 mannose 1.3064 1.8268 0.9512 1.1002 2.732 1.7971 0.348 0.6908 0.6459 0.9511 1.0488 0.6183 methylmalonate (MMA) 1.663 3.3306 0.8555 8.4437 6.8266 5.8193 0.9953 0.5165 0.7264 1.0047 0.935 0.9189 methylsuccinate 0.8874 1.5797 0.7069 3.9373 2.8081 4.6206 0.7711 0.767 0.7594 1.443 1.1126 0.7115 mevalonate 0.5809 1.2527 0.9359 1 2.2611 1.0189 0.7193 0.5809 0.5809 0.5809 1.4389 0.8258 myo-inositol 0.7106 10.9189 1.0088 1.6569 7.9812 0.8722 0.7706 6.477 0.7565 0.9912 5.435 0.9471 N-acetylalanine 1.2536 5.0868 0.8347 0.8776 7.5523 1.2014 0.5902 1.1224 0.6853 0.8368 3.4826 0.6033 N-acetylaspartate (NAA) 0.4815 1.0039 0.2422 0.9961 2.0137 2.1334 0.3992 0.2632 0.5516 5.3774 2.9918 2.561 N-carbamoylaspartate 1.5059 2.7519 0.6275 1.7199 11.588 6.2427 0.2145 0.0888 0.393 0.8377 1.1623 0.4138 N-formylanthranilic acid 1.3841 0.9947 0.851 2.1937 1.2689 1.0123 0.9547 1.3595 0.9666 1.0053 0.9411 0.8893 orotate 0.9472 5.4108 0.6764 3.3426 8.9319 2.4726 0.3772 0.537 0.4687 1.0528 1.5288 0.3674 orotidine 0.146 5.3582 0.146 1.3076 6.5653 0.196 0.1527 0.6924 0.146 0.146 9.0091 0.146 pantoate 6.3489 0.4635 1.0598 1.2913 0.4146 0.948 1.0248 0.9752 0.676 1.6026 0.8246 1.1094 pimelate (C7-DC) 0.7625 0.7625 0.7625 0.7625 0.7625 0.8664 1.0066 0.8117 1.3211 1.2989 1.5149 0.9934 pyruvate 0.9292 0.6458 1.0708 0.4908 0.3556 1.1543 1.2572 1.1749 1.4095 0.6164 0.7959 1.2114 quinate 0.933 0.8667 1 0.8461 0.3643 3.108 0.4559 0.3643 1.032 1.5818 1.773 1.5555 ribonate 1.3591 1.0503 0.4599 1.8854 5.0351 0.8371 0.3579 0.3579 0.3579 0.9497 0.3579 0.3579 ribose 1.8274 0.9908 0.7689 1.6574 0.6898 3.0821 1.0173 0.5311 1.0092 1.3554 0.5582 0.7816 ribulonate/xylulonate/lyxonate* 0.4113 7.2892 0.312 1.8237 13.22 0.7815 0.2809 1.2185 0.2809 0.5999 4.8951 0.2809 ribulose/xylulose 1.4899 1.5549 0.5756 1.0124 0.7955 2.0878 0.6567 2.8017 0.8643 0.5876 0.9973 1.0027 salicylate 0.6728 0.6728 0.852 0.6728 1.148 0.6728 1.2135 1.2551 0.6728 0.7873 0.6728 0.6728 sedoheptulose 1.1353 1.8667 0.5287 0.8865 3.0028 1.7371 0.4642 1.1135 0.5666 0.6893 1.4054 0.5175 suberate (C8-DC) 0.1882 0.2561 0.4475 0.4299 0.3364 0.6013 1.3987 1.6288 1.7735 2.1375 1.7485 1.5239 succinate 2.1406 0.2673 2.0375 14.4029 0.5459 24.3643 1.2633 0.3141 1.3159 0.7367 0.3325 0.7334 succinimide 1.0447 0.4915 1.2397 1.0286 0.6697 1.5732 0.93 1.0099 0.9901 0.9319 0.5249 1.39 succinoyltaurine 1.2542 0.6977 0.66 1.6223 0.7164 3.0546 1.0654 0.5186 1.5422 0.8106 0.9346 1.4666 sucrose 0.9595 0.4474 1.3088 0.5954 0.441 6.9654 0.8413 1.0405 2.5615 0.441 0.441 1.6215 threonate 0.6337 12.792 0.6621 2.4043 25.0327 0.9932 0.7459 5.2472 0.5534 1.0068 10.5204 0.6922 xylose 1.7042 0.834 1.0937 7.8987 0.2332 12.1085 0.4935 0.4333 1.2328 3.284 0.2077 0.9063 MS_METABOLITE_DATA_END #METABOLITES METABOLITES_START metabolite_name SUPER_PATHWAY SUB_PATHWAY CHEMICAL_ID RI MASS CAS PUBCHEM CHEMSPIDER KEGG HMDB_ID 2,3-dihydroxyisovalerate Xenobiotics Food Component/Plant 100002417 1050 133.05063 1756-18-9 677 657 C04039 HMDB12141 2-hydroxy-4-(methylthio)butanoic acid Amino Acid Methionine, Cysteine, SAM and Taurine Metabolism 100021372 1065 149.02778 583-91-5 2-hydroxybutyrate/2-hydroxyisobutyrate Amino Acid Glutathione Metabolism 100008928 1258 103.04006 2-hydroxyheptanoate* Lipid Fatty Acid, Monohydroxy 100019960 925 145.08701 2750949 2032206 2-hydroxylignocerate* Lipid Fatty Acid, Monohydroxy 100019894 710 383.35307 102430 92507 C17873 HMDB39540 2-isopropylmalate Xenobiotics Food Component/Plant 100000409 2605 175.06119 3237-44-3 77 76 C02504 HMDB00402 2R,3R-dihydroxybutyrate Lipid Fatty Acid, Dihydroxy 100002367 1543 119.03498 759-06-8 17215960 HMDB00498 2S,3R-dihydroxybutyrate Lipid Fatty Acid, Dihydroxy 100002284 1660 119.03498 5057-93-2 10964471 9139682 HMDB02453 3,4-dihydroxybutyrate Lipid Fatty Acid, Dihydroxy 100001730 2204 119.03498 51267-44-8 3-hydroxy-3-methylglutarate Lipid Mevalonate Metabolism 112 2850 161.04555 503-49-1 1662 4573695 C03761 HMDB00355 3-hydroxybutyrate (BHBA) Lipid Ketone Bodies 254 1480 103.04007 625-72-9 441 428 C01089 HMDB00357 3-hydroxyisobutyrate Amino Acid Leucine, Isoleucine and Valine Metabolism 111 1619 103.04007 2068-83-9 87 10140307 C06001 HMDB00336 3-hydroxysebacate Lipid Fatty Acid, Monohydroxy 100001145 2411 217.10814 73141-46-5 3017884 2285525 HMDB00350 3-hydroxysuberate Lipid Fatty Acid, Monohydroxy 100001143 3000 189.07684 73141-47-6 22328017 13498677 HMDB00325 3-hydroxyvalerate Lipid Fatty Acid, Monohydroxy 100002459 1241 117.05571 10237-77-1 107802 96952 HMDB00531 3-methyl-2-oxobutyrate Amino Acid Leucine, Isoleucine and Valine Metabolism 100000936 911 115.04006 3715-29-5 49 48 C00141 HMDB00019 6-oxopiperidine-2-carboxylate Amino Acid Lysine Metabolism 100004499 1692 142.05096 34622-39-4 3014237 2282737 HMDB61705 allantoin Nucleotide Purine Metabolism, (Hypo)Xanthine/Inosine containing 1002 1672 157.03671 97-59-6 204 199 C02350 HMDB00462 allo-threonine Amino Acid Glycine, Serine and Threonine Metabolism 100000272 2511.1 118.05096 28954-12-3 99289 89699 C05519 HMDB04041 alpha-hydroxyisovalerate Amino Acid Leucine, Isoleucine and Valine Metabolism 100001300 1052 117.05571 600-37-3 99823 90190 HMDB00407 alpha-ketoglutaramate* Amino Acid Glutamate Metabolism 100002397 1916 144.03023 18465-19-5 alpha-ketoglutarate Energy TCA Cycle 93 2700 145.01425 305-72-6;328-50-7;22202-68-2 51 50 C00026 HMDB00208 arabinose Carbohydrate Pentose Metabolism 828 1804.5 195.05103 28697-53-2 66308 59687 C00216 HMDB00646 arabonate/xylonate Carbohydrate Pentose Metabolism 100006115 2700 165.04046 ascorbic acid 3-sulfate* Cofactors and Vitamins Ascorbate and Aldarate Metabolism 100020409 2025 254.98146 11425365 9600241 beta-hydroxyisovalerate Amino Acid Leucine, Isoleucine and Valine Metabolism 1442 1149.8 117.05572 625-08-1 69362 62571 HMDB00754 dimethylmalonic acid Lipid Fatty Acid, Dicarboxylate 100004251 2702 131.03498 595-46-0 11686 11195 HMDB02001 erythronate* Carbohydrate Aminosugar Metabolism 100001320 2186 135.02989 88759-55-1 2781043 2061231 HMDB00613 ethylmalonate Amino Acid Leucine, Isoleucine and Valine Metabolism 2054 2785 131.03498 601-75-2 11756 11263 HMDB00622 fructose Carbohydrate Fructose, Mannose and Galactose Metabolism 878 2065 225.06159 57-48-7 5984 5764 C00095 HMDB00660 fucose Carbohydrate Aminosugar Metabolism 918 1626.4 209.0667 2438-80-4 17106 2299091 C01018 HMDB00174 fumarate Energy TCA Cycle 330 3084 115.00368 100-17-8 444972 10197150 C00122 HMDB00134 galactitol (dulcitol) Carbohydrate Fructose, Mannose and Galactose Metabolism 1003 2360 181.07176 608-66-2 11850 11357 C01697 HMDB00107 galactonate Carbohydrate Fructose, Mannose and Galactose Metabolism 100001026 3085 195.05102 299-28-5 128869 114198 C00880 HMDB00565 gluconate Xenobiotics Food Component/Plant 338 2922 195.05102 527-07-1 10690 10240 C00257 HMDB00625 glucose Carbohydrate Glycolysis, Gluconeogenesis, and Pyruvate Metabolism 572 2342 225.06159 50-99-7 5793 71358 C00031 HMDB00122 glucose 6-phosphate Carbohydrate Glycolysis, Gluconeogenesis, and Pyruvate Metabolism 291 4537 259.02244 103192-55-8 5958 19952394 C00668 HMDB01401 glucuronate Carbohydrate Aminosugar Metabolism 100000257 3233.3 193.03537 207300-70-7 444791 58552 C00191 HMDB00127 glutarate (C5-DC) Lipid Fatty Acid, Dicarboxylate 339 2900 131.03498 110-94-1 743 3618533 C00489 HMDB00661 glycerate Carbohydrate Glycolysis, Gluconeogenesis, and Pyruvate Metabolism 1052 2070.4 105.01933 600-19-1 752 732 C00258 HMDB00139 glycerophosphoglycerol Lipid Glycerolipid Metabolism 100001619 2430 245.04317 439964 388990 C03274 homoserine Amino Acid Glycine, Serine and Threonine Metabolism 100000458 2875.8 118.05096 672-15-1 12647 12126 C00263 HMDB00719 inositol 1-phosphate (I1P) Lipid Inositol Metabolism 370 4785 259.02244 573-35-3;106032-59-1 440194 17215924 C01177 HMDB00213 lactate Carbohydrate Glycolysis, Gluconeogenesis, and Pyruvate Metabolism 482 1468.8 89.02442 79-33-4 612 592 C00186 HMDB00190 maltose Carbohydrate Glycogen Metabolism 913 3329.4 387.11442 6363-53-7 10991489 388469 C00208 HMDB00163 mannitol/sorbitol Carbohydrate Fructose, Mannose and Galactose Metabolism 100001740 2320 181.07176 5780 440 C00794 HMDB00247 mannose Carbohydrate Fructose, Mannose and Galactose Metabolism 803 2200 225.06159 3458-28-4 18950 141983 C00159 HMDB00169 methylmalonate (MMA) Lipid Fatty Acid Metabolism (also BCAA Metabolism) 418 3078.4 117.01933 516-05-2 487 473 C02170 HMDB00202 methylsuccinate Amino Acid Leucine, Isoleucine and Valine Metabolism 2051 2800 131.03498 498-21-5 10349 9922 HMDB01844 mevalonate Lipid Mevalonate Metabolism 30 1462 147.06628 96949-03-0 439230 388367 C02104 HMDB00227 myo-inositol Lipid Inositol Metabolism 363 3506.3 225.06159 87-89-8 892 10239179 C00137 HMDB00211 N-acetylalanine Amino Acid Alanine and Aspartate Metabolism 1110 1564.8 130.05096 97-69-8 88064 79449 C02847 HMDB00766 N-acetylaspartate (NAA) Amino Acid Alanine and Aspartate Metabolism 100000787 3143 174.04079 997-55-7;997-55-7 65065 58576 C01042 HMDB00812 N-carbamoylaspartate Nucleotide Pyrimidine Metabolism, Orotate containing 1108 3800 175.03604 923-37-5 93072 4573859 C00438 HMDB00828 N-formylanthranilic acid Amino Acid Tryptophan Metabolism 100004561 900 164.03531 3342-77-6 101399 91624 C05653 HMDB04089 orotate Nucleotide Pyrimidine Metabolism, Orotate containing 445 1638.1 155.00983 50887-69-9 967 942 C00295 HMDB00226 orotidine Nucleotide Pyrimidine Metabolism, Orotate containing 100001416 2250 287.05209 314-50-1 92751 83729 HMDB00788 pantoate Cofactors and Vitamins Pantothenate and CoA Metabolism 100002613 1100 147.06628 470-29-1 439251 388387 C00522 pimelate (C7-DC) Lipid Fatty Acid, Dicarboxylate 100000101 2745 159.06628 111-16-0 385 376 C02656 HMDB00857 pyruvate Carbohydrate Glycolysis, Gluconeogenesis, and Pyruvate Metabolism 823 1083 87.00877 127-17-3 1060 96901 C00022 HMDB00243 quinate Xenobiotics Food Component/Plant 100000442 2432.9 191.05611 77-95-2 6508 10246715 C00296 HMDB03072 ribonate Carbohydrate Pentose Metabolism 100001007 2425 165.04046 8/3/5336 5460677 4574162 C01685 HMDB00867 ribose Carbohydrate Pentose Metabolism 914 1508.2 195.05103 50-69-1 5779 4470639 C00121 HMDB00283 ribulonate/xylulonate/lyxonate* Carbohydrate Pentose Metabolism 100019968 2350 165.04046 ribulose/xylulose Carbohydrate Pentose Metabolism 100006122 1400 195.05102 5289590 salicylate Xenobiotics Drug - Topical Agents 501 802 137.02422 69-72-7 338 331 C00805 HMDB01895 sedoheptulose Carbohydrate Pentose Metabolism 100002619 2255 209.06667 3019-74-7 5459879 4573620 HMDB03219 suberate (C8-DC) Lipid Fatty Acid, Dicarboxylate 100000016 2577.6 173.08193 505-48-6 10457 10025 C08278 HMDB00893 succinate Energy TCA Cycle 252 3149 117.01933 110-15-6 1110 1078 C00042 HMDB00254 succinimide Xenobiotics Chemical 100003696 2155 116.03532 123-56-8 11439 10955 C07273 succinoyltaurine Amino Acid Methionine, Cysteine, SAM and Taurine Metabolism 100021220 2572 224.02343 20509456 sucrose Carbohydrate Disaccharides and Oligosaccharides 935 3092 387.11442 57-50-1 5988 5768 C00089 HMDB00258 threonate Cofactors and Vitamins Ascorbate and Aldarate Metabolism 100001022 2384 135.02989 70753-61-6 151152 133224 C01620 HMDB00943 xylose Carbohydrate Pentose Metabolism 826 1727 195.05103 609-06-3 135191 85957 C00181 HMDB00098 METABOLITES_END #END