#METABOLOMICS WORKBENCH xiehuijing_20230707_012117 DATATRACK_ID:4149 STUDY_ID:ST002774 ANALYSIS_ID:AN004516 VERSION 1 CREATED_ON 09-19-2023 #PROJECT PR:PROJECT_TITLE Defective Branched-Chain Amino Acid Catabolism in Dorsal Root Ganglia PR:PROJECT_TITLE Contributes to Mechanical Pain PR:PROJECT_SUMMARY Impaired branched-chain amino acid (BCAA) catabolism has recently been PR:PROJECT_SUMMARY implicated in the development of mechanical pain, but the molecular mechanisms PR:PROJECT_SUMMARY are unclear. Here we report that defective BCAA catabolism in dorsal root PR:PROJECT_SUMMARY ganglia (DRG) neurons sensitizes mice to mechanical pain by increasing lactate PR:PROJECT_SUMMARY production and Piezo2 expression, a mechanotransduction channel. In high-fat PR:PROJECT_SUMMARY diet fed obese mice, we observed a downregulation of PP2Cm, a key regulator in PR:PROJECT_SUMMARY BCAA catabolic pathway, in DRG neurons. Mice with conditional knockout of PP2Cm PR:PROJECT_SUMMARY in DRG neurons (cKO) exhibited mechanical allodynia under normal or spare nerve PR:PROJECT_SUMMARY injury (SNI)-induced neuropathic injury conditions. Further, in patients with PR:PROJECT_SUMMARY peripheral neuropathic pain, we found that the Visual Analogue Scale (VAS) PR:PROJECT_SUMMARY scores were positively correlated with BCAA contents in plasma, highlighting a PR:PROJECT_SUMMARY link between peripheral neuropathic pain and dysregulated BCAA catabolism. PR:PROJECT_SUMMARY Mechanistically, defective BCAA catabolism promotes the production of lactate PR:PROJECT_SUMMARY through glycolysis in DRG neurons, which increases H3K18la modification and PR:PROJECT_SUMMARY drives Piezo2 expression. Inhibition of lactate production or silencing of PR:PROJECT_SUMMARY Piezo2 expression attenuated the pain phenotype of cKO to mechanical stimuli. PR:PROJECT_SUMMARY Therefore, our study demonstrates a casual role of defective BCAA catabolism in PR:PROJECT_SUMMARY mechanical pain by enhancing metabolite-mediated epigenetic regulation. PR:INSTITUTE West China Hospital of Sichuan University PR:LABORATORY Laboratory of Mitochondria and Metabolism PR:LAST_NAME Li PR:FIRST_NAME Tao PR:ADDRESS No. 37 Guoxue Road, Wuhou District, Chendu 610041, Sichuan, China PR:EMAIL 563234879@qq.com PR:PHONE +8628-85164154 PR:DOI http://dx.doi.org/10.21228/M8ZD8R #STUDY ST:STUDY_TITLE Metabolomics studies on L4-5 Dorsal Root Ganglia of Ctrl and cKO mice ST:STUDY_SUMMARY Metabolomics studies on Dorsal Root Ganglia (DRGs) (Ctrl and cKO).The specific ST:STUDY_SUMMARY knockout of PP2Cm in the DRG was achieved by intracellular injection of ST:STUDY_SUMMARY AAV9-Pirt-Cre (1.0×1013 vg/ml) or AAV9-Pirt (1.0×1013 vg/ml)) as control. Mice ST:STUDY_SUMMARY were used for experiments at 4 weeks after the injection. ST:INSTITUTE West China Hospital of Sichuan University ST:LAST_NAME Li ST:FIRST_NAME Tao ST:ADDRESS No. 37 Guoxue Road, Wuhou District, Chendu 610041, Sichuan, China ST:EMAIL 563234879@qq.com ST:PHONE +8628-85164154 ST:SUBMIT_DATE 2023-07-07 #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]Additional sample data SUBJECT_SAMPLE_FACTORS cKO1 cKO1 Genotype:cKO RAW_FILE_NAME=XHJ_DRG NEG/POS-20221214-XHJ_DRG_aqu_KO1.mzML SUBJECT_SAMPLE_FACTORS cKO2 cKO2 Genotype:cKO RAW_FILE_NAME=XHJ_DRG NEG/POS-20221214-XHJ_DRG_aqu_KO2.mzML SUBJECT_SAMPLE_FACTORS cKO3 cKO3 Genotype:cKO RAW_FILE_NAME=XHJ_DRG NEG/POS-20221214-XHJ_DRG_aqu_KO3.mzML SUBJECT_SAMPLE_FACTORS cKO4 cKO4 Genotype:cKO RAW_FILE_NAME=XHJ_DRG NEG/POS-20221214-XHJ_DRG_aqu_KO4.mzML SUBJECT_SAMPLE_FACTORS cKO5 cKO5 Genotype:cKO RAW_FILE_NAME=XHJ_DRG NEG/POS-20221214-XHJ_DRG_aqu_KO5.mzML SUBJECT_SAMPLE_FACTORS cKO6 cKO6 Genotype:cKO RAW_FILE_NAME=XHJ_DRG NEG/POS-20221214-XHJ_DRG_aqu_KO6.mzML SUBJECT_SAMPLE_FACTORS Ctrl1 Ctrl1 Genotype:Ctrl RAW_FILE_NAME=XHJ_DRG NEG/POS-20221214-XHJ_DRG_aqu_C1.mzML SUBJECT_SAMPLE_FACTORS Ctrl2 Ctrl2 Genotype:Ctrl RAW_FILE_NAME=XHJ_DRG NEG/POS-20221214-XHJ_DRG_aqu_C2.mzML SUBJECT_SAMPLE_FACTORS Ctrl3 Ctrl3 Genotype:Ctrl RAW_FILE_NAME=XHJ_DRG NEG/POS-20221214-XHJ_DRG_aqu_C3.mzML SUBJECT_SAMPLE_FACTORS Ctrl4 Ctrl4 Genotype:Ctrl RAW_FILE_NAME=XHJ_DRG NEG/POS-20221214-XHJ_DRG_aqu_C4.mzML SUBJECT_SAMPLE_FACTORS Ctrl5 Ctrl5 Genotype:Ctrl RAW_FILE_NAME=XHJ_DRG NEG/POS-20221214-XHJ_DRG_aqu_C5.mzML SUBJECT_SAMPLE_FACTORS Ctrl6 Ctrl6 Genotype:Ctrl RAW_FILE_NAME=XHJ_DRG NEG/POS-20221214-XHJ_DRG_aqu_C6.mzML #COLLECTION CO:COLLECTION_SUMMARY Mice were anaesthetized with volatile anesthetic isoflurane (3-4% for induction, CO:COLLECTION_SUMMARY 1-2% for maintenance, in O2≈ 2 L/min). DRG (left L4–L5) were surgically CO:COLLECTION_SUMMARY exposed and diessected. Fresh DRG samples were frozen in liquid nitrogen.5-6 CO:COLLECTION_SUMMARY DRGs were collected as one sample CO:SAMPLE_TYPE DRG #TREATMENT TR:TREATMENT_SUMMARY No treatment. #SAMPLEPREP SP:SAMPLEPREP_SUMMARY Fresh tissue samples were frozen in liquid nitrogen. After thawing on ice, 10 mg SP:SAMPLEPREP_SUMMARY tissue was homogenized in -80°C precooled labeled-solution (MeOH: H2O=4:1, v/v) SP:SAMPLEPREP_SUMMARY for 30 s, 4 cycles, and placed at -80°C for 30 minutes. In ice water bath, SP:SAMPLEPREP_SUMMARY ultrasonic wave was used for 10 min and centrifuged at 14000 rpm. The SP:SAMPLEPREP_SUMMARY precipitated protein was dissolved in no labeled-liquid (MeOH: H2O=4:1), SP:SAMPLEPREP_SUMMARY vortexed and centrifuged. After derivatization with SP:SAMPLEPREP_SUMMARY N-methyl-N-(trimethylsilyl)tri-fluoroacetamide for 30 min, the supernatant was SP:SAMPLEPREP_SUMMARY detected by GC-MS. Metabolites were identified by means of KEGG Metabolic SP:SAMPLEPREP_SUMMARY pathways. #CHROMATOGRAPHY CH:INSTRUMENT_NAME Nexera UHPLC LC-30A CH:COLUMN_NAME Waters BEH Amide (2.1 X 100mm, 1.7μm) CH:COLUMN_TEMPERATURE 40℃ CH:FLOW_GRADIENT 0～1.5min,90%B.1.5~5min,90-45%B.5~10min,45%B.10~11min,45~90B.11~23min,90B CH:FLOW_RATE 0.3ml/min CH:SOLVENT_A 10% acetonitrile/90% water; 0.2% acetic acid CH:SOLVENT_B 90% acetonitrile/10% water; 0.2% acetic acic CH:CHROMATOGRAPHY_TYPE HILIC #ANALYSIS AN:ANALYSIS_TYPE MS #MS MS:INSTRUMENT_NAME Nexera UHPLC LC-30A MS:INSTRUMENT_TYPE Triple quadrupole MS:MS_TYPE ESI MS:MS_COMMENTS - MS:ION_MODE NEGATIVE #MS_METABOLITE_DATA MS_METABOLITE_DATA:UNITS pmoles/l MS_METABOLITE_DATA_START Samples cKO1 cKO2 cKO3 cKO4 cKO5 cKO6 Ctrl1 Ctrl2 Ctrl3 Ctrl4 Ctrl5 Ctrl6 Factors Genotype:cKO Genotype:cKO Genotype:cKO Genotype:cKO Genotype:cKO Genotype:cKO Genotype:Ctrl Genotype:Ctrl Genotype:Ctrl Genotype:Ctrl Genotype:Ctrl Genotype:Ctrl 12S-HETE 281423.0850 61185.2340 68903.6890 114410.2715 73592.3235 135096.3350 231433.2400 207692.7820 242202.5345 76627.1070 296362.9995 320682.6100 13C2-Succinate 21633152.9300 20714556.7700 21817899.0500 20392039.7000 19668022.5900 22505750.2200 21846819.0400 20181282.3600 22584240.8500 19369891.7900 21282744.2400 19593000.9900 13C5-Glutamic acid-15N 15465834.2500 17024754.7700 16667308.7600 16033315.3700 17064649.9200 16372164.8500 17675200.6000 16422219.3400 17904261.4400 17339592.0000 17356158.6500 15422762.3900 13S-hydroxyoctadecadienoic acid 90409.4365 60908.5535 52085.7930 63667.5085 65321.0080 79380.8245 77866.8485 95654.0045 87655.9155 44643.4870 106680.2335 124198.8840 1-Methyladenosine 2835234.3970 1808619.4870 2377822.1300 2798336.1660 1758023.6080 2857406.7180 2409166.5080 2328229.7180 1990770.0220 1373320.0790 2155783.2260 2345778.2920 2-Hydroxyglutarate 1101671.5490 783174.0407 882752.8352 1623820.9710 768945.7667 1988246.1520 649284.4311 1130750.0320 693144.6425 395220.6015 663224.4670 585039.1325 3-Aminoisobutanoic acid 2629.2500 3539.3750 5357.8750 3033.7500 4854.0000 4244.8750 9909.2500 2021.2500 4649.7500 3842.3750 3-Hydroxy-3-methylbutyric acid 381674.1335 304696.8635 257516.1690 371693.6187 303337.3260 406522.3630 221650.5330 239020.1245 216959.0910 137827.0675 261098.6175 262776.3650 3-Hydroxyanthranilic acid 3032.6250 6774.7500 2831.5000 4852.3750 2831.6250 4954.1250 3640.5000 6470.6250 4852.0000 1820.2500 7483.2500 3-methyi-2-oxo-butanoic acid 65593.5910 34447.4545 30866.5565 36514.4545 30224.8853 45195.4320 33069.7040 18600.2500 24525.5000 32778.2028 14881.0000 34586.8300 3-Methyl-2-oxovaleric acid 62984.7957 68069.8865 78270.3190 49959.4505 31734.6187 52618.2601 16260.1025 25906.8295 20670.3525 56353.6025 24758.6357 28799.8300 3-Methylhistidine 2440531.5890 1503398.4710 1681803.1580 2029889.0310 1191066.9280 2550231.4860 1545224.9920 1197745.7040 873542.0210 883016.8108 1303365.8390 1285084.0310 4-Hydroxyproline 3679120.0080 2920775.1130 3107689.5810 4101985.2170 2827809.6080 3909615.7030 2807020.5920 2631491.5950 2306137.3220 1818341.6500 2058551.8570 2523306.2990 4-methyl-2-oxovalerate 6616.7045 6062.8520 31695.2385 8542.7040 45479.5455 10884.2780 21773.4090 5235.6020 17916.3860 4-Trimethylammoniobutanoic acid 249281.4065 191661.0815 192874.1549 221398.9725 3033.7500 3438.2500 232258.8780 215723.5290 134574.6425 121106.3231 185342.6600 229090.6195 5-Aminolevulinic acid 4468727.9760 395035.9986 447001.3140 81854.4729 405685.3783 336949.8900 320636.4959 5-Aminopentanoic acid 80095.8545 4852.6250 53794.1295 5359.6250 4953.1250 12132.5000 53389.4460 5256.6250 5660.1250 4953.6250 7078.6250 4044.1250 5-Hydroxyindoleacetic acid 251785.7450 150156.3550 118778.9715 141445.9425 122214.7460 181048.1800 187223.1055 118759.8475 110577.5740 74643.7680 126046.3625 122395.8455 6-Phospho-D-gluconate 492969.2712 322954.4570 381583.0828 514816.5430 270780.2280 580187.0017 229015.3962 204549.7205 207458.4945 150876.0270 250731.0890 219469.1755 Acetylglycine 365367.1290 329650.2030 180236.5465 525968.2210 297164.0935 416715.3340 278080.3200 214904.3185 166578.7585 145326.5110 210910.5560 156623.8145 Adenine 909683.1960 1556496.0340 1802317.8720 3127584.1620 1499963.2900 3012719.6410 242299.6121 213087.9855 258877.7810 143744.9215 319830.4630 180279.4205 Adenosine 40011097.1400 70611355.2700 80319215.4300 123331088.6000 66829551.5800 128161919.6000 10089934.0200 7411913.7550 8632873.5190 5041983.4100 11865080.8600 6128100.6320 Adenosine 5^-diphosphate 983051.6140 636847.8200 708762.3610 1253148.0680 628563.5710 1505448.0030 633205.6116 432364.0371 430598.9479 476907.2316 647693.6415 794337.3572 Adenosine monophosphate 542079.1160 357726.9046 587749.8619 462599.7732 547086.4647 1472968.1860 280488.6543 318270.6007 193502.6694 309688.0665 290195.9791 336134.2067 Adipic acid 6889.7500 16534.5000 5511.7500 2755.0000 9661.3822 6337.0000 10471.1250 3445.1250 7223.9128 6888.8750 3581.5000 9076.4297 ADP-ribose 2^-phosphate 19134.8400 24438.7745 34228.2970 50913.7615 36642.6710 44418.6545 6936.8311 11331.0300 6404.1700 7418.2500 8520.2800 7241.7200 Agmatine 25481.1840 34983.0000 29929.9340 4651.7500 5055.3750 23604.7189 8492.9335 5661.7500 34784.0590 14155.7500 12639.2500 28007.7500 Allantoin 295616.3570 194909.6455 198350.1167 280720.2455 179193.3590 311335.6810 192990.0120 248445.0020 172018.0635 142509.6915 199739.0695 224571.4270 Alpha-D-Glucose 12097.7469 11005.7436 10172.3240 14181.9679 10112.1043 10869.4466 7022.7110 3866.9660 2217.4415 3171.3787 5278.3752 1444.7112 Alpha-D-Glucose 1_6-bisphosphate 7425209.5870 5157309.8210 5552217.5490 5232238.2790 3717962.4330 4434785.8320 7614721.5940 5613814.9530 5413370.8320 5822492.6980 6160576.7770 5303908.0280 Arginosuccinate 139518.8580 74705.1880 88215.2315 94555.0140 57882.4860 77179.8345 100483.8755 79942.2135 52915.5765 57602.1555 67807.7230 100632.6865 ATP 10286.9660 15797.1975 4775.9660 3307.0000 Benzoic acid 89199.4445 313261.0125 117753.6815 109733.5045 109047.0335 160201.7040 112508.7660 138969.7560 110289.9420 124484.1225 102845.8330 170816.2195 Betaine 44123.2454 83120.5960 89801.4500 66439.2145 36810.4200 67753.4640 81103.0240 8899.6180 7483.2500 22852.8015 Choline 57405095.2700 48529265.1500 47537181.5000 51338660.2500 43714231.8700 47087101.7200 49590233.9900 44882746.0400 41391092.6900 39898148.6200 45706263.3200 49067049.2500 Citraconic acid 22874.7835 323827.2760 46850.9885 48231.6930 11437.9545 35827.3860 7441.5560 54294.2485 33349.4885 35279.8180 46575.9885 52362.9655 Citric acid 340909.2123 289736.2991 577870.5588 312045.4312 279754.1700 35666.1730 457670.3460 480435.0695 649528.9452 479360.7329 1076927.4900 558120.3411 Creatine 39400487.2700 32842589.0200 31987791.9400 46151842.0900 32898489.0800 54858154.7500 37705970.7100 35695652.6200 26026071.1200 25026059.4300 32248586.4800 33888607.1900 Creatinine 926987.2475 739195.7510 1015852.3270 566027.6055 1232375.8110 607176.1105 632884.6705 423814.9325 378366.9970 582975.8350 645884.7775 Cysteamine 94265.0800 3033.7500 121393.7180 106596.4450 5056.2500 57344.0020 68069.2670 5056.2500 Cytidine 584279.1130 377398.1855 457951.6450 470234.5635 387631.6680 466554.3495 365663.2255 261264.2595 213469.6810 173190.2950 290825.4985 226036.1470 Cytosine 226260.3245 152954.7860 186960.5580 12741.3090 32261.0375 139182.2805 37491.9599 91229.3190 117028.1485 D4-Glutaric acid 15765474.0800 13948474.7600 16051526.3100 14412345.0100 14315349.0200 15850852.2900 13928503.2900 14383703.0500 13942177.9600 14373988.4000 15553993.9300 16163839.5500 D-(Alpha)Lactose 1925.6475 15430.5000 8267.0000 17912.1020 7715.5000 1522.3532 3772.2659 12123.3750 2561.6414 6751.2500 7991.5000 7163.8750 D-Biotin 9094.1250 6062.6250 7715.7500 3581.7500 D-Fructose 6-phosphate 396076.3938 249413.6817 313158.2751 327395.6810 217927.1937 366003.2680 331859.9409 253625.4658 238613.4936 239200.0152 243325.3530 256056.4419 D-Glucose 6-phosphate 744811.3409 664263.7142 620982.0825 735233.0842 648799.4065 906738.0007 456427.2613 481422.4216 250485.4301 347449.0322 427029.5775 349126.7862 D-Glucuronic acid 14882.1025 12675.0000 14879.7500 13778.0000 16120.5000 24249.1250 20117.6025 14740.7500 22871.6250 26180.6025 22318.7500 22318.6250 D-Glyceraldehyde 3-phosphate 58632.5888 54499.2023 70426.9795 74500.0162 64274.5100 62793.3653 40967.7615 35234.6092 47788.1548 34018.1130 45094.6642 42332.6896 Dihydroxyacetone phosphate 326521.4175 279856.0728 277053.8808 233759.7163 212065.4211 167976.5553 310006.1069 265490.2420 234389.0200 253614.8530 284977.4494 286112.5116 Dimethylglycine 85887.8395 33899.3225 95063.9880 112259.6940 61180.2145 65742.1135 28316.0445 26700.8540 16582.3750 11932.9340 34328.2977 3641.3090 D-Leucic acid 85716.2840 80754.3525 78547.3745 103493.2390 89846.6020 117974.2395 74549.4435 67800.2730 76338.2945 45196.7840 70007.2505 74410.0450 DL-Kynurenine 15166.4340 6471.3750 12741.5000 15774.0000 7482.6250 23664.4270 22852.3090 36000.4860 41261.5380 14358.8750 37214.0450 28517.4270 DL-Malic acid 7439930.4570 1386247.1460 2607579.5650 5589727.1720 3981543.1590 3671239.5980 5862450.0080 5237276.4870 4547949.4310 4011422.6860 4803864.4310 6740327.7950 D-Sucrose 67258.0680 64221.8620 110000.4545 130418.3305 73044.4500 39687.9655 57056.1810 91113.0865 68224.7955 32244.2835 94277.9285 50988.1235 Fumaric acid 511757.6381 344655.0222 437095.7069 498457.6660 301732.7060 470054.9910 298241.9275 286408.9636 179334.1950 176197.1950 256085.5933 306681.2249 GABA 129191.6875 113551.8030 64986.0030 213909.7640 109990.7115 256125.7015 96682.9710 110717.1745 64581.1620 58241.7725 65268.8990 75373.4490 Gluconic acid 24069.4905 114476.8040 131567.8390 164162.5032 131195.5055 150092.7911 129105.7722 146813.8830 119800.2925 127330.0955 216827.4060 Glucose 1-phosphate 691667.2136 568805.5353 564939.3673 619502.7766 592997.8468 756333.1200 341419.1494 416811.0817 158445.7245 243918.9629 266613.1068 333686.9932 Glutaric acid 149968.6565 94016.2425 116170.6436 104889.2745 60094.3415 56789.1700 69190.8985 105313.0695 90147.1490 74078.6613 77328.0135 95246.2750 Glutathione 3231419.6980 2472791.2900 2886256.6830 2831817.7520 2027784.2740 3138632.2340 2401196.1720 1460953.7600 1029975.8780 1956419.5150 1520344.3370 1802168.6220 Glycerate-2P 5083297.7290 2437938.6580 2326971.9140 3052800.7350 1951177.3240 3885400.7160 4242423.4820 2214603.2120 3979196.5500 1995912.2680 3822095.3450 3936353.9540 Glycerate-3P 2270239.8390 3788171.7960 4408191.0230 3959664.0580 Glycerol 3-phosphate 1785238.9670 1231755.3180 1095506.2140 1367153.4530 1178192.4730 1224417.7680 708385.1884 559244.3258 364987.0085 450454.3660 781285.7250 543749.4220 Glycine 104398.5135 137991.7060 162327.6425 225813.7120 102569.7725 114311.3155 84160.2020 149140.7255 53198.2515 79704.9885 86180.8930 97309.6385 GMP 277189.3395 248249.1980 314871.5530 397531.4634 274484.3985 412661.8220 139774.7025 208577.0530 71300.5615 118529.1705 139378.4340 83529.1920 GTP 1425945.9870 920607.3182 1153543.0460 1558579.9570 909602.7645 1424845.6340 926815.3584 783538.8799 748006.7265 908057.0964 924229.2305 1170327.0360 Guanidoacetic acid 62697.2878 260344.6995 323052.0790 272151.6114 78827.1063 463364.1264 254515.9350 186104.1600 18887.0690 261493.1675 237078.0225 213565.4805 Guanosine 8657214.2370 6938888.9780 7247993.6240 5243851.0590 4949789.9230 4442103.2300 8203680.5630 6186736.2230 4433769.0610 4088131.8790 5045799.9220 5414958.1550 Guanosine diphosphate 231468.5790 202509.3005 204709.2175 313305.7195 251125.0510 381659.2175 139348.0840 142098.4015 112046.6120 137140.3490 135204.3685 159603.7965 Homogentisic acid 274488.3695 188856.1860 277366.7470 420916.2260 220667.4705 238231.6250 175328.1800 140308.6545 187747.9880 149266.7315 288736.8580 220407.5330 Homovanillic acid 12537.3750 7715.1250 10471.1250 6476.7500 5235.1250 6476.2500 Hypoxanthine 50096706.2400 35000226.1100 34248710.0000 47127974.2700 32168301.3200 38465826.1000 43126439.2500 37060478.0000 29807425.6300 24778854.6700 38443200.3300 41374656.1400 Indolelactic acid 13144.0000 7683.5000 6470.7500 19211.8680 8290.1250 12740.1175 3236.0000 3639.2500 2931.0000 5055.2500 11728.3750 Indoxyl sulfate 204961.6345 83263.8010 227359.1700 180671.5490 137342.3350 150301.3565 69196.0490 123819.3430 102848.5650 60095.1845 105338.3065 159159.6055 Inosine 13517705.0800 5872000.2630 5954990.9990 11221851.9100 5261868.7890 8825744.1890 7714654.8100 7284799.8770 5361763.5450 4651492.6530 5904881.3170 8351716.4320 Inosinic acid 87375.1118 53597.0335 76743.8065 95364.3558 10662.4364 25902.1250 21769.1250 13778.5000 61313.5335 68477.1815 54975.3065 78865.2986 Isocitric acid 20793.5893 7047.3950 14422.7323 6076.1979 10869.7792 13822.5231 11323.9565 6904.0950 2834.8358 5444.4394 8746.8379 6862.8156 Kynurenic acid 7991.1250 12676.7500 18598.7500 3030.5000 3583.1250 6200.8750 5787.0000 L-Alanine 6705466.1900 4983104.6510 4843624.1720 6764431.7970 4862629.2290 8529191.9780 6013114.1950 5783096.0830 4155634.1310 3819061.0330 4730702.4950 5587760.9870 L-Arginine 986643.6432 871617.3963 889440.7492 1008972.1530 648726.7256 652474.6023 894458.1341 851734.9133 1423547.7620 1572934.7940 1009294.4690 921930.5998 L-Asparagine 378084.6285 335785.4155 295785.6910 360625.2240 251806.9505 371066.0455 349686.9190 288979.4410 205199.9160 247142.8225 228574.1475 332402.4575 L-Aspartic acid 8157882.0610 6676952.6760 5770362.1080 6652993.2240 5244827.7290 6541640.5470 7391710.7380 6334620.2990 4996754.1190 5068835.2960 5399769.3750 7296630.0390 L-Carnitine 28739548.8700 29708322.4900 24646133.1700 22099157.6100 21147759.6100 34090324.7800 25148666.3000 21024478.8500 19648275.7000 18467848.3200 22995439.6000 24676870.6600 L-Citrulline 7572075.1050 4808249.8800 5567391.0280 6557234.0720 3817677.9690 6661300.9900 5315835.5580 4239666.7630 2591355.4870 3127701.6760 3581958.0930 5068079.9650 L-Cystathionine 31965.9080 29346.2270 28794.6250 36651.7830 21631.4770 28658.9310 24938.7040 24110.6020 15981.7270 16257.6020 21218.6020 26314.7270 L-Glutamic acid 55026160.0900 43808693.2900 44074630.7100 78828846.6100 35744373.0500 94865722.5200 61791229.8900 34545357.3600 26977636.7300 28112356.6200 50078458.0600 61130414.6800 L-Glutamine 38042046.5900 32693229.4500 26695968.4900 32457413.5400 25522558.4200 40229097.7000 19101896.8800 21834911.8600 13130971.7100 15084938.5200 17713811.1900 21273181.1900 L-Histidine 4746884.9680 6148288.2970 3792975.2910 7328938.8890 6139159.1590 17357885.6300 5816572.0500 6724167.4650 4102610.0160 3792681.6880 5990638.7080 5166326.0660 L-Homoserine 2278345.2970 1665180.3860 1742063.6250 1670850.6760 1200096.4840 1882675.7050 1825733.8860 1394218.1610 1093486.6770 1169291.1030 1184954.0170 1831713.6840 L-Isoleucine 1742407.0620 1481090.8480 1365594.5980 1585641.7720 1403904.2820 2074298.6890 1218777.6620 1164061.9020 900579.0072 741502.7126 905682.2783 1073864.3790 L-Lactic acid 4319408.5860 2793176.0780 3425042.1330 4777290.3140 3093282.0950 5970209.4460 3997049.3550 3898593.0590 3097058.5060 2698191.0370 3197919.6260 3920229.6410 L-Leucine 5893767.9240 4430045.3950 3994283.6710 4868823.4210 4239710.8600 5834094.1650 3863006.9970 3885430.2930 2944841.6720 2509811.3730 3091462.5880 3653646.4020 L-Lysine 385450.5119 458052.2290 325427.6912 398884.8838 324681.1191 359999.9108 235635.8082 426150.9388 380389.9080 185000.8475 334251.2419 239809.0362 L-Methionine 1079849.1650 788972.2115 936383.5395 884823.4030 635518.6535 938634.9880 1107131.3580 833575.5935 617871.8195 621954.8405 719156.3585 1088828.8670 L-Ornithine 448987.0575 516638.6925 430270.8690 536642.6313 357250.3025 573030.6680 522040.0512 401394.7645 293123.8743 285796.6811 312248.6629 368821.0021 L-Phenylalanine 16378214.5800 10468014.5100 11828179.7700 12603032.5500 9251238.3940 14676578.1200 13109000.5700 12274468.4100 9949939.5250 7917060.7720 10878307.7100 12834342.5400 L-Serine 2828546.7410 1967966.3290 2743990.4780 2485288.4540 1701777.4410 2653201.6900 1744018.9630 1337604.7800 919126.6005 1163767.7430 1112642.4640 1607254.6970 L-Sorbitol 6672.7500 8493.0000 5054.3750 5459.3750 4651.7500 3639.6250 2628.0000 L-Threonine 3383550.7570 2642185.2990 2742391.3370 2742228.8050 1977324.8770 2920679.9160 2804795.6040 2187272.1330 1686945.0330 1899606.4300 1902323.6320 2782773.2680 L-Tryptophan 1526409.1970 988088.6770 1093911.7180 1479101.0570 877767.6955 1707970.7080 1207756.3290 1154237.1600 1188451.4060 901435.4325 1209357.5770 1346860.7120 L-Tyrosine 2810196.5720 1736742.5000 2250565.6740 2707224.8190 1611029.5180 2652128.6790 2045891.0160 1831930.6500 1392177.2270 1246092.9640 1507494.8570 1841460.2250 L-Valine 869095.5718 715151.2675 614130.7144 700912.5182 626994.3613 893096.3315 507036.5956 594002.2603 493718.9625 420836.6630 490333.6706 580776.0363 Maleic acid 67258.8970 253846.4025 68912.2720 52515.5445 55961.9485 92897.1700 66709.1005 92893.1120 71670.3515 60365.8625 74150.6805 68908.6915 Malonic acid 36787.9310 61732.4980 21217.3750 69588.4060 47951.4645 82542.2350 50703.2600 46160.2145 38853.9310 20389.6250 73581.3265 39406.1580 Methylsuccinic acid 10884.3750 14329.2500 13226.8750 4408.3750 11023.0000 Mevalonic acid 118796.6355 79928.1815 91395.6027 81305.4540 70835.1255 108598.9540 84063.0800 40510.7045 51536.0110 49055.1590 49192.5110 65316.5445 myo-Inositol 8993391.9590 7048799.5950 7541437.7420 8056849.4620 6579741.2930 8937921.2320 6962552.6310 6321413.7530 5346117.6110 4505527.5260 5587582.3120 7450467.7840 N-Acetylputrescine 3033.7500 2629.2500 3337.1250 3842.7500 3438.2500 2629.2500 5662.1250 3033.7500 5056.2500 NADH 99525.7480 63672.2145 84356.1690 97601.8785 90967.2465 147542.5495 71947.8755 38584.8635 32798.0345 31422.9895 42717.7150 59259.8835 Niacinamide 23083428.9500 17310911.5700 16254743.1300 21595539.4100 15425521.0200 25237270.1400 19329949.5500 16588177.8400 11204315.5600 11050074.0700 14201134.6200 15989559.6400 Nicotinic acid 6066.6250 1921.1250 2730.3750 3640.5000 8291.5000 7887.7500 2224.7500 3032.1250 3842.7500 9911.0590 6168.6250 Orotic acid 29350.8070 34861.4315 27006.2270 56912.0680 31414.2270 36652.0565 16947.7270 30865.9315 27281.4770 21219.8520 25902.7275 27833.9545 Oxalic acid 71102.0096 76886.9090 82673.6825 70550.1365 65583.2045 92460.3415 85705.9890 76615.4660 45746.0800 57315.6250 60203.1746 101140.0680 Oxidized glutathione 26431584.2100 17650687.9600 18446941.3700 25722898.5500 17130006.6500 31626879.4900 17364327.9500 17305957.2600 12118315.4500 11040760.7000 15784301.8300 16041641.1300 Oxoglutaric acid 596552.0419 614148.9860 719904.4085 540707.5190 436394.2225 637116.0413 358170.1591 415539.3471 324168.2865 326040.1605 373566.3771 408807.6674 Pantothenic acid 2733738.0460 1867899.9870 2672149.1220 2355441.8340 1443789.8730 3864692.4490 1923949.7760 1479628.8890 1668681.0790 1924493.2360 1717671.5900 1945844.3310 Phosphoenolpyruvic acid 163048.2396 72749.3862 73907.6739 92472.7730 58607.7622 110728.9298 178629.0600 53481.2270 128910.1556 63985.7959 120495.1044 147698.8887 Pipecolic acid 2977961.5030 1835502.9610 1958375.9580 580184.0627 783513.7992 Pyridoxal 5^-phosphate 31826.8750 12726.9649 36373.7500 38578.1250 55939.6250 33617.8750 37888.8750 9644.6250 14329.3750 15982.6250 Pyroglutamic acid 490031.8815 525576.3970 485217.9755 448917.8005 508920.1890 507104.6930 528559.8185 540015.4205 527220.9165 545067.4410 537539.9480 515391.2145 Pyruvic acid 71100.9002 46496.5336 61397.6162 65146.0235 50071.9740 65041.0445 48505.3635 38609.8235 39148.7651 30555.8244 47889.4044 59473.4160 R-3-Hydroxybutyric acid 1216006.8710 1551275.4220 590343.2225 2213691.4280 1477938.2000 2406694.8080 1567002.2930 1630373.5280 1072575.6670 888337.6232 2086290.6170 1390850.8750 Ribose-5P 3723866.5450 2404252.2290 3219842.3460 3833871.1720 1961193.5180 3266396.3110 3395996.5790 3159307.3240 1783260.7270 2084581.2690 3039005.2710 2336643.4800 Ribulose-5P 5294542.1310 4123349.9570 3986241.3420 4627510.6360 3300474.0330 4225967.9020 4236037.3980 3977829.7630 2177262.0690 2527950.4250 3874835.5810 3159511.0850 S-Adenosylhomocysteine 277261.4465 170396.3100 161574.1515 206269.6840 125705.5055 194974.5130 189715.0185 160187.4835 134261.2065 108333.4525 158532.4510 202431.5750 Sarcosine 21231.3675 22446.6250 17695.0590 4247.2500 11931.2425 14763.3090 7279.7500 11930.5000 10111.3750 8898.7500 17490.6250 Serotonin 2224.7500 4651.5000 5258.0000 3842.0000 4449.5000 4651.5000 6269.0000 Shikimic acid 16808.7270 7853.3750 11985.8750 12261.8750 13087.7500 27005.5560 7715.0000 9780.8750 26731.0565 15431.0000 Spermine 6470.6250 5055.5000 3033.2500 2224.7500 2224.7500 2831.5000 5865.2500 4043.6250 5054.3085 Succinic acid 1673561.9440 1108009.2940 1458379.6760 2230528.0890 1329013.6910 2741290.0530 772189.9315 880337.2190 531038.8710 592776.8830 817596.5160 860581.0615 Taurine 35604674.3700 30204632.9700 25243879.6200 43849375.2400 28368282.5700 58622668.4500 33871403.6800 31853829.1700 21379137.3500 19624710.0000 28083096.5800 30131214.8900 Trimethylamine-N-oxide (TMAO) 1024714.7030 1134796.5390 1097664.1740 947291.7160 912773.9940 383313.8384 317828.5087 871648.1020 1073231.9980 941517.4220 424279.4399 960680.2615 Tryptamine 6067.2500 9302.7500 3639.2500 7685.5000 5864.7500 3033.7500 3640.2500 3841.3750 3841.8750 Tyramine 6269.7500 5461.5590 10919.6250 6269.2500 10516.1250 12737.5000 10110.8750 7483.1250 13851.2500 13244.8750 8492.6250 6878.1180 Uracil 15706.7500 8541.8750 10195.2500 6613.3750 16808.8750 14054.1250 13227.3750 9920.0000 12675.1250 12124.3750 Uric acid 424489.5294 232692.8355 273388.4845 351329.2300 296410.7925 441339.0930 515476.0335 425283.7685 333383.5095 314626.2725 412883.1225 502947.2096 Uridine 995136.5575 589570.4875 618000.4705 629211.8600 590378.0735 458536.0270 892499.4290 759775.5790 719386.9900 638899.9235 645901.3305 723132.2020 Uridine 5^-diphosphate 1429836.4590 967559.5533 1311577.0310 1533902.1340 1036629.6500 1517783.3560 986347.6887 992193.9970 597412.5340 776828.8208 917729.8125 975298.9635 Uridine 5^-monophosphate 2261086.9710 2088337.4040 2521712.3300 3631795.0000 2629379.8780 6388221.2300 970842.5004 1540452.3110 793859.4295 736683.1843 1167529.5120 1187430.1880 UTP 8331676.2850 5215612.5760 5862956.5020 8008740.8920 4702575.5600 6881201.9320 5429753.7500 4335305.0120 3740283.4900 4204844.4530 4702514.3110 6073461.8880 Xanthine 9397741.3700 4738445.9160 5279219.0720 5864026.4580 4091212.0580 4988730.7350 9812073.0740 6917127.9980 6215491.5090 5560858.2820 7888018.0440 9588143.0990 Xanthosine 132196.7300 72219.1935 87938.7645 95793.1390 61191.1035 82145.4010 198830.0555 144737.8410 125440.4700 104750.6495 159777.8865 251536.6580 Xanthurenic acid 7683.0000 6268.7500 7280.3750 8695.2500 11528.9340 11930.9340 9707.2500 4246.3750 4448.8750 5055.7500 6268.3750 7684.1250 Xylulose-5P 4916205.3980 4064117.4560 4070472.5380 4848029.7200 3075098.1920 3973944.2470 4383181.6260 4331700.5970 2267498.1270 2452477.1630 3693295.7140 3259719.6170 MS_METABOLITE_DATA_END #METABOLITES METABOLITES_START metabolite_name pubchem_id inchi_key kegg_id other_id other_id_type ri ri_type moverz_quant 12S-HETE 13C2-Succinate 13C5-Glutamic acid-15N 13S-hydroxyoctadecadienoic acid 1-Methyladenosine 2-Hydroxyglutarate 3-Aminoisobutanoic acid 3-Hydroxy-3-methylbutyric acid 3-Hydroxyanthranilic acid 3-methyi-2-oxo-butanoic acid 3-Methyl-2-oxovaleric acid 3-Methylhistidine 4-Hydroxyproline 4-methyl-2-oxovalerate 4-Trimethylammoniobutanoic acid 5-Aminolevulinic acid 5-Aminopentanoic acid 5-Hydroxyindoleacetic acid 6-Phospho-D-gluconate Acetylglycine Adenine Adenosine Adenosine 5'-diphosphate Adenosine monophosphate Adipic acid ADP-ribose 2'-phosphate Agmatine Allantoin Alpha-D-Glucose Alpha-D-Glucose 1,6-bisphosphate Arginosuccinate ATP Benzoic acid Betaine Choline Citraconic acid Citric acid Creatine Creatinine Cysteamine Cytidine Cytosine D4-Glutaric acid D-(Alpha)Lactose D-Biotin D-Fructose 6-phosphate D-Glucose 6-phosphate D-Glucuronic acid D-Glyceraldehyde 3-phosphate Dihydroxyacetone phosphate Dimethylglycine D-Leucic acid DL-Kynurenine DL-Malic acid D-Sucrose Fumaric acid GABA Gluconic acid Glucose 1-phosphate Glutaric acid Glutathione Glycerate-2P Glycerate-3P Glycerol 3-phosphate Glycine GMP GTP Guanidoacetic acid Guanosine Guanosine diphosphate Homogentisic acid Homovanillic acid Hypoxanthine Indolelactic acid Indoxyl sulfate Inosine Inosinic acid Isocitric acid Kynurenic acid L-Alanine L-Arginine L-Asparagine L-Aspartic acid L-Carnitine L-Citrulline L-Cystathionine L-Glutamic acid L-Glutamine L-Histidine L-Homoserine L-Isoleucine L-Lactic acid L-Leucine L-Lysine L-Methionine L-Ornithine L-Phenylalanine L-Serine L-Sorbitol L-Threonine L-Tryptophan L-Tyrosine L-Valine Maleic acid Malonic acid Methylsuccinic acid Mevalonic acid myo-Inositol N-Acetylputrescine NADH Niacinamide Nicotinic acid Orotic acid Oxalic acid Oxidized glutathione Oxoglutaric acid Pantothenic acid Phosphoenolpyruvic acid Pipecolic acid Pyridoxal 5'-phosphate Pyroglutamic acid Pyruvic acid R-3-Hydroxybutyric acid Ribose-5P Ribulose-5P S-Adenosylhomocysteine Sarcosine Serotonin Shikimic acid Spermine Succinic acid Taurine Trimethylamine-N-oxide (TMAO) Tryptamine Tyramine Uracil Uric acid Uridine Uridine 5'-diphosphate Uridine 5'-monophosphate UTP Xanthine Xanthosine Xanthurenic acid Xylulose-5P METABOLITES_END #END